Rad Onc Clinical Boards '23 Review

What method do we commonly use to cool down hotspots if IMRT not approved?

"field in field" or segmented fields which essentially just blocks part of the field out to cool down the hotspots.

Most common histologies for peds LGG?

#1) pilocytic Grade I #2) Grade 2 Diffuse fibrillary astrocytoma

A disease is more common in one town than another. What type of study would be best to determine if there is a difference in *incidence* of the disease between the two towns?

*Cohort study* (can be prospective or retrospective) - prospective looks ahead comparing two groups without a condition on the basis of their +/- risk factor. - retrospective looks back at people +/- the risk factor to see what the incidence of the condition ended up being in those groups Look at two groups with set different risk factors and look at the incidence of the condition between the two groups. This data can then be extrapolated to estimate the incidence in the total population and compare incidences between groups. The key here is *incidence* of the disease based on a risk factor and thus the relative risk for developing the condition based on the presence of the risk factor can be determined.

Methods for reducing coufounders?

*Randomization* Restriction (if sex is a counder, only include men - introduces problems w/ generalizability) matching (used in case control studies)

If given the relative risk calculated by a study, how do you determine the % of cases of the disease that are due to the risk factor studies?

*attributable risk percent* ARP = (RR - 1)/RR or another way to calculate: ARP = (risk in exposed - risk in unexposed)/(risk in exposed)

Increased incidence of pseudoprogression after TMZ + RT found in +/- MGMT methylation?

+ MGMT methylation (66% of MGMT pts) 30% of all patients will have pseudoprogression Essentially you only know it is pseudo if subsequent scans look better. Can use MR spect for this - increased lactate, decreased choline = radiation necrosis - recurrence = increased cholin, decreased creatine

General Treatment paradigm for the following SM scores - 1-2 - 3 -4-5

- 1-2: Embolization + Surgery - 3: Embolization + Surgery if good ECOG; SRS if bad ECOG -4-5: If no prior bleed - can argue to obs; If prior bleed = SRS

Brain mets from SCLC -- - how many have brain mets at diagnosis? - 2 yr incidence? - how much does PCI decrease it by? - PCI have survival advantage?

- 10-15% have brain mets at diagnosis (~2/3 are ES at diagnosis though) - 2 yr incidence more like ~60 Auperin Meta-analysis data: - PCI decreases incidence of brain mets nearly by half (3 yr 33% vs 59% in one study) - About a 5% OS advantage to PCI (21% vs 15%) in LS setting (slotman data showed slight advantage in ES, but other studies don't) NOTE: Old trails, brain imaging was not required so they may have been treating some brain mets that they didn't know about -- thus you would see an RT benefit.

Small Cell Lung Cancer - what % of lung cancer? - mutation examples? - differences in workup? - definition of limited vs extensive stage? - early stage role for SBRT and surgery?

- 15% of lung cancer. --99% are smokers, centrally located, 30% have limited stage, most have ES-SCLC (high rates of mets at presentation) - mutations: Rb LOH (13q abn), 3p delection, N-myc, C-myc, KIT, etc. Brain imaging required for any stage SCLC - small round blue cell tumor - high ki67 Limited stage = 1/3 of cases - encompassed in one tolerable port - controversial: SCV, contralateral LAD, pleural effusion Extensive stage 2/3 of cases - mets outside of chest For very early stage there are actually some surgical series that look at lobectomy for T1-2 tumors. Lobectomy w/ MLND technically still preferred in these cases --> but chemo always given adjuvant regardless. SABR actually can be considered for early stage inoperable. But they still get chemo after.

Dutch Trial - Red Journal 2003 - POST-op based on positive CRM - 120 pts in TME arm of the Dutch trial had a CRM+ - 74 pts had post-op XRT (50.4 Gy) - results?

- 2 yr local recurrence not different compared to no post op XRT --> no XRT 15.7% --> XRT 17.3%

RISK -Annual risk of bleed from AVM? -Chance of death at each hemorrhage? -Lifetime chance of a bleed? -More common to have hemorrhage in children or adults? -Small or large vessels more likely to hemorrhage? - Other major predictors for bleed risk?

- 2-4% annual risk; increases once bleed happens - Death = 10-15% risk with each bleed - Lifetime chance of bleed = 105 - age -More common to have hemorrhage in children -Small vessels more likely to hemorrhage Other major predictors for bleed risk: - Prior hemorrhage, seizure, deep draining vein for AVM, exclusive deep venous drainage - smaller AVMs - HTN (avoid contact sports or heavy lifting) - Prior hemorrhage is the BIGGEST RISK FACTOR FOR ANOTHER BLEED ----> first year after hemorrhage, risk increases to 7% from 2-4%, in the first year, then goes to 2-6%/yr - SEIZURE is also bad - almost as much increased risk following seizure presentation as if they had a bleed

RTOG 0424 - p2 study, 129 pts w/ 3 or more risk fators (age >40, bihemispheric, pre-op tumor diameter of 6 cm or more) - RT 54 Gy in 30 fractions and concurrent and adjuvant TMZ - results?

- 3 yr OS was 73.1% statistically improved compared to historical controls of RT alone - this data is why we say TMZ concurrent/adjuvant is a 2B recommendation No prospective R3 controlled trial Not many people actually do concurrent TMZ in LGG, some may do adjuvant

MGMT methylation - found in what % of LGG and HGG? - mechanism? - predicts what? - what effect on OS?

- 30% of both HGG and LGG - MGMT is a DNA repair enzyme -- it removes damage -- removes alkyl group from O6 guanine When MGMT promoter is methylated the repair enzyme isn't made and DNA damage done by alkylating agents like TMZ can't be repaired --> cancer death - MGMT methylation is GOOD -- improves OS regardless of treatment (most predictive of response to TMZ) TMZ is a pro-drug that is converted to MTIC (active drug) methylates DNA that promotes single and double stranded DNA breaks -- it is an alkylating agent.

Oropharynx - rate of occult node? - mechanism of p16 positivity? - rate of p16 positive?

- 30-50% = occult node - Activates E7 → Turns off Rb → ↑ p16 (see rad bio lecture 08) - 40-80% positive E6 --> interacts with p53 - causes degradation E7 --> interacts with Rb - inhibits positive growth regulation -- rb binds to E2F transcription factor --> interacts w/ DNA synthase for S phase progression. E7 binds to Rb to release E2F which allows movement through G1 without regulation -- this is what leads to p16 upregulation

British Columbia data - RCT for PMRT: - how many and what women included? - surgery? - chemo? - LRR decrease by PMRT? - what OS benefit at 10 years? subset analysis looked at 1-3 nodes and 4 or more nodes -- what did it find?

- 318 pre-menopausal women - 1 or more positive nodes got modified radical mastectomy and had median of 11 lymph nodes removed. - chemo was CMF (old chemo) - RT was old (cobalt, 37.5 Gy to RNI, 35 to IMNs) - radiation was PMRT CW/RNI + IMNs vs obs - LRR 26 --> 10% - OS = 10% OS benefit at 10 years OS benefit was seen in both 1-3 and 4 or more LN groups -- data doesn't separate 1 vs 2 or 3. High local regional failure rates -- criticized because of older chemo and older surgery.

Canadian Wheelan Hypofractionation (NEJM 2010) - dose? - inclusion? - pt characteristics? - outcomes?

- 4256 cGy / 16 fractions - RCT, n=1234, T1-2 invasive breast cancer, ANY AGE, pN0, negative margin, breast maximum width of 25 cm - pt characteristics: 25% <50 years old, 20% T2, 19% grade 3, 71% ER+, 11% chemotherapy, 41% HT, 48% none Long-term update HF CF - excluded large breasted women (used separation distance >25 cm -- was done to minimize hot spots), but didn't use more modern techniques to improve homogeneity - nurse evaluated cosmesis HF CF 10yr CI LF 6.2% 6.7% NS 10yr IBTR 7.4% 7.5% NS G3 15.6% 4.7% SS 10yr OS 85% 84% NS Subgroup: similar regardless of age, size, ER status or use of systemic therapy - "patient reported" outcomes (nurses) for cosmesis -- same as CF. CI = cumulative incidence A later secondary analysis showed no difference with respect to grade. Wheelan didn't do boost, but some people do 4 fraction 2.66 boost.

Endometrial cancer - how common? - risk factors? - protective factors? Life type risk of endometrial cancer is Lynch Syndrome + = ?

- 4th most common in women - obesity, nulliparity, tamoxifen, diabetes, unopposed estrogen - protective: breast feeding, smoking, physical activity - genetic risk = lynch syndrome (due to mutation in mismatch repair genes) - lifetime risk of 40-60% ---> Lynch syndrome endometrial cancer typically diagnosed YOUNGER than sporadic Excess estrogen is a huge risk factor!!! -- BMI is more significantly associated w/ risk of enodmetrial cancer than essentially any other cancer affecting women. Very important to point out microsatellite instability genes for endometrial cancer

PORTEC 2 - given that 75% of recurrences were in vaginal cuff --> can we just do cuff brachy - TAH/BSO (no LND) --> VBT (21 Gy in 3 fractions HDR or 50-70 cGy/hr for LDR) vs WPRT - what was the main differences between failures in those arms? - what was the rate of vaginal recurrence in those treated with VBT? - what is the interpretation of the high rate of pelvic nodal treatment in the VBT arm?

- 5 yr pelvic recurrence SS lower in WPRT vs VBT (10 yr 0.9% vs 6.3%) -- remember NO LYMPH NODE DISSECTION -- all surgeons now do PLND or SLNB for high/intermediate risk. - NS difference in 5 yr vaginal recurrence, 5 yr LRR (vagina/pelvis), distant mets VBT vaginal failure = 3.4% compared to 2.4% w/ EBRT (NS) Since NO LYMPH NODE DISSECTION was done -- this makes it possible that some of these patients actually were n+ at time of surgery but we weren't checking. If we knew that, they would have gotten EBRT. Now with PLND or SLNB we would know which ones are positive/negative and if negative can offer VBT probably with lower rate of pelvic failure. Toxicity better in those getting VBT than WPRT.

Cervix treatment timeline - what timeline do you need to complete all therapy? - why is this important?

- 8 weeks -- generally 5 weeks EBRT followed by brachy boost w/in 3 weeks after finishing Survival is WORSE the longer you take to complete therapy - 5 yr OS - 8 weeks - 65% - >10 weeks - 52%

LGG - patterns of failure? - rate of transformation/higher grade at recurrence?

- 80% local, 5% marginal, 10% out of field, 1-2% leptomeningeal - 70% are transformed at recurrence

Lymph Nodes in Vulvar Cancer Sentinel Lymph Node Biopsy - GOG173 - aimed to determine the NPV of SLNB - pIII, validation trial - eligible if clinically node negative and limited to the vulva measuring 2-6 cm - results?

- 92.5% of pts had at least 1 SLN identified at surgery - Sensitivity = 91.7% NPV was lower in tumors <4 cm

Craniopharyngioma - rare, benign neoplasm (2/100,000) - bimodal distribution (55% children, 45% > 20 yrs) - remnants of the Rathke's pouch - histologic types? other buzzwords? - MRI features? - symptoms? - treatment? - imaging during treatment? What to do if they develop symptoms? - dose of RT?

- Adamintomatous type (more common in kids) - WNT abnormalities, papillary squamous type (BRAF V600E), mucoid epithelial - crank case oil - cholesterol laden fluid, calcifications - T1 hyperintense, contrast enhancing, T2 variable, solid with cystic component - endocrine dysfunction, obstructive hydrocephalus, altered growth, diabetes insipidus, visual field defects, cognitive and behavioral changes - upfront surgery - DO NOT go for GTR (this leads to excess morbidity/mortality (up to 4-17%) -- STR + RT has equal control to RT and less morbid. STR alone has ~85% recurrence rate - LC of STR+RT = 80-90% at 10 yrs RT can be alone or post-STR - important to surgically decompress the cystic component to decrease dose to normal brain - timing should be immediately after surgery. If peds case <3 yrs, defer RT to allow brain development. Most adults often treated at recurrence as well though. - remember the frequency of cystic change during treatment -- if symptoms develop get MR immediately and replan. --- 24% of pts will have growth of cystic component outside of treatment field during treatment --- MRI recommended q1-2 weeks while on treatment. --- 35% of pts will require some treatment intervention while on RT (re-draining cyst, replanning RT, etc). 1/7 (14%) will require a replan. RT Dose = 50.4 - 54 Gy (we do 54). SRS ~12.

PROFIT - design type? - randomized 1206 men to IMRT (preferred) to 3D 78Gy/39 fractions vs 60 Gy/20 fractions - BFFS diff - toxicity diff

- BFFS was the same on both arms (all hypofrac studies) - GI toxicity was not THAT different - acute short term GI tox was a little worse in hypofrac (16% v 10%) but late GI tox was actually worse in conventional frac (9 % v 16%) hypo v conv. Not sure why standard fract had worse late tox. Note about PROFIT constraints: D50 <37 Gy, D30 <46 Gy -- tough on is that none of the rectum is suppose to get 60 Gy which is tough since the rx is 60 Gy - this is why we do rectal spacer when doing PROFIT dose.

Hypofractionation - major four papers - guidelines say you should do this in what risk groups?

- CHiPP, PROFIT, RTOG 0415, and DUTCH HYPRO study - do this in all risk groups -- essentially very little role for 44 fraction anymore (maybe when you need dose escal and can't tolerate brachy boost, diabetes/IBD issues that hypofrac might worsen bowel outcomes) HYPRO study is actually better 5 yr PFS (~13% better) but worse acute G2+ GI and late G3+ GU in hypofrac arm. SUMMARY CHHip = 60/20 (most int, ~12% high risk) - worse acute GI; PROFIT = 60/20 (100% int) - worse acute GI G2+, better late GU G2+ (random, opposite hypro study) RTOG 0415 = 70/28 (100% low risk pts) - increased late G2+ GI/GU with hypofract HYPRO = 64.6/19 (74% high risk, 26% int) - worse acute GI/late GU control arms were 37-41 fractions Note: meta-analysis of 9 studies including these 4 showed no diff in cancer outcomes, worse acute G2 GI and no difference in late GI/GU outcomes over all.

ECOG 1308 - 3 cycles of induction cis/paclitaxel and cetuximab - Clinical CR - gets 54 Gy + Cetuximab - <CR --> gets 69.3 at 2.1 Gy + Cetuximab results?

- CR rates = 70% - early results show PFS 91% vs 87%

Contents of: - Cavernous sinus - Superior orbital fissure - Foramen Rotundum - Foramen Ovale - Foramen Spinosum - Pterygopalatine fossa - Meckels cave - foramen lacerum - Internal Auditory Meatus. - Dorello's canal - Stylomastoid foramen - hypoglossal canal - jugular foramen Describe the course of the facial nerve?

- Cavernous sinus = III, IV, V1/V2, VI -- note: NOT V3 and all go through the superior orbital fissure except V2 (its in Rotundum) - Superior orbital fissure = V1, III, IV, VI - Foramen Rotundum = V2 - Foramen Ovale = V3 - Foramen Spinosum = Recurrent meningeal nerve of V3, middle meningeal artery/vein - Pterygopalatine fossa = V2, Petrosal nerves, Maxillary artery - Meckels cave = Trigeminal ganglion - foramen lacerum = Greater petrosal nerve, cartilage of eustacian tube (+ascending pharyngeal artery) - Internal Auditory Meatus = CN VII and VIII - Dorello's canal = CN VI - Stylomastoid foramen = CN VII - hypoglossal canal = CN XII (runs out of the base of skull through the hypoglossal canal on the lateral aspect of the foramen magnum and immeidately joins the bundle running out of the jugular foramen) - jugular foramen = IX, X, XI, inferior petrosal sinus and transverse sinus join to make internal jugular vein inferiorly Facial nerve exits from brainstem through IAM along with VIII in the petrous bone. Takes a turn anterior to geniculate ganglion. Then runs inferiorly until it exits in the stylomastoid foramen (also runs just lateral to the cochlea and semicircular canals through the facial nerve canal -- pictured above)

NCDB data surgery alone vs surgery and adjuvant tx - 1574 pts w/ T1-2 SCLC - all got surgery , 954 w/ R9 resection - adjuvant chemo given to 59% - results? multi-institutional data for SCLC SABR - 76 pts -- LC is excellent 97%, median OS is 3 yr 34% Thoracic RT in SCLC - Meta-analysis data of 13 trials and 2140 pts with LS-SCLC - outcomes?

- Chemo improved OS significantly based on NCDB data - local control 25% improved with RT - 5% OS benefit (20 v 15%)

Important dose constraints - Chiasm - Temporal - Retina - Cochlea - Brainstem - Parotid mean - Larynx - Spinal cord - Brachial plexus - pharyngeal constrictors

- Chiasm = max point <55 - Temporal = max point <55-60 - Retina = max point <45 - Cochlea = max point <45 - Brainstem = < 60 Gy allowable, strict guidelines < 54 Gy - Parotid mean = mean <26 Gy or V30 <50% - Larynx = V50 < 30% - Spinal cord = <45 if chemo; maybe a bit higher <50-55 if RT alone - Brachial plexus = <66 Gy max point dose - pharyngeal constrictors = ideal <50 Gy if near target mean dose, ideally <40 if far from target

Pancreatic Cancer - 85% is adenocarcinoma Rick Factors? Oncogenes involved?

- Chronic Pancreatitis - Diabetes - smoking - obesity - Partial Gastrectomy/Cholecystectomy - h pylori - hereditary syndromes - ipmns and pancreatic cysts Oncogenes - KRAS Tumor Suppressors - inactivated - p53, p16, SMAD4, BRCA2, MLH1, MSH2

LungART trial - 89% got 3D-conformal, 11% IMRT - mostly lobectomy - allowed neoadjuvant/adjuvant chemo (>80% got adjuvant chemo) - randomized to control vs PORT after surgery (96-98% had pN2 dz) - results? - specifically what outcome WAS better with PORT? Take home?

- DFS was NOT improved (HR 0.85, NS) with PORT compared to - OS was no different Lung ART excluded positive margins. Mediastinal relapse was lower with PORT (25% vs 46%) but DEATH WAS HIGHER WITH PORT. G5 tox was higher in PORT (1.2% v 0%) Death from cardiopulmonary causes was higher in PORT. Death from progression of cancer was lower with PORT. This suggests that the patients died from the radiation treatment. Take home: - pN1/2 and can get chemo --> NO PORT - pN1/2 and can't get chemo --> PORT (45-50.4 Gy) - microscopic positive margin --> seq chemo -- then PORT or chemoRT (54 - 60 Gy) - post-op gross dz = 60 Gy chemoRT is that you can consider PORT for pN1/N2 if they can't get chemo or still do chemoRT for positive margin. Also may consider for pN1 if they can't get chemo.

RADIATION FOR ACOUSTIC NEUROMA Fractionated SRS (GK extend/ICON) - Dose? - hearing preservation difference between this and SRS? - hearing preservation %? Protracted Linac Based Fractionated EBRT - Dose? -% hearing preservation - problem with this compared to SRS or fractionated SRS?

- Dose = 20 Gy/4 fx - hearing preservation difference between this and SRS = great option if the person has serviceable hearing - ~80% hearing preservation - Dose = 50.4 Gy /28 fx; @1.8's to 54 Gy - 80% hearing preservation (around same as frac SRS) - problem is the potential for cognitive toxicity (memory loss d/t proximity to hippocampus) - 95% CNVII preservation; CN V preserved

GYN CANCER CARDS Major sites to think about for Rad Onc: - Endometrial - Cervical - Primary vaginal - Vulvar

- Endometrial - Cervical - Primary vaginal - Vulvar No so much involved in ovarian; however this is a radiation sensitive histology, its more that the ovary is mobile and we can't target it at that point in the pelvis given significant bowel in that area.

Wilms Tumor RT doses - Flank: __ ---> boost to __ if diffuse anaplasia/rhabdoid tumor ---> boost gross residual disease +1 cm w/ another __ (__ Gy total) - WAI: ___ -- if diffuse unresectable peritoneal implants OR Diffuse anaplasia OR rhabdoid = __ - WLI: ___ (<12 months, gets ___) Probably won't ask these - Whole brain: ___ if <5 mets - Whole brain: ___ if >5 mets - __ for bone mets For WAI what can you do to improve N/V and bowel toxicity?

- Flank: 10.8 @1.8's for FH ---> boost to 19.8 if diffuse anaplasia/rhabdoid tumor ---> boost gross residual disease +1cm w/ another 10.8 Gy (21.6 Gy) - WAI: 10.5 @1.5's; diffuse peritoneal = 21 Gy - WLI: 12 Gy @1.5's (<18 months, gets 10.5 Gy) - 21.6 Gy @1.8 Gy whole brain (if <5 mets) - 30.6 Gy @1.8 Gy whole brain (if >5 lesions) - 25.2 Gy @1.8 Gy for bone mets Pre-medicate with Zofran and use slow dose rate prior to treatment. Dose reduce doxorubicin by 50%

Meningioma radiation control - Grade 1 = STR + RT = LC of __ - Grade 3 = GTR + RT = LC of __, GTR alone = ?

- Grade 1 = GTR Simpson 1 = LC of 90% - Grade 1 = STR + RT = LC of 90% - Grade 3 = GTR + RT = LC of 80%, GTR alone = 55%

CATNON trial - non-1p19q codel anaplastic glioma - p3, 748 pts randomized - started with RT vs RT + concurrent TMZ vs RT + adj TMZ vs RT +conc./adj TMZ - interim analysis showed what?

- HR reduction for improved OS with adjuvant TMZ (0.645, SS) - MGMT status was known for 74% of pts and 42% were methylated - MGMT methylation was prognostic for OS (HR 0.54, SS) but did not predict for improved response to adjuvant TMZ - for PFS, the risk adjusted HR for adjuvant TMZ was 0.59, SS Conclusion - 12 cycles of adjuvant TMZ improved OS in anaplastic glioma w/o 1p19q codel

Genetics - what history is important? Criteria to get genetic consult?

- Hx of ovarian cancer. - Breast cancer <50 - TNBC < 60 years, - two BC primaries in a single individual Breast cancer +: - >1 blood relative with BC <50 - >1 blood relative w/ ovarian cancer - >2 relatives with Bc, prostate, or pancreatic cancer - increased risk populations -- Ashkenazi jew Blood relative: 1st, 2nd or 3rd degree

Unknown Primary - Management?

- If primary identified, treat as that primary. Otherwise, treat based on nodal stage group: --N1 = if just 1 node and lvl 1-4 dissected, close follow up alone may be appropriate. Failure rate ~15% after neck dissection alone. If only excisional biopsy done, needs RT. --N2-N3, (+) ECE, (+) margin, or if had excisional/incisional bx without full neck dissection: Don't start with a neck dissection for these (Lvl 2 evidence saying neck dissection + CRT was not better than just starting with definitive CRT [Balaker Laryngoscope 2012]) Definitive ChemoRT alone RT to the most likely mucosal sites: NP, OP and bilateral neck 70 Gy to gross disease 63 Gy to high risk nodal regions 56 Gy to mucosal axis and low risk nodal regions If HPV +, consider omitting NPx if lvl 1a/1b then tx OC and OP, exclude NPx hypopharynx, larynx consider adding if level III,IV LN+ --CRT for +ECE, N3 disease, bilat disease

Screening - PLCO study - American Study - prostate lung, colorectal and ovarian cancer study - prostate study looked at ~76,000 men randomized to PSA screening x 6 years and DRE x 4 years vs control of usual care and no planned PSAs. - who got PSAs drawn anyway? - how many more detected in exp arm? - did this affect survival?

- In screening group - 85% got PSAs. In control group, 52% still got PSAs. - 22% increase in rate of PCa diagnosis. - DID NOT affect survival. No cancer specific survival difference.

RTOG 0236 - Bob Timmerman study - 72 pts, 60 Gy in 3 fractions (no heterogeneity correction) - results? - what was 5 yr involved lobe and local-regional failure rates?

- LC of 97.6% initial results, 93% in 5 yrs. - LRC 87.2% initial results, 36% failure in 5 yrs - OS 55.8% - DM rates of 24% (same as with surgery) Note: 5 yr rate of involved lobe failure (20%) and local-regional failure (36%) Regional lymph node recurrence is the highest site of recurrence after SBRT accord to Steven Lin.

MR Fusion Biopsy - Trio study - - what does MR fusion add to sensitivity of prostate cancer - specifically what is the benefit of MR added to systematic biopsy in terms of what types of prostate cancers are detected?

- MR adds about 10% likelihood of picking up cancer but specifically MR increases the likelihood of detecting "clinically significant prostate cancer" -- which means non-GG1 cancers. Things like higher ADC/DWI signal indicates more tightly packed cells so this is why MR can detect clinically significant prostate cancers.

IMPRINT Trial - phase II, n = 45 - MDACC and MSKCC - P/D followed by IMRT 50.4 Gy to a rind of pleura and sparing lung - results?

- NO grade 4/5 toxicity survival is med 23.7 and PFS 12.4 if resectable, 2 yr OS 59% if unresectable, 2 yr OS 25%

Unknown Primary - Would you do PET before or after panendoscopy? - What is yield of PET scan to detect primary? - Cystic appearing LNs on CT suggest what? - Sites to biopsy on panendoscopy?

- PET before -- inflammation from surgery would give false positive. - PET yield = ~30%, high rate of false positive (danish data) - Cystic appearing may suggest p16+ - The NearBy Suspicious Points = Tonsil, NPX, BOT, Suspicious areas, Pyriform sinus (Tonsillectomy improves sensitivity over just biopsy - unilateral/bilateral more controversial)

Rhabdomyosarcoma - Special Cases - Paratesticular tumors --> how are these removed --> if >10 yrs, what needs to be done? - rt done? - Bladder = ? - Intracranial extension = ? - Vaginal/vulvar = ? - Orbital = ?

- Paratesticular tumors --> Tumor removed by inguinal orchiectomy and resection of the spermatic cord. If >10, you need to do a RP lymph node dissection -- not usually treating unless they had positive nodes - PA field (not scrotum typically) - Bladder = chemoRT to attempt bladder conservation - Intracranial extension = consider treatment day 0 - has sort of fallen out of favor but used to be done more as sort of emergent treatment. This is more historical - Vaginal/vulvar = chemo, 2nd look wk 28, no RT if negative - Orbital = biopsy --> chemo --> 45-50.4 Gy (CR/PR)

Special situations for dose Elderly >65 yo - Poor PS = ? - Good PS = ? - tx volume = ?

- Poor PS = 40.05 Gy/15 fxn WITHOUT temodar -- according to Ryan, more recent studies show you can do 40/15 + TMZ even with bad PS- Good PS = 40 Gy/15 fxn WITH temodar- tx volume = T2 flair only, no boost or expansion ROA study

Anal cancer - what to do in the following situations after local excision - R0 --> - AIN3 at margin --> - R1 with invasive cancer at margin

- R1 with invasive cancer at margin --> single modality RT is essentially if you were excising AIN and you find microinvasion -- not entirely clear this is what everyone would do -- Hanna says go to 40 Gy in 15 to anal canal and nodes to 30

LGG - risk factors? - types? - genetics? -->What is most common? -->dominant prognostic factor for olgiodendroglioma? - what proportion of these transform to GBM?

- RF: NF, lack of allergies G1: JPA, Pilocytic astrocytoma, Subependymal giant cell tumor G2: Diffuse astrocytoma (ATRX better prog), oligodendroglioma (1p19q codel), oligoastrocytoma Genetics - MOST COMMON: LOH17p (TP53 gene located here) - IDH1 mutation (80% LGG, 15% HGG) - oligo, IDH2 - astro - MGMT methylation - predicts better TMZ response, ~30% (same as hgg) - 1p19q = DOMINANT PROG for OLIGODENDROGLIOMA MOST transform to GBM (~80%) --> these people are often not cured, they just live a long time and then eventually transform

Liver SBRT vs RFA - U. of Mich Study - looked at SBRT with larger tumors. - size correlated with local failure with which modality? - improved FFLP with SBRT for tumors of what size?

- SIZE correlated with local failure with RFA but NOT SBRT - specifically 2 cm was the cuttoff where there was improved freedom from liver progression for SBRT (SS) No diff in OS or g3 tox

NSCLC - Early stage (I-II) - SOC? - borderline operable? - medically inoperable?

- SOC = surgery - borderline operable = tend to lean toward SBRT - medically inoperable = SBRT is SOC

Screening - ERSPAC study - European men - ~160,000 men randomized to obs vs variable practice of screening but usually some sort of PSA+DRE where PSA >3 or abnormal DRE --> biopsy - who got PSAs drawn anyway? - what was finding and major diff from american study?

- Screening group - 82% got PSAs and control only ~20% (so not as many had PSAs drawn anyway like in america). - Found HR 0.80, p 0.01 screening DID reduced PCa death (214 vs 326). More gleason 6 or less found in screening group compared to obs (72% v 55%); - Major diff is that the control group wasn't getting PSAs checked like the american study where the control was getting checked anyway at a pretty high rate

CNS Constraints -- 1.8 Gy/fxnDose tolerance per fraction --> Total --> Risk - Spinal Cord - Brainstem core - Brainstem surfance - Optic chiasm - Optic nerve - Retina - Lens - Cochlea

- Spinal Cord = Dmax 50 Gy or less (generally <45 if chemo) - Brain = whole brain 50 Gy, partial brain 60 Gy, temporal lobe 70 Gy (according to osler course) - Brainstem = 1.8-2 Gy --> Dmax < 55 Gy, 55-60 Gy "Acceptable" (only go here if pushed to accept higher dose to cover target better for malignant things); one fraction max <12.5 Gy - Brainstem surface = ventral 3 mm of brainstem from 9 O clock to 3 O Clock - Dmax <55 Gy, 55-64 Gy "acceptable" - Optic chiasm = 55 Gy, 55-60 acceptable; <8 Gy one fraction - Optic nerve = 55 Gy, 55-60 acceptable; <8 Gy one fraction - Retina = Dmax = 45 Gy, 45-50 acceptable - Lens = Dmax <7 Gy, 7-10 acceptable - Cochlea = Ideally one side mean <45 Gy (one fraction cochlea dose 4.2 Gy) - Lacrimal gland - Dmax = <40 Gy - Pituitary gland - Dmax = <50 Gy

General treatment paradigms for mesothelioma: - Best? how often is this possible? - otherwise what do you generally consider? - do you ever do concurrent chemo?

- Surgery best if resectable (only 5% of cases are resectable) - options: EPP, pleural decortication, talc pleurodesis If N(+) do not offer surgery (instead → palliative combo chemo) Aggressive surgery alone even in carefully selected pts has not improved 2yr OS (10-30%). Combined modality → improved LC and survival rates (LR still most common site of relapse). All pts that can tolerate PORT should get it after EPP, no RT after pleurectomy/decortication though Induction chemo OR adjuvant (not both) can be considered for all patients stage I-III operable --> re-eval with CT. - if stage IV or sarcomatoid = consider chemo alone. NO CONCURRENT CHEMO -- field is huge and you would kill them.

Unknown Primary - T stage? - Most common presentation of unknown primary HN cancer? - Standard workup? - What % of HN cancers are unknown primary? - What % is the primary site eventually identified? - Most common site of primary? - When to consider NPX?

- T0 by definition; Tx would mean no workup done - Painless neck mass Workup: - Physical exam - FNA of involved LN (HPV/p16 can be strong predictor of OP as primary site; EBV - NPX) - PET/CT scan - Thyroid/neck CT w contrast; CT CAP +/- MR head/neck - Panendoscopy - typically with BOT biopsies/Nasopharynx biopsies - Surgically -- often will get b/l tonsilectomies - Skin exam 3-5% of HN cancers 40-50% of primaries identified eventually - Most common site: BOT or Tonsil (~80%) - Consider NPX if junctional or Lvl 5 node - near skull base -

What do you need in order to be a candidate for larynx preservation?

- T1-T3 larynx cancer with a FUNCTIONAL larynx (need to be able to breathe and swallow) - UF criteron for tumor volume <3.5 cc with no airway compromise to qualify for larynx preservation

Vulvar staging - size <2 cm vs >2 cm - any stromal invasion >1 mm? - any size with extension to adjacent perineal structures (lower 1/3 urethra, vagina, anal involvement) - any size extending to upper 2/3 urethra/vagina, bladder, rectum or fixed to pelvic bone - what is T4? - nodes? IIIA, IIIB, IIIC, IVA - what node counts as IVB (distant mets)

- T1a is <2 cm; T1b is >2 cm w/o extension to structures below - any invasion >1 mm is at least T1b - any size with extension to adjacent perineal structures (lower 1/3 urethra, vagina, anal involvement) = T2 - any size extending to upper 2/3 urethra/vagina, bladder, rectum or fixed to pelvic bone = T3 - what is T4 = there is no T4 NODES = FIGO III - size is hard to remember, make sure you know the extreme ones -- ENE = N2c and ulcerated = N3 - IIIA -----1a: 1-2 nodes <5 mm (N1a) -----1b: 1 LN >5 mm (N1b) - IIIB --> ------3 LNs <5 mm (N2a) ------2 LNs >5 mm (N2b) - IIIC --> LNs w/ ENE (N2c) - IVA --> fixed, ulcerated LNs (N3) - pelvic nodes are NON-regional (thus metastatic; IVB) OVERVIEW T1a (IA): ≤ 2cm, confined to vulva/perineum, ≤ 1mm stromal invasion T1b (IB): > 2cm, confined to vulva/perineum, any size with stromal invasion >1mm T2 (II): any size, extension to adjacent perineal structures (lower ⅓ urethra/vagina or anal involvement) T3 (IVA): any size, extension to upper ⅔ urethra/vagina, bladder, rectum, or fixed to pelvic bone Nodal laterality doesn't matter -- only size and number.

Mediastinal germ cell tumors - 10% of mediastinal - 1-3% of germ cell tumors Where do these come from? Most common subtypes?

- These are not "metastases" from testicles - malignant transformation of germinal nests They are histologically comparable to testicular/gonadal type tumors Benign teratoma - 60% of mediastinal GCT Seminoma, 30% of malignant GCTs Malignant GCT - typically present with chest pain, cough, SVC sydnrome, etc Benign tumors usually identified incidentally on imaging

Treatment - T1N0 - Tis, T1a or T1b = ? If LVSI/high grade/positive deep margin/submucosal --> ? If LNs+ suspected on EUS --?

- Tis, T1a or T1b = endoscopic resection (EMR - endoscopic mucosal resection) or submucosal resection (ESR or ESD) If LVSI/high grade/positive deep margin/submucosal --> surgery if medically operable, definitive XRT in medically inoperable (chemo NOT indicated) OS affected by mucosa vs submucosa involvement - mucosa - 1,2,3 yr OS --> 95, 90, 90% - submuc - 1,2,3 yr OS --> 90, 81, 70% If LNs+ suspected on EUS --> then definitive or preoperative chemoradiation Several studies show equalivence of surgery to ChemoRT for T1N0 disease

CREST Study - Ben Slotman study - 498 pts - ES-SCLC who responded to chemo - randomized to 30/10 w/ 3D or 2D RT - all got PCI - primary endpoint was OS at 1 yr - results?

- Trial did NOT meet its primary outcome because OS wasn't significant at 1 yr but it WAS significantly different at 2 years. - 1 yr: 33 v 28% OS (NS) - 2 yr: 13% v 3% (SS) PFS improved by 6 months (24 v 7%, SS) This is palliative RT and local recurrence can happen. Thought would be there may be a benefit to dose escalation

SABR for operable tumors - Uematsu - 50 pts, med fu 36 months - results? - Onishi - 257 pts, med fu 38 months - results? Important comparison to look at survival in stage IB pts that all got surgery +/- adjuvant chemo -- - CALGB 9633 - all stage IB -- results?

- Uematsu - 50 pts, med fu 36 months - 3 yr OS 86% - Onishi - 257 pts, med fu 38 months - 3 yrs OS 80%, 5 yr 71% Survival seen in these two Japanese series is actually better than any surgical series of similar patients. Good example is CALBG 9633 - CALGB 9633 - all stage IB --> control 3 yr OS 73% (5 yr 58%) --> adj chemo 3 yr OS 80% (5 yr 60%) - 3 yr SS, 5 yr not SS - showed benefit to adj chemo for tumors >4 cm (T2b, stage II) -- note: specifically at 3 yr - important point is that 3 yr OS was actually better in Japanese SABR studies in operable patients than the control group -- actually as good or better as surgery + chemo in 9633

Oropharynx General Tx Paradigms - general upfront approach?

- Unlike OC, OP is a situation were definitive RT or definitive Chemo-RT can certainly be considered as sole therapy. - If in an area with an active group of surgeons, the role of TORS and talk of using surgery to decreasing need for either post-op treatment as an option is more common. In those cases, they say you may not need RT or possibly may avoid chemo and only have to do RT if surgery is done (say you know you have 2 nodes on imaging, so you know you will have to do RT, but if no + margins or ENE, you won't have to do chemo)

N0574 - 1-3 cerebral mets - P3 randomized trial of SRS +/- WBRT - 213 pts, med age 60 - lung primary most common - clinical progression was >1 SD decline in baseline from any of 6 neurocognitive tests - results?

- WORSE immediate recall, delayed recall, verbal fluency -- all SS - intracranial tumor control at 6 and 12 months --> SRS alone: 66 and 50.5% -->SRS+WBRT: 88.3 and 84.9% Median OS HR 1.02, NS Conclusion thus = decline in cognitive function is significantly worse with WBRT and thus SRS alone is better even with worse intracranial tumor control. You can just salvage other failures with SRS

Lymphatic dissemination in anal canal - above dentate line --> - below dentate line -->

- above dentate line --> mesorectal and internal iliac - below dentate line --> superficial inguinal and external iliac Hematogenous spread to liver is most common > lung

T3N0 - what to do with these patients?

- bascially all retrospective/SEER type data that looks at this specific subtype. - this is a nuanced state that depends on other patient specific factors (age, LVSI, etc) - most people wouldn't do PMRT for T3 as a sole indication There is some data for and some data against it. SEER analysis (2008) - says it benefits women over 50 another SEER (2014) - says it improves OS and CSS - low grade and martial status were predictors of CSS...wut NCDB (2017) - OS benefit of about 8% at 10 yr

Partial breast irradiation - thought process? - in what patients might this be appropriate?

- can treat less breast tissue and deliver it over a smaller period of time (1 day (iORT) - 2 weeks - given bid, also can do interstital brachytherapy/mammosite). Makes sense since the majority of recurrences are in the tumor bed (80-90%) - may allow patients who have had BCT before to undergo BCT again if they have large enough breast. The problem is that mostly the cosmetic outcomes have been worse. Basically you can only consider PBI in the LOWEST risk people: - Age >= 50 yrs - T1 disease with margins of at least 2mm - for DCIS—screen detected, low to intermediate grade, size <=2.5 cm, margins of at least 3 mm. Cautionary criteria: - age 40-49 yrs - patients >=50 yrs with the following: size 2-3 cm, T2 (2-5 cm) - margins < 2mm for invasive disease, limited or focal LVSI, ER negative, invasive lobular disease, EIC <=3 cm, DCIS <3 cm not meeting the requirements for suitable group. considered unsuitable: Patient age <40 yrs positive margins DCIS/IDC> 3cm Problem with IORT is that it is delivered at time of lumpectomy and you don't know anything about the tumor pathology at that time including markers, margins, etc -- so if you find that they aren't good candidates, you may have to bring them back for additional treatment. PBI: - Margins 1.4-2 cm, Ratio PTV/breast <20%

Meningioma Pathology - classic histology - grade - path characteristics of grade

- classic histology (benign) = whorls, psammoma bodies - grade 1 (benign), 2 (atypical) or 3 (malignant) - path characteristics of grade Grade 1 = BENIGN = ~80-90% - Whorls, psammoma bodies - <4 mitoses/10 HPF Grade 2 = ATYPICAL = ~10-15% - Clear cell - choroids - 4-19 mitoses/10 HPF -≥ 3 of the following: Increase N:C ratio, Prominent nucleoli, Sheet like growth, Necrosis, Brain invasion by itself - Atypical OS = 12 yrs Grade 3 = MALIGNANT = ~5% - papillary-perivascular, psuedopapillary pattern, Rhabdoid or Anaplastic - 20 or more mitoses/10 HPF or frankly malignant cells - Malignant OS = 3.3 yrs

Follicular Lymphoma - management of early stage, low grade? - what is the most common pattern of failure after therapy? - what is the coverage called? - what is freedom from tx at 10 yrs an what is OS?

- definitive RT - 24 Gy - preferred for stage I and contiguous stage II - most common site of failure = DISTANT relapse outside of RT fields - RT fields are "generous involved site" - understanding that no systemic therapy is given - 10 yr freedom from treatment = 56% - 10 yr OS = 85% Can consider OBSERVATION in selected patient due to indolent nature - so if they have lots of other comorbids.

Pituitary adenomas - adenomas most common pituitary tumors - usually benign but can be invasive. Carcinomas rare (0.1-0.2% of pituitary tumors) - develops from _____ - hormones released from here are controlled by POSITIVE releasing factors from the hypothalamus except for WHAT?

- develops from the Rathke's pouch located in the sella turcica - anterior pituitary (adenohypophysis) - 80% of the organ - DOPAMINE is a negative regulator of prolactin Anterior pituitary hormones - ACTH, POMC, endorphins, TSH, FSH, LH, GH, Prolactin

Staging workup - differs based on risk group but what should everyone get? What do you get beyond that for each group? - low risk - fav intermediate - unfav intermediate - high risk - very high risk (LN+ dz)

- everyone should get DRE, PSA, prostate biopsy (consider MR fusion biopsy, 3T or endorectal coil) - low risk = nothing more - fav intermediate = nothing more - unfav intermediate = +/- bone scan/CT A/P per NCCN but not required - high risk = bone scan/CT A/P or PSMA pet - very high risk (LN+ dz) = bone scan/CT A/P or PSMA pet

AVM -Workup - gold standard imaging? - CT good for what? - Angiography good for what? - MR good for what? - what might you need fMRI for? - diffusion tensor imaging might be used for what? SRS for AVM - Obliteration rate? - cure rate depends heavily on what? - what is the latency period? - major reason for failure? - risk of hemorrhage after tx? - Dose response plateaus at what dose? - poor obliteration below what dose? - What does the dose depend on?

- gold standard imaging = Angiography - CT good for what = good for r/o cerebral bleeds - Angiography good for what = good for vascular detail - take AP and laterals and project onto MRI - MR good for what = good for anatomy detail, but is dynamic imaging process and averages over time so NOT good for planning - what might you need fMRI for = Good for determining if eloquent areas are involved - diffusion tensor imaging might be used for what = to determine if white matter tracts are involved. - 80% obliteration rate - cure rate depends HEAVILY on the size of the lesion -- if it is larger than 3 cm, you have to reduce dose (so ideal if <3 cm) - latency period is 1-5 years -- the problem is that you don't know that it has failed for years - major reason for failure is inadequate dose due to large size - during latency, risk of bleed drops by half to an absolute risk of around 2%; isn't eliminated until obliteration - 22 Gy (above this, there isn't much benefit) - 17 Gy (below this, failure rate is high) dose depends on size: - <3 cm = 22 Gy to 50% IDL, if lesion is in the brainstem, lower dose to <16 Gy - >3 cm = >17 Gy to 50% IDL or with staged approach, favoring the deeper, more difficult part first, second half treat 3-6 months later

Treatment planning for Thymoma/Thymic Carcinoma - target - gtv - ctv - ptv

- gtv = all visible disease - ctv = entire thymus - historically covered whole mediastinum to include pre-op extent of disease. Really just cover entire surgical bed/clips in the mediastinum where the surgeon was - ptv = 0.5-2 cm (depending on IGRT) -- 0.5 w/ CBCT. If you just had a port film, you'd do a bigger margin

Pituitary adenoma - general presentation? - ACTH presentation? - GH presentation? - TSH presentation?

- headache, visual field defect (bitemporal hemianopsia), oligomenorrhea/amenorrhea, reduced fertility, loss of libido, ED, galactorrhea - ACTH: Cushing disease - same as above + centripetal fat distrubtion, neuropsychiatric symptoms, striae, easy bruising, skin thinning, osteopenia, hirsutism - GH: Acromegaly - same as above (HA, etc) - coarse facial features, carpal tunnel, excessive sweating, osteoarthralgia, dysmporphia, etc - TSH - symptoms of hyperthyroidism

For local excision -- adjuvant therapy - when is radical surgery preferred over local excision -- based on what risk factors? - what is better if you see these things - immediate re-operation or salvage surgery?

- high risk features = margins +, LVI, PNI, >T1, >N0 - IMMEDIATE reoperation is associated with improved outcomes (Borschitz; 2008) - fewer local recurrences - 8% vs 37% - fewer distant failures - 10 vs 23% - 10 yr OS 89 v 72%

Meningiomas Epidemiology - how common? - female vs male? - how are most found? - most common presenting symptom? - growth rate if progressive? - who grows slower? - cells of origin? - most common location? - risk factors?

- how common 6/100,000 = 30% of primary CNS tumors - female vs male = 2x more common in women - how are most found = 2/3 are found incidentally on imaging - tend to remain stable - most common presenting symptom = if sx, HEADACHE most common > focal deficits in 30-70% of cases (osler course said seizure was most common) - growth rate if progressive = grows at rate of 2-4 mm/year - who grows slower = older patients, calcifications, hypointense on imaging - cells of origin = originate around arachnoid cap cells, has high concentration of somatostatin receptors - most common location = cerebral convexities - makes them easy to resect surgically usually - risk factors = mostly unknown etiology, genetic rf (NF2, DAL1, chromosome 22q merlin protein defect), previous cranial RT

RT Toxicity of pituitary RT - hypopituitarism - how common? - CVA - optic nerve damage (_% risk) - neurologic dysfunction

- hypopituitarism - 50% at 10-20 yrs - CVA - optic nerve damage (1 % risk) - neurologic dysfunction

Paradigms for endometrial - risk factors that buy RT usually? - who can be observed after TAH+BSO? - what does G3 buy you in stage IA? - what does stage II buy you? What if G3?

- if young, usually need more risk factors (if 3, any age; 50-60 = need 2 RFs); if >60, only need one other. - obs can be IA w/ G1/2 w/ no other risk factors - G3 stage IA = EBRT + brachy - stage II = EBRT+ brachy standard for stage II; if G3, consider CRT IF stage III --> chemoRT - CRT w/ cisplatin --> carbotax - sandwich chemo -- platinum/taxol x 3 --> RT -- > chemo x 3

Timing of surgery - meta-analysis of 3584 pts showed waiting longer than 8 weeks had what effect on pCR? One RCT compared <2 weeks to 6-8 weeks (39 Gy in 13 fractions) - pCR difference? GRECCAR-6 trial - 7 weeks vs 11 weeks - difference in pCR - difference in sphincter preservation?

- increased pCR by 6% w/o increasing complications - pCR was higher in longer wait (26% vs 10%) - of course - OS was similar GRECCAR-6 trial - 7 weeks vs 11 weeks - difference in pCR = no - difference in sphincter preservation no - higher post-op morbidity with longer wait including perineal healing - higher post-op morbidity with longer wait including perineal healing

ASTRO consensus statement for boost - invasive: ? - omit for whom? DCIS: ? - omit for whom?

- invasive: <50 yrs old, age 51-70 yrs, high grade, +margin - omit: >70 yrs ER+ w/ negative margins >2 mm DCIS: <2 mm margin/+ margin, high grade, <50 yrs old - omit: >50 yrs, screen detected, <2.5 cm, low-int grade, margins >3 mm

Watch and Wait for Rectal Cancer - Habr-Gama - reported the first series of 71 pts w/ clinical CR at 8 weeks

- median fu of 57 mo, no cancer deaths, no pelvic recurrences and only 2 local recurrences

total mesorectral excision = ?

- mesorectum surrounding the rectum is also removed Total mesorectal excision (TME) is a specific surgical technique used in the treatment of rectal cancer in which the bowel with the tumor is entirely removed along with surrounding fat and lymph nodes.

Imaging differences between wilms and neuroblastoma List the disease with the characteristic listed here: - more likely to have calcifications (90% vs only 10%) - displaces adjacent structures - appears to arise from the kidney - +claw sign around mass - displaces adjacent structures without insinuating between them - crosses the midline - well circumscribed and does NOT cross midline - peak age 3-4 yrs - peak age <2 yrs - extension to the chest - extension to the IVC/renal vein

- more likely to have calcifications (90% vs only 10%) = neuroblastoma - displaces adjacent structures = wilms tumor - appears to arise from the kidney - +claw sign around mass = wilms tumor - displaces adjacent structures without insinuating between them = wilms tumor - crosses the midline = neuroblastoma - well circumscribed and does NOT cross midline = wilms tumor - peak age 3-4 yrs = wilms tumor - peak age <2 yrs = neuroblastoma - extension to the chest = neuroblastoma - extension to the IVC/renal vein = wilms tumor

Nasopharynx review questions - most common location of NPX cancer? - subtypes of NPX cancer associated with EBV? - INT 009 showed what 3 yr OS benefit for pts treated with chemoRT? - at what plasma concentration of EBV DNA was OS and RFS found to be decreased based on lin et all in the NEJM?

- most common location of NPX cancer? Fossa of Rossenmueller - subtypes of NPX cancer associated with EBV? WHO types II and III differentiated and undifferentiated types - 78% OS -- ~30% benefit - 500 copies (i think, his slide said 1000, but he said 500)

Prolactinoma - observation for who? - medical management? - toxicities of medicines? - when is surgery considered? - RT used when? - RT dose - ebrt vs srs - control likelihood with subtypes (just read)

- obs = <1 cm = micro; >1 cm = macro - uncommon for untreated microprolactinomas to have significant growth - bromocriptine - D2 agonist,D1 antagonist , cabergoline - Selective D2 agonist (DA inhibits) -- effective 70-90%. Cabergoline is used in "DA-resistant cases" - side effects: N/V, headache, drowsiness, hypotension, sycope, migtral regurge, mania hallucinations, mood changes, CSF rhinorrhea, pulmonary fibrosis. - surgery used to be standard (trans-sphenoidal hypophysectomy - goes between lip and gum line) - reserved now for cases w/ sudden visual changes, altered consciousness, vascular collapse (pituitary infarct, hemorrhage), failure of medical management, progressive tumor on medical management -- surgical - 1 out of 6 micro; 1 out of 3 macro - RT reserved for medically unresponsive, unresectable, STR w/ persistent hypersecretion - dose is 50.4-54 Gy (nonfuncitonal vs functional) - SRS dose is 12-34 Gy (keep Chiasm <8 Gy) - i would think 12 for non-secr and closer to 20-22 for secretory. Don't think we could get 34 to a tumor w/o overdosing chiasm often - Long latency before response is seen after RT - PRL normalization 5-10% per year -- can take years to get effect. "Cure rate" 30-35% Non-functioning - 10 yr DFS S+RT =90% vs RT alone = 80% - ACTH secreting tumors - 10 yrs remission rate 50-60% - TSH secreting tumors - aggressive, always treat with post-op RT

Adjuvant RT - what is most important risk factor? - side effect of adjuvant RT?

- positive margin most important - there was acute and late GI and GU toxicity, no QOL or erectile function differences

EBV is associated with malignant transformation and nuclear antigen/viral DNA can be measured in the blood by PCR - what is the meaning of pre and post treatment EBV levels?

- pretreatent EBV DNA can prognose survival and predict for distant mets - post-treatment EBV DNA can monitor for response and predict recurrence. Persistently elevated EBV DNA after completion of therapy is a poor prognostic feature

types of bias - define and say what prevents it - selection bias - recall bias - funding bias - atrrition bias - confounding bias - lead-time bias

- selection bias = selection of patients creates a difference between the treatment and control groups --> prevented by randomization and blinding - recall bias = systematic error caused by differences in the accuracy or completeness of the recollections retrieved (recalled) by study participants regarding events or experiences from the past --> the further back you go, the more likely someone doesn't remember and that worsens recall bias - funding bias = groups are treated differently based on their funding sources - attrition bias = differences in rates of loss to follow up between two groups. This can happen when the outcome in question limits a patient's ability to come in for follow up appointments. - confounding bias = associated risk factor in one of the study groups is related to the outcome. Can be controlled in study design or statistical analysis - groups matched for particular confounders. Exclud subjects with the confounding factor. Use of regression models. - lead-time bias = especially true with chronic disease. This would be if you said that a method to screen a disease resulted in longer survival compared to people that were not screened and presented with symptoms. You didn't affect the natural history of their disease, you only knew about it earlier, so lead time bias would say that you made them live longer. - this occurs if a test affects the perceived survival of a disease without actually treating the disease in anyway or effecting the course of disease

Unresectable stage III disease - soc ? - RT dose came from where?

- soc = chemoRT --> durvalumab (PACIFIC) - RTOG 7301 - Perez -- this was the four arm trial that looked at 40-->60 and questioned split course and found that split course was bad and 60 Gy was best.

Mesothelioma prognosis: - stage I/II - stage III/IV

- stage I/II - MS 34 months - stage III/IV - MS 10 months

Brain mets - symptoms? - how often asymptomatic?

- symptoms = HA (most common, increased ICP), NV, vision changes, FND, seizure, stroke, mental status change, cognitive issues - >2/3 are asymptomatic HA is usually unilateral, early morning, worse with straining Seizures -- usually supratentorial - not actually alot of data for seizure prophylactic medication in the case of brain mets - stroke = tumor emboli or hemorrhage

HN001 - NPX cancer - ongoing trial looking at EBV as a biomarker - everybody gets standard chemoRT with cis what is this looking at?

- this is looking at post-tx EBV level - if positive you get randomized to standard of care Cis/5FU vs gem/paclitaxel If EBV-, randomizing to SOC Cis/5FU vs observation So basically escalating treatment for those with poor prognosis and de-escalating for those with good response

Pelvic LNs - top border? - how far do you cover pre-sacral? - how far down do you cover external iliacs? - how far down do you cover internal iliacs?

- top border classically defined as L5/S1 bifurcation of common iliac (RTOG) but update in 2020 said it should be higher at L4/5 (bifurcation of aorta) - cover presacrals to the bottom of S3 - external iliacs become inguinals at the top of the acetabulum as the iliac vessels leave the pelvis - internal iliacs is top of pubic ramus

BC2001 trial - James, 2012 - 360 pts - asked RT to bladder or bladder+LNs AND asked RT +/- chemo (5FU/MMC) - four arms - Mostly men, good PS, transitional cell, T2 (85 v 80% crt v rt), complete TURBT (57 v 53% of pts) - 95% completed RT in both arms, 96% got MMC - which was more toxic? - results?

- toxicity - chemoRT grade 3-5 GI tox (SS) - GU tox not that different. CT led to higher DFS (SS), lower rates of 2 yr cystectomy (SS), 5 yr OS trended toward SS benefit (not quiet tho) Locoregional control - 2 yr 67% v 54% (CRT v RT) - SS OS - 5 yr 48% vs 35% (not SS)

Best test for comparing - means between two groups = ? - means between three groups = ?

- two means = two sample t test - three means = ANOVA

Techniques - whole breast only - breast/chestwall regional node - left sided if supine

- whole breast only = prone - breast/chestwall regional node = supine - left sided if supine = SDX breath hold, if can't tolerate consider IMRT/VMAT

Chemo options: - wilms - neuroblastoma - rhabdomyosarcoma - GGCT - NGGCT - LGG - HGG - Peds Hodgkin

- wilms = DD4A - neuroblastoma = DICCE x 5 cycles;immunotherapy+isotretinoin-outback(IGD2) - rhabdomyosarcoma = VAC (VActinomycin-C) - Ewings = VAC-IE (VAdriaC-IE) - GGCT = Carbo/Etop x 4 cycles - NGGCT = Carbo/Etop alt with Ifosfamide/Etop x 6 cycles - LGG = chemo controversial, probably PCV - HGG = not as good as adults, we tend to do TMZ, but PCV, CCNU, etc all seem to improve PFS and OS - Peds Hodgkin = AVPC (low) and AVPC-BE (int/high)

Testicular mass - workup?

- work up = general lab markers (AFP, b-hCG, LDH, chem) and testicular ultrasound + H&P If abnormal labs or imaging --> radical inguinal orchiectomy, if CL testicular abnormality, consider CL inguinal biopsy - do NOT pierce the scrotum mostly because this changes LN drainage from para-aortic to inguinal lymph nodes

Mediastinal germ cell tumors - workup? Benign teratoma - management? - RT if positive margin? Seminoma - management? - RT alone indicated? - survival rates Non-seminoma disease - management? - role of RT? - survival rates

- workup = bhcg, afp, blood counts, full testicular exam (to r/o mets) + normal stuff - management -- teratoma - surgery, even with +margin, we wouldn't do RT (no literature to support) Seminoma - cisplatin based chemo alone - resection of residual masses +/- RT - definitive RT NOT recommended, high relapse rates - survival rates as high as 60-90% at 5 yrs Non-seminoma disease - management = cisplatin based chemo (BEP) - role of RT = not much - survival rates = much worse, 40% at 5 yrs w/ modern chemo

PORTEC 1 - prosp, P3, RCT - TAH/BSO (no LND) --> OBS vs RT (WPRT - 3D) - no brachy - stage IC OR G1-2 pr stage IB, G2-3 - what were inclusion criteria - what was benefit of RT? - where were most of the failures? - what were the high-intermediate risk features on Portec 1

- ~10% LRR benefit XRT (10 yr - 14% vs 5%, 15 yr - 16 vs 6%) -- 75% recurrences were in the vagina - HIGH RISK FEATURES: - Age >60, G1-2 -->DOI >1/2 - Age >60, G3 w/ <50% DOI - 10 yr OS, CSM, and DM NOT different PORTEC 1 - FIGO 1 - G1 if >50% DOI - G2 any DOI - G3 <50% invasion (G3 with more was thought too high risk to get randomized to obs) Pts treated with EBRT had some poorer mental health, pain, etc than those with surgery alone - this lead to the idea that vaginal brachy would be better for these people if most recurrences were at the cuff and people tolerate it better, then you should do that --> Portec 2

Cord complications Reversible vs irreversible symptoms - timeline of onset - timeline of resolution

-Lhermitte's sign: transient early delayed - electic shock-like numbness radiating from neck to limbs - triggered by neck flexion. Thought to be due to transient demyelination - onset 3-4 months after RT and spontaneously resolves 3-6 months later - Irreversible - progressive weakness/numbness typically 6-12 months after radiation. Acute plegia can occur. - 50-75% happy within 20-30 months - cause is multifactorial - demylination, white matter necrosis from oligodendroglial cell depletion and microvascular injury -- clinical diagnosis basedm on dose review, onset of symptoms, and workup to rule out recurrent tumor/progressive disease - no effective treatment. 70% of C and 30% of T cord myelopathy -- die.

Oropharynx - likelihood of nodes for each subsite? -Pharyngeal Wall - BOT - Tonsil - Soft Palate

-Pharyngeal Wall = 57% - BOT = 78% (29% bilateral) - Tonsil = 69% (32% subclinical) - Soft Palate = 40%

conventional fractionation duodenum constraint?

1 cc < 55 Gy

How many data points are contained within 1, 2 and 3 standard deviations

1 deviation = 68% 2 deviations = 95% 3 deviations = 99% Remember that its half of that % on either the upper and lower boundaries 2.5% are on either extreme 2 standard deviations from the mean

How likely is craniopharyngioma to have cyst exp outside CTV? How likely is this to be symptomatic? How do you evaluate for this during tx

1 in 3 1 in 7 I would perform an MRI weekly during treatment or with any neurologic changes.

IMPORT LOW Trial, what was the 5-year local relapse rate in women without high-risk factors (ER+, H2N-, grade 1-2, no LVI, negative lymph nodes)? Import Low was low risk + 40.05 in 15 fxn without boost. This was PARTIAL breast - APBI 50 yrs, IDC, any grade, T1-2 - 2018 pts, 5.8 yr follow up - compared whole breast 40/15, 36/15 whole breast with SIB partial to 40, partial breast 40/14

1% The 1088 women in the IMPORT LOW Trial who had no high-risk factors had experienced a total of 10 local recurrences after receiving 40.05 Gy in 15 fx. This confirms data from the EORTC 22881 boost trial - namely that women over 50 with low to intermediate grade disease derived a very small benefit from the boost and highlights the viability of avoiding a boost in this population. No diff in any of the arms

What are some ways you could reduce heart dose?

1) Change gantry/collimator angle 2) Sim prone 3) Mixed field approach (electrons/photon) 4) Deep inspiration breath hold 5) IMRT - randomized data from British (half were inverse planned) and Canadians (forward planned). 6) Heart block

Mesothelioma - rare, 3000 cases per year, rate decreasing because of decreased asbestos exposure. - pathology? Best to worst? - good prognostic factors? Staging/resectability

1. Epithelioid (best prognosis, 60%) 2. Mixed or biphasic (30%) 3. Sarcomatous or mesenchymal (worst; 10%) - med OS 8 months Meso is (-) for PAS, CEA, and Leu-M1, TTF1(rare), (+) for calretinin, vimentin, WT1, and cytokeratin 5/6 Meso = Long microvilli, Adeno = short microvilli. Good prognostics: Epithelioid, Stage I, <65 yo, >6mo of symptoms, (-) margins The origin of the tumor is in the parietal pleura, and invades over from there. T1 - limited to pleura T2- diaphragm or lung parenchyma T3- locally advanced, resectable - through chestwall T4 - locally advanced, unresectable - crossing through the diaphragm/chestwall/adjacent organs 7th edition used to break N into N1-3 - now its N1 and N2 in 8th edition -- ---N1 = IL bronchopulmonary, hilar, mediastinal, internal mammary (used to be N3), peridiaphragmatic, pericardial fat pad, intercostal ---N2 = CL nodes (SCV, hilar, etc) Workup is basically the same as NSCLC

post-TORS path report basically divides people into what three groups?

1. Low Risk = "Home run" - T0-2, N0-1 (7th edition; 1 node <3 cm) - no need for any adjuvant therapy 2. Intermediate Risk = "base hit" - This means you only had indications for PORT (<2 mm margins, PNI, LVSI, pT3-4, >1 node) but NOT chemo - can take to lower post-op doses compared to definitive RT or CRT of 60 Gy (combined toxicity of CRT to 70 or TORS with 60 Gy is pretty much the same and we are ok with having made this decision) 3. High risk = "strike out" - They had positive margins or ENE - This is the worst case because now they ended up getting trimodality therapy and all of the toxicity of surgery, chemo, and radiation, rather than just CRT. - Now your post-op dose w/o gross disease is 66 Gy (if you can localize +margin, data for taking ENE to 66 is weaker, but not out of the question) and potentially 70 Gy for gross residual disease left behind - the combined toxicity of TORS and 66 Gy Chemo-RT is WORSE than CRT to 70 Gy alone. The surgery provided these people NO benefit. - if you think this will happen, you argue AGAINST surgery

Most common brain tumors in kids

1. Low grade glioma 2. Medulloblastoma 3. Ependymoma 4. Craniopharyngioma

Major Subdivisions and General Paradigms for Each - OVERVIEW CARD: 1. Oral Cavity 2. Oropharynx 3. Larynx 4. Hypopharynx 5. Nasopharynx 6. Major salivary glands

1. Oral Cavity - Surgical disease, post-op RT generally (T3/4, >1 node, LVSI, PNI, or <2 mm margins) or post-op CRT (+margins/ENE) generally 60-66 Gy/30-33 fxn (post op area and high risk/previously involved; 66 if pos margin/?ENE), 54/30 to elective or low risk nodal areas - generally cover +/- 1a, +1b, II, III, and IV - can tx IL if well lateralized gingiva, buccal mucosa, and RM trigone. - Need 3 month PET/CT + contrast CT neck/thyroid 2. Oropharynx - Def. RT or ChemoRT OR TORS +/- adjuvant RT/chemoRT: Essentially think of this as def. RT for up to T2N1 (based on AJCC 7th, <4 cm and 1 node) and def. chemoRT for anything more. TORS+neck dissection can be appropriate for early stage (same up to T2N1) and could mean you get no adjuvant tx., or adjuvant RT, or worst case is needing all three (avoid this because much more toxic than def chemoRT) - Need 3 month PET/CT + contrast CT neck/thyroid 3. Larynx Really think of as supraglottic/subglottic and glottic larynx Glottic: T1/2/3 = think larynx preservation with RT (T1/T2a)/ChemoRT (T3) - T1 = 63 Gy / 28 fractions using opposed laterals (contour the cords, spinal cord) - typically is a 5x5 or 6x6 box around the larynx to ensure appropriate coverage of the vocal folds. - T2 = 65.25 Gy/29 fractions (add a fraction) vs 68-70/34-35. Some selected cases may benefit from ChemoRT. - T3 = Larynx preservation equal to TL (RTOG 9111)= ChemoRT - T4 = SURGICAL DISEASE = think more laryngectomy (not all attempts at larynx preservation can be salvaged w/ surgery) --Post-op RT for T4 = close margins, skin/soft tissue invasion, >1 cm subglottic extension, TRUE thyroid cartilage invasion, multiple positive LNs (ChemoRT = positive margins/ENE) - cover post-op bed/neopharynx, LN II-IV, and VI Supraglottic: Tend to lean toward ChemoRT for most of these (Sx might be appropriate for some very early stages) - up to pT2N1, like oropharynx, definitive RT ok; above that chemoRT Subglottic: Rarer, more aggressive, present later. May present with airway obstruction. - more advanced usually go for TL, low tracheostomy and post-op RT/ChemoRT - Need 3 month PET/CT + contrast CT neck/thyroid 4. Hypopharynx - SURGICAL disease T1 = can do def RT T2 = can do def chemoRT Anyone else is surgical disease w/ standard post-op RT or chemoRT indications. - Cover LNII-IV + VI + RP (VIIa) - Need 3 month PET/CT + contrast CT neck/thyroid 5. Nasopharynx - NOT a surgical disease, ChemoRT disease - WHO III (EBV assoc. Nasopharyngeal Carcinoma), II (+/- EBV), and I (typical sqcca) - Only T1N0 treated with def. RT; Anyone else gets concurrent ChemoRT with 70 Gy/35 fractions with concurrent chemo (cisplatin; intergroup 0099 showed ChemoRT better than RT) and consolidation 3 cycles cis/5FU (it is toxic, but MAC-NPC meta-analysis showed it was needed) - Coverage of retropharyngeal Ln and posterior triangle (V) is mandatory (VIIa) + II, III, and IV (probably cover +/-Ib is II involved) - Need 3 month PET /CT+ MRI skull base (w/wo) 6. Major salivary glands - Surgical disease - Post-op RT for: high grade, close or +margins, PNI (all adenoid cystic) lymph nodes, recurrence, tumor spillage - role of chemo not well established

Solitary plasmacytoma treatment

1. Radiation 2. Surgery reserved for instability or cord compression with symptoms and rapid progression

What dose per fraction would you use if doing whole lung, with just flank RT? Would you do them at the same time ? Where is your iso?

1.5 Gy/fx always to lung or whole abdomen. If doing just flank it is 1.8 Gy/fx If doing flank with whole lung simultaneously... lung wins do everything at 1.5 Gy/fx

Acoustic Neuroma - risk factors? - path - Important CN deficiencies to ask about? Grading scale for facial nerve dysfunction?

1/100,000 NF2 (bilateral) Loud noise exposure /Parathyroid adenoma Childhood exposure to RT - also true of meningioma path (buzzwords) = Antoni A (compact fusiform cells, reticulin, collagen, anuclear palisading cells) and Antoni B cells (loose stellate round cells in stroma) CN 7 - Hypesthesia, corneal twitching, ask to tighten platysma (Graded with a House Brackmann 8 point scale - just know the name of this scale for Mock Orals, don't need details) CN 8 - Have them march in place with eyes closed - pts will often veer to the side of the lesion, ask about tinnitus, speech discrimination

French IMN Trial - AGAINST treating IMNs - 1334 pts w/ medial/central and/or node positive breast cancer - mastectomy and RT to CW, SCV fossa, and axillary apex if N+ - powered for a 10% OS advantage to be seen - randomized to treat the 1-5 intercostal spaces or not - results?

10 yr DFS 53.2% v 49.9% (NS) 10 yr OS 62.6% v 69.2% (NS) No excess in cardiac death in IM arm. NO significant benefit seen for IM radiation

BASO II study - another omission study - 1135 women with T1N0, G1 (VERY early stage) - lumpectomy + ALND - randomized 2x2 design - Obs v tam v RT v RT + TAM - result?

10 yr LR - obs - 22% - tam - 8% - RT - 8% - Tam + RT - 2% The BASO-II trial randomized 1135 women with grade 1 (or favorable histology) breast cancer treated with lumpectomy and ALND in a 2x2 factorial design of: Observation, Tam, RT, Tam + RT. The per annum rates of recurrence were: - Observation 2.2% - Tam 0.8% - RT 0.8% - Tam + RT 0.2% 10 yr rates for surgery + tam vs surgery +tam/rt are there for 8% vs 2%. These per annum rates were stable across the first 10 years after treatment. Both the low rate of recurrence without RT and the large relative benefit of RT are comparable to other trials of similarly well-selected patients receiving endocrine therapy (CALGB 9343, PRIME-II, ABCSG trial). ABCSG was an austrialian trial - looked at G1/2 T1-2 - lumpectomy + ALND - 50 Gy+/- boost - 5 yr LR was 0.4% v 5.4%

CALGB 8984 study - local excision for T1-2N0 rectal cancers - T1 --> no further treatment - T2 --> if negative margins, still got RT (54 Gy) + chemo (5 FU) - results?

10 yr OS and LR was still worse for T2 -- clearly anything more than T1 needs escalation of therapy

Florence trial - p3, 40 yrs or older, <2.5 cm, margins >5 mm - compared 50 Gy in 25 whole breast vs 30 Gy in 5 fractions every other day (equiv to 54-60 Gy) - external beam IMRT - CTV - 1 cm expansion around clips limited to 3 mm from skin surface, 1 cm expansion for PTV - 4 mm into lung and 3 mm from skin - results?

10 yr data - IBTR - not different (3.7 v 2.5%) - OS and BCSS not different - better overall cosmesis in APBI by patient and physician outcomes - lower overall toxicity in APBI acute and late

Adjuvant Chemotherapy Japan ACTS-GC trial - D2 resected GC randomized to S1 vs obs - result?

10% OS benefit at 5 yr (note ARTIST II would say SOX better than S1 alone)

Bonner study - Cetuximab - 70 Gy qd, 72-76 bid - randomized to RT +/- cetuximab - results? - what AE predicted for improved outcome?

10% OS difference (46 vs 36%) primary outcome of LRC was not reported 13-15% LRS benefit Survival was improved with G2 rash or greater

Is WVRT needed for germ cell? SFOF TGM-90 60 pts - chemo and local RT only - 40 Gy w/ 2 cm margins NOT whole vent - results? SIOP GCT 96 - non-randomized -190 pts - looked at pts between N Europe/UK and S Europe/Poland - some got chemo + local RT (FOCAL, not whole vent) - some got 24 CsI + 16 Gy local RT - OS was the same (96%) - Changed the pattern of failure -- the chemoRT people almost all failed in the ventricles (6) and 1 in the spine - all the CSI failures happened in the tumor bed

10/60 relapses, 8 of 10 were in the ventricles OS10 yrs = 96^, EF10 = 82% Focal is NOT adequate - you need WVRT

Meta-analysis of neoadjuvant RT (alone) vs surgery alone - 5 trials, 1147 pts - med fu 9 yrs - benefit?

11% reduction in mortality - absolute survival benefit seen - 3% at 2 yrs, 4% at 5 yrs Post-op RT -- 2 RCTs failed to show any survival benefit despite improvements in locoregional control -- high rates of gastric complications RT alone is NEVER curative. Just palliative

Regional lympadenectomy for colon cancer AND rectal cancer -- what # is standard of care?

12 lymph nodes

What is the approximate rate of PEG tube dependence following chemoRT in HN cancer?

12-15%

Appropriate # of lymph nodes taken in dissection if upfront vs neoadjuvant CRT?

15 if upfront surgery 10 if CRT --> no data for this though

Who should have Oncotype testing per Tailor Rx

18 - 75 yo, ER(+), PR (+), or both HER 2 (-), Node negative (note: RXponder now includes N+ 1-3 nodes) Tumor size 0.6 - 1.0 cm if G2 or G3 1.0 - 5.0 cm any grade score of 0 to 10 got TAM alone Score of 26 or more got TAM + chemo The 11 - 25 group was randomized to chemo + TAM or TAM alone No benefit w/ chemo DFS-5invasive = 93% no diff OS5 = 98% Lowest score 0-10 had 3% risk recurrence at 9 yrs TAM alone Highest score 26 + had 13% distant recurrence rate at 9 yr w/ TAM + chemo

ACNS 0331 trial for standard risk medulloblastoma - ages 3-7 randomized to 18 Gy vs 23.4 Gy CSI --> then randomized to 54 Gy boost to either PF or IF - age 8-21 all got 23.4 Gy CSI then randomized to 54 Gy boost either to PF or IF results?

18 was worse than 23.4 Gy in standard risk - low dose was NOT non-inferior PF was EQUAL to IF though so now IF is the standard for standard risk (IF was NOT inferior to PF) None of the IFRT failures occurred outside of the boost volume so wouldn't have been helped with PF boost Note most people don't actually do PF for high risk either.

1st 2nd 3rd echelon of draining nodes for vulvar sites? What is the exception? What is Cloquet's node?

1st superficial inguinofemoral 2nd deep inguinofemoral 3rd external iliacs --> DISTANT METS Clitoris - can skip direct to pelvic through the pre-symphyseal plexus Highest of the inguinofemoral nodes

Nasopharynx followup

1st year clinical exam and scope q1-3 months 3 month post-RT PET/CT and MR skull base Yearly CT chest 2nd year - can space clinical visits to 4-6 months 3-5 yr - can space clinically to 6-12 months Monitor TSH

RCT data of open surgery vs minimally invasive surgery - Bierre 2012 - results?

2 week pulmonary infection 29% v 9% in favor of MIS (SS) No difference in mortality or anastomotic leak

XRT sp EPP - MSKCC - EPP --> hemithroacic XRT (54 Gy) - huge fields - single arm study - results?

2 yr OS 33% w/ acceptable toxicity -- can do this because they don't have a lung there anymore. but hard to get patients through this treatment. This was 1990s-early 2000's Local failure = 64% - still very higher

Adjuvant Therapy in Pancreas Cancer - GITSG trial - RCT of 5-FU-CRT vs observation in resected pancreas pts - RT was split course w/ 2 week rest (20 Gy in 10 fractions AP/PA 20x20 field - Adj 5FU for 2 more cycles - 49 pts - results?

20 vs 11 m median overall survival for CRT 2 yr OS : 42 v 15% (favors CRT) 5 yr OS: 19 v 5% (favors CRT) No difference in LR No difference in Hepatic Mets 20% of pts in treatment group did not actually receive any treatment (postop complications and refusal)

RT doses for MM

20-30 Gy -- higher end for very bulky mass or cord compression Be mindful of bone marrow and keep field tight to reduce toxicity because they need their BM for future systemic therapy

Oncotype? - how many genes? - what does it predict? - what are the groups?

21 Gene panel with 16 genes taken into consideration and 5 controls Looks at ER, PR, HER2, etc -- only validated in the ER+ population Helps to predict distant recurrence risk at 10 yrs Divided into: For women older than 50 years of age: Recurrence Score of 0-25: The cancer has a low risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects. ---------------------CHEMO GIVEN---------------------- Recurrence Score of 26-100: The cancer has a high risk of recurrence. The benefits of chemotherapy are likely to be greater than the risks of side effects. For women age 50 and younger: Recurrence Score of 0-15: The cancer has a low risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects. Recurrence Score of 16-20: The cancer has a low to medium risk of recurrence. The benefits of chemotherapy likely will not outweigh the risks of side effects. -----------------------CHEMO GIVEN------------------- Recurrence Score of 21-25: The cancer has a medium risk of recurrence. The benefits of chemotherapy are likely to be greater than the risks of side effects. Recurrence Score of 26-100: The cancer has a high risk of recurrence. The benefits of chemotherapy are likely to be greater than the risks of side effects. Now keep in mind the RxPonder data -- - this looked at the oncotype in the pN1 (1-3 nodes) group. - take home is that you can use oncotype to guide chemotherapy in POST-menopausal women (so any post-menopausal woman with a oncotype <26 - you could omit chemotherapy) - Premenopausal women that were pN1 benefitted from chemo regardless of score.

What is Oncotype Dx, is it validated?

21 gene assay Predicts DISTANT recurrence rate, who will benefit from chemo and TAM vs TAM alone It was validated in prospective studies If pushed B14, and B20 validated Oncotype Dx Oncotype Dx now valided in the N+ (1-3 nodes) group in RxPonder. - N+ w/ Oncotype <26 if pre-menopausal --> benefit to Chemo (abs ~2.4% distant recurrence benefit) - N+ w/ Oncotype <26 if post-menopausal --> no benefit to chemo If Oncotype >26, everybody gets chemo just like in N0.

secondary malignancy rate in peds if you go over 60 Gy

22% at 20 yrs if you go over 60 Gy if you stay under 60 Gy its like 5-10%

Management of non-gastric MALT

24 Gy in 12 fractions for NON-gastric MALT -- typically you target the entire organ

What were the 5 yr OS numbers on Turrisi?

26% vs 16% w/ BID winning

In an analysis of the 5 pelvic failures in GOG88 -- what was the actual dose in those cases?

3 out of 5 had inadequate dose

UNFOLDER trial - DLBCL - abstract only - no manuscript - DLBCL, 18-60 yrs (younger) - aaIPI = 1 or IPI=0 w bulk (7.5 cm) - patients w bulky or EN disease randomized to 1. R-CHOP-21 x 6 2. R-CHOP-21 x 6 --> if CR --> RT 3. R-CHOP-14 x 6 4. R-CHOP-14 x 6 --> if CR --> RT No RT arms were closed early after planned interim analysis of 285 pts results?

3 yr EFS significantly worse if RT was omitted so that arm was terminated

APBI dose and fractionations

34 Gy/10 BID for brachy 32 Gy/8 BID for brachy (GEC-ESTRO) 38.5Gy/10 BID w/ EBRT (RAPID) 30 Gy/5 daily fractions (Florence) --CTV: clips + 1cm; PTV = CTV + 1cm -PTV for EB and HDR -Excision cavity + 2 cm -1.5 cm if close to surface or chest wall

Dose planned based on risk? Definitive vs Post-op? High risk intermediate risk low risk Planning volumes for CTV and PTV?

35 fractions - Gross = 70 Gy High risk = 63 Low risk = 56 Post op 60 Gy / 30 fractions - to post/op/high risk 54 Gy / 30 fractions to low risk If ENE/pos margins: 66 Gy/59.4 Gy/56.1 Gy all in 33 fractions In general CTV70 = GTV + 7-10 mm +/-PTV70 = CTV + 3 mm CTV63 = nodal level + 5 mm PTV63 = CTV+3 mm (We tend to treat nodal level +3 mm) PTV56 = CTV+3 mm A 3 mm PTV assumes CBCT daily In practice, we tend to just contour the nodal level as CTV and do a 3 mm expansion for PTV

Radiation fields for mesothelioma and dose - post op fields - issues with IMRT

3D - APPA mid inf liver block, central electron patch to diaphragmatic recesses around liver - total 54 Gy/30 fractions - 41.4 Gy to contralat vertebral body border. - 12.6 Gy boost, medial border extends to ipsi vertebral body IMRT - 45 Gy to larger volume, boost to 60 for close/positive margins - Contour resection cavity/insertion of the diaphragm and the crura - careful about saying IMRT -- the issue is that the Harvard IMRT series killed patients because of significant dose spillage into the CL lung -- increased MLD significantly. - CTV = all surgically violated spaces w/ 1 cm margin - PTV = 0.5 cm

FORT Trial - 4 Gy vs 24 Gy for pts with Indolent Lymphoma - FL 86%, MZL 14% - palliative 60%, curative 40% - stage I-II 60%, III-IV 30%, unknown 10% - result?

4 Gy (2x2) was NOT non-inferior to 24 Gy in terms of progression free survival (left) PFS - 5 yr - 24 Gy = 89.9% - 4 Gy = 70.4% HOWEVER - the OS was not different 24 Gy 4 Gy CR or PR 91% 81% CR 68% 49% OS EQUAL Toxicity higher with 24 Gy Conlusion is that the optimal dose for indolent lymphoma is 24 Gy when durable local control is the aim. So this is still considered standard of care. However, since survival isn't different and 70.4% 5 yr PFS isn't terrible, 4 Gy is reasonable for palliation

Endometrial Molecular High yield details from the Cancer Genome Atlas Project (TCGA) - 4 molecular subsets of endometrial cancer identified - what are these? - which is most common? - which type does serous fall into? WHAT IS THE BEST PROGNOSIS/LEAST COMMON? Which two are similar in survival? Which one has the worst survival?

4 subsets: 1. Ultramutated/POLE mutated - 7% 2. Hypermutated/MSI-H (microsatellite instability high) - 30% 3. Copy number low (MSS - stable) - 65% - MOST common (type I endometrioid type) 4. Copy number-high (predominantly serous histology) - 26% POLE is the BEST prognosis, but least common (PFS ~100%) Copy number low and MSI have similar survival Copy number high (serous) has the WORST survival

RTOG 0618 - Bob Timmerman for "operable" pts - 33 pts, borderline operable according to Steven Lin - results?

4 yr - LC 96% - DFS 57% - OS 56%

Timing of surgery for esophagus - what was median time to surgery on CROSS - what impact does time to surgery have on pCR

4-8 weeks Get imaging at about 6 weeks after chemoRT to help surgeon evaluation Waiting longer can increase pCR rates without impact on complication rates or OS CROSS trial had median time to surgery of 45 days - increased TTS was associated with an increased probability of pCR after each additional week (OR 1.35)

RTOG 0129 - showed g3 or 4 rates in what % of pts?

40% of patients

Thymus - primary lymphoid organ where T cells mature - active in childhood, atrophic in adults - cortex stromal portion is actually what gives rise to cancer - epithelial cells within the stroma - Most common neoplasm in the anterior mediastinum - most thymomas are benign, but some can invade and some can become thymic carcinoma - 40-60 yrs most common age - 1/3 can have MG symptoms, 1/3 can have compression symptoms, 1/3 are asymptomatic - can have other paraneoplastic: Myasthenia (30-50%), pure red cell aplasia (5-10%, or hypogammaglobinemia ~6% (present with infections) What % of pts will have improved symptoms of MG with surgery? How often is MG associated with thymoma?

44% of MG pts have improvement of symptoms with surgical removal of thymoma 75% of pts with myasthesia gravis HAVE a thymoma Can tx w/ physostigmine (AChE inhibitor) to increase Ach in synapse

When using brachytherapy alone for medically inoperable Stage I endometrial cancer, the ABS consensus statement recommends that the D90 of the CTV receive an EQD2 of at least

48 Gy

Local Excision for T2 cancers - ACOSOG Z6041 analysis - 72 pts w/ distal T2N0 rectal cancers - Initially treated with neoadjvuant chemoRT (CAPOX/54 Gy --> then CAPOX 50.4 after toxicity analysis) - 56 months median fu - results?

49% ypT0/Tis - majority had pCR 14% ypT1 31% ypT2 4% ypT3 (2 had APR, 1 refused and recurred) 1 R1 -- apr- - no cancer 3 yr - DFS - 88%, 91% had preserved rectum - OS 96% 10% recurred, 6% distant and 4% local 29% Gr3-4 tox - 15% pain - 15% heme

BLADDER CANCER CARDS

4th most common diagnosed cancer in mend men --> prostate - lung - colon/rectum - bladder) associated w/ age, tobacco and analine dyes other countries - schistosoma haemotobium, chronic uti, bladder stones.

Dautzenberg PORT Study - made up >30% of pts on meta-analysis - stage I-III pts randomized to PORT (60 Gy), Co-60 or linac - results?

5 year OS was worse with PORT (30 vs 43% obs) 5 yr mortality from death from intercurrent dz was 31% PORT vs 8% obs Mortality from PORT mostly due to non-cancer deaths such as cardiac, infection, respiratory. You are NOT going to see a survival benefit if your treatment kills patients.

OVERALL risks of recurrence: Older, low risk pts -- T1N0 s/p lump and (-) margin with ER+/PR+/Her2- 5 yr Lumpectomy + obs Lumpectomy + TAM Lumpectomy + RT 10 yr Lumpectomy + obs Lumpectomy + TAM Lumpectomy + RT Lumpectomy + TAM/RT General risk we quote for more all comers for BCT? DCIS - low risk cohort - high risk cohort

5 yr Lumpectomy + obs = 9% Lumpectomy + TAM = 4% Lumpectomy + RT = 1% 10 yr Lumpectomy + obs = 15% Lumpectomy + TAM = 9% Lumpectomy + RT = 4% Lumpectomy + TAM/RT = 2% All comer risk of recurrence more like 30% (10-15 yrs) if you include nodes and all and we say we reduce by 2/3 (~10%) DCIS 12 yr ECOG trial -- refer to other card for specifics - low risk cohort - 14% - high risk cohort - 24.6%

GORTEC study - stage III/IV oropharynx - two arms - arm 1 = 70 Gy in 35 fractions - arm 2 = same RT w/ concurrent 5FU/carboplatin - results?

5 yr OS - RT: 16% - CRT: 23% 5 yr LRC - RT: 25% - CRT: 48%

MAGIC trial - 503 pts - randomized to surgery alone vs peri-op ECF - 20% D1, 41% D2 - 24% had esophagectomy - result?

5 yr OS 36% vs 23% for ECF (SS) ECF - surgery -ECF so this is often the paradigm we stick to once they start either ECF or FLOT. Survival advantage seen to periop chemo - 13% benefit

Dose escalation in Esophagus - Chinese study - Red journal 2005 - Looked at hyperfrac boost after convention +/- chemotherapy - 41.4 to initial fields, conedown to tumor + margin w 1.5 Gy BID to 27 Gy (total 68.4 Gy)

5 yr OS 40% 26% w/ LRR as first failure

UCSF data for adjuvant RT for Meningioma - - 140 pts, 117 benign STR - RT given 54 Gy w/ 1-2 cm margin - results? In general good outcomes -- but what is the thing that Chan always points out about PFS difference if <__ Gy vs >___ Gy?

5 yr OS 85% 10 yr PFS 77% Dose <52 Gy --> PFS 65% Dose >52 Gy --> PFS 93% So that's why we do 52.2 Gy rather than 50.4.

CRITICS study - "ChemoRadiotherapy after Induction chemoTherapy in Cancers of the Stomach" - 788 pts w/ stage Ib-IV gastric cancer - ECC or EOC chemo for 3 cycles then D1 sugery - randomized post-op to 3 cycle of ECC/EOC or 45 Gy concurrent with cis/capecitabine - 84% completed 3 cycle preop, 46% completed 3 cycles postop, 55% completed CRT -- very tough to complete this regimen - results?

5 yr OS not different - 41.3% vs 40.9% No difference in GI toxicity So the take home is that the chemo is just as good as the RT i guess

HD16 - another pet directed therapy - GHSG trial - stage IA--IIB FAVORABLE, non bulky, 1-2 sites - No unfav characteristics - everybody got ABVD x 2 - one group got IFRT 20 Gy - iPET negative --> obs - iPET positive --> IFRT 20 Gy Prim endpoint - 5 yr PFS, non-inferiority results?

5 yr PFS - RT - 94% - ABVD - 86.1% No significant difference in OS Again, omission of RT just reduces PFS - doesn't affect survival.

Chemotherapy in HN Cancer - HIGH YIELD - MACH-NC - meta-analysis of chemotherapy in HN cancer - analyzed 87 phase III trials (16,000 pts) - OP most common site - chemotherapy had what benefit? - induction or concurrent? Remember this is the gross disease setting - we aren't talking about RTOG 9501 adjuvant chemoRT for ENE or R1. This is just chemoRT vs RT for gross disease so there are big differences

5 yr survival benefit w/ concurrent chemo - 8% (27% --> 35%) Cisplatin had 11% benefit HR 0.8 for chemoRT v RT alone HR death 0.96 for chemoRT vs induction (so no major benefit to induction)

What is the risk of transformation of JPA?

5% transform to HGG over lifetime 15 % recur as a LGG, can happen up to 30 yrs later Patients can't ever really stop follow up

PCNSL management - chemo? - what dose to get BBB penetration? - WBRT dose if CR? - what about if salvage RT?

5-7 cycles R-MPV (high dose methotrexate) - need >3-3.5 g/m2 to cross the BBB CR = 23.4 Gy PR = 24-50 Gy w/ boost of residual to 45 Gy include posterior aspect of the field and C1-2 vertebral bodies age is super important and if >65 yrs probably just do re-challenge methotrexate if they fail

Summary card - whats the take home for benefit of RT in the pre-retuxan era? SWOG 8736 ECOG 1484 - 14-8(c)-4 GELA LNH-93-1 LNH GELA LNH-93-4

50% reduction in local failure with RT addition in pre-retuxan era SWOG 8736 ECOG 1484 - 14-8(c)-4 GELA LNH-93-1 LNH GELA LNH-93-4

% that recur after RT and type of recurrence

50% reduction in recurrence after RT 50% risk of recurrence as DCIS or invasive Rick factors for occult microinvasion - comedo necrosis - size >5 cm - palpable Risk factors for recurrence after BCT - comedo necrosis - size >4 cm - positive margins - younger age (<40-50) - residual microcalcs on imaging

Major RCT for endometrial adjuvant RT

6 Large studies Norwegian - no nodal sampling; TAH/BSO - Vaginal brachy LDR VS 60 Gy randomized to EBRT or obs. - similar outcomes - >1/2 invasion, higher rates of death from cancer and higher risk of failure in general - higher rates of 2ndary cancers in those that got EBRT Portec-1 - next slide GOG99 - 1B/1C -TAH/BSO + node dissection-> pelvic RT or obs. - no sig OS different; less pelvic recurrence pelvic RT (9 --> 2%) Portec-2 ASTEC Swedish

DAHANCA fractionation

6 fractions per week (66-68 Gy) showed LC benefit, but not OS benefit Consider this if you can't do chemo

meta-analyses for neoadjuvant chemoRT for esophagus

6 out of 7 show a OS benefit to chemoRT neoadjuvantly 2 studies showed association with increased mortality post-operatively w/ CRT

ADORE trial looked at ypT3-4N0 or anyT w/ ypN1-2 after chemoRT - randomized them to 5FU-LV x 4 cycles or FOLFOX x 8 cycle

6 yr DFS (SS) and OS (NS) favored FOLFOX benefit restricted ypN2 (stage 3)

Hypofrac constraint overview

60/20 especially doable with a spacer

GOG 205 - PII study of locally advanced vulvar cancer - primary endpoint was clinical and pathologic response rate following pre-op ChemoRT RT was 57.6 Gy in AP/PA fields - IMRT not allowed - weekly cisplatin 40 mg/m2 Surgical resection of the residual tumor or biopsy 4-6 weeks after EBRT results? - how many had clinical and pathologic response here? - how does it compare to GOG101 and why is that most likely?

63.8% had complete clinical response and 50% had complete pathologic response - so better outcome than GOG101 probably because there was no break

IMN South Korean Data - Red Journal 2021 - RCT P3, pts w/ pN+, both BCS and mastectomy +/- ALND - excluded distant disease or neoadjuvant chemo - all pts had RNI (breast/CW) 45-54 Gy - randomized to IMN-irr or no IMN-irr - prim endpoint was 7 yr DFS - 747 pts enrolled - nearly everyone had taxane chemo - results?

7 yr DFS was 81.9% v 85.3% (no IMN-RT v IMN-RT) - NS Subgroup analysis showed significant DFS and breast cancer specific mortality in the pts with mediocentrally located tumors. DFS in that group was 81.6% v 91.8% (SS) (no IMN-RT v IMN-RT) with 7 yr BCSM 10.2 v 4.9 (SS) (no IMN-RT v IMN-RT). No difference in adverse effects.

DBCG-IMN study - FAVORS treating IMNs - 3072 pts w/ 1 or more ALN+ treated with RT - mastectomy (65%) or lumpectomy (35%) - all received some systemic tx (chemo 53%, endocrine 81%) - IMN-RT of 48/24 given to RIGHT breast cancers but not left - result?

7 yr OS benefit to IMN-RT of 78% vs 75% (SS) Death from cardiac disease NOT different. Death from breast cancer higher in no RT group.

GELA LNH-93-4 -- OLDER patients - older pts (>60) w stage I and II aggressive NHL - age adjusted IPI0 and normal LDH, more homogeneous group and lower risk than other studies - CHOP x 4 +/- RT (40 Gy) results?

7 yr fu - NO difference in EFS or OS 5 yr OS 72% - worse than SWOG Delayed RT start (median 7 weeks) 12% on RT arm didn't get RT questionable RT quality - 21% in field failures (abnormally high)

NPX - dose? What lymph node levels MUST be covered.

70 Gy in 33-35 fractions (T1 may do 33 fractions) CTV 60/59.4 Gy/33 fractions is most important planning consideration -- large number of structures should be covered in a tricky area. Use a checklist of structures to avoid missing any. - entire nasopharynx (including soft palate, clivus, skull base, up to sphenoid bone) - if involved, cover entire clivus, if not involved, cover 1/2-2/3 of the clivus - Pterygoid fossa - Foramen ovale (V3) - Pterygopalatine fossae - Parapharyngeal space - Sphenoid sinus - Posterior 1/3 of the maxillary sinus - Posterior 1/3 of the nasal cavity - Cavernous sinus to Meckel's cave for advanced T3-4 lesions Coverage of RP (VIIa) and level V is mandatory but 1b is optional (can omit if clinically N0) - IB-V + VIIa

Marginal Zone Lymphoma - 10% of all NHL, relatively common - Subtypes - nodal MZL, splenic MZL, extranodal MZL (aka MALT - mucosa associated lymphoid tissues) - markers - pan B cell markers (CD19, CD20, CD22, CD79a), but not CD5 or 10 - note: FL would be CD5+ and Mantle cell would be CD10+ - how common is stage I-II? hint: diff than FL/SLL - 5 yrs OS is what? How does it change for increasing stage - most common locations? Key for MALT - there are unique infections associated w/ different MALT sites. Typically the first step is to TREAT the infection and see if that causes tumor regression. If not, the answer is typically then RT. There are particular features associated w failure of therapy. List the infection for the site: - Stomach - Ocular adnexa - Skin - Small bowel What is the treatment for Gastric MALT if H. pylori positive? What is the expected response rate if translocation (which one?) is positive? What do you do if antibiotics don't work? What if the H pylori clears and the tumor doesn't regress on endoscopy? What is the response rate to RT? What tx if RT is contra-indicated?

75% is stage I/II - kind of oppose for FL and SLL 5 yr is 85-90% REGARDLESS OF STAGE GI tract is most common (50%) - about 80-90% of that is stomach MALT - think t(11;18) - orbit 7-12% - lung 8-14% - skin 9-12% Overall prognosis is VERY good for MARGINAL ZONE type lyymphomas - Stomach = H. pylori (remember t(11;18) associated w/ failure of ABX) - Ocular adnexa = Chlamydia psittaci - Skin = Borellia burgorferi (lyme) - Small bowel = campylobacter jejuni H pylori - management is this is positive, you give triple therapy (PPI, clarithromycin, amoxicillin) - rate of lymphoma regression is 70-90% for pts that do NOT have t(11;18) - if this is present, this usually means the antibiotic is less likely to work --> <5% response rate if they have this translocation - if antibiotics don't work, can consider 2nd line quad therapy antibiotics - if H pylori is cured but tumor doesn't regress -- the answer is to observe for up to 18 months if the pts is asymptomatic. If progressing or symptomatic you can treat with RT. - if that still doesn't work of they are symptomatic/progressing -- can do RT - 30 Gy @1.5 Gy/fx or 24 Gy in 12 fractions - response rate to RT >90% (CR and EFS of 100% after IFRT to 30 Gy on some studies) - tx w/ Rituximab if you can't do ISRT Other features associated with failure of abx therapy - 30-40% of cases - are due to t(11;18) - >5% response rate to antibiotics - infiltration below mucosa - involvement of adjacent organs or nodes

mycosis fungiodes focal vs total skin

8 Gy in 2 fx better than 2x2

How often to AVMs have aneurysms and where are they located typically?

8% of AVMs have aneurysms (usually on the feeding artery - has stretchy walls), 1 % of aneurysms are caused by AVMs

EBCTCG for PMRT: - how many women - looked at 1-3 and 4 or more nodes -- found what?

8135 women from 22 randomized trials - Improved isolated local recurrence in both 1-3 and 4 or more node groups (19.5% --> 5.8% and 35.2% --> 15.4% respectively) - no benefit for node negative patients - BC specific mortality benefit more like 8% here - NOTE: BCSM benefit to PMRT was seen in 1-3 nodes and 4+ nodes but OS benefit lost when looking at subset of 1-3 nodes only They postulated that a 4% reduction in LRR leads to a 1% reduction in mortality at 15 yrs. Most LRR happen by 5 years. Equivalent benefit was seen regardless of age, ER+, or # of LNs. Larger benefit was seen in larger tumors or high grade tumors.

Rate of voice preservation in T1/T2 larynx?

85-95% (very good LC)

% node involvement at presentation for nasopharynx?

90% N+ and 50% bilateral

Codel Trial/RTOG 1071 - p3 - initially was RT vs TMZ vs RT + concurrent and adjuvant TMZ - the tmz arm was eliminated based on RTOG 9402 I think an RT + adj PCV was there somewhere

9402 showed no benefit to concurrent

3 and 6 fraction QUANTEC liver (mean dose) SBRT constraints?

< 13 Gy for primary liver cancer, in three fractions < 18 Gy for primary liver cancer, in six fractions < 15 Gy for liver metastases, in three fractions < 20 Gy for liver metastases, in six fractions i think 15 - 20 for 3 - 6 fraction and subtract 2 for primary liver. for 5 fraction remember 700 cc <21 Gy for 3 fractions remember 700 cc <15 Gy Mean dose 13-17 Gy based on dose

Which sites have the highest risks of nodes - rms

<1% for orbit ~20% for extremity 20-30% for paratesticular 20-40% for bladder prostate

Relationship between depth of invasion and recurrence? What is the definition of DOI?

<2.5 mm = 0% recurrence 2.5-10 mm = 23.6% recurrence >10 mm = 36.4% recurrence The DOI is the measurement from the deepest part of the tumor in the stroma to the most superficial epithelial stromal junction.

Appropriate liver constraint if fractionated?

<32 Gy whole liver - metastasis <28 Gy - HCC

Larynx T staging -- just for reference bonus question: % chance of nodal involvement in a T1 larynx?

<5% (probably 2-3%)

Post-op RT indications for meningioma - less than complete excision - including dural attachment/bone involvement - atypical and high grade - surgery for recurrence - after deliberate partial resection - in grade I/II --> PFS and OS increased to what?

>90%

Early stage follicular lymphoma - 5 an 10 yr OS/CSS is very high - >90% LC is what dose is used? - what is the role of RT here really? - generally what is the treatment paradigm for a rad onc?

>90% LC when 30 Gy is used (note: Lowry study did show that 24 Gy is adquate tho) Role of RT is essentially to give local control - no evidence that survival is improved with increasing field size. Low Grade (G1/2) --> are they early or advanced stage - if early treat definitively wiht 24 Gy. If they are advanced --> palliatively with 4 Gy (boom boom) High Grade (G3A) - somewhere in the middle -- treated on the RT alone papers but the overall clinical picture matters here. High Grade (G3B) - treated more like DLBCL

prognostic score for advanced HD

AA SHAWS: She says you should memorize these Age > 45, Albumin <4 Sex Male Hgb < 10.5 ANC < 8% WBC >15K Stage IV

What trials do we reference for pN1 after SLNB for early stage breast cancer (T1-2) to support NOT doing completion ALND for 1-2 positive lymph nodes on SLNB? Briefly cover what each compared and outcome - paper for lumpectomy? - paper for mastectomy?

ACOSOG Z11 and AMAROS - paper for lumpectomy = Z11 (100% lumpectomy) - paper for mastectomy = Amaros (82% lump; 17% mastectomy) ACOSOG Z11, EORTC AMAROS, EORTC 22922 ACOSOG Z11 - 891 pts - T1-2 cN0 --> pN1 after SLNB -- randomized to completion ALND or observation (all got whole breast XRT in supine position covering low axilla - not RNI) - Surgery: 100% lumpectomy - ALND increased lymphedema with NO oncologic benefit. - when analyzed by Jagsi, 19% had RNI actually (none were supposed to get it), 50% had high tangents that covered some of the axilla - no difference in LRFS, DFS, and OS EORTC AMAROS - same group as above, randomized to completion ALND or Breast/RNI (w/ SCV) - 1425 pts. IBC, 0.5-5 cm, clinically node negative, BCT or mastectomy, any age. - Surgery: 82% lumpectomy; 17% mastectomy - if pt in ALND arm had 4 or more nodes, they got RT. - cancer outcomes the same with better lymphedema in RT arm (lympedema 2x as high in the ALND arm) - no diff in ax recurrence, DMFS, OS or LRR

NSABP B35 - postmenopausal women - looked at tamoxifen vs anastrozole - ~3k pts - med fu 9 yrs - treated with RT - results?

AI did improve breast cancer free survival -- mostly women in 50-60 yrs group

WHO histologic features for gliomas?

AMEN criteria WHO I - no factors WHO II - atypia WHO III - Mitoses + atypia WHO IV - Endothelial proliferation/Necrosis

anti-GD2 therapy comes from where?

ANBL0032 immunotherapy group did better in terms of EFS and OS ~20% EFS and 10% OS benefit

How would you describe a whole abdomen field?

AP/PA 1 cm above dome of diaphragm 1 cm beyond abdominal wall/flash skin Inf: Bottom of obturator foramen shield femoral heads Clam shells on testicles

Rectum radical surgery options

APR and LAR Abdominoperineal resection --> doesn't spare the sphincter Low Anterior resection --> spares the sphincter Important to remember TME is not a type of surgery like these -- it is excision of the rectum along with the fatty mesorectum around it -- it is done with either a LAR or APR.

ARTIST Trial - adjuvant CRT in stomach cancer - 458 pts w/ resected gastric cancer + D2 dissection - Randomized to Xeloda-cis vs Xeloda-cis + RT - results? --> subgroup showed what group DID have a benefit?

ARTIST trial - showed NO benefit to adjuvant chemoRT all comers if they had adequate D2 dissection. - DFS similar (3 yr, 78 v 74%, NS) - subgroup analysis showed superior DFS specifically in the N+ patients (SS) - held up in MVA

AVM - Arteriovenous Malformation - Epidemiology - how common? - average age? - majority located where? - male to female predominance? - risk of hemorrhagic stroke? - associated conditions?

AVM - Arteriovenous Malformation - Epidemiology - 10/100,000 - average age - 30's - majority located where = Supratentorial - male to female predominance - no, 1:1 - risk of hemorrhagic stroke - 2-4% annual risk, but once first hemorrhage happens, risk is now like 7% - associated conditions - Osler Weber Rendu, Sturge Weber No RCT to guide decisions for AVM.

Accelerated Whole Breast dose/fractionations? Relevant constraints for this?

AWBI Fx: -UK FAST: 28.5 Gy in 5 weekly fx (30/5 w/ worse toxicity) - UK FF: 26 Gy in 5 daily fx (27/5 fx worse cosmesis) - 26/5 had non-inferior IBTR to 40/15 and similar toxicity. --UK F + FF fields: CTV = whole breast; PTV = CTV + 1cm -FF constraint: --Ipsi Lung: V8<15% --Heart: V7<5%, V1.5<30% --PTV: Dmax<110%, V105%<5%, V107%<2%, D95%>95

Pathophys of AVM

Abnormal communication with an artery and a vein (feeding vessels and draining veins) unbalanced stress across the vessels The artery avm goes straight into the vein without capillaries to disperse pressure first. This puts a lot of pressure on the veins and they get engorged, then pushes back and puts more pressure on the arteries. As this pressure builds up, the vessel walls weaken and stretch. Lack of arterial smooth muscle wall → ↑flow, ↑venous pressure → vessel growth w/ incomplete elastic lamina

Neck management pearls About __% of patients with clinical/radiographic CR have residual disease About __% of patients with residual disease are pathologically negative. May integrate PET/CT into the evaluation and observe patients with negative findings.

About 25% of patients with clinical/radiographic CR have residual disease About 40% of patients with residual disease are pathologically negative. This is important to point out that you need like >10^9 cells to have a 1 cm node on a CT scan.

GOG 249 study - P3, RCT - pts had HIGHER risk features that GOG 99 and PORTEC1/2 studies Stage I w/ risk factors (g2/3, IB, LVSI) - Age 70 with 1 risk factor - Age 50-69 w/ 2 risk factors - <50 with all three risk factors - BUT ALSO included stage II endometrioid (cervical stroma involved) AND stage I or II serous/clear cell histologies Primary outcome was recurrence free survival Randomized to either: 1. EBRT - 50.4 Gy (note: 32% also got brachytherapy) OR 2. Vaginal brachytherapy + chemotherapy x 3 cycles (carbo/taxol) Brachy was 6-7 Gy at 0.5 x 3 or 10-10.5 at surface for 3 or 6 Gy x 5 fractions or LDR 65-70 Gy to the surface in 1-2 insertions at 4-10 Gy per hour Outcomes?

Absolutely no difference in RFS or OS -- there was WORSE nodal recurrence in the vaginal cuff + chemo arm compared to EBRT 5 yr pelvic or para-aortic nodal recurrence rate: - VBT+chemo = 9% - EBRT = 4% VBT/chemo also had worse toxicity (acute fatigue and worse neurotoxicity)

What is new about T staging for oral cavity?

Accounts for depth of invasion now T1 up to 5 mm T2 between 0 to 10 mm (meaning >2 cm and 2 mm do is still T2) T3 anything > 10 mm

RTOG 9410 - Seq or Concurrent chemo? - results?

Acute tox worse with concurrent Survival best in concurrent QD (17 mo) compared to sequential (14.6 months) or concurrent BID (15.6 months) The survival benefit is really actually very small though really -- HR 0.88 -- so its better, but the absolute survival difference is very small.

What are late toxicities of treatment for wilms/general pediatric?

Acute: N/V, diarrhea, fatigue, skin irritation, radiation recall, pneumonitis Chronic: ⅓ have some form of renal dysfunction in the opposite kidney at 10 yrs Growth abnormalities, secondary malignancies, HTN, Renal failure, Liver Failure, Pulmonary Fibrosis, Potential need for transplants Cardiac, thyroid , fertility, bowel adhesions, SBO, vaginal stenosis

Pathology of rectal cancer

Adenocarcinoma - most common 90% If you have a squamous cell of the rectum you treat like an anal cancer and vice versa.

Which salivary histology has the highest rate of PNI? What HN tumors have a propensity for late distant failures?

Adenoid cystic carcinoma

Salivary histologies -- just read over

Adenoid cystic follows nerves Parotid - think about facial nerve CN7 and CN V3 -- have to follow them back to the skull base HER2 expression has been seen in some salivary cancers Pleomorphic adenomas not usually treated until there are multiple recurrences and re-resections.

Adjuvant vs Salvage Prostate RT What is AUA definition of failure?

Adjuvant means if the PSA is undetectable and you have post-op indications -- pos margins, SVI or EPE -- not done anymore really Salvage is what is done if post-op PSA is >0.1. Biochemical recurrence is PSA >0.2 x 2 Phoenix definition is nadir +2 (post-RT failure) -- date of failure is time PSA rise occurred

Chemotherapy - what does ABVD stand for? - what are the doses? - what is a cycle? - what is an option for advanced stage disease? - what are the toxicities

Adriamycin - 25 mg/m2 -- cardiac toxicity (sharp increase >400 mg/m2 lifetime dose) b1e0mycin - 10 mg/m2 - pneumonitis, allergic reaction Vin6lastine - 6 mg/m2 - hematologic Dacabazine - 375 mg/m2 - N/V, allopecia A cycle is 1 month - chemo given day 1 and 15 (parts A and B) Brentuximab-Vedotin is an option for more advanced, but bleomycin omitted in those cases to reduce pneumonitis risk.

Brain metastases -20-40% of cancer patients will develop brain mets - 25% of pts that die from cancer have brain mets at diagnosis - 60% of lung and breast cancer patients die from brain mets - ratio of metastasis:primary is increasing (10:1) because people are living longer with better systemic control - so they eventually fail in the brain Distribution of met number: 1/3 solitary 1/3 oligo 1/3 multiple mets (>4 mets)

Adults: - lung (50%) - breast (20%) - skin (melanoma) (10%) - kidney (10%) - GI (5%) RARE in prostate, oropharynx, and non-mel skin cancer Children - Neuroblastoma, RMA - osteogenic - 10-15 yrs - germ cell tumors if >15 yrs Mets tend to pop up at the gray/white interface (terminal arteriole) Dif diagnosis: metastasis, demylinated disease, radiation necrosis, resolving hematoma, abscess, GBM, infarct, contusion, or lymphoma

Chemo for GB/distal cholangio

Advanced - metastatic Gem/Cis FolFOX Concurrent 5FU or Capecitabine Adjuvant Capecitabine or Gemcitabine

SRS in Brain mets - most mets are small <3 cm, spherical, distinct margins, displace rather than infiltrate - the probability of LC is equal or better and more cost effective - also easier when tumors in difficult location to resect - no direct comparison to surgery - advantages of SRS over surgery

Advantages - availability - 1 day out paitent procedure - multiple lesions - inaccessible lesions easier to treat - more conformal - no surgical morbidity/mortality

CLASSIC TRIAL - Noh - 1035 stage II-III gastric cancer D2 resection randomized to CAPOX vs obs

Again about a 10% OS at 5 yr benefit to CAPOX

Oral Cavity volumes and doses - treat unilateral or bilateral? - typical dose? - post-op area - involved LN areas - elective/CL uninvolved node chains - what if node had ENE? - what levels are standard to cover? - when should 1a be covered - when can you treat IL?

Again, surgical disease, so you should be talking post-op indications for PORT or post-op-CRT Most oral cavity structures are truly midline -- THUS BILATERAL neck coverage is safest answer - Primary post-op bed coverage should be generous and b/l neck coverage (usually +/-1a, +1b,2,3,4a) and technically IX (buccofacial) - from caudal orbit to caudal edge of mandible (lateral to buccinator and anterior to masseter) -1a if lower lip, anterior tongue/mandibular gingiva anteriorly) - if anterior oral tongue, usually CTV60 is entire tongue and FOM complex. Post op bed and high risk = 60 Gy/30 fractions Lower risk elective CL neck = 54 Gy / 30 fractions - if ENE or positive margin, CHEMO-RT to 66 Gy just to the involved area then 59.40/33 (1.8s) to the rest IL can be considered if: - retromolar trigone - buccal mucosa - well lateralized gingiva

HPV vaccination guidelines

Ages 9-26 People up to age 45 you can get vaccinated (its not licensed above 45)

Cervical cancer screening guidelines - what age groups shouldn't be screened?

Ages <21 and >65 (w/ adequate prior screening) and those who have had a hysterectomy (that removed the cervix) shouldn't be screened 21-29: cytology q3 yrs 30-65: cytology q3 yrs or cotest w/ HPV q5 yrs

When should Radiation start after surgery?

Aim for day 9 At latest day 14 Before starting RT Clear with surgeon Are they making urine Do they have bowel sounds/making gas

Neoadjuvant Summary CHEMO - Rosell (Spanish) and Roth (MDACC) looked at induction chemo and showed benefit in OS to chemo - both stopped early because of chemo benefit. CHEMO RT Induction ChemoRT vs Def ChemoRT (Albain INT 0139) - 396 resectable IIIA patients randomized to chemoRT vs def ChemoRT - results? Induction Chemo vs ChemoRT --> Surgery - German Lung Cancer Cooperative Group - 524 stage IIIA/IIIB pts - randomized to: 1) cis/etop x 3 cycles --> concurrent carbo/vindesine + 45 Gy/1.5 Gy BID --> surgery (weird like Turissi for SCLC) 2) cis/etop x 3 cycles --> surgery --> PORT (54 Gy) - inoperable - continue at 24 Gy @1.5 BID - positive margin - continue at 24 Gy @ 1.5 BID or 68.4/38 - result?

Albain INT 0139 - no OS difference between groups. - LF was better for surgery arm, but no diff in OS or DM - subset analysis showed that OS benefit WAS seen in patients that got lobectomy. This was due to very high death rates in patients that got pneumonectomy. German Group - No diff in OS between groups - Patients that got mediastinal downstaging or complete resection had better survival. But as a whole, there was no clinical outcome difference between induction chemo or induction chemoRT.

What are the components of the ALBI score

Albumin Bilirubin MORE predictive of survival than Child Pugh score

GBM dose and volumes vs grade 3 HGG dose and volumes

All generally holds true if <65 yo (RPA 3 and some 4) -- 5 wouldn't get surgery Surgery - "maximum safe resection or stereotactic biopsy" + adjuvant RT - for preservation of neurologic function -if you wreck their PS, they will do worse overall. But get as much tissue as you can safely. - bx if the lesion is not amenable to resection, potentially severe neurological morbidity if surgery done, poor performance status, diffuse process, suspected lymphoma followed by --> RT to 60 Gy @ 2's or 59.4 Gy in 1.8's. Generally take T2 flair to 46 Gy and then boost T1 enhancing to 60 Gy - CTV = 1 cm (shave out of anatomical barriers) - PTV = 0.5 cm On trials -- they did GTV_46 = T2 FLAIR + 2 cm + CTV/PTV and GTV60 = T1 enhancing + 2cm + CTV/PTV -- we don't do the 2 cm expansion here. Multiple studies have shown no benefit of dose escalation. Shave at tentorium, bone, falx -- must cross midline if near corpus callosum Technique = Linac based RT with 5 non-coplanar beams, be sure not exiting through mouth/eyes This is in comparison to general "HGG"/grade 3 glioma -- take entire volume to 59.4 Gy w/ 1 cm CTV and 0.5 cm PTV.

Risk factors for cervix cancer

All things related to HPV early age of sexual intercourse multiple sexual partners low SES low education status low income smoking - increases risk by about 1.7x immunosuppression

Adjuvant vs Early Salvage Papers RADICALS -1396 pts (LARGEST) - undetectable post-op PSA AND any of pT3/4, gleason 7-10, pos margin, or pre-op PSA >10 - randomized to Adjuvant RT vs Observation --> early savage when PSA failure occurred (note, what was failure considered) - RT was 52.5 Gy in 20 fx or 66 in 33 fractions - ADT allowed - randomized to 0 vs 6 vs 24 months - results? - what was worse in adjvuant? RAVES - 333 pts undetectable post-op PSA, EPE, SVI, positive margins - randomized Adjuvant RT vs early salvage >0.2 PSA - RT 64/32 fractions, no ADT allowed - G6-10 included here - freedom from RT ~60% at 5 yrs. - results? GETUG-17 - 424 pts, undetectable post-op PSA and pT3/4, positive margins, pN0/Nx - all patients received ADT - early salvage defined as PSA >0.2 - randomized to adjuvant RT or early salvage RT - 66 Gy in 33 fractions - results? Artistic Meta-Analysis - meta-analysis of these 3 major trials - total of >2k patients. 5.5 - 6.9 yrs median fu - ADT variable on Radicals, not allowed on RAVES, required on GETUG - most studies didn't allow LNs, but radicals had a few - results? - caveats to trials?

All very recent trials. Take home is that early salvage is now SOC over adjuvant as these trials showed essentially equivalent cancer control and delayed side effects. RADICALS used cutoff for failure of 0.1 or 3 rises below 0.1 (or technically 2 rises >0.1). The rest all used 0.2 as cutoff for failure. RADICALS - 67% of observation did not require RT by 8 yrs. - No difference in 5 yr bPFS between adjuvant vs salvage (85% v 88%, NS) - worse AEs in adjuvant group (incontinence and stricture) RAVES - Freedom from biochemical failure was not different between the groups. Did not meet non-inferiority criteria - worse GU tox in adjvuant; no diff in GI tox. GETUG-17 - 54% of pts in salvage group required RT. - FFBF 94% in adj RT group and 90% in salvage group - tox again worse in adjuvant arm Artistic Meta-Analysis - overall no major difference between adjuvant and early salvage radiation therapy - major caveats 1. alot of the patients were on the more favorable risk side with Radicals being the largest including ANY of the following: pT3/4, gleason 7-10, pos margin, or pre-op PSA >10. RAVES and GETUG were a bit more selective of the truely high risk. 2. Time bias -- PSA progression wasn't counted in salvage arm until they failed, got RT and then got another PSA. This made failure look later than it really was. 3. Concurrent ADT - ADT delays time to progression so this might have been convoluting the picture.

What should you ask your surgeon for WT?

Always ask your surgeon the following questions: Did they assess the contralateral kidney Did they assess bowel and peritoneum for mets → automatic WAI Was it piecemeal excision → auto stage III Was there spillage ALWAYS ASK EVEN IF THEY DON'T TELL YOU TYPICALLY EXAMINER WON'T TELL YOU → WAI Ask if they felt nodes, felt along bowel Ask that they felt along aorta and IVC for thrombus

General treatment paradigm for LGG?

Always surgery - adding adjuvant therapy depends on fav vs unfav features: Favorable features: - seizures at presentation - age <40 - good PS KPS >70 - steroid dependence - surgery extent, RT at diagnosis, chemo at diagnosis Unfavorable - SATAN Size >6 cm Age >40 Tumor crossing midline Astrocytic component Neuro symptoms Treatment Favorable: - GTR and <40 years old (~30% get GTR) - tx: Can just observe these after surgery - RT might be offered if refractory seizures Unfavorable: - Subtotal resection OR age >40 with gross total

Organic thiophosphate that donates thiol and acts a a free radical scavenger in HN to reduced xerostomia?

Amifostine

Trigeminal Neuralgia - CN5 exits where - where do we target with GKRS

Anatomy: Dorsal Root entry zone "DREZ" Where CN V comes out of PONS, Most susceptible portion of nerve Where myelination changes CNS to peripheral nerve oligodendrocytes → schwann cells Prepontine cistern: CSF space just in front of DREZ Petrous dura: Dura over the petrous portion of the temporal bone Meckles Cave: Past the dura, where gasserian ganglion sits, where synapses occur, and the nerve branches out You have to tx before this location or you would only affect one branch Pars Triangularis: Portion of the nerve just in front of the DRE that is shaped like a triangle GK targets this area because width of nerve there is about same as GK collimator

Retuximab = ?

Anti-CD20 monoclonal antibody order hep B because it can re-activate in generaly R added to CHOP increases 5 yr OS by about 10%

Who should receive adjuvant RT for wilms (either flank or abdomen)

Any unfavorable histology w/ anaplasia including stage I or II Any stage III The lungs and abdomen are staged for treatment purposes independently You could have disease in the lungs meaning it is stage IV but at the same time a stage I or II favorable histology in the abdomen that would not require treatment.

Kid is 1.4 yo and has gtr anaplastic ependymoma, do you tx?

Anyone > 1 yo is beam on, unlike medullo where you wait till > 3 yo

Describe general tx paradigm for brainstem tumors.

Anything other than dorsal exophytic tumors Steroids/Shunts → RT (54 Gy in 1.8's) Up to ⅔ will have some stabilization or sx improvement after RT but always recurs ~ 6 months later No role for TMZ concurrent or after RT No clear role for other chemo either For Dorsal exophytic BSG's - fills 4th ventricle and increases ICP This is a buzz word descriptor, frequently these are JPAs Means it is a rare case where surgery is possible (could be different histologies, usually turn out to be JPA's) 10-yr OS = 75% If chan says this for a brainstem tumor just do surgery - call it a day - Focal tegmental BSG - observation is reasonable in the absence of symptoms - surgery if feasible and RT if progression -- RT alone - 40% LC -- surgery + RT - 80-90% LC

Meningiomas that can be safely observed?

Asymptomatic No infiltration or edema Calcification present >60 y iso/hypointense of T2 smaller

What defines "serviceable hearing" Workup for AN

Audiometry = Best screening (asymmetric sensorineural loss, more prominent at ↑ frequencies) 50/50 rule- Patient has "serviceable hearing" IF the following two conditions are met. - Gardner Robinson Rule 1. Can discriminate pure tone average b/t 0-50 Decibels AND 2. Has >50% word discrimination is considered serviceable (functional hearing) Always ask if they can use telephone on affected side (helps you get an idea of their hearing) CN exam (look for deficits in CN7 and 8 esp) Weber/Rinne exam Audiometry (HF hearing loss) Brainstem evoked potentials MRI thin slice (1-1.5 mm) w/ contrast - if NF suspected, do neuraxis MRI, if not possible, do high res CT +/- contrast

Non-Hodgkin Lymphoma - heterogenous group of tumors - there are some that are indolent with long expected OS even for no treatments vs those with very aggressive lymphomas that can be fatal w/in months if untreated Treatment varies - obs - rt alone - chemo alone - combined modality Typically older adults M>F 2/3 have extranodal disease 1/3 have B symptoms etiologies?

Autoimmune disease - Sjogrens - parotid/orbital MALT Virus (EBV, HTLV1) bacterial (H pylori) HIV alkylating agents pesticides diet

Optic pathway glioma in NF1 - about 15% of NF1 pts will get OPG - median age is 4.9 yrs - pathology is usually WHO gr1 pilocytic - symptoms = visual acuity loss, abnormal pupillary reflexes, optic atrophy, and precocious puberty - what do we do with these?

Avoid treating with RT Monitor them for precocious pubert serial optho exam if proptosis, vision loss, clear radiographic progression --> then consider starting treatment - Surgery is the most useful is just ONE optic nerve is involved - can sacrifice just one nerve. PFS is 50% at 3-5 yrs RT has better efficacy long term because we can treat the entire target and maintain their vision (PFS at 10 yrs 80%). However down side is secondary malignancy ~10% in some cases. RT is target + margin only. NF1 -- concern for moya moya disease with RT (this with 2ndary malignancy is the main reason we avoid here).

Major data to quote for BCT in general? 2 major studies - how many people in each? - what stages included? - effect of RT overall on LRR, DFS, OS or DM? At what time point do you start to see breast cancer specific mortality for BCT? What is the 4 to 1 rule?

B06 - Fisher NEJM has 5, 8, 12, 20 yr outcomes EBCTCG META Analysis - 5, 10, 15 yr data Uppsala-Orebro Milan data All showed between 63-75% relative risk reduction from addition of RT to lumpectomy B06 - 1851 pts, stage I-II (<4 cm, 26% had 1-3 LNs, 12% had 4+ LNs) - ARMS: A) Total mastectomy B) Lumpectomy alone C) Lumpectomy + XRT (50/25 no boost) - Outcomes: LRR cut by 2/3 at 20 yrs by adding RT to lumpectomy. No difference in lumpectomy+RT vs mastectomy. (Lump alone 39%, Lump+RT 14%) - NO differences in DFS, OS or DM EBCTCG META Analysis (there is one large meta-analysis for BCT and one for PMRT) - n=10,801 10 yrs: 50% relative risk reduction of rate of any recurrence (local and distant) 35% → 19.3% (SS) The relative risk reduction for only local regional recurrences was still ~ ⅔ 25% → 8% (SS) Risk of distant mets --> No diff if RT or not 15 yrs: When you see CSS benefit NO difference in OS, or CSS in each individual trial @ 15 yrs -- BUT... 15 yr Cancer specific mortality was improved by ~ 6% with RT when all trials analyzed together 36 → 30% (SS) Benefit larger for N+, but seen in both N- and N+ CONCLUSION: An absolute 20% or relative 2/3 local control benefit at 5 yrs → absolute 5% CSS benefit at 15 yrs What is the 4 to 1 rule? From EBCTCG: Ignoring other causes of death, for every 4 local recurrences that we stop, we also stop one breast cancer death over the next 15 years Effect more pronounced in young women and LN (+) women

DCIS - what trial looked at BCS + RT +/- tamoxifen? - median follow up - margins allowed?

B24 - BCS + 50 Gy/25 (+/-boost) randomized to Tamoxifen or no Tamoxifen - 1804 pts - median follow up was 13.58 yrs - positive margins allowed - 9% vs 6% benefit for tamoxifen - not that big of a diff - patients that had ER+ had the most benefit from tamoxifen usage (technically a 10 yr OS benefit)

RT dose escalation studies with intrahepatic cholangiocarcinoma - showed what?

BED 80 or higher shows OS benefit 3 yr OS - BED >80 --> 73% - BED <80 --> 38%

Data for dose intensity needed in SBRT came from Onishi study - Cancer 2004 showed what? MD anderson experience with in field failure? MD anderson NCDB analysis of BED 130?

BED >100 needed Disease Recurrence BED 100 or more = 8.1% - 92% LC BED <100 = 26.4% (SS) - ~74% LC MD Anderson looked at 1092 pts and looked for ones that had infield local recurrence. - predictors of local failure were 1) minimum BED10 to 95% of PTV was 86 Gy or less 2) GTV greater than or equal to 8.3 cc 3) PTV mean BED10 <130 Gy BED >130 --> shows a OS benefit (small but SS) 50 Gy in 5 fraction is most popular regimen but BED is only 100 Gy. 3-4 fx regimens have a higher BED

RT Boost strategies - most conformal approach is brachytherapy - 50% IDL around 1 cm away from prostate - brachy also gives ~200% IDL nicely in the peripheral zone -- mean dose can be upwards of 200 Gy which can't be achieved with EBRT Major trials - ASCENDE RT + "Big 5" (EBRT alone) + Kishan 18 all showed dose esc. benefit in high risk ASCENDE RT - 400 mostly high risk (31% intermediate) -- excluded PSA >40, T3b+, and pre-ADT prostate volume > 75 cc both arms pelvic RT 46 Gy --> randomized: 1. EBRT boost to 78 Gy 2. Brachytherapy boost I125 115 Gy (we do 110 Gy) + 1 year ADT - not super advanced pts, median PSA was ~10, mostly high risk (~70%) - cancer outcomes that showed benefit? - toxicity? Kishan '18 paper - retrospective multi-center paper -- 12 centers. 1809 pts, 5 yr f/u and only GS 9-10 cancer --> brachy did what?

BIOCHEMICAL FAILURE FREE SURVIVAL favoring brachy boost No OS difference. If you break up Intermediate and high risk -- both groups benefit in terms of BFFS. Toxicity = GU toxicity much worse (5% G3 in EBRT vs 18% in EBRT+brachy) - half of those could be fixed. You triple chance of late GU toxicity for doubling the chance of biochemical free control. - GU tox was higher catheterization (12% v 3%), any pads (16% v 6%). - Erectile function NOT different -- 34 v 31%, GI function no stat diff (8% v 3%) Kishan 18 - brachy improved prostate cancer specific survival and DMFS OVER EBRT alone or prostatectomy for gleason 9-10 cancers. - within first 7.5 yr fu OS was even better for brachy - but this was lost after 7.5 yr fu

Data for advanced stage treatment

BV AVD is a consideration because it increased PFS

What medication would you give during whole lung RT?

Bactrim - reduces risk of interstitial pneumonitis

Interesting point about response of Barrett's to chemoradiation Study from Barthel et all (2010-2011) Lookedat 43 pts undergoing chemoRT for esophageal AC -- looked at associated Barrett's - how often did Barrett's persist?

Barrett's persisted in 93% of cases. Even if pCR -- (59% of pts had pCR) Since it can undergo malignant transformation this is further rationale for why they should undergo surgical resection after chemoRT.

BNI pain score for TN?

Barrow Neuro Institute "BNI" Pain score: "How bad is the pain right now?" No pain, no meds Occasional pain, no meds Some pain, meds control it Some pain, meds do NOT completely control it Severe pain, meds do NOT help AT ALL

Ryan summary of DLBCL management

Based on SWOG 8736, for early stage non-bulky DLBCL, 3 cycles of chemo + RT SHOULD be standard, but in reality the med oncs usually don't go this route. They are usually doing 6 cycles of R-CHOP which equals a definitive course of therapy by itself. Reasons to add RT to 6 cycles are upfront bulk/extranodal disease OR incomplete response after all 6 cycles (PR - take it to ~45 Gy ideally). We do RT for bulk/EN disease based on the RICOVER-60 trial. Remember RICOVER was We typically do 30 Gy ISRT for CR and 36 Gy for PR/residual disease. May boost up to 45 for DS4-5 disease

DCIS - Omission of RT - basis for this discussion - What data looks at omission?

Based on the concept that DCIS is a pre-invasive cancer -- will turn into invasive if left. De-escalation in an attempt given that its caught early. Women with recurrence of DCIS will likely go on for mastectomy and RT may compromise their reconstruction later if needed. RTOG 9804 - didn't accrue well. - 636 pts out of planned 1790. - >3 mm margins, lumpectomy or lumpectomy + RT - median f/u 7 years. LC was 6.9% vs 0.9%. SS -- thus hard to omit based on this. At present, no clear consensus where we can omit RT at present.

How will future studies possibly change our thinking about TORS for HPV positive?

Based on the results of ECOG 3311 - If the TORS + 50 Gy vs RT or ChemoRT is non-inferior and has better toxicity, than it would be the better recommendation for early stage OP cancers Based on the results of NRG HN002 - if definitive RT alone or CRT to 60 Gy is equiv. to 70 Gy then this would tilt the balance toward definitive RT/CRT if lower doses work just as well (because lower dose is really all the TORS is buying them anyway).

CCG 9892 - 71 pts, age 3-10 - chemo trial - Questioned if you could reduce the RT dose if they got chemo (CCNU) - concurrent vinc w/ RT - results?

Became standard of care because outcomes were similar to 36 Gy w/o chemo but you could reduce dose of radiation PFS3 = 86% PFS5 = 79% EFS3 = 83% EFS5 = 78%

LGG Trials to know Believers - EORTC 22844 - Karim et all - p3, 343 pts, WHO g1/2 - 25% GTR, 30%STR, 40% bx only - randomized to 45 v 59.4 Gy - results? INT/NCCTG trial - Shaw trial 2002 - P3, 203 pts, who g1/2 - 50.4 Gy vs 64.8 Gy - results? Nonbelievers - EORTC 22845 - p3, 311 pts who grade 1/2 - 42% GTR, 19% STR, 35% bx only - randomized to obs vs 54 Gy post op RT - results?

Believers = answer dose question - 59.4 vs 45 --> no real difference between doses (no diff in OS or PFS) - established prognostic factors - you don't need to go to high dose INT/NCCTG trial - Shaw trial 2002 - results = no difference in 5 yr OS (72% low dose, 64% high dose) - more toxicity in the high dose arm. Dose escalation arm LOST - established more prognostic factors - patterns of failure = 93% in field, 3% w/in 2 cm of field, 5% outside of field Nonbelievers = Answered timing question = no chemo; asked if we should do RT upfront or defer upfront and wait until they recur -- randomized to 54 upfront vs 54 at failure; upfront RT has PFS benefit (5.3 vs 3.4 yrs) and better seizure control, but no OS benefit. - no difference in the rate of malignant transformation --major critique is no QOL data so hard to assess if worth it. Low risk was defined as 0-2 of the factor in the picture High risk was 3-5 of these

OPERABLE RT vs surgery trials that are pending

Benefit of the VALOR study that is ongoing is that the randomization is done by pulmonologists and thus isn't dependent on CT surgery referral

DLBCL with osseous involvement

Benefit to RT for osseous involvement - 75% vs 36% 3 yr EFS if RT was excluded

Components of the Childs Pugh score?

Bili Albumin PT (INR) Encephalopathy Ascites Pretty common that they ask to at least know which things are considered in the score

Management of the Axilla: What do you do in the following: - cN+ - cN(-) -- SLNB 1-2 nodes positive - cN(-) -- SLNB 3 or more positive

Biopsy the node to confirm -- and clip the node in the case the neoadjuvant chemo is planned. If confirmed -- they MUST get ALND OR they have to get neoadjuvant chemo upfront (only way to avoid ALND) Possibilities: cN(+) --> biopsy to confirm --> ALND or neoadjuvant chemo cN(-) --> SLNB --> 1-2 Ln+ --> RNI (no completion ALND) - Z11 and AMAROS --Z11 = steep tangent whole breast (not technically nodal) - only lumpectomy --AMAROS = regional nodal irradiation cN(-) --> SLNB --> 3 or more LNs + -- may need completion dissection

How can you control for observer's bias?

Blinding This is "detection" bias - this means that the observe may identify things differently between groups if it is known which group is which.

Take home for cetuximab - what initial data said it was good? - what did that actually compare RT+cetuximab too? - what major data is evidence AGAINST use of cetuximab?

Bonner NEJM trial showed an advantage of RT + cetuximab compared to RT alone (in stage III/IV) Generally better tolerated than Cis, but he didn't compare ChemoRT with Cis to RT+cetuximab. Evidence AGAINST Cetuximab - RTOG 1016 showed inferior OS, and PFS for cetuximab compared to HD cis in HPV+ population (newer descalation data) - When that was compared in a RR (2011) out of MSKCC for locally advanced HNSCC, there was a significant benefit of LRC, FFS (freedom from salvage), and OS for RT+cis compared to RT +cetux (thus it is relagated to a ~3rd line chemo option now)

DCIS Boost - multi-institutional analysis - Moran et al - result?

Boost reduced IBTR at 5/10/15 yrs -- relatively small benefit like we see in invasive

Practical staging for pancreas is based on resectable, borderline resectable or unresectable Borderline -- what things goes into this?

Borderline - ABC - A = arteries - most important - B = Biology - nodal mets, high CA19-9, etc - C = compromised PS due to tumor

High Risk/Metastatic Prostate Cancer - standard of care for high risk? Two major randomized studies looked at addition of RT to lifelong ADT (for T1b-T3, G2-3, and PSA<70) --> SPCG-7/SFUO-3 (875 pts) and MRC PR07 (1205 pts) -- pts had much more advanced disease, PSA >20 (~40% of patients), T3 (79%) based on exam -- both studies found what?

Both studies found significant benefit to RT added to ADT to 10 yr prostate cancer specific mortality. (about a 10-12% benefit) -- HR ~0.46 in both studies.

General Categories to know and basic paradigm Breast Conserving Therapy - node negative - whole breast only - node positive or high risk - breast + regional nodes Post-Mastectomy XRT

Breast Conserving Therapy Node negative - whole breast only --4256 cGy/16 fractions (Canadian, Wheelan 2010) --4005 cGy/15 fractions (UK Start B) --Astro consensus guidelines say 4256 cGy is appropriate for N(-) IDC or DCIS minimizing the 105% (used to be 107% hotspot max) - RT reduces LRR by 2/3 for IDC, and 1/2 for DCIS. - This improvement in LC leads to improved CSS by ~5% at 15 yrs (EBCTCG meta-analysis) -- for every 4 local recurrences we prevent, we prevent 1 death (4:1 rule) Node positive or high risk - breast + regional nodes --50 Gy/25 fractions to breast/CW and regional nodes (ax levels 1,2,3 and scv +/- IMNs) Post-Mastectomy XRT --Major indications: T3/4, positive margins, positive nodes -- Minor indications (T1-2N0): Menopause status (pre), close margins (<2 mm), LVSI, size (>2 cm), high grade, histology -- (Truong/Jagsi MVA RR) -----> Base this on +/- chemo; Truong, no chemo; Jagsi chemo. If you are getting chemo, you need more of the factors above to think about RT, if not, need less. -----> These factors drive LR so if enough of them, you treat to prevent local recurrence which MA20 and EORTC tell us will decrease distant mets and will eventually affect OS.

RTOG contouring atlas -- what is included in the breast/cw contour?

Breast, chestwall including pectoralis muscles and ribs. We don't usually include ribs at WF.

Basis of SDX? Heart constraint

Breath hold pushes the heart back/inferior and moves it away from chestwall Heart constraint: - Mean <4 Gy; V20 <5%; Strategies to reduce dose - prone, change gantry/collimator, mixed field approach (Field in Field-segmented field "poor man's IMRT") (photon/electrons), SDX, IMRT, heart block -- Rate of major coronary events increased by 7.4% with every 1 Gy mean delivered to heart. Ex: mean dose of 10 Gy would mean (10 x 7.4 = 74% increased risk of event from their baseline).

uterus is held in place by which four ligaments

Broad ligaments - lateral from uterus to pelvic sidewall Round ligaments - anterolateral from uterus to sidewall then through inguinal canal to labia majora Cardinal ligaments - lateral from cervix to side wall Uterosacral ligaments - posteriorly from cervix to sacrum - inserts S1-3 - cervical cancer can track along posteriorly into the pre-sacral space by following these ligaments Note: the first three all connect to the side wall the utero-sacral goes from uterus to sacrum...its in the name

What structures divides the superficial and deep parotid gland?

Buccal branch of CN VII

Burchiel Classification of TN

Burchiel Classification of TN Type 1: "Typical" extreme. sharp, >50% episodic pain, seconds to minutes, better outcome than type 2 Type 2: >50% Constant aching, burning, lower intensity than Type I Pain Descriptions Symptomatic TN: if caused by MS, this is neither Type 1 or Type 2, instead call it symptomatic. TN neuropathic pain: incidental trauma, like deafferentation pain Atypical facial pain: Somatoform, generally does not respond to GK well, or recurs quickly

Post-op CA19-9 of ____ is a good prognostic factor.

CA19-9 <90 is a good prognostic factor OS was better in those w/ good quality QA of plans and with head lesions that had CA19-9 <90

Just in case there is a question on this for ER - patients what trial showed a benefit to chemotherapy in the recurrent setting

CALOR trial This lady in osler also said there is a benefit to RT + hyperthermia to increase CR rates but nobody really does this anymore

Screening - CAP trial --> ProteCT trial - CAP trial -- (UK study) 550,000 men randomized by family practice to PSA screening vs no screening. If a case was detected --> that lead to a trial called the ProteCT trial (1643 pts) - screening rates were bad - 36% had valid PSA results - result of CAP?

CAP trial showed no PCa survival benefit to screening Take home -- ERSPAC showed survival benefit to screening whereas PLCO didn't

Workup for breast cancer?

CBC/CMP (incl. alk phos and LFTs) - mostly for chemo LN+ or Locally advanced, you typically need CT CAP, bone scan or PET scan (any acceptable) -- need to discuss metastatic workup if LN+

Targeted Radioimmunotherapy - what is the target of Ibritumomab (Zevalin) and what is the radiotag - what is the half life - what type of emitter - max energy - mechanism? - when is it indicated? - WHEN IS IT CONTRAINDICATED?

CD20-Y90 Monoclonal antibody against CD20 present on B cells - IgG1 mouse antibody 64 hours beta emitter 2.3 MV mechanism = antibody dependent cytotoxicity - recruitment of effector cells NK cells and macrophages - and phagocytosis indications: Low grade NHL or transformed DLBCL - dose 0.3-0.4 mCikg based on platelet counts Key to know = CONTRAINDICATED - all have to do with blood count stuff 1. BM involvement is >25% due to cytopenias 2. Platelets <100,000 3. Hb <8 g/dL

RTOG 1016 - non-inferiority cetuximab trial - HPV+ OPX patients, T1-2+N2-3 or T3-4 any nodes, M0 - 849 pts - randomized to 70 Gy + cis vs cetuximab - results? De-ESCALate trial - HPV de-escalation - european trial - 334 pts HP+ low risk - same randomizatino as RTOG 1016 - results?

CETUXIMAB was INFERIOR (not non-inferior) to cisplatin 5 yr OS - Cis - 84.6% - Cetux - 77.9% PFS significantly worse (67% vs 78%) LRF was higher in cetuximab group (17.3% vs 9.9%) Toxicity was EQUAL De-ESCALate trial showed the same thing -- (2 yr OS 97% for cis, 89.4% for cetux) -- toxicity again not different

Contents of cavernous sinus?

CN III, IV, V1-2, VI + carotid arteries

Contents of the cavernous sinus

CN III, IV, V1/2, VI and the ICA

What nerves run through the parapharyngeal space?

CN IX, X and XI

OVERVIEW CARD Basic Tx Paradigm - - Surgery = ? - Chemo = ? - RT = ? CNS - medulloblastoma - LGG - HGG - craniopharyngioma - ependymoma - germinomas (GGCT vs NGGCT) Non-CNS - Rhabdomyosarcoma - Neuroblastoma - Wilms tumor (nephroblastoma) - Ewings

CNS Medulloblastoma - Surgery = Extent of resection very important, ideally GTR, second look surgery may be needed (pts either Standard risk (SR; GTR or <1.5 cc resid, M0, OR age >3 yr), High risk (HR; STR or >1.5 cc resid) or infant medullo (generally we don't treat, chemo and wait) - Chemo = Concurrent weekly vincristine (Vcr) w RT followed by adjuvant chemotherapy (Cis/Vcr, cyclophosphamide, or CCNU); HR concurrent Vcr or Carbo - RT = CSI to 23.4 (SR)/36 (HR) Gy CSI + IF boost to 54 Gy (Standard risk) -- still technically have to do PF for HR patients (weren't including on ACNS study comparing PF to IF) LGG - Surgery = Max safe resection -- if GTR or even STR = monitor with MRI to determine pace of progression (or lack thereof) - 50% won't progress and you can hold RT - Chemo = start with chemo (vincristine/carboplatin) -- delay RT for 3 years on average - RT = if you are forced to treat -- usually 50.4 to 54 Gy (1 cm CTV) HGG - Surgery = max safe resection, may send back for second look - Chemo = not as good as adults, we tend to do TMZ, but PCV, CCNU, etc all seem to improve PFS and OS - RT = standard 59.4 in peds tho (2 cm CTV) craniopharyngioma - Surgery = GTR NOT critical; STR + RT better than GTR for long term control and toxicities - Chemo = no chemo, maybe injected Bleomycin, but more for salvage, not standard. - RT = 50.4-54 Gy @1.8's ependymoma - Surgery = Extent of resection Dominant Prognostic Factor - second look surgery/GTR critical - Chemo = limited role of chemotherapy (vcr, cyclophosphamide, etoposide, cis if used) - RT = +IF radiation of 54-59.4 Gy (respect the brainstem though) germinomas (GGCT) - Surgery = extent of resection not that important - Chemo = Young - Carbo/Etop x 4 cycles; older, can do RT alone - RT > M0 young: Carbo/Etopx4 cycles + 21-24 Gy WVRT + boost to 30 (CR) or 36 (PR) @1.5's >M0 older: can do definitive RT: 24 Gy WVRT + boost gross disease to 45-50.4 Gy >M1 young: Carbo/Etop + CSI 21-24 Gy - boost original disease to 30 (CR) to 36 (PR) >M1 older: RT alone = CSI to 24 Gy + boost to 45 Gy primary site and spinal nodules -- CSI 30 Gy if cord diffusely coated (@1.5's) germinomas (NGGCT) - Surgery = done AFTER neoadjuvant chemo -- Extent of resection more important - Max safe resection +/- 2nd look surgery - Chemo = EVERYONE before surgery = Carbo/Etop x 4 cycles alt with Ifosfamide/Etop x 6 cycles -- CR by tumor markers/MRI, go to RT, if not, consider second look surgery - RT = 36 Gy to CSI + boost 54 Gy to IFRT; 45 Gy to spine sites of disease Non-CNS Rhabdomyosarcoma - tx driven by 1. site - favorable/unfavorable - BiONG and BlEPP 2. pre-op staging (M0/1, SITE, size, LN status) 3. post-op pre-chemo clinical group (resection status R0/1/2, LNs resected or not, M0 or M1) 4. Risk stratification (Low - FOXO1 neg - CG1/2 or favorable site up to CGIII, intermediate - any alveolar, embyonal if unfavorable site, high - metastatic) - Surgery = Max resection - Chemo = VAC (vincristine, actinomycin, cyclophosphamide) - think "VACtinomycin-C" - to distinguish from VAC-IE for Ewings, A is adriamycin there; think VAdriaC-IE for Ewings. - RT: Group 1 embryonal/FOXO1 neg = 0 Gy - NO RT Group 1 R0 - alveolar (FOXO1 pos) = 36 Gy Group 2a - microscopic - (R1) = 36 Gy Group 2b - resect. lymph node dose - (LN+) = 41.4 Gy Group 3 - gross disease <5 cm at diagnosis = 50.4 Gy Group 3 - gross disease > 5 cm at diagnosis = 59.4 Gy ORBIT = 50.4 (technically can do 45 Gy if CR to chemotherapy first - NOT according to Dr. Brown) Technically no surgery for orbit or PM sites ideally - by definition are usually CG3 - need 50.4 or 59.4 Neuroblastoma - sick kids/blue berry muffin skin/racoon eyes , N-MYC bad (L1/2/M/MS) General Tx paradigms/Dose: - We mostly treat high risk patients -- metastatic/N-myc amplifications who are older than 1.5 years. - tx seq: mibg as part of staging 1. Induction chemo - DICCEx5 (DICCE) Doxorubicin, Ifosfamide, Cyclophosphomide, Carboplatin, Etoposide 2. surgery -- then MIBG re-eval, need to RT anything active here (if initial MIBG had >5 spots; if not, RT all on initial MIBG) 3. high dose chemo x 2 with tandem transplants 4. RT (21.6 Gy @1.8's to residual disease, used to boost residual 36 Gy -- recent data showed no benefit to boosting) 5. Post-consolidation therapy with immunotherapy and isotretinoin (differentiating agent)/immunotherapy - "IGD-2" Special situations -- 4S: Favorable (low risk): supportive care only, observe, spontaneous regression in 85% 4S Unfavorable (intermediate-risk): Chemo × 8 cycles. RT is NOT indicated for consolidation even w/ persistence - Reserve RT for symptoms d/t bulk ( i.e. resp. distress), cord compression, or not responding to initial chemo, or recurrence Pepper Syndrome Respiratory Distress not responding to chemo due to liver mets --> Whole liver, 4.5 Gy/ 3 fx at 1.5 Gy/fx; Can treat partial liver strip to decrease bulk. Stay off lungs/kidney/heart Cord Compression: < 3 yo, 9 Gy (1.8 /fx); ≥ 3 yo, 21.6 Gy (1.8 /fx) Wilms tumor (nephroblastoma) - Surgery = surgery +/- chemo for earlier stages. ---stage I/II = no RT unless inadequate chemo or relapse; still treat if unfavorable histology ---stage III: treat flank/WAI if spillage (B-SLURRP things) ---stage IV: tx metastatic site - Chemo = DD4A (doxorubicin, dactinomycin, vcr) - RT: >Flank: 10.8 @1.8's --> boost 900 cGy to 19.8 if diffuse anaplasia >WAI: 10.5 @1.5's (boost WAI to 21 Gy if diffuse peritoneal seeding UNLESS <12 months -- only go to 10.5 Gy in that case) >WLI: 12 Gy @1.5's (<18 months, gets 10.5 Gy) - some data suggests omission of WLI in CR's, but has worse EFS (only an option if favorable histology and NO LOH 1p/16q AND has pulmonary only metastastic disease) -recurrent wilms gets 21.6 to resected post-op bed. Ewings - Surgery = max resection - Chemo = VAC-IE (A = Adriamycin) -- A not given with RT; think "VACtinomycin" in RMS - to distinguish from VAC-IE for Ewings, A is adriamycin there; think VAdriaC-IE for Ewings. - 3 main indications for RT = 1. + margins 2. Tumor spill 3. >10% viable tumor in resected specimen after induction chemo (poor chemoresponse) - gross = 55.8 Gy - microscopic disease = 50.4 (this would be the larger volume pre-chemo/preop extent, and cone down to 55.8)

CONSTRAINT STUFF General Info V20 IL lung - TANGENTS ideal and acceptable? V20 IL lung - T+RNI ideal and acceptable? V20 CL - ideal and acceptable CL V5? PTV coverage Whole breast/Chestwall - axillary nodes - IMNs -

CONSTRAINT STUFF General Info V20 IL lung - TANGENTS only ideal <15, acceptable <20 V20 IL lung - T+RNI ideal <30, acceptable <35 V20 CL ideally 0. on B51 CL V5 <10% PTV coverage Whole breast/Chestwall - 50 Gy axillary nodes - 95% rx (47.5 Gy) IMNs - 90% rx (45 Gy)

treatment of T2N0

CONTROVERSIAL The problem is the accuracy of diagnosis studies show high rate of inaccurate staging -- significant number were upstaged on NCDB data In general, <2 cm and no nodes --> consider going straight to surgery If you hear nodes, T3 or size >2 cm --> chemoradiation +/- surgery

CONVERT - UK P3 study LS-SCLC - 547 pts. QD vs BID - what were the arms? - superiority or non-inferiority trial? - when did radiation start? - what was chemo? - what was major outcome? - esophagitis rates? - pneumonitis rates? - which toxicity was worse in the bid group? spinal cord constraints for convert compared to Turissi?

CONVERT - UK P3 study LS-SCLC - 547 pts. QD vs BID - 45 bid vs 66/33 w/ concurrent cis/etop - no difference in survival for bid vs qd (30 vs 25 mo. med OS p=0.14) - powered to show OS superiority of 66 Gy over 45 Gy. - toxicity not different - XRT started at cycle 2 - G3-4 esophagus was 19% on both arms- NOT different - G3-4 pneumonitis was 3% v 2% - NOT different - G4 neutropenia was worse on bid arm (49% vs 38%) Spinal cord constraint for bid was 36 for Turissi study, 41 for Convert (more modern RT techniques allowed for this) Problem is study is SUPERIORITY study and showed that daily wasn't superior; WASN'T powered for non-inferiority and thus can't say that 66 is non-inferior to 45 -- just that QD is not superior (essentially saying something is superior is a much harder benchmark, so 66/33 could still be inferior to 45) Based on this, BID should still be the standard

EORTC (Lefibvre, 1996) - 202 pts with operable pyriform sinus tumors - randomized to surgery --> RT (50-70 Gy) vs induction chemo (cis/5FU) --> RT (70 Gy) -- nonresponders go to surgery results?

CR with chemo = 51-54% Decreased distant mets with with chemo (36-->25%) Functional larynx at 3/5 years = 42/35% (high yield for boards) No diff in LRC No diff in survival 5 and 10 yr probability of being alive were 21.9 and 8.8% (in the larynx preservation arm)

Criteria for MM

CRAB - still part of criteria but now there are extra CRAB-SLM To meet these criteria, pts have to have the following: clonal bone marrow plasma cells >10% OR biopsy proven bony/extramedullary plasmacytoma AND any one or more of the CRAB MM defining features C-hyperCalcemia R-renal failure A-anemia B-lytic Bone lesions OR any one of the following biomarkers of malignancy Any one of the following S-60% or greater clonal plasma cells on BM exam L-serum involved/uninvolved free light chain ratio of 100 or greater M-More than one focal lesion on MRI >5 mm in size

CROSS Trial - DUTCH study - RCT, 368 pts - randomized to neoadjuvant CRT w/ 41.4 Gy w/ concurrent Carbo/Taxol followed by surgery vs surgery alone - med fu 84 months - what was surgical approach? - results? --how often was R0 resection obtained in each group? -- pCR was ___% in all pts. __% in AC and __% in SqCC. -- median OS difference? - what was the local and peritoneal recurrence rate in each arm?

CROSS Trial Results -- KNOW THIS CARD - 92% R0 resection in chemoRT. 69% in surgery alone. - Surgery was transhiatal approach pCR = 29% overall - 23% for adeno - 49% for SqCC - BETTER RESPONSE Median OS - overall - CRT = 49.4 months - Sx alone = 24 months - CRT doubled survival (SS) -- SqCC = 81.6 m vs 21.1 m (SS) -- Adeno = 43.2 m vs 27.1 m (SS) Local and Peritoneal recurrence rate was SIGNIFICANTLY lower with preoperative chemoradiation - 35% vs 58% overall recurrence - 14% vs 34% local recurrence

Major evidence for post-op ChemoRT?

CRT - both found +margins and ENE as groups to benefit - RTOG 9501 (SS LC benefit) - EORTC 22931 (SS OS and LC benefit) RTOG 9501 and EORTC 22931 -- NEJM Both looked at patients with +margins and/or ECE showing OS benefit with CRT vs RT alone. - OS was SS improved in EORTC and close in RTOG study (strong trend), but both did have SS improvements in local control.

Metanalysis of 6 trials looking at adjuvant chemo vs chemo and chemoRT - 1171 pts, included ARTIST trial - showed what?

CRT associated with significant increase in DFS but not OS

Imaging workup for anal

CT CAP MRI pelvis Colonoscopy with biopsy is not already obtained PET/CT - changes nodal stage in ~28%

Standard CNS SIM Set up?

CT simulation with short thermoplastic mask for immobilization in the supine position with arms at side. Would fuse in MRI for target delineation (if glioma, etc).

Kidney Cancer - stage IV - what to do?

Can be very slowly progressing and can surveil it, or it can be fast and you don't even put a dent in it. Metastatectomy or SBRT are in guidelines as things you can do for oligometastatic cases. These are usually just getting sunitinib or immuno Most of the data for kidney is pre-clinical or phase I/II single arm studies

Data for BCT in re-RT setting? - parital or whole? - dose? - how long ago much last BCT have been? - margin status requirement? - what imaging is required? Results: - who was included (size, ER,PR,HER2, nodal status, DCIS, invasive - what was 5 yr LC, freedom from mastectomy, distant met free and OS?

Can consider PBI (RTOG 1014) - PARTIAL breast - Dose = 45 Gy / 30 (@1.5's) bid fractions - 10 days - last BCT must've been >1 year ago - MUST have negative margins (no tumor on ink in this case) - mammogram and MRI required prior to PBI for re-RT - only really applies to women with pretty large breast in the re-irradiation setting. Results JAMA 2019 - 65 women enrolled; 58 evaluable - 40% were DCIS, 60% invasive - 91% had tumors <2 cm - all had cN0 - 76% ER+, 57% PR+, 17% HER+ - LC ~95% (5% had local recurrence in 5 yrs) - 10% had IL mastectomy (~90% 5 yr freedom from mastectomy) - distant met free survival and OS were ~95%

Take home message on hormones in salvage setting

Can justify doing 6 months ADT in PSA 0.2-2 pts in salvage setting with improved bPFS and DMFS - GETUG AFU 16 for 2 yrs of therapy -- think secondary analysis of 9601 where PSA < 0.6 was worse for hormones. PSA 0.7 or more in RTOG 9601 associated with higher OS

Role of RT in renal pelvis and ureter cancers

Cancerization effect type cancers Neoadjuvant and adjuvant RT hasn't improved outcomes in addition to negative margin surgery May have improved local control in patients with locally advanced and node positive disease -- may be a role in neoadjuvant setting in order to improve margin negative resection - possibly adjuvant in the case of node positive, but this is less common Data is essentially all retrospective. - Kansas red journal paper -- RT reduced LF from 24% to 10% in T3/4 or node positive patients chemo-immuno becoming much more common and role of RT shrinking

Concurrent chemo for locally advanced NSCLC w/ doses

Carbo AUC 2, taxol 45 mg/m2 weekly

What type of study would look at a group of people who ALREADY HAVE A DISEASE and look back to determine the natural history of the disease

Case series - major disadvantage is that there is NO control group with which to compare

Causes of TN

Causes of Trigeminal Pain: Vasc. compression: Most common cause of trigem cases Nerve compressed by superior cerebellar artery. MRI can be normal, and you just can't see the artery compressing nerve (sensitivity not great) With aging, there can be brain atrophy, which allows the artery to fall into the cranial vault → contact nerve Multiple Sclerosis: Plaques and demyelination at DRE (2% of MS pts have TN, and 2% of TN pts have MS) Can be bilateral, can be type 1 or 2 Effectiveness of surgical decompression (MVD) is controversial, Chan says it doesn't work We offer GK upfront here at WF. Better durability than rhizotomy Charcot Marie Tooth: Relatively common inherited neurodegenerative disorder → Bilateral TIC Lymes: Rarely causes trigem, but can be bilateral

Specific biopsy questions Central mass and/or endobronchial involvement? Peripheral? --What does peripheral mean? Suspected nodal disease? Pleural effusion? Solitary met site?

Central mass and/or endobronchial involvement = bronch Peripheral = Nav bronch, transthoracic needle biopsy ○What does peripheral mean? OUTER 1/3 Suspected nodal disease biopsied by EBUS, EUS, nav bronch, mediastinoscopy, chamberlain (LN lvl 5/6 - AP window) Pleural effusion: thoracentesis and cytology; negative cytology does not exclude involvement Solitary met site: biopsy that site 1st

HPV vaccinations

Cervarix - protects only against HPV 16/18 Guardasil - quadrivalent and nine-valent --quad also protects against 6,11 (warts) --nine valent has those + 31,33,45,52,58

Medulloblastoma - staging

Chang staging --but only use M part now (not T) Essentially - M0: no mets M1 : positive LP M2 : brain mets M3 : spine mets M4 : mets outside of CNS

Chemo Major indications for neoadjuvant chemo? Chemo choice in: - HR+ - HER2+ - TNBC - Inflammatory Breast Cancer Adjuvant (after neoadjuvant) - Her2 w/ <CR - TNBC w <CR

Chemo Indications for Neoadjuvant chemo: HER2+, T2+, LN+, IBC, TNBC HR+: ddACx4 + Tx12 -->Adriamycin/Cytoxan + Taxol (paclitaxel) HER2: TCHP --> TC (x6) - before RT; HP (x12) - during/after RT - Taxotere (docetaxel), Carboplatin, Herceptin (Trastuzumab), Perjeta (pertuzumab) TNBC: TC+io -> AC+io - Taxotere (docetaxel), Cyclophosphamide, Adriamycin/Carboplatin - Pembrolizumab if nodes, x 9 cycles --> x9 more cycles (regardless of response) --> pCR done, <pCR = add xeloda to pembro. IBC: based on markers Adjuvant: HER2+ w/ residual dz = kadcyla, EnHer2 TNBC w/ residual dz = capecitabine (xeloda)

Nasal NK T cell lymphoma - chemo - what dose of RT do you need?

Chemo is unclear - VIPD vs SMILE RT first and then chemo You need at least 50 Gy -- this is asked all the time

JCO 2007 - retrospective analysis of 181 pts with LAPC enrolled onto prospective phase II and III GERCOR studies - compared survival of patients that had chemoRT vs pts that just continued on Chemo alone. Neoadjuvant chemoRT vs Chemo for LAPC results?

ChemoRT vs Chemo median PFS was 10.8 m and 7.4 m (SS) median OS was 15 m and 11.7 m (SS)

Local excision -- adjuvant therapy (Borstlap 2016) Meta-analysis 2016 for adjuvant chemoradiation compared to immediate re-operation with radical surgery - 14 studies - Looked at T1 and T2 rectal cancers sp local excision - results?

ChemoRT was WORSE than radical surgery Local Failure - 14% vs 7% (true for both T1 and T2) No difference in distant failure

Locally advanced (stage III) - soc for inoperable Lung Ca?

Chemoradiation (carbo/taxol) durvalumab outback (Pacific) Pacific: CRT +/- durva - 2 yr OS: 66.3% (durva) vs 55.6% (placebo) - SS - Median PFS: 17.2 vs 5.6 mo (SS) - overall response rates: 30 v 17.8%N

Thymoma workup

Chest CT w contrast Serum b-hcg, afp, cbc platelets PET/CT scan PFT to assess for surgery Chest MRI -- will help to discern degree of involvement for surgical resection

Best statistical analysis to compare proportions (e.g. 2x2 table comparing response high or low in two treatment groups)

Chi-square test - compared observed values w/ expected values

Concurrent chemo for LS-SCLC w/ doses

Cis 60 etop 120 q 3 wk

1st line Chemotherapy for head and neck? Ideal dosing? 2nd line dose? 2nd line chemo if can't do first line? 3rd line chemo if can't tolerate others? Data comparing dose levels in first line option?

Cisplatin either 100 mg/m2 q3 week OR 40 mg/m2 qweekly. Generally thought that bolus is better but LD is better tolerated if comorbids/kidney function is bad. HN009 is testing this 100 mg vs 40 mg Only recently, data out of India shows a SS improved LRC in the bolus arm compared to weekly (P3, RCT non-inferiority -- ie. weekly was inferior to bolus) Major Criticism is that they used 30 mg/m2 instead of 40 which is what we use in the US for weekly -- so no way to know if SS difference would have still been there if they used 40. Commonly used chemo: - HD Cis 100 mg/m2 x3 cycles (usually get in 2) > LD Cis 40 mg/m2 weekly x6-7 cycles > if not tolerated can consider carbo/taxol weekly > if can't do those -- cetuximab (has acneiform rash, but otherwise much better tolerated)

Reed-Sternberg cells are what? What % of the tissue due they make up?

Classic cells described in HL - these are the clonal malignant cells in HL though. They are counterintuitively the rare population to find (below) large, bilobed nuclei, w/ prominent nucleoli --> "owls eye appearance" - they comprise <1% cells in the tissue -- background cells accumulate due to cytokines

Classical HL - four major subtypes 1. Nodular sclerosis (70%) - most common 2. Mixed cellularity - older adults 3. Lymphocyte predominant 4. Lymphocyte depleted (1%) - worst prognosis Classical HL is DIFFERENT than "Nodular" Lymphocyte predominant -- What are the marker differences between classical HL and nodular lymphocyte predominant major differences between these: - Reid sternburg cells are called what in each variant? - Fibrosis more common in which? - EBV more likely positive in which?

Classical is CD30+, CD15+, and CD20-, CD45- Note: NODULAR lymphocyte-predominant is a different entity. These are CD30-, CD15-, and CD20+ Remember Rituxan not used generally for Classic HL -- could be used for NLP disease. RS cells = popcorn cells in NLP Fibrosis more common in classical EBV more common in classical

N staging for OP (p16 negative)

Clinical cN1 = Single IL node <3 cm cN2a = Single IL node 3-6 cm cN2b = Multiple IL nodes <6 cm cN2c = B/L or C/L node < 6 cm cN3a = nodes >6 cm and no ECE cN3b = any extranodal extension Clinically: Any ENE makes you N3b immediately. Pathologic pN1 = Single IL node <3 cm pN2a = Single IL node 3-6 cm OR Single IL node <3 cm with +ENE pN2b = Multiple IL nodes <6 cm pN2c = B/L or C/L node < 6 cm pN3a = nodes >6 cm and no ECE pN3b = any extranodal extension in >1 node (or 1 node w/ EVE that is >3 cm technically) For pathologic, ENE can be N2a if only single and if <3 cm. Remember ENE is NOT in the staging for p16 positive AT ALL (clinical or pathologic)

What location for a vulvar cancer has a risk of spreading directly to the pelvic nodes w/o going to the inguinal first?

Clitoris tumors - directly through the parasymphyseal plexus

Management of node positive epithelioid mesothelioma w/o metastatic disease?

Combination chemotherapy -- no surgery for n+ mesothelioma

Alliance A11202 study is looking at clinical N+ -- the comparison of cALND followed by RNI vs RNI alone with no dissection

Companion study to B51

IMPORTANT FOR BOARDS - Adjuvant Study Bolus vs Continuous Infusional 5-FU study - NCCTG led Intergroup study Compared PVI 5-FU (225 mg/m2/day for 5 weeks) vs bolus 5 FU (500 mg/m2/day on days 1-3 and days 36-39) during RT - 660 stage II or III pts randomized to 5fu or 5fu + semustine (bolus vs continues infusion) - RT was concurrent - 50.4 - 54 Gy RESULTS? Which was better?

Continuous (PVI - protracted venous infusion) won - reduced distant metastasis (31% v 40%) - 4 yr RFS (53% v 63%) - improved 4 yr OS (70 v 60%) NO difference in local recurrence rate PVI had HIGHER rates of severe diarrhea Bolus had HIGHER risk of leukopenia No benefit of semustine (Methyl-CCNU)

Hodgkin Lymphoma 8500 new cases per year <1% of cancer diagnoses Bimodal age distribution - younger in 20's and older in 60's Major differences in Hodgkin vs Non-Hodgkin

Continuous spread is like neck nodes to mediastinum - more rare for HL to have a neck node and groin node. That would be more typical of NHL Uncommon to have extranodal involvement for HL and rare to involve Waldeye's ring

Describe how you would define your flank field?

Contour the presurgical volume and add 1 cm margin, flash skin laterally Extend medial edge to include entire vertebral body. AP/PA Carve your CTV out of organs that have settled into the field post-operatively

Recommended dose contraints based on the MDACC IMRT series?

Contralateral lung MLD < 8.5 Gy V20 <7% This is why you DONT think IMRT after EPP because you end up putting too much dose into the CL lung. AP PA is better if they have 1 lung

Role of PORT after surgery?

Controversial because every study shows an improvement in LC with PORT BUT None of them show a survival benefit to PORT and some show WORSE survival with PORT.

General Treatment Paradigms (GBM) :- first step? - who gets adjuvant CRT?

Craniotomy with maximal safe resection -- for everyone (except RPA 6, will probably go to hospice) EVERYONE gets adjuvant TMZ regardless of MGMT (~30% of LGG/HGG have this) STUPP 2005 showed 10.9 vs 27% 2 yr OS benefit for CRT vs RT alone. - median OS benefit 12.1 mo --> 14.6 mo - MGMT methylation status was a strong predictor of outcome - degree of resection still shows strong association with outcome. TTF (optune) can be offered to everyone -- significant PFS/OS benefit but must be worn >18 hrs a day and must shave head

DCIS - proliferation of cancer cells confined to the ductal structures w/o evidence of basement membrane invasion - Stage 0 Tis is the stage - diagnosis was rare prior to mammo - incidence increased between 1982 and 1988 since more screening - 95% presents as mammographic abnormalities - rare to have a mass a symptom. - 76-90% have microcalcs - linear, branching patterns more likely to be high grade - types? Primary concern is the risk of DCIS progressing to invasive disease.

Cribriform type papillary type +/- necrosis Solid type comedo type - solid sheets of malignant cells filed with dilated ducts, center involved with ducts undergoing necrosis and calcifications

In general with MIBC, what are treatment options and who is an ideal candidate for trimodality bladder preserving therapy

Cystectomy and BPT considered to be equivalent in terms of oncologic outcomes IF the following criteria are met: - max TURBT with fully resected gross disease - non-metastatic disease - no pelvic nodes - no T3/4 disease (involvement of peri-vesicular tissue or invading nearby organs) - technically up to T4a - no hydronephrosis (interestingly, Osler guy said this is because you can't give cisplatin if they have hydro) - no multifocal disease - lack of widespread in situ disease - able to give full dose RT (not a ton of bowel falling into the pelvis that preclude delivery of full dose RT) - able to get chemotherapy (although, even without chemo, probably only lose 10-15% LC, no diff in OS) - functional bladder (bladder is worth preserving) + no severe LUTS - <6 cm in size (per OSLER) In reality, if patient isn't a candidate for surgery, BPT can be given with tempered expectations.

Extent of lymphadenectomy for stomach - D1 vs D2 vs D3 lymphadenectomy how many LNs are required ON the topic of extent of lymphadenectomy for stomach -- data shows what?

D1 - perigastric D2 - D1 + celiac trunk and branches D3 = D1+D2 + ometectomy, splenectomy, distal pancreatectomy, porta hepatis, and paraaortic minimum of 15 LNs required for dissection for stomach Minimum of 12 LNs for colon Three trials shown here essentially all show that there was no improved survival for more extensive dissection and higher operative complication rates for more extensive dissection.

Optimal duration of ADT in high risk prostate cancer DART study (355 pts, int - high (55%) -- 4 months ADT vs 28 months ADT + dose escalated RT - found what? PCS4 - 18 months vs 36 months ADT in addition to 70 Gy EBRT. Superiority trial. Frizzell wisdom -- 7 major trials showed benefit to ADT. Duration is supported by which study for each time below: - 6 months - 12 months - 18 months - 24 months

DART study - 95% OS in long term ADT vs 86% in short term. so 28 months better than 4 months PCS4 -- 36 months WAS NOT better than 18 months in terms of cancer specific or overall survival. It was better for biochemical free survival (duh, but who cares about that). It will ALWAYS be better with more hormones if castrate sensitive so that doesn't matter. Frizzell Wisdom - 6 months - TROG 9601 - 12 months - ASCENDE-RT - 18 months - NABID, RADAR - 24 months - RTOG 9202 (+8531, 8610) Overall, exact correct duration unclear but 6-24 months commonly accepted.

How thick is the aquaplast bolus?

DB Typically 2mm every day, we do not include this during boost KW If your institution does not have aquaplast bolus you can use 5 mm every other day, including boost

High grade/aggressive lymphoma

DLBCL - most common (25% of all NHL) Burkitt's lymphoma

Which change with changing disease prevalence? - sensitivity - specificity - PPV - NPV

DO NOT CHANGE: - sensitivity - specificity This is the case because the TP and FN always correspond to the patients with disease and this is a property of the test itself, not the population it is used in. DO CHANGE with increase/decreased prevalence: - PPV - NPV These change with disease prevalence because the calculation involves including true positives and false positives thus if a disease is more prevalence the PPV is better. If a disease is very uncommon, the NPV is better and PPV is poor. Think of this like the test is cheating and is more likely to be right about you not having a disease if the disease is unlikely in the first place. This can be extended by saying that the NPV isn't as good because if you get a negative result for a condition with high prevalence and high suspicion for the patient having the disease, what do you do with that negative - you don't trust it.

just for reference - sbrt pancreas constraints

DO NOT MEMORIZE

What depth of invasion is used as an predictor of LN failure >10% risk?

DOI >5 mm

Known LCIS, what is the risk of invasive cancer?

DONT EVER TREAT LCIS WITH RADIATION LCIS has 7% risk of invasive cancer at 10 yrs, ~ 20% at 15 yrs LCIS IS A MARKER FOR BILATERAL BREAST CANCER Need bilateral mammogram if LCIS detected on biopsy, but regardless you are going to end up getting an excisional biopsy, so do either excisional biopsy or lumpectomy and look for any invasive disease, then close observation The risk of developing invasive breast cancer is 9-12 times higher in a patient w/ bx proven LCIS vs the normal population

what is the deauville criteria?

DS 3 or below is usually considered to be negative The PET directed therapy trials considered 2 to be negative.

RTOG combined analysis of phase II single arm and some III studies (RTOG 8802, 8903, 9506, 9906, 0233) - Looked at bladder preserving efficacy - results?

DSS and bladder impact survival is about 60% at 10 yrs with BPT T2 pts have better survival

Danish 82b and 82c - Overgaard data - what was chemo? - what was the surgery? - who was included? - what were arms? - reduction in LRR - OS benefit? - median FU What is the difference between Danish 82b and 82c?

Danish 82b - Overgaard - NEJM 1997 - Modified radical mastectomy - Chemo = CMF x 8 cycles - stage II-III BC (1708 pts) -- PRE-menopausal - arms = PMRT (CW + regional nodes incl. IMNs) vs Obs - LRR: 32% --> 9% (72% reduction if PMRT) - 10% 10 yr OS benefit - median follow up = 114 months These women got ALNDs. Median number of nodes was 7 taken. This is the most important take away about a possible problem, radiation was possibly taking the place of a good dissection. They are both 1708 women randomized to obs vs PMRT but 82c was POST menopausal women and included tamoxifen after chemo. IN 82c (Overgaard Lancet 1999) PMRT reduced LRR from 35-->8% (18 yr fu showed 49% vs 14% LRR diff) - again ALND, randmoized to tamoxifen or tam + RT - distant mets subsequent to LRR was much higher in no RT arm (35% vs 6%) - thus PMRT was seen to change the pattern of recurrence and this affects seeding from the LR of distant disease -- probably why it showed an OS benefit. Both trials showed no evidence of excess cardiac morbidity or mortality and both trials showed benefit for RT in LN+ disease. OS benefit was 10% in BOTH studies

What are heart associated risk of breast irradiation?

Darby NEJM 2013. 2168 women 1958-2001. Rate of major coronary events increased by 7.4% for each increase of 1 Gy in the mean radiation dose delivered to the heart (95% CI, 2.9 to 14.5; P<0.001). A mean cardiac dose of 10 Gy would result in a relative increase of 7.4 x 10 = 74% from the patient's baseline risk. If Mean cardiac dose were 10 Gy, her absolute risk of death from ischemic disease would increase from baseline of 1.9% to 3.3%. Because 74% of baseline is 1.4% add that to 1.9 = 3.3 new risk of heart tox. This is stochastic The risk of heart toxicity increases from baseline for each additional Gy of heart dose

Why is there controversy about PMRT for 1-3 nodes? What are the major trials to quote for this and the major subset analysis to know?

Data in the picture showed summary of LR risk in T1-2N1 pts from a bunch of trials if axillary RT wasn't given - the rates of recurrence are actually not that high. And the picture is clouded by Z11 since Z11 was supposed to just be whole breast after SLNB for 1 or 2 nodes. Jagsi's analysis of Z11 showed that most people actually got their axillas treated (19% just flat out got RNI and 50% got high tangents covering levels I and II). So like 70% of those people actually got their axillas treated. 1-3 LN+ - DBCG subset analysis - 82b and c found OS benefit to PMRT even in 1-3 nodes. Criticism is that it is not clear that this is true if a better dissection was done (median 7 nodes taken). - this subset analysis looked specifically only at 1,152 pts with 8 or more lymph nodes dissected --> There was still an LR (27 v 4%) and OS benefit (9%) in the 1-3 LN group. - in the 4+ nodes group it was a larger benefit with LRR (51 v 10%) and the same OS (21 v 12%) benefit. - 9% OS benefit in BOTH groups. British Columbia Retrospective (Truong) - looked retrospectively at 821 women w/ pT1-2 tumors with 1-3 nodes positive sp MRM wo XRT - did UVA and MVA looking at risk factors that gave a 10 yr LRR risk >20% --> young age (<45), T2, grade 3, ER-, medial location, >1 LN+, >25% LN+. MVA confirmed age <45, ER-, medial location, >25% LN+ - age <45 was the MOST powerful prognostic factor. IBCSG retrospective data - looked at same population as Truong and found the same sorts of things. EBCTCG also showed a benefit in the 1-3 lymph node group.

Defintive ChemoRT for esophagus cancer trials - RTOG 8501 --- randomized to 64 Gy RT alone or chemoRT - 5FU/Cis + 50 Gy --- 90% sqCC --- trial closed early because of benefit what? --- 5 yr OS CRT v RT alone? ---how many CRT patients had persistent disease at 12 mo? - INT 0123 - high dose RT vs low dose RT --- RCT, 236 pts ---Exp arm of RTOG 8501 (50.4 Gy 5FU/Cis) vs Dose escalation + chemo (64.8 Gy + 5Fu/Cis --- which arm won? - EOCG 1289 --- pts w/ SCC esophagus RT or RT +5FU/MMC ---40% went to surgery ---survival diff? - RTOG 0436 (similar to SCOPE-1 trial, next card) --- RCT, 344 pts --- 50.4 Gy cis/taxol +/- cetuximab - results?

Defintive ChemoRT for esophagus cancer trials - RTOC 8501 --- randomized to 64 Gy RT alone or chemoRT - 5FU/Cis + 50 Gy --- 90% sqCC --- trial closed early because of benefit of chemo --- 5 yr OS CRT v RT alone = 27% vs 0% --- chemoRT had significantly better LC - but 46% of CRT pts had persistent disease at 12 months which led to INT 0123 trial - INT 0123 - high dose RT vs low dose RT ---the control arm won, median and 2 yr OS as well as persistent disease favored control arm. 13 v 18 months. ---7 patients died in the high dose arm (but note they died BEFORE even reaching 50.4 Gy -- so not exactly fair to say that) ---overall higher rates of toxicity in the high RT dose arm - ECOG 1289 - chemoRT good --- pts w/ SCC esophagus RT or RT +5FU/MMC ---40% went to surgery ---survival diff = 14.8 months vs 9.2 months med OS. 2 yr/5 yr 12%/7% and 27%/9%. - RTOG 0436 --- no difference in complete response rate, local failure, toxicity or survival (different than SCOPE-1 trial) -- SCOPE1 failed to accrue but did show worse treatment completion associated with cetux.

What is the dominant prognostic factor for ependymoma What do you do if they say then only got STR? What chemo do you give you are forced to suggest chemo?

Degree of resection Willing to accept higher morbidity from surgery or RT since mortality is so high If they tell you it is a STR then say do chemo and try to get to a second look surgery. Send to st jude for second opinion regarding surgery I don't beam on unless i have a gtr or all surgical options are exhausted If you do have to use chemo say cis based doublet Say cisplatin not carbo CHEMO IS NOT A SAFE BOARDS ANSWER ONLY SAY CHEMO IF THERE IS NO WAY TO GET A GTR AND YOU ARE TRYING TO GET TO A GOOD SECOND RESECTION OR LESS THAN 1yo Chan says if he had a STR on the orals he would press to get a second opinion to try to resect If they still say no GTR, then he may consider cis based doublet chemo to try one last time to get a GTR (you must use cisplatin, not carbo). If he still couldn't get a GTR after induction chemo, he would do RT with a STR but says there is no data for adjuvant chemo after the RT. Chemo has been tried in upfront, and adjuvant settings POG studies looked at Neoadjuvant setting to delay RT and kids did worse the longer you delayed RT The only time we do this is if < 1 yo, otherwise beam on There was a phase 2 study looking at adj cisplatin based chemo and didn't do better than historical controls Also a randomized study was performed and also didn't help but in that case they didn't use cis based chemo Now there is a randomized study underway with cis based chemo in anaplastic patient ACNS

Which medulloblastoma subtype can actually do well post-operatively without radiation - NEJM article showing ~85% DFS which is about what we expect for SR after RT

Desmoplastic histology with SHH signaling NOTE: intraventricular radiation

LGG Overall Survival

Diffuse astro: OS ~ 5yrs, this is about the same as grade 3 oligo Oligoastro OS ~ 7.5 yr Oligodendro OS ~ 10 yr 5 yr OS all comers: 60-70%: but most (~ 80%) eventually transform to GBM even after tx. We don't really see people "cured" of these (except Pilocytics), they just survive a long time → eventually transform → die Even if "cured", people tend to have a worse OS than the general population (SHAW)

Differential for brainstem tumors

Diffuse intrinsic pontine glioma (DIPG) Exophytic medullary glioma Midbrain or tectal glioma About 50% of brainstem gliomas are low-grade (WHO I-II) and 50% are high-grade (WHO III-IV). We tend not to biopsy them so don't necessarily know what grade they are

Standard of care for decades was mastectomy for DCIS No RCTs have ever compared BCT to mastectomy for DCIS Contra-indications for BCT?

Diffuse suspicious microcalcs Multi-centric disease prior rt active collage vascular disease pregnancy larger tumor size relative to breast persistently positive margins ATM (biallelic inactivation) Li-Fraumeni is a relative CI

Ewing's Sarcoma - what are the expendable bones? (not deforming)

Distal 4/5ths of clavicle inferior portion of scapula proximal fibula iliac wings ribs

Peds LGG gets a STR, what is your next step?

Do surgery and try your best not to tx with RT. Even with STR you can actually observe Only give RT for progression or symptoms, hypothalamic wasting etc... only tx if you really have to If G1/G2 - really reserve RT only for clinically significant progressive disease or symptoms (example OPG getting hypothalamic wasting syndrome). RT basically gives equivalent results to GTR, 15% fail as a LGG, and 5% fail but come back as GBM

Kidney cancer - size dictates what you do but options are generally surveillance, nephrectomy, ablative techniques (IR techniques) - SBRT phase 1 dose escalation paper out of Case Western -did not see a ton of G5 tox (3 PR observed with limited toxicity and no G5).

Dont know if its very high yield to know all of these details, but there are several SBRT trials for kidney Peter Mac Phase I dose escalation paper showed good local control Kidney function after SBRT showed decreased IL function by about 9 mL/min CrCl at 1 yr but the CL kidney more than makes up for it by increasing function to by 12.3 mL/min. You start to see a kidney function decrement by 10 Gy. Trevor Royce says this is reasonable if they only have one kidney and nephron sparing surgery is not feasible or if they are non-operable for some reason.

Surgery for anal canal Local excision - 5 yr OS good 88% but LR recurrence is 46% APR - 25-70% 5 yr OS - 23-35% LR recurrence - 10% distant disease

Dont usually talk about surgery Only consider local excision is you can get >1 cm margin - only for T1 perianal low grade. If <3 mm invasion and <7 mm diameter and R0 --> no further therapy APR typically reserved for salvage for local recurrence or persistent disease. Definition of persistent disease VERY important -- later card RS series looked at surgical salvage after CRT - Ellenhorn - 5 yr OS 44% - MD anderson - 5 yr OS 64%

AVM dose

Dose depends on size (17-22 Gy generally) < 3 cm = 22 Gy to 50% IDL > 3 cm = try to get > 17 Gy at least to 50% IDL Dose seems to plateau at 22 Gy for effectiveness, but < 17 Gy is bad If really big AVM try doing staged approach > 17 Gy to deeper part Treat the rest 3 - 6 mo later. If in brainstem, do <16 Gy to 50% IDL

What are the outcomes of DIPG and what is your dose? Does RT help symptoms? When do these kids progress? What is survival?

Dose is 54 Gy/30 fx GTV (as defined by T2/FLAIR) + 1.5-2 cm CTV margin with respect for natural boundaries. COG-recommended dose limits to chiasm, spinal cord, and cochlea are 50.4 Gy. About 75% improve clinically after RT, Typical time to progression is 5-6 months, and MS is 8-12 months.

SBRT dose Prescriptions Peripheral options vs Central Options

Doses NOT central - 34/1 - 54/3 ok for central or peripheral - 48/4 - not ultracentral - 50/5 - 60/8 - (ultracentral) - 70/10 - (ultracentral) - 60/15 - not used as often, mostly if very large and person not a candidate for chemo-RT

Marginal zone lymphoma of Orbit - doses used? High yield studies they may ask about: - Goda - 25 Gy - what were patterns of failure - Stanford - 4 Gy - what was ORR and CR rate - was was FFLR at 2 yr - Partial orbit RT - Standford - 30.6 Gy - what was LF rate at 5 yr and where were the failures? - benefit of 4 Gy?

Doses of 24-25 Gy give excellent local control. - Goda - 25 Gy - 68% distant, 23% CL orbit, 9% local -- overall 25% relapse rate - Stanford - 4 Gy - ORR 96%, CR 85%, CR pts had 100% FFLR at 2 yr , no in field relapse - Partial orbit RT - Standford - 30.6 Gy - LF 5.3% (8.3% were conjunctival, 0% lacrimal) - benefit of 4 Gy = 100% ORR in retrospective studies. 86% CR. EXCELLENT response and virtually no toxicity - you want to do this "staged" if you are going to do it and bring them back to ensure CR, if not go ahead with total 24 Gy But the 24 Gy dose is the more definitive approach.

PD-L1 inhibitors? (3)

Durvalumab Atezolizumab Avelumab

Patterns of failure after SBRT for early stage? Patterns of failure for locally advanced NSCLC?

EARLY NSCLC = MOST COMMON SITE OF FAILURE IS LOCOREGIONAL IN REGIONAL NODES. - Distant metastatic disease in the 10-25% range Locally Advanced = DISTANT METS is the predominant pattern (70%) - 20% fail locally - 10% recur locally and distantly

Management of the Penile Primary Tis, Ta, T1 (w/ minimal invasion) - options? More advanced T1 or higher?

EARLY cancers - doesn't involve RT at all Topical therapy (imiquimod 5% or 5-FU 5% creams) Laser therapy (CO2, YAG, KTP, etc) Surgery (WLE or Mohs micro) T1 or higher SURGERY - partial penectomy if margins can be negative - total penectomy if margins cannot be achieved - penectomy associated w/ high suicide rates Radiation - Brachytherapy - HDR 60-65 Gy in 5-6 days - Definitive EBRT - to 65 or 70 Gy Adjuvant chemoradiation given if inguinal or pelvic LN positive - LN chain to 45-50.4 Gy w/ boost to 65-70 for gross disease or ECE - include primary site if positive margin

Experience with Brachytherapy

EBRT + Brachy data out of MSK (Harrison) - - gives control between 82% (T3), 93% (T2) and 87% (T1) - 5 yr LRC good at 96% Sort of falling out of favor - some people do IORT with electrons.

What LN stations are sampled with the following EUS EBUS Mediastinoscopy Chamberlain

EBUS w FNA: -can access 1, 2, 3, 4, 7, 10 EUS - can access 4,5,7,8,9, adrenal Cervical - mediastinoscopy: - incision 1 cm above sternal notch - can access bilat 1, 2, 4, 7 Chamberlain/anterior mediastinoscopy: - incision at left 2 nd intercostal space - can access 5/6 - indicated for T3 or central T1/2 LN stations: 1: high mediastinal 2: upper paratracheal 3: retro-tracheal 4: lower paratracheal 5: AP window 6: paraaortic 7: subcarinal 8: paraesophageal 9: pulmonary ligament 10: hilar 11: interlobar 12: lobar 13: segmental 14: subsegmental 2 extends down to top of aortic arch 4R top of aortic arch to carina 4L top of aortic arch to mid pulm artery 3: pre-vascular 6: anterior and lateral to aortic arch 5: Bottom of aortic arch to pulm artery 7: subcarinal 8: paraesophageal 9: pulm ligament 10+: hilar and subhilar

Caveat to no induction chemotherapy for NPX cancer is relevant to what population?

EBV+ nasopharynx cancer Based on the Chinese paper in NEJM (next card

COG A9961 - average risk, Did 23.4 Gy CSI with 55.8 PF boost. - 421 pts - randomized to two different chemo regimens (CCNU/Cis/vcr vs Cis/cytoxan/vcr) results

EFS and OS were similar

rules of thumb for risk categories in neuroblastoma

EFS is horrible in high risk - old data EFS was 30% at 5 yr. Its probably 50-60% now Historical data we used to have ~15% survival. Now we are in 50% range.

Benefit of boost?

EORTC 22881 "boost-no boost" - WBI vs WBI + boost - ~4% benefit to boost for LC only (9 vs 13% SS) - 17 yr follow up was 16.4% v 12%. - severe fibrosis 4.5% v 1.6% - 20 yr update showed: ---IBTR for entire cohort was 15% ---young age (<50) and DCIS associated with increased IBTR ---DCIS 18% v 9% (no boost v boost) ---high risk: 31% v 15% (no boost v boost) EORTC 5318 - 16.4% vs 12.0% - fibrosis was greater in boost arm in this study - probably can be done better with modern techniques. No difference in OS, DMFS Lyon trial - 1024 women (10 Gy boost v 0 Gy) - 5 yr IBTR was 3.6 v 4.5% with higher telangiectasias.

ChemoRT vs RT - take home points to know?

EORTC and UKCCR trials looked at this Both did 6 weeks breaks and continued RT or went to surgery based on response EORTC --> SS difference in CR w/ chemo (80 vs 54%, SS), no diff in OS UKCCCR --> trend to better CR w/ chemo (39 vs 30%, NS) --> the difference is that they evaluated for complete response 6 weeks after 45 Gy in UKCCCR whereas it was 6 weeks after 60-65 Gy in EORTC This is way to early to eval for treatment response UKCCR update (CRT v RT for all below) - LF 30% w/ CRT, 60% w/ RT alone - CSS 70% v 55% - OS consistently 5% higher in CRT - no significant difference in toxicity -Statistically significant reduction in risk of dyring from anal cancer in the CRT arm

Type of biopsy you want for both HL and NHL?

EXCISIONAL either way - you want to see nodal architecture

Distribution of lung cancer stages at diagnosis

Early stage - 1/3 Locally advanced - 1/3 Metastatic - 1/3 Of note, the definition of Locally advanced is really stage III (T4N0, T3N1, T1-2N2, N3) but technically stage II that is N+ is treated like locally advanced from an RT perspective (chemo-RT) -- could still get surgery and chemo though Of the stage III patients, only single station N2 should be considered for surgery really. Bulky multistation N2 should not go to surgery.

NLPHL - smaller subset of HL - 5% of HL - popcorn cells - peripheral location (axilla pelvis) - b sypmtoms rare management?

Early stage - no high risk features - RT alone - 30 Gy "Generous Involved site" -- they aren't getting systemic therapy 5 yr PFS is 91.1% But late relapses can occur -- they need to be re-biopsied as these can transform into a T cell rich DLBCL - in 3-5% of patients

Treatment for hot flushes/doses?

Effexor 37.5 mg PO qd

Pediatric CNS constraints to memorize - Spinal Cord - Brainstem - Brainstem surface - Optic chiasm - Optic nerve - Retina - Lens - Cochlea - Lacrimal gland - Pituitary gland - Optic nerve/chiasm SRS constraint - Brainstem SRS constraint

Ependymoma - Just say you allow point max of 59 or no more than 1% of PRV getting 59 CNS - Spinal Cord = Dmax 45 Gy or less - Brainstem = 1.8-2 Gy --> Dmax < 55 Gy, 55-60 Gy "Acceptable" - Brainstem surface = ventral 3 mm of brainstem from 9 O clock to 3 O Clock - Dmax <55 Gy, 55-64 Gy "acceptable" - Optic chiasm = <54-55 Gy, 55-60 acceptable - Optic nerve = <54-55 Gy, 55-60 acceptable - Retina = Dmax = 45 Gy, 45-50 acceptable - Lens = Dmax <7 Gy, 7-10 acceptable - Cochlea = Ideally one side mean <45 Gy - Lacrimal gland - Dmax = <40 Gy (V30 <50%) - Pituitary gland - Dmax = <50 Gy - Optic nerve/chiasm SRS constraint = <8 Gy - Brainstem SRS constraint = no more than 1 cc >12.5 Gy

Differences on imaging w/ ependymoma vs medullo

Ependymomas creep downward through foramen magnum - toothepaste tumors Ependymomas have more calcs

GELA LNH-93-1 LNH (Reyes NEJM 2005) - YOUNGER pts - younger pts <61 yrs w/ stage I and II aggressive NHL - randomized to -- ACVBP x 3 + consolidation chemo OR -- CHOP x 3 + 40 Gy median fu 7.7 yrs results?

Escalated chemo was actually BETTER than chopx3 + RT 5 yr EFS 82 vs 74% 5 yr OS 90 vs 81% both SS

HPV screening vs PAP smear

Essentially HPV negative has a better negative predictive value for development of cervical cancer compared to cytology alone HPV testing is much more sensitive than PAP screening with cytology alone. HPV testing was not very specific in women <35. In older women, HPV testing is highly sensitive AND specific - this is why we DONT do HPV testing in younger women until you get to 30 -- it isn't very specific -- mostly because the majority of women will clear the virus

Y90 benefit?

Essentially only hepatic progression free survival benefit - no PFS or OS benefit otherwise.

Take home on induction chemo/chemoRT vs def chemoRT in locally advanced

Essentially there is data for whatever you want to do PRE-OP CHEMO - Roth and Rosell: chemo --> surgery is better than surgery - SAKK trial -- says Chemo --> surgery = chemo --> RT --> surgery; take home is surgeons think CRT not needed since OS the same and they did subgroup to show benefit to surgery regardless of response. PRE-OP CHEMO-RT - INT 0139 Albain: chemoRT --> surgery better than definitive chemo RT (suggests OS better than def chemoRT if patient gets lobectomy) - overall OS same. - German LCCG: chemoRT --> surgery is eqiv to chemotherapy --> surgery --> PORT Definitive Chemoradiotherapy - ESPATUE trial: Chemo --> ChemoRT --> surgery equivalent to ChemoRT alone - EORTC 089416: Chemo --> Surgery equivalent to chemotherapy --> RT

Chemo options for HCC

Essentially think Sorafenib - SHARP and ASIA Pacific trial - multi-kinase inhibitor There are others though -- tons of them. multi-TKI is kinda the idea though - immunotherapy also an option

When is TORS NOT appropriate?

Essentially when TORS would cause significant functional deficits Specifically - T3/T4 - more than minimal soft palate extension - Central tongue based tumors - medical contraindication - trismus or other difficulties with exposure - probably matted nodes or radiographic ENE, because that means you need ChemoRT after TORS generally is combined with a separate neck dissection.

What was the main purpose of the VA larynx trial? What are some of the criticisms of the VA larynx trial?

Evaluated larynx preservation in T3/4 larynx cancer. This trial compared induction chemo followed by XRT versus total laryngectomy followed by postoperative XRT for stage III and IV laryngeal cancer. -- Nearly half were early stage in the larynx w/ mobile cords. -- Short follow up, w only 2 yr OS reported -- Gave larynx preservation rates, but did not comment on quality of preserved larynx. --One critique of these studies has been that systemic therapy could have been potentially unnecessary and that these studies were in fact comparing XRT with laryngectomy

RTOG 9001 -- extended field RT improved OS but with awful toxicity - can you treat with just pelvic RT with chemo instead of extended field RT - compared concurrent 5FU/cis + RT vs EFRT (extended field) eligible pts had: - tumors >5 cm - FIGO IIB-IVA - biopsy proven lymph nodes EXCLUDED pts w/ disease in the para-aortics Primary endpoint was OS RT was 45 Gy (four field) + brachy to point A to at least 85 Gy note: this trial recommended that the entire treatment be completed in less than 56 days - this is SOC now, but before this point, that wasn't really stipulated - pelvic field = L4/5 - Extended field = L1/2 Results? which arm was better? - which arm had more toxicity?

Every outcome was significantly better in pts with pelvic RT + chemo compared to EFRT only - the only metric that was worse was para-aortic failure (as you would expect) - but this wasn't even statistically significant 7 vs 4% (but NS) EVERY other metric was improved in pelvicRT +chemo - at both 5 and 8 yr time points for all - OS ~26% better - DFS ~20% better - LRF ~17% better - Distant Mets 12-14% better - Cause specific failure 17-20% better NOTE - they had the same G4 toxicity (9%) in both arms but pelvic+chemo didn't have any G5. There was 2% G5 in the EFRT arm.

Effect of increasing dose on survival in GBM - RTGO 7401, 7918, 8302 ----> median surv increased in biopsy + RT >54.5 Gy - BTSG trials 6901, 7201. 7501 ----> increasing dose increases survival - <45 Gy - 13 weeks - <50 Gy - 28 weeks - <55 Gy - 36 weeks - 60 Gy - 42 weeks Other side shows things we tried that didn't work

Except in elderly.... this led to dose escalation studies up to 80-90 Gy -- trend to increase OS with increasing dose, but generally didn't find a benefit to dose escalation above 60 Altered fractionations didn't help either SRS boost also didn't help Brachytherapy - randomized trial didn't show any benefit - some trials are looking at this in things like Gamma-tile Radiosensitizers didn't show any benefit

Best stat to use if wishing to compared exposure w/ disease to exposure w/o disease?

Exposure odds ratio = ad/bc Consider this in a case-control study where disease is infrequent such that a cohort study would be impractical to follow waiting for the disease to happen. Relative risk = used in Cohort studies (outcome is common enough that you can follow two groups (one w/ an exposure and one w/o said exposure). Exposure Odds ratio = used in Case-control studies (outcome is rare). If the outcome is uncommon in a population, the odds ratio is a close approximation to the relative risk and the formula is the same. Example: - RR = following group w/ HTN looking at incidence of LVH - Exposure OR = comparing women using tampons vs not using tampons to look at incidence of TSS.

Lymphatic drainage for uterus? - round ligament? - uterine fundus? - cervical involvement?

External/internal iliac nodes - round ligament = superficial inguinal nodes - uterine fundus = PA nodes - cervical = pre-sacral nodes

Majority of cord compression is form lesions where?

Extradural lesions (95%) affects 5-10% of all cancer patients Soft tissue vs bony compression "Milder" subtypes - thecal sac compression - cauda equina - compression of nerve roots/neural foramina (radiculopathy) Intramedullary mets = ~5% Leptomeningeal = ~4% of patients 10-40% have lesions at other levels so image the whole spine

What is EPP? op mortality? who is this limited to?

Extrapleural pneumonectomy EPP - it removes: - entire pleura - entire lung/tumor - hemidiaphragm - Ispilateral half of pericardium Op mortality = 4-31% of cases - not done at many institutions - Limited to patients w/o disease through the diaphragm - very hard to get patients through this treatment with RT after EPP At one point this was the standard of care surgery for Mesothelioma.

Most important cervical cancer staging points? - no vaginal involvement, less than 4 cm, what is max stage? - >4 cm but not involving vagina? - upper 2/3 vagina involved? - parametrium involved? - lower 1/3 of the vagina involved? - hydronephrosis or pelvic sidewall? - FIGO stage for any node positive? - T4? Bonus - PORT indications? - Po-chemoRT indications?

FIGO staging follows T stage; if any nodes automatically at least FIGO IIIC. If metastatic FIBO IVB. TIA1 - IB2 = microscopic to <4 cm (no vaginal involvement) - IA1 = <3 mm depth - IA2 = 3-5 mm depth IB = is visible on exam but NOT invading vagina or parametrium - IB1 = 5 mm - 2 cm - IB2 = 2-4 cm TIB3 = >4 cm but NO VAGINAL INVOLVEMENT Stage II - has spread beyond the cervix (but not to lower 1/3 of vagina or sidewall) T2a = upper 2/3 vagina involved - stage IIA1 - <4 cm - no parametrium - stage IIA2 - >4 cm - no parametrium T2b = parametrium involvement T3a = lower 1/3 vagina - not going to sidewall T3b = hydronephrosis or pelvic sidewall FIGO Stage IIIC = node positive (including micromets) - IIIC1 = pelvic nodal mets - IIIC2 = para-aortic mets T4 = bladder/rectum FIGO IVA = spread to adjacent organs FIGO IVB = spread to distant organs PORT = >4 cm, LVSI, DOI >1/3 (2 of 3) PO-CRT = Pos margin, Pos node, Parametium (T2b)

What is the recommended minimal surgical margin for FIXED tissue for vulvar cancer? What is the margin for non-fixed (just in the OR like frozen) for vulcar?

FIXED = 8 mm is minimal margin Non-fixed = 10 mm - this accountsfor the shrinkage from fixation In the heaps paper: <8 = 52.3% RFS >8 mm = 100% RFS

Follicular lymphoma prognostic criteria score? - what does it include?

FLIPI-1 - SLASH - Stage III-IV - Age 60 or older - LDH >upper limit of normal - # of nodal Sites 5 or more - Hemoglobin <12 Risk Group According to FLIPI - Low - 0-1 - Intermediate - 2 - High - 3 or more What I do is remember that the pneumonic for IPI for DLBCL and then remember the difference. IPI or R-IPI = international prognostic index or Rituxmab adjusted version - APLES is the memory aid - Age >/= 60 - Performance status >/= 2 - LDH >ULN - Extranodal sites >1 - Stage III/IV So the FLIPI is essentially the same except you just swap out the ECOG PS for Hemoglobin <12 and the # of NODAL sites is 5 or more vs 2 or more EXTRAnodal for IPI.

FLOT4 trial - single arm P2 - RCT of FLOT vs MAGIC - 716 pts, gastric cancer (44%) and GEJ (56%) - 43 months med fu - result?

FLOT had improved OS compared to MAGIC results of ECF FLOT med OS was 50 m compared with MAGIC 35 months. 3 yr OS 57% vs 48% similar perioperative complications "Once you FLOT you can't stop"

Follow up needed for AVM

FOLLOWUP MRI q 6m for 1-3 yrs, then annually until no change Once MRI shows obliteration, Need to do angiogram to confirm

Pre-op RT for HN? RTOG 7303 - randomized OC, OP, supraglottis, hypopharynx, sinus to pre-op 50 Gy vs 60 Gy post-op - 10 yr data --> results?

Facilitates tumor regression but increases toxicity for HN cancer 10 yr LC was better with post op - 58% vs 70% Most failures happened >2 years greatest benefit in supraglottis (53-->77%)

Subsites of supraglottic larynx

False cords Arytenoids AE folds Ventricle Epiglottis FAAVE

Time course of symptom onset that portends worse prognosis for cord compression

Faster onset of motor deficit (<14 days) = worse functional outcome

Early IMRT - Harvard Retrospective - harvard data that was VERY NEGATIVE about RT - most patients got heated intraop intracavitary cisplatin (11/13 pts) - Dose constraints contra V20 <20% and MLD <15 gy - they had beams passing through contralateral lung because it was IMRT -- so IMRT is a horrible idea if they only have 1 lung. If you took out the whole - what were the outcomes?

Fatal Pneumonitis -- 46% HORRIBLE outcomes. Those that died of lung death MLD 15.2 and V20 = 17.6% So even meeting their metrics, outcomes were awful No pulm death MLD 12.9 and V20 ~10% MDACC has a series that has much lower CL lung metrics and fewer patients died.

Penile Anatomy Look over figure Lymphatics important to know First Echelon - glans penis - skin of the shaft and prepuce - deeper penile structures - corpora cavernosa or posterior urethra Second Echelon Third Echelon

First echelon: Glans penis - b/l inguinal or iliac Skin of the shaft and prepuce -- superficial inguinal nodes - deeper penile structures -- superficial or deep inguinal - corpora cavernosa or posterior urethra - internal iliac nodes Second Echelon -- external iliac nodes Third Echelon -- common iliac and PA nodes

Describe sim setup for prone, monoisocentric, dual isocenter

First, I wire the lumpectomy/mastectomy scar, and borders of the whole breast PRONE If pendulous breasts and not treating nodes, I consider prone breast with prone breast board to reduce heart/lung dose. I place the iso along the chest wall posterior to a rib, taking care not to place the iso in the nipple. I use half beam blocked tangents and set my beams at time of iso placement to ensure coverage. If small breasts or treating regional nodes, I position the patient supine, arms abducted and externally rotated above head, on a 15-20 degree breast board. MONO-ISOCENTER With breasts that are shorter than 20 cm, I can generally achieve a monoisocentric setup. I half beam block at the superior and posterior aspect of the tangents and bottom of the supraclav field. This avoids divergence of tangents into the lungs or into the supraclav field. I set my beams at the time of iso placement to ensure proper coverage is achievable.. Generally the iso is placed posterior to the first or second rib in line with the midpoint of the infraclavicular wire (usually just inferior to the humeral head). This is easily identifiable on a DRR and stable. There is no collimation as the top of the tangent abuts the bottom of the supraclav field, patients are on an inclined breast board which brings the sternum flush with the floor. Half beam blocking with a mono-isocenter in this manner eliminates the need for table kicks DUAL ISOCENTER If the breasts are too long, and I cannot reach the lowest wire with my field using a mono-isocenter approach then I will convert to a dual isocenter approach. I still place my SCV field iso along the mid point of the infraclavicular wire located just posterior to the 1st or 2nd rib, I then drop straight down into lung, to a point that allows me to encompass the lower breast wire with care not to place my iso in the nipple. Tangents are still half beam blocked posteriorly to minimize divergence into the lungs, can add mlc blocks if need to shield heart/lung. To account for divergence of the superior aspect of the tangents, I kick the feet of the couch away from the gantry by about 6 - 10 degrees until flush with the bottom of the supraclav field.

Which patients specifically had OS benefit with RT?

Fixed or ulcerated groin nodes 2 or more positive groin nodes and a ratio of more than 20% positive IL groin nodes/the number resected The people with only N0 or N1 disease did fine with surgery - same as groin RT.

How does focal vs diffuse anaplasia impact RT dose?

Focal anaplasia does not typically buy you a boost Diffuse anaplasia does usually buy a boost The only time the boost is to the whole abdomen is with diffuse unresectable implants, otherwise the boost is generally just to the flank. It's usually an extra 900 cGy for boost If there are peritoneal implants its an extra 1050 cGy boost to whole abd (21 to WAI if diffuse implants only if >12 months). That is when you need a partial transmission block over the remaining kidney from the PA (<14.4 Gy to the whole CL kidney - BLOCK SHOULD BE 0.5 CM WIDER THAN THE PROJECTION OF THE KIDNEY ON THE PA DIGITALLY RECONSTRUCTED RADIOGRAPH)

Standard pre-therapy pediatric workup and baseline evaluations? Baseline evaluation for CNS vs non-CNS? Imaging generally - specific imaging/tests >wilms rhabdoid variant >wilms clear cell sarcoma variant >RMS generally >RMS parameningeal sites >neuroblastoma Don't biopsy which suspected pediatric tumor?

Focused H&P focusing on risk factors/family history of malignancy/diagnosed syndromes and contraindications for radiation therapy. I would also get a development history (birth history, pediatric history). Labs: CBC/CMP/LFTs/Renal FT/Fertility counseling; CNS - Endocrine, Audiology, Visual testing, Neuropsych testing - TTE for cardiac function before adriamycin Imaging: Generally start with U/S if feasable followed by likely CT CAP for non-CNS or MR brain for CNS. For small round blue cell tumors that are non-hematogenous, often need B/L BMB. - Specific tests: >Rhabdoid variant Wilms: Brain MRI >Clear cell sarcoma variant Wilms: Bone Scan >RMS: PET/CT scan >RMS parameningeal sites: brain MR + LP >neuroblastoma: MIGB-Iodine uptake scan for staging/high dose one in COG trial for treatment Don't biopsy Wilms (unless stage IV) - upstages to stage III immediately

OVERVIEW CARD Major workup and basic paradigm for: - Early Stage NSCLC (stage I-II) - Locally Advanced NSCLC (stage III) - LS-SCLC/ES-SCLC

For ALL -- General order: History: "I would start with a focused history and physical focusing on risk factors for malignancy and contraindications to radiation therapy. I would obtain basic labwork including CBC and CMP" Other bonus: - including performance status and weight loss - counsel smoking cessation Workup: - I would obtain imaging including CT Chest/Abdomen + contrast, PET/CT, MR brain (for T2 = >3cm/N1 and up + all SCLC) - For tissue diagnosis, I would proceed with the "least invasive biopsy with highest yield preferred as 1st diagnostic study" (if no LAD in mediastinum, primary biopsy via TT-FNA or bronchoscopy) - I would also favor staging the mediastinum in those patients with primary cancers T1b = 2cm and up or with central location (w/in 2 cm of proximal bronchial tree). - For early stage patients for whom surgery is still an option (or in single station N2 stage III patients), I would obtain PFTs as part of pre-operative workup (SBRT if FEV1 <50%, <1-2L (lobectomy/pneumonectomy), and DLCO <50%) Treatment: Below Early Stage NSCLC (stage I-II) - Workup: Biopsy (TT-FNA or Bronchoscopy with biopsy), CT Chest/abdomen (adrenals) w contrast, PET/CT, EBUS (if >2-3 cm primary; boards answer everyone), MR brain wwo contrast (if >3 cm or central); PFTS CRITICAL TO SAY HERE (determine if surgical candidate) - Options: Surgery (lobectomy > wedge), SBRT (NOT chemo -- harmful unless >stage IB) - F/U: CT chest wo contrast q3 months for 2 years, then q6 months for 3 years, then back to q1 year screening RT Dose: 50 Gy/5 fractions particularly for more central lesions, 54; Gy/3 fractions can be considered for more peripheral lesions also not w/in 2 cm of the chestwall contour. A fractionated approach could be considered for ultracentral lesions such as 60 Gy in 8 fractions. Locally Advanced NSCLC (stage III) - Workup: Biopsy (EBUS > Bronchoscopy/TT-FNA - take bx that can stage too), CT Chest/abdomen (adrenals) w contrast, PET/CT, MR brain wwo contrast (ALL) - Options: Definitive chemo-RT, chemo-->surgery (N1) or chemo-RT -->Surgery if single station N2 - RT dose: 60 Gy/30 fractions (ChemoRT) - Chemo: Concurrent Carbo (2 AUC)/Taxol (45 mg/m2) + durvalumab consolidation out back after chemoRT - F/U: CT chest wo contrast q3 months for 2-3 years, then q6 months for 2-3 years, then back to q1 year screening LS-SCLC - Workup: Biopsy (EBUS > TT-FNA - take bx that can stage too), CT Chest/abdomen (adrenals) w contrast, PET/CT, MR brain wwo contrast (ALL) - Options: Definitive chemo-RT -- technically surgery for VERY early stage (very rare to find these people) - RT dose: 45 Gy/30 bid fractions (ChemoRT) Turrisi regimen is still SOC (66/33 per Convert) - Chemo: Concurrent Cis/Etop (Cis 60 etop 120 q 3 wk) + Atezo consolidation outback is being tested on LU005 (LU007 is doing concurrent atezo) - turrisi started on C1D1, we tend to start C2D1 -- - 6-8 weeks out, repeat brain MRI and if no mets, offer PCI 25 Gy/10 fractions - F/U: CT chest wo contrast q3 months for 2 years, then q6 months for 3 years, then back to q1 year screening + routine brain MRI Extensive stage SCLC - standard to start chemo/immuno (Cis/Etop --> induction/maint Atezolizumab - standard based on IMPower133) -- if at least some response, can offer consolidative RT to chest (30 Gy/10 fxn) - Slotman- chest consolidation RT (30 Gy in 10 fractions) found OS benefit of 10% at 2 yr (NOT 1 year -- was primary endpoint of study)- chemo = 4-6 C cis (80 mg/m2)/etop (100 mg/m2) q3 weeks

Treatment paradigm for GGCT? Is this CSI?

For GGCT you don't do surgery, and not everyone gets CSI If M0 then no, it is just ventricles getting treated If M+ then yes CSI If doing CSI, use your WVRT dose Institutional practice is neoadj chemo cabo/etop 4 C then RT WVRT 21 boost w/ IFRT to 30 (CR) If cant tolerate chemo WVRT 24 boost w/ IFRT to 36-45

GOG 101 - stage III and IV vulvar cancer - question was pre-op chemoRT - might allow for less extensive surgery - treatment regimen is NOT used anymore (1. because it involved a split course, 2. they did BID @1.7 Gy per for the first half of tx - greatly increased skin tox) -- RT + Cis (50)/5FU (1,000) in a split course Fields were different based on nodes if N0-1 - just treated primary site If N2-3 - treated inguinal and pelvic nodes Results? - how many had no visible primary left? - how many of those had pCR at surgery - how many of the ones with gross disease had an R0 resection at surgery.

For unresectable primary - 48% had no visible cancer remaining --> of the pts that then had surgery, 70% had pCR (31% of total patients) - 53.5% had grossly evidence tumor --> of these that had surgery, 84.4% had R0 resection For unresectable nodes - disease became resectable in 90.5% - following surgery, lymph nodes were pN0 in 40.5% of patients

Role for Consolidative RT in Extensive Stage SCLC - Jeremic, 210 pts w/ ES-SCLC - all pts w/ EP x 3 - pts w/ PR at local level and CR at distant level or CR at both sites -- randomized to accelerated hyperfrac RT - 54 Gy in 36 fractions BID w/ concurrent carbo/etop + 2 cycles EP or EPx4 - results?

Found a survival benefit with consolidation RT

ECOG 1484 - 14-8(c) - 40Gy - 352 pts, stage IX, IE, II, IIE - 2/3 were stage II and 1/3 bulky - Treated 8 cycles CHOP --> if PR --> 40 Gy IFRT (30% of pts) --> if CR --> randomized to 30 Gy vs Observation Less favorable pts than SWOG patients What is the effect of RT in pts with partial response to chemo based on the EORTC report.

Found that RT improved DFS but not OS at 6 yrs Note: not powered to detect OS diff - IPI data not collected - more bulky pts were on the RT arm so probably less favorable - % of relapses in initial disease sites were much higher in the chemo alone pts (48% vs 18% for combined modality) EORTC report that evaluated four NHL EORTC tials showed that for pts w/ PR to chemo, RT did improve OS ocmpared to other salvage regimns for all pts and bulky pts

Trials comparing pre-op RT to pre-op CRT French study EORTC study - 4 arms - RT - surg - rt - surg - chemo - chemort - surg - chemort - surg - chemo What's the take home?

French study showed equivalent rate of sphincter sparing surgery. - CRT had higher pCR rate than RT alone - 11.4% v 3.6% - CRT improved 5 yr LF rate (8 v 16.5%) - no difference in OS - higher toxicity with chemoRT EORTC 22921 -- - randomized >1000 pts - adjuvant chemo only benefited radiation responders in terms of DFS and OS Summary of these studies is that they essentially all showed a benefit in terms of pCR with chemo, maybe lower LR rate, but didn't affect OS or likelihood of sphincter preservation.

survival for the different subtypes of medullo

G3/4 worse - even worse when metastatic infants do poorly for all subtypes

TN dose and target

GAMMA KNIFE: TN and thalamotomy are the only times you Rx to 100% isodose line, otherwise Rx to 50% IDL 1st GK: 85 Gy to 100% IDL (Should see the 20% IDL abutting brainstem) Target the Pars triangularis just using one 4mm isocenter (Pitt data showed using 2 isos had more numbness) - we used to target the DREZ but this increases dose to brainstem Tell patient to stay on meds until pain free for a whole week, then start tapering down - response is ~50% at 5 yrs still have pain relief 2nd GK: 80 Gy to 100 % IDL (Some institutions go as low as 45 Gy for 2nd GK ) Target is slightly before or after previous target (but data shows could just tx same previous target) Same 50% @ 5 yrs, still 85% initial response rate Same toxicity rates, if had numbness first time, chance of worsening is ~ 25% 3rd GK: 75 Gy to 100 % IDL Target can be just on top of one of the previous target sites. Prescribe to 100% IDL (20% IDL abuts brainstem) Initial pain relief within 10 days for 94% of patients

What score is considered by medical oncology for follicular?

GELF criteria

Docetaxel chemo - GETUG-12 -- 413 men with new diagnosis high risk prostate ca given before RT - take home what was seen? RTOG 0521 - looked at docetaxel after RT

GETUG-12 docetaxel - no benefit in cancer metrics RTOG 0521 - OS and DFS improved but p value was one sided.

Response rate of GKRS for TN

GK Response: 85-94% Initial response rate, 75 % complete response, 50 % @ 5 yrs, 20% @ 10 yrs [Lopez JNNP 2004] Same success rates for MS population Better response and more durable for type 1 TG If they have numbness, it is likely they will have longer pain relief, think of this like you had more impact on the nerve.

Treatment for Advanced Intact disease

GOG 101 and 205

GOG 99 - prospective P3, RCT - FIGO I and occult stage II intermediate risk endometrial patients - TAH/BSO randomized to pelvic/para-aortic lymphadenectomy ---> + no more tx OR ---> EBRT to 50.4 Gy (3D) Essentially enrolled these patients and then figured out which ones were low risk (IA, G1-2, younger) and which ones were high-intermediate risk (features on back of card) and then - Prim outcome = Recurrence Free Interval How was "high-intermediate" risk defined? - how many patients did this apply to on GOG99? - Who benefited from EBRT?

GOG 99 - defined risk features of high-Intermediate Risk <50 - you needed all three risk features 50-70 - needed at least 2 of the features 70+ - only need one additional features Risk Features: G2-3 deep 1/3 invasion LVSI ~1/3 of patients were HIR Clearest benefit of RT was in cumulative incidence of recurrence for HIR + RT patients. Their survival also appeared to be improved by wasn't SS because it was a small trial (only 62 pts on this arm) Local recurrence reduced by about half at four years

Good prognostic features of LGG?

GOOD PROGNOSTIC FEATURES: 1p19q codel IDH1 mut (wt considered molecular GBM now) Age < 40 yo SEIZURES AT PRESENTATION (more likely to be LGG if no bx yet) - also indicates more cortical location and better chance of a good resection

Definition of GTR vs STR?

GTR is >90% removed SRT is 10-90% removed Bx alone <10% removed

T3 glottic larynx RT volumes? - dose to primary? - nodes covered? - concurrent chemo?

GTV 70 defined by imaging and fiberoptic exam CTV70 is 1.5 cm expansion in the sup/inf direction and ~1 cm radially PTV 70 is 3 mm expansion CTV60 is entire larynx - bilateral lvls II-IV, VI covered - cisplatin for T3 (concurrent chemo best based on 91-11 as above)

LGG tumor RT volumes GTV CTV

GTV = all gross tumor included as defined by T1 post gad, Flair,l or T2 sequences, optic tract radiation or T2/flair abnormalities included CTV = 5 mm expansion anatomically constrained

Medulloblastoma - volumes for: GTV CTV PTV

GTV = any residual tumor (enhancing or non) + resection cavity wall (fuse post-op and pre-op T1 post gad and T2 sequence) CTV = GTV + 1.5 cm margin (shave out of bone and tentorial interface) -- "anatomically confined to posterior fossa, trim inside tentorium/boney PF" PTV = 0.3-0.5 PTV around the CTV

Adjuvant Therapy in Pancreas Cancer - CONKO-1 trial - adj gem after R0 or R1 resection - 6 cycles of chemo - results?

Gem improved DFS (13.9 v 6.9 mo) (SS) No difference in OS Update - 5 yr numbers (all SS) - DFS - 16 v 6.5% in favor of gem - OS - 21 v 9% in favor of gem - median OS - 22.8 mo vs 20.2 mo (SS)

chemo for metastatic pancreatic cancer?

Gem-Abraxane - survival benefit of 8.2 vs 6 months FOLFIRINOX has median survival of 11 months if they can tolerate it

PEDS SECTION Pediatric Cancers Generally Epidemiology: - <1% of all cancer diagnoses in US - cancer is second leading cause of death in children 1-14 years - incidence overall is stable - mortality is dramatically improving over last 3-4 decades -- cure about ~80% of all peds cancers now. What are the major calcifying tumors? What are the small round blue cell tumors?

General information card Site specific information between cards Tumors that calcify: (5) - *MOMEC* - craniopharyngioma - LGG (oligodendroglioma) - medulloblastoma - ependymoma - Meningioma Small Round Blue cell tumors = *LEARN-NMR* - Lymphoma - Ewings - ALL - Rhabdomyosarcoma - Neuroblastoma - Neuroepithelioma - Medulloblastoma - Retinoblastoma

Hypopharynx - general treatment paradigm? - typically presents when? - when can RT or chemoRT be used definitive? - what lymph node levels need to be covered?

Generally seen a surgical disease - TL with partial pharyngectomy + flap reconstruction followed by RT and ChemoRT Typically presents VERY late and already involves lymphatics. Def RT alone: If you catch it as T1 (very rare) Def Chemo RT: If you catch it as T2 (also very rare) In general, ryan tends to say larynx pres is fine for these as long as they aren't T4. HP outcomes are just worse overall in general. T4 should really go to surgery like T4 larynx. LNs: II-IV and VI + RP (VIIa)

Single fraction regimens for SBRT RTOG 0915 compared single vs multifraction - 34/1 vs 48/4 - 86 pts - results?

Generally several studies showing LC is not quite as good ~79-83% RTOG 0915 - Videtic, Red Journal 2019 1 yr LC 97 v 92.7% (1 v 4 fraction) 4 yr outcomes basically all the same as well and no significant difference in toxicity Only in specific patients.

ASTRO and GEC-ESTRO (european) guidelines for partial breast irradiation -- when it can be recommended -- just look over

Generally things like: - age over 60 - no BRCA1/2 mut - small tumors (<2 cm - T1) - >2-3 mm margins - ER positive, HER2 negative, etc

Ann Arbor vs EORTC vs GHSG definitions of lymph node regions

German Hodgkin study group are broader regions - infraclav is separate for Ann arbor - neck and supraclav are together for Ann Arbor but GHSG includes infraclav/subpectoral along with them as 1 group. - axilla is separate (both for german and Ann Arbor) This is the biggest part to remember

Definitive vs Pre-operative CRT - german study, french study, chinese study - take home here is surgery arm had higher morbidity and survival wasn't different really German study - induction crt vs def crt w/ brachy - 172 pts w/ locally advanced Sqcc - randomized to: - induction chemo --> chemo RT (40 Gy) --> surgery vs - induction chemo --> chemoRT (40 Gy + boost of 15 Gy 1.5 bid or 20 Gy followed by Brachy boost?) French Study - - 444 pts randomized to - two cycle cis/5fu and either conventionally fractionated radiation (46 in 4.5 weeks) followed by surgery or continuation of radiation with split course radiation (15 Gy 1-5 and 22-25) - -her slides suck and the arms are hard to figure out. Dont' think its that important Chinese study - 80 pts with squamous - chemoRT with cis/5fu and 50-60 Gy concurrently

German study - OS was equivalent - PFS, LC, and treatment related mortality were sigificantly higher in surgery arm French Study - no difference in survival - local control and treatment related moratlity higher in surgery arm Chinese Study - no difference.

Pulsatile tinnitus - "hearing your pulse" Swallowing problems Hearing loss Loss of gag reflex Diagnosis? How common? Benign or malig? Workup?

Glomus tumor (paraganglioma, chemodectoma, glomus jugular) Very rare, usually benign Glomus cells of jugular bulb *No biopsy* - patient bleeds out, highly vascular tumor 1 in a million tumor more common in females mean age 52 yrs slow doubling time - median 4.2 yrs MR - strongly enhancing - fine salt and pepper appearance, vascular pattern suggestive of high intrinsic tumor vascularity

Supraglottic larynx pT1-2 N0-1 =? - difference compared to paradigm for glottic larynx? - paradigm for more advanced? - basic dose and nodal levels covered? - when is chemo needed?

Glottic larynx and supraglottic larynx are kind of the opposite in that early stage glottic is appropriate for larynx preservation, and later stage needs TL. For supraglottic, only early stage is appropriate for supraglottic TL, and otherwise main approach is definitive RT or CRT. pT1-2 N0-1 =? - For "selected early cases" -- supraglottic laryngectomy is appropriate --> requires good pulmonary status because risk of aspiration is higher after SUPRAglottic laryngectomy. Beyond the above -- so for more T1-2N0-1 even, the approach should be defintive chemoRT or RT - main approach is definitive RT or CRT. - need a functional larynx still. - 70/63/56 with chemo or accelerate if RT alone - cover II-IV and VI for bulky bilaterally - ChemoRT is >T2N1 OR if tumor volume >6 cc (UF approach) -- similar to OP cutoff for def RT A T4 supraglottic on the other hand should probably go to surgery first just like a T4 larynx or hypopharynx. Supraglottics were included on the VA larynx trial

GnRH agonist vs GnRH antagonist - examples - what is the problem in terms of convenience with antagonist vs agonist - what is the major difference and where is that major difference seen - other major hormone side effects

GnRH agonist - easy 1, 3, or 6 months injections - lupron - luprolide GnRH antagonist - firmagon (degarelix) -- problem is 1/month shot with 30% chance of injection site reactions - relugolix - pill, but has more GI side effects (but this is really hard to get even though its FDA approved) Meta-analysis and RCT (Shore 2020) trials shows that cardiovascular events were MUCH better in men if you used ANTAGONIST -- ANTAGONIST BETTER than agonist (particularly if man had hx of cardio problems) other major hormone side effects -- fatigue, hot flashes, mood/memory/concentration/cardiovascular

Low Grade NHL - follicular - G1/2 (G3 is debatable) - 2nd most common NHL (21%) - older adults - stage III-IV is ~60-80% of patients - very common to have BM involvement - ~50% - WHO grading is based on what? - whats the translocation? - what is 5 yr OS vs FFR (freedom from relapse)? - what is the leading cause of death from follicular lymphoma? --->how often does that happen?

Grading is based on the # of centroblasts per HPF - G1 = <5 centroblasts/HPF - G2 = 6-15 centroblasts/HPF - G3 = >15 centroblasts/HPF ---3A = still some centrocytes present ---3B = nearly entirely centroblasts Translocation = t(14;18) Survival is very good (70-80%) but they relapse alot (FFR ~40%) so they end up getting other treatments. High rate of relapse outside of RT fields Most are indolent, but the leading cause of death is transformatino to DLBCL --> 15% of cases (1-3% risk per year)

What is the most sensitive endocrine hormone to radiation?

Growth hormone -- affected 18-25 Gy Other pituitary hormones -- ACTH, TSH, LH, FSH - affected by 40 Gy

GASTRIC CANCERS 2nd most common cause of cancer mortality worldwide More important outside of US risk factors

H pylori dietary factors ntiroso compounds/salt preservatives less bacterial and fungal contamination atrohpic gastritis metaplasia obesity smoking abdominal rt low ses fruits/veggies nsaids, reproduction -- protective

How do your doses and volumes differ for different peds tumors

HGG 59.4 LGG 54 Pilocytic 45 DIPG 54 most common answer Brainstem 54 -59.4, can't go above 60

RTOG 8315 for PCNSL - take home?

HIGH dose RT - 40 Gy boost to 60Gy and they still failed in field (89% LF) - RT alone no good

Oropharynx general There seems to be some EGFR relationsihp - EGFR expression coorelated with decreased OS and LRC in Ang 9003 - but cetuximab really hasn't panned out Rate of second primary is pretty high - 4-7% annually after first diagnosis

HIV

Radiation for oligomet prostate cancer Treatment to Primary in metastatic patients HORRAD trial - 432 pts w/ de novo metastatic prostate, age <80, PSA >20 --> randomized to lifelong ADT or lifelong ADT + prostate RT 70 Gy or 57.56 in 19 fr. - showed what benefit? Stampede arm H (stampede '18) - 2061 metastatic prostate cancers randomized to lifelong ADT or lifelong ADT + RT (55 Gy/20 or 36 Gy/6 weekly) - high metastatic burden defined as what? - results? - what did they treat?

HORRAD -PSA progression survival benefit but no OS benefit. -benefit wasn't SS but favored treating the prostate if number of mets was <5 STAMPEDE 18 - low burden = 3 bone mets with none outside of axial skeleton and no visceral mets. - high burden = 4 or more bone mets with 1 or more outside axial skeleton or any visceral metastases. - results = OS no benefit if looking at all pts. All pts did have a failure free survival benefit. ---> in low metastatic burden patients there was AN OVERALL SURVIVAL BENEFIT. (HR = 0.68, p = 0.007) -- subgroup analysis tho...HORRAD showed same benefit in <5 mets group but WASNT statistically significant. - they treated prostate only -- NOT pelvic nodes. But pelvic node positive disease was ALSO concluded to benefit -- doesn't mean they treated the nodes. Brachy boost is NOT recommended by NCCN outside of clinical trial.

Workup for rectal cancer

HP colonoscopy MR rectum - eus if CI to MRI eval by colorectal surgery PET/CT (optional) CT CAP Blood work

Cervical Cancer Decreasing in frequency over time due to PAP screening -- not even in the top 10 most common cancers however, not the case worldwide -- incidence is still very high in places like subsahara Africa Average age at diagnosis is 53 yrs globally, 47 in the US Cause in >90% of cases?

HPV is the cause in >90% of cases HPV-16 and 18 are the most common subtypes related E6/7 overexpression are related to p16 expression as a failed negative feedback loop. E6 inhibits p53 E7 inhibits RB protein Inhibition of these leads to dysregulation of the cell cycle

OS in HPV for vulvar?

HPV positive has higher survival similar to HN -- 5 yr 93 vs 68%

PRODIGE study - NEJM - RCT of adjuvant gem vs FOLFIRINOX for 6 cycles - most pts had R1 - med fu 34 months - results?

HUGE benefit to FOLFIRINOX - med OS 35 vs 54.4 month - 3 yr OS 49% vs 63%

Most common site of minor salivary gland cancer?

Hard palate

Simpson Grade - explain

Has to do with degree of surgical resection for meningioma 1-3 = GTR --1=complete resection of tumor, dural attachments, and bony involvement --2=complete resection of tumor with diathermy of dural invasion --3=macroscopic tumor removed; may leave microscopic tumor foci in situ 4 = STR 5 = bx only

Pilocytics - path features - how is it treated? - risk of recurrence/transformation? - chance of no recurrence? Subependymal giant cell tumor associated with what?

Has ~ 5% risk of transforming to GBM, or ~ 5% risk recurring as G2 15% risk recurring as some sort of LGG (G1 or G2) almost always it is a cystic G1 80% chance of no recurrence Often presents with HA Lots of rosenthal fibers loose glial tissue punctated by vacuoles elongated cells with fine fibrillary projections treated with GTR when possible - observed STR -- re-excision Obs, re-resection - chemo - RT (50.4 Gy + edema) vs SRS Subependymal giant cell tumor associated with what = Tuberous sclerosis

Followup for SP

Have to follow the M protein on their SPEP/UPEP Persistent of M protein is associated w/ higher likelihood of progression to MM

Pancreas cancer - surgery is the only curative option - only 20% are resectable - 5 yr OS is 20% for resected patients - what surgery is required for lesions in the pancreatic head vs body and tail? What are the components of these surgeries? Know what is removed and what are the 3 major anastomoses Where is the most common location of positive margin? What are survival differences between R0/R1 and N0/N+?

Head lesion = Whipple Procedure - Pancreaticoduodenectomy - removal of the pancreas, duodenum, CBD, gallbladder +/- partial gastretomy +/- pylorus sparing. Involves anastomoses = gastrojejunostomy, cholodochojejunostomy and pancreatricojejunostomy Body and Tail = distal pancreatectomy and splenectomy Goal of surgery is an R0 resection. Retroperitoneal margin is the most frequent site of positive margin. Rate of R1 is 20-50% of cases.

Which ways should the wedges be oriented in a larynx plan? Where will the hotspot fall if under/over wedged? How would you decide on what wedge to use?

Heels out -- think about this as posteriorly, there is more soft tissue for dose build up, but anteriorly there isn't, so you have to add a wedge anteriorly so that the dose buildup is appropriate to get dose to the target Anterior = underwedged Posterior = overwedged I would start with 15-30 degree wedge, try not to let hotspot go above 107%, heel of the wedge is anterior

Imaging features of LGG?

High res thin sliced MRI well circumscribed often, round, solid calcification T1: Hypointense, does NOT enhance with gadolinium T2: High, FLAIR shows it best. CT In general oligos look just like astros, with edema (if they do happen to enhance then more likely oligo) Oligos tend to have more calcifications, more cortical involvement, enhance more

Describe standard vs high risk medulloblastoma? Does this impact treatment?

High risk: 1. < 3 yo 2. M1+ 3. >1.5 cc residual tumor post op 4. Anaplasia Everyone else is standard risk This does impact treatment dose Dose (some trials boost PF to 55.8) High risk: 36 Gy to CSI → 54 Gy to PF (This is done w/ vincristine for peds but without it for adults) Standard risk: 23.4 Gy to CSI → 54 Gy to IF (if chemo cannot be given, even standard risk patients need 36 to CSI) Newer protocols take IF to 55.8 Spinal nodule: Boost to 45 GY if below terminus - 50.4 Gy For high risk, you still have to treat whole Post fossa in boost -- for boars answer (in practice, chan may treat these just IF and practice patterns seem to be moving that way) For standard risk, can do involved field

What are high tangents vs standard tangents?

High tangents: superior border is just below or touching humerus Normal tangents end at top wire/clavicular head

Paradigms for endometrial - high intermediate risk features

High/intermediate risk - In general, deep invasion, age >60, G2-3, and LVSI PORTEC 2 --> need 2 of 3 RF GOG 99 >60 yo Any age +3 RF >50 +2 RF >70 +1 RF G3 G2-3 deep LVSI - IA --> G1/2 no other risk factors

TME adverse events?

Higher anastomotic leak rate associated with APR when done with TME TME improves survival compared to local excision

Workup for Wilms - presenting symptoms? What imaging and order of imaging? Is a bone scan ever indicated? Is a head MRI ever indicated?

History/PE -Asymptomatic abdominal mass -Abdominal pain -Hematuria (gross or microscopic) -Abdominal enlargement -Anemia -Fever -Hypertension (due to elevated renin) Imaging: Abdominal ultrasound (1st less expensive, less radiation) then CT CAP/MRI of primary Bone scan (for the clear cell variant) Head MRI (for the rhabdoid variant) Consult pediatric tumor board

Nigro Protocol, Wayne State Phase II, Cancer 1993 - RT was 30 Gy in 15 fractions AP/PA - chemo was 5FU/MMC - surgery 4-6 weeks after XRT, initially APR for all patietns (1st 12 patients) and then only in patients with gross residual disease - wide excision of the scar if gross CR Results?

Huge field - lower dose Note MMC only given once The initial 3 patients have pCR at time of surgery Additional 9 pts w/ APR after CRT --> 4 had no disease, 1 had only microscopic, 4 had gross and microscopic 45 total patients - 84% were free of cancer after chemoRT no recurrences in pts rendered free of disease 15% of patients with residual disease recurred --> all in distant site and all died of disease

Omission of radiation CALGB 9343 (Hughes; JCO 2013) - how many pts? - Who was included? - what were arms? - SLNB required? - benefit of RT on DFS or OS? - Locoregional control difference? - difference in time to mastectomy, time to DM, BCSS or OS? - conclusion? Prime II was another similar study that looked at age >65 years, T1-2, R0m ER+, G3 or LVSI - 1326 pts - local recurrence higher in tam alone (4.3%) vs 1.3% (rt + tam) - NO difference in overall survival

Hughes - how many pts = 636 - Who was included = women 70 and older, T1N0 ER+ (any grade) - what were arms = TAM alone or RT+TAM - SLNB required = NO (cN0 required) - benefit of RT on DFS or OS = NO (10 yr, 12.6 yr followup) - Locoregional control difference (10 yr) = 98 vs 92% (for RT vs TAM alone; 8% recurrence risk if TAM alone vs 2% RT+TAM) - No difference in time to mastectomy, time to DM, BCSS or OS - Tamoxifen is a reasonable option alone, but stands that RT does still provide LC. Problems: - Tamoxifen compliance isn't great and that isn't captured in this study - should have compared RT alone and TAM alone Benefit to hormone therapy is also that it prevents CL breast events

Structure that: Separates oropharynx and hypopharynx Separates oropharynx and nasopharynx

Hyoid Soft palate

What is taken w/ total laryngectomy?

Hyoid bone Thyroid cartilage, cricoid cartilage, and epiglottis Strap muscles Permanent tracheostomy Reconstruction of the pharynx Total laryngectomy you have a permanent tracheostomy -- so you have ZERO aspiration risk. If you have a supraglottic laryngectomy and have the epiglottis and such removed, there's no neopharynx and higher risk of aspiration.

NSABP B21 - 1009 women with T1N0 breast cancer <1 cm - lumpectomy and ALND -- randomized to tamoxifen, RT or RT + tam - results? Fyles (canadian trial) - RT vs no RT - hypofract + boost was RT - >50 yrs, <5 cm T1-2N0 tumors - lumpectomy + tamoxifen - results?

IBTR was - lowest for tam + RT (2.8%) - middle for rt alone (9.3%) - highest for tam alone (16.5%) Fyles study - 8 yr LR was 17.6% vs 3.5% ( no RT v RT) - 5 yr DFS (84% v 91%) - 5 yr IBTR (7.7% v 0.6%) Liu et al - Luminal A - not as much benefit to RT

What is negative margin for IDC and DCIS? Positive margin at ink associated with what risk of IBTR?

IDC = negative at ink DCIS = requires 2 mm margins to be sufficient margin - Risk of LF if tumor on ink was NOT nullified with RT Thought to be because of the intraductal nature of DCIS that it could be present in more of the specimen thus larger margins needed. JCO 2014 "ASTRO guidelines" - Systematic review of 33 studies - (+) margins (AT ink for invasive or DCIS) is associated with a 2x increased risk of IBRT vs negative margin. No evidence that more widely clear margins reduce IBTR for the following pts: Young, unfavorable biology, lobular cancers, or EIC

WHO 2016 categorization of an astrocytoma?

IDH mut p53 mut ATRX mutation leading to loss lack of 1p19q codel Specifically p53 mut/ATRX today = Astro

Main GBM mutations to know?

IDH wt (85% hgg) > IDH mut (15% hgg) MGMT methylation ~30% in both LGG and HGG EGFR amp LOH10 (+7/-10) TP53 mutation (>2/3 of secondary GBM) tert mutation

Molecular overview IDH1-mut + 1p19q codel = ? Oligodendro by classic histo + inconclusive mol = ? Oligodendro by classic histo + IDH1-wt + Tert-mut + +7/-10, EGFR amp = ? IDH mut + p53 mut + ATRX mut (1p19q NOT codel) = ?

IDH1-mut + 1p19q codel = oligodendroglioma (definitive molecular signature) Oligodendro by classic histo (fried egg appearance) + inconclusive mol = oligodendrolgioma NOS Oligodendro by classic histo + IDH1-wt + Tert-mut + +7/-10, EGFR amp = NO SUCH THING as oligodendroglioma like this - this is a molecular GBM signature IDH mut + p53 mut + ATRX mut (1p19q NOT codel) = Astrocytoma If shown picture, things to recognize - 1p and 1q stain show in single pain as control to show that you have the p and q arms here. - a normal cell would have 2 of each, so if you have just one dot, that means you have lose

Stage II seminoma - RT plays a larger role Volume and dose?

IIA is N1 (<2 cm node or multiple <5 nodes all <2 cm); IIB is N2 (2-5 cm or >5 nodes all 2-5 cm or with ENE) and IIC is N3 (>5 cm node) III is metastatic Stage IIA (N1 or S1) - think Dog leg RT RT to para-aortic + IL iliac chain to 30 Gy or BEP for 3 cycles or EP x 4 cycles Stage IIB BEP for 3 cycles or EP x 4 cycles (preferred) or RT in select non-bulky cases (3 cm or less) to para-aortic and IL iliac to 36 Gy Stage IIC/III - good risk BEPx 3 or EPx4 - intermediate risk = BEPx 4 or VIP x 4

survival in thymoma/thymic carcinoma in stage III and IV?

IIIA = touching nearby great vessels broken through capsule IIIB = invasion of great vessels.

Nasopharynx planning

IMRT needed MRI imaging required in planning (and in follow up at same time as 3 month PET)

Conventional RT vs SABR for early stage - which trials and what did they show?

INOPERABLE RADIATION TRIALS SPACE - didn't show a difference in 3 yr PFS and OS similar. - tox profile better with SABR CHISEL - TROG 09.02 - SABR superior for survival and toxicity - freedom from local failure HR 0.32 (p = 0.008) and OS HR 0.52 (p = 0.027) BETTER with SABR - 101 pts (conventional 66/33 or 50/20 vs 54/3 or 48/4) LUSTRE: Canadian study (2:1 randomization of 48/4 or 60/8 for central vs 60/15 CRT) - P3 RCT, closed early for slow accrual - median fu 36 months SBRT vs CRT (60/15) - 3 yr LC: 87.6% vs 81.2%, NS - DFS and OS not different - "trial confirms efficacy for SBRT" - 60/15 isn't exactly what people mean when they say "conventional RT" Important point made that local control is very important in lung cancer. Salvage when tumors recur locally is difficult so LC translates to survival benefit as long as you don't compromise their survival with the treatment.

INT 0113/RTOG 8911 Kelson NEJM 1998 and JCO 2007 - 440 pts randomized to upfront surgery vs 3 cycles cis/5FU + 2 cycle postop - results? MRC OE2 - RCT of 802 pts randomized to upfront surgery vs 2 cycles Cis/5FU pre-op - results?

INT 0113/RTOG 8911 Kelson NEJM 1998 and JCO 2007 - NEGATIVE TRIAL FOR CHEMO - 440 pts randomized to upfront surgery vs 3 cycles cis/5FU + 2 cycle postop - results = NO difference in survival (2 yr 35% vs 37%) MRC OE2 - POSITIVE TRIAL for CHEMO - RCT of 802 pts randomized to upfront surgery vs 2 cycles Cis/5FU pre-op - results = 5 yr OS 23% vs 17% (SS) --> note, 10% on each arm received pre-op RT here. Differences in these studies - twice as many patients on the RMC trial - INT trial ahd even distribution of SCC and AC while AC was mostly on the MRC trial - INT allowed more chemo meaning a longer delay to surgery for those that didn't respond - fewer pts underwent surgery on the INT trial

Major trials to know for gastric cancer - adjuvant chemoradiotherapy trials

INT 0116 - McDonald Trial ARTIST trial Meta-analysis

Pre-operative CHEMOTHERAPY alone trials - overall 11 RCTs performed - 4 confirmed a survival benefit, 7 didn't - having a good response to chemo confers a survival benefit Two major trials to know

INT0113 (US) trial - negative MRC (UK) trial - positive

When should you start RT in HN after surgery?

Ideally w/in 4-6 weeks because of the package time

Mesothelioma Management Stage I-IIIA Epithelioid or Biphasic - options?

If resectable --> Pleurectomy/decortication -- adjuvant consider hemithoracic pleural IMRT (IMPRINT trial) -->EPP --> hemithoracic RT - AP/PA - don't care about IMRT because there is no lung there. Unresectable --> systemic therapy

Thymoma/thymic carcinoma management? surgically resectable? - biopsy indicated first? - adjuvant chemo therapy indicated for thymoma? - locally advanced, unresectable? - first step?

If surgical -- resect it - diagnostic and therapeutic -- then adjuvant RT considered - can avoid biopsy if you are going to resect it, there is a TRANSPLEURAL SEEDING RISK if you biopsy a resectable thymoma - complete thymic resection is indicated with examination of the pleural surfaces - adjuvant chemo is NEVER indicated for just thymoma, but NEOadjuvant chemo may be indicated if locally advanced and unresectable, - first step is to biopsy to find out what it is for sure.

Locally Advanced Thymoma/Thymic Carcinoma Potentially resectable or Unresectable

If unresectable -- concurrent chemoradiotherapy (usually carbo/taxol) Potentially resectable -- induction chemotherapy -- re-evaluate for resectability

Imaging Workup 3 major scans you want and what stages you need them? Tissue - type of biopsy preferred? - best place to biopsy? Markers for subtypes - Primary lung adeno: (3) - Neuroendocrine: (3) - mesothelioma: (4) term-0 Important molecular testing: - major things to test?

Imaging Workup - CT Chest/Abdomen with IV contrast (all stages) - PET/CT (all stages) - MR Brain (stage II-IV) -- primary >3 cm Tissue - Preferred biopsy addresses diagnosis and stage (node > primary) - Core biopsy preferred Markers for subtypes - Primary lung adeno: TTF1, CK7, Napsin-A - Neuroendocrine: synaptophysin, CD56, chromogranin A - mesothelioma: WT-1, calretinin, CK5/6, D2-40 Important molecular testing: - EGFR, ALK, KRAS, ROS-1, BRAF, and PDL-1 status

False positive vs False negative Positive Likelihood ratio vs Negative Likelihood ratio

Important difference in positive/negative likelihood ratio compared to positive and negative predictive value : PLR says how likely is it that a patient with a disease will have a positive test results compared to the likelihood of a patient without a disease having a positive test results. NLR is the probability of a patient with the disease testing negative compared to the probability of a patient without the disease testing negative LR+ = sens/(1-spec) LR- = (1-sens)/spec *Likelihood ratios ARE NOT affected by disease prevlance*; whereas the positive/negative predictive value are changed by disease prevalence

BILCAP study - looked at adjuvant capecitabine - 447 pts with resected cholangio - results?

Important to know that per protocol analysis showed a survival benefit of adjuvant cap (53 vs 36 months)

RTOG 7920 - randomized pts to standard pelvic RT +/- para-aortic RT in pts with high risk cervical cancer - eligible pts: tumors >4 cm OR any clinical invasion into the parametria Old school RT was 40-50 Gy pelvic field -- 1.6 to 1.8 Gy - brachy was 30-40 Gy to point A Para-aortic group - extended field RT to 45 Gy to the entire PA chain up to the renal hilum Result -

Improved OS in patients with extended para-aortic RT ~10-12% benefit HOWEVER - toxicity was WORSE (grade 4 or 5!!) Grade 4 and 5 toxicity is RARELY ever seen from adjuvant RT so the fact that they were killing people is very bad. Essentially this level of toxicity was deemed not worth the OS benefit. 10 yr 8% gr4/5 is pretty damn high This trial led to the RTOG 9001

Al sarraf trial = INT 009 = RTOG 8817 - randomized trial of NPX cancer that was stopped early due to significant survival benefit - 147 pts - NPX cancer - stage III-IV - WHO I (25%), II (35%), III (41%) - randomized to RT alone vs ChemoRT + adjuvant Cis/5FU - results?

Improved PFS and OS PFS - 66 vs 26% OS - 76% vs 46% HUGE survival beneift

Major takehome of difference in SRS vs whole brain shown in data?

Improved distant brain failure with WBRT, worse with SRS Better cognition with SRS instead of whole brain Also, better LOCAL CONTROL w/ SRS+WBRT compared to SRS alone - probably dose escalation effect Generally no differences in OS

When can you treat OP with definitive RT vs definitive chemoRT

In general according to ASTRO refresher, use AJCC 7th staging and can treat anything that is up to T2N1 (2-4 cm and 1 node <3 cm, no clinical/rad evidence of ECE) DEFINITIVE RT for OP and supraglottic larynx (rule of thumb, use AJCC7th) - up to T2N1 -- basically never done 1. T2 or less (2-4 cm) 2. up to N1 (only 1 IL node <3 cm) 3. No evidence clinically/radiographically of ENE This really depends on your referral patterns -- here ENT would take virtually all of these people for TORS and refer them based on PORT or PO-CRT indications afterwards. We really never see these people and if we did, we would probably still recommend definitive chemoRT. DEFINITIVE CHEMO-RT for OroPharynx 1. >1 node 2. Single node >3 cm 3. clinical/radiographic ENE 4. T3/T4 disease (>4 cm primary or invading structures) Olser guy says T1-2 = definitive RT T3 = chemoRT T4 = surgery + adjuvant (chemo)RT - this is a weird ohio state thing according to ryan and nobody else does this

In general, what do you do if you have a pCR rate after neoadjuvant chemo in the breast/nodes?

In general if you had an indication for XRT before chemo, you proceed as if there wasn't a pCR. If cN1 prior to therapy, even if pCR, we still treat nodes. B51 is looking at this: - BCT and cN1 --> pCR in node, get either WBI or WBI+RNI - Post-mastectomy initially cN1 --> pCR in node = No XRT or XRT to CW and RNI Will help us decide how much benefit we add in PMRT or pCR node setting. The Mamounas data would suggest we don't add much benefit because ladies that had a pCR in the breast/nodes had 0% recurrence rate even without radiation -- but that only applies to like 11 women, so not enough numbers to just go on that.

treatment overview for rectal cancer

In general: T1 - can consider local excision T2 - usually needs radical LAR/APR with TME +/- chemo after or chemoRT if N+ or R1 (not done alot). If you are considering local excision for T2, you need to make sure they don't have any of the factors on the next card) - and they probably would need neoadjuvant therapy to do LE (so not something that's typically done) T3/4 or N+ --> generally an indication for multi-modality therapy with chemoRT and surgery. Sequence used to be upfront chemoRT --> surgery --> more chemo. This has largely been supplanted by TNT (chemo-chemoRT-surgery or chemoRT-chemo-surgery) -- idea being all neoadjuvant therapy up front - data for this later

When should you use whole lung RT, what if the patient responds to chemo and the lung mets go away at 6 wks?

In the study seeing if we could eliminate WLI from rapid responders, the 10 yr EFS dropped with the omission of WLI, therefore I would offer WLI to patients with lung metastases regardless of their response to chemo. I would want a biopsy of the lung nodule prior to lung RT.

SWOG 0809 - Ben Josef - MOST IMPORTANT to know - PII -- 79 pts - surgery --> adjuvant xeloda-Gem x4 cycles --> xeloda XRT for resected extrahepatic cholangio and GB cancer (small number) - important to know inclusion criteria -- list them. What was RT?

Inclusion criteria - pT2-4 EXTRA-hepatic cholangiocarcinoma and gallbladder cancer Positive margins OR Positive nodes So we say these people would be eligible for this style of adjuvant xrt. RT was 45 Gy to LNs and 54 Gy to 59.4 (pos margin) Median OS - 35 Months 2 yr OS for R0 vs R1 - 67% vs 60%

SRS - RTOG Trials RTOG 9005 Maximum tolerated doses -- <2 cm = 24 Gy --2-3 cm = 18 Gy -- 3-4 cm = 15 Gy RTOG 9508 - 333 pts, MRI confirmed 1-3 mets, <4 cm, RPA class 1-2 - WBRT = 37.5 Gy +/- SRS (surgery and crossover allowed) - WBRT +/- SRS - all pts - increased KPS, LC and decreased steroids - UVA --- increased OS if solitary met - MVA --- increased OS if 1-3 mets and RPA class 1 and squamous NSCLC

Increased LC and QOL w/ no increase in OS seen when SRS added to wbrt - 20% SRS arm never got SRS - 30% WBRT only pts crossed over the wbrt + SRS - unknown how many pts had upfront surgery - rate of CNS deaths equal - best LC yet for WBRT seen - 71% at 1 yr (probably because of the crossover)

MR spectroscopy - Choline/NAA ratio of >2 indicates what?

Increased choline, decreased creatine, and decreased NAA == implies recurrence Radiation necrosis = increased lactate, decreased choline, creatinine, naa

Imaging features of LGG surveillance that may indicate recurrence/transformation?

Increased enhancement, esp nodular Increased cerebral blood volume (up to a year before)

When is an PAB needed? How is it given?

Indication: >50% LN, ECE, obesity leading to inadequate LND Helps compensate for inadequate midplane dosing SCV field mirror and shaved out of lung

Lowry Paper for Follicular Lymphoma - Gives dose for low grade and high grade lymphoma - British National Lymphoma Investigation - BNLI Lowry study - 361 sites mostly indolent NHL (mostly FL and MZL) requiring RT for any reason - 640 sites of aggressive NHL (mostly DLBCL) Randomization was for: Indolent - either (70% stage I-II, 72% curative, 28% palliative) - 24 Gy in 12 fractions - 40-45 Gy in 20-23 fractions Aggressive - either - 30 Gy in 15 fractions - 40-45 Gy in 20-23 fractions Results for indolent?

Indolent - NO difference in freedom from local progression, PFS, or OS - trend toward less side effects in the lower dose Therefore 24 Gy is the standard for indolent definitive intent RT.

Chemotherapy in NPx?

Induction = NO ROLE (multiple level 1 studies, only consider if delay to tx) -- this paradigm is changing a bit now because of newer data -- basically its probably more relevant in EBV positive population that's at higher risk of distant failure (Sun 2016 Lancet and Zhang 2021 NEJM show DM, PFS, FFS, OS benefits to induction TPF and gem/cis, resp specifically in EBV population) Concurrent = 40 mg/m2 weekly HN001 level 1 data shows CRT > RT alone Adjuvant = 80mgm2 cis on d1 /5Fu 1000mgm2 d 1 -4 q 4 wks x 3 cycles (see data section - debatable benefits)

CALGB 39801 -- showed what?

Induction chemo doesn't help when added to concurrent chemoradiation. Just had higher side effects. Also no role for consolidation chemotherapy after ChemoRT.

INDUCTION CHEMOTHERAPY What popularized the idea of induction? What trials showed no benefit? In what specific situation might induction have a role?

Initially popularized by TAX324 trial, which showed advantage of taxane (docetaxel) added to PF for induction compared to same induction without taxane, but DIDNT compare induction to pure concurrent strategy. DECIDE and PARADIGM showed no advantage for induction. Very limited situations for induction chemo: - could have a role in the setting of impending airway compromise to prevent tracheostomy or if rapidly progressive disease with need to start therapy immediately before the IMRT can be planned. If they can't safely lie on the table. That's about it.

Intention to treat analysis vs per protocol anaylsis

Intention to Treat (ITT) = Includes all patients randomized to either treatment arm regardless of whether or not their completed the study - this prevents the loss of statistical power that may be encountered with a failure to complete study protocols (dropout) or non-compliance. - The problem with this type of analysis is that you may end up with patients in the group who make the effect of treatment look less significant because they didn't actually get or complete the treatment at all so maybe their worse outcome is because they didn't get the intended treatment. Per Protocol (PP) = This includes only the patients that were randomized to their treatment arm if they actually completed the treatment. - the problem with only doing this type of analysis is that it can lead to bias. You might be only analyzing people that had some additional factors that allowed them to complete the treatment (might have been essentially only the best performance status patients or those with tolerable treatment fields with smaller disease). In general, in non-inferiority trials, it is recommended that both types of analyses be completed.

DLBCL - RIVOVER-60 vs RICOVER-noRTH - pts 61-80 yrs - any stage or IPI - aggressive BCL - treated with R-CHOP-14 x 6 cycles + RT to bulky or EN sites (winner arm of RICOVER-60) compared to R-CHOP-14 x 6 without RT (RICOVER noRTH) RICOVER-60 was RT to bulky sites (>7.5 cm) or EN lesions RICOVER - noRTH was - noRT

Intention to treat analysis pts with bulky disease had better EFS with RT - trends for PFS and OS Per Protocol analysis - RT had better EFS, PFS, and OS with RT - for pts w/ bulky disease Note: EFS includes salvage treatment whereas PFS does not

GHSG HD11 - similar trial but with early unfavorable - UNfavorable stage IA-IIB (IIB only allowed if NON-bulky AND no-extra nodal disease) - so had at least 1 of the 3BEE risk factors - here they were testing ABVD vs BEACOPP (very toxic chemo) and 20 vs 30 Gy RT -- a little odd in that it was a superiority study for BEACOPP and non-inferiority study for 20 an 30 Gy - primary outcome - FFTF, 2ndary endpoiunt - OS, PFS, response rates, toxicity - IFRT was used, PET/CT not used. - results?

Interesting results - the only arm that kind of fell off was the ABVD x 4 with 20 Gy. If you did BEACOPPx4 and 20 Gy, that was sufficient. ABVD +20 was inferior compared to BEACOPP and 20 Gy -- this was in terms of FFTF and PFS Since BEACOPP is so toxic, most people would say the standard is thus ABVDx4 + 30 Gy is the standard. No difference in OS at 5 or 10 yrs Toxicity - BEACOPP - 73.8% - ABVD - 51.5% --> the major concern though is the late toxicities like high infertility rates, secondary leukemia 30 Gy vs 20 Gy - 12 vs 5.7% (mostly GI, mucositis) Note: Most people especially in the US don't use BEACOPP due to the toxicities.

Example question Pts w/ 2 cm L tonsil SCC p16+ with multiple involved lymph nodes and a 15 pack year history what risk group?

Intermediate risk Think of KK Ang paper that showed that p16+ non-smoker = low risk p16+ smoker = intermediate risk (>10 years of smoking) p16- + smoker = high risk

IPI score?

International Prognostic Index APLES Age 60 or older Performance Status 2 or higher LDH >ULN Extranodal >1 site Stage III/IV Revised score involves doing this in the Rituximab era - so all of the numbers are just higher for survival because Rituxmab just improved OS by ~10% for all categories -- didn't change the components of the score 4 yr OS listed below 0-1 = low --> 82% 2-3 = low intermediate -->81% 3-4 = high intermediate --> 49% 5= high risk --> 59% So as you can see there is a huge drop off between low int and high int. The revised R-IPI numbers say: Very good - 0 points - 94% Good - 1-2 points - 79% Poor - 3-5 points - 55% They will ask questions about these based on how many risk factors so you can think of it as ~95 --> ~75 --> ~55% for every 2 points added

Presentation of AVM?

Intracerebral hemorrhage - ~50% Seizures - ~20% Headache > focal neurologic deficit (10%)

Bladder cancer dosing studies -- Meta-analysis looked at 2 studies enrolling T2-4 pts -- BC2001 and BCON comparing 64 Gy in 32 fractions to 55 Gy in 20 fractions - results?

Invasive locoregional control was improved with 55 Gy in 20 fractions (HR 0.71) w/ similar toxicity Most people think we should be moving toward hypofrac. Europe they do NOT treat pelvic lymph nodes also. Convention is moving away from treating lymph nodes in bladder cancer anyway though. NCCN guidelines say to treat whole bladder with or without regional nodes to 39.6 - 50.4 Gy -- boost th whole or partial bladder to 60-66 or to consider reasonable alternative of 55 in 20 to whole bladder.

What should you ask your pathologist?

Is there any evidence of anaplasia Margins Nodes LOH at 1p or 16q or both

Treatment paradigm for unresectable primary disease - T3 (FIGO IVA) - T2 (>4 cm) - primary surgical treatment? - how does that change the subsequent therapy?

It is UNRESECTABLE disease - so the question is can you perform an inguinofemoral lymphadenectomy? if yes --> EBRT + concurrent Cis --> Node negative: to the primary tumor only --> Node positive: to the primary tumor + pelvic lymph nodes if no --> EBRT + concurrent Cisplatin to primary tumor and inguinofemoral and pelvic lymph nodes This is based on NCCN guidelines

Abiraterone is an inhibitor of what?

It is a CYP17 inhibitor -- dirty inhibitor that also decreases production of cortisol -- thus why we give prednisone. Androgen is produced at testes, adrenal glands, and prostate tumor cells.

Two major nerve involvement syndromes in nasopharynx cancer?

Jacob syndrome (Petrosphenoidal syndrome) - due to cavernous sinus involvement - CN2-6 affected - Causes ptosis, unilateral Tic, Complete ophthalmoplegia and amaurosis (vision loss w/o apparent lesion affecting the eye) Villaret syndrome (retroparotid space syndrome) - compression of these nerves as they pass through the parapharyngeal space - IL loss of CN 9-12 - loss of gag reflex/dysphagia/horner's syndrome (9) - deviation of the uvula (9) - tongue deviation (12) - Trapezius atrophy (11) - Vocal cord paralysis (10) Another is Vernet's syndrome -- jugular foramen syndrome - compression of CN IX-XI by extension into the jugular foramen -- leading to difficulty swallowing, vocal cord paralysis, and paralysis of the SCM/Trapezius -- so only real difference between Vernet and Villaret is that Villaret has tongue deviation due to CN XII involvement

Why is larynx hypofractionated (2.25 Gy fractions)

Japanese study compared conventional (2 Gy) to 2.25 Gy/fraction and found SS LC benefit to 2.25 92% vs 77% = was a randomized study (a 15% LC benefit) Problem with this paper: 2 Gy only had 77% LC rate. This is a problem because most other data shows a ~92% LC rate at 2 Gy/fraction and thus 77 seems oddly low. - nonetheless we still use this level RCT data to support our use of hypofrac

ARTIST II TRIAL - compared 2 adjuvant chemotherapy regimens and chemoRT in D2 dissected stage II or III node positive gastric cancer - 546 pts - 1:1:1 randomization to three adjuvant regimens - S1 for 1 y VS S1 + oxaliplatin (SOX) for 6 months VS SOX+RT - med fu 47 months - results?

Just as an FYI -- S-1 is a novel oral dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF) based on a biochemical modulation of 5-fluorouracil (5-FU); S-1 contains tegafur (FF) and two types of enzyme inhibitor, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. In pharmacokinetic studies, S-1 showed high 5-FU concentration in blood for long periods of time. -- basically a special type of 5-FU Estimated DFS results - S1: 64.8% - SOX: 74.3% - SOX-RT: 72.8% No difference was found in DFS between SOX and SOXRT. Both SOX and SOXRT were better than adjuvant S1 alone, but SOXRT did not significantly reduce rate of recurrence after D2 gastrectomy.

Liver Cancer

Just gonna try to focus on the high yield points here Hepatocellular carcinoma Cholangiocarcinoma - intrahepatic vs extrahepatic

What are your brainstem constraints for ependymoma?

Just say you allow point max of 59 or no more than 1% of PRV getting 59

Stage grading system for acoustic neuroma?

KOOS STAGE I : Confined to internal auditory canal, (0 - 10 mm) II : Protrudes into CPA "extracanalicular", < 20 mm III : Protrudes to CPA "extracanalicular" [20 - 30) mm total; or touching the brainstem but no displacement/compression IV: ≥ 30 mm, OR brainstem/CN displacement/compression

Kidney Cancer - major risk factors?

Kidney cancer Risk factors - tobacco smoking is a definite risk factor. We are finding more with increased use of CT scans. - Sickle cell trait/disease is associated with renal medullary carcinoma - cystic disease of the kidney - VHL -- assocated w/ red birthmarks, kidney cancers, CNS hemangioblastomas, retinal angiomas, pheochromocystomas, pancreas tumors. - hereditary clear cell renal cell carcinoma - rare AD disease. Also associated with VHL mutation - hereditary papillary renal cell carcinoma

Testicle dose constraints Kidneys CL testicle

Kidneys V20 <10% if 2 functional kidneys D50% <8 Gy, D15% <20 Gy CL testicle <6 cGy -- use a clam shell

CSF Flow

LATERAL VENTRICLES >> INTERVENTRICULAR FORAMINA (foramen of Monro) >> THIRD VENTRICLE >> Cerebral AQUEDUCT of Sylvius >> FOURTH VENTRICLE >>> Foramen of Lushka (lateral) and Magendie (midline) --> SPINAL CORD >> SUBARACHNOID SPACE >>> SINUS >> CYCLE REPEATS * lateral ventricles get CSF from choroid plexus *third and fourth ventricles also receive CSF from choroid plexuses

Benefit of chemo addition to PORT in ECE and positive margin?

LC and DFS RTOG 9501 When looking at all post op HN, the addition of chemo did not improve LC, DFS, or OS When looking a specifically those w/ (+) margin and or (+) ECE there was a benefit in LC and DFS 10 yr data: LRF 33.1% vs 21.0% (SS) -- ABOUT 12% benefit DFS 12.3% vs 18.4% (SS) OS 19.6% vs 27.1% (NS) EORTC 22931 did have a LC and OS benefit

LDR vs HDR for gyn brachy

LDR is really a relic of the past

Summary of RT in Ewing's trials

LF rates with RT are very low (10-20% range) RFS is pretty poor though (50-60%) - thus distant failure is the bigger problem in Ewing's. Pts with lung involvement have better outcomes with lung RT (5 yr improved EFS --> 36% EFS at 5 yr with rt)

Pop-RT - 224 high risk patients based on MR and PET/CT (80% PSMA PETs - kinda nuts cause that was in india) - randomized to prostate or prostate + LNs (commons, internal/external - most people don't cover commons) found what?

LN RT increased biochemical failure free survival and disease free survival Didn't improve OS. Unclear what DMFS benefit means in the era of PET scanning. Pelvic nodes increased GU toxicity about 12%. Take home about most of the trials that added pelvic RT was that they usually increased tox a bit and improved biochemical survival or DFS but usually didn't affect OS. Elective RT to pelvis is somewhat controversial for these reasons. Major ones - RTOG 9414, GETUG-01, Pop-RT

Stage I clear cell renal tumor, what is your recommendation

LN sampling and central path review - if negative no RT

Node involvement w/ T1, T2, T3, T4 glottic larynx?

LNs: T1 < 2%, T2 < 8%, T3 ~ 15%, T4 ~ 25%

Which is associated with the worst outcomes in Wilms tumor

LOH of 1p AND 16q

Workup for ependymoma

LP if no increased ICP, do fundoscopy first MRI of brain and spinal cord Post op brain within 48 hrs (don't wait longer d/t post op gliosis) Can get CSF and MRI spine 14 days post op if you didn't do upfront At some point you need to get csf though and image spine

GORTEC Trial - stage III/IV OP pts - 222 pts - Randomized to RT +/- chemo (Cis/5FU) - results?

LRC at 5 yrs improved dramatically - 25% --> 48% OS not significantly different (16 --> 22%)

Cairo adjuvant trial - randomized trial - more modern - 2002 - 2008 - pts w/ pT3b, grade 3 or +LNs - randomized after cystectomy to RT + cis/gem or cis/gem alone - note: Egypt trial - so there was a predominant of SCC (45-48% which is NOT what we see here) - more advanced than we see here - results?

LRFS was improved with CRT over chemo alone. DFS trended toward significant benefit for CRT. Toxicity was higher in CRT v chemo arm. Note: We tend to do neoadjuvant chemo in US that probably downstages patients so we don't get as many high risk patients adjuvantly as they had in the Egypt trial.

SCLC overview card LS-SCLC - workup - treatment options - rt dose? - chemotherapy? - follow up? ES-SCLC - standard treatment?

LS-SCLC - Workup: Biopsy (EBUS > TT-FNA - take bx that can stage too), CT Chest/abdomen (adrenals) w contrast, PET/CT, MR brain wwo contrast (ALL) - Options: Definitive chemo-RT -- technically surgery for VERY early stage (very rare to find these people) - RT dose: 45 Gy/30 bid fractions (ChemoRT) Turrisi regimen is still SOC (66/33 per Convert) - Chemo: Concurrent Cis/Etop (Cis 60 etop 120 q 3 wk) + Atezo consolidation outback is being tested on LU005 (LU007 is doing concurrent atezo) - turrisi started on C1D1, we tend to start C2D1 -- - 6-8 weeks out, repeat brain MRI and if no mets, offer PCI 25 Gy/10 fractions - F/U: CT chest wo contrast q3 months for 2 years, then q6 months for 3 years, then back to q1 year screening + routine brain MRI Extensive stage SCLC - standard to start chemo/immuno (Cis/Etop --> induction/maint Atezolizumab - standard based on IMPower133) -- if at least some response, can offer consolidative RT to chest (30 Gy/10 fxn) - Slotman- chest consolidation RT (30 Gy in 10 fractions) found OS benefit of 10% at 2 yr (NOT 1 year -- was primary endpoint of study)- chemo = 4-6 C cis (80 mg/m2)/etop (100 mg/m2) q3 weeks

MSK data of 95 pts wiht LAR and ARP for T3N0 -- all had TME. What was the only factor important for locoregional recurrence?

LVI

Omission of RT for favorable DLBCL - LYSA 02/03 - FLYER - SWOG 1001

LYSA 02-03 shown here. Full on next card

RTOG 91-11 - 520 pts - three arms: 1. RT alone 2. induction chemo (Cis/5FU) + RT 3. concurrent chemoRT primary endpoint - larynx preservation RT was 70 Gy to gross disease and 50 Gy ENI Planned neck dissection for nodes >3 cm or multiple at diagnosis What were rates of larynx preservation?

Laryngeal preservation 1. 66% - RT alone 2. 70% - induction chemo - RT 3. 84% - CHEMO-RT LRC was 1. 51% 2. 55% 3. 69% OS and DM was not difference. Not induction did have about a 10% lower DM rate. Better larynx preservation with chemoRT arm. Note: N3 was an exclusion criteria

Pulmonary Carcinoid tumors - M:F 1:1 - med age 47 yrs - 1-2% of lung tumors - 25% are in the mediastinum/lung Pathology - neurosecretory granule containing tumors - there are low grade, intermediate atypical), high grade (large cell neuroendocrine) and frankly malignant like small cell lung cancer Mostly found in major bronchi and more common in right lung than left for some reason Management?

Laser - relieve obstruction - surgery best chance of cure - RT if truly unresectable RT is rare as primary therapy - no indicated in margin negative/node negative - no role for N1 but maybe benefit for N2 - multiple lymph nodes multiple levels -- can consider RT

What is included in the WVRT volumes

Laterals, 3rd, 4th, prepontine cistern Vent is ctv, add 3 mm ptv

Pelvic floor muscle anatomy - what is the pelvic floor made up of - what muscle is lateral to the prostate gland

Levator ani is the bottum of the pelvic floor -- the fusion of the three muscles - iliococcygeus, pubococcygeus, and puborectalis The oburator internus are the muscles lateral to the prostate

What genetic syndromes ARE associated with a higher risk of secondary cancers after radiation thus you should caution if patient desires BCT?

LiFraumeni - p53 mutation (~1% risk per year of 2nd cancer) Neurofibromatosis - NF

Local control for Ewings - extremity = ? - pelvic tumors = ? Prognostic features for LC - size if >8 cm - LC = ? - size if <8 cm - LC = ?

Local control for Ewings - extremity = 90-95% post RT - pelvic tumors = ~70-80% Prognostic features for LC - size if >8 cm - LC = 80% - size if <8 cm - LC = 90%

What outcomes were improved w/ hypofractionation in larynx?

Local control improved by ~20% compared to standard fractionation -- 92% vs 77%. The problem with the Japanese data is that most other trials showed conventional fractionation LC was in the 90's -- so doesn't make much sense that we don't question their LC in the 70's for standard fractionation. In any case, we consider their data Lvl 1 data for improving LC in T1 and early T2 larynx cancers.

Lobectomy vs Wedge resection - LCSG 921 - showed what? How many early stage LC pts are candidates for surgery?

Local recurrence much lower for lobectomy (6%) vs wedge resection (18%) No difference in OS between these though. SBRT control rate is about the same as lobectomy for early stage. Only about 25% are surgery candidates 5 yr survival of 10% if you do nothing for stage I LC (med OS ~11-14 months)

PEG tube dependence? When can you remove the PEG tube?

Long-term PEG tube dependence is 15-20% but that is probably improving Remove PEG at 4 weeks once gaining weight and eating PO average PEG duration is 12 weeks with CRT

Low Grade/Indolent types

Low grade follicular lymphoma Small Lymphocytic lymphoma Marginal Zone lymphoma

RTOG 0539 - red journal 2016 - P2 trial for low risk meningioma (obs), RT for intermediate and high risk - "Group 2" - int/high risk = newly diagnosed atypical G2 meningioma w/ GTR (simpson 1-3) or recurrence grade I - RT was 54 in 30 - outcomes?

Low risk - surgery alone with GTR = 3 yr PFS 91.8%, 5 yr 86.1%, 5 yr LF 12.5% Low risk with STR -- 40% local failure rate Group 2 = int/high + RT had 5 yr PFS 83.7% -- so with RT similar to low risk with surgery alone

Pelvic radiotherapy for endometrial cancer should target what lymph node areas? What would prompt covering pre-sacral?

Lower common iliacs External iliacs Internal iliacsparametria Upper/paravaginal tissue pre-sacral lymph nodes -- MUST be covered if cervical stroma is involved

Mayo compared surgery to radiosurgery and showed what?

Lower recurrence with SRS (2%) vs surgery (12%) and showed less side effects with SRS

Major constraints to know - spinal cord (SBRT vs conventional) - brachial plexus - chest wall - lungs - heart - esophagus

Lung V20 -if SBRT <10%, MLD <6 Gy -if CRT <35%; ideal <20% CRT for spinal cord, tend to lean toward <45 spinal cord (in general for SBRT 6 Gy/fxn) - 50/5 = 30 Gy - 54/3 = 18 Gy - 34/1 = 14 Gy - 60/30 = closer to 45 with CRT (~50-55 if w/o Chemo) - 45/30 bid = 41 (was 36 in Turrisi because of bigger fields - because they did ENI) brachial plexus - in general for SBRT <3 cc getting 6 Gy/fxn - fractionated = <66 Gy to 0.1 cc Chest wall - V30 < 30 cc OR - V30 < 70 cc Lungs - 50/5 = V20 < 10% - 60/30 = V20 < 20-30% (technically can go up to like 37%-40, but that increases RP significantly) -- goal is <20 = NO Grade 5 tox and g2+ RP is ~18.4% Heart- V30 <50%- Median dose <20 Gy - breast data says risk of late CAD event increased by 7% per Gy (10 Gy = 70% increase from baseline risk) - takes a long time before this is realized though (15-20 yrs, lung pts might not live that long) Esophagus Mean Dose = 34 Gy -- CRT V60 < 17% SBRT: Max dose 0.1 cc 30 Gy kind of made up: 10 cc to 60 Gy - max 66 Gy

Where do Rhabdos typically met

Lungs and Bone marrow DMs 25% of the time

Refer to staging quizlet for staging guidelines - but important for rad onc is differences between N1, N2 and N3

Lymph Node Size is the difference clinical - for path, N1 is that AND <5 nodes, N2 is > 5 nodes N1 = 2 cm or smaller N2 = 2-5 cm N3 = >5 cm 3 cm is a good marker for good control with radiation based mostly on retrospective studies

Papers for covering RN in N+ BCT - MA20 and EORTC Poortsman)

MA20 - Wheelan - ONLY LUMPECTOMY - N = 1832 - same group (pN1 = 1-3 ax nodes; 85%, 5% >4 LNs, 10% node negative) or high risk node negative (T3; or >2cm w/ <10 nodes removed and at least one of ER-, G3, LVSI+) randomized to WBI or WBI+RNI - excluded T4, N2-3 or unable to tolerate RT - randomized to RT to LNs or no RT to LNs - RT 50/25 + boost allowed (10-16 Gy) Nodal Dissection: Required lvls 1 - 2 ALND w/ any (+) SLNB - Addition of RNI did NOT improve OS, but did improve PFS (3%), DFS (5%), and DMFS (~4%) - interesting that here you are MOSTLY looking at 1-3 node positive patients and the addition of RNI didn't help that much. These are relatively small % improvements. Probably got better dissection so probably is saying that insufficient dissection was an issue in the Danish 82b/c trials. EORTC 22922 (Poortsman) - LUMPECTOMY OR MASTECTOMY (24%) - N = 4004 - addition of RNI reduced breast cancer specific mortality and reduced breast cancer recurrence - regional nodal irradiation in the setting of node-positive breast cancer improved disease-free survival and reduces breast cancer death and should therefore be strongly considered. Outcomes- No RT RT 10yr DFS 69.1% 72.1% SS (lost at 15 yr) 10yr OS 80.7% 82.3% NS 10yr DMFS 75.0% 78.0% SS 10yr BCSM 14.4% 12.5% SS (still SS at 15 yr)

Data for Peri-operative chemotherapy - major trials to know

MAGIC FLOT CRITICS Meta-analysis

Poet study - STAHL study , JCO 2009 study - RCT of pre-op chemo vs pre-op chemo followed by CRT --> both followed by surgery - trial was stopped due to poor accrual -125 of the planed 354 pts accrued - induction chemo was cis/5FU, LV and RT was 30/15 concurrent cis/etop (weird) - med fu 46 months - results

MAJOR thing to know if the pCR difference from this trial - with the caveats of kind of odd treatment - CRT = 16% - chemo = 2% Trend toward improved OS in CRT vs chemo alone - 3 yr OS --CRT 47% --chemo 27% (NS)

ADAURA Phase III study - adjuvant osimertinib in resected EGFR mutated NSCLC - NEJM 2020 - 682 pts randomized EGFR mut NSCLC pts to Osimertinib vs placebo - stage IB-IIIA pts - no PORT allowed, adjuvant chemo allowed - results?

MASSIVE improvement in DFS (HR 0.17, SS) -- 83% improvement in DFS improved outcomes in basically all subsets -- most benefit in highest risks pts. Recurrences were more likely to be locoregional in osimertinib arm and more likely distant in control arm. CNS relapses were reduced in the Osi group. Early look at OS - trend toward improvement but results too early.

Data for IMRT vs 3D for esophagus

MD anderson series essentially looks at higher heart dose with 3D and attributes survival difference to that

Rates of LC with T1-2 BOT with RT alone?

MDACC Spanos data, Footee (UF) and Wang (MGH) - T1 LC = 90% - T2 LC = 70-90%

Pituitary adenomas associated with what syndromes?

MEN-1 Carney complex Familial acromegaly

MGUS vs smoldering multiple myeloma

MGUS - no end organ damage - just the monoclonal protein smoldering - a step up - 10-60% clonal bone marrow - 60 would be criteria for MM. Have the M spike but still don't have any of the CRAB features

ACT II - 2x2 design RT 50.4 Gy + 5FU + MMC or cisplatin - randomized to +/- maintenance therapy with 5FU and cisplatin for 2 cycles 940 pts take home here?

MMC more toxic Non-heme tox similar NO difference in CR, RFS, or OS Maintenance chemotherapy without benefit The ACCORD3 trial is another 2x2 that looked at induction cisplatin - increased RT dose to 60 or 65 Gy-70 Gy --> take home here is No difference in 5 y CSF, LC, Tumor free survival or cancer survival

Do you need MMC? toxicities = renal, pulmonary, bone marrow toxicity Not a radiation sensitizer and modest activity against squamous cell cancers PIII - RTOG 8704 - randomized to 45-50 Gy + 5FU +/- MMC - Key result? what was MMC associated with?

MMC was associated w/ fewer colostomies (9% vs 23%, p = 0.002) The impact of MMC was confined to T3-4 tumors (SS) Higher local control with MMC 84 v 66%, SS Better DFS 73 v 51% MMC had higher toxicity OS was higher but NS for MMC

Gastric cancer genes

MMR lynch - risk 1-13% Juveile Polypsis - SMAD4 - risk 9-50% Peutz Jeghers - STK11/LKB1 - risk 29% FAP - APC gene - 10% risk

Imaging findings for GBM MR -- ? Perfusion imaging -- ?

MR - T1: hypointense, gad enhancing - T2 hyperintense with significant FLAIR edema Other buzzwords: - vasogenic edema, nodular enhancement from newly formed vessels - heterogenous enhancement, central necrosis, widespread increased T2 signal, infiltrating tumor + edema

Medulloblastoma - f/u evaluation - imaging - other major evaluation needed? Specific adverse effect seen here?

MR brain q3 months in year 1, q4-6 months year 2-3 and annually after year 3 annual audiogram neurocognitive endocrine q6 months Cerebellar mutism/posterior fossa syndrome -- if this happens, you continue treating through it - happens 1-2 days after resection of posterior fossa tumor (rare in adults) - happens 25-40% of the time. 20% have lasting issues, most recover at least somewhat and can last months. - symptoms = diminished speech, progressing to mutism, emotional lability, hypotonia and ataxia - not well understood why this happens.

CNS imaging modalities MRI - T1 = fat appears ___ and fluid is ____. - T1+ gad = paramagetic contrast agent -- GAD associated with nephrogenic systemic fibrosis, avoid if GFR <30 - T2 = fat, water, and fluid are ____. brain matter is ____. - FLAIR = ? Post-op imaging w/in 48 hours -- why?

MRI - T1 = fat appears bright and fluid is dark. - T1+ gad = paramagetic contrast agent -- GAD associated with nephrogenic systemic fibrosis, avoid if GFR <30 - T2 = fat, water, and fluid are bright. brain matter is dark. - FLAIR = Fluid attenuation inversion recovery - recmoves CSF signal on T2 images w/in 48 hrs -- get post-op gliosis, maturation of blood product -- acumulation of iron products that complicates reading blood product from residual tumor

Data for PORT for subtotal resection - no randomized data, we just do it because expected benefit Wally Curan JCO 1988 paper - stage I R0 resection - 43 pts, 1 got PORT - 0 recurrences (so they don't need PORT) Stage II/III pts w R0 resection - 26 pts - 5 got RT, 21 didn't -- - Local failure is worse w/o PORT - recurrence rate shown below --> GTR w/o PORT is 53% -->GTR w/ PORT is 0% --->STR w/ PORT is 23% These are not statistically significant, but it was essentially the only data at the time and it became standard to say -- This is why we say R0 stage II-IV = give PORT MSKCC and MDACC review - 156 pts w/ definitive RT or PORT - looked at failures -- where did they happen?

MSKCC and MDACC data showed that recurrences corresponed to Masoaka stage but also showed that recurrences are either out of field (pleura surfaces) - majority OR in field failures --- NOT in the nodes RT wo ENI showed LC >90% w/ infrequent marginal failures You just cover all the surgical surface

Surgery and Rhizotomy options for TN

MVD: Surgery behind the ear Puts teflon between the nerve and the vessel. Very effective, and generally curative (~ 70% over decades of follow up) - tends to be more durable than GKRS If it comes back, that is usually in the first few years. Can repeat MVD, (2nd time 60% effective) Depends on surgical experience, usually if MVD was done at an outside hospital with less experience then we may recommend Dr. Tater try MVD here, Mortality rate is very low 1/1000 the risk are mostly anesthesia related, Can cause unilateral hearing loss 1%, so may not be a good option if just one good ear. Rhizotomy: (Glycerol, balloon, radiofrequency rhizotomy "most toxic" ) Not curative Won't last as long as MVD or GK (med duration for rhizotomy is ~ 2 - 3 yrs) Only use rhizotomy when you need pain control IMMEDIATELY Glycerol Found by accident, used to put alcohol in CSF to see nerves on imaging, before we had MRI (it surprisingly decreased TIC symptoms) Now we go thru skull base and inject glycerol directly into the gasserian ganglion Balloon Inflates inside the gasserian ganglion,deadens the nerve out Toxicity for glycerol and balloon higher than GK Radiofrequency: Highest toxicity, anesthesia dolorosa 5% risk.

Modern Adjuvant Chemo Trials for NSCLC after surgery - just look at trials LACE Meta-analysis for chemo after surgery - shows what?

Majority of trials show harm or no benefit in stage IB and benefit mostly seen stage II and up 5.4% OS benefit with adjuvant chemo in stage II and up - Survival is WORSE in stage IA - chemotherapy more likely to kill them than help them. THUS >4 cm or node positive gets chemo

Things to look for to ensure proper mammogram

Make sure you see good strip for pec muscle to mid-breast Flash on underside of breast so you can see inframammary fold Need to see CC and MLO views

RT considerations for Gastric MALT

Manage gastric distention (NPO) and breath hold for motion (+4DCT) - CTV = entire stomach + any involved nodes - PTV = ITV + 1-1.5 cm - 24-30 Gy - daily CBCT - heart kidney and spleen on DVH

PACIFIC TRIAL - stage III, unresectable pts who didn't no progress after chemoRT - randomized 2:1 to durvalumab vs placebo - results? - who did NOT benefit?

Massive PFS improvement for durvalumab (HR 0.52, SS) Specifically EGFR mutants didn't benefit (but AUDORA trial shows they can get osimertinib after surgery with huge benefit, so question will be if outback osi is beneficial in locally advanced setting) 4 yr update - placebo vs Durva PFS benefit of 19.5% vs 35% med OS benefit of 36.3 months vs 49.6 months (3 yr vs 4 year) Comparing control arm of pacific to 5 yr update of 60 Gy arm on 0617 shows they are very similar (~36% vs 32% on 0617) Toxicity very similar between groups on Pacific - RP wasn't statistically worse (G3 was ~3%) which is about the same as you expect from other trials. Durva if given <14 days from end of chemoRT, this actually seems to improve outcomes compared to >14 days. Start ASAP.

Types of mastectomy and what is taken

Mastectomy Types Total (simple): used for prophylactic cases Entire breast removed without ALND Modified radical: Entire breast, ALND (1 & II), removes only pec major fascia (does NOT remove pec muscles) Radical (Halstead): Entire breast, ALND (I, II, & III), both pecs (major/minor) Reserved for pec major inv. or recurrence inv. chest wall Skin-sparing/Nipple sparing mastectomy: Occult nipple involvement in 18% of IDC mastectomy specimens Incision made around areola, allows more skin to be used for reconstruction Anatomically nipple derives blood supply from underlying breast tissue If removal of all breast tissue is necessary oncologically, the nipple will die when the breast tissue is removed. Tumor must be small and at least 2 cm from nipple with no skin or nipple inv. Clinically N0, Minimal ptosis of the breast, Can do Nipple/Skin sparing in BRCA patients

What do we mean by trimodality bladder preserving therapy

Maximal TURBT (ideally completely resected bladder tumor) - <6 weeks prior to RT Concurrent chemoradiation (either MMC/5FU or cisplatin) RT is typically 55 Gy in 20 fractions when you can treat whole bladder alone easily without bowel issues. Could also do 64 Gy in 32 fractions (more conventional) - typically sim with empty bladder - Boost volume typically is GTV + 2 cm CTV (Constrained to bladder) + 0.7 cm PTV - Osler guy says to include the prostate in the 46 Gy initial volume...we don't do that. -- if you have bowel issues in the pelvis -- usually 5040 to whole bladder with 6480 to gross disease cone down.

Samples from each participant are tested for the presence of a disease using two different tests. What type of statistical test would compare the sensitivity between the two tests?

McNemar test

Esophageal Cancer 90% of cases are squamous cell carcinoma worldwide Adenocarcinoma predominates in western countries --> obesity and gerd Male predominant What are the divisions of the esophagus cervical = ? upper T = ? middle T = ? lower T = ? GEJ = divided into what?

Measurements always from the incisors Cricopharyngeus ~15 cm to the GE junction ~40 cm cervical = CP to thoracic inlet (15-20 cm) upper T = Thoracic inlet to the azygous vein (20-25 cm) middle T = Azygous vein to the inf pulmonary veins (25-30 cm) lower T = Inf pulm veins to the GEJ GEJ = divided into Siewart classification

TOGA trial - rct phase 3, Cis/5FU +/- trastuzumab - results?

Med OS 13.8 mo vs 11.1 mo - highest benefit seen in IHC 3+ No benefit of lapatinib

Critical pre-RT referrals?

Med onc if chemo needed Nutrition PEG tube eval SLP Dentistry Audiology

MUNICON - German chemo trial - 35% reduction in PET SUV after 1 cycle of chemo conferred a survival benefit - pts w/ distal esophageal or GEJ treated w/in 2 weeks of cis/5fu - PET was performed 14 days after cycle 1 - responders went on to additional 12 cycles chemo - non-responders went to surgery - median OS results?

Median OS NOT reached in responders but was 25.8 months in responders (SS) Suggests big survival advantage to chemo in those that have response to chemo

Ben Josef paper - JCO 2005 - 128 pts w/ colon mets or primary unresectable hepatobilliary tumors - RT concurrent with hepatic arterial floxuridine - RT was 1.5 - 1.65 Gy BID to median dose of 60.75 (40-90 Gy) - results?

Median survival 16 months 60% PFS at 3 yr 64% intrahepatic recurrence

Risk Factors to remember -- again, different for GHSG, EORTC, and NCCN -- these make disease "unfavorable" risk for stage I and II

Memory Aid for GHSG - 3BEE - Bulky mediastinum (tranthoracic diameter >0.33) - Extranodal disease - ESR >50 wo B symptoms or >30 w/ B symptoms - 3+ LN regions involved Width of the mass compared to the diameter of the thorax Only differences from this is that EORTC includes age of 50 or older and NCCN defines bulky as >10 cm. Otherwise they are the same really. Remember B symptoms aren't the "B" above NCIC includes mixed cellularity or lymphocyte depleted as unfavorable. Really need to memorize this card

What secondary neoplasm are these kids at risk for?

Meningioma most common RT induced neoplasm 25 % develop meningiomas at 25 yo

ARTS 1431 - whats the one exception to metastatic being high risk?

Metastatic embryonal that's <10 yrs = intermediate risk Orbit tumors = low risk

Patterns of recurrence for pancreas patients after surgery

Michelassi series looked at this 133 of 647 pts had resection, 97 survived perioperative. Relapsed patients - 29.4% local recurrence only - 47.1% local and distant recurrence - 23.5% distant recurrence only so 76% had local recurrences

Easy definitions: Mode Median Mean

Mode = them most frequent number Median = the middle number when all values are arranged in orer Mean = the addition of all values divided by the number of samples What's more important is recognizing that in a symmetrical distribution, mean = median = mode they DO NOT equal when you have an asymmetrical distribution. So if you have a tail to the right, the order is Mode < Median < Mean Think about this logically if the tail skews right, this means that you have a small number of high values that will increase the mean relative to the most commonly repeated number or the median in the center. Opposite for left skewed curve. Normal = all equal Positive = Mean > Median > Mode Negative = Mean < Median < Mode This makes sense since you know that the mean is more susceptible to change due to outliers - it will have to be closer to the outlier values than the other two. The mode will always be at the top of the peak because that is where the most frequent value occurs in the population. The median will be between the mode and mean.

How is your workup different for peds glioma vs an adult glioma?

More leptomeningeal spread in childhood gliomas ALWAYS SCAN THE SPINE (33% in HGG, 15% in LGG)

Pineocytoma treatment paradigm

More like a LGG GTR → observe, STR → consider adj/obs Can do GKRS

Genetics of Primary GBM vs Secondary GBM

Most important = IDH wt more likely primary GBM, if IDH mut, more likely to have transformed from lgg and be secondary GBM Primary GBM: - increased EGFR/MDM2 amplificiation - LOH 10/p16 loss Secondary GBM: - 2/3 have p53 mutation - more likely to have IDH1 mut.

Where are patients with unknown primary treated with neck dissection alone most likely to recur?

Most likely in the dissected neck ~20-25% of pts. <10% recurred in the undissected neck, unidentified primary site, or other mucosal recurrence

Bladder anatomy pathologic types?

Mostly transitional cell carcinoma - 92% other types: squamous cell carcinoma and adenocarcinoma, then other (small cell, etc)

What is posterior fossa syndrome? should you delay treatment?

Mutism, dysphagia, truncal ataxia, hypotonia, trouble swallowing, respiratory failure This is a side effect of the surgery d/t dorsal brainstem injury "bruise" when removing tumor Can happen in up to 15-20% This is more common if tumor is right on brainstem Develops w/in 12 - 24 hrs post tx PROCEED WITH TX, do not let it delay your RT It can last MONTHS but can resolve sooner, always recovers somewhat, 20% have long lasting issues. Physical therapy may help.

Outcomes better of margin negative/node negative

N - vs N + 5 yr OS -- 38% <10% R0 vs R1 5 yr OS -- 19-47% 0-12%

What is one reason that 1-3 nodes is more of an indication of PMRT now than it used to be?

N2 or 4-9 nodes is a strong evidence based guideline mostly because that was when people were getting their full dissections. This is NOT really standard anymore and because of Z11 and amaros, we aren't doing as many completion dissections as we used to since RNI and completion ALND have the same cancer outcomes and RT is less toxic than ALND (less lymphedema) So 1-3 nodes on SLNB is really just saying that you know they are node positive -- you don't actually know the number of true nodal metastases these days without a complete dissection. Also think about MA20 and Poortsman (EORTC 22922) data that showed benefit in high risk N0 or 1-3 node patients.

Early GHSG trials - just know key facts about these NCIC study/HD6 trial - ABVD x 4-6 vs "Sub-total nodal irradiation" +/- 2 cycles ABVD - showed what? - what's the problem with this? HD7 - Early Favorable HL pts randomized to EFRT (extended field) vs ABVD x 2 with EFRT 30-40 Gy - result? HD8 - Early Unfavorable randomized to COPPx2 and ABVD x 2 with 30 Gy EFRT vs the same with 30 Gy IFRT - result?

NCIC - HD6 - showed "increased death" from RT in the STNI arm...but 5 deaths on the STNI arm were non-treatment related (Alzheimers, suicide, drowning, etc) - this is criticized because STNI is NOT SOC HD7 - Early Favorable HL pts randomized to EFRT (extended field) vs ABVD x 2 with EFRT 30-40 Gy - chemotherapy improved FFTF (freedom from treatment failure) but NOT OS HD8 - no significant difference in any cancer outcomes but EFRT had more side effects

When would you do embolization alone for AVM? When would you do embolization with SRS?

NEVER Embolization alone = very high rate of recanalization -- should only be used to pair with surgery. NEVER The mechanism of SRS for AVM is to cause intimal hyperplasia/hyalinization and the vessel closes up -- if you emoblize, you would essentially put a glue plug in the vessel which would keep it from collapsing.

Why do you care about NF1?

NF 1, you can cause secondary malignancy with RT Be careful about treating NF1 patients about 3 x higher risk of secondary cancers. Really try to observe and basically force them to make you treat it because you can cause cancer (50% risk) w/ RT WAS A CHAN ORAL BOARDS Q

Genetic syndromes associated with CNS malignancies NF-1 - chromosome? - genetic inheritance? - symptoms? NF-2 - chromosome? - genetic inheritance? - symptoms? VHL - chromosome? - genetic inheritance? - symptoms? Tuberous Sclerosis - chromosome? - genetic inheritance? - symptoms? Retinoblasoma - chromosome? - genetic inheritance? - symptoms? Li-Fraumeni - chromosome? - genetic inheritance? - symptoms? Turcot and Gardner's syndrome - chromosome? - genetic inheritance? - symptoms?

NF-1 - Von Recklinghausen Syndrome - chromosome = 17q11.2 - genetic inheritance = AD - symptoms = Peripheral sheath nerve tumors, cafe au lait spots, optic and intracranial gliomas NF-2 - chromosome = Ch 22 - genetic inheritance = AD - symptoms = b/l acoustic neuroma, glioma, ependymoma, meningioma VHL - chromosome = Ch 3 - genetic inheritance AD - symptoms = RCC, pheo, hemangioblastoma, pancreatic tumors Tuberous Sclerosis - chromosome = Ch 9 and 16 - genetic inheritance = AD - symptoms = subependymal giant cell astrocytoma Retinoblasoma - chromosome = Ch13 - genetic inheritance = b/l retinoblastoma, cell cycle - symptoms = white reflex Li-Fraumeni - chromosome = germinline p53 mutation - genetic inheritance - symptoms = breast, sarcoma, CNS malignancy Turcot and Gardner's syndrome - chromosome = APC associated syndrome - genetic inheritance? - symptoms = colorectal and CNS tumors and the weird dermatofibromas/teeth things

CER vs EER? Number needed to harm (NNH)/number needed to treat (NNT)? ARI or ARR? Relative risk (RR)? Relative risk reduction vs increase?

NNT = Number needed to treat is defined as the number of people that need to receive a treatment in order to prevent 1 additional adverse effect. NNH = Number needed to harm is the number of people that need to be exposed to a given risk factor to result in the disease in question. NNH = 1/(absolute risk increase) NNT = 1/(absolute risk reduction) Control Event rate = c/(c+d) Experimental Event rate = a/(a+b) Absolute risk change = EER - CER ARR = if negative (<0) ARI = if positive (>0) Example = - CER = NONsmokers and got lung cancer anyway divided by all nonsmokers. - EER = Smokers who got lung cancer divided by all smokers with and without lung cancer. NNH = 1/ARI (100/ARI if as %) NNT = 1/ARR (100/ARI if as %) Relative Risk = EER/CER = (a/a+b)/(c/c+d) Examples if RR = 20 = 20 times more likely to get lung cancer if you smoke. Relative risk change = (EER-CER)/CER - increase = >0 - reduction = <0 Another way to calculate RRR is = 1 - RR (EER/CER)

Is BRCA mutation a contraindication for BCT?

NO CBTR is higher 10-yr/15-yr recurrence risk is 26%/39% in carriers vs. 3%/7% in wild-type Significantly reduced w/TAM or Oophorectomy

BIOPSY after chemoRT - Cummings Red Journal 1991 showed what? what was median time to regression? What CR was seen at 11 vs 18 vs 26 weeks on ACT II

NO BENEFIT to biopsy at 6 weeks post-CRT Median time to complete response is 3 months -- continued regression for up to an entire year ACT II showed that there was continued response clearly up to 6 months. 5 yr OS is excellent at 85-87% regardless of when you respond

LAP07 trial - 2x2 phase III trial - Question was about Erlotinib and ChemoRT in the locally advanced setting - CRT was 50.4 with Fluoropyrimidine - +/- erolotinib and +/- CRT - result?

NO benefit to CRT or Erlotinib - med OS not diff between chemo vs chemoRT

GOG 258 - RCT, P3 - looked at adjuvant chemo alone vs adjuvant chemoRT - this was FIGO III-IVA or I or II with clear cell or serous histology Primary endpoint was FFS Vaginal brachy only was allowed in the chemoRT arm. - ebrt was 45 Gy - brachy was 6x2-3 ro the surface and proximal 4 cm or ldr 20-35 Gy - indications for vaginal brachy were invasion into the cervix or vagina, lower uterine segment, and LVSI - chemo was same as portec 3 - cisplatin during rt followed by carbo/taxol x4 cycles results? - was FFS different? - was vaginal failure different? - nodal recurrence rate? -- this is asked about - which had worse distant recurrence rates?

NO difference in FFS between the arms Vaginal recurrence was lower in the ChemoRT arm (SS; 7% vs 2%) Pelvic or para-aortic recurrence was also lower in the chemoRT arm (20% w/ chemo vs 11% with chemoRT). Distant recurrence was actually significantly worse in the chemoRT arm than chemo alone.

Laparoscopic vs Open TAH/BSO -- difference in outcomes for endometrial?

NO difference in outcomes for endometrial NOT true for cervical (later)

Local excision for T3 cancers? - what is failure rate?

NOT recommended Only considered for clinical trial or patients that are unfit for surgery Meta-analysis of 20 studies - shows 1068 pts with ~1/3 with T3 tumors -- local failure rate was 60% with ypT3 tumors Local failure rate ypT0 -4% ypT1 -12% ypT2 -24% ypT3 -60% Anything more than a ypT0 --> needs to go back for radical surgery essentially

DCIS - think B17/24, EORTC 10853, SweDCIS, UKCCR -- all show the same thing really -- essentially all looked at lumpectomy vs lumpectomy + RT? - median follow up - lumpectomy alone vs lumpectomy + RT LC differences? - OS, DFS difference? EORTC 10853 - reduction in LR of RT? What do we mostly use to justify hypofractionation for DCIS? SweDCIS trial - 17 yrs fu - 1046 pts undergoing BCS +/- RT (50/25) - results? UKCCR - 1701 pts undergoing BCS +/- RT (50/25) +/- tamoxifen - again, recurrence was decreased with RT (32 v 13% wo tam, 24 v 10 w tam) - hormonal therapy reduces the risk of IBTR and contralateral breast events Good data for recurrence risk without RT to memorize RTOG 9804 and ECOG E5194 - looked at "risk categories" and defined likelihood of recurrence - ECOG E5194 study - 665 pts undergoing BCS for DCIS --> divided into low risk and high risk - low risk = low/intermediate grade + size <2.5 cm - high risk = high grade, size <1 cm - 30% got tam - some got RT - omission of RT and size were associated with IL recurrence which didn't plateau what were recurrence rates - RTOG 9804 was a trial randomized to +/- RT - either 50/25 or 42.56 - did not accrue. Did report outcomes --> - did find that LF was 6.7 v 0.9% w/ ~7 yrs f/u. for w/o or w/ RT - looked at small <2.5 cm low and int grade DCIS (so like low risk group in ECOG study)

NSABP B17 - 818 pts undergoing BCS for DCIS - negative margins found in 83% of pts on central review - 17 yrs - 20% (no RT) vs 10% (RT) - RT was 50/25 - No diff in OS or DFS EBCTG 10853 - 1,010 pts undergoing BCS +/- RT (50/25) - negative margins, <5 cm - 15 yr outcomes - 31% vs 18% overall ---invasive 16% vs 10% ---Noninvasive 14% v 7% Risk factors for IBTR - age <40, clinical detection vs mammo, + margins, solid or cribriform histology HF is Mainly extrapolated from invasive data ASTRO consensus guidelines says that its fine. There probably won't be large randomized trials for this. Small series have showed excellent local control. In breast tumor recurrence was associated with increased mortality if it came back as invasive disease - not if it recurred as DCIS. Its about 50:50 chance of coming back as invasive vs DCIS. SweDCIS trial - 37.5% reduction in LR with RT - 20 yr - 32 v 20% The point is all of these huge trials showed ~50% reduction in recurrence with RT. RT didn't show survival benefit. ECOG - 12 yr follow up - low risk = 14% - high risk = 24.6% after lumpectomy (note after mastectomy rate of recurrence is <10% even for close or positive margins - so pay attention to question stem asking about who gets most benefit, high grade sp lumpectomy will be answer) - of note, the Oncotype DCIS was validated in this cohort - "even the low risk group has an unacceptably high rate of LR - 7.2% risk" - osler lady says she only gets this test if someone is hesitant to get RT for DCIS EBCTCG: There is a meta-analysis that showed decrease in IBTR - from 28.1% to 12.9% -- incorporates all of these studies.

Wilms tumor trial groups

NWTS - north american post op studies comparing chemotherapeutic agents and radiation doses amongst groups SIOP - european pre-op studies of CT/RT

Just breeze over this card NWTS1 (1969-74) - group 1 = Actinomycin D alone or Act D + RT - group II-III - all got RT with different chemo (AMD v VCR, VCR + AMD) - group IV - AMD + Vcr (preop vcr then amd + vcr) - findings? NWTS II (1974-79) - group I - no RT, changed chemo now - group II, III, and IV all got RT and tried different chemo - group 1 didn't benefit from longer chemo NWTS III - most important Radiation study - stage I don't need RT - stage II +/- RT depending on factors but didn't get randomized to it - stage III randomized to +/- adriamycin and +/- 10-20 Gy radiation - findings = for stage II-III FH, there was no diff in chemo regimens. For stage II, there was no benefit to RT. for stage III there was no diff in the RT doses. - any stage with unfav histology, CPM benefit for anaplastic only --> essentially this study told us that FH can get ~10 Gy of radiation NWTS IV - no radiation questions answered here - shows that FH histology does great and UH does awful. Totally different diagnosis. Don't memorize these probably -- just historical that got us to where we are now.

NWTS1 = G1 did not benefit from post-op local RT if 2 yrs or younger G2-3 - did better with combo chemo G4 - no diff between arms

What were the recurrence patterns of GOG37

Nearly 2/3 of recurrences were locoregional - vulva and groin in the surgery arm

spinal dose overview

Need for re-rt is higher with shorter fractionations Higher dose as better LC

AREN0533 - sort of a European approach - goal was to avoid RT to the lungs for stage IV - note -- SIOP in Europe already does upfront chemo and 75% of patients never get RT. In America we do upfront surgery and more of them get RT. - this study looked at stratifying patients based on chemo response and LOH --> rapid responders with no LOH --> no RT to lungs --> slow responders OR LOH 1p/16q The requirements for omission of whole lung irradiation in AREN0533 for upfront management of wilms tumor?

Need to satisfy the following: - ONLY lung metastatic disease - rapid complete response after 6 weeks of chemo - cannot have LOH 1p/16q - requires favorable histology (no anaplasia) About half of them had CR (45%) Patients with pulmonary CR and 1q gain had significantly reduced EFS relative to those without 1q gain. Patient with 1q with lung CR treated without RT had predominately lung failures (9/11 patients). -1 q gain did worse. Therefore you can't omit RT with LOH. Wilms lung doses = 12 Gy/1.5's (10.5 is <18 mo) Ewings and Rhabdo = 15 Gy/1.5's

EGFRvIII receptor amplification -- good or bad?

Negative prognostic factor - found in 30% of GBM

Neoadjuvant chemotherapy - general guidelines - when do we generally give it - what is the goal typically pCR rate in breast cancer - how does hormone receptor status influence pCR?

Neoadjuvant given mainly to reduce T stage to allow for BCT, given if TNBC >0.5-1 cm, or given if Her2+ breast cancer. Pathologic CR Rates - Hormone positive cancers are slower growing and not as sensitive. Best pCR seen in hormone negative, HER2 + cancers -- TCH pCR rate ~40%, TCHP = ~60-70% (with addition of perjeta) Most responsive to Least responsive - HR (-) and HER(+2) > TNBC > HR(+)/HER2(+) > HR (+)/HER2 (-) - A lot of medical oncology trials (I-SPY, etc) are looking at the additional of various agents for different HR status cancers to try to improve pCR rates in neoadjuvant settings as generally better pCR tends to correlate with better OS eventually. So using pCR as a surrogate, we can expect better OS in the 10-15 f/u data for combos that improve pCR significantly.

Differential for abdominal tumor What helps you differentiate wilms from neuroblastoma

Nephroblastoma (Wilms' tumor) Neuroblastoma Clear Cell renal sarcoma Rhabdomyosarcoma Rhabdoid tumor Hepatoblastoma Cyst Wilms usually a little older, a litle less sick looking, imaging less calcs, claw sign, appears to arise from kidney rather than compress it

Major differential for optic sheath meningioma -- do what test?

Neurosarcoidosis - do CXR and ACE levels

Current Standard of Care treatments for Stage I endometrial cancer - think about what studies led to this Stage IA - G1/2 - G3 Stage IB - G1 - G2 - G3

Next cards will be where this SOC came from

PD1 inhibitors? (2)

Nivolumab Pembrolizumab

MRC Astec Trial for stage I endometrial cancer -- the role of lymphadenectomy - women w/ presumed stage I endometrial cancer randomized to standard TH-BSO or TH-BSO + lymphadenectomy - women w/ intermediate or high risk disease were further randomized to obs vs pelvic RT (45/25) ---> intermediate/high risk defined as: ----- <50% myometrial invasion + G3 disease OR serous/clear cell histology ----- >50% myometrial invasion and grade 1 or 2 disease ----- Endocervical gland involvement (FIGO II disease) - what was the effect of pelvic lymphadenectomy? - what was the benefit of adjuvant XRT for the high/intermediate risk patients? - major caveat of the obs arm?

No benefit to PLND for early stage in terms of DFS or OS Lympadenectomy was NOT needed in early stage endometrial Second randomization showed there was a "isolated pelvic and vaginal recurrence" benefit -- 6.1% obs vs 3.2% WPRT (SS) Note: Acute and late toxicity were about double the obs arm (acute 27 v 57% and 3% v 7% late) No differences in OS or DFS from WPRT HOWEVER -- major caveat -- 51% of the "obs" arm actually got vaginal brachytherapy - MAJOR criticism

What JPAs would you treat and what dose would you go to?

No benefit with OS or PFS with RT The only ones you ever treat w/ RT are if they are progressive or can't get out with surgery (Only go to 45 Gy in 1.8's) High rate (70%) of pseudoprogression after SRS or EBRT

Do you biopsy dipg? What does the histology typically turn out to be?

No bx, unless the clinical or imaging picture is atypical, surgery is usually not recommended outside of a formal clinical trial. The morbidity associated with surgery in this region and sampling error associated with biopsy precludes doing it in all patients. It may help patients select for therapy in the future (Foundation testing). Prognosis ~ 100% fatal Generally 12 mo. survival Non surgical, RT is the only modality that prolongs survival w/ local control Usually diffuse astrocytoma

How do treatment delays impact your dose for wilms?

No change for breaks up to 3 days Add an extra fraction for any 4 - 7 day break Add two extra fractions for any break over 7 days

ACNS 1123 - newer study, controversial - M0 germinoma - everyone got induction Carbo/Etop x 4 cycles --> if CR (imaging, normal markers) --> RT was 18 Gy WV, boost to 30 Gy --> if PR --> RT was 24 Gy WV + boost to 36 Gy

No data on this yet....why did he show these

Espatue trial - 246 pts out of 500 (closed due to poor accrual) - all got induction chemo x3 --> CRT 45 Gy then randomized to continue chemoRT or surgery - results?

No diff in OS Suggests that definitive chemoRT is acceptable approach for most patients.

SABR vs Surgery - major trials to know STARS, ROSEL (Chang 2015 was combined analysis of these two), and ACOSOG Z4099 - all have been terminated early due to failure to accrue. Thoracic surgeons don't refer their patients for these trials STARS + ROSEL - both closed early only accrued 58 total pts - Chang Lancet 2015 - 31 SABR, 27 lobectomy - all had operable T1-T2a (<4cm), operable - STARS: cyberknife 54/3 for peripheral, 50/4 for central - ROSEL - linac based, 54/3 or 60/5 fx - results of combined analysis? ACOSOG Z4099

No diff in pts characteristics OS was better in the SBRT group compared to lobectomy (95% vs 79%, 3 yr OS, SS) - no diff in local control, distant metastatic disease, RFS, or regional failure. Adverse Events is important - only 10% had g3 events in SABR; surgery had 1 pt die of surgical complications, 12 had g3-4 complications. This is probably why OS was different. This was a very small study, so KM curve showed difference. So keep in mind OS benefit is in a tiny number of pts.

N107C - SRS cavity vs WBRT - P3 study, - postsurgical SRS vs WBRT for 4 or fewer - doses based on cavity size - results?

No diff in survival Post-op SRS for patients with resected brain mets should be standard of care with equiv survival and less toxicity than wbrt

IRS IV - group III tumors compared 50.4 @1.8's to 59.4 Gy @1.1 GyBID (hyperfx) - results?

No difference Increased mucositis for hyperfrx 5 yr LC was very good for group 3 Extent of surgical resection correlates with outcome G1 embryonal does not benefit from RT - 0 Gy GIII pts benefit from RT ->no benefit of hyperfractionation - VAC is standard chemo, others not clearly superior - VA only is ok for low-risk patients 3 yr IRS-IV was 86% (Very good)

EORTC H9U - 3 arm randomized arm - ABVD x 6 + 30 Gy IFRT vs ABVD x4 + 30 Gy IFRT vs BEACOPP x 4 + 30 Gy IFRT results?

No difference in FFTF or OS conclusion: ABVD should be used because its less toxic than BEACOPP

1996 Pachell study (surgery vs surgery + WBRT) showed what?

No difference in survival time (48 v 43 weeks) or functional independent survival But did improve local recurrence, distant recurrence, local + distant recurrence, any brain recurrence AND decreased change of neurologic death

Describe lowest PTV coverage you will accept for HN cancer

No more than 1% of any distinct PTV should receive ≤ 93% of the prescribed dose -90% per 1016

RT for mesothelioma

No randomized data for radical or palliative RT vs no RT ~10% patients fail at biopsy tract, but prophylactic tract RT is probably not beneficial (i think this was based on the SMART trial randomizing to 21 Gy/3 fractions that didn't show benefit of biopsy tract RT prophylaxis vs salvage) Indication for RT is: - EPP -- hemithoracic RT - PD -- hemirthoracic IMRT - as part of trimodality Data for LC and OS benefit is retrospective versus historical controls (Yajnik 2003,Rusch 2001) Historical data Local failure 80% LF rate (not covering entire hemithorax dose ~ 31 Gy) The 2001 paper drastically improved OS and LF: 88 pts, LF only: 2(2%), LF + DM: 5 (6%), DM only: 30(34%) Failures that did happen in this paper at the margin of the field → emphasize covering whole hemithorax

LU005 - LS-SCLC, currently open - RT can be 45 bid or 66 daily - randomizing to chemoradiation vs chemoradiation + atezo

No results yet

MD Anderson experience with central tumors - 100 pts w/ central lung tumors <6 cm - they use either 50 Gy in 4 fractions to 70/10 if you can't meet OAR constraints - results?

No significant difference between OS, PFS, LC, RC, or DC comparing 4 or 10 fraction regimens. Chang, red journal 2014

Adjuvant Therapy in Pancreas Cancer - RTOG 9704 - RCT of 451 resected pts - Chemo - 5FU OR Gem - CRT - concurrent w/ 5FU w/ 50.4 Gy

No significant difference in cancer outcomes Toxicity worse in Gem arm

Downsides of P32 for craniopharyngioma?

No, I would not use it. That is a beta emitter sometimes used in the recurrent setting, I would prefer bleomycin instead which has also been used for recurrence. My institution does not use P32. It is difficult to avoid contamination and the effective depth is 3-4 mm, this actually gives a large dose to chiasm, which can cause visual decline in up to 30% of pts

Effect of p16 status on treatment?

None as of yet -- early results of dose DE-escalation trials: NRG HN002 - P2 defintive RT 60 Gy (in 5 weeks) vs def. CRT to 60 Gy (in 6 weeks) -- closed in 2017, no manuscript - IMRT+Chemo met 2 yr PFS threshold and IMRT alone didn't. No difference in 2 yr OS - both met MDADI metrics for toxicity Other important upcoming studies: - ECOG 3311 -- no results yet (compared TORS for HPV + then randomized to 60 vs 50 Gy) RTOG 1016 - Definitive ChemoRT for HPV positive - RT/HD Cis x 2 cycles VS RT/weekly cetuximab - Cetuxmab had inferior OS and PFS compared to CIS (shown in pic) Cetuximab generally thought to be better tolerated and was shown a long time ago to be better than RT alone; however, was eventually shown to be inferior to chemoRT with Cis when looking at HN pts not stratified by HPV. Thought here is that if HPV maybe can be treated less aggressivley, maybe it would have worked in the HPV positive cohort. Apparently not.

Workup for Bladder cancer

Normal stuff (H&P) cystoscopy abdominal pelvis imaging - CT urogram EUA with TURBT (important to see if there is muscle involvement)

PENILE CANCER - risk factors - types of non-invasive penile cancers?

Not a huge role typically - Found among men with chronic irritation, poor hygeine, hindered inspection (uncirc'd peens less likely to see it). STDs (HIV, HPV 45-80% of cases), smoking, trauma Non-invasive - Bowen's disease, in situ disease, red solitary plaque crusting and oozing - Erythroplasia of Queyrat and Lichen Sclerosis are also types of in situ disease

Do you need a BM biopsy for NHL?

Not absolutely indicated in all NHL -- but alot end up getting them. PET/CT actually is pretty good for ruling out BM disease in NHL.

Do you always need a biopsy for pineal masses?

Not always May not need if HCG > 100 (NGGCT ~ chorio) Any AFP elevation (NGGCT) Asian male w/ HCG < 100 probably germinoma

Adjvuant RT in bladder

Not generally considered. Evidence is not good that there is a benefit. Usually only consider if T3/4, N+, or positive margins

Urethral cancer

Not much to know -- this seems pretty low yield high points: - very rare - older patients - transitional and squamous cells - prostatic urethra and membranous urethra are the penile urethra. veromontanum - structure at the floor of the prostatic urethra that marks the boundary between the membranous and prostatic urethra fossa navicularis is the distal widening of the anterior urethra within the glans penis lymphatics --> superficial and deep inguinal nodes -- external iliac, internal iliac, and presacral Most cancers in the bulbomembranous urethra (60%) Management is transurethral resection, segmental resection, partial penectomy, total penectomy, or total cystourethrectomy or cystoprostourethrectomy lymph node management similar to penile cancer gross disease 70 Gy, lymphatics 50 gy if you get pushed into treating this

bile duct cholangio subtypes picture

Not that hard I - tumor below confluence II - tumor up to the confluence IIIa - common hepatic duct --> right hepatic duct IIIb - common hepatic duct --> left hepatic duct IV - either involves both left and right hepatic duct or multicentric

GERM CELL TUMOR Pathologies seen?

Not treating a ton of these - but still a randomly high yield topic for boards Pathology: - Seminomas (pure) - Nonseminomatous (NSGCT) - considered Non-seminomatous if seminoma has a Non component. Types are: Embryonal, yolk sac (endodermal sinus tumor - Schiller Duval Bodies), Choriocarcinoma, Teratoma Others - Sertoli cell tumors, Leydig cell tumors, Lymphomas, or RMS

Do you want a biopsy in Wilms, why or why not? If you did do a biopsy, how would you do it?

Not usually, this would automatically upstage the patient to stage III If stage IV or V already, this could help with knowing anaplasia vs not. A posterior retroperitoneal approach, avoid contaminating abdomen/seeding peritoneal cavity

GOG88 - can we just do RT instead of groin dissection if the survival is the same or better with RT compared to dissection? - 58 pts randomized to either bilateral LND vs bilateral groin radiation - all pts clincially node negative - note: criticism of the trial --> in the surgery group that was node positive, 5 of the patients (out of 25 total) had adjuvant radiation to the IL pelvis... Radiation was; - 50/25 fx - dose was calculated at 3 cm below the anterior skin surface - primary site and the pelvic nodes were not treated in this study - at least 50% of the dose was with 12-13 Results - which arm had better PFS?

Note the block in the center since the primary site wasn't treated The PFS was actually BETTER with the groin dissection group - 3 yr PFS (92% vs 70.4%) Interpretation was that we should stick with groin dissection since RT had worse PFS and worse OS on this study HOWEVER -- 20% of the surgery arm got post-op radiation for positive nodes. -- CT wasn't used for nodal staging up front - just did a pelvic exam -- CT wasn't required for RT planning --> these were just treated using electron fields to a depth of 3 cm. super important -- when this data was re-analyzed looking at the dosimetry of the actual fields (next slide)

histology of gland anatomy

Note the verumontanum ventrally just posterior to the urethra in the central zone area - people pimp about this anatomy

RTOG 0529 - dose painted IMRT protocol for anal canal - showed reduced acute toxicity rates compared to historical results - equivalent outcomes to RTOG 98-11 - several series showed reduced treatment breaks with IMRT --> which has been shown to give you better control

Note: T1-2 primary: 50.4 Gy T3-4 primary: 54 Gy For nodes <3 cm --> 50.4 Gy For nodes >3 cm --> 54 Gy Elective nodes if T1-2N0 primary goes to -->42 Gy elective Elective nodes if T3-4N0-3 (N1a-c) primary goes to --> 45 elective Overall equivlent control to 9811 and BETTER toxicity. IMRT accepted as standard for anal canal

Typical indications for PORT now?

Now usually just positive margins, maybe N2 if they can't get chemo, but lung ART showed no benefit to PORT in N2 population (specifically excluded positive margin people)

Type I error = ? Type II error = ?

Null hypothesis = There is no difference in the treated vs untreated groups. Type 1 = alpha error = False positive = type I error occurring. Type II error = beta error = False negative = The probability of accepting the null hypothesis when it was wrong (the alternate hypothesis was correct) Type II error occurs when the p value fails to reach statistical significance when the groups being compared truly were different. Type II error occurs when the groups are too small.

Muscles that open the jaw vs close the jaw?

OPEN = Lateral Pterygoids CLOSE = Medial Pterygoids

Which peds LGGs are not resectable? For a LGG that gets a GTR what is the 5 yr PFS? How does that compare to STR?

OPG, Thalamic, Hypothalamic, Tectal GTR 5 yr PFS 90%, essentially cure Don't do any adjuvant therapy STR 5 yr PFS 50% So after STR - 50% wont progress Try your best to avoid Can try carbo vincristine

Oral Cavity - structures in the OC? - dividing line between OC and OP? - Changes in OC staging from 7th to 8th edition?

ORAL CAVITY IS A SURGICAL DISEASE In ALL STAGES the correct answer if possible is resection of the primary and nodes. The only time to get pulled into definitive RT for ORAL CAVITY management is in the following situations: 1. medical contraindication for surgery 2. "unresectable" 3. Being considered for definitive brachy (although not done much now) And then in general after surgery, you use the same features to guide PORT (T3/T4, >1 node, LVSI, PNI, <5 mm margins) or post-op ChemoRT (ENE or positive margins) . SURGERY = Complete resection + at least IL neck dissection

RTOG 9610 - 5FU + hydroxyurea and RT 60 Gy in 1.5 Gy bid results?

OS at 2 yrs - 15% OS at 5 yrs - 4% 8% treatment related death General rule - allow for minimum of 6 months of time between HN RT - 1 yr is better

Intermediate risk prostate cancer - D'Amico Trial - looked at 206 men w/ T1b-2b, PSA>10, GS7 or more, or evidence of ECE --> randomized to 70 Gy EBRT or 70 Gy EBRT+ADT (2 mo neo, conc, adj - 6 months after) - showed what benefit to ADT?

OS benefit (p = 0.04) and Prostate Ca specific mortality benefit (p = 0.02) Rare to show OS benefit.

Turrisi Regimen (RTOG 8815, INT 0096) - compared 45 Gy in 1.5 Gy BID vs 45 Gy to 1.8 Gy daily (not equivalent biologically) - 417 pts - pts with CR offered PCI (2.5 Gy x 10) - results?

OS benefit at 5 yrs of 10% (26% v 16%) -- however these are totally not comparable regimens G3 esophagitis 27% v 11% (however this was defined as pain requiring narcotics, which is G2 now). Turrisi was 2D planning. Elective nodes + SCV - 5 cm below carina. Fields were HUGE.

Medulloblastoma - POG 8631 - dose reduction question - 126 patients - T1-3M0 - <1.5 cc residual (GTR) - randomized to 36 vs dose reduction with 24 Gy - all patients got PF boost to 54 Gy Not a chemo study

OS was WORSE w/ reduced dose - EFS was 14% worse OS was 11% worse.

MSKCC Marginal Zone Lymphoma Data - 490 pts with stage I/II MZL --> 50% tx with RT alone - 50% stomach, 18% orbit, non-thyroid HN 8%, skin 8%, breast 5% - RT was 30 Gy in 15%, <30 Gy in 17%, and >30 Gy in 15% - OS results?

OS was excellent - 5 yr 92%, RFS was 74%, cumulative disease specific death 1.1% at 5 yrs Gastric site associated w/ inferior RFS No effect of dose on relapse Only 4 pts transformed to large cell lymphoma 3 secondary malignancies in field

GOG 120 - this is the trial that established weekly cisplatin as the standard of care eligible pts: - FIGO IIB, III, or IVA with NO para-aortic chain involvement - EBRT was 40.8 - 51 Gy in 1.7 Gy fractions + brachy (4 field box and brachy to point A - 80.8 Gy for IIB pts and 81 for III and IV pts) - chemo arms were 1. Cisplatin 40 mg/m2 2. Cis (50 mg/m2), 5FU (4 gm/m2), Hydroxyurea (2 g/m2) 3. Hydroxyurea (3 gm/m2) Outcomes? Note: all of these trials are essentially why we are always aiming for EQD2 to disease of 80-90 Gy

OS was the same for Cis (53%) and Cis/5FU/Hydroxyurea (53%)and no significant diff in toxicity Hydroxyurea was significantly worse (34%) So this made Cisplatin 40 mg/m2 weekly standard since there was no benefit to addition of more chemotherapy

PORT Meta-analysis - 2,128 pts, 9 RCT - old radiation treatment (cobalt 60, etc) - results?

OS was worse with PORT (HR 1.21) - but less of a detriment for N2 disease. Still didn't show a benefit tho

Surgery vs RT for early stage disease - Italian data - no IMRT available then - Surgical was radical hyst + pelvic lymphadenectomy - RT was 4 field box + LDR Cs 137 prescribed to median point A dose of 76 Gy (nobody does this anymore) results? - specifically in what pts was OS worse with surgery?

OS was worse with surgery in pts with tumors >4 cm This is why standard treatment is definitive chemoRT with brachy for larger tumors >4 cm Pts with stage I disease -- can be treated with surgery followed by risk adapted RT (sedlis criteria) or chemoRT (peters criteria)

VA Larynx Study - 332 pts - stage III or IV larynx (excluded T1N1) cancer of the glottic and supraglottic larynx - arm 1 = classic wide field TL + regional LND + post-op RT - arm 2 = induction chemo (cis 100 mg/m2 and 5 FU 1000 mg/m2) + radical RT --> if not at least PR to chemo after 2nd cycle -- underwent surgery and post-op RT Primary endpoint was rate of larynx preservation results?

OS was ~50% in both arms but larynx preservation was ~62% in the RT arm -- paved the way for RTOG 91-11

Optic nerve sheath meningiomas - how common? - first line tx? - local control? - dose? - should you biopsy?

Of note, cavernous sinus meningioma is generally also considered unresectable similar to optic nerve sheath

Who should you offer SRS for AVMs to?

Offer SRS for previously ruptured AVMs with SM grade >III or w/ comorbidities that exclude from surgery

Data for 2 vs 3 cycles of HD cis?

Often the 3rd cycle is skipped because its essentially only due for the last week of RT, and since its NOT a systemic dose, rather a chemosensitizing dose, there is argument about its necessity. For definitive HPV+ disease, RTOG 1016 used 2 cycles with a high PFS rate. Thought that this may be ok based on that data. Note -- they did the "RTOG standard dose" of 70 Gy in 6 weeks, thus the 100x2 covers the whole course of RT (and RT is technically accelerated) For definitive HPV- we tend to lean toward thinking the third cycle is indicated

Seminal Trial - CCG 3891 -- HISTORICAL DATA FOR REFERENCE - randomized 539 pts - high risk - mostly stage III MYC+/UH or Stage IV pts - all patients got induction chemo, followed by standardized surgery/rt to achieve local control - pts w/ no progression after 2 cycles of chemo randomized to continued chemo vs BMT - second randomization to cis-retinoic acid

Older study - got surgery/rt between cycles 4-5 chemo before tranplant, now we do it after RT was local, 10 Gy to abdomen, 20 Gy to extraabdominal abomen + TBI of 10 Gy -- so total 20 Gy to abdomen and 30 to other sites. This was old and we don't do this anymore Half had locoregional recurrence in the chemo alone arm and only a third in the BMT arm -- led to the concept of tandem transplant eventually

Paratesticular rhabdo, who needs LND?

Older than 10 yo

UK Rapid - stage IA or IIA - no bulk or b symptoms, no prior treatment - ABVD x 3 --> PET scan --> if positive - 4th cycle of ABVD + IFRT 30 Gy --> if negative - randomized to either obs or IFRT 30 Gy Notea: - About 1/3 of the patients on this trial would have been considered unfavorable per German criteria. - 31% had 3 or more nodal sites involved - PEt negative rate was ~74% - also PET at baseline wasn't require

Ommision of RT resulted in worse PFS - no statistically worse 3 yr PFS - no RT - 90.8% - RT - 94.6% Absolute diff 3.8%, p = 0.16 (ITT analysis) The Per Protocol analysis showed an absolute 6.3% (97.1% vs 90.8%) p = 0.02 The 26 people excluded from the PP analysis -- 20 declined RT, 5 died, 1 PNA NO difference in OS Their conclusion was even though non-inferiority couldn't be demonstrated, these patients have a good prognosis and it is a relatively small improvement in PFS only so you should consider these factors when deciding

Is Oncotype DCIS validated?

Oncotype DCIS is retrospectively validated 12 gene assay, must be ER/PR + Predicts local recurrence Reported w/ two graphs for ipsilateral recurrence (any and invasive) regardless of tamoxifen < 39 is good > 55 is bad

Primary mediastinal B cell lymphoma

Options: - R-CHOP + RT (if cant' do DA-R-EPOCH) - DA-R-EPOCH The take home here is typically young women - similar to DLCBL - DA-R-EPOCH is standard and usually omit RT untless DS 4-5 after chemo - then do RT vs biopsy/salvage DA-R-EPOCH (Dunleavy, NEJM) - showed patients do very well without RT Note: consider biopsy because high false positive rate in this disease after chemo

Oral cavity odds of LN involvement for different subsites?

Oral tongue ~ alveolar ridge/RMT > FOM > lips > buccal/gingiva

What nerve is responsible for ear pain in each? Oral tongue Base of Tongue Larynx Hot potato voice?

Oral tongue: CN V3 (auriculotemporal) BOT: CN 9 (Nerve of jacobson) LarynX/hypopharynX: Auricular branch of the Vagus (Arnold) CN X hot potato = base of tongue involvement

Oropharynx - structures? - major differences between 7th and 8th editions of staging?

Oropharynx: - structures: base of tongue, soft palate, anterior/posterior tonsillar pillars, tonsillar fossae, lateral and posterior oropharyngeal walls, vallecula (potential space between the base of tongue and the epiglottis) Superior border = soft palate/hard palate junction Inferior border = hyoid bone Staging differences are done because of p16 prognostic differences: In general, remember: - p16 positive cases prognosis typically better by ~15-20% clinical nodal staging: --cN1= any number of IL nodes as long as <6 cm --cN2= any number of bilateral or CL nodes as long as <6 cm --cN3=>6 cm node pathologic nodal staging --pN1= 4 or fewer nodes --pN2= more than 4 --pN3= no such thing anymore - ENE+ makes no difference for clinical or path staging for OP p16 positive Graph is from HPV and survival in OP cancer (KK Ang; NEJM 2010), 3 sets of lines represent error bars -- massive difference in 5 yr OS and PFS

RT dose overview

Osler guy says 41.4 is going away and most people are doing 36 to nodal bed. Dropping dose to 45 Gy for orbit is controversial (refer to brown notes) - but also this was done on older studies which higher dose cyclophosphamide, so less clear thats ok with lower dose cyclophosphamide)

Dose for vulvar cancer for definitive?

Osler guy says he usually doesn't actually do pre-op because surgeons aren't comfortable with it. He does Definitive ChemoRT - 65 Gy to primary disease - 60 Gy to gross nodes - 45 Gy to elective nodes Tough treatment to get people through and they will often end up getting a few days off, but avoid breaks as much as possible

Risk of transformation to MM of - solitary bony plasmacytoma - solitary extramedullary plasmacytoma (non-osseous)

Over 10 years - solitary bony plasmacytoma - 65-84% - solitary extramedullary plasmacytoma (non-osseous) -10-30% Bone is 40% more common than non-osseous T spine is the most common for osseous upper aerodigestive track (HN) is most common site for extraosseous solitary plasmacytoma

Adjuvant Therapy in Pancreas Cancer - ESPAC 1 Trial - 3 concurrent randomized trial 1. CRT (GTSIG) vs observation 2. Chemo (5FU-folinic acid) vs none 3. 2x2 (CRT, chemo, neither, both) Factorial design randomization result?

Over all - chemoradiation didn't show difference in median OS in the initial study Chemotherapy did show a significant difference in median OS - 19.7 m vs 24 m (w/ chemo) UPDATE later showed Chemo vs Obs 5 yr OS - 21% v 8% (SS) ChemoRT vs Obs 5 yr OS - 10% vs 20% (SS) - WRONG WAY!! -- Nevine is an idiot and doesn't point this out, but adj chemoRT was actually HARMFUL in this trial

Overall Treatment Paradigm for Hodgkin Lymphoma Early stage IA/IB and IIA/IIB, favorable, non-bulky IA/IB Unfavorable, IIA Unfavorable or IIB (if due to ESR or 3+ nodes, non-bulky) IIB bulky stage III/IV

Overall Treatment Paradigm for Hodgkin Lymphoma Early stage IA/IB and IIA/IIB, favorable, non-bulky - ABVD x 2 cycles followed by ISRT to 20 Gy IA/IB Unfavorable, IIA Unfavorable or IIB (if due to ESR or 3+ nodes, non-bulky) - ABVD x 4 cycles followed by ISRT to 30 Gy/30.6 Gy IIB bulky - ABVD x 6 followed by ISRT to 30 Gy For more advanced stage III/IV --> can consider RT consolidation to initial sites of bulk/large CT residual IIB bulky were not included in the early unfavorable trials -- was considered advanced, so the ABVD x 4 with 30 Gy doens't apply -- so they get more chemo So really for these just think about what stage are they, if I or II then think about if they have any unfavorable risk factors. If not 2 cycles of chemo an 20 Gy. If so, 4 cycles and 30 Gy.

Accuracy of PET/CT in mediastinal staging? How does false negative rate with PET compare for peripheral vs central, small vs large

Overall accuracy is ~82% Sens/Spec DONT change w/ population - Sensitivity = 80% - Specificity = 88% - NPV is ~94% in small (<2 cm) peripheral lesions. Decreases dramatically in larger or more central tumors thus not as trustworthy - PPV is ~75% in same population - meaning an avid node has to be biopsied to confirm. So in some "frail" patients and small tumors, you may be able to forego invasive mediastinum staging procedures. However, PET/CT does have HIGH false POSITIVE rates (as high as 25%) and thus PET positive nodes then need to be confirmed (EBUS, etc) before proceeding empirically with concurrent chemoRT Around 5% false neg if small and peripheral likely dont need node bx if negative. If larger or more central tumor then the PET false negative rate goes up 24 - 83%, EBUS is suggested in these cases of central tumors, even small primary. ACOSOG Z0050 suggested false negative rate for PET overall is ~27% so has been reported quite high.

TROG 99-02 -- inguinal coverage in anal canal - T1-2 anal treated with CRT omitting inguinals - 40 pts - 50.4 Gy w/ MMC/5FU - results?

Overall inguinal failure was 25%, isolated inguinal ~12.5% 4 yr LC 82% 4 y OS 71% 4 y CFS 85%

Adjuvant Chemotherapy after SBRT - Chen 2008 - 65 pts, T1-3N0 treated w sabr - 17 pts tx with adjuvant cisplatin - results and problem with this?

Overall local tumor response was 91% 6 months Problem is that the adjvuant chemo group tumor volume was 117 cc vs 54 cc (so there was a selection bias in the ones that got chemo) Did show a significant chemo benefit to OS Distant failure - sbrt + chemo 17% - sbrt alone 33% SS Median survival - sbrt + chemo 47 months - sbrt alone 36 months Suggests there may be a group (pts with larger tumors) that might benefit from adjuvant chemo Trials are now looking at adding immunotherapy tho - MD anderson pII/III - NRG foundation has pIII - SWOG 1914 Take home is that adjuvant chemo might be beneficial but the data as of now is only retrospective so not standard of care.

Summary of 4 different papers looking at RT and patterns of failures for Follicular - just look over and know the gist Know which paper had pts staged with PET - what's the significance of this? Know the FFP rate for stage I vs stage II for the ILROG brady paper What was local control on the brady paper?

Overall these papers are all showing that most relapses are DISTANT and RT with involved site is justified for stage I/II FL DFCI paper said that most relapses were distant Campbell paper looked at INRT vs IFRT (5 cm margins) and the in field relapse rate wasn't different. Thus INRT is reasonable - long term follow up paper just confirmed ISRT is reasonable with low in field failure rate either way ILROG Brady paper - study that staged with PET/CT showed again extremely low in field relapse rate. - stage I vs stage II FFP was 74.1% vs 49.1% - Local control was 97.6% - the significance of the PET/CT thing is that the other papers DIDNT stage with PET so this showed that proper patient selection with PET identifying truly early stage disease gave BETTER disease outcomes So just know that these 4 papers all justify the use of RT for local control with low in field failure rates.

LC data for SBRT for early stage NSCLC

Overview shown here 2-3 yr LC rates of 85-95% BED <100 shows worse LC rates. These papers showed that you need BED >100 Note that 2-5 yr OS is not great, but keep in mind that these are "inoperable" lung cancer patients which means that they aren't in the best shape so they often die from their comorbidities

Hypofractionation vs Conventional Fractionation RCT for PMRT - what patients and how many? - surgery? - dose? - LRR difference?

P3 RCT - first for hypofrac PMRT - 2019 Wang et al. Lancet. - 820 pts; age 18-85 - mastectomy and either T3/4 OR at least 4 nodes positive after ALND - dose = 3 week 43.5 Gy vs 5 week 50 Gy - no difference in LRR (8.3 vs 8.1%) - no difference in acute or late toxicity other than less grade 3 acute skin toxicity in hypofractionation arm - there isn't long enough follow up in this data to look at brachial plexopathy which is why brown is concerned about hypofrac in CW/RNI. There are other open trials ongoing in US (RT-CHARM)

RT treatment field and dose for stage I seminoma

PA field Dose = 20 Gy in 10 fractions PA field - top of T12 to bottom of L5 including nodal areas at level of renal hila - ~10 cm wide

PCNSL - do you need partial brain or whole brain

PARTIAL BRAIN NOT SUFFICIENT Out of field recurrence is common dose-de-escalation is appropriate if CR to chemo (MSKCC Morris JCO paper)

important imaging to get for cervical cancer

PET/CT is preferred for initial workup MRI is most helpful for brachy planning Most of this is more useful for oral boards

HD17 - unfavorable Hodgkins - 1100 early stage - everybody got 2 cycles BEACOPP esc + 2 cycles ABVD --> PET iPET negative = randomized to 30 Gy IFRT vs OBS iPET positive = randomized to 30 Gy IFRT vs 30 Gy INRT results?

PET4 negativity after 2+2 chemo = this allows omission of RT without clinically relevant difference loss of efficacy

GHSG HD10 - Early Favorable - NEJM 2010 - Stage IA - IIB (NON-bulky), No ENI, ESR <30 if B and <50 if not - no risk factors - four way randomization to either 2 or 4 cycles of ABVD and 20 or 30 Gy IFRT - PET was NOT used to assess response Primary endpoint - FFTF; 2ndary = toxicity Results?

PFS and OS at 10 yr were 87 and 97% resp. for BOTH No difference in FFTF, PFS, OS at 5 or 10 yr between either 2 or 4 cycles of chemo or 20 or 30 Gy RT Thus standard for early favorable is ABVD x 2 + 20 Gy IFRT

Peter's Criteria -- GOG-109/SWOG 8797/RTOG 9112/INT 0107 - Comparing adjuvant RT and chemoRT in patients that had Peter's criteria - had stage IA2, IB, or IIA treated with radical hyst and PLND and had at least one of: positive margins positive nodes parametrial involvement RT was 49.3 in 29 fractions, four field box Pts w/ high common iliac nodes - they did 1.5 Gy pops -- 45 Gy in 30 fx Brachytherapy was NOT permitted in this study Chemo was Cis/5FU x 4 cycles q3 weeks results?

PFS and OS were significantly improved 4 yr PFS (27% benefit) - RT 53% - CRT 80% 4 yr OS (10% benefit) - 71% - 81%

Post-op ChemoRT indications for cervix = ?

PO-CRT = Peter's Criteria Posisitive margin Positive node, Parametium involved (T2b)

Poor prognostic features of LGG? - what is dominant prognostic feature for all comers LGG?

POOR PROGNOSTIC FEATURES Astro histology Age > 40 (most important LGG prog factor for all comers, older people do worse) STR (but age > 40 is more important) Size > 4-6 cm (in literature >6 cm is bad cutoff) NOT having 1p19q co-deleted: G2 oligo w/ co-deletion med OS 13yrs, vs w/o med OS 9 yrs, by new definitions if you don't have 1p19q then you aren't oligo Focal neurologic deficits Not having IDH1 mutation is very bad, behaves like a GBM

General Indications for PORT vs post op Chemo-RT

PORT = 5 major indications 1. close margins <2 mm 2. PNI 3. LVSI 4. T3/T4 5. More than 1 LN involved CHEMO-RT 1. Positive margins 2. ECE Ideally concurrent chemo is HD cisplatin (100 mg/m2 q3 weeks) > LD Cisplatin 40 mg/m2 q week >>> cetuximab (almost never the right answer)

PORT indications for cervix = ?

PORT = Sedlis Criteria (2 of 3) >4 cm LVSI DOI >1/3 -- this is the easiest way to think of it, but technically, they are shown in the table. You can see that there are some technical cutoffs for size at 2 and 5 cm based on DOI -- so if LVI+ and not >1/3 doi -- need 5 cm size -- if LVI+ and middle 1/3 involved, need 2 cm size

Global retrospective database - IMTIG - 1263 pts w R0 resection in stage II or III - 55% got PORT - results?

PORT improved OS in both stage II/III -- if you examined together or independently. conclusion - still controversial - stage I - generally no port - stage II - may consider for specific cases - WHO high grade histology, thymic carcinoma, <1 mm margins, pleural adhesion (T2b) - consider RT here - stage III = do PORT

SEER DB analysis - thymoma and thymic carcinoma - results?

PORT improves OS for stage II and III regardless of localized or regional (66 v 76% - 5 yr OS) No improvement in cause specific survival for either group and actually worse with PORT for localized group - odd

Major including criteria for: - PORTEC 1 - PORTEC 2 - PORTEC 3

PORTEC 1 - FIGO 1 - G1 if >50% DOI - G2 any DOI - G3 <50% invasion PORTEC 2 - >50% invasion (used to be >2/3 IC) G3 patients excluded from PORTEC1 because thought to be too high risk to randomize. These were prospec. randomized to RT - outcomes were worse. - Age >60, IC Grade 1-2 or IB Grade 3 -- excluded stage II PORTEC 3 - HIGH risk patients - FIGO I grade 3 WITH Deep DOI and/or LVSI - FIGO II or III

PORTEC 1 vs 2 vs 3 - summary - major comparisons? - major outcomes?

PORTEC 1 - TAH/BSO (no LND) --> OBS vs RT (WPRT) - no brachy - ~10% LRR benefit XRT (10 yr - 14% vs 5%, 15 yr - 16 vs 6%) -- 75% recurrences were in the vagina - HIGH RISK FEATURES: Age >60, G3, DOI >1/2 - 10 yr OS, CSM, and DM NOT different PORTEC 2 - given that 75% of recurrences were in vaginal cuff --> can we just do cuff brachy - TAH/BSO (no LND) --> VBT vs WPRT - 5 yr pelvic recurrence SS lower in WPRT vs VBT (10 yr 0.9% vs 6.3%) - NS difference in 5 yr vaginal recurrence, 5 yr LRR (vagina/pelvis), distant mets PORTEC 3 - TAH or TLH/BSO (+/- LND) --> WPRT vs CRT (during/after) - NO 5 yr OS, 5 yr FFS benefit for all-comers when analyzed together. - CRT showed ~11% FFS benefit in STAGE III (SS) - all comers showed reduced ANY pelvis failure with chemo (SS)

Positive predictive value What influences PPV?

PPV = a/(a+b) Prevalance. High prevalence = better PPV for a given test

Assuming disease prevalence stays the same, what does decreasing the specificity and increasing the sensitivity do to the PPV?

PPV DECREASES and NPV increases I was confused by this thinking that the PPV and NPV only changed w/ prevalence and pre-test probability.

PROSTATE CARDS

PROSTATE CARDS

Whats included in Active Surveillance - what are triggers to treat? - when should you stop?

PSA x 6 months DRE x 1 yr Biopsy x1 yr MRI x 1 yr Note: some people will alternate the biopsy and Mr each every other year. Safer boards answer is the above however - clear increase in # of cores. Upstage in in GG. Sig increase in PSA. - stop when life expectancy is <10 yrs

definition of borderline resectable

PV or SMV >180 degrees SMA or CA <180 degrees solid tumor contact w/ IVC These are the big ones to know

ASCO/ASTRO guidelines for IMNs

Panel essentially says yes you should do IMNs

Early studies - BTSG 6901, BTSG 7201, SGSG - looked at older chemo's like BCNU, CCNU, bleomycin - these studies did 45-60 Gy to the whole brain - median OS was ~20-40 weeks where were the failures?

Patterns of failure - point is ALL in field failures - nearly all recurrences in all of these studies was w/in 2 cm of the gross lesion IN FIELD - 80% of cases - 3 cm margin would have included all of the cancer - all biopsies positive w/in the T2 signal - after WBRT - >90% recurrences were w/in 2 cm This lead to fields like we use now

Pediatric Hodgkin Lymphoma - RT details - What is treated? - Low risk - Intermediate risk - High risk Dose?

Pediatric Hodgkin Lymphoma - RT details What is treated: - Low risk - ISRT if D3-5 after chemo - Intermediate risk - ---->ISRT if D3-5 after chemo OR ---->Slow early responders interim pet (<60% reduction in product of perpendicular diameters for all target lesions) - High risk ---->ISRT if D3-5 after chemo OR ---->Slow early responders interim pet (DS 4-5 on interim PET) ---->Initial sites of LMA CR = 80% or more reduction in the product of perpendicular diameters and DS 1-2 Dose = 21 Gy @1.5Gy

Role of immunotherapy in HN?

Pembrolizumab (q3 week) and nivolumab (q2 or q4 week) Approved in the recurrent/metastatic setting after failure of platinum chemo. Both are PD1 blocking antibodies. Ongoing trials for chemoRT + immuno but NONE approved yet for this indication.

Lvl 1 data for chemo in mesothelioma?

Pemetrexed 500mgm2 and cisplatin 75 mgm2 q3 wks usually 3 cycles LEVEL ONE DATA MDA (Vogelzang JCO 2004) N =456, (226 combo, 222 cis alone) Med OS 12.1 m vs 9.3 m cis alone (SS) Time to progression 5.7 m vs 3.9 m (SS) Response rate 17% w/ cis alone vs 41% w/ cis pem combo (SS) Toxicity reduced with vitamin supplementation Consider adding avastin 15 mg kg q3 weeks until progression (Ceresoli 2013

SIM SETUP for AVM - what do you do on day of Tx?

Perform CT angiogram on day of Tx Find Nidus on AP and laterals and outline it Outline is then projected on the MRI and the AVM has to be in the projection If >10 cc can do half now and half later as staged approach

How could you reduce hotspots?

Planning: Adjust weight and use EDWs to limit hotspots. Then use forward planning w/ multiple FIFs (2-5 per beam; each w/ 4-10 MUs) to limit hot spots to V105<10%, V108<0% while covering 95% PTV-eval w/ 95% Rx dose. Normalization/calc point 0.5 cm anterior to lung/breast interface.

What is pleural decortication? - when is this an option? What is talc pleurodesis?

Pleural decortication Resection of ENTIRE pleura but NOT lung removal Op mortality 2% -- MUCH lower than EPP Only curative for T1 tumors confined to pleura Patients tolerate this much better. P/D vs EPP -- much lower operative mortality with higher local recurrence (33% vs 65%) - but improved survival in P/D vs EPP because of the higher perioperative mortality of EPP - therefore PD considered reasonable alternative because of the morbidity/mortality of EPP Talc Pleurodesis (palliative) Remove tumor/affected pleura Re-expand collapsed lung w/ talc Would consider adjuvant hemithoracic IMRT -- based on IMPRINT trial if talking about this surgery

MGH experience with Bladder cancer (retrospective) - different approach - Treatment Paradigm -- TURBT maximal --> induction chemoRT (45 Gy) --> re-evaluate with cystoscopy --> if CR --> complete CRT (75% of pts). -->If no CR --> cystectomy (25% of pts) Large experience of ~500 pts. Majority were T2, with complete TURBT - found DSS was 66% (pretty good) and 59% at 5 and 10 yr fu. major findings associated with worse outcomes?

Poor Prognostic signs for BPT approach - incomplete TURBT - older age - higher T stage T2 vs T3/4 - hydronephrosis - widespread tumor associated CIS This is largely what informs our "ideal bladder preserving candidate" information

Effect of positive margin on LR risk?

Positive margin increases risk of LR (HR 2.4, SS) which is not reduced by RT boost, systemic therapy or favorable biology Based on Houssami Meta-analysis -- no clear association with margin distance, thus why guidelines is negative at ink. NO benefit for wider margin for IDC. ASTRO/SSO Consensus Guidelines (Moran et al. 2014) Positive margins (ink on invasive carcinoma) are associated with 2-fold increase in the risk of IBTR compared with negative margins The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR For: - Invasive: Negative at ink is negative - DCIS: Need 2 mm margin, if <2 mm, need to re-excise No tumor on ink DOES NOT APPLY: PARTIAL breast irradiation, DCIS, pts treated with neoadjuvant treatment If lumpectomy for invasive and have <2 mm margin on DCIS component, invasive negative trumps and you don't need 2 mm margin on DCIS. Doesn't really make sense to me.

Locally advanced or Node + breast cancer - General indications for PMRT? - Classic studies supporting PMRT? - PMRT LN negative patients? - Management of the axilla in BCT, mastectomy, etc - Indications for neoadjuvant chemo?

Post-Mastectomy XRT --Major indications: T3/4, positive margins, positive nodes (strongest indication 4 or more; 1-3 is WF indication, but more strong consideration otherwise) -- Minor indications (T1-2N0) -- generally PMRT avoided but some risk factors associated with higher risk of LRR: *Menopause status (pre) *close margins (<2 mm) *LVSI, size (>2 cm) *high grade *histology -- (Truong/Jagsi MVA RR) -----> Base this on +/- chemo; Truong, no chemo; Jagsi chemo. If you are getting chemo, you need more of the factors above to think about RT, if not, need less. -----> These factors drive LR so if enough of them, you treat to prevent local recurrence which MA20 and EORTC tell us will decrease distant mets and will eventually affect OS. - Classic studies supporting PMRT = Danish 82b/c (Overgaard), British Columbia, and EBCTCG ---all essentially show ~60-70% relative risk reduction of LR and all show ~10 yr 10% OS benefit. - PMRT LN negative patients = Retrospective data - Management of the axilla in BCT, mastectomy, etc --> Z11, Amaros and EORTC 22922, MA20 - Indications for neoadjuvant chemo = TNBC (>2cm), HER+ breast cancers, large tumors (with goal to downstage to allow BCT) --in clinically node positive patients before chemo, clip the node so it can be found after chemo, if ypN0 after chemo, can consider for B51.

CNS Anatomy Pre-central gyrus Post central gyrus Broca's area Wernicke's area

Pre-central gyrus = primary motor strip Post central gyrus = primary somatosensory cortex Broca's area = dominant frontal lobe superior to sylvian fissure, site of expressive aphasia Wernicke's area = dominant temporal lobe at the posterior end of the lateral sulcu - site of receptive aphasia

Definition of pre-epiglottic space and paraglottic fat space

Pre-epiglottic space (in front of the glottis) Inf thyroid cartilage Sup hyoepiglottic ligament Ant. thyrohyoid membrane Post. epiglottis Paraglottic fat space (on the sides of the glottis) Inner surface of thyroid cartilage Post. hypopharynx Top of cricoid

German Rectal Cancer Group Study - comes up on boards - clinical T3/4 or N+ patients (all pts w/ TME) - 421 pts - randomized to pre-op RT (50.4 Gy)/PVI 5FU VS 55.8 Gy post-op RT/PVI 5-FU - 4 additional cycles of bolus 5FU - which had higher rate of sphincter sparing surgery? PVI = protracted continous venous infusion -- not in some questions they still describe this as bolus (but 120 hour infusion)

Pre-op CRT better- 39% v 19% w/ sphincter preserving surgery DM, DFS, OS -- all similar 8% pCR 5 y pelvic recurrence 6 v 13% favored pre-op Less acute and late toxicity in preop (SS) The main difference between these approaches was high rate of preserving the sphincter and less toxicity in pre-op. + 5 yr local failure lower with pre-op.

Esophageal radiation - concurrent better than sequential - no benefit to dose escalation beyond 50 Gy - consider lung and heart dose - chemo regimen - 3D vs IMRT vs Protons - brachytherapy - preop, definitive, and post-op

Preoperative (41.4 is CROSS regimen) - 41.4 - 50.4 Gy - 41.4 - 45 Gy w/ concurrent carbotaxol --> she said DONT go to 50.4 Gy w/ the carbotaxol because of the higher risk of pneumonitis with concurrent. Definitive - 50-50.4 Gy --> Cis/5FU or FOLFOX (especially with adenocarcinoma) Post-operative - 45 - 50.4 Cervical --> 50.4 --> 70 - but likely 60-66 w/ weekly carbotaxol

What is the actual typical depth of a groin lymph node?

Prescription was 3 cm Actual depth is more like 5.5-6 cm

What is parinaud's syndrome?

Pressure on superior colliculus → Paralysis of upward gaze Pupil has accommodation, but doesn't react to light, nystagmus Accommodation meaning it changes focus moving stuff close

Prevalence

Prevlance = Incidence x Duration

Major treatment paradigms for nasopharynx cancer? Who can be treated with RT alone? Fundamental paper that compared RT vs CRT+consolidation chemo? What about the paradigm above is unique to this HN site? What major publication looked at de-escalation?

Primarily a RADIATION THERAPY disease T1N0 = RT alone (RFS 75-95% 5 yr, OS 70-80%) ALL OTHERS need ChemoRT Intergroup 0099 - compared radiation with CRT (concurrent Cis) followed by additional 3 cycles of chemo consolidation (cis/5FU) -- significant benefit in PFS and OS of chemo-RT compared to RT Consolidation chemo is unique in nasopharynx patients. This has a very high level of toxicity. Many have studied if this can be de-escalated. All boiled down in the MAC-NPC meta-analysis which stated the following: - most important take home: The risk reduction is significantly better when consolidation chemo is added to concurrent -- additional randomized studies have shown this is beneficial. Induction chemotherapy is generally not felt to be indicated (particularly in this country) - this was evaluated in 5 randomized trials; two showed a small DFS benefit but NONE showed an OS benefit. Meta-analysis suggests that there isn't much benefit to induction or adjuvant chemo Int 009 study above showed concurrent chemo + adjuvant chemo had a PFS and OS benefit - more on this next card

Extrahepatic cholangiocarcinoma and Gallbladder Cancer - major risk factors?

Primary sclerosing cholangitis/UC Fibropolycistic liver disease Parasitis (chlonorchis) among many others

Esophageal margins

Prior studies show that 96% of locoregional failure occured w/in the RT fields 3-4 cm proximally and 4-5 cm distally measured along the mucosa for advanced tumors - typically 1-1.5 radially - cover gastrohepatic ligament and celiac trunk for distal GEJ For cervical/upper thoracic tumors - cover the bilateral SCVs For distal esophageal and GEJ - cover celiac nodes and nodes along the left gastric argery for GEJ - nodes based on the Siewert classification of disease

RTOG 0813 -- looked at safety and efficacy of five fraction SBRT for central tumors - PI/II study of 120 pts - medically inoperable T1-2 NSCLC, <5 cm, w/in 2 cm from the proximal bronchial tree/adjacent to mediastinum/pericardium - dose escalation 5 fx SBRT (10-12 Gy/fx) over 1.5-2 weeks q2-3 d - dose escalation study looking at increasing dose until DLT was found - results?

Probabiliy of DLT was only 7.2% at the highest dose level (12 Gy/fxn) 2 yr LC was 87.9 - 89.4% for 11.5 and 12 Gy/fx doses.

ACNS 0232 - did not accrue - RCT - randomized between RT alone (24 Gy WVRT + boost IF to 45 Gy) vs Carbo/Etop x2-4 cycles - decided boost dose based on response after 2 or 4 cycles. If CR after 2-4 cycles they went to 30 Gy IFRT. If PR they went to 45 Gy (most people 36 if PR) - all M+ pts had CSI - this study didn't accrue but its what the olser guy said he does

Probably not that crucial to know this

Most common type of pituitary adenoma?

Prolactinoma - more common in females

ProteCT adverse effects differences between surgery and RT - erection and incontinence diff? - bowel and bladder bother scores?

Prostatectomy causes immediate worse erections that may improve over time might be as good as RT, but RT will slowly decline. Protectomy also causes much worse leakage that may get better but always worse than RT RT dose worse with urinary irritation (LUTS voiding scores go up but same by 6-12 months usually) and worse with rectal irrtiation (but again improves over long term)

ProteCT Trial - remember from CAP trial of PSA surveillance - men from CAP that had positive PSA enrolled onto ProteCT --> randomized to: --> active surveillance - what was trigger to treat? --> RT - what was RT? --> Prostatectomy - how many upstaged with ECE? - what sorts of patients were included? - PCa specific mortality between groups? - what was diff between the groups?

ProteCT Trial --> active surveillance (PSA q3 mo x 1 yr - q6 mo after, trigger was 50% or more rise) --> RT (74 Gy in 37 fractions + 3-6 mo ADT) --> Prostatectomy (66% nerve sparing, PLND is PSA >10, gleason >7; 29% were upstaged with ECE found at surgery) First study to look a these three interventions compared - mostly this was white guys (99%), median PSA was ~4's, gleason 6 (75%), gleason 7 (20%), gleason 8-10 (2%) - thus higher grade not really represented in these studies. - 98.8 v 99% v 99.6 (AS v sx v RT+EBRT) - ALL THE SAME for PCa mortality -- no diff between age, psa, gleason score, clinical stage, etc. - Freedom from progression and DISTANT METS WERE DIFFERENT -- 112 (AS), vs 46 (sx) vs 46 (RT+EBRT) but survival not different - curves separate at about 3 yrs - downside would be indefinite hormones if you met out which would hurt quality of life but probably won't kill you

growth pattern and recurrence - what has the lowest chance of recurrence - pushing, infiltrative or mixed

Pushing vs infiltrative vs mixed Pushing has the lowest risk Infiltrative has the highest risk Mixed is obviously in between

LYSA 02-03 - confusing randomization but idea is more favorable DLBCL to omit RT based on good response to chemo - stage I/II non-bulky pts - without risk factors R-CHOP x 4 then get PET and randomized to +/- RT based on that - any risk factors - R-CHOP x 6 and then randomized to +/- RT based on interim PET to get RT or not RT was 40 Gy IFRT

R-CHOP alone is non-inferior to R-CHOP + RT for non-bulky early stage DLBCL with low R-IPI risk factors

Advanced stage DLBCL treatment

R-CHOPX6 + consider ISRT to initial bulky sites or isolated osseous sites

Thymoma/Thymic carcinoma ADJUVANT management R0 resection - stage I --> ? - stage II-IV --> ? R1 resection - thymoma --> ? - thymic carcinoma --> ? R2 resection - thymoma --> ? - thymic carcinoma --> ?

R0 resection - stage I --> NOTHING - surveillance. like NSCLC, stage I - stage II-IV --> (capsular invasion present, even micro) --> consider PORT even if negative margins R1 resection - thymoma --> PORT - thymic carcinoma --> PORT +/- chemotherapy R2 resection - thymoma --> Definitive RT +/- chemotherapy - thymic carcinoma --> Definitive RT +/- chemotherapy

PREOP-PANC (Dutch trial; ASCO 2018) - RCT of 248 pts w/ borderline resectable pancreas cancer - Arm 1 - upfront surgery followed by 6 months gem - arm 2 - gem-CRT (36 Gy in 15 fractions) - surgery - 4 months gem - results?

R0 resection rate higher in pre-op group (65% vs 31%) Med OS higher in pre-op group - 17.1 m vs 13.5 m Benefit more clear in the T3/4 group

Kidney Cancer

RCC radiation resistant folklore likely came from red journal 1996 paper that showed that RCC is the most radiation resistant that is really based on one cell line - based on malignant pleural effusion of a papillary renal cell -- cell line made from this 22 yo with metastatic kidney cancer (so may be very odd cell line to base this on).

Purpose of CALBG 30610? - any benefit to QD dose escalation? CALGB was originally a P1 small study that showed it had slightly better OS than Turrisi and lower Esophagitis rates. This leads to the 30610 study.

RCT P3 trial - initially randomized to 1:!:1 to 45 BID vs dose escalation to 70 Gy/35 fractions vs a concomitant boost (CB) arm of 61.2 Gy over 5 weeks. The CB arm was discontinued at interim analysis and patients were then randomized to either - 45 bid vs high dose XRT (70 / 35 fxn) - median follow-up of 2.84 years (IQR:1.35 -5.61) for surviving pts - QD compared to BID did not result in a significant difference in OS (HR 0.94, 95% CI: 0.76-1.2, p = 0.9) QD v BID - Median OS 30.5 mo vs 28.7 months (NS) - 2 yr OS 56% vs 59% (NS) - 4 yr OS 39% vs 35% (NS) - PFS HR 0.96 (NS) - toxicity not significantly different.

Test for analysis of a continuous independent variable and a continuous dependent variable

REGRESSION

Small Lymphocytic Lymphoma (SLL) - 7% of NHL - nodal equivalent of CLL - express pan B cell markers (CD19, CD20, CD22, CD79a), CD5, CD23 - what is the term for when these transform to DLBCL? - how often are they stage IV - what should you consider prophylaxis for before treatment?

RICHTER's sydnrome = Transformation to DLBCL 80% are stage IV Tumor lysis syndrome prophylaxis

Classic and Non-classic RILD- time course? - major difference between the two?

RILD = Radiation induced liver disease - Time course: 2 weeks to 8 months - Symptoms: Anicteric hepatomegaly, ascites, elevated liver enzymes (alk-p = classic, AST/ALT = non-classic), fever, RUQ pain - related to VENO-OCCLUSIVE disease Classic: normal AST/ALT, elevated Alk-P - defined by veno occlusive disease, characterized by areas of marked venous congestion in the central portion of the hepatic lobules Nonclassic: - 1 week - 3 months - ELEVATION OF AST/ALT >5 times normal - Path - Veno-occlusive disease due to progressive fibrin deposition within the blood vessels, macrophage infiltration and consumption of fibrin products → further occlusion of blood vessels - or a decline in liver function (measured by a worsening of Child-Pugh score by 2 or more), in the absence of classic RILD

HN002 - Sue Yom study - NRG P2 trial. - p16+ , <T4, <N2c, <10 pk year - randomized to 60 Gy/6 weeks IMRT + Cis vs 60 Gy in 5 weeks RT alone. - essentially testing accelerated fractionation vs chemo This was asked on the inservice, what were the arms results?

RT alone lost - worse LRC 2 yr PFS - RT + chemo = 90.5% - RT alone = 87.6% -- PFS was non-inferior for accelerated RT alone -- LRF was inferior for RT alone --LRF RT alone 9.5% vs 3.3 for CRT (SS) CRT arm had distant failure as most common site of failure whereas RT alone had locoregional failure as most common site of failure. I find this to be very confusing overall. "unable to reject null hypothesis" Greater toxicity with chemo - 64.5% vs 50.3% "the primary purpose of this trial was to determine the appropriate experimental arm of HN005 rather than for clinical application" This lead to HN005 - 70 Gy in 6 weeks with chemo (6 fractions per week and they say that's SOC Cis 100 mg/m2) vs 60 Gy in 6 weeks (40 mg/m2 cis) vs 60 Gy in 5 weeks (6 fractions per week with nivo)....weird trial

RT intensification strategies

RT boost ADT intensification maybe chemo (Docetaxel)

RT Fields for SCLC - traditionally, fields were much larger like PORT w/ ENI --->Turrisi = parenchyaml tumor, b/l mediastinum, ipsilateral hilar nodes, mediastinal nodes - Current technique is only do involved field - PET directed. This came from RTOG 0538 protocol recommendations - GTV on CT/MR scan, FDG, or biopsy sites - allows for ipsilateral hilum coverage for potentially occult disease but you do NOT treat the mediastinum or SCV - often consider revising volumes based on adaptive simulation --> old GTV you consider like your new CTV and then expand PTV from there

RT field PET directed vs elective nodal irradiation - n - 60 w/ LS-SCLC - only about 10% failure so very low when you don't do elective nodal, most recurred distantly

What is the benefit of RT in Hodgkin disease? What are the arguments against RT in this disease?

RT improves PFS over chemo alone. Radiation DOES NOT have an overall survival advantage List of studies show that RT has shown benefit over and over. There is alot of discussion that is trying to omit RT as chemo has improved. Arguments to avoid RT: - recurrence rates may be lower with RT, but OS is the same - this is because there are a ton of salvage options (BMT, etc) - Negative PET scan after chemo allows RT to be excluded - not entirely true - salvage chemo is not as harmful as RT - not entirely true - New agents (immunotherapy) are highly effective

Supportive care vs whole brain RT - Chao 1954

RT increased survival by 2-4 fold compared to supportive care very early data

Constraint list - heart (mean and volumetric) - lung (IL V20 for tangent only vs tangent + RNI) - contralateral breast Coverage - V45 of axillary nodes - V40 of IMNs - hotspot allowed?

RTOG 1005 Heart - mean dose <4 Gy - V20 <5% - left V5 <40% - right V5 <5% or V10 <10% Lung - V20 <15% ideal (Tangent only), <20% acceptable (Tangent only) - V20 <30% ideal (RNI), <35% acceptable (RNI) - CL V5 <10%; ideally V20 = 0% Contralateral breast - <3 Gy; <5% getting no more than 1.8 Gy Coverage - V45 of axillary nodes = 95% - V40 of IMNs = 95% - hotspot allowed = minimize the 105% (no confluent areas); ideally <107% max hot spot

Trials for definitive ChemoRT with Brachy for stage IB3 (>4 cm), IIA2 (vagina + >4 cm), IIB (parametrium), III (lower 1/3 vagina, hydro, pelvic sidewall or nodes), IVA (adjavent organ)

RTOG 7920 RTOG 9001 GOG 120

BREAST SECTION DCIS Early stage Breast Locally advanced Breast

RTOG contouring atlas

Definition of Central tumors?

RTOG definition PTV that overlaps w/in a 2 cm volume superior to the carina extending to the lobar bronchi Comes from dose escalation 66-70 gy in 3 fractions -- 6 deaths were attributed to late toxicity 11 fold increase in risk of grade 3 or higher toxicity for tumors treated w/in 2 cm vs outside of that volume of tracheal/bronchial tree

role for radiatoin - red journal paper comparing 8/1 vs 20/5 vs 30-40/10-20 fractions specifically for cord compression in MM showed what?

Rades 2006 - showed longer course was associated with higher rates of motor function improvement in MM

Meningioma - causes? - genetic factors? - other associations

Radiation is the only known cause NF2 Inflammation, viral causes assocaited as well as association with hormone level - expresses ER and androgen receptors- increase in pregnancy. most common symptom is seizure. Most commonly these are found incidentally though.

AGGRESSIVE NHL

Rapidly fatal if untreated only 20% are stage I/II Histologies - DLBCL (most common) - peripheral T cell lymphoma - Anaplastic large cell lymphoma - FL G3 high grade follicular - mantle cell lymphoma - sometimes indolent

How common are skip mets w/ oropharynx vs oral cavity? What other common HN site has skip mets commonly?

Rare in Opx, common in oral cavity Other HN site is subglottis Skip mets = think Oral Cavity (15% - specifically oral tongue) and Subglottis

Surgery vs SRS comparison: - effect on risk of re-bleed? - time until AVM is obliterated? - risk of failure?

Re-bleed risk - SRS: During LONG latency period, risk of rebleed drops by half to around 2% per year until obliteration (can take 1-5 yrs to obliterate) - Surgery immediately eliminates bleed risk Lag time for obliteration - SRS = lag time of up to 1-5 years - Surgery = immediate Risk of Failure - SRS: ~1/5 risk of failure - Surgery: not sure

What do you do about close or positive margins?

Remember based on Heaps study - margins <8 mm was associated w/ recurrence Adjuvant RT improves local recurrence if unresectable close/positive margins Both margin negative and bigger effect in margin positive Left graft is close margin < 8mm Right graft is positive margin

Best way to remember what staging approach gets which LN levels?

Remember the following: - Mediastinotomy (chamberlain) = only one that gets both 5 AND 6 (doesn't get other levels really) - EUS = goes down esophagus = only one that gets 8/9 (under carina) + can get lvl 5 + 3p and others - Mediastinoscopy = can get 3a/p + others (can't get 5/6/8/9/11) I think of it like EBUS can get most but notably CANT get 5, 6, or 8/9 3a/p = pre-vascular and retrotracheal

Renal Pelvis and Ureter cancers - what comes out with a radical nephroureterectomy

Removal of Gerota's fascia and its contents, kidney, adrenal gland, and perinephric fat as well as IL ureter with cuff of bladder distally

Describe the process of a lumpectomy and SLNB? What needs to be confirmed in the lumpectomy path report?

Removes the tumor and margin - non-palpable tumors are marked at time of biopsy with a metallic clip and often a wireless "Savi" location device (two separate procedures as device is expensive you want to make sure it is cancer first). - You need to confirm that the following are removed in the gross on the path report: 1. Biopsy clip 2. Savi locator if wireless 3. calcifications if noted on initial mammogram If these aren't located in the specimen, you can do post-lumpectomy mammogram and ultimately you might need surgeon to go back because they indicate the presence of gross disease -- we treat BC with a microscopic dose, not sufficient likely for gross disease.

General rules for resectable vs not?

Resectable: - no distant mets - patent SMV and portal vein - celiac/SMA uninvolved Borderline - SMV/portal vein impingmenet - SMA/Celiac <180 degrees usually (there are different definitions) - the spleen and its vasculature are resected in a distal pancreatectomy so consider it sacrificable and ignore these answers - Superior mesenteric and celiac axis are important so they are considered unresectable if they are contacted by >180 degrees. If they give a % contact <180 degrees for these, they are borderline resectable If they mention any involvement of IMA, this is outside of the regional vasculature of pancreas and would be considered a MET. Unresectable

PORTEC 3 - HIGH risk patients - FIGO I grade 3 WITH Deep DOI and/or LVSI - FIGO II or III - FIGO IA-III w/ serous or clear cell histology - TAH or TLH/BSO (+/- LND) --> WPRT vs ChemoRT (during/after) RT was 48.6 Gy VBT was given if cervical stromal invovlement Chemo = Cisplatin during RT followed by carbo/taxol x 4 cycles Co primary endpoints were overall survival and failure free survival What did the molecular analysis of these patients show?

Results - NO 5 yr OS, 5 yr FFS benefit for all-comers when analyzed together. - stage I or II had no improvement with FFS or OS with the addition of chemo. - ChemoRT showed ~11% FFS/10% OS benefit in STAGE III (SS) - ChemoRT showed 11% FFS/~20% OS benefit for serous histology (SS) - all comers showed reduced ANY pelvis failure with chemo (SS) POLE does best p53 does worst Chemotherapy plays an important role in stage III pts for prevention of distant recurrence (particularly in clear cell and serous histologies) Chemo arm was more toxic

Surgical approaches for acoustic neuroma

Retromastoid Middle fossa Translabyrinthine

What is the difference between a retrospective cohort study and a case-control study?

Retrospective cohort study looks back and compares two groups +/- a risk fact and then looks at outcomes. A case control study looks at outcomes and then looks back for the risk factors comparing two groups with two different sets of outcomes. Ex: Look back at cases of MDR TB compared to pansensitive TB and look back at 5 years worth of data to look at risk factors -- you looked at outcome first so this is a case-control, NOT retrospective study

Benefit of RT in rituximab era?

Retrospective data - RT improves PFS and OS which existed for all stages PFS and OS for +RT and -RT --> 91 and 82% vs 68 an 50%

PET showed no uptake in mediastinum -- do you still need EBUS?

Review of 45 studies: •Sensitivity - 80% •Specificity - 88% •Positive predictive value - 75% •Negative predictive value - 91% (FOR small NON-central lesions) •2 studies show reduction in futile thoracotomies while 3 show no difference à PET/CT in general correctly upstages 20% of CT-operable patients (therefore spared thoracotomy) •Other data show false negative rate of PET/CT about 25% •False-negative rate of PET/CT for primary lesion is 27% on ACOSOG Z0050

Roach equation for lymph node risk

Risk % = 2/3xPSA + (GS - 6)x10 So that is essentially saying extra 10% risk for every GS point above 6 + 2/3 PSA. Generally most studies say if LNs if risk is >15%, observed rate is actually 40%. if <15%, observed is 6%.

more risk group overview

Risk groups: --Low risk = localized, embryonal (FOXO1 neg), any fav/unfav resected site (group I/II) as long as embryonal, favorable sites including CGIII if embryonal; If unfavorable site, need CGI/II to be low risk (meaning unfavorable, embryonal, gross disease isn't low risk) --Intermediate risk = ANY Alveolar, ANY histo if unfavorable site + R2 resection (CGIII) - gross disease + <10 yrs old and embryonal metastatic --High risk = mets (unless <10 yrs old and embryonal - intermediate)

Chemotherapy R-CHOP-21 - what is this? - how often is it given - how is that different than HL

Rituximab Cyclophosphamide Adriamycin -hydroxydaunorubicin is old name Vincristine (Oncovin) Prednisone Given every 21 days, remember ABVD given ever 2 weeks

Multiple myeloma - sprectrum of MGUS to MM - 1-2% of cancers - more common in men - older pts 65-75 yrs Classic blood smear finding?

Rouleaux formation

SRS for spine mets - pain relief 85%, LC 80-90% - most srs studies excluded cord compression - good for re-rt - less time, one or just a few treatments

SBRT may be appropriate for re-RT (decreases dose to cord), oligomet, radioresistant histology (RCC, NSCLC, etc)

Describe SCV field, any angles, blocks

SCV field is angled 5-10 degrees away from the spinal cord Left SCV field uses a RAO beam To match the superior divergence of breast field for a 2 iso plan Kick the patient's feet AWAY from the gantry for both tangents BreAst= feet Away for both tangents Such that it is matching the supraclav field For a mono-iso plan there is no couch kick or collimation

Description of nodal levels scv imn axillary

SCV: From cricoid down to clavicle head lies underneath/inside the SCM between scalenes in the back and SCM to the front and side Cut out thyroid, trachea, and esophagus IMN First 3 intercostal spaces "from the TOP of the 1st rib to the top of the 4th rib" Contour the internal mammary/thoracic vessels in the first three intercostal spaces as CTV The PTV is 5 mm all around except 0 ant and post. The IMN PTV = IMN CTV in the front and back. Axillary Level 3 Start where pec minor inserts on the coracoid, stay medial to it. Then between pec major and ribs, bounded by pec minor on the lateral side go down to where thoracic vessels touch the medial edge of pec minor Level 2 Between pec minor and ribs The top is where the vessels touch the inner edge of pec minor The bottom is once they hit the other side The width is the same width of the pec minor, literally these are just behind pec minor along the vessels Level 1 Once the vessels make it to the outer edge of pec minor is the top of level 3 It goes down to where pec major inserts on the ribs (pretty vague) - usually this is the 4th rib Keep it between pec major and intercostal muscles

Is there a role for local therapy in metastatic stomach?

SEER data -- looked at 5k patients (med OS) - no surgery and no xrt - 4 months - no surgery; +XRT - 6 months - surgery; no XRT - 8 months - surgery + XRT - 15 months MVA -- surgery and XRT reduced mortality in all patients. XRT reduced mortality in surgical patients. Age only predictor in non-surgical patients The REGATTA P3 trial looked at surgery in metastatic patients - chemo alone vs gastrectomy followed by chemo - study closed early - 2 yr OS showed surgery and chemo had benefit

SHORT COURSE RT vs none Swedish rectal cancer trial - NO TME - 1168 pts randomized to pre-op short course 25 Gy in 5 fractions vs surgery alone (LAR/APR - no TME) - results? - benefit of short course restricted to what size tumors? DUTCH trail - +TME (CKVO 95-04) - 1805 pts, TME only vs short course RT + TME -half of patients were stage I/II disease -results? - benefit of short course restricted to what size tumors? - what are long term toxicities of short course? - what major factor was found to correlate with effect of RT? Didn't really go over Candian or Uppsala - but summary slide is on the other side of the card

SHORT COURSE RT vs none Swedish rectal cancer trial - NO TME - not SOC surgery - 5 yr LF favored short course 11% vs 27% - 5 yr OS 58% vs 48% - ONLY one to show a survival advantage to pre-op - but compared short course to nothing - long term follow up showed higher rates of hospital admissions for GI disorders (bowel obstruction, abdominal pain, etc) 13 yr update --> OS 31% vs 20% (SS) --> LR 9% vs 26% (SS) - benefit of rt was restricted to 10 cm or smaller. DUTCH trail - +TME - 2 yr OS the same - 82% - 2 yr LR was 2.4% vs 8.2% - CRM <1 mm - 9.3% vs 16.4% -- NS - benefit of rt restricted again to <10 cm -- curiously benefit also not seen for <5 cm in dutch study - short course is associated with higher incidence of sexual dysfunction, slower recovery of bowel function, more fecal incontinence and poorer QOL - the LOCATION of the disease correlated with the effect of RT - was improved with increased distance from the verge Canadian trial - +TME

paraneoplastic syndromes of SCLC

SIADH - hyponatremia -- treatment is water restriction ANP syndrome (atrial natriruetic peptide release) -- > increased Na and water excretion - hyponatremia Ectopic ACTH --> Cushing's syndrome Lambert Eaton syndrome - proximal myopathy improving with activity

Pediatric Extra CNS constraints

SINGLE ORGAN Bladder < 45 Gy Heart <30 Gy Liver-whole <23.4 Gy Liver-partial (50%) < 30.6 Gy Rectum <45 Gy Small bowel <45 Gy Spinal Cord < 45 Gy Peritoneum (whole abdomen pelvis) < 24 Gy PAIRED ORGANS Kidney <14.4 Gy -- important for Wilms WAI esp. (Partial transmission block for WAI after CL nephrectomy) Lung - whole 12 Gy (dose for WLI is 12 @1.5's)

RADIATION FOR ACOUSTIC NEUROMA SRS (single fraction) - SRS or frac worse for hearing preservation? - SRS or frac better option if patient already has "less than serviceable hearing"? - hearing preservation %? - SRS prescription? - SRS LC%? - SRS, hearing preservation decreases at doses above what? - Single fraction dose constraint to the cochlea? - effect of SRS on normal ear aging?

SRS - SRS or frac worse for hearing preservation = SRS WORSE - SRS or frac better option if patient already has "less than serviceable hearing" = SRS good if patient already has hearing loss - 50-60% hearing preservation - SRS prescription = 12.5 Gy to 50% IDL (54 Gy if EBRT) - SRS LC% = 90% - SRS, hearing preservation decreases at doses above what = >13 Gy - Single fraction dose constraint to the cochlea = 4.2 Gy - effect of SRS on normal ear aging = accelerates

Androgen depletion intensification - STAMPEDE - multi-arm platform trial that changes as SOC changes. The different arms are activated at different times. Arms were A-L and activated slowly over time.l - Stampede arm G was looking at ADT alone vs ADT + abiraterone/pred (think STAMPEDE 17 STAMPEDE 17 - stampede was looking at the addition of Abi/pred to high risk or metastatic prostate cancer that was starting hormones. - med PSA was high ~56, ~half were localized, ~half were metastatic - what are the major things to know about this one? CRITICAL -- who was eligible for this "max ADT" approach if they were node negative/non-metastatic? - were metastatic patients given RT - what is viewed as the benefit to giving RT in the N+ setting (on trial it was encouraged for N+ but only mandated for N- high risk)

STAMPEDE '17 - node negative guys only eligible if 2 of the following 3 were met: 1. cT3/4 2. Gleason 8-10 3. PSA 40 or higher In other words they had to be super high risk prostate guys if they weren't already metastatic to be eligible for this hormone intensification strategy. Metastatic patients not given RT here. Major benefit to giving RT to primary for node positive is that if you do, you get to stop the ADT after 2 years. If not, Abi/pred is 2 yrs and ADT continues lifelong. STAMPEDE didn't treat lymph nodes so if you say RT, you are talking about treatment to the primary. Abi/pred improved FFS in all groups, improved OS in metastatic group (not localized group). Fu was only 3.4 yrs which is probably why we don't see benefit in non-met patients yet.

Chemotherapy for Anal cancer - SOC chemo?

STANDARD OF CARE - concurrent - IV 5-FU (1000 mg/m2) - days 1-4 and days 49-32 (week 1 and week 5) - MMC 10 mg/m2 D1, 29 or - Capecitabine 825 mg/m2 M-F on days of RT - MMC 10 mg/m2 D1,29 "Acceptable" - concurrent - Cisplatin 75 mg/m2 D1,29 - 5FU or capecitabine alone as above - PII MDA data on CAPOX Metastatic - Cis/5FU, FOLFOX, carbo/taxol, Cis/5fu/cetuximab

STARS Trial - published in 2021 - P3 RCT, sort of a combination of Sedlis and Peters trials - eligible patients had EITHER Sedlis or Peters criteria - 3 arms to trial - randomized to 1. Adjuvant RT alone 2. Adjuvant Concurrent ChemoRT (weekly cis) 3. Adjuvant Sequential ChemoRT (cis/paclitaxel q21 days) Sequential chemo was given as 2 cycles of chemo up front, followed by RT, followed by 2 cycles of chemo (sandwich style) Primary endpoint = DFS RT was 45-50 Gy Results?

STARS Trial - think Stars = Sequencing of Chemo - Surprisingly, sequential chemoRT arm had the best DFS and OS 3 yr DFS - RT 82% - CCRT 85% - SCRT 90% 5 yr OS - RT: 88% - CCRT: 89% - SCRT: 92% This is a weird ass trial -- its very confusing to me why you would randomized patients with peters criteria specifically to only get RT alone when GOG-109 showed inferior OS with RT alone which is why we do chemoRT in the first place for them. Note limitations of this trial: CCRT was tolerated much worse than would normally be expected and there was 38% attrition from this arm; LN mets were biased toward CCRT and SCRT arms - 20% of the pts in these arms required neoadjuvant chemo to permit upfront surgery which is a higher risk population than would typically be getting surgery at all in the US.

What were the arms of the START A trial? What were the arms of the START B trial? Bonus Qs: - what were inclusion criteria? - what was surgery? Was mastectomy included? - was boost done? - why do we use Canadian at WF instead of fractionation per START B? - interesting point: Was there a different in distant recurrence rate or OS between the 40 Gy and 50 Gy arms?

START A -- ARMS: 50 Gy/25 fractions vs 41.6/13 daily vs 39/13 over 5 weeks (3 fxn per week) -- 13 fraction arms were inferior. START B -- ARMS: 50 Gy/25 fractions vs 40.05 Gy/15 fractions - arms were equiv for local control and cosmesis was technically better for hypofrac. - db says short followup (although was 9.9 yrs) and were provider reported outcomes, not patient. Cosmetic pt reported outcomes were excellent to good in Wheelan w/ longer follow up. - Take home: Cosmetic outcomes better in 40 Gy/15 compared to 15 with equiv LRC outcomes. UK start A and B (Lancet 2013) were RCT comparing stardard frac w/ hypofrac - inclusion: T1-3N0-1 - surgery = lumpectomy + SLNB (85%) or mastectomy (15%) - boost allowed (10 in 5), not required - Not for great reasons for why we do 16, LRR was similar between 40/15 (~4.3% HF vs 5.5% CF) and 42.56/16 (6.2% HF vs 6.7 CF) but patient reported outcomes thought to be better for Canadian than start B and generally db says Canadian was longer fu and better quality data - INTERESTING POINT: 40 Gy/15 had a statistically significant DECREASED distant metastasis and overall mortality rate (Distant recurrence 10.3% vs 16% HF vs CF, p = 0.014; overall mortality was 19.2% vs 15.9% HF vs CF, p = 0.042.) HF = Hypofrac CF = Conventional Hypofrac Blurb about nodes: Generally speaking there is always the question of XRT for 1-3 nodes (N1) but there is no question about benefit for 4 or more nodes (N2). So the N1 people on these hypofract studies (Start A/B/B39) -- accrued very small numbers and treating nodes were optional, so N1's didn't necessarily get nodal XRT. Thus we still don't have enough data regarding the role of hypofrac in regional nodal.

Metastatic directed therapy - STOMP trial - OST paper - metastatic patients randomized to site directed therapy or nothing. - results? Oriole Trial - - metastatic patients randomized to site directed therapy or nothing. - results?

STOMP - RT improved ADT free survival and biochemical free survival Oriole - RT improved PFS and BPFS Important point -- these weren't compared to ADT - just compared to doing nothing. So not clear if site directed therapy would improve outcomes if you were comparing to what is really standard for metastatic prostate which is ADT.

Larynx paradigm for T4 Indication for adjuvant XRT and chemoRT?

SURGICAL DISEASE -- T4 had BAD outcomes in VA trial with larynx preservation (56% had salvage laryngectomy) Total laryngectomy is standard of care up front The problem is not all recurrences can be salvaged -- The "olsen hypothesis" - Larynx cancer is the only major HN site where survival is FALLING -- believed to be due to trying larynx preservation in T4 cases. Post-op RT: post-op bed + b/l II-IV + VI (below) - based on pathologic evidence of cartilage invasion, treat the tumor bed from the neopharynx from the distal tongue to the upper esophagus with margin = 60 Gy/30 fractions --Post-op RT for T4 = close margins, skin/soft tissue invasion, >1 cm subglottic extension, TRUE thyroid cartilage invasion, multiple positive LNs (ChemoRT = positive margins/ENE) Nodes: - lvl II-IV 54-60 depending on nodal involvement - Level VI if subglottic extension (most treat for all cases though)

Briefly Adjvuant Trials - has declined in popularity in favor of early salvage -- question does immediate post-prostatectomy RT improve outcomes in high risk patients -- 4 major studies looked at this SWOG 8794 - 425 pts --> obs vs adjuvant RT (60-64/30-32 fx. - criteria T3a/b, SVI, pos margins - no IMRT, PLND not required, undetectable PSA NOT required (some patients were actually salvage - ~2/3 were actually adjuvant) - results? EROTC 22911 - 1005 pts --> wait and see vs RT (50/25 + 10 boost w/in 16 weeks of surgery) - <75 yrs, pT2/3, SVI, +margins, EPE - endpoint bPFS >0.2 PSA over post-op nadir. - undetectable PSA again not required so about 2/3 were actually adjuvant (rest were actually salvage) - result? German ARO 9602 - 338 pts - Study DID require undetectable PSA before enrollment. - T3/4, pos margins - results? Finnish Trial - 250 pts --> obs vs 66.6 Gy in 37 fxn, no pelvic nodal RT. - 40% of obs arm ultimately required salvage. - undetectable PSA NOT required on this one either. - result? Meta-analysis of all of these showed what?

SWOG 8794 - results showed PSA FFS benefit RT and freedom from hormone therapy. - in 15 yr update, metastatis free and OS were both significantly improved with RT (HR 0.72, p = 0.23) -- THIS IS THE ONLY STUDY THAT SHOWED OS BENEFIT EROTC 22911 - bPFS benefited from RT. - OS/Clinical PFS, etc NOT benefiting from RT. - Toxicity higher in RT group. German ARO 9602 - bPFS improved with RT (HR 0.51) Finnish Trial - bRFS benefit (HR 0.26) Meta-analysis showed benefit of RT with HR 0.5 for bRFS, and DMFS (driven mostly by SWOG trial).

Summary of Adjuvant trials SWOG 8794 EROTC 22911 German ARO 9602 Finnish Trial ONLY one that required undetectable PSA? Which was only one to show OS benefit? What did all of them show?

SWOG 8794 --> Improved bPFS, DMFS, OS (only one) EROTC 22911 --> Improved bPFS German ARO 9602 --> Improved bPFS Finnish Trial --> Improved bPFS ONLY the German ARO study required PSA 0 and was really a TRUE adjuvant study. ONLY one to show OS benefit was SWOG trial All of them showed bPFS benefit but most didn't require PSA of zero and so they were really ~1/3 salvage pts which would probably improve RT outcome.

Future directions for bladder cancer

SWOG S1806 Looking at immunotherapy for T2-4N0 giving CRT vs CRT + atezo x 9 Looking at bladder intact event free survival Ongoing study

Salivary gland types?

Salivary glands major and minor Major: - Parotid - Submandibular - Sublingual Minor: - scattered nests of salivary tissues throughout the upper aerodigestive tract - hard palate most common site

Volumes and doses for OP - general dose paradigms - minimal nodal level coverage - when is Ib included? - when is V included - when can you consider IL RT in OP?

Same as before Gross disease or clinically involved nodes GTV70 High risk nodes CTV63 Low risk nodes CTV56 Typically minimum elective nodal coverage for OP is: - minimal IL lvls 2-4, IL RP (VIIa) - Ib included IF bulking (or really any) level II OR tumor extends up to oral cavity - Lvl V covered if there is bulky II, III, or IV involvement (or any really -- doesn't add much in terms of volume if already treating 2-4) NEED BILATERAL IN: - tongue base and soft palate -- MIDLINE structures IL Considered if: TONSIL CANCERS - IL can be considered if well lateralized tonsil (if <1 cm extension to soft palate) and >1 cm from midline - nodal burden not excessive enough to cause retrograde lymphatic flow - generally no bulky adenopathy - NO clinic ENE

EORTC 26951 - looked at RT w/ 59.4 vs 59.4 + PCV

Same results, difference was seen in the 1p19q codels in the g3 population Difference is this was an intention to treat population, not subgroup analysis like RTOG 9402 Median OS was 42.3 (RT+PCV) v 30.6 (RT alone). 1p/19q co del patients had longer survival QOL analysis showed worse side effects with PCV.

GI section Anal cancer 8300 cases per year <3% of GI malignancy female gender HPV status receptive anal intercourse HIV AIDS chronic immunosuppression

Screening HPV associated lesions Low and high grade SIL AIN = anal intraepithelial neoplasia grade 1-3

Screening - what are the current USPSTF screening guidelines? - age cutoffs?

Screening means PSA and DRE 2013 - USPSTF = grade D recommendation 2020 - USPSTF = updated to grade C that it should be shared decision making for men 55 - 70 to discuss prostate screening with physician. Grade D recommendation to discuss above age of 70 tho

High risk screening criteria for EGD

Screening should be considered for Age >50 Male Caucasian Chronic GERD high BMI hiatal hernia intraabdominal fat distribution Endoscopic surveillance q3-5 yrs if no biopsy eividence for dysplasia If you have low grade dysplasia then q6-12 months but if high grade q3 months

Lymphatic drainage for testis vs scrotum - how is this different? Left vs right testicle?

Scrotum is inguinal --> iliac drainage vs testis is para-aortic. Left= drains into the L renal vein Right = drains into the IVC directly If scrotum is violated this means you now have to worry about inguinal and iliac whereas if you didn't, you only think about paraaortic and up. Of note: first site of failure after paraaortic is L supraclav as thats where the thoracic duct goes next.

Trimodality - indications? - why would you do port if upfront surgery? Summary of what you should say for trimodality approach: - What is basic paradigm - What is pCR rate of neoadjuvant chemo vs chemoRT - in what subgroup might surgical resection offer benefit?

Select single station N2 (IIIA) or some IIIB if based on size Indications for PORT: N2 (not really anymore after lung ART unless no chemo), positive margins Anita: Adjvuant chemo +/- PORT -- RT had OS benefit for all N2 disease - only benefited N1 pts if they couldn't get chemo (if they can get chemo, that's better than PORT) NOT indicated for N0-1 w/ negative margins due to INCREASED mortality The basic paradigm for trimodality treatment is treat with chemoRT (to 45 Gy), reassess mediastinum, and proceed to surgical resection. pCR rate of CRT is ~40-60% compared to chemo alone for ~10-20%. People with pCR do best with resection, however, based on SAKK, even those with only partial response still had a benefit with resection over those that were treated definitively (specifically if you excluded the pneumonectomy patients). Those that benefit from resection tend to be those who are able to undergo lobectomy rather than pneumonectomy.

serum markers for germ cell Seminoma - what should be negative in order for this to be a pure seminoma?

Seminoma = AFP must be negative and b-hcg should only be modestly slightly elevated (>5 but not more than 100 IU/L). If highly elevated this is more consistent with choriocarcinoma

FIRES trial - what was the sensitivity and NPV of SLNB for endometrial?

Sensitivity = 97.2% Specificity = 99.6% This made SLNB more commonplace

When is SLNB indicated?

Sentinel lymph node biopsy (SLNB): Indications: -Clinically node-negative -DCIS undergoing mastectomy Type of dye: radioactive (Tc99-labeled sulfur colloid) or blue dye (isosulfan blue / methylene blue) Injection periareolar (where most of the lymphatics are), either in 4 spots N/S/E/W of areola or in the superior/lateral region to drain to axilla Less morbidity than ALND (7% lymphedema) False negative rate = 8% overall After NAC up to 12.6% If obtain 3+ nodes and ensure clipped node (if applicable) taken, ~6.8% Axillary lymph node dissection (ALND) Indications: Clinically node negative does not need ALND Positive SLNB probably does not need ALND unless mastectomy (Z-11 was only lumpectomy) Clinically node positive → ALND standard Inflammatory ALWAYS needs ALND

Short Course RT vs Long Course RT Polish-1 trial RCT - 5x5 vs pre-op CRT - 316 pts w/ distal T3/4 tumors randomized to 25/5 then TME w/in 1 week VS CRT w/ 50.4 Gy/bolus 5-FU followed by TME w/in 4-6 weeks - results? Overview slide attached for short v long course

Short course vs Long Course chemoRT Sphincter preservation 61 v 58% - same HIGHER pCR in CRT (1% v 16%) Fewer circumferential margins in CRT (13 v 4%) Acute toxicity higher in long course - 3.2% v 18.2% (SS) Severe late toxicity - 10.1% vs 7.1% (makes sense, hypofrac) In the Polish-2 trial (similar but used FOLFOX as chemo) 3 yr OS favored short course (73% vs 65%) (SS) No difference in local or distant recurrence No difference in post-op complications Note the Stockholm III trial - short course vs short course + delayed surgery vs long course - no chemo - LR favored short course w/ no delay...

Role of PCI in SCLC? Evidence for benefit in LS-SCLC - RTOG 0212 - results? Trials for ES-SCLC - slotman vs Takahashi - which showed OS benefit - what is the problem with these studies?

Should still be offered - is still the standard LIMITED STAGE Evidence: - RTOG 0212 - 25 Gy/10 fractions - ↓ 3-yr incidence brain mets (33% v. 59%) - ↑ 3 yr OS (21 v. 15%) - PCI ↓ cumulative risk of brain mets at 1 yr: 15% vs 40% - ECOG 0-2, Give PCI w/in 3-6 wk after last chemo cycle There is LS-SCLC propensity matched data out of MD Anderson that suggests no difference in intracranial failure OR OS in the era of MRI. For extensive stage: Slotman (compared PCI and no-PCI after favorable response -- showed benefit of med OS (6.7 vs 5.4; 1 yr 27% v 13%) -- problem with this is they didn't have brain MRI up front so some may have had occult brain mets --> similar to data for LS-SCLC Takahashi -- did require upfront MR, and didn't show survivial benefit (Actually might have been detrimental- 15 months vs 10 months favoring no PCI group but not significant) -- however the Japanese GK'd a ton of lesions in a bunch of these people and then said they didn't get "whole brain" radiation - brain relapse rates were higher in the no PCI group but survival not different because they could just get salvage RT after they developed brain mets -- cumulative incidence of brain mets in the observation arm was 59%; RT arm was 38% -- but the OS was not different. The MAVERICK Trial (SWOG S1827) - open world wide, question of OS in both LS and ES to see if this is beneficial.

IMRT - PARSPOR Trial - showed benefit in what metric?

Showed IMRT improved xerostomia at 12 and 24 months (38 v 74% and 29 v 83%) - also shown in Asian data set Michigan data also showed IMRT improved salivary flow at multiple time points >30 Gy = no recovery of salivary flow That's why we say mean <26 for parotid -- if mean dose <24 Gy then have recovery at 12 months -- if you don't push this, they will have persistent dry mouth

RTOG 0129 - stage III/IV T2, N2-3, or T3-4 any N, M0 - randomized to 70 Gy in 35 vs Accelerated (daily for 3.5 weeks then BID for rest) - both with concurrent cis - risk stratified pts low risk = <10 pk-yr smoking + HPV+ intermediate risk = >10 yr pk-yr smoking + HPV+ high risk = >10 pk-yr smoking and HPV-

Showed major differences in outcomes for HPV neg and HPV positive ~20% PFS and OS difference

CALGB 8433 --> role of chemo - 155 pts stage III - RT vs induction cis/vinblast + RT - results?

Showed seq chemo --> RT was better than RT alone Med OS 13.7 vs 9.6 months This benefit helped BOTH squamous and adeno (unlike CHART)

RTOG 1203 - 4 field 3D compared to IMRT for endometrial cancer?

Showed significantly lower abdominal and GI toxicity compared to those treated with 3D

Meta-analysis data (Horgan, JCO 2012) - + 2 SEER analysis exist for cholangioa, RCT of adj chemo, 17 retrospective studies - 6712 pts - all had curative intent surgery alone as control group - R0 and R1 resection status - adj treatments included 8 studies of CRT, 3 chemo alone, 9 RT alone - results?

Showed that 5 yr OS for adjuvant treatment had no benefit compared to surgery alone. Data became significant for adjuvant therapy when 2 large registries were excluded (OR 0.53, SS) Chemo and CRT showed a significant benefit for GB and CC -- no benefit to RT alone OS advantage to any N+ or R1 Possibly detrimental for R0

MDACC retrospective - 226 pts - looked at locally advanced BC that had pCR - showed what?

Showed that RT was still associated with OS benefit in each nodal subgroup (ypN0, ypN1, and ypN2) -- all SS Continues to support the idea that we should treat PMRT if there were upfront indications. B51 will prospectively address this issue.

Kidney cancer - Kjaer 1987 study - 65 pts after nephrectomy were randomized to adjuvant RT (50 Gy in 20 fractions) vs obs - showed what?

Showed that there was a ton of G5 toxicity (20% of patients died from RT) This made observation arm survival much better than RT. This was the era of 2D RT therapy which was more than 50% of the abdomen to 50 Gy with hotspots >112%. Not that shocking that this killed a bunch of people.

Zhang - NEJM - Gemcitabine/Cisplatin INDUCTION in NPX Cancer - EBV endemic population - induction gem/cis x 3 cycles followed by chemoRT with Cis --> high compliance (97% got 3 cycles inductino, 92% got 2/3 cycles concurrent) vs standard therapy - results?

Significantly improved 3 yr DM (7%)/OS (4%)

Describe CSI technique and feathering

Sim Setup: Prone position, clamshell mask over head (both front and back) Adjust faceholder angle to reduce exit dose through mouth/chin Neck is slightly hyper-extended This is done before the scan Set desired neck tilt Body (chest/abdomen/pelvis) in a vac loc Shoulder retractors Want the shoulders pulled down as far as possible to prevent brain laterals shooting through the shoulders Determine what the upper border of the upper spine field is Open field as much as possible sup/inf, go up as high as possible without dose exiting through mouth This is usually around C5-C6 Need to make sure this is 2 cm above the top of the shoulders Move cursor to midline anterior edge of the spinal canal Scroll up to middle of brain and place iso This iso is marked on the mask This is the only iso set at the time of sim Iso(s) for spine fields will be set in dosimetry At my institution we perform intrafractional feathering We construct a short medium and long versions of each field The long upper spine field is adjusted by 1 cm from each end to make these and the brain and lower spine fields are adjusted by 1 cm to match The long upper spine field is 40 cm Medium upper spine field is 38 cm Short upper spine is 36 cm Lower spine field is added if needed and the same fields are generated to match inferior borders of upper spine field All fields are treated every day at 50 cGy each, for a total of 150 cGy to each region. Standard width for the spine is minimum of 5 cm

Meningioma -- Surgical Resection = uses what grading system?

Simpson Grade = reflects how well the tumor was excised

Site: Craniopharyngioma Workup: Important genetics: Prognostics: Dose: Misc. notes:

Site: Craniopharyngioma Benign, peds adaminomatous type (adult squamous epithelial type) Workup: HP, emergent symptoms, CN exam, Visual, audiometry, neuropsych, endocrine, CT head - imaging = calcifications, T1 hyperintense, contrast enhancing, suprasellar location Important genetics: - Adamamtinomatous = WNT; Squamous = BRAF/V600E Prognostics: General Tx Paradigm/Dose: - move away from trying to get GTR as it is morbid, and STR + RT does just as well. Long term control with limited surgery + RT = 85-90% - if <3 yrs, operate and hold RT until at least 3 to allow for continued normal development - Dose = 50.4-54 Gy, 54 most common at 1.8's (wake dose = 54). - SRS = 12-14 to 50% IDL but dose constraint of <8 Gy for optics for SRS is usually limited -- SRS usually then limited to recurrent/residual tumor setting Misc. notes: Cysts are decompressed before RT VOLUMES : GTV = residual tumor + entire cyst; CTV = GTV + 0.3-0.5 cm expansion plus any surface the tumor touched, + PTV = 0.3 cm. - IMPORTANT: Intra-tx imaging with MR at least every other week, move to 1/week if any change on imaging or change in symptoms --> ~24% experience growth of cystic component during treatment; --> 1/7 will require replan/be symptomatic --> Around 1/3 will require some treatment intervention during TX (1/3 will expand outside of CTV -- get repeat MRI for any change in symptoms, regardless of last normal MRI - options if cyst expands: expand CTV volume or have NS decompress cyst again MRA screening needed after tx to evaluate for Moya Moya -- puff of smoke, need to confirm with angiogram. Diabetes insipidus is a SURGICAL COMPLICATION -- NOT RADIATION -- more IQ decrement, endocrinopathies, etc from trying to get GTR

Site: Ependymomas epi Workup: Important genetics/pathology: Prognostics: Dose:

Site: Ependymomas epi - 3rd most common CNS tumor in kids, med age 4 yrs, may occur anywhere w/in the CNS (60% = posterior fossa/IVth ventricle, classically tracks out of the foramen of lushka through foramen magnum; 30% supratentorial, 10% in spinal cord Workup: 5-10% can have CSF seeding 1. Brain MR preop/post-op (24-48 hrs), Spine MR, and LP (ideally >10 days after surgery) Important genetics/pathology: 3 major types 1. WHO grade 1 = Myxopapillary ependymoma (SPINAL CORD ONLY) - different biology, more common in adults BRAIN TYPES 2. WHO grade II = ependymoma 3. WHO grade III = anaplastic ependymoma Not clear if anaplasia makes a difference. Prognostics: - DOMINANT PROGNOSTIC -- MOST IMPORTANT: Extent of resection -- STR + RT PFS is very bad 0-25% vs 50-75% - others: tumor grade, 1q gain worse General Tx Paradigms/Dose: - GTR whenever possible (maximal safe resection) - +IF radiation of 54-59.4 Gy (respect the brainstem though) -- if going to 59.4, you boost w/o a CTV after 54 coning down to just GTV (initial has 1-1.5 cm CTV) - limited role of chemotherapy (vcr, cyclophosphamide, etoposide, cis if used) - generally for boards, just say 54 Gy (59.4 is ideal if supratentorial; but very hard to meet that) Only people on ACNS 0121 that could avoid was supratentorial GTR G1-2 --> 5 of 11 patients failed --> so now we decided we shouldn't observe them.

Site: Ewing Sarcoma Workup: Important genetics: Prognostics: Dose: Misc. notes:

Site: Ewing sarcoma 2nd most common bone tumor of childhood (2nd to osteosarcoma -- only seen if unresectable or positive margins); more common in extremities compared to axial skeleton (Rad oncs see these more commonly - unresectable) 87% occur at the diaphysis 8% soft tissue Workup: Plain film Ct/ MR primary site (need to see soft tissue extension of tumor) HP bone scan PET scan helpful CT esp chest b/l BMB No commonly accepted staging system This almost always presents with micrometastatic disease like small cell -- local treatment alone - only 10% cure. Poor Prognostic features: MASSiveLDH Response Male Age >15 Stage Site - pelvis, axial skeleton, rib/askin's LDH elevated Reponse Important genetics: - t(11;22) 90% or t(21;22) 10% - small round blue cell tumor; vimentin positive Prognostics: <10 years = good prognostic General Tx Paradigm/Dose: In general, never go over 60 Gy in kids and if given the option of RT or surgery, always pick surgery - high rate of 2nd malignancy -VAC-IE (A = Adriamycin) x 6 cycles (week 1-12) -- A not given with RT --> then surgery or RT or both --> 11 cycles chemo outback - this is different than RMS because you do the local treatment after chemo, not upfront (either RT or surgery after 12 weeks of chemo). RMS you would only do that if you have unresectable disease - 3 main indications for RT = 1. + margins 2. Tumor spill 3. >10% viable tumor in resected specimen after induction chemo (poor chemoresponse) - gross = 55.8 Gy - microscopic disease = 50.4 pre-op or post-op Rt both acceptable - but prefer pre-op. Generally shouldn't be going to surgery if positive margin expected. Typically you would treat pre-chemo volume to 45 Gy and then cone down to boost the post-chemo residual disease to 55.8 Gy. If lung mets, treat WLI 15 Gy @1.5's (12 Gy if <6 yo) --> same is true for RMS

Site: Germ cell tumors epi: location: which more common in boys vs girls? Workup: Important genetics: Prognostics: Dose: Misc. notes:

Site: Germ cell tumors --> NGGCT and GGCT (non and germinomatous) epi: 2% of peds CNS tumors. 60-70% germinomas; Nongerminomas (embryonal carcinoma, endodermal sinus tumors, choriocarcimomas, and teratomas) location: most are in the pineal or suprasellar region (uncommonly in the basal ganglia or thalami) - pineal = tends to happen in boys - increased ICP + parinaud's syndrome = decreased upward gaze + prostitute pupil - suprasellar = tends to happen in girls = classic triad of DI + abnormal sexual development + visual impairment DI w/o clear imaging evidence = think multifocal occult disease -- include the suprasellar region in the boost! Workup: - Markers: b-HCG and AFP. Still need biopsy because there can be mixed components to tumors Germinoma = mild bHCG (<100) or negative + negative AFP AFP elevation = definitively NON-germinomatous (NGGCT) - >100 bhcg Choriocarcinoma = very HIGH bHCG (>1000) Endodermal sinus (yolk sac) tumor = very HIGH AFP - basic stuff otherwise, MRI Imaging characteristics: Contrast enhancing, calcifications, T1 iso-hypotense vs T2 iso-hyperintense Important genetics: NA -- just know types GERMINOMAS (tx for NGGCT on next card) Prognostics: Two stages essentially: M0: localized disease M+: metastatic - if pineal + suprasellar multifocal = still M0 Treatment Paradigms/Dose: Essentially two options for each M option above People say 1.5 Gy for pure germinoma M0 = localized Extent of resection is more important for NGGCT - not for GGCT. 1. Young patients = neoadjuvant CHEMO + RT = 4x Carbo/etop + WHOLE VENTRICLE RADIATION (WVRT; reduced because of chemo) 21-24 Gy + boost to 30 (CR) -36 Gy (PR) @1.5's 2. Older patients = definitive RT -- If no chemo then WVRT to 24 Gy then IF boost to 45-50.4 Gy (having to go through chemo could be more difficult for older adults for 5-6 months) M1 = mets -- germinomas are different because cure rates are still in the 90's even with mets -- just have to know about them. 1. Chemo + RT (again younger) = CSI 21-24 Gy boost original gross disease to 30-36 Gy 2. RT alone = CSI to 24 Gy + boost to 45 Gy primary site and spinal nodules -- CSI 30 Gy if cord diffusely coated (@1.5's) Misc. notes: Occult multifocal, if patient has pineal mass but also has DI, even if nothing in suprasellar region, you need to include this region in your IF because it is involved. Studies looked at patterns of failure for just IF, and found that people failed most commonly in the ventricle thus you do need to do WVRT.

Site: Medulloblastoma How common: Workup: Important genetics/pathology: Prognostics: General Tx Paradigms: - standard risk - high risk - infant medullo Dose: Misc. notes:

Site: Medulloblastoma How common: 2nd most common brain tumor, most common MALIGNANT brain tumor; most common location in kids is cerebellar vermis, more likely in hemispheres in adults (group 3/4 more likely in midline; Wnt/SHH more likely off center or hemisphere). SHH most common subtype in both adults and infants . SHH in infants have high frequency of desmoplastic histology Workup: MRI pre/post op (24-72 hrs post-surgery due to post-op gliosis) - spine MRI pre-op if possible, note inferior border of thecal sac on MR to ensure full coverage - can go to S4 also. - MR brain/spine up front and LP if possible; if they go to surgery for emergency decompression, you need to wait 14 days to do LP to check - labs: CBC, LFTs, RFTs, and endocrine if symptoms - baseline audiology/neuropsych testing - Difference on imaging between medullo and ependymoma: Ependymoma is more a "toothepaste" tumor squeezing through the foramina of luschka - - Collin's law = if you survive your age + your gestational age, very high chance you are cured. Important genetics/pathology: - Classic histology - Wnt signaling - Desmoplastic variant histology - associated w/ SHH signaling (worse than wnt, better than anaplasia) - diffuse anaplasia or large cell variant -- these are worse than non-anaplasia (classic histology). MOST IMPORTANT GENETIC GROUPS: - WNT pathway, SHH, Group 3 and 4 - Wnt = excellent (90-100% Survival) - monosomy 6 - CTNNB1 mutation - RARELY metastatic - SHH = good (80%) = desomoplastic type, PTCH1/SMO/SUFU mutation - uncommonly metastatic at diagnosis - group 3 (C) (MYC) and 4 (D) = more guarded (intensifying therapy currently) - group 3 worse than 4. Both can be metastatic routinely Prognostics: Essentially three major groups 1. Standard risk: M0 + GTR or <1.5 cc resid. Classic or desmoplastic histology - no anaplasia. >3 years 2. High risk: M+ disease or STR (>1.5 cc), anaplasia. <3 years old 3. Infant medullo -- no RT typically (bad adverse effects) -- chemo until 3 yr (vs 1 yr in ependymoma) General Tx Paradigms: - Everyone Requires CSI - high rate of CSF dissem (~33% at diagnosis). Trends are moving away from posterior fossa (PF) boost to involved field (IF) boost 1. Standard risk: CSI to 23.4 Gy + IF boost to 54 Gy +/- weekly vincristine (Vcr) followed by adjuvant chemotherapy (Cis/Vcr, cyclophosphamide, or CCNU) 5 year EFS, OS = ~81%, 86% 2. High risk: CSI to 36 Gy + PF boost to 54 Gy + concurrent chemo (Vcr or carboplatin) 5 year EFS = ~60%-70% 3. Infant medullo : Usually high dose chemo with stem cell rescue +/- RT (NO CSI because of significant toxicity of RT in infants) -- rt is controversial. Biology of the disease is also different. Dose: generally -- 23.4 (SR)/36 (HR) Gy CSI + IF boost to 54 Gy Misc. notes: No difference between whole posterior fossa and involved field and IF is less toxic so we do that -- but those studies looked at standard risk only. - use of SHH inhibitors in patients not skeletally mature, their growth plates close - during tx = DO NOT HAVE TREATMENT BREAKS EVEN FOR LOW COUNTS. Disease control worse if you have treatment breaks. Hold chemo -- keep going with RT

Site: Neuroblastoma - Workup: Important genetics: Prognostics: Dose: Misc. notes:

Site: Neuroblastoma epi: most common extraCNS solid tumor in peds. Arises from sympathetic nervous system, neural crest cells - most commonly adrenal gland (but could be anywhere there is sympathetic innervation) - come from fetal neuroblasts. This is why you can get cord compression if it arises from the nerve roots near the cord. Assoc. w/ Beckwith Wideman (like WT) and Neurofibromatosis. Fetal exposure to phenobarbital, etoh, and diuretics associated Labs: Urine markers - HMA, VMA -- elevated in most patients. (extremely high sensitivity/specificity) serum ferritin often low Wide range from spontaneous regression all the way to widely metastatic and aggressive. These kids present and look SICK. Paraneoplastic syndromes - Opsoclonus myoclonus - myoclonic jerking movements and random eye movements. due to anti-neural antibodies - good oncologic prognosis, but late neurocognitive sequelae in >70%. - kerner morrison - intractable secretory diarrhea due to VIP secretion. - horner's syndrome - ptosis, miosis, anhydrosis - in IL face - Hutchinson's - limping and irritability due to bone mets - Pepper syndrome - massive hepatomegaly +/- respiratory distress - typically 4S infants. 1.5 Gy x 3 is dose. Workup: H&P CT and MR of primary (calcifications on imaging), CT Chest esp, staging MIBG*/PET, Bone scan, and b/l BM biopsies (all LEARN-NMR probably). MIBG is a neuroepinephrine analog *SSK-I Lugol solution to protect thyroid with MIBG scan. Parotids normally take up tracer, no significance. PET/ct often used now All patients get BM biopsy for staging INSS is older system 1-4S (similar to this) in picture for reference Simple staging (INRG) -- newer system (1-4 and 4S was old system) L1 = local resectable L2 = local not totally resectable (invading important structure) -- INSS system essentially broke this into contralateral type things like CL nodes or crossing midline M = mets MS = 4S, skin, liver, and BM mets (<1.5 year) - better prognosis, a large number spontaneously regress -- some say 1 yr. 35% regional LN and localized disease 70% are metastatic at presentation in age >1 but 25% if <1 yr. Really only need to know low risk and high risk - intermediate is very complicated Low risk - stage I (including Myc-N) - stage II (except worst stage II) - best 4S - FH, hyperdiploid, no MYC-N HIGH RISK N-Myc (age over 18 months) any stage IV (except 4S) worst stage II - MYC-N + unfavorable histology MS + 11q abberation Important genetics: N-MYC = BAD Prognostics: Good prog: Young age (<1.5 y, low stage, stage 4S, Hyperdiploidy, favorable Shimada, and NO N-myc amp). Shimada = SADMIND S = Stroma rich (Schwann cell stroma) A = Age young D = well Differentiated Mi = low Mitotic index Nd = Non-noDular Pseudorosettes (homer-wright) and neuritic processes common 3 histologic patterns in order of increasing differentiation - Neuroblastoma, Ganglioneuroblastoma, Ganglioneuroma stains = neuron specific enolase, synaptophysin, chromogranin A, neurofilaments N-myc BAD (25% of patients) - proto-oncogene on 2p - amplification usually defined as more than 10 copies Low risk - surgery +/- chemo Intermediate -- complicated -- probably surgery/chemo High - N-MYC, metastatic --> General Tx paradigms/Dose: - We mostly treat high risk patients -- metastatic with N-myc amplifications who are older than 1.5 years. - tx seq: 1. Induction chemo - DICCE x 6 cycles 2. surgery -- then MIBG re-eval, need to RT anything active here 3. high dose chemo x 2 with tandem transplants 4. RT (21.6 Gy @1.8's to residual disease, used to boost residual 36 Gy -- recent data showed no benefit to boosting) 5. Post-consolidation therapy with immunotheray and isotretinoin (differentiating agent)/immunotherapy - "IGD-2" Baby with a huge liver causing resp distress is pepper syndrome If this is not responding to chemo RT to whole liver, 4.5 Gy/ 3 fx at 1.5 Gy/fx, stay out of lungs, kidney, heart Cord Compression: < 3 yo, 9 Gy (1.8 /fx) ≥ 3 yo, 21.6 Gy (1.8 /fx) RT = 21.6 Gy = microscopic OR metastases (if CR after chemo, don't treat it) --- we stopped doing boost to 36 because there was no difference on the boost trial compared to historical control RT only for emergent settings for low risk disease typically don't do RT for intermediate risk - maybe in salvage settings.

Site: Pediatric HGG epi Workup: Important genetics: Prognostics: Dose: Misc. notes:

Site: Pediatric HGG epi = 12% of peds tumors, bad prognosis like in adults, 66% hemisphere, 20% diencephalic, 14% post-fossa/brainstem -20-50% will ultimately disseminate; Median survival 1-2 years, infants do better Workup: MR pre-op and <72 hrs post op. Important genetics: Prognostics: - extent of resection critical - WHO grade 3 better than 4 - site (central bad. lateral good - probably related to resectability) - Worse: MGMT Overexpression (not methylated) and H3.3K27M histone methylation - Better: IDH mutations, but less common in peds HGG. General Treatment Paradigm/Dose: - Surgery (radical resection) - XRT = 54-60 Gy, prolongs survival, improves symptoms - chemo = improves PFs and OS, but regimen unclear - CCNU, VCR, prednisone; TMZ not as good alone as in adults) They do slightly better than adults but still very bad prognosis (med survival 1.5- 2 yrs)

Site: Pediatric Hodgkin Lymphoma - Workup: - staging: - Deauville staging - Dose:

Site: Pediatric Hodgkin Lymphoma Workup: ---- H&P, CBC, CMP, ESR, CRP, LDH, pregnancy test, BMBx ONLY if cytopenias and PET/CT negative (otherwise PET is sufficient in HD) ----Imaging: US area of concern, CT N/C/A/P W contrast, PET/CT ----Pre-therapy considerations: TTE, PFTs, ECG, HIV/Hepatitis testing, Fertility counseling Staging: Ann Arbor staging (I = 1 nodal group, 2 = 2 nodal groups on one side of the diaphragm, 3 = both sides of diaphragm involved; 4 = diffuse metastatic disease both sides ----Just pick one system and know for now -- COG is what i'm going with here ----Picture showed all of the systems but for COG here is the best thing to remember ----low risk = IA and IIA ----intermediate risk = everything else (IB/IIB, IA+E/X, IIA+E/X); IIIA/IVA ----high risk = IIIB/IVB - Deauville staging: - DS1 and 2 considered CR 1 - no uptake 2 - uptake < mediastinum 3 - uptake >mediasintum, but < than liver 4 - uptake moderately higher than liver 5 - uptake markedly higher than liver or new areas of uptake

Site: Pediatric Hodgkin Lymphoma - general treatment paradigm - Low Risk chemo - Intermediate/High risk chemo What chemo is avoided in pediatrics and why?

Site: Pediatric Hodgkin Lymphoma - everybody gets chemo, then you assess response after 2 cycles, slow responders on initial PET and those without CR all will get ISRT This is written different ways for the chemo between low and intermediate/high, but remember the backbone is always AVPC for peds (rather than adult ABVD) - think PC for the pediatric children, not BD big daddies. LOW RISK CHEMO - AVPC x 3 --> PET Intermediate Risk - AVPC-BE x 2 --> interim PET --> AVPC-BE x 2 --> another PET High Risk - AVPC-BE x 2 --> interim PET --> AVPC-BE x 3 --> another PET Chemo list: - Adriamycin - Vincristine - Prednisone - Cyclophosphamide ------ - Bleomycin - Etoposide Alkylating agents like dacarbazine are avoided because of infertility and risk of AML (2nd malignancy generally). Bleomycin also avoiding because of pulmonary toxicity and infertility

Site: Pediatric LGG Epi Workup: -- Important difference between adult and children Important genetics: Prognostics: Dose: Misc. notes:

Site: Pediatric LGG Epi: The most common pediatric brain tumor (40%) two Grades - WHO grade 1 (pilocytic astrocytoma), WHO grade II (fibrillary, gemistocytic, and protoplasmic) -- somewhat more aggressive but all treated as LGG Workup: MR brain preop/prechemo fused to planning scan. Always scan the spine -- this is different from adult. Higher rate of leptomeningeal spread (33% in HGG and 15% in LGG) Important genetics: NF1 is VERY IMPORTANT IN DECIDING TREATMENT ASK FOR NF1 HISTORY IF MOCK CASE Prognostics: General Treatment Paradigm/Dose: If resectable - Maximal safe resection -- if GRT or even STR = monitor with MRI to determine pace of progression (or lack thereof) If unresectable - start with chemo (vincristine/carboplatin) -- delay RT for 3 years on average - When tumor progresses or after chemo -- RT is used and has a 70% control at 10 years (control better for optics, hypothalamic lesions than for thalamic) - DOSE = 50.4- 54 Gy HGG = resect and RT is standard Resection matters more for HGG in peds, if STR go back and second look surgery Chemo is controversial LGG = resect and try to avoid RT, even if STR only 50% progress Misc. notes: - psuedoprogression = relatively common in LGG

Site: Rhabdomyosarcoma Associated syndromes: Workup: Important genetics/path: Favorable vs Unfavorable sites: Dose: complicated - CG1 embryonal - CG1 alveolar - CG2 LN + dose - CG 3 gross disease dose <5 cm vs >5 cm at diagnosis - orbit dose Timing to RT = ? Misc. notes:

Site: Rhabdomyosarcoma Associated syndromes: Li-Fraumeni, Beckwith-Wiedemann, NF1, Noonan, and Costello epi - 3-4% of childhood cancer, peak 2-5 yrs. - cancer is 10% of childhood deaths, RMS is 4% of children deaths by itself Workup: - H&P - biopsy for genetics and histology type - CT CAP with contrast/PET scan; Most commonly go to chest, but go to LNs too so you need PET too. - Bone scan = not needed if you have PET - Parameningeal site = need CSF cytology + MR brain - b/l BM biopsy if alveolar or LN+ - RPLND if paratesticular if >10 yrs Important genetics/path: - FAVORABLE: Embryonal (50%)/Botryoid (FOXO1 neg) (6%) and Alveolar (FOXO1 +) - 20% ----> hyperdiploidy is good, LOH11p15.5 typically for Embryonal - UNFAVORABLE: FOXO1 translocation t(2;13) is most important (most common in alveolar, if alveolar doesn't have FOXO1 they act more like Embryonal) - t(2;13) --> fuses PAX3 to FOXO1 - t(1;13) --> fuses PAX7 to FOXO1 - 20% of alveolar don't have the FOXO1 fusion and they behave more like embryonal - both alveolar and embryonal overexpress IGF-II Favorable Sites - "BiONG" - Billiary - Optics - Non-parameningeal HN sites - GU (except bladder and prostate) Parameningeal sites - "MMNNOOPP" (only ~8% of total RMS but we treat a lot because they are typically not resectable) - Mastoid air cells - Middle ear - Nasal cavity - Nasopharynx - infratemporal fOssa - pterygopallatine fOssa - Parapharyngeal space - Paranasal sinus Unfavorable sites - "BLEPP" - BLadder - Extremities/Trunk - Prostate - Parameningeal sites - most common we see STAGING - based on location, size, nodes Grouping - based on how much is removed Risk group - based on both Pre-op staging: I = non-metastatic, any favorable SITE regardless of size or lymph nodes II = non-metastatic, unfavorable SITE < 5 cm and NO lymph nodes III = non-metastatic, unfavorable SITE >5 cm and/OR positive lymph nodes IV = metastatic Simplified RMS Clinical grouping - POST-OP/PRE-CHEMO CG I = GTR, no residual (R0), no lymph nodes CG II = GTR but R1 (positive margins - microscopic) (IIA) or resected positive lymph nodes (IIB) CG III = STR (R2), gross disease left, unresected positive lymph nodes (or chemo started BEFORE resection, this makes them CGIII by definition) CG IV = metastatic Risk groups: --Low risk = localized, embryonal (FOXO1 neg), any fav/unfav resected site (group I/II) as long as embryonal, favorable sites including CGIII if embryonal; If unfavorable site, need CGI/II to be low risk (meaning unfavorable, embryonal, gross disease isn't low risk) --Intermediate risk = ANY Alveolar, ANY histo if unfavorable site + R2 resection (CGIII) - gross disease --High risk = mets Highest rate of lymph node mets - paratesticular/bladder (25%) and prostate (42%) - anyone that's 10 yrs or older w/ paratesticular has to get RPLND Dose: Group 1 embryonal 0 Gy - NO RT Group 1 R0 negative margins but alveolar = 36 Gy Group 2A- microscopic - (R1) 36 Gy (if surgery done up front they are actually group 2A based on R1, if chemo --> group 3 delayed primary excision, R1 dose is 41.4) Group 2B- lymph node dose - (LN+) 41.4 Gy Group 3 - gross disease <5 cm at diagnosis 50.4 Gy Group 3 - gross disease > 5 cm at diagnosis 59.4 Gy --> 50.4 vs 59.4 actually depends on their response to chemo. If CR at 9 weeks of chemo, then you can drop the dose to 36 Gy actually; If <CR you treat based on what the pre-chemotherapy size was --> so if <CR you give 59.4 if they were 5 cm before chemo (regardless of current size; so a 10 cm mass that responded and shrunk to 4 cm would still get 59.4 whereas). ORBIT = 50.4 (technically can do 45 Gy if CR to chemotherapy first - NOT according to Dr. Brown). --ARST 0331 study --> orbital patients had a 11.5% rate of local failure w/ 45 Gy compared to prior failure of 4% on IRS-IV. --if no CR to chemo, 5 yr LF was 17%! --full dose cycophosphamide --> 50.4 = excellent control --osler says only do 45 if complete response to chemo. Timing = Low and Intermediate RT = 12 weeks post-op High risk = 20 weeks post op (more chemo first) Misc. notes: -Orbit and PM sites - no surgery. -CHEMO = VAC (vincristine, actinomycin, cyclophosphamide) - no actinomycin during RT

Site: Wilms tumor Workup: Important genetics: staging: Prognostics: Dose: Things to ask the surgeon

Site: Wilms tumor = Nephroblastoma 3-5 yrs. (median 3 yrs) 90% of pts survive 5 yrs after diagnosis w/ unilateral disease and favorable histology (even stage IV disease) - 12% multifocal and 7% are bilateral. Workup: HP, asymptomatic abdominal mass, abdominal pain, hematuria, abdominal enlargement, anemia, fever, hypertension abdominal US or CT CAP with contrast MR primary No biopsy up front - upstages them Bone scan if clear cell sarcoma variant MR brain if rhabdoid variant Important genetics/syndromes: 10-13% have one of these WAGR - Wilms, Aniridia (no iris), Genitourinary malformation, Retardation - deletion of 11p13 (1% of wilms pts) Beckwith Wiedemann - macroglossia, hemi-hypertrophy, wilms, omphalocele, exophthalmos, ear pits - 10% have deletion of 11p15 Denys-Drash - Wilms, Proteinuria in infancy, nephritic syndrome, progressive renal failure, male pseudohermaphroditism - llp13 deletion other mutations - WT1: 11p13 gene - WT2: 11p15 gene Survival with genetics: 5 yr EFS 5 yr OS 1p-/16q- - codeletion --> 84% 95% 1p-/16q+ 85% 92% 1p+/16q- 93% 95% 1p+/16q+ 70% 89% - gain of both is worst - LOH at these locations predicts for relapse and death - 1q gain is BAD Pathology -- Anaplasia and No anaplasia. Beyond that there are 3 typical cell types with varying mixtures - Epithelial, Blastemal, Stromal. It is best if there is a mixture of all three components (ie. "triphasic") Other important genes: POOR = LOH 1p + 16q and 1q gain; others = FWT1 (17q), and FWT2 (19q) **LOH 1p+16q is the important one. If they have this or anaplasia** -- can't skip whole lung regardless of response to chemo in setting of lung mets. Only favorable histology w/ lung mets included on that trial. The combination of LOH 1p+16q is associated with the worst outcomes Chemo: DD4A - doxorubicin, dactinomycin, VCR (only the vincristine is given concurrently) Staging Stage 1 = R0 complete resection, renal capsule intact, never biopsied or ruptured, limited to kidney, no involvement of the renal sinus/blood vessels. Simple protrusion of the encapsulated tumor into the renal sinus is still stage I. - Special case where chemo may be omitted: Stage 1 --> <2 yrs + <550 g kidney + FH Stage 2 = R0, can have regional extension beyond the capsule or invasion of the soft tissue of the renal sinus/blood vessels Stage 3 = R1/R2 (incomplete resection) - think B-SLURPPP (indications for WAI w/ essentially spillage) - biopsy - Spillage of tumor - LN's positive - Piecemeal removal of the tumor - Hx of a biopsy or rupture of the tumor - Hx of preoperative chemotherapy - Peritoneal penetration or implants - Tumor cells found in the adrenal gland removed separately - Extension of the primary to the IVC or heart Stage 4 = hematogenous mets to lung, liver, bone, brain, etc), any LNs outside of the abdomen/pelvis Stage 5 = Bilateral kidneys (earlier age, more likely to have congenital abn) UH = Unfavorable histology --> GETS RT regardless FH = Favorable histology --> stage III and up (MOST cases- 88% are FH) - triphasic histology with blastema, epithelium (tubules) and stroma components RT starts w/in 9-14 days of surgery Stage 1 - Surgery, No RT unless UH or relapse (RT flank boost - 1.8's) - osler guy says we dont do it for anaplasia in stage I....NTWS V didn't do it. 1/3 of diffuse anaplasia stage I patients relapsed on this study. Stage 2 - Surgery + chemo, No RT if adequate chemo as long as no UH or relapse, then locoregional RT (RT flank boost - 1.8's) Stage 3 - Do RT for SLURPPP (RT to whole abdomen @ 1.5's) Spillage -- WAI LNs + -- Flank Unresectable disease (R1/2) -- Flank Rupture (spillage) -- WAI Peritoneal seeding -- WAI Pre-op biopsy -- Flank Positive margins -- Flank Stage 4 Now per protocol typically giving chemo upfront, assess at 6 wks for lung response but still wait till finish chemo (25wks) → surgery → RT RT to primary site and whole lung RT to 12 Gy (At wake we tx lung and primary simultaneously - at 1.5's), (It would be exceptionally rare to have lung mets and not need primary tx) Stage 5 Consult tumor board, attempt chemo VAdActCyE and nephron sparing surgery first, let pathology then guide your RT decision Main 3 chemos esp if FH = Vincristine, Dactinomycin, Doxorubicin (DD4A) Complete nephro-urereterectomy with low ligation of the ureter to prevent future UTIs. These are basically all questions to assess for need for WAI Questions to ask the surgeon: 1. Did they assess the CL kidney 2. Was there spillage - they won't always tell you 3. Ask if they ran the bowel and felt for nodes 4. Did they do a piecemeal excision -- auto stage III and WAI 5. Did they assess bowel and peritoneum for mets 6. Ask if they felt along the aorta and "milk" the IVC for thrombus Doses: - Flank: 10.8 @1.8's ---> boost to 19.8 if diffuse anaplasia/rhabdoid tumor ---> boost gross residual disease +1cm w/ another 10.8 Gy (21.6 Gy) - WAI: 10.5 @1.5's - WLI: 12 Gy @1.5's (<18 months, gets 10.5 Gy) - 21.6 Gy @1.8 Gy if <5 mets - 30.6 Gy @1.8 Gy whole brain (if >5 lesions) - 25.2 Gy @1.8 Gy for bone mets Setup: - Superman position - frog leg w/ arms up w/ vac loc, need anesthesia - pre-op tumor volume + 1 cm and shave out all normal organs that have fallen into the post-op bed Constraint for CL kidney: <1/3 getting 14.4 Gy WAI Field Borders: - Superior: 1 cm above dome of diaphragm taking care to avoid excess heart dose - Laterally: Flash ribs by 1 cm - Inferiorly: To the bottom of the obturator foramen, blocking the femoral heads Flank Treatment - Contour the pre-operative/pre-chemo extent of disease and expand by 1 cm carving out of normal organs that have fallen into place - add 0.5 cm PTV Important Constraints: - limit 1/2 of uninvolved liver to 19.8 Gy, if mets 75% of liver <30.6 Gy Limit CL kidney to <14.4 Gy mean dose - treat all vertebral body on both sides to at least 18 Gy through whole body at involved level Note: clear cell sarcoma and rhabdoid are TOTALLY DIFFERENT histologies -- not types of Wilms tumor. They are just included in the WT studies since they are in the kidney.

What gene expression correlated with local recurrence more than distant recurrence?

Smad4 overexpression

General Tx Paradigms: 1. Small (<2 cm) or no/slow growth/elderly/ w/o Sx progression 2. If patient rejects observation, or is having symptoms, or > 2cm When is surgery 1st line over RT for acoustic neuroma?

Small (<2 cm) or no/slow growth/elderly/ w/o Sx progression Observation f/u audiometry and MRI scans q 6-12m W/ Obs only ~ 40% grew, ~ 50% stable, and 6% regressed spontaneously If patient rejects observation, or is having symptoms, or > 2cm: - RT (SRS or fractionated) or Surgery are viable options SURGERY preferred over RT ONLY if: - >4 cm -- associated w/ 100% hearing loss rate (vs 52% if <2 cm) OR - Causing severe symptoms OR - Recurrence/progression after RT

Treatment overview for cervix cancer based on stage stage IA1 LVSI- (microscopic) stage IA1 LVSI+ (microscopic) stage IA2 (microscopic) stage IB1-IIA1 (upper 2/3 vagina involved <4 cm) stage IB3 (>4 cm), IIA2 (vagina + >4 cm), IIB (parametrium), III (lower 1/3 vagina, hydro, pelvic sidewall or nodes), IVA (adjavent organ)

So basically think size >4 cm, parametrial involvement and up - needs chemoRT + brachy Typically I think of vaginal involvement as RT - but I guess if <4 cm, can still consider surgery, but really goes back to the old Itialian study that showed worse outcomes if >4 cm with surgery.

Current Wilms treatment guidelines if Unfavorable histology

So here he says RT or any anaplasia even stage I which is correct. NWTSV didn't for those and a lot of them failed

Where do you get life expectancy from?

Social security actuarial life survival tables you can look up for specific ages https://www.ssa.gov/oact/STATS/table4c6.html Rules of thumb: 62 yr = 20 yr, 77 yrs = 10 yr

Solid 5 mm nodule is seen on LDCT in a high risk patient, what should be done?

Solid lesions, 8 mm or any growing nodule is where you start to worry

Major two scoring systems for AVM?

Spetzler-Martin = Surgical Morbidity Pollock Flickinger = Chance of excellent outcome w/ SRS Components of Spetzler Martin score? Diameter - <3 cm = 1; 3-6 cm = 2; >6 = 3 Location - Non-eloquent = 0; Eloquent = 1 Venous draining patterns - Superficial = 0; Deep = 1

How does spinal ependymoma compare to brain ependymoma?

Spine ependymoma is almost like a different disease much more benign If able to achieve GTR then you are done. Generally easy to get GTRs and Cure rate ~ 90% If STR could argue RT or actually could even argue for observation but LF is much higher with STR, so not unreasonable to do RT to 54 Gy Would NOT do the whole spine, just a 1 cm margin (old school did 2 vertebral bodies around it, but Chan just does 1 cm margin) These tend to have a long natural hx

Is surgery necessary in esophagus

SqCC appear to benefit a bit less than adeno Monjazeb study (WF) - showed that in patients with negative PET scans after therapy showed no difference in survival associated with surgical resection

Anal histology

Squamous cell vs adenocarcinoma vs other

Seminoma - this is where RT is more relevant - treatment options - stage IA pT1 - pT3

Stage 1 is any T and node negative (S1-3 is IS) 1. Strongly Preferred is surveillance 2. single agent carboplatin (AUC = 7 x 1 or 2 cycles) 3. RT (20 Gy or 25.5 Gy) Generally if patient is unreliable and won't come back for surveillance, consider chemo or RT in those patients.

Prognostic staging differences for OP for p16 postive

Stage I is up to T2 and N1 (any number of <6 cm IL nodes) Stage II needs at least T3 or N2 Stage III needs T4 or cN3 (no pN3) Only M1 is Stage IV in HPV positive cancer Path staging makes this more complicated as in T4 can be as low as Stage II if pN0. Just worry about clinical for now and look up path staging

Who should get chemo after surgery for NSCLC

Stage IB is the cut point - nobody at 1B or below will get chemo (T1a,b,c,2a - no chemo). Adjuvant chemo --> T2b (>4 cm - stage IIA) or N1 (stage IIB)

Locally advanced breast cancer includes which groups?

Stage groups IIIA - C - T0-2N2, T3N1-2, T4 N0-2 including inflammatory or any N3 - unresectable non-metastatic - inflammatory - skin/chest wall involvement Not hard to defend doing PMRT in these people -- the data you have to know is for N+ people not considered to be locally advanced (so data for LN+ 1-3 nodes)

Standard Treatment for Stage II -- cervical stromal involvement

Standard = EBRT and/or brachytherapy This comes from the GOG 249 study

Pancreas SBRT - ideally plan gold fiducials to monitor position during treatment - tumor +2-3 mm margin - need 4D to account for margin Stanford series - 3 pts at 15 Gy, 5 pts at 20 Gy and 7 pts at 25 Gy - stopped at 25 Gy - used fiducials - breath hold technique done - 50% IDL on duodenal wall adjacent to tumor Demark series - did 45 Gy in 3 fractions Stanford also did a SBRT boost in pts getting 45 Gy to initial volume -decent outcomes.

Stanford Found no G3 toxicity 100% LC in evaluable pts Found no DLT Pic shows the collaboration pancreas protocol sbrt overview

RTOG 0937 - GORE trial - took pts and randomized to 45 Gy/15 + PCI vs PCI alone - study was closed unfortunately because there were poor outcomes in the thoracic RT group -- failure rate was lower, but the toxicity and survival was worse in the thoracic RT group.

Steven Lin says 30 Gy is standard, but can consider in a small number of good PS patients with small volumes

Rectal Cancer Anatomy - defined as upper, middle, and lower - 15 cm long - 5 cm segments for each - levator ani made up of what three parts?

Strep bovis and clostriudium septicum occurs in 10-25% of patients with rectal cancer. Levator = 3 parts = iliococcygeus, pubococcygeus, and puborectalis muscles

Most of our data about PMRT and RNI comes from what?

Studies where upfront ALND was the standard approach with older chemo and radiation. So now most of our approach is changed by Z11 and Amaros because we don't need to do completion ALNDs anymore -- so we don't know the true number of nodes with a +SLNB in 1 node

GHSG - HD14 - stage I and II unfavorable - randomized to ABVD x 4 + 30 Gy RT vs BEACOPP x 2/ABVDx2 + 30 Gy Essentially trying to give some BEACOPP but less and supplment with a little ABVD. results?

Study closed early becasue FFTF was better in the 2+2 arm Os was not different Still BEACOPP is not widely used because of the toxicity

Majority of vulvas first lymphatic drainage is to which nodal group?

Superficial inguinal

Lymphatic drainage of the rectum

Superior Half of rectum - peri-rectal - presacral/sacral - sigmoidal - inferior mesenteric Inferior Half of the rectum - peri-rectal - internal iliacs Lower rectum and anal canal - peri-rectal - internal iliacs - superficial inguinal nodes Note T3/4 you have to move the anterior border in front of the pubic symphysis to cover the external lymphatics

Anatomy - proximal zone from top of puborectalis to the dentate line Two parts to anus - anal canal - mucosa lined - anal margin - epidermis lined --> treated like a skin cancer - not treated w/ chemoRT like anal canal........ Superior border = ? Inferior border = ?

Superior border = begins when the rectum enters the puborectalis sling at the apex of the anal sphincter complex Inferior border = ends at the squamous mucocutaneous junction with the perianal skin - anal verge is the point at which the hair shafts are seen

Define borders of the posterior fossa

Superior: Cerebellar tentorium Anterior: Clivus Lateral: Bony occiput and temporal bones Inferior: Foramen magnum/top of C1 Note PF boost takes the WHOLE brainstem to near tolerance

What is the benefit of an incline breast board

Supine on breast board 10-15 degree, angled so gravity will push breasts inferiorly and line sternum parallel to couch. Head turned away from Tx field Why do we use a breast board? - It brings the chest wall parallel to the treatment couch

Sim setup

Supine, arms at side, neck extended (if larynx) Thermoplastic long mask +/- arm straps to pull shoulders back Oral devices - dental trays, bite wings, custom mouth guards -- protect mucosal surfaces from ulceration due to scatter radiation from fillings, or to hold tongue down if oral tongue cancer (tubular bite block) CT scan head and neck - boards answer with IV contrast - 2 mm slice thickness

Larynx - anatomically divided into what three anatomic boundaries?

Supraglottic Larynx - FAVE - Epiglottis -Ary-epiglottic folds - Arytenoids - False cords Glottic Larynx - apex of the laryngeal ventricle to just below the cords - true vocal cords Subglottic Larynx -from just below the cords to the bottom of of the cricoid

What is taken w/ supraglottic laryngectomy? What are contraindications?

Supraglottic laryngectomy What is taken: Epiglottis Aryepiglottic folds FVCs Upper 1/3-1/2 of thyroid cartilage Hyoid (if pre-epiglottic space involvement) Preserves 1 or both arytenoids & both TVCs Contraindications Exo Laryngeal spread Fixation Arytenoids inv. < 3 mm b/t tumor - ant commissure Thyroid/cricoid cartilage inv. Inadequate PFTs (high aspiration risk)

Describe the surgery performed for WILMS

Surgeon removes tumor and ipsilateral kidney with low ligation of the ureter (helps to follow the distorted anatomy) and careful attention to not rupture or spill tumor. This should not be piecemeal. Sample any suspicious nodes and inspect the contralateral kidney.

Patchell - Cord compression - rct, 101 pts - max decompression surgery + RT vs RT alone (30/10) - which was better - inclusion was radiological MESCC - true displacement of the spinal cord by epidural mass + 1 neurologic sign + >48 hrs of paraplegia + >3 months survival expected - excluded multiple non-contiguous levels of compression, compression of the cauda equina or nerve roots, radiosensitive tumors (MM, leukemias, etc)

Surgery + RT better than RT alone - primary endpoint was ambulatory rates (84% v 57%, SS) - better continence, muscle strength functional ability, need of steroids, opioids - median survival was 126 days vs 100 days Basically every metric favored surgery + RT

NCDB database - Stokes JCO 2018 - comparing surgery (76,623) v SBRT (8,216) - results?

Surgery had higher 30 and 90 day mortality particularly in elderly early stage NSCLC - >70 yo pts specifically in 30 and 90 day - this mortality isn't seen in SBRT

Glomus tumor treatment? How does RT work on glomus tumors? Expected outcomes?

Surgery if brainstem compression Or young w/ functional CN loss (can have significant morbidity though) SRS 16 Gy, mostly retrospective, LC >90% Fibrosis of feeding vessels - not direct glomus cell kill ⅓ shrink, ⅔ no change 50% w/ clinical improvement ~10% further growth If below the lvl where you can treat with GKRS, can treat fractionated with 45 Gy/25 fxn @1.8's (Red Journal paper reports 100% LC, KG says >95% LC)

Adjuvant Therapy in Pancreas Cancer - EORTC trial - RCT of 5-FU-CRT vs observation in resected pancreas pts - RT same as GITSG trial - No adj 5 fu here - more pts than GITSG - 218 pts (T1-2N0 pancreatic and T1-3N0 ampullary) - results?

Surgery v CRT Median OS - 12.6 v 17.1 (NS) 2 yr OS - 26 v 34% (NS) 5 yr OS - 10 v 20% (NS) So bigger trial than GITSG was negative. No diff in LRR Criticism of EORTC trial - T3 lesions excluded for pancreas - Path distinction between ampullary and pancreas not clear - RP margin not independently assessed - 20% of CRT pts did not get treatment - No PP analysis done of treatment patients actually treated with CRT - No adj chemo - Study lacked sufficient numbers to see benefit - likely underpowered - fu times not mentioned - one sided log rank test was significant at 2 yrs (p = 0.049)

G3 anaplastic treatment paradigms

Surgery → RT to 59.4 Gy in 1.8 Gy/fx +TMZ (doses below concurrent then 1 m break then 6 cycles adj) Take T2 flair to 59.4 CTV = 1 cm, PTV = 0.5 cm

Take home for salivary cancers? General tx paradigm? Post-op RT indicated? Role of chemo?

Surgical disease unless unresectable Post-op RT indicated for: - high grade - close or + margins - PNI (all adenoid cystic cases -- they all have PNI - lymph node involvement - recurrence - tumor spillage Role of chemo NOT well defined.

Extent of resection in HGG Benefits to additional resection?

Surgical intervention before RT improves outcomes Gives you tissue for molecular analysis detect oligodendro components improved neurologic function if its a mass effect decreased epileptic risk increased OS when >90% of tumor is removed - facilitates adjuvant tx

Low Risk Prostate Cancer - treatment options?

Survival >20 yrs 1. Active surveillance (preferred for very low and low risk) 2. Brachy monotherapy 3. EBRT (less ideal if pt age <65 yrs - higher risk of 2ndar malig) 4. Prostatectomy If survival is 10-20 yrs -- supposed to only do AS If survival is <10 yrs -- watchful waiting

High risk MB - Phase II study - 161 pts - M+ disease - weekly vcr during rt - adds daily carboplatin during rt - 36 Gy CSI and 55.8 Gy to entire PF - + adjuvant chemo

Survival shown here. If you broke it down by anaplasia - there was clear separation between OS based on just anaplasia

RTOG 0617 - 544 pts - tested 60 vs 74 Gy +/- cetuximab - results?

Survival worse with 74 Gy and cetuximab didn't help anything IMRT improved outcomes compared to 3d (50:50 got each) - IMRT had bigger volume of disease compared to 3d (negative selection) but no difference between survival G3 pneumonitis risk was lower in IMRT group (this is why IMRT is standard for locally advanced)

Standard of care therapy for stage III/IV disease?

Systemic therapy +/- EBRT +/- vaginal brachytherapy

Analysis of a nominal independent variable and a continuous dependent variable

T test or anova

Larynx Treatment Paradigms? T1 and T2 on this card

T1, T2, T3, and T4 all have very different approaches T1-2: Radiation vs Cord stripping - XRT preferred unless very superficial - T1 = 63 / 28 fractions using opposed laterals (contour the cords, spinal cord) - typically is a 5x5 or 6x6 box around the larynx to ensure appropriate coverage of the vocal folds. - T2= 65.25 Gy/29 fractions (add a fraction) vs 68-70/34-35 - T2b selected cases may benefit from ChemoRT We typically do 3D but the question in the field is 3D or IMRT for carotid/skin sparing? Borders of T1 Larynx: Larynx opposed lateral wedge paired field - sup: top of thyroid cartilage - post: ant edge of vertebral bodies - ant: anterior to thyroid cart -- usually flash skin, may need bolus to cover anterior commissure - inf: bottom of cricoid cartilage (for T2 would extend to first tracheal ring below cricoid)

Dose and fields for T1 vs T2 larynx?

T1: Dose: 63 Gy in 28 fractions (@2.25's) Fields: Classically 5x5 cm field - Superior: Top of thyroid cartilage - Posteriorly: Ant. edge of vertebral bodies - Inferiorly: Bottom of cricoid cartilage - Anterior: anterior to the thyroid cartilage - flash skin possibly bolus to get dose to AC T2: Dose: Add a fraction -- 65.25 in 29 fractions (@2.25's) Fields: Same except extend field inferiorly to 1st tracheal ring below cricoid (classically 6x6 cm) and superior is to hyoid bone (some say 1 cm above thyroid notch) Always adjust field size based on patient anatomy, not soley based on size.

5 yr OS for larynx cancer?

T1N0 = 70% T2N0 = 60% T3 or N1 = 50% T4 or N2 = 35-40%

Briefly: T Stage T1a T1b T1c T2 T3 T4a T4b T4c T4d N Stage N0 Ni+ Nmi N1 N2 N3

T1a = 0-5 mm T1b = 5-10 mm T1c = 10-20 mm T2 = 20 - 50 mm T3 = >50 mm T4a = direct extension to the CHESTWALL not including the pectoralis muscles T4b = satellite nodules, edema (Peau d' Orange), and ulceration T4c = Both A and B T4d = Inflammatory (more about having T4c characteristics but the timeline is development in <6 months -- rapid onset; neglected locally advanced BC is different entity) N0 = node negative TREATED AS NODE NEGATIVE Ni+ = isolated tumor cells <0.2 mm (<200 cells) Nmi = 0.2 - 2 mm TREATED AS NODE POSITIVE N1a = 1-3 ax nodes N2a = 4-9 N3a = >10 nodes, infraclav N3b = internal mammary N3c = Infra/supraclav If any nodes have macromet, then all nodes count toward number even if micro met in that node. Prognostic stage grouping is super complicated now incorporating t, n, m, oncotype, ER/PR status, Grade (required)

Neoadjuvant therapy - idea is based on sparing the sphincter - some data suggests that rt with local excision for T1-2 tumors may offer survival rates comparable to APR - pre-op chemoRT helpful for larger and more invasive tumors to promote tumor regression to convert a planned APR into a LAR What are the indications for neoadjuvant therapy?

T3-4 tumors - T3 w/ threatened radial margin (<2 mm) - T3 with >5 mm penetration - Mesorectal invasion - any T4 Positive Lymph nodes Distal tumors (would need APR unless you can get LAR after neoadjuvant) Biological and clinical advantage over adjuvant - better tissue oxygenation - better target delineation - better tolerability - response assessment possible

Meningioma imaging findings - CT? - MR? - Angiography? - Octreotide scan

T: hyperdense and uniform enhancement MR: gadolinium enhancing, isointense on T1, hyperintense on T2 Angiography: tumor blush Octreotide scan: can help distinguish scar from residual - remember high concentration of somatostatin receptors Image is T1+gad showing enhancing lesion with dural tail

What is the target in AVM with GKRS?

THE NIDUS ONLY Do not target the feeding arteries or draining veins.

What are the Heaps factors for vulvar?

THESE ARE THE MOST IMPORTANT FACTORS FOR LOCAL RECURRENCE STAGE MARGIN DEPTH GROWTH PATTERN VASCULAR INVASION KERATIN AMOUNT MITOTIC ACTIVITY

TIME-C trial --> this included cervix and endometrial post-op patients - randomized to four field box vs IMRT - looked at toxicity - found what?

TIME-C trial - think Time = Toxicity trial - mean EPIC bowel score declined less in the IMRT group - 23.6 points in the standard RT group and 18.6 points in the IMRT group (P = .048) - mean EPIC urinary score declined less in the IMRT group - declined 10.4 points in the standard RT group and 5.6 points in the IMRT group (P = .03) - At the end of RT, 51.9% of women who received standard RT and 33.7% who received IMRT reported frequent or almost constant diarrhea (P = .01) - More patients who received standard RT were taking antidiarrheal medications four or more times daily (20.4% v 7.8%; P = .04).

How is TMZ given?

TMZ is given as an oral pill 7 days/wk - 75 mg/m2 concurrent w/ RT → 1-mo break → 6 cycles adj - TMZ 150 mg/m2 give 5 d of every 28 d

Major chemo for LGG?

TMZ or PCV

Toxicity of GKRS for TN

TOXICITY (same for MS patients) GK Numbness but NOT bothersome = 25%, rhizotomy numbness 60% (⅓ persistent) GK Numbness that is bothersome = 2% Anesthesia dolorosa Severe numbness that actually hurts inside the numb area with constant burning/aching 0.25% or 1 in 400 w/ GK, increases to 4% w/ rhizotomy (potentially tx with a motor cortex stimulator, stimulates at a subclinical lvl, distracts the brain from pain)

Who do we treat with GKRS for TN? Medical management?

TREATMENT OPTIONS: Generally we don't treat w/ GK unless > 70 yo, unless they have MS, then we treat young patients upfront because surgery won't help there Medications: Always 1st line 80% response rate Commonly if put in remission then can taper off of meds and see if they stay in remission Tegretol "Carbamazepine" is most effective, (usually 200 - 1200 mg daily) however all of the antiepileptics cause drowsiness, dizziness, anxiety, loss of motivation Oxcarbazepine "trileptal": Similar efficacy to tegretol, but less side effects (if tegretol has too many side effects then try oxcarbazepine, usually 600 - 1800 mg/day) Baclofen, Gabapentin ( 300mg TID, used in elderly pts, least toxicity) Benzo's

Optune - how does it work? - mechanism? - PFS and OS benefit?

TTF = Tumor treating Fields - EF14 study - Antimitotic Mechanism ○ Delivers low intensity, 200 kHz alternating electric fields through transducers applied to shaved scalp ○ Disrupts mitotic spindle formation → mitotic arrest → disrupting cell division → apoptosis Suspected synergistic effect lead to Phase III randomized controlled Jama trial [Stupp 2015] ○ TTF w/ TMZ vs TMZ alone ○ Interim analysis showed improved PFS and OS with TTF + TMZ ○ Increased med PFS by 3 months, Increased med OS by 5 months (more of an effect than TMZ+rads in 2005) Generally, starts within 4-7 weeks of last CRT fraction. Lasts >18 hrs/day for 9 months median duration.

Endometrial cancer work up

TVUS Hysteroscopy Endometrial biopsy CT CAP Pelvic MRI (especially for medically inoperable)

SWOG 8736 NHL (Spier 2006) - stage I and non-bulky stage II pts randomized to --CHOP x3 + RT (45-50 Gy) -- CHOP x8 - NON-rituximab era Initial report results? Updated results?

Take home here is that 5 yr PFS and OS was better with 3 + RT than 8 cycles CHOP. Important to know that this is the only study to show OS benefit with addition of IFRT for early stage NHL HOWEVER - PFS and OS benefit were BOTH lost on the long term median 17.7 y follow up - 3C + RT still winner with less toxicity - the 8c CHOP arm did have a higher rate of cardiovascular death however - med OS 13 vs 13.7 for 8 v 3+RT So the standard is still CHOPX3 + RT

AS trials - what is take home point? - details in pic

Take home is that PCa specific survival is like 98-100% survival And only 33-50% will need intervention w/in 10 yrs so you can delay symptoms from treatment

CALBG 9633 - Talked about it earlier in context of SABR for operable - 344 pts with Stage IB - 4 cycles of carbo/taxol vs obs after surgery - RT was NOT allowed - shows what?

Take home is that it initially showed a benefit at initial analysis but this was lost on subsequent analysis So no OS benefit. Chemo NOT recommended in stage IB because of this Unplanned subgroup analysis showed benefit if tumor was >4 cm -- suggests that T2b tumors benefit (stage IIA) --

Mechanism of action of tamoxifen, arimidex, exemestane When should these be used, pre vs post menopause, or does it matter

Tamoxifen = SERM = Premenopausal AI = post menopausal - blocks androgen conversion to estrone/estradiol Nonsteroidal: Femara Steroidal: Exemestane

Inflammatory fractionation

Technically standard of care is still 50 Gy/25 fractions w/ 10 Gy in 5 fraction boost to the scar. Alternative -- and what we do at WF (DB) MD ANDERSON DOSE 51 Gy in 34 BID fractions; boost to 66 Gy (15 Gy/10 BID fractions) to the scar plus margin Generally management must always include neoadjuvant chemo (based on markers), always modified radical mastectomy w/ ALND and NO reconstruction prior to RT, always gets RT. BID regimen is MD Anderson fractionation. Statement on Bolus from MD anderson: "Tissue equivalent bolus (3- to 5-mm thick) was placed on the chest wall every treatment for the first 10 treatments, every other treatment for the next 10 treatments, and then as needed based on the clinical response of the skin overlying the chest wall. The goal of the bolus schedule was to cause brisk erythema with dry desquamation, which we had reported previously to correlate with the highest probability of LRC" Increased G3 tox skin, lymphedema, fibrosis, brachial plexopathy

DIPG = special kind of HGG = diffuse intrinsic pontine gliomas

Terrible tumor short interval of symptoms Generally diagnosis made radiographically, used to say couldn't biopsy, but some places like MSK do it for genetic testing. think H3K27M mutations (80-90% of cases have this mutation) -- bx may be done to determine eligibility for study - 50% low grade, 50% high grade tumors Median time to death 8-12 months Tx with 54 Gy/1.8 Gy/fxn -- concurrent chemo may be given but not really helpful. . - alt dose = 39 Gy in 3 Gy fractions (hypofrac really to spend less time in their life - randomized data non-inferiority out of Egypt -- it was NOT non-inferior but the actual difference wasn't very much so considered reasonable) RT gives some relief of symptoms, but median progression typically w/in 6 months 80% diffuse, 20% are focal (<50% of brainstem, <2 cm, well circumscribed) These present typically with CN palsies, ataxia, head tilting, difficulty swallowing Without RT - they would die w/in weeks to months after diagnosis. - tons of things have been tried and nothing really helped.

RTOG 9802 - Shaw 2012 - p3, 362 pts - low risk --> observe - high risk (STR OR age >40) randomized to 1. RT alone or 2. RT followed by 6 cycle PCV - results? - toxicity?

The "SATAN" risk factors went out the window in RTOg 9802 -- just used STR and >40 years old. - <40 + GTR = low risk - everyone else was high risk (<40 with STR or >40 with any resection) RESULTS - Essentially, benefit was seen with PCV (and probably represented 1p19q people) - median OS 7.5 yrs RT alone; not reached in PCV. - 5 yr OS rates 63% (RT) v 72% (RT+PCV) - not SS - 5 yr PFS rates 46% vs 63% - SS -- OS and PFS curves started to separate after 2 yrs Weird analysis done - they essentially said there wasn't a difference w/in 2 yrs in OS or PFS - so they did an analysis where they looked at people that survived 2 yrs and said that if you survived 2 years, the probability of an additional 5 yrs of survival was 74% vs 59 % (PVS vs without PCV) (SS). - in other words, this suggested a "delayed" benefit to chemotherapy Buckner et al 2016 -- updated results of 9802 "aged like a fine wine" UPDATED results w 11.9 yrs median follow up - median OS ---RT+PCV = 13.3 yrs ---RT alone = 7.7 yrs 5 yr and 10 yr OS - 72% and 60% (RT + PCV) 5 yr and 10 yr OS - 63% and 40% (RT alone) - it tends to be very hard to tolerate with >50% w/ G4 neutropenia - so we tend to use TMZ more often. Procarbazine 7mgm2 oral, Lomustine 130 mgm2 oral, Vincristine 1.4 mgm2 IV: 4 Cycles q 6 weeks Has PFS and OS benefit -- especially in 1p19q codel -- Shaw RTOG 9802 The treatment effect was largest in the oligodendroglioma. This implied there was a group of G2 patients that don't benefit from chemo.

More about Z11 What are some caveats?

The ACOSOG Z-11 trial enrolled women with T1-T2 clinically node negative breast cancer who underwent breast conserving surgery and SLNBx with 1 or 2 positive nodes. - They were randomly assigned to axillary dissection or no further surgery. All patients subsequently received whole breast RT in the supine position, likely encompassing the low axilla in the tangent fields. - Axillary dissection increased morbidity (notably lymphedema risk) without improving any oncologic endpoint. CONCLUSION: Therefore, axillary dissection should be omitted for women receiving RT. Also, results from the MA-20 and EORTC 22922 suggest that the addition of regional nodal irradiation in the setting of node-positive breast cancer improved disease-free survival and reduces breast cancer death and should therefore be strongly considered. Other caveats: - 46% of +SNs were micromets - only 27% of pts undergoing ALND had additional LNs involved - radiation fields were NOT centrally reviewed (so patients that had a +SN probably had "high tangents" so the rad oncs might have been more generous to treat those Ln areas even tho it was "breast only" radiation - Z11 applies to BCT only So overall Z11 essentially says you don't need completion dissection and kind of argues you don't need RNI for SN+ only patients. However with the strong caveats above. Other data specifically supports use of RNI in 1-3 LNs + patients (MA20 and EORTC 22922)

Partial breast data

The basis for partial breast is that the majority of recurrences occur close to the tumor bed. APBI is different from IORT -- volume coverage for APBI is a minimum of 1 cm around the lumpectomy cavity. TARGIT IORT - 25% of Rx at 1 cm (5-6 Gy) - so gives much less dose to the same volume as other forms of APBI. 3D techniques: RAPID: 2135 pts, >40 yrs, IDC or DCIS, APBI was non-inferior to WBI - 38.5 Gy bid NSABP-B39 - Whole breast vs APBI 34 Gy in 3.4 Gy bid x 5-7 days mammosite OR 38.5 Gy in 3.85 bid x5-6 days 3D conformal - DDFI, OS and DFS not SS different from WBI. - APBI was deemed inferior to whole breast in this trial (4.6 v 3.9% diff - so less than 1% difference, but based on their stats, this was still a negative trial IMRT: Florence trial

Difference between a cohort study and a cross-sectional study in terms of prevalance vs incidence?

The cross-sectional study (prevalence study) takes a sample or snap shot of a given population at a particular time so the prevalence of a condition can be determined - (number of people w/ a given risk factor who have a disease vs do NOT have the disease) however, the incidence CANNOT be determined from a cross-sectional study. This is in contrast to a cohort study where two cohorts of people are followed on the basis of a risk factor to determine the incidence of a disease w/in the two populations (thus allowing determination about relative risk)

GOG33 study that showed the risk of LN involvement based on myometrial invasion and Grade of disease Important to know this table

The diagonal line shows you that with increasing grade, there is a higher rate of lymph node mets that is essentially equivalent to outer one third myometrial invasion for low grade disease Risk of LN involvement is ~10% therefore for three groups: - low grade w/ outer third invasion - grade 2 with middle one third invasion - grade 3 with inner third invasion Thus anything to the left of that line is <10% and anything to the right (higher grade w/ higher depth invasion) is >10% up to ~30% for G3 outer 1/3 invasion

Post-op treatment of musculocutaneous flap - is the flap at risk for recurrence? - how is this targeted?

The flap came from a different part of the body and has no cancer cells for sure - thus it isn't the target; however, the CTV needs to include the entire flap + about 1 cm margin plus any clips to make sure the entire surgical bed is encompassed. The flap itself isn't at risk for recurrence, but the highest risk tissues are adjacent to the flap-normal tissue interface Remember Nancy Lee -- if the surgeon looked at it, include it.

Advanced stage low grade NHL treatment overview

The idea here is these are often slow growing and they may be able to be watched if asymptomatic

Hazard ratio = ?

The likelihood of an event occurring in the treatment group relative to the control group HR < 1 = treatment arm has lower event rate than control arm HR > 1 = treatment arm has HIGHER event rate If 95% confidence interval crosses 1, this means the result is NOT significant - p value will be >0.05. Note: Difference in HR and RR is very small - RR considers time factor in following risk whereas HR looks at risk of in Exposure vs control at some point in time. RR follows a group and says the risk of developing disease based on exposure in a cumulative sense -- it is typically calculated at the end of a study. RR and HR are typically very similar. HR, in contrast, is a measure of the instantaneous risk of an event occurring, usually during a subset of a total study period. *Remember the adenoma question in Uworld* -- they graphically representing decreasing HR's as quintiles of physicians performing colonoscopy -- those in the 5th quintile, had the lowest HR (meaning that the event of CRC was least likely in their treatment group)

Statistical power = ? How is this increased?

The likelihood of avoiding Type II error. Low power = higher chance of having to say the groups weren't different when they were. Increase in sample size increases the power of the study.

Take home points and three most important papers for hyperfractionation?

The moral of the story for hyperfrac is the 1 and 2 below showed benefit of accelerated or bid fractionation BUT was only in the context of RT alone. When compared in setting of concurrent chemo in RTOG0129, there was NO difference in accelerated or bid fractionation. #1 RTOG 9003 was 4 arm RT only prospective trial that compared 3 hyperfrac arms bid arms with once daily control arm -- early on showed improved LC with pure hyperfrac and concom. boost arms and improved OS with pure hyperfrac arm (lost with later follow up) - essentially these were equivalent - no OS benefit Another HN altered fractionation trial -- all RT alone Standard: 70 Gy in 35 - 7 weeks Hyperfractionation: 81.6 in 68 bid fractions - 7 weeks Accelerated fractionation with split course: 67.2 Gy bid with 2 week break after 38.4 Gy Accelerated fraction with delayed concomitant boost: 72 in 42 fractions - partial BID (twice daily during last 12 fractions) 2 yr numbers: LRC better with HF and DCB arms (SS) HF had better LRC and OS The local control benefit was no longer statistically significant with longer follow up. This made accelerated fractionation standard however in the pre-chemoradiation era #2 DAHANCA trial - compared 5 vs 6 fractions per week. Showed improved SS LC with primary site for 6 fractions. 6 was more toxic but didn't use chemo. - no OS benefit - LRC improved by ~10% - if you think about hyperfrac- - think about 6 fractions per week #3 RTOG 0129 - compared once daily with concom. boost accelerated RT with concurrent cisplatin. - NO benefit if concurrent chemo was used. RTOG 0522 -- another conc. boost or 6 per week -- negative trial CHART trial - extreme hyperfractionation - 54 Gy/36 bid -- 10 yr outcomes no difference in LRC, DFS or OS - suggestion that high EGFR expression did better with CHART TWIST analysis - showed quality adjusted life analysis - showed benefit for hyperfrac only

Recent study - ACNS1123 for NGGCT - 6 cycles Carbo/Etop alt w/ Ifos/Etop - If CR/PR --> RT 30.6 Gy WVI + 23.4 Gy boost (54 total) - PR/SD --> second look surgery, if mature teratoma/fibrosis, remove. - RT did not include CSI --> what was the result?

The study was closed to accrual because SPINE FAILURES WERE HIGHER THAN EXPECTED Result = you can't drop CIS for NGGCT -- all patients NEED CSI

Important to think about what route of spread/failure from the tonsillar pillars?

The tonsillar pillars run to the pterygoid plates so that area is generally covered all the way to the plates

Time of RT in SCLC - meta-analysis (Pijls-Johannesma) showed what?

There is a survival advantage to starting RT w/in 30 days of chemotherapy compared to late start of RT. In order works, after 1 cycle (3 week cycle) you should be starting RT. This is why we say we want to start w/in 30 days. Overall the shorter the duration from the start of any treatment to the end of RT -- data suggests survival at 5 yr is better

Comparison of surgery vs xrt in Ewings

There is no data to suggest surgery is better than RT

TMZ in LGG instead of PCV?

There is no upfront randomized trial of TMZ vs PCV yet PCV is extremely toxic and most patients can't complete the whole course. TMZ better tolerated

Does heart dose matter? What are your heart constraints?

There is some data saying V50 was an independent predictor for worse overall survival. The ASTRO speaker recommended V50 < 25% NCCN recs V40 < 80 V45 < 60 V60 < 30 Mean < 35 (this seems very liberal shoot for 26) Other people's constraints for Heart V30 < 50% Mean dose < 20 Gy (OSLER STEVEN LIN)

EORTC/LYSA/GELA H10 - confusing randomization Has Favorable and unfavorable patients - Favorable --> everyone got ABVD x2 --> PET scan --> standard was to get another cycle of ABVD + INRT -->PET negative --> 2 cycles ABVD -->PET positive --> 2 cycles BEACOPP + INRT (this was essentially the 2+2) - Unfavorable --> everyone got ABVD x 2 --PET scan -->standard was to get 2 more ABVD + INRT --> PET negative --> 4 more cycles ABVD --> PET positive --> 2 cycles of BEACOPP + INRT EORTC risk - main difference is that age 50 or older also makes you unfav Negative pet was considered a D1-2 -- wanted to make sure they were getting the most low risk people for de-esc. Results?

There was an interim analysis and there were unexpectedly high event rates in the negative PET arms So the iPET negative arms were closed to accrual early 1 yr PFS Fav-stand = 100% Fav-exp = 94.9% Unfav -- stand = 97.3% Unfav -- exp = 94.7% For the iPET positive patients - there was a significant PFS benefit to switching to BEACOPP as always and there was a PFS benefit to INRT When iPET negative, risk of relapse was higher if RT was omitted Fav 5 yr PFS - ABVD x 3 INRT (99%) vs ABVD x4 alone (87.1%) Unfav 5 yr PFS - ABVD x 4 + INRT (92.1%) vs ABVD x 6 alone (89.6%) Note there is a much more signifcant benefit for RT in the fav group than the unfav group. Conclusions: - There is still an important role of RT for early stage favorable and unfavorable pts - cannot eliminate RT based on PET response. You still need to remember this is a PFS difference, NOT an OS difference - Omission of RT was NOT non-inferior to chemo alone - patients who were PET2 negative and did not get INRT had worse PFS - Fav HL - PET2 negative --> 3 cycles ABVD + 30 Gy INRT was best - Un Fav HL - PET2 negative --> 4 cycles ABVD + 30 gy INRT - PET2 positive patients benefit from intensification of chemotherapy - field reduction from IFRT to INRT is valid

What are the pre-PET era early stage trials for favorable vs unfavorable?

These are all GHSG studies Early favorable = HD10 Early UNfavorable = HD11 and HD14

Tell the type of bias: what are all of these type of bias? - studied population differs from the target population due to nonrandom selection methods - patients are lost to follow up - high nonresponse rate to surveys/questionnaires can cause error if nonresponders differ in some way from responders - disease studied using only hospital-based patients may lead to results that are not applicable to the target population - exposures that happen long before the disease assessment can cause study to miss disease patients who had the exposure who simply died earlier or recovered

These are all subtypes *SELECTION* bias: - *Ascertainment/sampling bias* = studied population differs from the target population due to nonrandom selection methods - *Attrition bias* = patients are lost to follow up - *Non-response bias* = high nonresponse rate to surveys/questionnaires can cause error if nonresponders differ in some way from responders - *Berkson bias* = disease studied using only hospital-based patients may lead to results that are not applicable to the target population - *Neyman bias (prevalence)* = exposures that happen long before the disease assessment can cause study to miss disease patients who had the exposure who simply died earlier or recovered

Tell the type of bias: what are all of these type of bias? - Common in retrospective studies in which subjects with a negative outcome (e.g. liver cancer) are more likely to "recall" or report certain exposures than control subjects - Observers misclassify data due to individual differences in interpretation or preconceived expectations regarding the study - Subjects over/under report exposure history due to perceived social stigmatization - risk factor itselff causes increased monitoring in exposed group which increases the probability of identifying the disease

These are all subtypes of *OBSERVERS bias*: - *Recall bias* = Common in retrospective studies in which subjects with a negative outcome (e.g. liver cancer) are more likely to "recall" or report certain exposures (e.g vinyl chloride) than control subjects - *Observer bias* = Observers misclassify data due to individual differences in interpretation or preconceived expectations regarding the study - *Reporting bias* = Subjects over/under report exposure history due to perceived social stigmatization - *Surveillance (Detection) bias = risk factor itself causes increased monitoring in exposed group which increases the probability of identifying the disease

Treatment -- Major Acceptable Standards of Care

These are pretty much our standard Frizzell options for each category.

MORE data for RT in R0 resection in thymoma patients Singhal 2003 R0 resection in stage I and II --> no difference between +/- PORT Mangi 2002 R0 resection in stage I and II --> no difference between +/- PORT interpretation?

These are single institutional series and ALL retrospective data so there is undoubtedly selection bias that favors the no PORT arms because those are probably the lower risk people that wouldn't have recurred and the people that got PORT were probably inherently higher risk

Confidence intervals

These are the range in which the magnitude of the effect lies If its reported as 95% CI, this means the alpha is 0.05 They are statistically significant if the CI doesn't span the "no point effect" of one or zero for risk ratios like RR or OR The confidence intervals for two groups you are comparing need to NOT overlap -- if they do, there isn't a statistically significant difference between them

Syed/Venezia applicators

These are used for more advanced cases with sidewall or parametrial involvement where TO based brachy can't adequately cover the disease. This involves placing needles through a template directly in to where the residual tumor is.

Explain the difference between the: - Relative Risk - Hazard ratio - Odds ratio When does the OR approximate the RR?

They are all three essentially the same calculation but technically imply different things about the study, studied conditions, or outcomes in question. - Relative Risk = *Cohort study* = looks at situations where the outcome is common enough that you could follow two groups +/- exposure (lack of exercise and HTN). More costly but implies that you followed over time and accounted for disease incidence. RR = EER/CER = (a/a+b)/(c/c+d) = ad/bc - Hazard ratio = *Cross-sectional* study to look at a snapshot in time of the odds of having a disease with a given exposure. Assumes they are related. - *O*dds *r*atio = What are the odds people with a disease having been exposed to a risk factor compared to people without the disease being exposed = used when *O*utcome is *R*are (e.g. tampon use and TSS) = ad/bc. This assumes at *LOW PREVALENCE* of disease

What are the indications for RT to the whole abdomen

Things that buy you whole abdomen Basically things that contaminate the whole abdomen Spillage/rupture Peritoneal implants Malignant ascites Anaplasia diffuse or not, does not impact your field shape, just your dose

Japanese Data - Kondo for R0 resection of thymic tumors - 2003 - 1320 pts all with R0 resection - recurrence rate was actually very low in this paper -- stage II 4.7 v 4.1% for +/- PORT stage III 23 v 26% for +/- PORT

This data suggested there wasn't a benefit to PORT in stage II and III R0 patients Its thought there was some selection bias here -- retrospective analysis and there was a reason why the radiation patient GOT radiation - probably were higher risk and the ones that didn't get RT were probably lower risk so this is probably not a fair comparison

<5 cm and >5 cm show difference in local control on older studies (IRS III, etc) --> essentially LF ~10% if <5 cm and ~25% if >5 cm. ARST 1431 did dose escalation that we do now what is dose for <5 cm and >5 cm

This is a confusing point generally. Osler guy says this is investigational, but your decision about 50.4 vs 59.4 is based on their response to chemo if NO CR at week 9 of chemo (you go based on what size was BEFORE chemo) --> <5 cm = 50.4 Gy --> >5 cm = 59.4 If they get a CR at week 9 (ie. no visible tumor by CT/MR) --> then you give it only 36 regardless of size before chemo. DPE = Delayed primary excision --> so if you had an excision after chemo and had negative margins, same as CR --> 36 Gy. If R1 resection --> 41.4 Gy. If R2 after DPE --> 50.4 or 59.4 based on size at diagnosis Since this is technically investigational, 50.4 is really the SOC gross disease dose.

Why is brachytherapy needed for cervical patients -we treat to 80 Gy prostate - why can't we do that in cervix?

This is because the target ends up being much larger in cervical cancer -- after you add CTVs and PTVs its much larger than a prostate This is also typically a moving target if intact - EMBRACE-II protocol showed how to contour the ITV to account for uterus movement with bladder empty vs full Its still critical to monitor this on CBCT as they may not be able to get their bladder as full on treatment days as they did for SIM and this could mean their uterus sits further foward and you aren't covering it.

Is hypofractionation used for regional nodal?

This is being explored in trials but at this time there is insufficient evidence to routinely offer it for RNI. A small number of pts on UK Start B were treated with HF in the setting of +nodes, but not most.

primary intra-ocular lymphoma

This is essentially like PCNS limited to the eye most important to know there is a risk of CNS failure EVEN with RT include entire orbit

GOG 37 - RT compared with Pelvic Node resection for node positive vulvar - included FIGO I-IV w/ a groin lymph node identified during surgery - all pts underwent radical vulvectomy and bilateral groin dissection - underwent "intraoperative random telephone allocation" - ipsilateral pelvic node dissection vs pelvic and groin radiation RT started 6 weeks post-op fields covered bilateral groins, obturator, external and internal illiac areas Dose was 45-50 Gy to the midplane of the pelvis halfway between the superior border of the obturator foramina and L5-S1 interspace with AP/PA fields - inguinal and femoral nodes treated to what depth? - what group had better RFS, cancer related death, and OS?

This is kind of a critical old study because it shows an important point about treatment technique - groin nodes were treated to a depth of 2-3 cm RT improved 6 yr recurrence free survival (59 vs 48%, SS) and trend toward improved OS (51 vs 41%, p value NS) The 6 yr incidence of cancer related death was also reduced with RT (51% vs 29%)

Where in theory did point A and B correspond to?

This is pretty antiquated 2D based planning points point A - 2cm up from OS and 2cm lateral - paracervical triangle point B - 2 cm up and 5 cm over - obturator nodes

CNS IPI score

This is used if you are talking about DLBCL in the following sites - testicular - PCNSL - breast - or CNS risk factors ---> CNS risk factors = IPI risk factors + kidney and/or adrenal gland involvement If 4-6 risk factors do baseline LP and consider CNS ppx (IT methotrexate is a consideration in these cases)

McDonald Trial - INT 0116 - 556 pts - randomized to surgery vs surgery - chemo - chemoRT - chemo - 85% of pts were N+ - 1st cycle of chemo was 5-FU/leucovorin - RT started 28 d after C1 - 45 Gy in 1.8 Gy - 35% had major/minor deviations in contouring - most important - what was the extent of lymphadenectomy? results? - 10 yr fu data showed what subgroup didn't benefit?

This is what is pointed out here -- most were node positive however dissections were: - D0 - 54% - D1 - 36% - D2 - 10% (considered adequate typically So 90% had insufficient lymph node dissections. Major result - 3 yr OS - CRT: 36 mo - surgery: 27 months - 3 yr OS 50 v 41% 3 yr Relapse Free Survival also favored CRT - 30 m v 19 m; 3 yr RFS 48% vs 31% The thought was that the radiation was probably making up for insufficient lymph node dissection. So this data is most relevant if N+ and they didn't get good therapeutic dissection 10 yr median follow up data -- demonstrated continued strong benefit to CRT. OS and LR relapse significantly better Subset analysis showed that most subgroups benefitted EXCEPT for those with diffuse histology (minimal NS treatment effect)

typical statistical power of 80% is accepted. what does this mean?

This means that if there is a true difference between two groups, there is an 80% chance of detecting it with the study.

Sedlis criteria comes from GOG-92 - RCT, P3 - compared post-op EBRT (46-50.4) to obs - included - women with FIGO IB cervical cancer (size visible but not invading vagina or parametrium) AND negative lymph nodes results?

Those patients that met Sedlis criteria (easy way to remember is 2 of 3 of size >4 cm, DOI >1/3 and LVSI+) PFS was ~12% higher (65 vs 78.1%) favoring postop RT (SS) OS there was a trend toward improvement (71 vs 80%, NS)

Hypopharynx - three subsites of the anatomy?

Three subsites: 1. Pyriform sinuses 2. Post-cricoid area 3. Posterior pharyngeal wall The posterior pharyngeal wall is in contact anatomically with the post-cricoid area thus not really seen on DL. Yellow is pyriform sinuses posterior to the aryepiglottic folds

Thymoma Pathology -- - thymoma vs thymic carcinoma pattern of spread?

Thymoma tends to predominantly spread by direct extension into adjacent sites May metastasize to other thoracic sites -- pleural plaques, effusions, diaphragmatic masses -extrathoracic mets are very rare Thymic carcinoma - invade locally and can met out distantly. These commonly involve the pleura and regional nodes Type A = spindle cell shape Type B = more thymic architecture with lots of immature T cells and stuff

Thymoma/Thymic Carcinoma doses - unresectable PORT --clear/close margin --microsopic R1 --STR

Thymoma/Thymic Carcinoma doses - unresectable = 60-70 Gy w/ concurrent chemo PORT --clear/close margin = 45-50 Gy --microsopic R1 = 54 Gy --STR = 60-70 Gy w/ concurrent chemo list in pic are constraints -- just for information, probably not memorizing these - similar to NSCLC

The purpose of randomization?

To *equally distribute confounders* between groups (helps to control for known and unknown confounders) To assess this, look at the distribution of baseline characteristics in two groups. Lack of randomization results in selection bias. Participants in groups are unequally selected on the basis of certain traits resulting in the accumulation of confounders.

To what lymph nodes do esophageal tumors in the cervical and upper third of the thoracic drain? Tumors in the middle third dtrain where? Tumors in the lower third drain where? Siewart 3 tumors?

To what lymph nodes do esophageal tumors in the cervical and upper third of the thoracic drain = cervical, supraclavicular, upper mediastinal nodes Tumors in the middle third drain where = paratracheal, hilar, subcarinal, peri-esophageal Tumors in the lower third drain where = peri-esophageal and CELIAC nodes Siewart 3 tumors = more like gastric - periportal, peripancreatic, periduodenal, perigastric, and paraaortic

Define the following types of hysterectomy in terms of what is removed: - Trachelectomy - Supracervical - Simple TAH - Modified Radical - Radical - Extended Radical - Pelvic Exenteration

Trachelectomy - Cervicectomy - removes cervix, small rim of cuff, and some parametrium. Preserves fertility Supracervical - NOT an oncologic procedure because it only removes the uterus and leaves the cervix. Done for benign indications. Simple TAH - Class I - Extrafascial hysterectomy - Takes uterus and small rim of vaginal cuff. - This is done for early stage endometrial Modified Radical - "Total Hysterectomy" - Class II - Takes uterus and 1-2 cm of vaginal cuff + wide excision of parametrium and paravaginal tissue - ligates the uterine artery at the ureter - Limited to cervical cancers with invasion up to 5 mm Radical - Class III - Upper 1/3 - 2/3rd of vagina - Dissection of the paravaginal and parametrial tissues to the pelvic sidewalls - ligates the uterine artery at the internal iliac artery Extended Radical - Class IV - Adds full mobilization of ureters past the bladder - Removes more paracervical tissue Pelvic Exenteration - Ant. exent: Tubes, ovaries, vagina, bladder - Post. exent: Tubes, ovaries, rectosigmoid - Total exent: All pelvic organs

surgical approaches for esophagus - Transthoracic vs Transhiatal In general which one claimed to have better oncologic outcomes? Which one has higher rate of recurrent laryngeal nerve damage and increased leaks?

Transthoracic thought to have better oncologic outcomes Transhiatal higher leak and nerve damage

Treatment breaks RTOG 8704 (50.4 continuous) compared with ROTG 9208 (59.4 split course) --> showed what?

Treatment breaks should be avoided as much as possible but this is unavoidable in some cases in anal RTOG 8704 (50.4 continuous) compared with ROTG 9208 (59.4 split course) --> showed that overall, disease free, colostomy free --> ALL INFERIOR with split course radiation Pooled analysis of RTOG 9811 and RTOG 8704 --> showed that TOTAL TREATMENT TIME (not total RT duration) was significantly associated with colostomy failure and local failure on UVA ACT II showed high complete response and 3 yr relapse free survival of 74% with 50.4 --> attributed to lack of treatment break

grading for RP Describe tx for RT pneumonitis

Treatment for symptomatic acute pneumonitis is typically oral corticosteroids. Generally, 1 mg/kg/day https://www.medscape.com/viewarticle/446886 We recommend oral prednisone, 40 to 60 mg daily for 1 to 2 weeks followed by a slow taper (reducing ~10 mg every 1-2 weeks). P Ghafoori - ‎2008 Just say slow taper over about 6 - 8 wks. Pneumonitis: - 6 wks to 6 months post RT - Sx: low fever, dyspnea, dry cough, tachy. Get chest CT. Grade 1: radiographic Grade 2: minor sx/steroids Grade 3: O2 Grade 4: hospitalized/intubated Grade 5: death Graham 1999: 2-yr G2 pneumonitis risk predicted by V20 and MLD V20: 22% = 0 22-31 = 7% 32-40 = 13% > 40 = 36% We typically calculate this as total lungs - GTV and that is what was done on 0617, on Bogart's small cell protocol it is lungs - CTV MLD < 20 = 8% MLD > 20 = 24%

Pre-op ChemoRT trials -- 12 RCTs bottom line - response to chemoRT confers a stronger survival benefit

Trials listed here -- Dutch CROSS trial most important

Salvage trials Trock JAMA 2008 (retrospective) - major result? - biggest benefit seen where? - any benefit of ADT? Stephenson (retrospective) - 3 papers -- Tendulkar last paper - 2004 paper --> determine factors that predicted for progression after salvage RT. 50% had progression, 10% developed distant mets, 4% died from prostate cancer. Major risk factors for progression PSA>2 prior to RT, Gleason 8-10, negative margins (?), fast PSA doubling times, and SVI - These papers are where BF gets the nomogram that gives his 0.2-0.5 (best time to intervene), 0.5-1 (should intervene but give expectation of lower control), 1-4 (odds much lower) and >4 (no RT) GETUG-AFU16 - addition of hormone therapy to salvage RT - 743 patients --> randomized to RT +/- goserelin for 6 months - all pts had PSA detectable 0.2-2 - results? RTOG 9601 (Shipley) - pT3, pT2 with + margins AND PSA 0.2-4 ng/mL - randomized to RT +/- biclutamide x 24 months (150 mg - high dose) - results? RTOG 0534 SPPORT trial - 1792 pts, pT2-T3 N0, PSA >0.1 but <1 at least 6 weeks after RP, gleason 7-9 - 3 ARM: Randomized to prostate bed alone (group 1) vs prostate bed + ADT (group 2) vs RT to prostate bed and pelvic LNs

Trock JAMA 2008 (retrospective) - Pts with salvage RT had 3x increase in PCa specific survival - benefited men with short PSA-DT (<6 months) - no benefit of ADT oddly Stephenson (retrospective) - take home is better to treat when PSA is low rather than high. There are risk features that predict for failure after RT. - Take home -- showed --> early SRT at low PSA --> improved FF-biochemical failure and DM - NOTE: Positive margins is actually a FAVORABLE prognostic finding because that lends some credibility that the disease is actually in the prostate fossa. GETUG-AFU16 - improved bPFS and DMFS with ADT in salvage setting RTOG 9601 - Bicalutamide improved OS 76 v 71%. Benefit most significant in patients with PSA >1.5. SPECIFICALLY benefit of ADT seen in the PSA >0.6 group -- 2yrs of ADT. Positive margins patients also benefit - PCa mortality and DM also better with ADT - 9601 secondary analysis --> Spratt --> if PSA <0.6, 2 yrs ADT caused higher other cause mortality and no difference in PCa specific mortality. --> FENG 2021 secondary analysis showed that only DECIPHER int/high men had OS benefit (0.45 and up) regardless of PSA level RTOG 0534 SPPORT Trial - Lancet 2022 - as you add more interventions, freedom from progression gets better and better - FFP --> G1,2,3 --> 70.9%, 81.3%, 87.4% - G2 AE worse in G3>2>1 (44%, 36%, 18%) - interesting point in supplemental data, shows there is no difference in PBRT+ADT and PBRT+ADT+pelvic nodes but PBRT alone is clearly worse if pre-salvage PSA is 0.34 or less (in terms of freedom from progression). If PSA is >0.34 then PBRT + ADT + pelvic nodes is best. SAKK 09/10 - No improvement in PFS with higher dose RT - toxicities were higher in high dose arm RTOG 0526 - biochemical failure rate was about 54% at 5 yrs. The ones that failed would then go on to hormone therapy. Similar to prostatectomy and less toxic.

Constraint for mandible

Try to keep max < 70 Gy No more than 1 cc > 75 Gy no hotspots > 105%

Treatment paradigm for stage V wilms

Tumor board and expert pediatrics consult Rare cases, require multidisciplinary approach upfront chemo may allow a nephron sparing surgery (AREN 0534) There may be a role for partial nephrectomy if possible. Any biopsy should be done via posterior approach to minimize chance of spill or seeding the abdomen Protocol allows for up to 12 weeks of chemo and assessment Once surgery is done, the pathology guides your decision for post op RT In the bilateral case, just having a biopsy is not by itself an indication for RT like a typical stage 3 patient. You assess each kidney after chemo/surgery like it is the only disease Give each kidney its own stage Any local stage 3, any patients with lung mets, or stage 1,2, or 3 with focal or diffuse anaplasia get RT Regarding treatment volume Any peritoneal soilage/spillage/rupture, implants, gets WAI Otherwise just tx flank

Describe meckel's cave

Tumor in meckel's cave - trigeminal ganglion lives there Outpouching of dura surrounding the trigem ganglia It is where the branches split V1 and V2 go into cavernous sinus V3 goes through foramen ovale

Diffuse Large B Cell Lymphoma (DLBCL) - CD20+, Cd45+, CD3 - - high Ki67 - GEP identified distinct mlecular subtypes based on genetic signature - what are the types? Hint - CD10, BCL6, and MUM1 expression is different - which type has the worse prognosis? - whats the Hans algorithm? What is meant by "Double" and "Triple" hit? What is a "double expressor"

Two types - Germinal center (GCB) - CD10+, BCL6+, MUM1- - Non-GCB - CD10-, BCL6- or +, MUM1+ --> WORSE prognosis? - Hans: ---CD10+ --> GCB type ---CD10- --> then look at BCL6, if positive and MUM1- --> GCB type ---CD10- --> if BCL6- --> then non-GCB regardless So basically MUM1+ and BCL6- = BAD CD10+ = GOOD High Grade B cell lymphoma with derrangements in MYC, BCL2, and BCL6 - don't really use the terms double and triple anymore, just name the translocation Double hit = MYC re-arranagement + BCL2 Triple hit = MYC + Bcl2 + Bcl6 DOUBLE expressor = different than double hit - this is OVEREXPRESSION of MYC and BCL2 by IHC

General tx paradigm for pineoblastoma?

Tx like high-risk medulloblastoma (CSI 36 Gy + local boost to 54 Gy) DO CONCURRENT VINCRISTINE AND 8 C of PCV outback PCV for 8-9 cycles (P = platinum, C = CCNU, V = vincristine)

Endometrial cancer types? What type is more commonly associated with p53 mutation?

Type 1 Endometrioid type - most common Type 2 - poorer prognosis Serous Carcinosarcoma Clear cell carcinoma Type 2 is associated with p53 mutation

Siewart classification

Type I, II, III I = distal esophagus and may infiltrate GEJ from above: 1-5 cm above GEJ II = epicenter is w/in proximal 2 cm of cardia arising immediately adjacent to the GEJ (1 cm above, 2 cm below) III = epicenter is >2-5 cm below GEJ (classified as GASTRIC) Siewart 1/2 are treated as esophageal cancers

When is RT involved for thymoma?

Typically earliest we are involved is Stage IIB or B2-3 WHO subtypes ("consider RT") - stage IIB: macroscopic fatty invasion into surrounding tissue or grossly adherent to (but not through) mediastinal/pericardial pleura (but negative margins) - B2-3 subtypes = increasing amount of tumor relative to lymphocytes (still with negative margins) - essentially anytime there are positive margins For thymoma and thymic carcinoma - RT is recommended if stage III/IV (ie. gross invasion into neighboring structures) RT also involved of course if unresectable and typically done with chemoradiation in that case In some cases of borderline resectable, RT or chemo in the neoadjuvant setting can be considered with re-evaluation for possible resection after

Modern data on PORT suggests less toxicity than older studies showed U. Pen Machtay et al 2001 JCO - all linac based, modern techniques - 202 pts at Mayo, surgery + port - what was death from intercurrent dz number? ECOG 3590 - 488 pts randomized to PORT vs PORT + chemo - all modern technniques - what was death from intercurrent dz number? IMPORTANT - ANITA TRIAL - - this was actually a post-op chemo trial, but some patients got PORT based on physician preference - PORT was recommended for pN+ - looked at PORT outcomes retrospectively - results? LALLY SEER Meta-analysis - stage II-III, all had surgery, excluded pts that died w/in 4 months of surgery - 7,465 pts, 47% got PORT - showed what effect on OS in N0-1 vs N2? NCDB Robinson analysis --> showed what?

U. Pen Machtay et al 2001 JCO --> 13.4% v 10% matched control ECOG --> 12.9% vs 10.1% So shows that with modern techniques, its probably not as toxic as previously shown --> probably only like 3% ANITA TRIAL - 840 total pts --> 232 got PORT (45-60 Gy) - overall -- PORT HAD WORSE SURVIVAL -- EXCEPT IN 2 groups ---> pN1 patients that COULD NOT get chemo (med OS 50 vs 26 months)* ---> pN2 patients +/- chemo (med OS 47 vs 24 months, 23 vs 13 months) *However pN1 pts that got chemo, PORT had harmful effect --> med OS 47 v 94 months) Lally SEER --> N0-1 = PORT had WORSE survival --> N2 = PORT improved survival (in agreement with Anita trial) NCDB also showed benefit in N2 disease

PET directed therapy trials The idea of these trials was that you are taking lower risk disease and trying to de-escalate by removing RT if they had complete response to chemo.

UK Rapid H10 (different than HD10) HD16 HD17 Take home of these studies -- there was a loss of PFS when RT was omitted based on PET response (EXCEPT HD17, no difference with escalated chemo if PET neg) Need to discuss the pros/cons of radiation with every patient as fields will determine possible toxicity

Intermediate risk prostate cancer - Castle Red Journal - Which intermediate group is worse and needs hormones?

Unfavorable intermediate gruop - 4+3 or 2 IRF that makes the unfav - if 3+4 alone, no hormones (biochemical free survival is fine without it)

Mesothelioma Treatment Philosophy - Unresectable vs Resectable Unresectable - Who is considered unresectable? -----> how to manage these? Resectable - who is considered resectable? ----> how to manage these?

Unresectable - stage IV - M1 - stage III - N2 - Sarcomatoid (or biphasic) -----> how to manage these = chemo +/-RT Resectable - stage I-III - epithelioid ----> how to manage these = Chemo --> Surgery --> RT

Stanford central tumor experience - 68 pts (50:50 central and peripheral) - 50 in 4 or 5 fractions - how did they define ultracentral? - results?

Used the RTOG 0813 definition of ultracentral = GTV abutting the central airway Two year OS and LC similar regardless of location and toxicity rates low (only 2 cases of G3 CW pain and 1 case of G4 pnuemonitis)

Type of surgery for early stage NSCLC How does mortality compare to SBRT early after surgery?

VATS vs Open thoracotomy - VATS has less blood loss, less complications, shorter hospital stay - no improvement in long term survival More deaths early from surgery -- complication rate obviously higher from surgery

When do you cover retrostyloid? When do you cover retropharyngeal?

VIIa = Retropharyngeal = Cover both lateral RP volumes in any primary pharyngeal case OR cover IL RP volume only if the pharygneal wall is involved in an oropharynx case, but bilateral RPs for all nasopharyngeal and hypopharyngeal cases Cover medial RP volumes only in the lateral RP nodes are involved VIIb = Retrostyloid = Cover whichever side as level 2 involvement

Effect of age of vaccination on likelihood of cervix cancer diagnosis?

Vaccination <17 yrs of age was associated with lowest chance of cancer

What chemotherapy is typically given for Wilms? How does focal or diffuse anaplasia impact chemo?

Vincristine, Actinomycin, and Adriamycin = DD4A AREN 0321 Focal anaplasia = DD4A (dactinomycin/doxo/vincristine) Diffuse anaplasia = addsCCE carboplatin/cyclophosphamide/etoposide

What is the chemo for malignant mesothelioma?

Volgelzang JCO 2003 - Cisplatin/Pemetrexed - 456 pts w/ unresectable disease (no XRT) - Response was 41.3% vs 16.7 for Cis/Pem vs Cis alone - TTP and OS better with Cis/Pem vs Cis alone

LGG - When is RT indicated? - What is standard dose?

WHEN TO GIVE RT: RT if unfavorable features 1. STR or 2. GTR+>40 yrs Dose 45 to 54 used in RTOG trials -- (54 Gy) - WF: Usually take whole T2 flair to 54 with no boost GTV = T2 FLAIR - CTV = 1 cm - PTV = 0.5 cm No role for dose escalation, no boost. Just treat whole T2 flair volume to 54 Gy (or 55.8 also reasonable answer) VERY important = do NOT go to 60 Gy (too toxic)

DOMINANT PROGNOSTIC FACTOR for all gliomas

WHO grading system

Nasopharynx cancer - what are the pathological types? What is a useful treatment response indicator? - Most common location?

WHO types I, II, and III III: EBV related (45%) -- Undifferentiated/lymphoepithelial carcinoma -- endemic to East and Southeast Asia - Better LC, but higher rates of DM II: Non-keratinizing SCC (35%): Some cases are EBV related I: Keratinizing SCC (20%)Non-EBV related which act more like typical HN SCCa. Non-asian populations. Keratinizing is an adverse feature. Lower LC (but lower DM rates) Preliminary data suggests that following serum EBV levels before and after treatment might be an effective indicator of treatment response. - MC site: Fossa of rosenmuller

Major cord constraints to know?

We generally say 45 Gy max dose <0.03 cc for chemo RT 50 Gy in 2 Gy fractions to a full cord cross section is 0.2% risk of myelopathy single fraction - partial cord max dose of 13 Gy or 20 Gy/3 fractions <1% risk 5 fraction sbrt - 30 Gy to <0.03 cc 3 fraction sbrt - 18 Gy to <0.03 cc

When can you consider unilateral neck RT

Well lateralized tonsil primary T1,2 and up to N2a Don't do it for N2b (that is just not two be) Don't consider for any central tumors No if tonsil primary has extension over to base of tongue Allow 1 cm soft palate

QUARTZ study - 69 centers in UK and Australia - 538 pts randomized to WBRT + Optimal supportive care vs Optimal supportive care - results = NO difference in OS, QOL, and no diff in dex use. What are the interpretations of this study and what are the problems with this study?

Whole brain RT was interpreted as having no benefit which did patients a huge dis-service. Major issues -- they used 20/5 which we do NOT typically do unless extremely poor KPS. Look at plot in pic - If you were <60 years old, RT statistically significantly better than OSC - if >5 brain mets, RT favored SS - If GPA class 2.5- 3 - RT favored SS

How does age impact RT related IQ changes

With increasing age, the effect on IQ lessens Try to get them to 12 yo

Maxillary sinus cancer major risk factor?

Woodworkers - have a 500x increased risk compared to the general population

SBRT for Early Stage NSCLC - most important steps in workup? PFTs that generally mean inoperable?

Workup: - everyone should have CT Chest + contrast - everyone should have PET - anyone with primary lesion that is central or >2 cm should have mediastinum thoroughly interrogated (probably not wrong to say EBUS for all patients, but DEFINITELY over 2 cm) - anyone with central or primary lesion >3 cm should get MR brain as part of work up - everyone should have tissue diagnosis if possible (TT-FNA/EBUS/EUS/bronch) PFTs that general mean inoperable - Pneumonectomy: FEV1 <1.5-2 L - Lobectomy: FEV1 < 1-1.2 L (<50%) - DLCO predicted post op <40-50% ; pre-op DLCO <60% - FEV1/FVC = 50% min (ideal >80) - V/Q scan for post-op predicted FEV1 (min 40%) and cardiopulm testing - Absolute CI to surgery: cor pulmonale, severe CAD, renal failure Mortality from surgery tends to be in the range of 25-30% if less than these numbers

Does whole brain for brain mets improve survival? - change of symptomatic improvement? - median time to improvement of symptoms - median time to progression after wbrt? - how much of remaining life is stable or better neuro condition? - what is the main reason we treat with wbrt? - which cancers respond best to wbrt? Which ones don't respond well?

YES - older data 1-2 months --> 3-6 months (can have as much as 10-15% 1 yr OS) Note: QUARTZ trial suggested it doesn't improve OS compared to best supportive care, but those caveats will come up later. - 50-80% response rate in terms of relief of neurological symptoms - median time to improvement is 1-2 weeks - median time to progression is 2-3 months - 70-80% of remaining life in stable/improved neurological condition - decreases change of dying neurologic death --30-50% will die of persistent/recurrent disease --OS determined in these cases to extent of systemic disease Lung and breast respond better to whole brain. Unlikely to die of brain disease. Opposite for melanoma, GI and renal cancer -these do worse

Pt w/ indictations for neoadjuvant chemotherapy was clinically node positive and after chemo is ypN+ Tx? Data? Recurrence risk?

Yes, generally we say that if there are indications to treat before chemo, we still treat after XRT, especially if they did not have pCR in the node. B51 is addressing the question of the need for regional nodal for ypN0, but for now we offer if they had up front indication. Left side of pic is lumpectomy, right side is mastectomy Mamounas B18 and B27 Combo Analysis 2012 JCO Lumpectomy pts received breast radiotherapy alone; mastectomy patients received no radiotherapy. NO REGIONAL NODAL RT ON THIS STUDY Retrospective review of NSABP B18 and B27 data included BCS and Mastectomies N = ~ 3000, 335 had LRR in 10 yrs follow up No data on hormone or HER2 status Used an MVA to try to find factors predicting for LRR Made a nomogram based on this MVA to predict risk of LRR 10 yr cumulative LRR Mastectomy: 12.3% (8.9% local; 3.4% regional) BCS: 10.3% (8.1% local; 2.2% regional) Surgeons will use this data to say in the cN(+) groups those w/ pCR had 0 LRR However notice that numbers are very small and most were cT1 or cT2 N0 patients anyway It also makes no sense that cN(-) pts with a CR have a higher LRR than those who were cN(+) This is likely an effect of having such small numbers in each group Furthermore, notice that almost all of the failures are regional in the < 5 cm cN(-) This should have been more Chest wall failures mostly so this makes us question this data Keep in mind false negative for SLN after neo-chemo is ~ 12% FOR QUESTIONS BELOW, i think these were made before 10 yr paper, see abstract below.

A classic case for oral boards is as follows: You check serum BHCG and AFP: Both come back negative surgeon goes in and does a craniotomy, resects tumor - path says this is pure germinoma You check CSF levels of BHCG and AFP and now the CSF BHCG is 150. As in > 100 (this is your key)

You have to realize that this is too high to be pure germinoma (they don't go over 100), even though pathology told you it was germinoma this is NGGCT Another case is that Chan will show you labs that look like diabetes insipidus (high serum Na, low urine osmolarity, high serum osmolarity) This means there is OCCULT MULTIFOCAL DISEASE in the sella. You need to include it in your boost volumes

Important thing to know about esophageal staging -- high yield T stage to know?

You really just need to know T2 = muscularis propria and T3 = adventitia. T1 invades the other superficial layers like lamina propria and muscularis mucosa T4 invades adjacent organs. So if you can recognize T2 and t3 you can figure out the others. N is number (1-2 (N1), 2-6 (N2), 7+ (N3) Prognostic grouping is probably too complicated to be asked All submucosal tumor shave substantial risks of LN mets -- technically T1 is subdivided into specific depth within the specific layers that the tumor invades to give a better idea of risks of LN mets M1/2 - not involved with LN mets (just to epithelium/lamina propria) M3 if no LVI - 8-10% M3 + LVI = 50% risks of LNs

When is MRI breast helpful? What are some cons?

Young pts dense breast BRCA 1/2 mutation Strong family history invasive lobular carcinoma high risk of a second primary DOWNSIDES - prone - difficult if claustrophobic - higher rate of false positive - hard to know when the stop - repeated contrast may not be harmless (may concentrate in pituitary according to DB)

A patient with N3 vulvar cancer has what?

a fixed/ulcerated LN --> stage IVA (note ENE is stage N2c which is stage IIIC)

pre-op RT in gastric cancer overview

actually did have improved OS in these trials Meta-analysis - showed that pre-op RT significantly reduced mortality

For stage II - III - what is local failure rate for TME alone without RT (adjvuantly)

actually fairly low with TME and no radiation - 4-12%

If p16 not tested in OP, how would you treat the cancer?

as if it were p16 negative -- really doesn't currently change management -- so doesn't matter

Who should get screened with high res anoscopy?

at high risk MSM HIV + women history of cervical/vulvar HSIL immunocompromised perianal hpv lesions vaccines decreased incidence of LSIL and HSIL

What is the FLIPI-2 score?

b-2 macroglobulin > ULN + BM marrow involvement Hb <12 g/dL LN >6 cm in long axis Age >60

how is cholangiocarcinoma defined as internal vs extra

basically extrahepatic is below the confluence of the hepatic ducts

IMPower133? Caspian trial?

chemo trial for SCLC - P3 carbo/etop +/- atezo in 1st line ES SCLC - 1:1 +/- atezo - median OS benefit of 2 months (SS) and median PFS (SS) not a huge benefit, but was significant (12.3 months vs 10.3 months) practice changing non-the-less Caspian trial - randomized to durvaluamb vs placebo vs durva + tremelimumab + EP --> shows again about 2 months (12.9 vs 10.5 and improved PFS) -- same as IMPower133 -- tremelimumab DID NOT have any improvement in OS But durva is approved based on the Caspian trial.

analysis of a nominal independent variable and a nominal dependent variable

chi square (think degrees of freedom/goodness of fit)

RTOG 0933 - Memantine or placebo in pts getting whole brain

cognitive outcomes were better with memantine -- specifically delayed time to cognitive decline and processing speeds, and executive fucntions

constraints for WAI

constraints for WAI

Unresectable /potentially resectable Thymoma/Thymic carcinoma - MDACC 2004 series - induction chemo -- surgery -- PORT +/- chemotherapy - results?

control was actually good 18/19 had disease control w/ median FU 50 months

meningioma Treatment doses G1 G2 G3

conventional linac fractionation = 1.8 Gy/fraction grade 1 = 52.2 Gy, CTV = GTV + 3 mm PTV --> SRS = 12.5 Gy to 50% IDL (if <3 cm) grade 2 = 55.8 Gy, CTV = 1 cm, 3 mm PTV grade 3 = 59.4 Gy, CTV = 2 cm, 3 mm PTV (if STR, cover preop bed and residual) optic nerve sheath meningioma = 52.2 Gy, CTV = GTV + 3 mm PTV (same as Grade 1) In general, also ok to think of dose for CNS as follows: - benign things = 5040 cGy Frac or 12.5 Gy GKRS 50% IDL - atypical/lgg, etc = 5400 cGy or ~14-16 Gy GKRS 50% IDL - malignant/hgg, etc = 6000 cGy These doses are in 2's rather than 1.8's and are generally acceptable doses to give as well. Risk Factors: fam hx of breast cancer, oral birth control, prior radiation

RT fields

data for IMRT is mostly single arm phase II data that shows lower toxicity

Management of solitary plasmacytoma How does "SP w/ minimal marrow involvement <10%" affect the treatment strategy.

definitive RT with 35-50 Gy SBP < 5 cm - 35-40 Gy SBP >5 cm - 40-50 Gy SEP - total dose 40-50 Gy --> for small well defined, or post-excision with + margins, 40 Gy is sufficient For patients with SP with minimal bone marrow involvement <10%, lower doses in the range (and hypofrac) can be considered given the VERY high likelihood of progression to MM

Other systemic options for meningioma

don't memorize - just for reference Chemotherapy (CAV) Tamoxifen Mifepristone - was tested in SWOG S9005 - well tolatered but no effect on meningiomas Hydroxyurea INF-a2b

Background data for GBM - just for reference really RTOG analysis of GBM patients - partial (64%) vs total resetction (19%) - survival is better with more resection - median survival ~11.3 months Biopsy alone study (17%) - <54.4 Gy - med surv 4.4 mo - >54.5 Gy - med surv 8.3 mo

don't need to know this data really -- just the idea is our principles came from somewhere

Hippocampal avoidance - RTOG 0933 --> NRG BN001 - NRG BN003

dose was 30/10 HVLT test - p2 trial single arm showed between than historical control

Esophageal lymphatics what layer is esophageal mucosa missing?

drainage is intramural and longitudinal extend from periesophgeal cervical to celiac nodes present in the submucosa but also in the lamina propria lymphatics in muscularis propria more limited but channels pierce this layer and drain into the regional LNs NO SEROSA in the esophagus - just adventitia

symptoms of HL What is the technical definition of B symptoms?

dysnpea, chest pain, lymphadenopathy, pain, fever, itching, pain w/ alcohol Fever >38 C, >10% weight loss in 6 months, drenching night sweats ANY ONE of these counts as a B symptom

Brain mets - radiologic features

enhancing multiple vs solitary distrubtion gray/white interface circular expansile increased edema - T2 signal csf/spinal eval needed for dural based lesions

FLYER - is 4c R-CHOP + 2 R alone non-inferior to 6c R-CHOP for pts w/ favorable prognosis - younger pts (18-60) - Age adjusted IPI - 0 - RT reserved for testicular lymphoma - non-bulky (<7.5)

essentially found you could do 4 cycles chemo + 2 extra R alone and that was just as good in terms of EFS, PFS and OS Not an RT trial Excellent outcomes for early stage low risk DLBCL without RT

Surgery for HCC is best in what group

essentially lowest risk pts

Gunderson pool analysis for adjvuant in rectal

essentially surgery + chemo is as good or better than surgery + rt or chemort

STATS section Things they are most likely to ask: - sensitivity - specificity - PPV - NPV - ARR --> Number needed to treat (very easy) Otherwise its pretty much all questions about types of studies and basic things.

example of NNT If a pill reduces the risk of mortality such that the placebo has a 20% risk of death and the pill has a 2% risk of death. That is 20-2 = 18% ARR or 0.18 NNT = 1/0.18 or 100/18 = 5.5 people needed to treat to prevent one death

outcomes for solitary plasmacytoma - LC - likelihood of progression

excellent LC 85-90%

HL - work up - what type of biopsy do you need? - labs you need? - imaging? - other things you need?

excisional biopsy, core if diagnostic is ok, no FNA labs = CBC w/ diff, ESR, albumin, LDH, LFT, HIV, pregnancy - contrasted PET/CT scan - PFTs, echo, fertility, smoking cessation bone marrow biopsy NOT indicated - cytokine release that makes the BM involved but this doesn't mean the BM is involved. If you have more discrete lesions that more suggestion of BM involvement.

Expected outcomes for stage III and IV thymoma/thymic carcinoma based on what?

extent of resection is critical as seen here regardless of adjuvant therapy

What does the path look like for Germinomatous germ cell tumor?

fried egg appearance

LC for SRS -- retrospective data over view

generally shows LC in the 80-90% range

RTOG 9310 - combined modality with MPV and RT - 45 Gy if PR and 36 Gy if CR

had unacceptable toxicity significant neurotoxicity - leukoencephalopathy - for pts >60 -- significant fatal neurotox

adverse effects of cytoxan?

hemorrhagic cystitis infertility - reason they were trying to decrease the dose

testicular dlbcl

high yield points - elderly men - LP and MR part of workup Tx: - surgery - radical inguinal orchiectomy - R-CHOP x 6 - IT methotrexate - consolidation scrotal RT - 30 Gy +/- regional lymphatics -- decrease relapse in CL testis because chemo doesn't do great because its a privileged site - testosterone loss is the big side effect to remember RT has huge difference in PFS and OS -- both statistically significant.

Dose Escalation study - Krishnan red journal 2015 - 200 pts - 47 pts w/ tumor >1 cm from luminal organs treated with BED>70 Gy and compared with Cohort of 50.4 (BED = 59.4 Gy-10) - what was the only predictor of OS on MVA?

higher BED was the only predictor of OS on MVA BED > 70 had superior OS (p = 0.03) - med OS 18 vs 15 m. No diff in toxicity

Norwegian Trial of high dose vs standard dose BID (2021) - THORA trial - randomized P2 - 170 LS-SCLC pts - all got carbo/etop - 60 Gy BID vs 45 Gy BID - results?

higher dose BID actually improved PFS and OS compared to 45 Gy - no added toxicity (G3+ esophagitis was 21% v 18% NS)

When should a simple cholecystectomy be followed by returning for radical surgery with lymphadenectomy?

if beyond T1a

Schematic of CRM

if tumor approaches the CRM the likelihood of having recurrence is much higher -- good removal of CRM gives better local control

structures contained in the different compartments of the mediastinum

important point - LNs contained everywhere so lymphoma could be from anywhere - thymus is anterior - 50% of tumor arise in anterior - posterior has neural structures (neurogenic tumors) - heart and great vessels are middle

What is the impact of the addition of whole brain radiation to surgery?

improved control

How do you obtain a biopsy of a rhabdomyosarcoma?

in a way that minimizes exposure of other compartments, shortest route, NOT FNA, get a core or incisional, you need architecture

treatment paradigm for T1-2 disease Stage I-II: - 1a disease (<2 cm w/ <1 mm DOI) If >2 cm or >1 mm DOI or the lower third of the vagina/urethra or the anus is involved: - 1B-II if tumor size <4 cm and >2 cm from midline - 1B-II if tumor size <4cm and <2 cm from midline

in general... for early stage - surgery w risk adapted adjuvant - negative margins - obs - positive margins - re-excision - persistently positive margins - EBRT So essentially as long as its no T3 which is like T4 for other sites w/ upper 2/3 urethral/vaginal involvement, bone invasion, rectum or bladder involvement -- the paradigm would be surgery --> obs, RT, or chemoRT. Stage I-II: - 1a disease (<2 cm w/ <1 mm DOI) --> these would go for simple partial vulvectomy (IA) - no lymph node dissection needed if no DOI If >2 cm (T1b) or >1 mm DOI (T1b) or the lower third of the vagina/urethra or the anus is involved (T2): radical partial vulvectomy + lymph node dissection - 1B-II if tumor size <4 cm and >2 cm from midline = unilateral inguinofemoral lymph node dissection - 1B-II if tumor size <4cm and <2 cm from midline = bilateral inguinofemoral lymph node dissection Then adjuvant treatment is essentially based on path features - persistent positive margins after attemped re-excision = RT - positive nodes = chemoRT

General Treatment Paradigms -incidental/asymptomatic - Grade I and symptomatic/progressive - Grade II or III Optic sheath meningioma

incidental/asymptomatic = - either observe - consider Sx if >3 cm and easily accessible Grade I and symptomatic/progressive = - Surgery +/- RT (depends if GTR vs STR/location) - RT alone Grade II or III = - Surgery + RT, ideally GTR -for mock orals, say Linac based fractionated for grade II or III Optic sheath meningioma - NEVER do surgery - RT alone -- 90% will be controlled (50% will improve and 50% will be stable after) benign (grade 1) - can do SRS - prescription = 12.5 Gy to 50% IDL - For SRS, just GTV, no CTV or PTV atypical (grade 2) - can probably do SRS, 16-18 Gy to 50% IDL - mock orals = just say conventional linac based RT malignant (grade 3) - surgery + linac based RT (NO SRS)

Toxicity of MMC on RTOG 8704

it was thought that the deaths from the MMC arm was due to essentially protocol deviations

SBRT Trial overview - early Madsen paper looking 33.5 in 5 daily (EQD2 78, ab = 1.5). Biochemical free survival was horrible (48 month -- astro def 70%, phoenix def nadir +2: 90%)-- this is what made people not like SBRT and really said 33.5 isn't enough for SBRT UTSW trial - 64% intermediate risk -- 45-50 Gy in 5 fractions -- problem there was significant G3 and 4 tox. Biochemical control was excellent 5 yr 98% -- so probably dose too high. HYPO-RT-PC trial -- 89 int risk; 11% high risk -- randomized 78 in 39 v 42.7 in 7 fractions (every other day) -- showed no diff in cancer outcomes median 5 yr fu. -- GI symptoms maybe smidge worse in SBRT. GU and erection same. PACE A/B/C trials (A/B are low and intermediate; C was intermediate and high) -- 36.25 dose is all to PTV (prostate is getting 40 Gy) - PACE A - prostatectomy vs SBRT 36.25/5 - PACE B - 78/39 or 62/20 vs 36.25 in 5 --> worse GI 2+, worse GU2+ in CONVENTIONAL, sbrt better. - PACE C - 60/20 + ADT vs 36.26/5 + ADT

just read SBRT definitely needs spacer

Nasopharynx important anatomy know the borders

know the Torus tubarius (just in front of Fossa of Rosenmuller) Fossa of Rosenmuller Eustacian tube orifice Superior: Sphenoid bone (edge of sphenoid sinus) Inferior: Soft palate Posterior: Clivus/C1-2 Anterior: Posterior edge of the choanae in nasal cavity

RT in the setting of transplant

localized relapse, bulky disease, etc -- these people benefit from LC

breast anatomy stuff

look at the clock face

LUNG CANCER CARDS Lung cancer screening - General USPSTF recommendation NLST major outcomes? - how many patients? - who was included? - positive screen rate? - false positive rate - mortality reduction with CT? - NNT to prevent one lung cancer death?`

low-dose CT (2020 update) - 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. (ACS/NCCN says 55-74) There have been 7 large controlled trials for CXR since hte 1960's -- these did NOT demonstrate a survival benefit nor did the Cochrane database. PLCO trial also did not reduce lung cancer incidence or mortality. CT SCREENING IS STANDARD OF CARE BECAUSE --> NLST compared ld-CT with CXR and found: - n=53,454 pts - high risk 55-74 yr, 30 pk/yr, current or ever smokers - positive screen rate: 24% vs 7% (CT vs CXR); - FALSE POSITIVE RATE: 96.4% vs 94.5% (CT vs CXR) - 20% relative reduction in lung cancer specific mortality from ld-CT vs CXR; 6.7% all cause mortality reduction also shown. - NNT = 320 (number needed to screen to save one life) Also seen in I-ELCAP - International Early stage lung -- didn't have control group however, didn't control for lead time or length time bias. Nelson study (2018) - CT screen vs usual care - netherlands, current or former smokers >15 cig per day for 25 yrs or >10/day for >30 years - mostly men (but a subsample of high risk women also included) - CT scan on a yearly basis compared to NO screening (usual follow up; vs NLST which compared to CXR) - Screening group diagnosed lung cancer at much higher rate and you capture them much EARLIER compared to usual care - Screening reduced lung cancer deaths (RR of 0.76, 24% reduction in lung cancer mortality) - much greater relative risk of reducing LC mortality in woman than men

Head and neck Boundaries of each LN level Ia Ib II III IV V VI VII VIII

lvl Ia: Submental - Between the anterior bodies of the digastric muscles (CC: geniohyoid to hyoid bone) - drains lower lip, chin, and secondary drainage for anterior tongue lvl Ib: Submandibular - From the upper to lower margin of the submandibular gland, medial to the mandible and lateral to the digastric muscle (CC: Mylohyoid - hyoid) - drains the oral cavity and the lower nasal cavity lvl II: Upper jugular - Inf. lateral process of C1 - inf. hyoid (anterior edge 2a abuts submandibular gland). Posterior edge is posterior edge of SCM. a and b divided by post. edge of IJV. Medial to SCM and lateral to scalene muscles - drains MOST HN sites including: Nasal cavity, nasopharynx, oropharynx, oral cavity (secondary), larynx, hypopharynx, and major salivary glands -- primary drainage for the supraglottis (II and III) - lvl III only unknown primary think larynx lvl III: Mid-jugular: Bottom hyoid - bottom cricoid, medial to SCM/lateral to scalenes - drains: most HN sites inlcuding nasopharynx, oral cavity, oropharynx, larynx, and hypopharynx lvl IV IVa/b: low jugular/medial supraclav- Bottom cricoid - 2 cm above sternoclavicular joint, medial to SCM, anterior to scalene muscles. - drains: hypopharynx, larynx, thyroid, cervical esophagus, distal drainage from higher cervical levels lvl V: Posterior Triangle - Top of hyoid - transverse cervical vessels, posterior to II, III, and IV. Is posterior to tail of SCM and anterior to trapezius from the platysma to the scalene muscles - drains: the nasopharynx, oropharynx, thyroid, posterior scalp lvl VIa (anteriorly)/b (posteriorly): Anterior Compartment: Top of thyroid cartilage/lower hyoid - sternal manubrium. Anterior to infrahyoid muscles and between SCMs - drains: lower face, tip of tongue, FOM, anterior neck, hypopharynx, thyroid, larynx, and cervical esophagus - contains the "delphian node" - Oracle of Delphi - spoke for the God Apollo - the God of Art/Medicine, etc. lvl 7: VIIa: Retropharyngeal - top of C1 to body of hyoid (anterior to VIIa posterior to pharynx), between the constrictors and longus colli/longus capitus muscles - drains: the nasopharynx, soft palate, tonsillar fossa, posterior pharyngeal wall VIIb: Retrostyoid "high level II" - tissue surrounding the carotid, jugular vascular bundle from the jugular foramen to the upper border of level II. - drains: nasopharynx -- + retrograde drainage pathway for bulky level 2 involvement lvl VIII: Parotid node group (zygomatic arch/external auditory canal to angle of mandible; Ant = post. edge of mandibular ramus - to post border which is anterior SCM, posterior belly of digastric)

diagnostic workup for esophagus cancer

make sure to say bronchoscopy for upper and middle thoracic tumors -- must r/o tracheobronchial invasion

Primary mediastinal tumors - heterogenous, can be neoplastic, congential, or inflammatory - can be germ cell tumors (metastatic from testicles) - 60% benign - can cause compression or invasion of adjacent structures

may not grow, benign ones may just stop More symptomatic indicates more rapid growth and more likely to be malignancy you want core or excisional biopsy for workup

SWOG 0014 - Rituximab + 3 cycles CHOP plus IFRT - included DLBCL, mantle, Burkitt results?

median 5.3 yr Fu IN limited stage DLBCL - addition of rituxan had 2 yr PFS which met pre-specified study criteria for efficacy This is what led to further investigation for Rituxan

FLAME - micro BOOST - ~600 pts, 84% high risk (15% int. risk) - looked at EBRT SIB boost to MRI detected lesion. - randomized 77 Gy in 35 fractions vs 77 in 35 + a micro boost to 95 Gy. - median fu 6 yrs - outcome? - side effects?

microboost improves biochemical free survival and DFS but not DMFS or OS side effects -- unlike brachy boost, there was no significant diff in side effect profile.

Meningioma path grade Additional histologist features of meningiomas for each grade and buzzwords for histology? Typical --> _% recurrence rate Atpyical --> __% recurrence rate Malignant --> __% recurrence rate

mitoses per 10 HPF G1: 1-3 G2: 4 - 19 G3: 20 + G2 also includes necrosis, brain invasion, clear cell, choroid G3: Rhabdoid, Anaplastic, Papillary (RAP) +vimentin, GFAP, anti-leu7 Fatty degeneration, hemorrage, calcium, cyst formation Typical --> 3% recurrence rate Atpyical --> 38% recurrence rate Malignant --> 78% recurrence rate

Data for dose escalation in whole brain - Just look over some of the numbers.

most just say 30/10 20/5 is about the fastest the majority of people would consider Deangelis 1989 study showed 11% RT induced dementia -- all had >3 Gy /fx -- NONE of the 30/10 patients got dementia Recurrent brain tumors are more likely to cause dementia than 30/10 PCI for SCLC data do not clearly suggest increase dementia incidence

Post-op RT for esophagus - mostly benefit seen where?

mostly seen in N+ group (MacDonald trial had 10% GEJ - most gastric tho)

Indications for whole brain

multiple mets CSF leptomeningeal involvement 30/10 most common 20/5 can be used but doses >300 cGy per fraction associated with worse cognition and shorter courses probably cause increase steroid need

Penile Cancer Management - who doesn't need inguinal lymph node dissection? - who does need inguinal node dissection?

no palpable nodes - LOW RISK disease -- only T1a men (LVSI -, PNI -, low grade) - all others need lymph node dissection - >T1a is high risk disease - needs inguinal dissection (ILND) or "dynamic sential node biopsy" Palpable nodes - controversial - FNA of node is recommended (some sources say 4-6 weeks of abx, but usually don't do this) - low risk - negative FNA - you should do excisional biopsy - high risk (>T1a) - negative FNA - you should do superficial inguinal node dissection If positive --> neoadjuvant chemo

TACE is done when?

note CI: PV thrombosis, encephalopathy, biliary obstruction No direct effect on tumor killing induces hypoxia chemotherapy increased vessel sclerosis to induce hypoxia data suggests that there isn't much difference between bland embolization vs TACE -- the chemo itself probably doesn't do much - its the particles that cause hypoxia

RTOG 98-11 - this one tested induction --> induction Cisplatin/5FU --> concurrent MMC/5FU vs MMC/5FU concurrent (no induction) RT T1-2 --> 30.6 Gy to the pelvis --> cone down to 45 Gy larger tumors --> boost of 10-14 Gy

now we all use RTOG 0529 for dosing -- this is oldschool RT dosing overall result here higher toxicity with induction DFS, OS SS better in 5FU/MMC group

What ependymoma could potentially avoid RT? Patterns of failure

obs only if well differentiated low grade, and supratentorial Everyone else gets treated Mostly local 70 - 90% Very rare to see isolate spine failures < 1% Ependymoma is curable Overall patients do pretty well actually GTR makes the biggest difference, RT makes a difference too St Judes RT 1 study is one of the most recent large studies All comers 5 yr LC 80%, 5 yr OS ~ 70% Anaplastics did worse 5yr OS ~ 60 - 65%

Patterns of spread of LNs - list all nodes - whats most commonly involved

obturator - MOST COMMONLY INVOLVED pre-sacral - rarer, but still have to cover common iliac external iliac internal iliac parametrial para-aortic

Princess Margret Data for Oropharynx - 228 pts - T1-2 N0-1 - treated IL neck to decrease xerostomia. - Note: treated tumor + margin and IL Pterygoid, IL neck, and IL RP nodes - what was the rate of CL failure?

only 3% overall risk of CL failure 1.7% when primary tumor was well controlled If nodal involvement, ~10% failure rate after

esophageal brachy vs stent

only thing that favored stent was time to improved symptoms

Meta-analysis of trials in 1-4 brain mets of SRS +/- WBRT

outcomes SRS alone had better survival in pts <50 yrs. Omission of WBRT did not impact distant brain relapse Pts w/ 1 brain met lived longer than 2-4 brain mets Conclusion: SRS alone may be the preferred treatment in <50 year olds in 1-4 mets

Shah JCO 2007 - evaluting adding Rituximab to chemo - R-MPV and RT (45 Gy if PR, 23.4 Gy if CR) - then HD Ara-C

overall

Major trials for Adjuvant Pancreas Cancer - GITSG - EORTC - ESPAC - RTOG 9704 trial

overview - GITSG - CRT-5FU - CRT was beneficial (OS) - EORTC - CRT-5FU- CRT was NOT beneficial - ESPAC - CRT (fact design) - CRT was HARMFUL - CONKO1 - surg +/- gem - Chemo had DFS and OS benefit (5 yr) - RTOG - RT +/- gem or 5FU - no major difference

Induction chemo vs chemoRT path CR rates?

pCR - chemo = ~10% - chemoRT = 30% Mediastinal downstaging - chemo = 30% - chemoRT = 60%

Total Neoadjuvant Therapy (TNT) - giving all tx before surgery - more likely to be able to complete all therapy if done before surgery - increased response may allow for observation in some cases vs surgery MSK Retrospective study looking at: - pCR for TNT vs chemoRT alone Review looking at idea of - 2017 - CRT followed by chemo - chemo followed by chemoRT - whats the take home?

pCR 31% for TNT vs 21% for ChemoRT She breezed over this -- will have to fill this in later For sequence, people tend to favor chemo first if higher nodal burden vs CRT first high higher T stage lower N stage

Burmeister - chemo-surg vs chemoRT-surg -- rct, p2, of 75 ps - randomized to pre-op chemo (Cis/5fu) vs pre-op chemo followed by chemoRT (35 Gy in 3 weeks w/ cis) - results?

pCR 31% v 8% favors CRT (SS) R1 0% v 11% favors CRT (SS) med OS favors chemoRT but NS 5 yr 45% v 36% (NS) but only 79 pts

VULVAR cancer - incidence has been increasing over the last 20 years - 3-5% of gyn cancers - 1-2% of all cancers - mostly squamous cell, but can be adeno, basal, melanoma etc risk factors

pagets hpv - only 2/3 of cases smoking lichen sclerosis - 6% 20 yr risk (risk even higher if they also have VIN - 20% if you have VIN w/ LS) etc In vulvar cancers only about 2/3 are from HPV -- 1/3 are hpv negative (still 16 and 18 are most common types) - 33, 6 and 31 have also been seen Remember in cervix, its 90% younger patients - hpv more likely older patients - hpv less likely

Types of data that helps you know what type of statistical test should be used parametric non-parametric

parametric = these are usually ratios or intervals like measures of temperature, age, etc where is a zero level. non-parametric - these are nominal or ordinal with a rank or classification (things are higher or lower or one or the other like gender). based on the picture the osler guy says to figure out what sort of data they are giving you and think of it as parametric variables - probably t or Z test non-parametric variables - probably chi-square, KS, Mann-Whitney or McNemar tests

Describe 2 techniques for IMN coverage

partially wide tangents; electron strip

Prostate Anatomy - review picture on other side - know zones - what zone has most cancers - what zone has most BPH issues - what zone has no cancer

peripheral zone wraps around the periphery of the prostate. For guys w/o BPH, this makes up most of the tissue of the prostate and is where 70% of prostate cancers are located -- this is what you can feel with your finger. Central zone is ~25% of the gland and is larger toward the base (superior side of the prostate) - this area is larger in BPH - just posterior to the urethra. TZ - transitional zone. Just anterior to the urethra -- about 25% of prostate cancers here. Anterior Fibromuscular stroma (non glandular tissue) - 0% of cancers -- not as crititcal to make sure this is implanted as much as rest of the gland

Classic path finding of ependymoma

perivascular pseudorosettes

survival in thymoma/thymic carcinoma in stage I and II?

pic shows stage I and left with no invasion stage II with breaking through of the capsule (IIB since gross, IIA is microscopic)

Lui paper suggested luminal A BC benefited less from RT - this lead to multiple trials - lumina, IDEA, precision, expert trials

planned interim analysis of the IDEA trial - 13 US institutions 50-69, stage I BC, >2 mm margins - oncotype <18, at least 5 yrs of endocrine therapy - at 400 person years, there was no disease recurrence at any site

MM prognostic findings

plasma cell index >1% b-2 microglobulin bad low alb bad hyperviscosity is caused by IgM extramedullary disease is associated with aggressive MM avoid contrast scans for MM - renal function lytic lesions caused by overexpression of RANKL - receptor activator for NFKB that activates osteoclasts

Ewings Dose - what does you initial CTV to 45 Gy include - what do you boost?

pre-chemo volume - bone/soft tissue volume + 1-1.5 cm --> 45 Gy Boost = pre-chemo bone + post-chemo soft tissue or positive margin --> 55.8 Gy total (gross disease) Microscopic disease = 50.4 Gy You don't decrease the bone coverage. 0.5 - 1 cm PTV Metastatic site = 40-50 Gy Whole lung = 12-15 Gy (12 Gy if <6 yrs) Poor response to chemo = LF ~12% Post-op RT decreases this to 6%

MM treatment

primarily systemic treatment induction followed by eval for stem cell transplant

Treatment of NSGCT - role of RT?

radiation limited role surgery is radical inguinal orchiectomy (NOT trans-scrotal) In more advanced stage RPLND and add chemotherapy

Recurrent GBM options

re-resection re-RT w/ bev chemotherapy immunotherapy gliadel waifers gamma tiles

Data for surgery for stage I SCLC

reasonable 5 yr OS in these people actually

benefit of IMRT in pancreas?

red journal paper showed lower toxicity -- similar control and survival

Data for SPACE-OAR

reduces side effects lol

P3 trial out of Iowa looking at human pancreatic vaccine

result is negative against alpha-galactosidase - highly immunogenic protein

ROAM Trial/EORTC 1308 - surgery vs obs for atypical meningiomas after surgery - RT was 60/30 - primary outcome - time to MR evidence of tumor recurrence - secondary was mostly QOL studies

results are pending...

what areas are boosted for total skin electron beam therapy

scalp axilla perineum soles inframammary

SPEP

serum protein electrophoresis Abnormal peak is seen - look for what protein is causing it M protein = Monoclonal protein from malignant plasma cells M protein spike = MOST commonly IgG > IgA and less commonly others Heavy chains and light chains can specifically be involved

Chemotherapy for gastric

she used the same slide as esophagus like across the board Thing to know is FLOT - surgery - FLOT Gastric has become more immuno heavy so in metastatic setting they are probably looking at PD1 and PDL1 CTLA 4 drugs Pembro approved based on KEYNOTE 059 - response was shown in ALL PDL1 pts Nivo approved in JAPAN based on the ATTRACTION 2 study - 1 yrs OS 27% vs 11%

SAMIT trial

showed no benefit to sequential chemo ITACA-S trial showe no benefit to chemo intensification

ECOG trial of locally advanced pre-op - 74 pts randomized to gem or gem-RT (50.4)

showed similar G3-4 ox but higher G4-5 toxicity (41 v 9%) MS was better in chemoRT - ms 11.1 vs 9.2 m (SS) but underpowered

Intermediate risk prostate cancer - brachy alone vs EBRT + brachy boost - RTOG 0232 - showed what?

showed that there was no difference between brachy alone or combo so brachy alone is fine for IR particularly if favorable

Consolidation with WBRT vs autologous transplant for PCNSL

similar PFS and OS

SWOG 1001 - can we omit RT with good outcomes - again early stage, non bulky, stage I/II - 3 c RCHOP --> if iPET negative --> 1 extra cycle RCHOP --> if iPET positive --> 36 Gy IFRT + boost to avid disease up to 9 Gy + Zevalin

similar outcomes in both arms R-CHOPx4 alone consider standard for those with CR

DBT differences from mammogram

similar to CT scan in that you scroll through to look at slices of breast tissue - increases detection rates and small cancers - decreased false positives and callback rates - improves margin analysis and helps to distinguish skin lesions from breast lesions - similar amount of radiation (not much more)

NGGCT stardard tx

similar to GGCT but more aggressive -- they are less radiosensitive so need up front chemo, surgery, and higher RT dose. More like high risk medulloblastoma. Note that there isn't an RT alone option for NGGCT. These all need chemo and get MORE chemo than germinomas. They always get CSI whether M0 or M+. typically chemo CSI 36 Gy if M0 or M+ -- 54 Gy boost to primary (45 Gy boost to bulky disease in spine) - tx paradigm is more similar to high risk medulloblastoma (everybody gets CSI to 36 Gy and boost IF to 54 Gy) Much worse OS than GGCT (OS ~70% vs 90%) Extent of surgical resection more important for NGGCT More likely to fail in the spine Multimodality preferred - Chemo - Surgery - RT = best outcomes Emergency surgery for symptoms Chemo for all --> carbo/etop --> Max safe resection +/- 2nd look surgery --> RT for all CR by MRI and normal tumor markers --> go on to RT PR --> then possibly second look surgery then RT Chemo = Carbo/Etop alterating with ifosfamide/etop x 6 cycles 36 Gy to CSI + boost 54 Gy to IFRT 45 Gy to spine sites of disease Fields = CSI (whole brain, spinal cord and fluid, thecal sac, meninges) - GTV = pre chemo tumor volume, tumor bed, residual tumor - CTV = GTV + 1 cm - PTV = CTV + 3 mm

Anaplastic RTOG 9402 - - looked at adjuvant PCV for anaplastic after RT - result?

similar to LGG data, found benefit to PCV if they were the 1p19q codel patients -- if not, didn't make a difference. This was before the time that this essentially made them oligodendroglioma by definition Note med OS was 15 yrs for 1p19qcodel + seq RT and PCV (14.7 yrs vs 7.3 yrs with RT alone) Take home is that PCV improved things for 1p19q people but nobody else. If tumors were codeleted, they lived long than non-codel - median survival in codel patients that got PCV after RT was double those that just got RT. This was all based on an unplanned subset analysis tho

Major constraint to know for mesothelioma

similar to NSCLC just know -CL lung V20 <7% - MLD < 8.5 Gy Kidney - V18<33% - normal, mean <18 Gy

IntraOp RT - TARGIT trial - electrons via NOVAC7 as in ELIOT trial - photons (kV) via intrabeam as in TARGIT trial TARGIT - 20 Gy to the surface w/ 50 kV photons (5-6 Gy at 1 cm) - 20-45 min treatment. - 3451 pts - WBI 40-56 Gy vs IORT (20 Gy in single fraction, 15.2% received whole breast for close margins based on final pathology, extensive DCIS, ILC, positive nodes) - median 2.5 yr fu -- (very short follow up) -- and there was a statistically significant increase in recurrences in IORT (5.4% v 1.7%) - they technically randomized some pre-pathology vs post-pathology and found that if you randomized at the time of surgery and you knew their path, there wasn't a difference (2.1 v 1.1 NS) but if you randomized after, there was a decreased LC. ELIOT trial - equivalence trial, age 48-75, <2.5 cm - WBI vs IORT (electrons) - increased LR with IOrT (4.4% vs 0.4%) - higher rates with larger tumors, node postive or TN histology

so take home is IORT kinda sucks

Seminoma RT overview stage I stage IIA stage IIB

stage I - 20 Gy (para-aortic T12 --> L5) stage IIA - 30 Gy (para-aortic + IL iliac) stage IIB - 36 Gy (para-aortic + IL iliac) option is always this or chemo (for stage I = obs, chemo, or RT) Borders for dog leg is: - top of T12 - top of acetabulum - lateral transverse processes (cover ipsi renal hilum) Think prophylactic for stage I node and definitive stage II nodes

Seminoma Chemo overview stage I stage IIA stage IIB stage IIC (N3) or III (M1)

stage I = single agent carboplatin (AUC 7 x 1 or 2 cycles) stage IIA = BEP x 3 or EP x 4 stage IIB = BEP x 3 or EPx 4 stage IIC (N3) or III (M1) = BEPx 3 or EPx 4 OR - high risk = BEPx4 or VIP x 4

Local excision - for whom might this be appropriate . - risk of nodal involvement with this?

stage T0-1 (not invading muscularis propria) Tumor size <3 cm tumor involving less than 30% circumference mobile tumor able to get R0 N0/M0 No LVSI/PNI patient compliant with post-operative surveillance protocol Multiple surgical approaches for this but most commonly referenced is the TEMS - transanal endoscopic microsurgery As you can see, once you move to T2, risk of nodes goes from 0 to 28% --> so this is only appropriate for T1 tumors.

Penile cancer work up

standard H&P stuff, risk factors, labs, biopsy, etc Specific things - urethroscopy, cystoscopy, MRI helpful, US (inguinal)

INPACT Trial -EA8134 trial - looking at more advanced penile cancer to see if there is a role for neoadjuvant therapy - includes ENE, 3+ LNs involved, positive pelvic nodes - randomized into three arms - therapeutic ILND alone, or either neoadjuvant chemo OR with neoadjuvant chemoradiation prior to ILND - then further randomized if didn't get neoadjuvant chemoRT -- +/- adjuvant RT after - inguinals covered to lesser trochanter, covering obturator, internal, external iliacs, up to commons -- presacrals not typically covered - 45 Gy- boost to 54 or 57 based on gross disease

still open - just to give an idea of whats happening with RT in the field

HCC - 70-85% of primary liver cancers worldwide - 3x higher in men - rates increasing worldwide and US - most likely because of Hep C and NASH Risk factors - hep B/C - alpha1-antitrypsin - alcohol - cirhosis - NASH/NAFLD - idiopathic, etc

surveillance criteria shown here

Altered fractionation studies in NSCLC - Modern Attempts - just to know it was done - DONT memorize -- RADIATION ALONE Standard Frac w/ dose escalation - RTOG 9311 - took to like 90 Gy, based on V20 - go as high as V20 would allow. Significant number of recurrences were still locoregional - so didn't seem to help to increase RT Hyperfractionation - RTOG 8311 - RT alone -- 1.2 Gy bid to 60 --> 79.2 Gy --> no OS differences - ----subset analysis of "favorable pts" w/ good PS -- 69.6 Gy arm was better than other arms. - RTOG 8808 - RT alone -- 60 Gy/30 vs 1.2 Gy BID to 69.6 --> no diff in OS but if induction chemo was added, that improved OS. CHART - "continuous hyperfractionated accelerated RT" - tid, 12 continuous days, including weekends compared to 60/30 - Sauders 1996 --> severe dysphasia worse in CHART group (19% v 3%) but OS and LC were both better with CHART (HR 0.65 and 0.63, SS) - squamous specifically did better with CHART. Non-squamous did not benefit from CHART. HART - "hyperfractionated accelerated RT" - ECOG 4593 - tid, but 5 days per week, not 7 days - still high acute tox CHART vs Conventional Fractionation - ARO 97-1 --> no difference in LC or OS and more toxicity in CHART This was sort of the death of these regimens

survival is awful for radiation alone -- elderly pts may benefit from RT alone but these are all retrospective CHART isn't done

Mantle cell lymphoma - often grouped more with aggressives but some are indolent - 7% of NHL 80% are stage III/IV 2/3 have BM involvement GI involved frequently early stage is more rare - translocation? - 5 yr OS? - treatment?

t (11;14) --> Cyclin D1 5 yr OS is 20-30%, FFS 10% so MUCH lower than we see for the indolent lymphomas Extremely radiation sensitive - so typical dose is 24-36 Gy if early stage, but 4 Gy works very well for palliation. Consider prophylaxis for tumor lysis syndrome because its so RT sensitive

basic difference between t test and anova

t test compares means between two groups anova compares means between 3 or more groups

High yield translocations - know the gene thats expressed too t(8;14) t(14;18) t(11;14) t(11;18)

t(8;14) - Burkitt's lymphoma - c-MYC t(14;18) - Follicular lymphoma - bcl2 t(11;14) - Mantle cell lymphoma - Cyclin D1 t(11;18) - MALT marginal zone lymphoma - associated w/ failure of abx therapy - MALT1

meta-analysis for chemo after surgery for GC?

take home is chemo after any surgery does better than now chemo

Subglottic larynx - how common compared to others? - access to what lymphatics - clinical scenario more likely with these? - typical paradigm?

tend to be more aggressive and rarer than supraglottic and glottic access to tracheal lymphatics may result in airway obstruction can be treated with definitive ChemoRT, but salvage TL is usually difficult. More advanced tumors usually go for TL, low tracheostomy and post-op RT/ChemoRT cover b/l II-IV and VI

with CT based brachytherapy planning you can actually map out where the uterus, cervix, tumor, etc all are with MR based brachy planning you can actually see the tumor as well as identify T2 signal, etc to delineate gray zone

the figure shows the 2D vs 3D based planning 3D planning gives you much more conformal dose around the actual target

sbrt for liver mets

the most you dose escalate the better the local control, but location matters diaphram above and bowel below are concerns

Stage II Thymic CARCINOMA - series from China - 31 pts -- stage II thymic CA w/ RO resection - No OS benefit to RT but did have a DFS benefit (not SS, but strong trend)

there just isn't alot of data and we still recommend doing PORT for thymic carcinoma Take home is: - R0 resection - probably only stage II-IV thymoma and all thymic carcinoma (steven lin says he doesn't necessarily do PORT for stage II thymoma if R0, but does if thymic carcinoma) - R1/R2 resection you are doing PORT or def RT for essentially all stage thymoma/thymic carcinoma.

SCOPE-1 trial - R pII/III trial - did not meet p2 endpoint - was looking at cap/cis + 50 +/- cetuximab

there was increased toxicity with increased failure to complete treatment associated with cetuximab So cetuximab is the wrong answer

Key to workup is to rule out MM

think CRAB skeletal survey - now a days PET/CT probably but plain films is an option vs low dose whole body CT SPEP/UPEP with IFE (immunofixatino electrophoresis) CD138 and Cd38 ar important markers

Brain mets - definitive management - radiation, whole brain vs stereotactic - surgery, chemo symptomatic management - steroids with decadron, etc - control neurologic symptoms and increase survival is goal Look at RPA for survival with metastasis -- early data

this is old data that shows poor survival from early RTOG RPA studies This doesn't account for histology, size, number of lesions, location, systemic tx extent/response updated RTOG RPA - 9508, 1960 pts - showed updated graded prognostic assessment - lung cancer -- kps, age, extracranial disease, #mets - breast - kps, age, tumor subtype - melanoma, rcc -- kps, #mets - 9508 was the WBRT +/- SRS boost trial that showed OS benefit of SRS IF only a solitary brain met. SRS also improved LC (82% vs 71%), and improved performance status at 6 months. MVA showed SRS improved outcomes for RPA class I and "squamous and non-small cell" histology so you can see they have different predictive things

Gastric high grade lymphoma

thought to come from gastric MALT or de nevo tx entire stomach and gastric noes R-CHOP x 6 followed by RT

Treatment delays can have what effect on local control?

time line of <56 days should be aimed for 1.4% per day LC lost --> 0.6 Gy increased per day lost is said to compensate for difference This is due to repopulation

types of hysterectomy and what they remove extrafascial hysterectomy modified radical hysterectomy radical hysterectomy

types of hysterectomy and what they remove extrafascial hysterectomy = basically just the cervix modified radical hysterectomy = dissects about halfway through the parametrium - dissects medial portion of the cardinal ligament and proximal uterosacral ligament - uterine vessels ligated at the ureter - medial half of parametrium - 1-2 cm of the vagina removed radical hysterectomy - dissects all the way to the pelvic sidewall - uterine vessels ligated at the origin at the hypogastric artery (some sources say internal iliac artery) - upper 1/3 of the vagina removed The uterosacral ligament is the structure that allows the cervix to track posteriorly into the sacral fossa.

Orthotopic transplant considered in what pts

unresectable because of underlying dysfunction would need a new liver to compensate for what you take out essentially 4 yr OS not bad when transplant is done

Median survival time for untreated brain mets?

untreated = 4 weeks

Diff between low risk and very low risk prostate cancer?

very low risk must be - PSA density <0.15 - cT1c prostate (low risk can be cT1c-T2a) - PSA <10 ng/mL - <3 cores + and <50% of each core w/ cancer

NWTS V - modern study and gives us how we treat now mostly - for stage III and IV -- we give 10.8 Gy to the abdomen for FH. - for stage IV --> 10.8 to abdomen and 12 Gy to lungs only stage III and IV patients got RT. They added RT for stage II if anaplasia. Major findings?

very low risk patients <2 yrs, stage I FH, <550 g --> excellent EFS and doesn't need adjuvant tx high relapse rate in stage I diffuse anaplasia (10 of 29 relapsed, 5 died). --> they didn't get RT on this study stage I focal anaplasia 3 of 9 relapsed and 2 died --> didn't get RT on this study - so 1/3 of anaplasia (focal or diffuse) relapsed and alot of them died. Spillage makes a huge difference. 84% EFS if no spill, 70% EFS if spill. - so now spill makes them stage III

Timmerman 2006 - JCO - "coined the no-fly-zone" - defined it how? which SBRT dose do you NOT use there

w/in 2 cm of proximal bronchial tree as defined as 2 cm of distal trachea, carina, and the named major lobar bronchi up to their first bifurcation Timmerman paper showed that 2 yr freedom from G3-5 toxicity was 83% for peripheral but only 54% for central lesions. Dose was 60 Gy in 3 fractions - so you do NOT use 3 fraction regimens in the no fly zone

waldenstrom's macroglobulinemia systemic AL amyloidosis

walen - IgM specific

extent of resection in lgg

we don't often get gtr - so we go for "maximally safe resection" because patients do better if you get more out - these are sometimes more infiltrative and you just can't get more out though.

Summary of adjuvant RT for rectal

we don't typically do it often - its the "high risk" part like R1 or nodes

Advantages vs disadvantages of neoadjuvant chemoRT for pancreas

we tend to do neoadjuvant more often than adjuvant now a days

Surgical indications for cord compression

you need tissue spinal instability bony compression - multiple retro studies show bony retropulsion to be poor predictor of ambulation even if you do rt - rt doesn't fix broken bones neurologic progression after RT or cord tolerance would be exceeded if re-rt

OS difference between type I and II endometrial cancer

~16% 5 yr OS difference Serous and carcinosarcoma have the poorest prognosis

Pembrolizumab in HN cancer pts - phase I/II trial of 132 pts - >80% had prior chemo - objective response rates = ?

~25% >50 had regression of disease HPV+/- responded the same

Epidemiology - HGG how common? what % of malignant CNS neoplasms in adults? what % are multicentric?

∼12 K/yr malignant primary brain tumors in the U.S ~ 80% of malignant CNS neoplasms in adults < 5% are multicentric

Recursive partitioning analysis-- older way of prognosticating OS w/ treatment, before we had molecular/genotype profiling What are the RPA groups for GBM? ● For Mock orals does it mean if they have had surgery?

● RPA = 3 is the best that any GBM can have (< 65 yo (older sources say 50), normal mental status, and some type of resection was performed) ● RPA = 4 is the same as RPA 3, except older than 65 yo (older sources say 50), KPS ≥ 70 ● RPA = 5 means biopsy alone/no surgery ● RPA = 6 means severely altered mental status, very poor KPS (usually goes to hospice rather than treating) If yes to surgery -- then you know you are RPA 3 or 4. Then ask are they younger than 50 (RPA 3) or older than 50 (RPA 4)