RadOnc Question Bank High Yield Facts

Classic imaging appearance of PCNSL?

"Cotton wool" appearance - homogenous with fuzzy borders

Rough estimate, what is the risk of pelvic and para-aortic lymph node mets for a stage IIA2 cervix cancer?

"Rule of 15's" = Risk of pelvic lymph node involvement stage 1= 15% risk stage 2=30% risk stage 3=45% risk Risk of para-aortic involvement is ~50% of pelvic involvement

synchronous vs metachronous tumors?

"Synchronous" tumors refer to cases in which the second primary cancer is diagnosed within 6 months of the primary cancer; "metachronous" tumors refer to cases in which the second primary cancer is diagnosed more than 6 months after the diagnosis of the first primary cancer.

Taghian JCO pooled analysis of 5 NSABP trials looked at rates of locoregional failure in pts treated with mastectomy and systemic therapy but NOT radiation. 10 yr Locoregional failure rates: LRF broken down as a function of 1-3 nodes, 4-9 nodes, vs 10 or more nodes had what impact on LRF? Hint: starts around 13% LRF broken down as a function of 2 cm or less, 2-5 cm, >5 cm had what impact on LRF? Hint: starts around 15%

# of NODES 1-3 nodes = 13% 4-9 nodes = 24% 10 or more nodes = 32% For nodes, you add about ~10% for each category SIZE OF PRIMARY 2 cm or less = 15% 2-5 cm = 21% >5 cm = 25% For size you add about ~5% for each category

Important points about RTOG 9601 - randomized T2 w/ pos margin or T3 men w/ post-prostatectomy PSA 0.2-4 to 64.8 Gy +/- 2 yrs biclutamide - initial manuscript showed OS benefit of biclutamide in WHAT groups? - feng secondary analysis showed benefit in WHAT groups? - Spratt secondary analysis showed harm in what group?

- Biclutamide increased 12 yr OS (76 v 71%) and improved 12 yr DM rate (14 v 23%). Specifically in those with PSA of 0.6 and lower, there was no OS benefit. Only those w PSA 0.7 and higher have survival benefit - FENG 2021 paper looked at the DECIPHER score - kinda like oncotype Dx 0-0.45 = low risk 0.45 - 0.6 = intermediate risk >0.6 = high risk FENG paper showed that men with INT and HIGH risk had an OS benefit (8.9% abs benefit vs 2.4% abs benefit in int/high vs low risk) REGARDLESS OF PSA Spratt --> if PSA <0.6, 2 yrs ADT caused higher other cause mortality and no difference in PCa specific mortality.

Mechanism of action of: - cisplatin (platinum drugs) - topotecan/Irinotecan/Etoposide/Teniposide - anthracyclines (examples?) - cyclophosphamide/iphosophamide - Bevacizumab (avastin) - Cetuximab - Pantimumab - Sunitinib - Sorafenib - Vemurafenib - Infliximab - Pembrolizumab/Nivolumab - Durvalumab/Atezolizumab/Avelumab - Ipilimumab - 5 flurouracil - mitomycin C - Dactinomycin - Bleomycin - Plicamycin - taxol drugs - Gemcitabine/capecitabine - Abraxane - FOLFOX - FOLFIRINOX

- Cisplatin forms crosslinks between two DNA strands, which prevents the normal synthesis of DNA which leads to cellular lethality - topotecan/Irinotecan/Etoposide/Teniposide = Topoisomerase II inhibitors (topoisomerase allows DNA single (topoI) or double (topoII) strand breaks during replication. - anthracyclines (doxorubicin, epirubicin, daunorubicin, idrarubicin): DNA intercalation/topoisomerase II poison - cyclophosphamide/iphosophamide: intercalating agent - Bevacizumab (avastin) = VEGF-A ligand inhibitor - Cetuximab = EGFR - Pantimumab = humanized IgG2 monoclonal antibody targeting the EGFR - Sunitinib = multi-tyrosine kinase receptor inhibitor - Sorafenib = multi-tyrosine kinase receptor inhibitor (affects VEGF/PDGF/Raf kinase - Vemurafenib = BRAF kinase inhibitor - affects BRAF/MEK/ERK signaling - approved for V600E - Infliximab = anti-TNF antibody - Pembrolizumab/Nivolumab = PD1 - Durvalumab/Atezolizumab/Avelumab = PDL1 - Ipilimumab = anti-CTLA4 antibody - 5FU = thymidylate synthase inhibitor - mitomycin C = DNA crosslinker (undergoes metabolic reductive activation in hypoxic cells to generate an alkylating agent that cross-links DNA) - Dactinomycin = binds to double stranded DNA through intercalation between adjacent guanine-cytosine base pairs, inhibits all forms of DNA-dependent RNA synthesis - Bleomycin = induces strand breaks in DNA - Plicamycin = RNA synthesis inhibitor - taxols = stabilizes tubulin/microtubule complex preventing cell division - Gemcitabine/capecitabine: anticancer nucleoside that is an analog of pyrimidine -- depletion of deoxynucleoside triphosphate pool - Abraxane: protein bound paclitaxel - FOLFOX = Folinic acid "FOL", Fluorouracil "F", and Oxaliplatin "OX - FOLFIRINOX = FOLFOX + irinotecan

Overview of PMRT benefit?

- Classic studies supporting PMRT = Danish 82b/c (Overgaard), British Columbia EBCTCG metanalysis ---all essentially show ~60-70% relative risk reduction of LR and all show ~10 yr 10% OS benefit. Except meta-analysis which showed 5% benefit. 82b = pre-menopausal 82c = post-menopausal BC = pre-menopausal Take home is that there is about a 10% survival benefit unless talking meta-analysis data. And remember the subset analysis of 1-3 was from the metanalysis which showed a BCSM benefit to RT in that group (not OS).

Goal dose constraints for prostate brachytherapy - D90 - V100 - V150 - RV100 - UV5 - UV30 - UV150

- D90 = dose to the hottest 90% of the prostate = ideally >100% Rx dose - V100 = volume of prostate receiving 100% Rx dose - ideally 100% but >90% acceptable - V150 = measure of how hot the plan is - volume of prostate receiving 150% of Rx dose - we want to minimize the V150. Generally should be <50-60% of the prostate - RV100 = volume of rectum getting 100% Rx dose = generally <1 cc - UV5 = average dose to the hottest 5% of the urethra - <150% rx dose - UV30 = average dose to the hottest 30% of the urethra - <125% rx dose - UV150 = volume of urethra receiving 150% of the rx dose - we do not want ANY of the urethra getting this much - so this value should be 0

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. Note -- this is relevant because 89% had 3D treatment and 0617 showed reduced toxicity of imrt compared to 3D 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.

- RTOG 8501 - Herskovic NEJM 1992 --- randomized 129 pts 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?

- RTOC 8501 --- randomized to 64 Gy RT alone or chemoRT - 5FU/Cis + 50 Gy --- 86% sqCC -- almost all squamous (14% adeno) --- trial closed early because of benefit of chemo --- 5 yr OS CRT v RT alone = 26% vs 0% --- chemoRT had significantly better LC - but 46% of CRT pts had persistent disease at 12 months which led to INT 0123 trial chemo was Cisplatin-5FU

2018 ILROG guideline doses for solitary plasmacytomas: - bone <5 cm - bone >5 cm - extraosseous

- bone <5 cm = 35-40 Gy - bone >5 cm = 40-50 Gy - extraosseous = 40-50 Gy

acoustic neuroma - gkrs vs surgery - hearing preservation - speed of symptoms relief - facial nerve damage

- hearing preservation = GKRS better (70% vs 37.5) - speed of symptoms relief = surgery better - facial nerve damage = GKRS better (0% vs 37%)

Sarcoma important points - when to image? - what type of biopsy - when would you need an MR brain? - when would you need an MR spine?

- image before biposy - these are often heterogenous so its better to be able to plan where to biopsy (usually need CT and MR w contrast) - ideally core needle or incisional biopsy - when would you need an MR brain = angiosarcoma - when would you need an MR spine = myxoid liposarcoma

CeteG NOA-09 trial looked at addition of Lomustine (CCNU) - 131 MGMT methylated GBM patients randomized to standard STUPP regimen or up tot 6 courses of CCNU + TMZ RT - how was the chemo given? How is this different than Stupp? - results?

- median OS was improved from 31 months to 48.1 months with addition of lomustine. G3+ AE was 51 vs 59%. - controversy is that lomustine appeared to improve OS without change PFS (this was also the case on the Thora 60 gy bid trial for SCLC). Also power was a question in the study. Toxicity also thought to be worse with CCNU. This was also a "modified ITT analysis" Chemo = lomustine (100 mg/m2) on day 1 + TMZ (100-200 mg/m2 per day on days 2-6) every 6 weeks for up to 6 cycles. Thus only done during the 1st week of radiotherapy. Stupp is 75 mg/m2 given daily for 7 days per week (NOT JUST WITH RT) -- followed by 150 mg/m2 for 5 days per 28 day cycles x 6 cycles

Wilms vs Neuroblastoma key differences 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 - this one is critical because arising from kidney parenchyma is one of the most important things - displaces adjacent structures without insinuating between them = wilms tumor - crosses the midline = neuroblastoma - this is not a very accurate sign, sometimes wilms can cross the midline too - well circumscribed and does NOT cross midline = wilms tumor - this is not a very accurate sign, sometimes wilms can cross the midline too - 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

Adjuvant merkel cell carcinoma doses for the following: - primary site negative margins - primary site positive margins - primary site gross residual disease

- primary site negative margins = 50-56 Gy - primary site positive margins = 56-60 Gy - primary site gross residual disease = 60-66 Gy Nodal dose: if sentinal node negative technically can omit. If high risk of false negative - can do 46-50 Gy to nodal basin; IF SLN+ can do 50-56 to nodal basin - gross nodes go to gross dose 60-66 Gy

risk of radiation myelitis with a spinal cord dmax of 50 for conventional frac?

0.2% (full thickness)

recommended CTV margin for complete resected atypical meningioma per RTOG 05-39?

1 cm RTOG 0539 - observed low risk GTR/STR G1 meningioma - treated intermediate risk (G2 GTR meningioma or recurrent G1) with 54 Gy - treated high risk pts (recurrent G2/STR G2 or G3 GTR) to 60 Gy Intermediate risk - CTV 1 cm High risk - CTV-60 was 1 cm; CTV 54 - 2 cm (treated like an SIB) -- question asked this as "what was the recommended 'low dose' CTV margin for malignant meningioma"

What is appropriate CTV field margins for a skin SCC <2 cm?

1-1.5 cm

STAMPEDE definition of low metastatic burden

1-3 axial bone mets no visceral meds regional node mets don't count as visceral Revised definition 1-3 NON-regional node mets - these men also benefited from RT to primary

steroid dose for radiation pneumonitis

1-4 mg/kg for 2 weeks followed by slow taper over 4-6 weeks Ends up being 60-100 mg for 2 weeks with slow taper

What is the 10 yr breast cancer mortality in DCIS pts that undergo treatment?

1-5% No diff in breast cancer mortality if they get RT with breast conserving surgery for DCIS (not true for invasive, meta-analysis data showed BCSM benefit for RT in that case)

What are indictions for post-op radiation to inguinal and pelvic lymph nodes for vulvar cancer?

1. Clinically palpable or matted lymph nodes on physical exam 2. 2 or more pathologically positive lymph nodes 3. Nodal extracapsular extension 4. Lymph node positivity ratio 20% or higher Based on GOG37 - surgery alone vs surgery + RT -- treated post-op inguinal/pelvic nodes (not vulva) - closed early because significantly lower rate of nodal failure in Sx+RT (5%) vs Sx alone (24%) and improved overall survival (68% vs 54%) - subset analysis showed benefit of RT was in those w/ 2 or more nodes, ENE, or palpable/matted lymph nodes -- of note, updated paper showed at 6 yrs OS benefit no longer significant, but there were less cancer related deaths in the radiation arm still (29% v 51%).

What are examples of ABSOLUTE contraindications for definitive resection for RP sarcomas?

1. Spinal cord involvement 2. Distant metastases 3. Peritoneal implants 4. Involvement of the superior mesenteric vessels 5. Extensive vascular involvement

spinal cord re-irradiation highlights Neider 2006 red journal paper - put into risk groups of low risk, intermediate and high risk risk of myelitis is low risk 3 or fewer points - 3% int risk 4-6 points - 25% risk high risk >6 points - 90% risk What three major factors determine the risk score?

1. cumulative BED2 of 120 or more - scale of 0-9 points based on 10 Gy2 increments above 120 2. interval of treatment <6 months - 4.5 points if yes 3. BED of either course along being >102 Gy2 - 4.5 points if yes remember we consider spinal cord recovery to be about 50% at 2 yrs, 33% at 1 yr and 25% at 6 months = spine QUANTEC paper or Nelson DUKE paper

What is the most common radiation induced soft tissue sarcoma histology?

1. high grade undifferentiated Pleomorphic sarcoma 2. angiosarcoma 3. leiomyosarcoma 4. fibrosarcoma

NCCN guideline definition of post-menopause?

1. hx of b/l oophorectomy 2. age >60 yrs 3. age <60 yrs and amenorrheic >12 months in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression (if on these <60, must have FSH in menopausal range)

What are the goals of TBI?

1. immunosuppression to allow grafting of the donor bone marrow 2. eradication of malignant cells (leukemic cells, etc) 3. eradication of cells with genetic disorders (fanconi anemia, etc)

What were the arms of RTOG 91-11

1. induction chemo (cis 100 mg/m2/5 fu 1000 mg/m2) x 3 cycles (assessed for response after 2) - if <PR after 2 cycles -- went to laryngectomy + adjuvant RT 2. Radiation alone 3. Radiation + chemotherapy (Cisplatin 100 mg/m2) 2 yr Larynx preservation = 88% CRT, 75% IndCT, 70% RT (SS) 2 yr LRC - 78% CRT, 61% IndCT, 56% RT (SS) 5 yr distant mets actually higher in RT alone - 15% CRT, 12% IndCT, 22% RT (SS) Overall survival not different Larynx preservation at 5 yr - 84% CRT, 71% IndCT, 66% RT (SS) 10 yr - 82% CRT, 68% IndCT, 64% RT (SS)

PACIFIC trial showed what benefit to the addition of durva to chemoRT?

10 mg/kg durvalumab q2 weeks for 1 year Initial publication showed PFS benefit Subsequent longer follow up pub showed by PFS and OS 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) 5 yr OS - 42.9% vs 33.4% 5 yr PFS - 33.1% vs 19% 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. subset analysis also showed if PDL1 >25%, benefit seems to be stronger

What is the rate of transformation of oral dysplasia to invasive cancer?

10%

V30 < 30 cc for chestwall pain associated with what % chance of late chestwall pain?

10-15% chance

In RTOG 90-05 was a study to determine the MTD for brain tumors - what % had prior brain radiation?

100%

in the Third spanish germ cell cancer group study, what was the 3 yr OS for all patients? JCO 2011 study compared surveillance to chemotherapy (carbo x 2 cycles) in stage 1 seminoma? what were predictors of relapse?

100% 3 yr OS Predictors of relapse- old 2002 study, these didn't hold up later on Tumor size > 4 cm Rete testes invasion DFS was 88% vs 98% for surv vs chemo.

Common total skin electron therapy dose for MF?

12 Gy to total skin Areas you may need to boost - scalp - palms and soles - inframammary region - perineum

GKRS glomus tumor doses?

12-15 Gy

What genetic alteration is associated with well differentiated/dedifferentiated liposarcoma

12q amplification - involves the MDM2 and CDK4 genes

Pts with PET/CT negative N2/3 disease have what % chance of actually being positive?

15% chance NPV is better in smaller/more peripheral tumors randomly RUL tumors have a higher likelihood of actually having positive N2/3 nodes

SRS dose for a 1 cm lesion in the pons?

15-18 Gy because its the brainstem Cutoff seems to be 1 cc for complications from treatment in the brainstem, complicate rate is ~40-60% if >1cc and 0% if <1 cc. Max point dose is 12.5 Gy per quantec <5% risk of neurtoxicity Ideally limit 10-12 Gy to 1 cc standard dose ~16 Gy

What was the biochemical failure rate at a median f/u of 8.9 years in the dose escalated arm vs the conventional arm of the proton dose escalation trial for prostate cancer?

16 v 32% Low and intermediate risk prostate cancer randomized to 70.2 GyE vs 79.2 GyE high dose had better control The interesting part is they did the first 50.4 Gy with photons then did either 19.8 GyE or 28.8 GyE with protons. OS was not difference

Women treated with radiation of HL matched with a sporadic breast cancer control group -- median time to BC diagnosis was what?

18 yrs median time After radiation, BC was more likely screen detected, earlier stage, bilateral and metachronous Screening detects earlier disease

What is the locoregional recurrence rate after sublobar resection in the lung cancer study gruop 821 (Ginsberg, 1995)

18% LR was 6% v 18% (lobectomy v sublobar) This established lobectomy as standard of care

At what dose should the heart be blocked during radiation for a left sided pleural mesothelioma after EPP? when is the stomach blocked? What's the danger of IMRT here?

19.8 Gy - to reduce the risk of pericarditis The stomach is blocked throughout the entire hemithoracic radiation course. An electron field patch is used to supplement dose to the pleural space under the block. Dana-Farber/Brigham experience showed IMRT after EPP caused fatal radiation pneumonitis in the CL lung in 6 of 13 pts. - they used V20 of 20% and MLD of 15 Gy for the remaining lung - WAY Too high - Pts that developed RP had V20 of 17.6% vs 10.9% (no RP) and a V5 of 98.6% vs 90% (none) The Rice MDACC red journal 2007 found that limited V20 <7% was associated with substantial reduction in risk of death. Note the IMPRINT trial is for pleurectomy/decortication with IMRT adjuvant

What TBI dose has the same secondary solid cancer risk as chemotherapy alone regimens?

2 Gy in 1 fraction

definition of the central tracheobronchial tree?

2 cm rind around the proximal bronchial tree from carina, right and left upper lobe bronchi, bronchus intermedius, right middle lobe bronchus, lingular bronchus, and right and left lower lobe bronchi)

HD16 again attempted to omit RT for favorable stage I-IIA/B HL -- how many cycles of ABVD did they get?

2 cycles if CR - they got randomized to RT or obs - RT improved PFS All of these trials for HL showed that omission of RT always resulted in worse PFS (never affects OS) The only one I can think of that DIDNT result in loss of PFS with omission was HD17 HD16 - favorable PET response omission trial HD17 - unfavorable omission response trial -->this was ABVD x2 + BEACOP x2 - if PET neg -- randomized to 30 Gy vs obs -- there was NOT a difference in PFS or OS in this one. People still hate BEACOPP

How many cycles of induction chemo were done before assessment on the VA larynx trial?

2 cycles Cis/5FU If at least PR, they got 1 more cycle and then chemoRT vs if progression or stable --> surgery if PR after chemoRT --> surgery Surgery v ChemoRT 2 yr OS 68 v 68% 2 yr DFS NS different recurrent disease: - primary: 2% v 12% (SS) - nodes: NS Distant Mets: 17 v 11% (SS) Larynx Preserved (4 yrs): 12 v 62% - note: 12% had partial laryngectomy in surgery arm T4 tumors did worse than <T4 tumors - T4 = 56% salvage TL - <T4 = 29% (SS)

Describe field borders for a 2 field vs 3 field PMRT technique

2 field = this is more like Z11 fields where you are hitting chestwall and lower axillary levels I and II - without a specific supraclav field Superior border = Determine the inferior border of the clavicular head (delineated by wire at time of CT sim) Inferior border = 2 cm below the inframammary fold (use CL breast if post-mastectomy). This isn't sometime we routinely do because we almost never treat PMRT not intentionally covering regional nodes Important points to remember: 1. set the medial field first to ensure the CL breast isn't in the field 2. add collimation to the medial tangent field and either match the posterior border of each tangent field to avoid divergence into the lung or half beam block each tangent posteriorly 3. isocenter located at the midpoint between the superior and inferior borders and at the midpoint between the medial and lateral wires (sternum and mid-axillary line) and at a depth just inside the chest wall 4. oppose the medial tangent to create the lateral tangent. 5. tangents will cover most of ax level I/II 6. "high tangents" are sometimes utilized with the superior border placed at the superior border of the humeral head to treat the I and II levels if the axilla was not dissected (ala Z11) 3 field = this is the two opposed tangents + SCV field Superior border = Cricoid cartilage Inferior border = inferior clavicular head lateral border = coracoid process (sometimes brought to the lateral edge of the humerus) medial border = ipsilateral vertebral pedicles 1. set up the SCV field based on the above borders 2. angle the supraclav field 10-15 degrees AWAY from the spinal cord such that a RAO beam is used for left sided SCV fields and LAO for right sided SCV fields 3. Add medial and lateral tangents as above but you are also half beam blocking superiorly to match the tangents with the SCV field -- if the tangent field is >20 cm, you have to do a 2 iso technique Four field technique refers to adding a PAB (posterior axillary boost field) -- opposed SCV field

What is the median OS for a brain met patient with RPA class III? review all classes

2 months Class 1 = 7.1 months Class 2 = 4.2 months Class 3 = 2.3 months Class 1 = KPS 70 or greater, age <65, controlled primary, no extracranial mets (solitary). Class 2 = KPS 70 or greater, age >65, uncontrolled primary, extracranial disease Class 3 = KPS <70 - worst prognosis

when is RILD considered to be possible after radiation?

2 weeks to 8 months - most commonly w/in 3 months 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

What was the result of the FORUM trial (Peters JCO 20) - high risk pediatric ALL w CR from induction chemo randomized to TBI vs chemo conditioning prior to transplant?

2 yr OS was actually significantly higher in the TBI arm (91% vs 75%, SS)

classic post-op pancreas 4 field field borders

2-3 cm anterior to pre-operative GTV and posteriorly splitting the vertebral bodies

Eisbruch RTOG 0022 delivered what dose per fraction to gross disease

2.2 Gy per fraction (66 Gy in 6 weeks)

RTOG 93-10 CNS lymphoma treated with MVP followed by 45 Gy or 36 Gy (1.2 bid) if CR followed by cytarabine - what was the % of pts >60 yrs that developed severe delayed neurotoxicity?

20%

What % of pts with Ewing's sarcoma have macroscopic metastases at diagnosis?

20% note: virtually all pts are thought to have micro-metastatic disease at presentation.

Flinkinger 2002 showed best LC is achieved with AVM with what SRS does?

20-24 Gy

whats the overall rate of pseudoprogression for GBM?

20-30% higher for MGMT methylated- as high as 66% think 30% all comers - 60% MGMT

SCORE-2 trial compared 20/5 to 30/10 for cord compression and found what?

20/5 was non-inferior

STUPP 2005 NEJM showed what median OS benefit to addition of TMZ? STUPP 2017 JAMA showed what median OS benefit to addition of TTF?

2005 - TMZ improved OS from 12.1 - 14.6 months 2017 - TTF improved OS from 16 m to 20.9 months Simplied terms think 12 m --(TMZ) --> 14-16 months --(TTF)--> 20 months

What is the change to the low dose CT chest screening?

2013 - 55-80 yrs, 30 pack yr history, quit w/in last 15 years 2021 - 50-80, 20 pack yr history, quit w/in last 15 years

median age of presentation for neuroblastoma?

22 months

treatment for SR medulloblastoma

23.4 Gy CSI + 54 Gy total boost involved field 18 Gy was INFERIOR in terms of EFS and OS for standard risk

Recommended dose for orbital MALT lymphoma?

24 Gy in 12 fractions

Patients with T cell acute lymphblastic leukemia with testicular involvement that do NOT have CR in the testicle after chemotherapy need what radiation?

24 Gy in 12 fractions CNS 3 = 18 Gy CNS 2 = 12 Gy if int/high risk CNS 1 = 12 Gy if int/high risk Pts only get testicular radiation if the testicle remains positive (often by biopsy) at the end of induction chemo

How far from the incisors is the carina?

25 cm

Non-bulky stage IA grade 1-2 follicular lymphoma - after ISRT what is the % chance of relapse anywhere else in the body?

25% freedom from progression stage I = 75% stage II = 50%

What is the % cutpoint identified by Truong et al 2005 for LN involvement in the 1-3 node positive group?

25% Between different study the ratio is about 20-25%

12 yr LR rate for high grade DCIS with WLE alone?

25% - invasive disease at recurrence is about 50:50 chance low grade 14.4

IAEA (Roa 2015 JCO) looked at frail/elderly/or elderly and frail and compared further hypofrac 25/5 to 40/15. results?

25/5 is also non-inferior to 40/15

minimum decadron dose for which PCP prophylaxis should be considered in a pt undergoing cytotoxic chemotherapy?

3 mg for 1 month - consider PCP prophy

following concurrent chemoradiation for anal cancer, what is the median time to regression of the tumor and how long can tumors continue to regress for?

3 months is median time can regress for 6 months after therapy - don't biopsy in this time

3BEE is the unfavorable definition memory aid for Hodgkin lymphoma based on which group definition?

3 or more nodal sites involved Bulky mediastinum (TTD >0.33) Extranodal sites 1 or more ESR >50 if A >30 if B This is the German Hodgkin Study Group definition

ARTDECO trial (JCO 2021, Hulshof) - prospective, RCT - SIB of 2.2 Gy/fx to a total of 61.6 in 28 fractions to the primary tumor vs - standard dose 50.4 Gy in 28 fractions 260 Pts were T1-4, N0-3, M0-1 (limited to supraclav nodal disease) - chemo was carbo/taxol 61% squamous cell, 39% adenocarcinoma results?

3 yr L-PFS = 70 SD vs 73% HD (NS) 3 yr LR-PFS = 52% SD vs 59% HD (NS) G4-5 toxicity no different 50.4 Gy is still the standard based on this - no benefit to dose escalation in esophageal cancer based on the ART DECO trial.

DOSE ESCALATION IN ESOPHAGEAL CANCER -- this trial was essentially in response to the previous esophageal dose escalation trials like RTOG 8501 (Herkovic) that had 5 yr OS 26% vs 0% for chemoRT with Cis/5FU to 50.4 vs 64.8 RT alone. INT 0123 trial then tried dose escalation up to 64.8 with chemo but OS was actually worse on the higher dose arm. People then thought that this was because the chemo was 5FU based rather than cross style carbo/taxol. Also on INT 0123 most of the deaths that contributed to worse survival on the DE arms happened before they even got to 50.4 ART DECO trial -- more modern trial - looked at dose escalation in inoperable esophageal cancer - used IMRT and carbo/paclitaxel - compared 50.4 Gy in 5.5 weeks to 61.6 Gy in 5.5 weeks (dose painted - 50.4 Gy to the larger field with 2.2 SIB to 61.6 Gy) - keeps shorter treatment time and dose intensifies - primary objective was improved LC of 15% (looking for 50% --> 65%) - median fu was 48 months - most pts were squamous cell carcinoma (typical for inoperable studies) - but majority was actually upper and mid T tumors - only 3-6% had cervical tumors). 31% were medically unfit for surgery. results?

3 yr Local progression free survival was NOT different at all (71 v 73%) by histology - better local control in squamous cell but not statistically significant (77 v 62%). Squamous cell of 77% for inoperable squam is pretty damn good though No improvement in essentially any metric though with dose escalation So ART-DECO confirms the result of the RTOG 8501 and the INT 0123 studies that say there is no benefit to dose escalation for esophageal

Ang NEJM 2010 - RTOG 0129 - 3 yr OS for OPX cancer regardless of HPV status

3 yr all comer = ~60-70% 3 yr OS HPV + 82.4% HPV - 57.1% 8 yr OS - HPV + 70.9% - HPV - 30.2%

What is the rate of facial numbness after SRS for TN?

3-15%

CTV margins for esophageal cancer

3-4 cm above the GTV or 1 cm above gross periesophageal nodes - whichever is more caudal --*for proximal cases never above the cricoid unless there's gross disease there 3-4 cm below the GTV -- but only 2 cm margin along the gastric mucosa when a 4 cm geometric expansion into the stomach would result in unacceptably high stomach volume. 1-1.5 cm radial CTV expansion - only 0.5 cm into cardiac tissue and liver

peak age for wilms tumor

3-4 years

What CTV margin should be used for a merkel cell carcinoma of the trunk

3-5 cm HUGE margins

median age of ependymoma

3-5 years

What was the median OS on convert trial for 66 vs 45 bid?

30 months bid and 25 months daily - NS

What is the rate of distant metastases for a FIGO IB G3 endometrioid adenocarcinoma treated with TH and EBRT?

30%

ACNS 1123 for germinomatous and non-GGCT - what is the experimental arm?

30.6 Gy WVRT with 54 Gy IFRT for patients that get a CR to chemo This arm was closed early due to failures

12 yr IBTR (inv/non-inv) for NSABP B-17 for DCIS post-lumpectomy +/- RT?

32% vs 16% in favor of RT. 50% LC benefit 50% of recurrence are invasive No OS benefit

ASTRO/ASCO/AUA recommendations for prostate SBRT doses?

35 - 36.25 Gy in 5 fractions to the PTV may be offered to low and intermediate-risk patients with prostate size <100 cc

CSI and boost dose for gross disease in the spine for medulloblastoma?

36 Gy --> 45 Gy total to gross disease (50.4 Gy below terminus of spinal cord)

What is the RT dose for trilateral retinoblastoma?

36 Gy CSI 45 Gy to the cranium 50.4 Gy to the pineal gland

unfavorable risk features (ANY 1 of them) for hodgkins based on the GHSG definition?

3BEE 3 or more nodal sites Bulk ESR >50 if no B symptoms or >30 if B symptoms Extranodal disease ANY ONE makes you unfavorable (not a candidate for HD10 - ABVD x2 + 20 Gy). Think more HD11 (ABVDx4 + 30 Gy) if any of 3BEE factors

how should CSI be set up when using a two field approach

3D CSI w/ two parallel opposed cranial fiels matched to a single posterior spinal field between C2/5 if spinal cord is >40 cm, use extended SSD or two matched fields Matched PA fields should match at or below L1 (termination of the spinal cord) Field matching for the junction should have them meeting ANTERIOR to the spinal cord to ensure no hot spot in the cord. Fields should be "feathered" every 5-7 fractions or w/ every 9 Gy

dose for gynecomastia prophylaxis?

4 Gy x 3 to a 10 cm diameter circular block or 10 Gy x 1 en face electrons prescribed to 85% IDL NO bolus - skin not target

What is the dose to the remaining testicle without vs with the clamshell for a dogleg field?

4 cGy per fraction without 1.5 cGy per fraction with more modern series from Princess margeret suggest its actually: - ~1.4 cGy/fraction without - 0.13 cGy/fraction with

length of ADT for intermediate risk prostate cancer

4-6 months Don't forget the D'Amico trial showed a CSS and OS benefit to the addition of 6 months of ADT in Int risk prostate cancer Note: Zumsteg 2013 suggested NO benefit to ADT in fav int risk w/ only 1 int risk factor (ie. we only do ADT in unfav int and up) Of note the recently published RTOG 0815 evaluated 6 months ADT in int risk and found only PCSM (n = 1 v n = 10), biochemical recurrence free survival benefit (2% v 10%), and decreased distant met rate (but didn't affect OS)

What is the crude recurrence rate after pre-op RT followed by GTR per Toronto Sarcoma Group, MDACC experience and the STRASS trial?

40-50%

analysis of 5 major trials for aggressive NHL comparing chemo alone vs chemo + RT showed what % of relapses are at the original site of disease in the chemo alone patients

40-60% Number is roughly half for chemo+RT pts

when treating a malignant pleural mesothelioma after EPP, at what dose during hemithoracic radiation is the medial field border shifted from the CL to the IL side of the vertebral bodies to prevent excess spinal cord dose

41.4 Gy Stomach and liver are blocked through the entire course electron field patch used to supplement the pleural space under the block on left side, the heart is blocked at 19.8 Gy

orbital RMS with CR to chemo = what RT dose?

45 Gy if CR 50.4 Gy if <CR

EORTC 26951 (van den Ben JCO 2013) randomized pts to surgery followed by radiation +/- PCV -- what was the radiation dose for anaplastic oligodendroglioma?

45 Gy to initial volume followed by 14.4 Gy boost (59.4 Gy total)

What is the dosing for a definitive treatment of a stage IIB cervical cancer for EBRT + LDR brachy

45 gy EBRT + 40 Gy LDR brachytherapy to point A and a 5.4 Gy parametrial boost LDR is usually 35-45 Gy to point A For parametral extension, you need an extra 5.4-9 Gy boost

Correct dose for glomus tumor?

45-54 Gy LC ~90% after definitive RT

What % of penile cancer is associated with HPV infection?

45-80% of cancers

Tandem transplant vs single transplant for poorly differentiated high risk neuroblastoma (ANBL 0532)-- what is DFS difference

48% --> 62%

Basch et all JAMA 2017 showed what benefit to real time response to worsening symptoms via patient reported outcomes questionnaire vs usual care?

5 month OS benefit 31.2 vs 26 months

5 yr OS for MSK series of pts getting IFRT for pre-chemo disease for pts salvaged with RT followed by transplant

5 yr OS ~60%

What % of BC is related to BRCA1

5%

What % of pts with cutaneous T cell lymphoma (MF) present with Sezary Syndrome?

5%

Auperin JCO 2010 metanalysis for sequential chemo - RT for LA-NSCLC, what was the benefit of concurrent chemoRT compared to sequential?

5% OS benefit (15 vs 10%) favoring concurrent chemoRT

What benefit in OS was seen for the addition of RT to chemo alone in LS-SCLC in the Pignon NEJM meta-analysis (1992)?

5% OS benefit like all MA studies 14.3 vs 8.9% (SS) Benefit the highest in pts <55 yrs

Recommended interval from pre-op chemo RT for T3 or N+ rectal cancer to surgery?

5-12 weeks for conventional fractionation NOTE: Lefevre JCO 2017 RCT PIII study randomized to 7 v 11 weeks after pre-op CRT and found worse morbidity in the 11 week group with worse quality of meseorectal excision in the 11 week group. The Garcia paper in the picture essentially just showed increasing chemo in the TNT style approach was associated with progressively increasing pCR rates

PCNSL additional card

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 eyes in the (retina and optic nerves) field and C2-3 vertebral bodies age is super important and if >65 yrs probably just do re-challenge methotrexate if they fail

median age of medulloblastoma?

5-9 years

What was the chemo on the MacDonald INT 0116 trial?

5-FU/leucovorin 1 cycle prior to RT start 2 cycles with RT 400 mg/m2 per day with RT

What are acceptable HDR brachy boost doses for cervical brachy after 45 Gy EBRT?

5.5 Gy x 5 fractions - pts with <4 cm residual disease after CRT 6 Gy x 5 fractions - pts with >4 cm residual disease after CRT 5 Gy x 6 fractions 7 Gy x 4 fractions Dose constraints: - ICRU bladder point, ICRU rectal point: <3.7 Gy x 5 fractions - D2cc bladder = =/< 90 Gy EQD2 - D2cc rectum = =/< 65-75 Gy EQD2 - D2cc sigmoid = =/< 75Gy EQD2

What is the relapse rate when intracranial germ cell tumors get chemotherapy alone?

50%

What is the PFS of a low risk low grade glioma (<40 yrs and GTR) who DOES NOT get adjuvant RT?

50% Crazy, seems higher progression than I would expect. Shown on RTOG 98-02 OS for these people was 99 and 93% at 2 and 5 yr. PFS was 82 and 48% at 2 and 5 yrs. Factors predictive of worse PFS were - preop tumor size >4 cm - astrocytoma/oligoastrocytoma histology - residual tumor >1 cm (don't get this one because this shouldn't have counted as GTR?)

What % of pts with Paget's disease of the breast have a palpable mass? If a mass is detected, what % of these will be invasive breast cancer?

50% 90% are found to be invasive breast cancers Pagets presents with crusting, bleeding, itching, and ulceration of the nipple. 50% will have an underlying mass. Tx of Paget's is usually resection of the nipple-areolar complex followed by RT

how much vagina is covered if no vaginal involvement in cervical cancer

50% if no involvmeent 2/3 if upper vagina involved entire vagina if extensively involved

RT dose for desmoid tumors?

50-56 Gy

What are expected 5 yr RFS rates for "radiorecurrent" prostate cancer (and what are examples of salvage treatments)

50-60% depending on the intervention Types of things that are done after prostate recurrence followed definitive RT - prostatectomy - HIFU - cryotherapy - LDR/HDR salvage

What is the recommended radiation dose for an atypical teratoid rhabdoid tumor in a 2 yr old?

50.4 Gy to primary site alone if age >3 yrs, can consider CSI to 36 Gy

quantec recommendation for whole volume brainstem?

54 Gy Can give up to 59 Gy to smaller volumes. The risk of toxicity increases significantly when dose is >64 Gy to even point

RT dose for DIPG?

54 Gy in 30 fractions

In the INT study (Loehrer 1997) for unresectable thymomas or thymic carcinomas with induction chemo - followed by 54 Gy RT followed by chemo - what was the 5 yr freedom from failure?

54%

5 yr OS for superior sulcus tumor sp CRT and complete resection?

54% 44% all pts w/. resection - so improved by 10% if complete resection

What was the optic nerve max point dose for ROTG 08-25 (RT + temodar +/- bev) w/ max dose defined as vol of 0.03 cc?

55 Gy Optic chiasm max dose was 56 Gy Retinal max dose was 50 Gy Note - nerve = 55 - chiasm = 56 - retina = 50 - brainstem = 60 Gy (note if they say whole brainstem - think 54 gy) Note: Per QUANTEC, Dmax is 55 Gy for nerve and chiasm to keep optic neuropathy <3% (if 55-60 Gy, risk is 3-7%, if >60 Gy, risk is 7-20%)

What fractionations to the primary were done on STAMPEDE 18?

55 Gy in 20 daily fractions or 36 Gy in 6 weekly fractions

What was the RT dose on the STAMPEDE '18 trial?

55 Gy/20 fractions or 36 gy in 6 fractions

What is vaginal brachy dose if used as boost with EBRT for endometrial?

6 Gy x 3 to the surface (if with 45 Gy) 6 Gy x 2 to the surface (if with 50.4 Gy)

What is vaginal brachy dose if used alone after TH/BSO for endometrial?

6 Gy x 5 to the surface 5.5 x 4 to 0.5 cm 7 Gy x 3 to 0.5 cm (here we do 10 Gy x 3 to surface which works out to 7 Gy at 0.5 cm - very odd because nobody does this)

How should a keloid treatment be prescribed?

6 MeV prescribed to the 85% IDL

recommended adjuvant chemo for T4N2 colon cancer

6 months of FOLFOX T1-3N1 = 3 months is non-inferior

What was the 5 yr OS difference shown in PREOPANC-1 trial?

6.5% vs 20.5% 5 yr OS favoring chemoRT for borderline and resectable pancreas cancer RT was 36 Gy in 15 fractions with gemcitabine pre and post RT

dmax 60 = __% risk of myelitis dmax 69 - __% risk of mylitis?

60 = 6% 69 = 50% risk

RT dose for positive margin basal cell?

60 Gy-64 in 30-32 fractions or 50 Gy in 20 fractions Consider adjuvant for these if + margins or substantial PNI

Doses recommended for a 1 cm basal cell carcinoma of the skin?

60-64 Gy over 6-7 weeks OR 55 Gy in 20 fractions over 3-4 weeks 40 Gy over 2 weeks 30 Gy in 5 fractions over 2-3 weeks Daily fraction size <4 Gy reduces the risk of necrosis (skin or cartilage)

Dose range for concurrent chemoRT for LA-NSCLC

60-66 Gy w/ concurrent carbo/taxol This comes from 60 Gy being established as started on RTOG 7301 - Perez study Of note, the Perez study is crazy old and didn't use heterogeneity corrections so since lung was = water, that means with modern heterogeneity corrections, the dose to the tumor would actually be about 10% higher or ~66 Gy - so that is why some people use 66 Gy in 33 fractions if they can meet constraints. RTOG 0617 compared 60 vs 74 and +/- cetuximab and found 74 wasn't better and was maybe worse with worse survival (thought to be due to heart dose). Cetuximab made no difference. - chemo was carbo/taxol but interestingly also did two cycles of consolidation carbo/taxol after CRT.

5 yr OS for grade 2 LGG (all comers)

60-70% According to RTOG 0424 - 3 yr OS is ~73%

Mahajan analysis (MDACC) of adjuvant SRS after resection of 1-3 brain mets showed what?

61% had a single brain met 12 month freedrom from local recurrence was 43% v 72% in SRS (SS) - 57% WILL RECURR IN 1 YEAR IF JUST SURGERY, ONLY 28% OF SRS PTS WILL RECUR significant predictors of local recurrence were SRS and metastasis size median OS wasn't different No tx related deaths in either group + no radiographic radionecrosis in the SRS group. LC was worse for pre-op tumor size 2.5 cm or larger-- this impacted delivered dose.

Dose for T1N0 larynx cancer?

63 Gy in 28 fractions (2.25 Gy per fraction) 15% LC benefit Note weird dose levels based on "size" of tumor No OS benefit

5 yr LC expected with desmoid tumor treated with RT alone?

65%

What % of pts had pathologic evidence of malignant transformation to high grade glioma followed recurrence in each arm of the non-believers trial (EORTC 22845)

65-70% in both arms More modern series suggest this is lower actually

What was the overall response rate in RTOG 9714 - 30 Gy vs 8 Gy for uncomplicated bone mets?

66%

what was the dose/fractionation on POP-RT?

68 Gy in 25 fractions to Prostate +/- SV +/- 50 Gy in 25 fractions to pelvic nodes (up to commons) - SVs only included if radiologically involved all pts got 2 yrs hormone therapy all pts had 20% risk by Roach Formula Prostate+pelvis vs Prostate only 5 yr BFFS 95% vs 81.2% (SS) 5 yr DFS 89.5% vs 77.2% (SS) 5 yr DMFS 95% vs 87.9% (SS) 5 yr OS 92.5% vs 90.8% (NS) First trial to definitively show a BFFS, DFS, and DMFS benefit to adding pelvic nodes in high risk. NO OS benefit.

radio-isotopes used in PSMA Pets?

68-Ga-PSMA-11 or 18F-DCFPyL

What is vaginal brachy dose if used alone for adjuvant vaginal cuff?

7 Gy x 3 prescribed to 0.5 cm 6 Gy x 5 prescirbed to the surface 10 Gy x 3 prescribed to the surface (works out to about 7 Gy to 0.5 cm) - UK -what we do at Wake, not a good boards answer

Standard dose for HO?

7-8 Gy in 1 fraction either pre-op or post-op

Japanese Paper - JCOG 0802/WJOG4607L looked at pts w/ AJCC 7th stage IA NSCLC (2 cm or less). 1006 pts randomized to lobectomy vs segmentectomy results?

7.3 y fu Segmentectomy vs Lobectomy: 5 yr OS - 94.3% v 91.1% Segmentectomy conisdered non-inferior compared to lobectomy for tumors 2 cm or smaller

Risk of major coronary events per Gy from breast literature?

7.4% per Gy with no threshold - darby NEJM 2013

MD Anderson dose escalation trial for prostate cancer (20% LR, 46% IR, 34% HR) compared what two doses? What was the benefit of dose escalation?

70 Gy @ 2Gy/fx 78 Gy @ 2Gy/fx Showed biochemical/clinical failure free survival benefit to dose escalation (8 yr FFBF was 78 v 59%) No OS difference Did show a 15 yr PCSM benefit however.

5 yr OS for pt with severe COPD?

70% This is important as median survival for stage I NSCLC is ~1 year and 5 yr OS is ~5-10% in those that do no have treatment. Thus even in someone with advanced COPD, they are more likely to die of the lung cancer than their COPD

What is the rate of CR for combined modality therapy in bladder preservation?

70% CR rate based on pooled analysis of RTOG studies (Mak JCO 2014) Modern rates appear to be even higher.

SRS for TN -- complete pain relief rate at 1 yr?

75% at 1 yr 50% at 3 yr long term is probably like 25-30%

What % of anal canal cancers are squamous?

75-80% ~15% are adenocarcinoma

FlAME trial showed what?

77 Gy in 35 +/- EBRT boost to DIL up to 95 Gy Showed improved bDFS and DFS - 5 yr 92 v 85% NO increase in G2+ toxicity NO diff in OS or DMFS

What is the 7 yr EFS difference for pediatric ependymoma (based on St. Jude series (Merchant 2009)

77% (GTR) vs 34% (STR) remember extent of resection is dominant prognostic factor for ependymoma

palliative dose for MF

8 Gy in 2 fractions

what is the time interval that EBRT and brachy should be completed in definitive cervical treatment

8 weeks - 56 days

The meta-analysis (Sjoquist Lancet 2011) compared neoadjuvant chemoradiation vs surgery alone for esophagus -- found what?

8.7% absolute improvement in 2 yr OS this one defies the 5% meta-analysis rule

d2cc for bladder

80 Gy

At time of presentation what % of pancreatic cancer is unresectable/metastatic?

80% ~50% are metastatic ~30% total are unresectable/borderline ~20% are resectable

Princess Margaret Hospital retrospective data of stage I seminoma receiving adjuvant therapy vs observation showed what 5 yr RFS rate for the observation arm?

82% 5 yr RFS Only one patient died of seminoma - so 5 yr cause specific mortality was 99.7% 5 yr OS was 97%

MDACC BID schedule for inflammatory breast cancer (51 Gy 1.5 Gy BID +15 Gy boost) has what LC? RR of 256 pts atreated at MDA w/ IBC. Compared those treated with 50 Gy/25 + 10 Gy boost to 45-51 Gy with 16 Gy boost. What specific subgroups benefited from dose escalation? Is dose escalation recommended in all patients?

85% LC (66 Gy bid) vs 58% (50 + 10 = 60 Gy daily) - 5 yr Benefits of DE: - pts with <PR to chemo - pts with +, close, or unknown margins - pts <45 years old (bigger benefit in younger patients) DE in all patients? - NO - G3-4 toxicity is WORSE in the BID arm --> late complications 29% vs 15% - lymphedema 9% vs 2.5% - fibrosis 6% vs 4% - brachial plexopathy 2% vs 0% In other words, standard 50 Gy + 10 Gy boost would be perfectly appropriate for someone >45 yrs, complete response to chemo and negative margins.

Meta-analysis of neoadjuvant chemoradiation studies (Sjoquist) for esophageal cancer showed what?

9% benefit in all cause mortality over surgery alone for both adenocarcinoma and squamous cell carcinoma Neoadjuvant chemo alone had a 5% all cause mortality benefit ONLY in adenocarcinoma.

What % of relapses occur within the first 2-3 years among clinical stage I seminoma and non-seminoma pts?

90%

What is the 10 yr survival of stage III Wilms with favorable histology?

90% -- shockingly high I - 97% II - 93% III - 90% IV - 81% pts with stage II-III with anaplasia - 49% 10 yr OS pts with stage IV with anaplasia - 18% 10 yr OS Stage IV without and with anaplsia - 81% v 18% - big difference

G1 meningioma sp STR + adj RT = ___% LC

90% LC most are observed even if subtotally resected and then salvaged later but you can offer adjuvant Simpson 1-3 is a fully resected tumor

DOREMY trial (remember myxoid = t(12;16)) - looked at de-escalation of pre-op RT dose for myxoid liposarcoma (these are very sensitive to radiation - that's why these are the most likely to change while on treatment) - phase II -- de-escalation to 36 Gy @ 2 Gy/fraction 79 pts

91% had 50% or higher treatment response LC was 100% Wound complications 22% 1 yr OS 99% conclusions = 36 Gy should be considered with less morbidity than historical data for this specifically radiosensitive tumor (myxoid 12;16)

Medical Research Council (UK) trial of periaortic versus dog leg fields found what % of pts treated with dogleg had normal sperm counts 3 yrs after treatment?

92%

RTOG 0236 (Timmerman JAMA 2010) - SBRT for T1-2 NSCLC - what was the 5 yr LC? What was the prescription dose when the trial was initiated?

93% -- LRF was 36% at 5 yrs (only ~12% at 3 yr) -- DM rates ~24% 20 Gy x 3 fractions Dose was reported ultimately as 54 Gy in 3 fractions (18x3) because they didn't account for heterogeneity corrections so they were overestimating dose

MD anderson series (Katz J am coll surg 2008) showed what R0 resection rate for borderline pancreatic cancer treated with neoadjuvant therapy (chemo or chemorads)?

94% Note: this is pretty misleading, the preo-panc study showed R0 resection was 65% vs 31% without chemoRT

What is the expected survival (10 yr) for a pt with stage I-II Nodular Lymphocyte Predominant Hodgkin Lymphoma treated with involved field RT alone?

95-100% recommended RT alone dose is 30-36 Gy, 40 Gy if bulky disease The addition of chemotherapy does NOT improve PFS but DOES worsen OS

QUANTEC estimated risk of radiation myelopathy with fractionated RT is <1% for <___ Gy. Risk if <10% if ___ Gy forfractionated Radiosurgery dose of ___ Gy in a single fraction to keep risk <1%.

<1% --> <54 Gy <10% --> 61 Gy Radiosurgery = <13 Gy or 20 Gy in 3 fractions

LC difference for BED10 <100 vs >100 Gy in NSCLC?

<100 = 42.9% LF rate >100 = 8.4% LF rate Onishi Japanese data showed this also 5 yr OS better for BED10 >100 (30 v 71%, SS)

single fraction dose constraint for radiosurgery to keep risk of myleopathy <1% per QUANTEC?

<13 Gy single fraction; <17 Gy if 2 fraction, <20 Gy if 3 fraction

QUANTEC <25 Gy for b/l parotid glands - what is risk o toxicity

<20% risk of long term parotid gland function reduced to 25% of pre-RT level

Per Quantec, what is the risk of symptomatic pneumonitis with V20 < or = 30%?

<20% symptomatic RP We often say MLD <20 Gy and V20<30% at wake - so just remember those both correlate to ~20% risk of RP

Dose for cord compression in neuroblastoma?

<3 yrs = 9 Gy >3 yrs = 21.6 Gy

What age group is typically diagnosed with ATRT?

<3 yrs old CT CAP to check for concurrent renal rhabdoid tumors (NOT metastases)

In the EORTC breast boost trial, who benefitted the most?

<40 yrs (nearly a 10% difference in LR in this age group) overall this study showed a ~4% difference in local recurrence with higher toxicity in the boost arm

RTOG 1014 for repeat breast conserving therapy (45 Gy in 30 bid fractions) partial breast had what rate of grade 3 breast fibrosis?

<5%

Risk of clinically relevant kidney dysfunction if mean dose to both kidneys is 15-18 Gy = ? If mean dose <28 Gy

<5% risk 28 Gy = <50% risk

Quantec - what max dose to the larynx with conventional fractionation gives <20% risk of permanent voice dsyfunction?

<66 Gy

SRS dose constraint to the optic chiasm to keep risk of optic pathway damage "rare" = ?

<8 Gy point dose Based on Mayo Retrospective data 8 Gy = 0-2.6% 10 Gy = 0-4.7% 12 Gy = 0-13.9% 12-15 Gy = >10%

Vulvar tumor <2 cm and <1 mm DOI - what are the odds of pathologic node positivity? What is the most important prognostic factor for OS?

<8% Nodal status is most important for OS

vaginal tumors > __ cm depth of invasion should be treated with interstitial rather than cylinder brachy alone

>0.5 cm

2016 consensus guidelines for partial breast irradiation What size of tumor is "unsuitable"

>3 cm is unsuitable age <40 is unsuitable

What is the tumor size used by med oncs as a cutoff to start recommending adjuvant chemotherapy in node negative resected NSCLC

>4 cm (NO CHEMO IN stage IB (T2a); GIVE CHEMO for stage IIA T2bN0) This is based on CALGB 9633 (Strauss JCO 2008) - randomized IB pts (T2aN0) to carbo/taxol vs obs. Trial stopped early due to survival benefit however final results were not significant. Exploratory analysis did show that chemotherapy improved survival in pts with tumors 4 cm or greater. Basically think Stage II = chemo

What doses are recommended for DLBCL with PR to chemo?

>40 Gy NCCN guidelines 30-36 Gy for CR 36-50 for PR

In the ILROG collaberative study (2019) what was the 5 yr LC rate in localized early stage follicular lymphoma staged by FDG/PET and undergoing definitive RT?

>95%

What did the LaCoix J Neurosurg 2001 study show regarding extent of resection in GBM?

>98% resection coorelated with improved median OS (13 v 9 months) -- retrospective data

What is the RO-ILS (pronounced Royals)?

A radiation oncology specific incident learning system sponsored by the ASTRO and the AAPM used primarily in the united states

How is a clinic's safety culture usually measured

A standardized survey of clinical staff

What is the CAHPS cancer care survey?

A survey of patients' experience with cancer treatment in the inpatient and outpatient setting

What are examples of absolute contraindications to breast conserving therapy

ABSOLUTE CONTRAINDICATIONS homozygous ATM mutation pregnancy diffuse suspicious appearing microcalcs large tumor (widespread disease that cannot be removed with a single incision) that would preclude good cosmetic outcome diffusely positive margins Relative contraindications - prior RT to the chestwall or breast - active connective tissue disease involving the skin - persistently positive pathologic margins - patient with known or suspected predisposition to breast cancer

EORTC H6 compared MOPP vs ABVD in early stage unfavorable Hodgkin lymphoma - what was the outcome?

ABVD had BETTER freedom from progression and reduced toxicity Kind of surprising because most hodgkin trials were trying to escalate chemo from ABVD to reduce RT and they essentially always find that omission of RT reduces PFS and that there are chemo options like BEA-COP that have better PFS than ABVD but they are always more toxic. So this time ABVD won

What did NSABP B27 test

AC x 4 --> Taxotere --> surgery increased pCR rate by ~23% (SS)

What was most common systemic therapy delivered in the STAMPEDE '18 (arm H) trial?

ADT alone

HCC associated with what elevated blood marker?

AFP

What NCCN risk groups are appropriate for moderately hypofractionated RT (240 - 340 cGy/fraction) in prostate cancer based on the ASTRO, ASCO, and AUA joint clinical practice guidelines What is the weird statement regarding pelvic nodes here?

ALL RISK GROUPS (KQ A-C strong recommendation) NOTE: There is an odd inclusion of for high risk men "but not including the pelvic nodes" is mentioned -- most people do no hypofrac the nodes but would treat nodes with the prostate/sv volume getting an SIB in the same number of fractions. The pelvic node thing threw me off, but the important part is to say that you can treat any risk category with hypofrac. They just make the statement about nodes to say its beyond the scope of the recommendations.

How was the spinal cord blocked on the Turrisi study?

AM and PM treatments on cord for week 1, then AM dose on cord, PM dose off cord using obliques for weeks 2 and 3 Dose constraint was <36 Gy for hyperfrac arm other trial cord constraints - CALGB 30610 = 41 Gy - CONVERT = 42 Gy

What are B symptoms and how many do you need to add stage B to Hodgkins?

ANY OF THEM weight loss >10% unexplained fevers >38 C drenching night sweats

median age of ATRT

ATRT is <3 yrs

What is the primary management strategy for desmoid tumors?

Active Surveillance

KEYNOTE 522 randomized >1000 women w/ stage II/III TNBC to get neoadjuvant chemo +/- pembrolizumab and adjuvant pembrolizumab x 9 cycles for a total of 1 year of immuno. - chemo was carbo/taxol/docetaxel or epirubicin and cyclophosphamide - what was result? - when is radiation given (with/before/or after immuno)?

Addition of pembro increased pCR rate absolute benefit of ~15% Increased EFS from 77 - 85% regardless of PDL1 status Radiation can be given concurrent with pembro or pembro can start after radiation ends. Either is fine.

What % of gastric cancer is adenocarcinoma?

Adenocarcinoma = 90% Gastric lymphoma = 3-5% GIST = ~1% other random <1% - sarcoma - small cell - carcinoid - undifferentiated - leiomyosarcoma

What histologies were included in the german POET trial (Stahl JCO 2009)

Adenocarcinoma ONLY pre-op chemo followed by chemoRT vs chemo alone neoadjuvant chemoRT vs chemo - pCR 15.6% vs 2% (CRT vs chemo alone) (SS) - path node negative - 64 v 36% (SS) 3 yr OS not technically SS but close p = 0.07 - 47 v 28% Chemo = Cis, 5FU, LV RT = 30 Gy in 15 fractions w concurrent Cis/Etop 127 month fu showed - 5 yr LR: 18% v 38% (SS) - 5 yr local PFS improved with CRT - 5 yr OS 39.5% vs 24.4% (p = 0.055)

young patient upper tracheal mass most likely histology

Adenoid cystic Adenoid cystic and SCC are the most common primary tracheal cancers - but younger and more proximal, ACC more likely

Interim results of the CATNON trial suggests a benefit of TMZ in what setting?

Adjuvant TMZ for G3 anaplastic glioma This benefit was only seen for IDH mutation pts No benefit seen with concurrent TMZ in Anaplastic

The GITSG rectal cancer study randomized rectal cancer patients in a 2x2 fashion to surgery +/- radiation +/- chemotherapy NEJM 1986 publication showed what?

Adjuvant chemoradiation improved OS Memory aid - the GITSG pancreas adjuvant chemoRT study was the only one that showed an OS to adjuvant chemoRT there. So think GITSG pancreas/rectal adj CRT improved OS disease recurrence 55% vs 46% vs 48% vs 33% (surgery + chemo+RT, SS) 24% improvement in OS in the post-op chemoRT arm. Of note, post-hoc analysis showed that the survival advantage didn't hold up on MVA

Management of contrast reaction in pediatric vs adult patient

Adult (>25 kg) - 0.3 mg IM epi Children (10-25 kg) - 0.15 mg IM epi Infants (<10 kg) - 0.1 mg IM epid

Portec 2 inclusion criteria

Age >60, G1-2 and >50% myometrial invasion Age >60, G3 and <50% myometrial invasion or stage IIA (any endocervical glandular involvement) + any age >50% invasion (except G3) The point is that G3 >50% invasion was considered too high risk to get randomized to brachy alone VBT v EBRT 5 yr vaginal recurrence: 1.8 v 1.6% 5 yr LR relapse rates: 5.1 v 2.1 (NS) isolated pelvic recurrence rate: 1.5% v 0.5% - NS on 5 yr fu On 10 yr fu data - isolated pelvic recurrences were higher in VBT (6.3%) compared to EBRT (0.9%). - no difference in vaginal cuff failure or survival

What is the mechanism of TMZ?

Alkylating agent - 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) alkylates DNA that promotes single and double stranded DNA breaks -- it is an alkylating agent.

The Patchell spine study compared surgical decompression followed by RT vs RT alone and showed improvement in what metrics with the addition of surgery?

All SS improvements of surgery Post-treatment ambulatory rates increased (84% v 57%) Retained ability to walk (122 days v 13 days) subset of pts that entered without ability to walk regained ability in 62 vs 19% of cases.

Treatment arms of RTOG 90-03

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

What is the mechanism of action of sorafenib?

Anti-VEGF/PDG-f/Raf kinase - multi-tyrosine kinase inhibitor Used for renal cell carcinoma, liver cancer, and thyroid cancer

How should you sim an endometrial cancer POSTOPERATIVELY when using IMRT?

Apparently they want bladder empty and full either way I would have thought bladder full like prostate to move it out of the way, but the answer says that vaginal cuff still moves alot with bladder variation so they aren't only thinking of sim setup this way for intact. Applies to post op as well. You are essentially making a vaginal cuff ITV Guidelines for post-op cervical IMRT - do bladder full/bladder empty - nodal ctv = obturator, internal/external iliac and common iliacs (presacrals to S3 like prostate) - superior border of the nodal ctv should be 7 mm inferior to the L4/5 interspace - nodal ctv is 7 mm around vessels and nodal ptv is 7 mm (making the PV extend to L4/5) - need to cover at least 3 cm of the vagina - make itv (ptv should be 7 mm and extend to the obturator muscle)

NCCN recommendation for breast cancer screening in women previously treated for HL who received chest or axillary RT?

At age 40 or w/in 8 yrs of treatment (whichever comes first)

When is the optimum time to deliver prophylactic radiation for gynecomastia?

At the initiation of ADT 4 Gy x 3 or 10 Gy x 1 - en face electrons prescribed to the 85% IDL - No bolus Note these questions are asking about PROPHYLATIC - so before they have it is optimal. Not when they have symptoms, that's no longer prophylactic

RT for limb sparing soft tissue sarcoma, what dosimetric measure is associated with reduced fracture risk?

Avoid circumferential bone coverage with 50 Gy isodose line V60 <64%, mean dose <37 Gy Max point dose <59 Gy

What is the recommended biologically effective dose (a/b 2) for post-op keloid treatment

BED2 of >60 Gy2 We do 12-18 Gy in 2-3 fractions 18/3 = BED2 of 72 -- so makes sense BED = D [1+d/a/b]

Rades red journal 2011 - examined 8 or 20 Gy in 1 or 5 fractions (short course) vs 30 or 50 Gy (long course) for cord compression and found what?

BETTER LC associated with long course (61 v 81%) but no difference in OS or motor function. There is a study somewhere that says long course is associated with better motor function for myeloma specifically...

What % of males with BRCA1 mutation will develop breast cancer over their lifetimes? What % of males with BRCA2 mutation will develop breast cancer over their lifetimes?

BRCA1 = 1% Weird, would have thought higher In contrast to 65% of females BRCA2 = 7% in males and 45% in females

For a pediatric pt with Hodgkin lymphoma that will be treated with RT to the mediastinum, what is the optimum treatment setup?

BUTTERFLY TECHNIQUE This is the inclined position, breath hold with static field IMRT - this was described by Voong et al 2014 - for Hodgkin that minimizes heart, breast, and lung dose - immobilized with both arms akimbo on a 10-15 degree inclined board with a headrest, thermoplastic mask and vac loc bag - axila planning images are obtained with breath hold gating - imrt technique uses 5-7 beams restricted to anterior and posterior obliqued entry angles that should be individualized - the basic principle is that you are avoiding lateral beams in order to minimize excess low dose radiation to large volumes of normal tissue Pure AP/PA would be wrong because that would give high dose to the entire mediastinum

Why is IGF1 measured rather than GH?

Because GH is released in pulses and a single measurement is not useful. GH leads to the release of IGF1 which is more steady and a better measure of overall GH levels

Macroglossia, macrosomia, midline abdominal wall defects, ear creases, neonatal hypoglycemia, hepatoblastoma. Associated with hepatoblastoma and wilm's tumor.

Beckwith-Wiedemann syndrome

RTOG 0825 and AVAglio both treated GBM pts with standard Stupp protocol and then randomized to +/- Bevacizumab -- found what?

Benefit in PFS but no benefit in OS

What is the updated NRG consensus atlas recommendation for pelvic lymph node volumes for intact/post-operative prostate cancer (Hall WA Red journal 2021)?

Bifurcation of the aorta -- corresponds to L4/5 Used to be L5/S1 (what BF still does)

Risk factors associated with increased risk of bone fracture after surgery and radiation for soft tissue sarcoma?

Big things that come up = - Periosteal stripping (29% vs 4-6% per MSKCC data) - age >55 - female gender - radiation dose - tumor size - compartment

Bladder and rectum point for brachy

Bladder point = defined as the posterior surface of the foley balloon filled with 7 cc of iodinated radiographic contrast material Rectal point = 5 mm posterior to the vaginal wall between the ovoids at the most distal extent of the last tandem source

What physical exam finding is pathognomonic for jugulotympanic paraganglioma (glomus tumor)?

Blushing tympanic membrane with pulsatile tinnitus

Whats the recommended pre-op boost volume for rectal cancer?

Boost field is often 3 cm margin around the primary tumor including the whole sacral hollow (RTOG 0012) describes it this way RTOG 0822 says 3D conformal boost to gross disease + 2cm margin including all of the presacral space

NCCN definition of borderline resectable pancreas cancer

Borderline - soli tumor contact with common hepatic w/o extension to the celiac axis or hepatic bifurcation allowing for safe and complete resection - solid tumor contact with SMA <180 degrees - presence of variant arterial anatomy and the presence and degree of tumor contact should be noted if present as this can affect surgical planning - solid tumor contact with PV or SMV >180 degrees with contour irregularity - solid tumor contact with IVC Basically resectable is no distant mets, no arterial contact, and has to be touching veins by <180 degrees with no contour irregularity If they say encasement of the splenic artery or something like that, its totally resectable because the spleen can be taken out

Overall RTOG 1016 (american) and HPV DE-ESCALaTE (european) both showed what? What was different about these two trials?

Both showed inferior overall survival and worse locoregional control outcomes with de-escalation with RT/cetuximab. Toxicity was also similar between cetuximab and cisplatin which was the whole point of de-escalating... 5 yr outcomes RTOG 1016 -- Cetux vs Cis - OS: 77.9% vs 84.6% (6.7% OS difference, pretty huge) - PFS: 67.3% vs 78.4% - LRF: 17.3% vs 9.9% 2 yr outcomes De-ESCALaTE -- Cetux vs Cis - OS: 89.4% vs 97.5% (8.1% OS difference, even bigger) - Disease recurrence = 16.1% vs 6.0% Overall cetuximab was worse in basically every way including overall survival which is rare to see. The two contemporaneous trials were essentially asking the some question and came to the same conclusion. BUT - RT was 70 Gy in 35 fractions for both BUT --- RTOG 1016 used an accelerated 6 fraction/week - 6 week overall design --- DE-ESCALaTE used convention 7 weeks ---Because of this, chemotherapy was also slightly different in that both used bolus 100 mg/m2 cis, but since 1016 ended in 6 weeks, they only got 2 cycles (200 mg/m2) vs 3 cycles (300 mg/m2) on DE-ESCALaTE.

AHOD 1331 - RCT P3 study Brentuximab Vedotin showed what 3 yr EFS for newly diagnosed high risk classical Hodgkin lymphoma?

Brent = CD30 with attached drug 92% 3 yr EFS

4 ligaments that hold the uterus in place in the pelvis

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

tumor markers associated with cholangiocarcinoma?

CA-19-9 CA-125 CA-50 19-9 can be elevated in pancreatic, esophageal, cholangio, HCC, and CRC 125 = cholangio and ovarian 50 = another generic GI marker NSE = neuroblastoma/SCLC

evolution of treatment for LA-NSCLC

CALGB 8433 (NEJM 1990 and JNCI 1996) - showed survival benefit of sequential chemo followed by RT over RT alone RTOG 9410 (Curran JNCI 2011) showed superiority of chemoRT over sequential chemo - then RT.

CNS categories for ALL?

CNS1 - negative cytology CNS2 - 1-4 WBCs CNS3 - 5 or more WBCs OR any CNS lesions/CN deficits

What group of pts with low risk pediatric leukemia require cranial radiation as part of therapy?

CNS3 18 Gy in 1.8 Gy's Entire brain plus posterior 1/2 of globes and optic nerves

What is the dose for PCNSL if radiation is being considered after CR vs PR tochemo?

CR= 23.4 Gy whole brain PR = 24-30 Gy WBRT + 45 Gy boost if PR

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 MR

CROSS trial key factoids - breakdown of histology - dose of radiation - chemotherapy used - pCR rate overall and between histologies? - rate of R0 resection? - survival difference between arms?

CROSS trial key factoids - breakdown of histology = 75% adenocarcinoma, 23% SCC, 2% large cell undifferentiated - dose of radiation = 41.4 Gy - chemotherapy used = carbo/taxol - pCR rate overall and between histologies = 29% pCR rate (higher pCR in SCC - 49% than adenocarcinoma - 23% ) - rate of R0 resection = 92% CRT vs 69% surgery alone (SS) - survival difference between arms 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)

Appropriate workup for newly diagnosed PCNSL with negative CSF?

CT CAP or PET/CT BM biopsy MRI of the spine only if CSF positive or symptomatic

radiation planning for post-operative sarcoma

CTV1 = - tumor bed + clips, consider pre-op MRI - radial = 1.5 cm - longitudinal 3-4 cm - be sure to encompass the operative bed, scar, and drains - constrain anatomic boundaries (fascial compartments, bone, etc) - expand to PTV1 = 0.5 if daily IGRT - this initial volume usually goes to ~50-50.4 Gy CTV2 = - truncated version of CTV1 - only 2 cm longitudinally -- with same radial expansion - still gettting all tumor related edema, biopsy tract, etc - expand to PTV2 = 0.5 if daily IGRT -- this is what you will boost to the 60-66 range (neg vs pos margins)

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 (T-DM1 bound to Her2) - based on KATHERINE trial, EnHertu (trastuzumab deretixcan) TNBC w/ residual dz = capecitabine (xeloda) - based on CREATE-X Note: destiny breast 03 showed Enhertu more than double PFS compared to Kadcyla in metastatic Her2+ breast

RTOG 90-01 randomized cervical pts IIB-IVA or those w/ + LNs to extended field RT vs concurrent chemoradiation found what? what was the superior border for the para-aortic field?

ChemoRT improved 8 yr OS (67% vs 41%, SS) and decreased disease recurrence (35% to 18%) Superior border = L1/2

what was odd about the experimental arm of RTOG 98-11 in anal cancer comparing MMC/5FU to Cis/5FU

Cis/5FU got 2 cycles of induction chemothearpy -- it is unclear how to interpret the results the total treatment time matters according to the Ben Josef study so maybe delaying initiation of concurrent was the problem and otherwise Cis5FU might have been fine. 5 yr DFS and OS were both better for MMC/5fU

Standard chemotherapy for malignant pleural mesothelioma?

Cis/Pemetrexed

GOG120 randomized stage IIB-IVA cervical pts to definitive chemoRadiation with - 1. cis alone 2. cis/5FU/hydroxyurea 3. hydroxyurea alone what was the result?

Cis/hydroxyurea and Cis had much better survival than hydroxyurea and Cis alone has less toxicity thus Cis alone became the standard

neoadjuvant chemo prior to cystectomy?

Cisplatin/Gemcitabine - 5% OS benefit

what histology of DCIS has the worse prognosis?

Comedonecrosis

Features of meningioma g1-3?

Commonly asked are how many mitoses per 10 HPF 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) --Best way to remember is that RAP and 20+ is G3. Everything else that sounds bad is G2. +vimentin, GFAP, anti-leu7 Fatty degeneration, hemorrage, calcium, cyst formation Typical --> 3% recurrence rate Atypical --> 38% recurrence rate Malignant --> 78% recurrence rate

Meta-analysis data of 20 different trials in NPX cancer Ribassin-Majed JCO 2017 showed what?

Compared to concurrent ChemoRT alone, adjuvant chemo added to concurrent chemoRT improved PFS and there was a trend toward improved OS, LRC, and distant control. The al sarraf trial showed a HUGE benefit to PFS and OS PFS - 66 vs 26% OS - 76% vs 46%

Nordic trial compared TMZ alone vs 34/10 RT vs 60/30 RT - found what?

Compared to standard 60/30, median OS was longer with TMZ alone. Not sign longer than hypofract 34/10 alone.

a study retrospectively compares surgery and radiation for a disease and finds that surgical patients have higher survival - the conclusion is that surgery improves survival what type of bias is likely impacting this study

Confounding bias the study is confounded by the fact that surgery patients have earlier stage disease and better PS than those referred to radiation Matching and randomization are methods to reduce confounding

Consolidation with WBRT vs autologous transplant for PCNSL

Consolidation with WBRT vs autologous transplant for PCNSL

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 CL V20 >7% = 42 fold higher risk of death from pulmonary related disease compared to <7%

NRG atlas definition of the chestwall for breast contouring

Cranial - caudal border of the clavicular head Caudal - clinical reference + apparent loss of CL breast (most say 1-2 cm beyond the inframammary fold for intact breast) Anterior - skin (typically includes mastectomy scar) Posterior - rib/pleural interface (includes pectoralis muscles, chestwall muscles, and ribs) Lateral = clinical reference + mid axillary line (typically excludes the lat dorsi muscle) Medial = Sternal Rib junction

RTOG 0813 guidline for brachial plexus?

D3 cc < 6 Gy per fraction (30 Gy total) d3cc = hottest 3 cc

What coverage of the CTV is minimum per ABS on post-implant LDR prostate dosimetry?

D90 >90% of the CTV is lowest you can accept

Define D90 and V100 on a prostate plan

D90 refers to the minimum dose in the "hottest" 90% of the prostate volume in Gy or % of prescribed dose. So to say the D90 >100% means the dose to 90% of the prostate volume needs to be at least prescription dose. V100 is the volume of prostate receiving 100% of the prescription dose.

standard treatment of primary mediastinal B cell lymphoma

DA-R-EPOCH if you can't do the hospital stay, can do standard R-CHOPX6 + RT CR 96% is ridiculous

The PSA bounce following definitive external beam radiation with combination brachytherapy boost is associated with what?

DECREASED biochemical relapse rate PSA bounce is associated with GOOD prognosis The mechanism isn't clear but might be an immune response in the prostate. PSA bounce was defined in this study as transient PSA increase of at least 0.2 ng/mL Median time to bounce = 15 months Median time to biochemical relapse = 37 months HR for bounce was DECREASED - correlated with lower chance of biochemical relapse

NCI amputation vs limb sparing surgery + RT? - high grade STS - both groups got doxorubicin, cyclophosphamide, and methotrexate What was the 5 yr OS for LSS +RT?

DFS and OS equivalent 5 yr OS = 83% (vs 88% for amputation).

Recommended time interval from surgery to start of radiation for oral cavity cancers?

Daly red journal 2011 - <6 weeks - LC = 80% - >6 weeks - LC = 40% Similar differences seen in total package time <12 vs >12 weeks <4 weeks is probably not enough time for healing - so 4-6 weeks is the sweet spot.

Pseudohermaphroditism, masangial renal sclerosis and Wilms tumor

Denys Drash syndrome

RTOG 0214 PCI NSCLC dose? Results to brain mets? OS?

Did reduce incidence of brain mets at 1 yr (7.7 vs 18%) No diff in OS or DFS (2 yr report DFS was better, but not OS) dose was 30 Gy in 15 fractions There was a cost of decline in memory (immediate and delayed recall was affected)

What is the most accurate way to assess distance from the anal verge of a primary rectal cancer?

Digital rectal exam and rigid proctoscopy

What is chance of a child of someone with a hx of genetic Rb developing retinoblastoma as well?

Dominant pattern of inheritance, so 50% chance happens earlier (often <1 yr) more likely b/l or trilateral (pineal involvement)

T1-2 larynx field borders and doses

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 1-2 cm 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) Rad onc Q bank says 1 cm superior to the thyroid notch for superior border

What is the meaning of double hit in DLBCL

Double hit = MYC re-arranagement + BCL2 or Bcl6 re-arrangement (this is usually by translocation) Triple hit = MYC + Bcl2 + Bcl6

How far down do you cover if you have involved level IV nodes?

Down to the sternoclavicular joint - SCV fossa

Dx = ? Vx = ?

Dx = Dose to a given volume of a structure Vx = Volume of a structure receiving some dose

Kupelian, red journal 2004 RP vs EBRT <72 Gy vs EBRT >72 Gy vs Brachy alone vs Brachy+EBRT What was the one group that had SIGNIFICANTLY worse bRFS?

EBRT <72 Gy

ESPAC1-4 trial overview for adjuvant pancreas cancer

ESPAC trials overview - the first one showed that chemoRT was harmful, so 2-4 are all chemo trials. 1 = 5FU benefit; chemoRT bad 2 = comfirmed 5FU good vs obs 3 = 5FU and gemcitabine no different 4 = Gem vs Gem+Cap improved OS (25.5 vs 28 mo med OS, SS) --> this would later be replaced by mFOLFIRINOX ESPAC 1 - this was the one that was factorial randomization that showed 5FU OS benefit but chemoRT harm ESPAC 2 - confirmed OS benefit of adj 5FU vs obs ESPAC 3 - 1000 pts w/ pancreatic adenocarcinoma randomized to 5FU or gem adjuvant - no diff in OS ESPAC 4 - adj gem vs gem-xeloda for 6 cycles - most pts had R1 (60%) and N+ (80%) - med OS 28 vs 25.5 (SS) - 5 yr OS 29 vs 16% - OS favored those who completed all 6 cycles of therapy Note: CONKO-001 showed benefit of gemcitabine compared to observation

RTOG 0022 was a hypofractionated IMRT Trial (1.8-2-2.2 Gy per fraction) that looked at what subsite?

Early stage oropharyngeal cancer T1-2 N0-1 oropharynx Chemotherapy NOT permitted 66 Gy in 2.2 Gy/fx to gross. Subclinical volumes 1.8-2 Gy per fraction

Who should get a bone scan for staging in prostate cancer?

Essentially unfavorable intermediate and up should get bone scans based on most recent NCCN guidelines

Pathologic risk feature that is the strongest risk factor for nodal recurrence after lymphadenectomy?

Extracapsular extension

What are the dose and fractionation for FAST and FAST-Forward

FAST = 5 fractions delivered weekly - 50 Gy in 25 DAILY - vs 30 Gy in 5 vs 28.5 Gy in 5 (all ONCE WEEKLY fractions) - Primary endpoint was change in breast appearance and 28.5 wasn't sig different than 50; but 30 was. So 28.5 in 5 (weekly) fractions was the winner here FAST-Forward = 5 fractions daily - 40 Gy in 15 fractions vs - 26 Gy in 5 vs 27 Gy in 5 (daily) fractions - 26 Gy had similar cosmesis to 40 Gy. 27 lost. Remember - FAST isn't actually fast (still takes 5 weeks) but Fast-Forward is actually fast (daily - 5 days total)

FIGO stage for vaginal cancer extending to sub-vaginal tissue?

FIGO II IA = <2 cm IB = >2 cm II = extends to subvaginal/parametrial tissue but NOT to the pelvic wall (<2 cm = a, >2 cm = b) III = tumor extends to pelvic side wall - defined as muscles, fascia, neurovascular structures or skeletal portions of bony pelvis -- also includes hydronephrosis and lower 1/3 of vagina -- these are technically all the same as T3 in cervix stage IVA = tumor invades bladder or rectum - bullous edema does NOT qualify as IVA Note: FIGO staging does not report nodes. AJCC 7th/8th do account for nodes - N1 = pelvic or inguinal lymph node mets

Chow Lancet Onc 2015 paper that looked at single fraction palliation for bone mets that treated with decadron prophylactical used what dose?

FYI there is a benefit - 10% benefit (26% vs 35%) Dose was 8 mg on day of treatment and for 4 days following treatment

ACOSOG Z4032 Fernando - attempted sublobar resection +/- mesh brachytherapy -- found what?

Failed to show a benefit to brachytherapy - no LC benefit. Thus lobectomy remained standard of care

What popular quality improvement tool can be used by medical staff to brainstorm possible causes of a patient safety incidence and/or medical error and sort them into useful categories?

Fishbone Diagram/Cause and Effect diagram

FORT trial - RCT P3 non-inferiority that compared 24 Gy/12 vs 4 Gy in 2 fractions for what cancer? - what was the result?

Follicular and marginal zone lymphoma 4 Gy was NOT non-inferior. Thus 24 Gy better - standard for localized lymphoma. 2 yr local PFS rates - 94.1% at 24 Gy and 79.8% at 4 Gy. 5 yr local PFS rates - 89.9% at 24 Gy and 70.4% at 4 Gy.

RTOG 1010 looked at addition of trastuzumab to chemoRT (concurrently) for definitive treatment GE junction cancers

Found no benefit to Herceptin in definitive setting

Albain Lancet 2009 (INT 0139) study looked at T1-3N2 people with limited stage IIIA (single station N2) and looked at induction chemoRT (45 Gy) followed by surgery compared to def chemoRT (61 Gy) - found what? - what was the 5 yr OS?

Found no survival benefit to induction CRT but subgroup analysis suggested that the patients that ONLY REQUIRED LOBECTOMY did have a survival benefit, but not if they needed a pneumonectomy (higher mortality in those pts). 5 yr OS (NS) - 27% (trimodality) - 20% (def chemoRT) On subgroup analysis - matched cohort of those who only required lobectomy 5 yr OS (SS) - 36% (trimodality specifically with lobectomy) - 18% (def chemoRT) However keep in mind this was an unplanned subgroup analysis on an otherwise negative trial. In the era of PACIFIC, nobody should be doing this. Overall mortality rate for pts requiring pneumonectomy was 26% and as high as 39% if R sided pneumonectomy

What are the soliman (red journal 2017) radiosurgery guidelines for delineation of the CTV post-operatively

Fusing the pre-operative MRI to aid in volume delineation Contouring the entire surgical tract regardless of the preoperative location of the tumor Extending the CTV 5-10 mm along the dura underlying the bone flap to account for microscopic disease extension in cases with pre-operative dural contact Creating a margin of 5 mm or less into the adjacent sinus when preoperative venous sinus contact was present

PARSPORT trial for HN cancer comparing conventional RT vs IMRT found what major difference? This is the basis for standardization of all HN being treated with IMRT really

G2+ xerostomia of 34% in IMRT vs 74% conventional RT at 12 months -- difference persisted at 24 months

NEO-AEGIS study - two standard treatments are Cross trial or peri-op chemo ala MAGIC/FLOT GE junction cancers were including in both of these trials This looked at T2-3N0 - 3 M0 (Sw 1-3) GE jxn cancers (tumors w/in 5 cm of the true GE junction) randomized to either EC(O)F(X) x3 --> surgery --> EC(O)F(X) -- magic style OR CROSS style chemoRT with 41.4 and carbotaxol --> surgery O and X = could get oxaliplatin or xeloda instead of C and F at investigators discretion. - Amended in 2018 -- when FLOT4 trial came out -- allowed modification of chemo to allow FLOT at investigator discretion results?

G3-4 toxicity - neutropenia, diarrhea, and vomiting all significantly higher in the MAGIC arm than the CROSS arm pCR favored CROSS (16% vs 5%) SS major pathologic response rate favored CROSS (32 v 12%) R0 favored CROSS (95% v 82%) SS higher node negative rate favored CROSS (60 v 44.5%) SS Post-op complications were slightly higher in CROSS (ARDS, but not SS). OS was not different however between the two (HR 1.02) -- despite all of the differences. So the conclusion is that there is no major difference between these two studies. R0 resection and pCR rates favor CROSS with essentially the same toxicity -- but OS is the same so these are considered equivalent. Most of the chemo was MAGIC and not new SOC FLOT but the CROSS regimen pts didn't get nivolumab which would have been the standard based on the new CHECKMATE 577

What toxicity was worse on CONVERT with twice daily compared to daily?

G4 neutropenia Esophagitis was the same ~19-20% range note esophagitis was worse on Turissi but they did ENI with huge fields.

Of Radicals, RAVES, and GETUG-17, which trial required T3/4 AND R1 resection for eligibility?

GETUG-17 - T3 or 4 AND - R1 resection RAVES - T3/4 OR - R1 resection RADICALS (ANY of) - GS 7-10 - pre-op PSA >10 - T3/4 - R1 All showed that adjuvant increased late G2+ GU toxicity relatively to early salvage. Radicals showed SS increase in G3/4 urethral stricture in adjuvant.

Basically every trial ever done for Hodgkin lymphoma showed that omission of RT was associated with worse PFS EXCEPT for which one?

GHSG HD17 - 2+2 alone was non-inferior to 2+2 + RT in DS1-2 pts. - 1100 early stage - everybody got 2 cycles BEACOPP esc + 2 cycles ABVD --> PET iPET negative (DS1-2) = randomized to 30 Gy IFRT vs OBS iPET positive (DS 3-5) = randomized to 30 Gy IFRT vs 30 Gy INRT PET4 negativity after 2+2 chemo = this allows omission of RT without clinically relevant difference loss of efficacy I think this is literally the only study that showed this

What's the only trial that demonstrated a survival advantage for chemoradiation in resected pancreatic cancer?

GITSG trial - 9173 - OS advantage

What study randomized stage IB2 cervical cancers to RT +/- chemo followed by adjuvant hysterectomy and what was the outcome?

GOG 123 - Keys NEJM 1999 Improved 3 yr OS Decreased LRR Improved 5 yr PFS and OS Increased pCR rate Even still, definitive chemoRT is more commonly done for these now

What hormone is the first to decrease after radiation to the pituitary after resection of a craniopharyngioma?

GROWTH HORMONE In this order: 1. growth hormone earliest 2. FSH/LH 3. TSH/ACTH late RT has no effect on ADH - common complication of surgery IGF-1 levels can be checked to measure growth hormone secretion by the pituitary

how does planning differ for subcutaneous tumors (like angiosarc of scalp or something)

GTV = T1 + gad and T2 seq CTV typically 3-4 cm circumferential + 0.5 - 1 cm into underlying non-involved muscle) - emcompass any tumor related edema, biopsy tract, etc PTV = 0.5 cm margin w daily IGRT

What were the PSA failure definitions on radicals, raves and GETUG-17

Generally PSA of 0.2 ng/mL or greater Radicals is the one that is different and there are TECHNICALLY two different definitions: - 2 consecutive rises > 0.1 ng/mL - 3 consecutive rises regardless of actual level

Hodgkin trial critical pieces to remember pre-PET ERA HD10 HD11 HD14 H6F H6U H9U PET ERA UK Rapid H10 (EORTC/GELA/LYSA) HD16 HD17

Generally speaking they all show that removal of RT worsens PFS EXCEPT for HD17 (thats the only one in early unfav that 2+2 alone didn't worsen PFS) - also UK rapid needed PP analysis to show PFS was worse technically. OS was always equal on these pre-PET ERA HD10 = early/favorable = 4x4 = abvd x 2 + 20 Gy equal to others HD11 = early/unfavorable = ABVD x 4 vs BEACOPP x 4 and 20 v 30 Gy --> ABVD x 4 + 20 Gy was NOT non-inferior, so ABVDx4+30 was standard HD14 = ABVD x4 + 30 vs BEACOPP x4 + 30 = closed early because BEACOPP arm was much better but still toxic so nobody wants to do it H6F = Favorable one where they showed STNI (subtotal nodal irradiation) was eqiv to laparotomy so they stopped doing surgery H6U = ABVD was superior and less toxic than MOPP for unfav H9U = confirms HD11 = ABVD x 4 + 30 Gy vs BEACOPP x 4 + 30 Gy vs ABVD x 6 + 30 Gy = all the same. PET ERA - these all did interim pets after a few cycles of chemo and all show that omission of RT based on negative iPET worsened PFS (RAPID wasn't worse on ITT but was on PP) - its more helpful to remember how many cycles the obs group got because they seem to ask questions like that UK Rapid = ABVD x 3 for obs group (if positive they got 1 more ABVD + 30 Gy). Omission of RT worse on PP analysis. H10 (EORTC/GELA/LYSA) = iPET at 2 cycles ABVD + 2 more if negative for fav and 4 more if negative for unfav (obs got 4 or 6 total cycles). If positive they got 2+2 therapy + RT. Showed the same thing as always HD16 = Early Favorable PET adapted - ABVD x 2 if pos got standard --> 20 Gy. If iPET negative they got randomized to obs vs 20 Gy. Omission worsened PFS. HD17 = 2+2 (ABVD x 2 + BEACOPP x 2) --> iPET - if negative randomized to obs v 30 Gy. If iPET pos -- got 30 Gy either INRT or IFRT. THIS IS THE ONE TIME THAT OMISSION DIDN'T worsen PFS. IFRT = INRT

What are the components of the Nottingham score?

Glandular/tubular differentiation Nuclear pleomorphism Mitotic count

What are the CTV targets in a post-op pancreas case?

Gross disease or tumor bed portal vein celiac axis SMA pancreaticojejunostomy aorta

Most common mutation in pediatric glioma

H3.3

MSK trial of brachytherapy for soft tissue sarcomas of the extremities (Pisters et all JCO 1996) showed the greatest benefit in what group of patients

HIGH GRADE TUMORS LC was 89 vs 66% for high grade tumors LC was improved with NEGATIVE margins actually and not positive margins

HPV+ oropharynx de-escalation trial overview?

HN002 HN005 RTOG 1016 DE-ESCALaTE HPV trial ECOG3311 Details on next cards

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?

HORRAD -PSA progression survival benefit (on UVA, not MVA) but no OS benefit. -benefit wasn't SS but favored treating the prostate if number of mets was <5 Take home here is that THERE WASN'T technically a survival advantage to treating the primary in metastatic pts but it looked like there was a good trend in those with low metastatic burden -- lead to the stampede H arm (stampede 18) Of note - the STOPCAP meta-analysis combined results from HORRAD and STAMPEDE and did NOT find a OS benefit to treating the primary among ALL pts. BUT it did find a 3 yr OS benefit in those with <3 bon mets (77 vs 70%, SS).

Standard WBRT dose for primary CNS lymphoma under the age of 60 who is otherwise healthy? What was rate of severe neurtoxicity in pts that got reduced dose WBRT with CR to chemo?

High Dose Chemotherapy (MTX) followed by 23.4 Gy consolidated WBRT if complete response, if partial response --> 45 Gy Shah study - in pts that had CR and 23.4 Gy WBRT - there was NO evidence of significant neurocognitive decline (except for motor speed) Shah 2007 and final results in Morris 2013 Prior trials showed unacceptably high neurotoxicity with doses of 45 Gy in pts >60 yrs.

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) Only phase II

what is the most common cancer in the 15-19 age group

Hodgkin lymphoma

biggest risk factor for development of heterotopic ossification?

Hx of prior HO (up to 90% recurrence rate without prophylaxis)

Roa trial (JCO 2004) - 100 GBM pts 60 yrs or older with KPS >50 were randomized after surgery to either 60/30 or 40/15 EBRT. Result? What was the median OS?

Hypofrac was non-inferior to conventional Median OS was 5.1 v 5.6 months (NS) Of note, more pts in the 60 gy are required increase in steroid dose (49% vs 23%, SS)

How do you remember the NCCN, NCIC and EORTC vs the GHSG definitions for unfavorable?

I remember the GHSG ones best - 3BEE 3 or more nodal groups Bulk Extranodal disease (any site) ESR >50 if no B; >30 if B Then just for each one, remember the thing that makes it different: - all use number of nodal sites, but GHSG is the one that is different. Know the GHSG is the only one that is 3 or more nodal sites, the others are all more than 3. - all use elevated ESR, but NCCN and NCIC say >50 or B symptoms; GHSG and EORTC use the 50 and 30 cutoffs. - all count bulk as >1/3 MMR at T5/T6 - NCCN and NCIC include size >10 cm as a measure of bulk whereas GHSG and EORTC don't. - Extranodal DOESNT count for any others as unfavorable. - NCIC also accounts for mixed cellularity or LD

LC expected for dose escalated EBRT to 80 Gy or more for stage I-IIIB NSCLC?

I/II = 67% III = 39% MSK retrospective data

NSABP B21 - 1009 women with T1N0 breast cancer <1 cm - lumpectomy and ALND -- randomized to tamoxifen, RT or RT + tam - results?

IBTR was at 8 yr - lowest for tam + RT (2.8%) - middle for rt alone (9.3%) - highest for tam alone (16.5%) No diff in OS between any group

D'Cruz NEJM 2015 - trial of IL ELECTIVE neck dissection vs therapeutic neck dissection (surgery for nodal relapse) for T1-2N0 oral squamous cell carcinoma was associated with what outcome? What was occult nodal positive rate in elective group? What was rate of positivity correlated with?

IMPROVED Locoregional control AND OVERALL SURVIVAL OS 67.5 v 80% - 3 yr Rate of nodal positivity for elective was 29.6% Most directly correlated with DOI - rate 5.6% for DOI 3 mm vs 16.9% for 4 mm This is essentially where the idea that with >3 mm DOI, you need to do an elective neck dissection.

MRC UK dose escalation trial for HGG found that 60 Gy vs 45 Gy had what effect?

IMPROVED SURVIVAL OS improved from 9 to 12 months (SS)

MSK series (alektiar 2011) comparing IMRT vs brachytherapy for STS of the extremities found which had better local control?

IMRT actually had lower local recurrence rates than brachy 5 yr - 92% for IMRT vs 81% for brachy Note this is different than the Pisters brachy vs no further therapy study that showed LC benefit of brachy (biggest in high grade and negative margins, no benefit in pos margin actually)

Mutation associated with ATRT

INI-1

what is the primary treatment for GIST tumor of the stomach?

Imatinib (Gleevec) has activity against Bcr-abl, c-kit and PDGF-R GIST has activation of c-kit

What type of bias occurs when in a randomized trial, the definition of a survival event is designed such that participates in one arm CANNOT experience that even by definition as soon as the other arm -- ie. one arm is randomized to upfront treatment and the other is randomized to delayed treatment. Their example was a situation where two prostate groups receive radiation at different time points, one immediately and one delayed. If the failure is defined as progression after completion of RT, the immediate RT group is at risk for failure sooner by definition since the delayed group isn't eligible to be called failure until after they finish RT.

Immortal time bias - especially important when one group CANNOT experience the defined outcome by design for a set period of time while the other can experience the outcome.

2021 updates to WHO glioma grading

Important things: Louis 2016 update - G2 = either oligodendroglioma (IDHmut + if 1p/19q codel) or diffuse astrocytoma (IDH mut, but not codel). - G3 = anaplastic -- either astrocytoma or oligodendroglioma (IDHmut + if 1p/19q codel) - G4 = GBM (in 2016 could be IDH-wt or technically mut - not true now) or diffuse midline glioma (H3K27M) Louis 2021 update - GBM must be IDH-wt and are G4 - Astrocytoma, IDH-mut can be 2,3,4 - Oligodendroglioma, IDH-mut, 1p/19q codel - can be g2,3 Important Biomarkers: - CDKN2A/B = homozygous deletion = CNS WHO grade 4 regardless of histological findings - TERT promoter mutation, EGFR gene amplification OR combined Chr +7/10 = diagnosis of GBM

Integration of early palliative care into the care of pts w metastatic NSCLC was shown by Temel NEJM 2010 to have what effect?

Improve QOL and reduce depressive symptoms Also IMPROVED MEDIAN SURVIVAL Less aggressive end of life interventions also

In the setting of HN re-irradiation after resection of locally recurrent disease (in areas that previously received at least 45 Gy), what is the benefit to re-irradiation? The Janot 2008 JCO paper used what chemo? whats the downside?

Improved DFS but NOT overall survival Janot randomized 130 pts (heterogenous population) to chemoradiation or observation after surgical resection -- found improved DFS but not better survival. Toxicity was worse with CRT (G3/4 39% v 10%, p = 0.06) G5 = 7 deaths in CRT attributed to treatment, 0 in obs. note: the chemo here was strangely 5FU and hydroxyurea

MSK adjuvant brachytherapy for sarcoma - 164 pts with adjuvant brachytherapy vs observation (Ir 192 42-45 Gy over 4-6 days) - did brachy improve LC? - did it improve LC in R0 or R1 resections or both?

Improved LC overall (82% vs 69%) - DID NOT improve LC if positive margin - only improved LC if negative margin

TROP 99.03 looked at inclusion immunochemo after ISRT for indolent lymphoma and found what (R-CVP)

Improved PFS (10 yr 59 v 41%) but not OS

Gomez MDACC oligomet trial was a PII - treated 3 or fewer oligomet NSCLC with first line systemic therapy for approximately 3 months and if they didn't progress, they were randomized to standard maintenance vs local consolidative therapy with surgery or SBRT (kind of like the oriole trial). What was the result?

Improved PFS and OS (note, initial publication didn't report OS, only improved PFS - update showed both) Median PFS: 14.2 vs 4.4 months Median OS: 41.2 months vs 17 months

Chen et al J Natl Cancer 2011 -- p3 RCT compared chemoRT vs RT alone for chinese Stage II (AJCC II/III) NPX cancer - showed what?

Improved PFS, DMFS, and OS with chemoradiation 5 yr OS 95.8 v 94.5% 5 yr PFS 77.8 v 89.9% 5 yr DMFS 83.9 v 94.8% 5 yr LRC was not different.

Prostate studies such as RTOG 0126 comparing 70.2 vs 79.2 Gy usually find what major outcome?

Improved biochemical control with dose escalation, but they are essentially never powered for OS - this one WAS and found no OS benefit to OS but it did improve biochemical control w/ increased late G2 GI/GU toxicity in the DE arm. So DE can be thought of as a way to reduce the need for future therapies, but doesn't increase OS Hypofactionation generally later shown to be essentially equiv in control to conventional DE but with expected increased G2/3 GI/GU tox -- RTOG 0415 (100% low risk), PROFIT (100% intermediate risk), CHIP (31% HR), and Dutch HYPRO studies (74% HR)

KeyNOTE 189 randomized pts with metastatic, non-squamous NSCLC to UPFRONT treatment with platinum/pemetrexed +/- pembrolizumab. Found what benefit to pembro?

Increased PFS and OS for all patients

What drug is an alternative to RT for HO prophylaxis?

Indomethacin

What are the Shaw RTOG 90-05 doses for SRS in - <2 cm - 2-3 cm - >3 cm - 4 cm What was the maximum tumor size allowed on study

Initial doses were - <2 cm = 18 Gy - 2-3 cm = 15 Gy - >3 cm = 12 Gy Doses were escalated in 3 gy increments - so MTDs reported were: - <2 cm = 24 Gy - 2-3 cm = 18 Gy - >3 cm = 15 Gy 4 cm was max tumor size Actuarial incidence of radionecrosis - 6 mo: 5% - 12 mo: 8% - 18 mo: 9% - 24 mo: 11%

where was the most common site of relapse on COG 0031 - study of intermediate risk pediatric hodgkin's lymphoma

Initial non-bulky AND bulky sites of disease

What are examples of relative contraindications for definitive resection for RP sarcomas?

Involvement of the IVC/iliac veins - these vessels can be ligated or replaced with grafts

Uterine carcinosarcoma is categorized as what?

It is an epithelial carcinoma - NOT truly a sarcoma. It is felt to be a high grade metaplastic carcinoma Types of uterine sarcomas are: 1. leiomyosarcoma (most common) 2. endometrial stromal sarcoma 3. undifferentiated sarcoma

What is the AJCC 8th staging for LCIS

It is not in the staging. It is a benign entity and removed from the 8th edition. DCIS = stage 0 Tis

What vertebral level correlates to the SMA?

L1

What vertebral level correlates to the pancreas?

L1-2

What is the superior border of treatment for a cervical cancer with positive common iliacs but negative para-aortics? per RTOG 0724

L1/2

What vertebral level correlates with the origin of the INFERIOR mesenteric artery?

L3

take away from pre-op RT for STS

LC is in the range of 87-97% on various studies 5 yr OS is between 45-74% thought to be pretty much equivalent to post-op RT with some pros and cons

S staging for seminoma includes what?

LDH, AFP and b-HCG S1 = LDH <1.5x ULN, AFP <1000, b-HCG <5000 S2 = LDH 1.5x-10x normal, AFP 1,000 - 10,000. b-HCG 5,000 - 50,000 S3 = LDH >10x normal, AFP >10,000, bhCG >50,000 Good way to remember S1 = AFP 1k, b-HCG 5k, LDH <1.5 S2 = in between S3 = >10k, bHCG >50k, LDH >10x

Bifocal intragranial germinoma is considered local or distant disease and can be managed with WVRT or CSI?

LOCAL Doesn't need CSI 24 Gy WVRT boosting gross disease to 45 Gy (if no chemo)

What determines N status in anal cancer?

LOCATION N1a = inguinal, mesorectal or internal iliac nodes N1b = external iliac nodes N1c = a+b N+ is stage III in anal cancer

What studies should be done to obtain M stage in medulloblastoma and when?

LP and MRI spine Typically should be done at least 10 days after surgery - this is because of false positives if done <10 days and typically isn't done pre-op because these kids often have hydrocephalus so LP would have a higher risk of herniation.

NCI study looking at post op radiation in high and low grade STS of the extremity - high grade randomized to post-op RT (63 Gy) + concurrent chemo VS chemotherapy alone - low grade randomized to post-op RT (63 Gy) vs observation alone

LR was reduced with addition of radiation in either high or low grade high grade = 0% vs 19% (chemo alone), SS low grade = 4% vs 33% (observation), SS Limb sparing surgery alone VS limb sparing surgery + RT +/- chemo - local recurrence - 4% vs 0% - 10 yr OS 75% vs 82% - 20 yr OS 64% vs 71%

What are the Li-RADS criteria - applicable in pts w HCC, hep B/C and non-vascular causes of cirrhosis What are the MAJOR criteria for LR-5

LR1-5 1 = definitively benign - 6 mo surv 2 = probably benign - 6 mo surv 3 = intermediate probability - 3-6 mo surv 4 = probable HCC - multiD discussion +/- biopsy 5 = DEFINITELY HCC - workup appropriately LR5 = things that mean for sure HCC - arterial phase hyperenhancement (non-rim like enhancement in arterial phase) - observation size 1 or greater cm - non-peripheral venous washout (Non- is Not good) - enhancing venous capsule - >50% in <6 months

In Linac based SRS vs GKRS to what IDL is the dose typically prescribed?

Linac = 80% IDL GKRS = 50% IDL These essentially represent the steepest point of dose fall off

What is the most common soft tissue sarcoma in adults?

Liposarcoma

Most common site of metastatic disease for RP sarcomas?

Liver (39%) > Lung (31%)

high risk skin cancer per NCCN?

Low risk things - trunk < 2 cm - well defined borders - primary instead of recurrent - non-immunocompromised - no prior RT or chronic inflammation in area - slow growing, no neurologic symptoms - well or moderate diff - No LVSI or PNI - <6 mm DOI and no invasion beyond subcutaneous fat VERY high risk - size >4 cm any location - desmoplastic - >6 mm DOI or invasion into subcutaneous fat - LVI+ - PNI + PNI makes high risk, but LVSI makes very high risk

What is the appearance of prostate cancer on T2 weighted prostate MRI?

Low signal hypointensity high ADC/DWI signal (restricts diffusion) +/- contrast enhancement In the picture, the darker area on patient left in the PZ is the concerning nodule. Blue is anterior fibromuscular stroma Yellow is peri-urethral zone red is peripheral zone green is transitional zone

Pts on RTOG 0617 had equiv survival if treated with IMRT vs 3D however pts with IMRT had significantly more clinically advanced disease. What metric is thought to account for this difference?

Lower heart dose with IMRT that led to better OS -- rad onc questions says V40 on secondary analysis. 0617 also showed IMRT associated w/ lower radiation pneumonitis (3.5 v 7.9%, SS), and decreased cardiac doses (IMRT associated with decreased V40 and cardiac doses correlated with OS)- secondary analysis V20 was associated with increased G3+ RP risk on MVA (SS) Note: 0617 was the study that looked at dose escal 60 vs 74 Gy +/- cetuximab - four arm - cetuximab had no benefit - no benefit to dose escalation with 74 Gy - and they actually had WORSE OS IMRT group had higher PTV/lung vol ratio, more stage IIIB disease, and larger PTVs compared to 3D group - but still had same survival metrics.

in the 2021 (second) update of the MACH-NC Head and neck cancer meta-analysis - what were the benefits of concurrent chemoRT compared to sequential (induction +/- adjuvant) chemoradiotherapy What was the absolute survival difference? What two subsets showed a significant benefit with chemotherapy?

MACH-NC analyzed 101 trials between 1965-2016 - most were looking at concurrent chemo in HN trials. CONCURRENT ChemoRT = improved overall survival, improved event free survival and improved loco-regional failure relative to induction -- NO OS benefit was seen for induction or adjuvant on this analysis. OS benefit was ~6.5% absolute benefit of concurrent compared to sequential Age and PS were significant factors. Older age and worse PS did worse.

The ADAURA trial showed what benefit to adjuvant osimertinib for resected EGFR positive NSCLC? What trial showed that osimertinib was better than other EGFR-TKIs?

MASSIVE DFS benefit ~83% DFS benefit -- ~80% reduction in risk of recurrence or death EGFR TKI was for 3 years or until progression 24 month DFS was 89% vs 52% (HR 0.2) - SS Osimertinib decreased rates of both LRR and DR relative to placebo Note: The FLAURA trail demonstrated superiority of osimertinib over other EGFR-TKIs in thef irst line treatment of LA or metastatic EGFR mut NSCLC

Expected LC for melanoma with these fractionation? - 30/5 - 48/20

MD Anderson study looked at Phase II looking at high risk pts (breslow depth 1.5 mm, clinically node positive, recurrence) and did 30 Gy 5 fractions electrons twice weekly - saw 88% LC and 47% OS TROG 02.01 did 48/20 for the indications like (1 parotid node, 2 axillary nodes, 3 groin nodes, any node w/ ENE, or node over 3 cm in the neck or 4 cm in groin) - did 48/20 -- found 82% LC vs 68% in obs group.

What have been shown to be predictors of systemic recurrence in breast cancer at time of IBTR?

MD anderson - initial lymph node involvement at time of IBTR - skin involvement at time of IBTR Dana Farber - invasive histology at recurrence - local therapy for recurrence (mastectomy, vs BCS, vs none) - short interval time to recurrence - age at initial diagnosis

5 yr OS for MGMT methylated vs unmethylated with RT vs RT + TMZ

MGMT unmethylated - RT 0% - RT+TMZ 8% MGMT methylated - RT 5% - RT+TZM 14%

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 trial asked if we need 5FU/MCC or Cis/5FU concurrent and if maintenance chemo (Cis/5FU vs obs) was helpful for anal canal What was the result?

MMC/5FU is SOC for concurrent and no benefit to adjuvant chemo ACT 1 established MMC/5FU as SOC first. For ACT II all cancer metrics were equivalent This trial was NOT a non-inferiority trial so the conclusion is that Cis/5FU is NOT superior to MMC/5FU and thus MMC/5FU is the standard of care still.

MRI surveillance protocol for G1-2 meningioma?

MRI at 3, 6, and 12 months - for first year q6-12 months for years 2-5 Every 1-3 years after that NCCN guidelines RTOG 0539 said q6 months for 3 years then annually for 10 years

type of brachytherapy applicator needed if treating an early stage (IA) endometrial cancer w/ definitive brachytherapy alone?

MUST HAVE A TANDEM to treat the entire endometrial cavity In generally for medically inoperable patients, you would need EBRT + brachy but in very early medically inoperable you could do brachy monotherapy. Dose and fractionations listed in the picture

overview of major gastric studies?

MacDonald INT 0116 - surgery --> chemoRT (5FU/Lv)- showed benefit but most didn't have D2 LN dissection. CRT probably made up for bad surgery. Diffuse subtype specifically didn't benefit much. ARTIST 1 - better surgery and N0/N+ --> chemoRT no benefit all comers to CRT, but subset analysis showed N+ did benefit and intestinal subtype benefited ARTIST 2 - better surgery and all N+ --> no benefit to chemoRT (note was S1 vs SOX vs SOX + RT) CRITICS - ECC - surgery - ECC vs ChemoRT -- no difference in DFS or OS MAGIC - ECF - surgery - ECF compared to surgery alone. Chemo had DFS and survival benefit (~10%) FLOT4 trial - compared ECF to FLOT and FLOT was better

STAMPEDE 16 had a four way randomization to 1) long term hormones alone 2) LTH + zoledronic acid 3) LTH + zoledronic acid + docetaxel 4) LTH + docetaxel 61% metastatic, ~15% node positive - about 24% N0 locally confined disease. what was the outcome?

Median OS improved in any arm that docetaxel was in by ~5-10 months (71 v not reached v 81 v 76 months) ZA made no difference. Expected increased AE in chemo arm

Perry NEJM 2017 looked at short course RT 40/15 for GBM in older patients +/- TMZ -- found what?

Median OS was better for TMZ arm (9.3 mo vs 7.6 mo, SS) Median PFS was better for TMZ arm (5.4 v 3.9 mo, SS) MGMT methyalated had sig med OS benefit (13.5 vs 7.7 mo, SS) MGMT unmethylated had trend toward benefit (10 v 7.9, p <0.055)

is there a survival advantage to adjuvant chemotherapy for soft tissue sarcoma?

Meta-analysis (Pervaiz et all Cancer 2008) - NO benefit to doxorubicin MONOTHERAPY - YES survival benefit if doxorubicin + ifosfamide (OR 0.56, SS) multiple other studies have shown no DFS or OS benefit to chemotherapy.

Bulky disease (10 cm) Large mediastinal mass (MMR >0.33) ESR >50 Any B symptoms >3 sites of disease What group definition is this for unfavorable Hodgkins?

NCCN definition NCCN adds bulk and need 1 more nodal site

Is there an increase in failures if post-induction chemotherapy volumes are targeted in SCLC?

NO

any imaging features to distinguish desmoid from sarcoma?

NO

Is there a benefit to resection of an asymptomatic primary in metastatic colorectal cancer with resectable primary and unresectable oligomets over going straight to chemo?

NO this was answered by the iPACS trial that compared 1) upfront systemic therapy, 2) upfront resection followed by either mFOLFOX +bev vs CapeOX It was stopped early because there was no appreciable difference between upfront resection vs upfront chemo in terms of survival metrics BUT there was worse toxicity in the upfront surgery group, SS delay to starting chemo and increased non-hematologic toxicity

was there a survival difference between surgery + rt vs induction chemo + chemoRT on the VA larynx trial?

NO - 2 yr OS 68% on both arms Interestingly DM rate was SS different favoring induction chemo 11 v 17% rarate of larynx pres was 62% at 4 yrs in CRT arm rate of salvage TL was 56% in the T4 pts tho (so more than half it failed) vs 29% in <T4 tumorste of larynx pres was 62% at 4 yrs in CRT arm rate of salvage TL was 56% in the T4 pts tho (so more than half it failed) vs 29% in <T4 tumors

Any benefit to postop RT for colon cancers?

NO - INT 0130 - Martenson 2004 P3 RCT with colon cancer w high risk features (tumor adherence, invasion of surrounding structures, or T3N1 or T3N2 disease) to adjuvant CRT (45-50.4 w/ 5-fu and levamisole) or adjuvant chemo alone 5 yr DFS and OS were the same There is some limited data to suggest benefit in cases of T4 disease (can be considered on case-by-case basis)

What is the role of concurrent chemotherapy with radiation in the setting of high risk resected cutaneous squamous cell carcinoma with R1 resection, ENE+ nodes, etc?

NO ROLE TROG 05.01 randomized people to +/- concurrent carboplatin and had NO difference in FFLR.

RTOG 9305 tested SRS boost + EBRT for GBM - found what?

NO difference

is there a difference in functional motor outcomes if a patient has 20/5 for cord compression for 5 straight days vs having an interruption for the weekend?

NO difference

STRASS trail (EORTC 62092) showed what effect of neoadjuvant RT on abdominal recurrence free survival? Post-hoc analysis showed possible benefit in what subgroup?

NO difference 60.4% vs 58.7% RFS (+/- RT) Possible benefit in liposarcoma subgroup RT was 50.4 Gy in 28 fractions

EORTC 24891 (Lefebvre 2012) trial comparing LA hypopharynx cancer - induction chemo and RT vs total laryngectomy + adj RT - what was the updated 10 yr OS difference?

NO difference - 13.8 v 13.1 (chemo-RT vs TL arms)

GOG 71 - 256 pts w stage IB2 disease (tumor >4 cm) and randomized to EBRT+brachy followed by observation or adjuvant hysterectomy - result?

NO difference in OS trends toward LC and PFS benefit with surgery Subset analysis did show OS benefit in pts with tumors 4-6 cm

Chen Lancet 2012 RCT P3 study of NPX (stage III/IV, except T3/4) pts randomized to concurrent chemoRT +/- adjuvant chemo (cis 80 - 5FU 800) showed what?

NO difference in distant failure free survival OR OS There are problems with the study

CRITICS trial - pre-op chemo - surgery - post op chemo vs - pre-op chemo - surgery - post-op chemoradiation round what?

NO difference in overal survival or EFS Chemo was ECC (epirubicin, cis, capecitabine)

What did the Recht trial (NEJM 1996, JCO 2005) trial comparing the sequencing of chemo and radiation after BCT for breast cancer show on long term analysis?

NO significant difference to chemotherapy prior to radiation vs after radiation Remember: Brown always said upfront or outback didn't matter but its more institutional preference the controversy is that in the initial report there was a benefit in freedom from distant metastases favoring chemo --> RT but this benefit was lost on longer follow up (35 v 36% NS).

Did the Caspian and IMPower133 trials allow chest consolidation? Was PCI permitted?

NO!!! NO CHEST CONSOLIDATION PCI was permitted

Dose for non-secretory vs secretory pituitary adenomas?

NON = 45 Gy - SRS ~12.5 Gy Secretory = 54 Gy - SRS ~18-20 Gy

What did NSABP-B39 show in terms of APBI vs whole breast?

NON-equivalence technically 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 -- this is because the trial was designed to show equivalence, which it technically wasn't

HD0607 (Gallamini, JCO 2020) looked at advanced stage HL (stage IIB-IVB) who underwent ABVD x 6 w/ negative (DS 1-3) PET2 and PET6 and then split into 3 cohorts based on tumor size (5-7, 8-10, >10 cm) and randomized to +/- consolidative RT (30 Gy) What group benefitted from RT?

NONE There was no improvement in PFS in any subgroup with RT. So this would be evidence to omit RT in more advanced HL if they have complete PET response. EORTC 20884 and HD15 both supported the role of consolidative RT in the setting of a PR to induction chemo.

Better trials to think about when thinking about conventional frac vs SBRT for NSCLC?

NOPERABLE 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.

COG A9961 was looking at 23.4 Gy CSI with a 32.4 PF boost and compared what adjuvant chemos?

NOT a CSI trial - compared adjuvant CCNU/Cis/vcr vs Cyclophosamide/cis/vcr No diff in these chemos

LCIS findings on mammogram?

NOT visible on mammogram

What is the difference between the NRG/RTOG and ESTRO-ACROP guidelines for CTV delineation for GBM?

NRG/RTOG: Standard 2 dose levels 46 Gy to FLAIR and 60 Gy to T1+c enhancing disease/resection cavity ESTRO/ACROP: CTV = Cavity + T1+c + 2cm +/- FLAIR (one dose level). They say "there is no definite data that inclusion of the FLAIR abnormality alters outcome"

Post-op doses for vulvar cancer?

Negative margins = 45-50 Gy Close margins (<8 mm) = 56 Gy Positive microscopic margins = 63 Gy Gross disease = 65-70 Gy

Appropriate management of a high grade inoperable osteosarcoma?

Neoadjuvant chemotherapy Radiation 60-70 Gy +/- sensitizers then adjuvant chemotherapy

Where does the nerve of the vidian canal come from and where does it go on either side of the vidian canal?

Nerve, artery and vein of the vidian canal runs through the vidian canal from the middle cranial fossa to the pterygopalatine fossa

What are some general indications for peri-autologous stem cell transplant IFRT for relapse DLBCL?

Ng Red Journal 2018 1. Localized recurrence such that radiation has acceptable toxicity 2. sites of bulky relapse >5 cm 3. sites with incomplete response to salvage chemotherapy 4. Skeletal involvement 5. Sites where local control is critical (threatened cord compression, etc)

Based on CheckMate 274, the addition of what immunotherapy drug to adjuvant treatment of bladder cancers sp neoadjuvant cisplatin and radical cystectomy improved DFS when given has a maintenance drug for MIBC?

Nivolumab median PFS 10.8 --> 20.8 months Note: Atezo was shown to have no benefit int he IMvigo010 study

Esophageal cancer - immunotherapy -- Checkmate 577 - NEJM 2021 - global randomized P3 - stage II/III Esophageal or GE junction - adeno or squam - all sp neoadjuvant chemoradiation followed by surgery -- needed to have an R0 resection and have residual disease - excluded the outliers with positive margins or the best with pCR. randomized to nivolumab 240 mg q2 weeks x 16 weeks then 480 mg q4 weeks (total 1 year) What was the result?

Nivolumab double median DFS (HR 0.69, SS) -- 11 months --> 22.4 months (SS) - essentially all subgroups benefited from nivolumab. This should be offered to all esophageal patients after neoadjuvant chemoradiation and R0 resection in anyone that has less than a pCR (1 year of nivolumab)

What did RTOG 0522 (R P3 study that looked at Cis vs Cis-Cetuximab with RT) in LA-HNC show?

No benefit of cetuximab in terms of OS, PFS, LRC, or DMFS compared to cis-RT alone

take home from SRS +/- WBRT for 1-4 brain mets ?

No diff in OS No diff in neurologic death Better LC and Distant control when combined Interestingly NO difference in cognition.

Retroperitoneal sarcoma - STRASS TRIAL - P3 RCT - 266 pts randomized to pre-op RT (median dose 50.4 Gy) vs surgery alone - 74% had liposarcoma primary endpoint = abdominal recurrence free survival - this is defined as relapse in local relapse in tumor bed + - progressive disease - pts reaching score of 3 on the American Society of Anesthesiologist scale - macroscopically incomplete resection - sarcomatosis

No difference in Abdominal recurrence free survival in the setting of pre-op RT However subgroup analysis showed possible aRFS benefit in the well differentiated liposarcomas No overall survival difference between the two arms Conclusion = preop RT should not be considered as a SOC STRASS 2 trial is a chemotherapy trial not an RT trial It is comparing pre-op chemo x 3 vs surgery alone - liposarcoma = doxorubicin/ifof - leiomyosarcoma = doxorubicin/dacarbazine

Aoyama JAMA 2006 (Japanese) study of SRS alone vs SRS + WBRT found what? RCT P3, 132 ps with 1-4 brain mets, <3 cm on MRI

No difference in OS between arms. No diff in neurologic death 12 month brain tumor recurrence distant and local (higher for SRS alone) New brain mets higher for SRS alone Salvage treatment more common in SRS alone Also no difference in long term cognitive outcomes surprisingly.

In the Dutch randomized trial (Belderbos 2021) for hippocampal sparing PCI vs standard PCI in SCLC -- what was shown?

No difference in cognitive decline and no difference in brain metastasis incidence So...it didn't hurt, but it didn't help

Vokes JCO 2007 - randomized stage III pts (366) w/ unresectable NSCLC to 2 cycles induction chemo followed by chemoRT vs definitive ChemoRT alone. result?

No improvement in survival for induction chemo (29% vs 31%) Toxicity was worse (G3 neutropenia)

RTOG 0529 compared to RTOG 9811 (historical control) showed improved hematologic toxicity based on what constraint?

No more than 50% above 30 Gy

RTOG 0631 8 Gy/1 for spinal mets for single fraction SBRT for 1-3 contiguous spine mets (16-18 Gy) - showed what?

No significant difference in pain scores or toxicity Note there was a canadian p2-3 trial (lancet 2021, presented at ASTRO 2020) that looked at 24 Gy/2 spine SBRT vs 20 Gy/5 ebrt. - found superiority of the SBRT for improving CR to pain - 35 vs 14% complete response pain relief - no significant difference in g3-4 toxicity between ebrt vs sbrt

INT 9901 - Le Pechoux Lancet Onc 2009 - 720 LS-SCLC in CR after thoracic CRT had 25 Gy in 10 vs 36 Gy in 18 -- found what?

No significant improvement in 2 yr incidence of brain mets (23 v 29%, NS) Interestingly, higher dose was associated with LOWER OS (2 yr OS 37 v 42%)

Involved site radiation therapy alone is appropriate for definitive management of which non-bulky early stage lymphoma subtype?

Nodular lymphocyte predominant Hodgkin Lymphoma ~36 Gy definitive radiation therapy alone - OS is ~95%

PET-Plan trial (Nestle 2020) compared PET based treatment planning vs conventional planning in LA-NSCLC found what?

Non-inferior local progression in the PET directed treatment group To clarify the study was looking at treating ONLY PET AVID disease vs what was more standard at that time treating PET positive disease + suspicious lymph nodes on CT scan and elective nodal basins) The idea here was that you were only targetting what was metabolically active -- thus you might not be hitting it all, but it was non-inferior with actually slightly better LC. LR progression was 17 vs 30% in PET vs conventional. No diff in OS, metastatic disease

Chinese phase III study (Lancet 2019) that looked at hypofractionation vs conventional for PMRT found what?

Non-inferiority of hypofractionation for PMRT (we don't normally do that) Details of trial - 820 women w/ T3-4 dz OR 4+ nodes - randomized to 43.5 in 15 (not standard HF) vs 50 Gy/25 fx to chestwall and regional nodes - all women got ALND - median 23 nodes removed - 97% of plans were 2D and axillary coverage was simplistic - low axillar yand chestwall were covered by single 6 MeV beam and SCV prescribed to 3 cm depth - lateral to median border of humeral head - 58 months median f/u - 5 yr LR 8.3 v 8.1 (NS) - non inferior - toxicity = fewer G3 acute skin tox in HF arm. No other significant difference in toxicity reported.

What is the expected 10 yr local control for secretory vs non-secretory pituitary adenomas?

Non-secretory ~90% Secretory ~66%

Relugolix (Orgovyx)

Nonpeptide GnRH receptor antagonist, tablets, ADT inhibits LH and FSH and lowers serum testosterone - no testosterone increase like agonists will cause initially Levels return to normal very fast Also SS lower adverse cardiac effects relative to leuprolide

Randomized P3 chinese study that compared Cis/Etop vs Carbo/taxol as concurrent chemo in stage III NSCLC found what?

Numerically higher OS in the Cis/Etop group than Carbo/Taxol Written that way because this was a superiority trial - predefined threshold for superiority was 17% -- trial showed 15% difference at 3 yrs. I guess that technically means this is a negative trial Pneumonitis was higher in the carbo/taxol group and esophagitis was higher in the cis/etop group.

The TOGA trial showed what benefit to trastuzumab with chemotherapy in the inoperable locally advanced or metastatic setting?

OS benefit Median overall survival was 13·8 months (95% CI 12-16) in those assigned to trastuzumab plus chemotherapy compared with 11·1 months (10-13) in those assigned to chemotherapy alone (hazard ratio 0·74; 95% CI 0·60-0·91; p=0·0046).

The Auperin meta-analysis (NEJM 1999) of PCI after complete response to chemoradiation in LS-SCLC -- what was the absolute improvement in 3 yr OS?

OS benefit = 5% (15.3% vs 20.7%, SS) Also decreased cumulative incidence of brain mets by ~half, SS The Meert BMC Cancer meta-analysis showed the same thing.

What was the OS benefit of bid radiation on the INT 0096 Turrisi study NEJM 1999? rates of G3 esophagitis?

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. Note: convert had similar esophagitis (no elective fields) - 19% on both arms in that study

Slotman CREST study - ES-SCLC -- chemo +/- RT chest consolidation - chest consolidation RT (30 Gy in 10 fractions) found what OS diff at 2 yrs? - what was the primary endpoint of the study

OS benefit of 10% at 2 yr -- 13 vs 3% 6 month PFS was improved - 24% vs 7% (DID NOT find a difference at 1 year -- was primary endpoint of study) - chemo = 4-6 C cis (80 mg/m2)/etop (100 mg/m2) q3 weeks 1 yr OS was 33 vs 28% (NS) Two slotman studies - CREST - didn't meet 1 yr primary endpoint of OS for chest consolidation - did show benefit at 2 yr - ES-SCLC +/- PCI DID show 1 yr OS benefit (27 vs 13%) -- didn't require upfront MRI - Japanese Takahashi 2017 paper DID require MRI upfront and DID NOT show a benefit to PCI for ES-SCLC (but allowed GKRS in the non-PCI group). Overall survival WAS the primary outcome of the study. Note, secondary outcome was brain met incidence which was lower for PCI (48% vs 69%)

Int 00-99 Al Saraf paper compared RT alone (70 Gy) vs chemoRT (70 Gy + cisplatin followed by Cis/5FU x3 cycles) - found what?

OS benefit of ~30% (47% --> 78%) PFS benefit of ~45% (24% --> 69%)

RTOG 0129 showed what impact of continuing to smoke through treatment on OS for oropharynx cancer

OS decreased by 25%

What do the results of the protecT trial show?

Obs vs RP vs RT for mostly low risk and some int risk prostate cancer - 15 yr fu shows no difference in --PCSM (3.1 v 2.2 v 2.9, NS) --overall survival --all cause mortality BUT -- Incidence of metastases is higher in the AS group - Active surveillance = 9.4% - RP = 4.7% - RT = 5.0% SS so about 5% higher chance of develop mets - but live the same amount of time Toxicity data from the first publication also showed worse leakage and sexual function in the prostectomy group and worse bowel bother acutely in the RT group that resolved.

Radiograph signs - Ewings or Osteosarcoma Onion skinning = ? Sunburst = ? Which is at the diaphysis vs epiphysis?

Onion skinning = ewing sarcoma (permeative or moth eaten) Sunburst = osteosarcoma Diaphysis = central portion = Ewings Epiphysis = toward the end = Osteosarcoma

International atomic energy Agency - phase III trial - Roa et al JCO 2015 - compared 25/5 vs 40/15 for elderly poor PS pts w/ GBM - KPS 50-70, age >50 OR age >65 KPS 80-100 - what was different between these arms?

Only difference was duration of therapy Median OS was the same, median PFS was the same, QOL was the same

what subsite showed the greatest improvement in LRC on the Bonner trial?

Oropharynx Arms of Bonner trial - ONCE DAILY: 70 in 35 daily - TWICE DAILY: 72 - 76.8 Gy twice daily - CONCOMITANT BOOST: 72 in 42 fractions (3.6 weeks of daily, followed by BID for rest of course) Note the concomitant boost had the MOST improved OS so most improved with cetuximab were concomitant boost and oropharynx

What is the common secondary neoplasm associated with retinoblastoma due to the Rb1 mutation?

Osteosarcoma

RT treatment field and dose for stage I seminoma What did the bruns Acta oncol 2005 study that changed the border from T10/T11 to T11/12 show?

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 No difference in relapse rate

NVALT-11 study for stage III NSCLC treated with 36 Gy in 18 vs 30 Gy in 12 fractions vs 30 Gy in 10 fractions showed what?

PCI did reduce the rate of development of symptomatic brain metastases (7 v 27.2%, SS) and significantly increased the time to develop symptomatic brain metastases. Did not affect OS G1 and 2 memory impairment was significantly worse in the PCI arm

What are the criteria for transanal local excision for rectal cancer?

PER NCCN GUIDELINES - <30% circumference of the bowel - T1 lesions ONLY - <3 cm in size - mobile, not fixed - Margin clear >3 mm - within 8 cm of the anal verge - Endoscopically removed polyp with cancer or indeterminate pathology - NO LVSI - well to moderately differentiated No evidence of lymphadenopathy on pre-treatment imaging

What did the long term 8 yr followup of SABR COMET show for PFS and OS?

PFS - 0-21% OS - 13-27%

GORTEC 99-02 Trial - LA HN cancers (66% OP, oral cavity, hypopharynx, larynx - stage III/IV - 222 pts - Randomized to 1. RT (70 Gy/35 fxn) +/- chemo (Cis/5FU) 2. Concurrent chemo with accelerated RT - 70 Gy in 6 weeks - Cis/5 FU 3. "Very accelerated radiation therapy (VART)" - 64.8 Gy in 3.5 weeks @1.8 Gy BID for 5 days per week - results?

PFS SS favored CRT over VART (37% vs 32%) OS SS favored CRT over VART (42.6% vs 36.5%) 3 yr LRF favored CRT and accel CRT over VART 3 yr DMFS not different G3-4 toxicity - SS worse for VART vs either CRT or Accel CRT Based on this trial conventional fractionation with chemo is standard of care

Benefit of pluvicto?

PFS and OS benefit seen per phase III VISION trial (NEJM 2021)

What was the result of chemotherapy addition to RT for positive margins, positive nodes, or parametrium involvement per GOG109 (INT0107)?

PFS and OS were significantly improved 4 yr PFS (27% benefit) - RT 53% - CRT 80% 4 yr OS (10% benefit) - 71% - 81% Re-analysis of the trial (Monk 2005) showed that tumors <2 cm or only 1 node DID NOT benefit from chemoRT.

Generally nearly all Hodgkin's trials showed that omission of RT was associated with equivalent OS but WORSE PFS. The cochrane meta-analysis of seven trials showed what?

PFS benefit with RT in all studies OS benefit is only seen when excluding the studies with a high number of patients not receiving treatment as randomized.

Genetics - best prognosis in endometrial cancer?

POLE 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% - TP53 mutations in 90% of cases (clear cell, carcinosarcoma, serous types)

Which of the Heaps factors (1990) for vulvar cancer has the strongest influence on whether or not to deliver post-op RT to the primary site

POSITIVE/close margin (<8 mm fixed) LR - <8 mm = 48% - >8 mm = 0%

10 yr results of Prime II study showed what rate of LR for RT group?

PRIME II was 65 or older, T1-2N0, ER+/PR+, 3 cm or smaller, no nodes, G3 OR LVI (not both) lumpectomy + tamoxifen +/- radiation - 10 yr LC was 0.9% vs 9.5% - no diff in OS. updated results published in 2023 NEJM CALGB 9343 - hughes trial showed essentially the same thing in 70 yrs

What pre-therapy workup for a rectal cancer should be done to ensure no occult malignancy in a nearby ogan for all men?

PSA - checking for prostate cancer -- harder to treat if you have now done APR/LAR/neoadjuvant RT

What is the phoenix definition

PSA >2.0 ng/mL above nadir counted as the date of failure

Take home points from the first and second Patchell brain met studies?

Patchell 1 = whole brain +/- upfront surgery (36 Gy Co-60...) Patchell 2 = surgery +/- whole brain (50.4 Gy...) BOTH showed reduction in dying neurologic death BOTH showed likelihood of recurrence at initial site was ~50% with single modality and ~10% (P2) -20% (P1) with combination) PATCHELL 2 did NOT show an improvement in OS whereas upfront surgery was associated with a survival benefit (40 vs 15 weeks) compare to WBRT alone in Patchell 1. Note: Patchell 1, 11% of people excluded because it wasn't actually a met Remember: Patchell 1 = everybody got whole brain, question was if surgery helped, answer was yes Patchell 2 = everybody got surgery, question was if whole brain helped, answer was yes

How was 5FU administered on the german rectal cancer study

Pay attention to how this is worded because it was PVI which is sometimes described as "continuous" but is is not exactly continuous venous infusion weeks 1-5 Its actually given as 1000 mg/m2 per day as a 120 hr "protracted infusion" during weeks 1 and weeks 5 This might be written as "bolus infusion" of 5FU during weeks 1 and 5

MAGIC trial 5 yr OS difference?

Peri-operative ECF -- 36% vs 23% (at 5 yr)

Based on CT scans from historical data (Halperin red journal 1989) what margin is needed to encompass histologically identifiable GBM?

Peritumoral edema + 3 cm

GOG 109 = ____ study - showed IA2, IB, and IIA w/ high risk features after radical hysterectomy benefited from the chemoradiation vs RT alone -

Peter's study Positive margins Positive nodes Parametrial involvement Improved PFS and OS for these patients PFS = 63 v 80% OS = 71 v 81%

Therapies for xerostomia

Pilocarpine - parasympathetic simulants Biotene Gustatory stimulants RCT Johnson NEJM 1993 showed pilocarpine (5 or 10 mg TID for 12 weeks) - improved xerostomia (44% v 25%, SS)

what is the risk of symptompatic pneumonitis if V20 is 32-40% based on Graham et al red journal 1999

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: (round numbers) 22% = 0 22-31 = 10% 32-40 = 14% > 40 = 47% 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% RR of 99 pts, only predictor that held up on MVA was V20 as predictor of radiation pneumonitis (true of 0617 as well)

What is the major complication of RFA for NSCLC?

Pneumothorax (up to 52% of cases) Risk factors for pneumothorax - male size - long length of lung traversed by electrode - middle or lower lobes - greater number of tumors ablated 30 day procedure specific mortality rate = 2.6%

what do point A and B correspond to

Point A = 2 cm superior from the external cervical os and 2 cm lateral to the tandem = paracervical triangle (where the uterine vessels cross the ureter) -- technically the ABS defines as 2 cm superior from the ovoids defined on 3D imaging Point B = 2 cm superior from the OS and 5 cm lateral from the midline = obturator nodes/parametrium

Combined analysis of TOG 9501 and EROTC 22931 showed what groups had a survival benefit from addition of chemo to RT for resected HN SCC?

Pos margin and ECE

What did NSABP B18 test?

Pre vs Post operative ACx4 neoadjuvant had benefit of down-staging tumors and increased ability to have BCS. Also decreased node positive rate (41 v 57%, SS)

The three major adjuvant radiation trials in prostate cancer (SWOG, ARO, EORTC) treated what as the radiation volume?

Prostate fossa only

How much of the seminal vesicles should you cover when treating an intermediate risk prostate cancer according to the RTOG?

Proximal 1 cm Only 7% of SV invasion extends beyond 1 cm in int patients. Only 1% of SV invasion beyond 1cm in low risk patients

OLIGOMET data for HN - retrospective - MSKCC series of 1,000 pts with HN cancer what was the conclusion regarding who had a survival advantage with local therapy?

Pts with 1 metastasis had a survival of 25 months vs 2-4 metastases (11.3 months) vs 5 or more (7.5 months). (SS) 1 met good more than 1 not so good

results of RAPID trial comparing WBI to APBI? which had worse acute vs late toxicity?

RAPID: 2135 pts, >40 yrs, IDC or DCIS, pN0 APBI was non-inferior to WBI - 38.5 in 10 bid fractions -5 days Acute toxicity was lower with APBI (28% v 45%) late radiation toxicity was WORSE in APBI (32% v 13%) - breast induration, skin telangiectasias Adverse cosmesis outcome was worse for APBI when was rated by nurse assessment - similar if using patient self assessment.

What causes Lhermitte sign and what is the management?

REVERSIBLE demyelination of the ascending sensory neurons after radiotherapy - causes electric shock type sensation radiating down into the distal extremities particularly on neck flexion Typically lasts 3-6 months and is self limiting just observation ~20% incidence with strongest predictor being cord receiving >40 Gy

2 and 5 yr OS for RT vs RT + TMZ on Stupp study?

RT RT + TMZ 2 yr OS 11% 27% 5 yr OS 2% 10%

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? This trial was meant to establish a experimental arm on HN005, not to be a standalone metric for how to treat.

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) - 60 Gy in 6 weeks (40 mg/m2 cis) - HN002 winner - 60 Gy in 5 weeks (6 fractions per week with nivo)....weird trial

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

Childhood cancer survival study suggests what is the most significant factor associated with the development of secondary sarcoma?

Radiation dose -- dose response relationship starts as low as 10 gy

To match the superior divergence of the tangent beams with the supraclav field for a two-isocenter breast plan, what do you have to do?

Remember, push breast patients away, pull CSI patients close So kick the couch feet away from the gantry for both the lateral and medial tangent fields

The first Patchell study looked at 48 pts with single brain mets - compared surgery + WBRT vs WBRT alone (36 Gy at 3 Gy per fraction, Co-60) - survival? - recurrence rate at site of original met? - median time to recurrence at site of original met? - Median time to death from neurologic cause? - Median length of functional independence? How many people were excluded from the study that were found NOT have have a metastatic brain tumor?

S+WBRT vs WBRT alone - essentially all metrics favored surgery followed by whole brain (all SS) - median OS survival = 40 vs 15 weeks - recurrence rate at site of original met = 20% vs 52% - median time to recurrence at site of original met = >59 weeks vs 21 weeks - Median time to death from neurologic cause = 62 weeks vs 26 weeks - Median length of functional independence = 38 weeks vs 8 weeks How many people were excluded from the study that were found NOT have have a metastatic brain tumor = 11% were excluded (6 of 54 pts found not to have cancer) Note: 1st patchell study included patients with 1 brain met -- there was a stupid question that was trying make sure you know that single brain met isn't the same as solitary brain met. Solitary means is the ONLY site of disease in the body whereas single brain met means 1 brain met and there could be other disease outside of the CNS. In other words, extracranial disease was NOT an exclusion criteria for the 1st patchell study.

Sahgal 2021 Lanc Onc compared 20/5 vs 24/2 for spinal mets - what was rate of complete pain response? What was the rate of vertebral spinal compression fractures after SBRT?

SBRT - 35% Conv - 14% SBRT vert compression fractures = 14% Saghal 2021 - positive spine SBRT study Ryu 2019 - negative spine SBRT study (single fraction 16-18 Gy vs 8 Gy 1 fraction)

Slotman EORTC 08993 included what ES-SCLC pts to randomize to PCI vs no further treatment after chemo benefit? what's the caveat? What trial disagreed with this result?

SLOTMAN trial pts with ANY response to chemo 1 yr reduction in incidence of brain mets (40.4% vs 14.6%) 1 yr OS benefit 27.1% vs 13.3% Pre-MRI era - so might have been treating some pts with asymptomatic brain mets and didn't know it. Japanese trial (Takahashi 2017) showed that with pre-PCI MRI there WAS NOT a survival benefit. But the problem with this trial is that lots of the no-RT group got GK salvage and they still didn't count that as RT...

What are the indications for whole abdomen radiation in wilms tumor

SPAR diffuse Spillage Peritoneal seeding Ascites/Gross Abdominal disease pre-opreative Rupture

Rectal constraint per RTOG 0534

SPPORT trial Rectum - V65 <35% - V40 <55% Bladder - V65 <50% - V40 <70% Bowel space V45 <150 cc

Randomized trial of post-op SRS vs WBRT for brain mets - (Brown Lancet 2017, Breen ASTRO 2022) - what were the results regarding cognitive outcome and local control

SRS had better cognitive outcome equivalent LC

What are the major STAMPEDE trial conclusions?

STAMPEDE '16 = ADT + Docetaxel better than ADT alone (improved OS with worse adverse effects) STAMPEDE '17 = ADT + abiraterone is better than ADT alone (30% FFS benefit in all groups, OS benefit in metastatic pts) STAMPEDE '18 = Primary RT in metastatic prostate cancer pts has benefit in all metastatic patients (4 month FFS benefit in all pts, 8% 3 yr OS benefit in those w/ low metastatic burden) - another STAMPEDE paper in '18 by Sydes showed Abi+ADT was better than Docetaxel + ADT (had superior bPFS)

results of ACNS 0331 for dose reduction CSI in medulloblastoma?

STANDARD RISK 23.4 vs 18 Gy and 18 Gy was inferior in terms of 5 yr OS (78 vs 85%) and 5 yr EFS (72 vs 83%) Also showed that there was no difference between involved field boost and posterior fossa boost for STANDARD RISK

Which was the ONLY rectal cancer pre-operative RT study that showed an OVERALL SURVIVAL benefit to pre-op?

SWEDISH RECTAL CANCER TRIAL - NEJM 1997 25/5 pre-op - 1 week - surgery vs surgery alone (pre-op vs surgery alone) - OS = 38 v 30% - CSS = 72 v 62% - LR = 9% vs 26% major caveat - surgery here WAS NOT standard of care TME - likely explains the higher recurrence rates seen in the surgery arm and the benefit of pre-op.

When treating a rectal cancer post-op that has undergone APR, what must be done with the scar regarding treatment planning?

Scar should be wired and treated with a 1.5 cm margin

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

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 important point here is that there was good response with 2/3 having CR and NOT additional neurotoxicity from adding in whole brain other data showed that dose up to 60 doesn't help - still get in field failures other data showed that you can't do partial brain, out of field recurrence is high if you do -- have to do whole brain

The RAPIDO trial for TNT consisted of what treatment groups? what was the outcome?

Short Course RT alone (25/5) no chemo followed by CapeOX x 6 cycles (or 9 cycles of FOLFOX) followed by TME vs Standard was 50.4 Gy in 28 fractions w/ concurrent xeloda followed by TME -- followed by adjuvant chemotherapy (8 cycles CAPOX or 12 cycles FOLFOX) at 3 yrs - rate of disease failure was significantly lower with TNT (23.7%) than standard therapy (30.4%) - this was driven by decrease in distant failure in TNT (20% vs 27%) - pCR rate was also higher in TNT group (28%) vs 14% in standard therapy arm. Note, German pre-op vs postop trial only had 8% pCR in the neoadjuvant arm. TNT is considered standard of care. Not necessarily always done with 5x5 but idea is all therapy before TME Note- the longer follow up of the rapido trial at 5 yrs showed that short course might have slightly worse local control actually (LRR 10% v 6%, breached mesorectum 21% v 4%; OS still similar)

Major criticism regarding the old INT 0123 (minsky) study of dose escalation to 64.8 vs 50.4 Gy for esophageal cancer - was what?

Showed increased treatment related death in the dose escalation arm, however an excess of these deaths occurred during the first 50.4 Gy portion of treatment thus didn't seem like it was actually dose escalation that was responsible.

Supratentorial neuroepithelial tumor (formerly known as PNET) - resected w/o anaplasia - LP and MR confirm M0 Adjuvant tx?

Similar to HR medulloblastoma + 1 fraction 36 Gy CIS + 19.8 Gy boost = 55.8 Gy (HR medullo would be to 54) + concurrent vincristine

Workup for ependymoma

Similar to medulloblastoma - LP of the spine 10-14 days after surgery - ideally pre-operative CSF is obtained, but if it wasn't done (because of increased intracranial pressure) then you need to wait 10-14 days after surgery to allow debris to clear Neuraxis dissemination occurs in 6-16% of the population. ependymoma - chemo used to delay rt in infant (<1 yr) - <18 months + supratentorial OR infratentorial any age = 54 - >18 months + supratentorial = 59.4 Gy

What is the treatment of pineoblastoma?

Similar to other high risk PNETs/medulloblastoma Treatment is 36 Gy CSI plus 9 Gy boost to spinal disease plus 19.8 (55.8 Gy total) to the posterior fossa. Concurrent Vcr and adjuvant Cisplatin based chemo. Note we do 54 Gy PF for HR medullo

SCORAD trial compared single fraction radiation to multifraction RT for malignant spinal canal compression -- found what?

Single fraction was NOT non-inferior to multi-fraction BUT OS was the same -- however it wasn't a huge difference -- 69.3% vs 72.7% -- at 8 weeks - non-inferiority was demonstrated for all other time points (1, 4, and 12 weeks) - as well as OS Single fraction = multifraction when it comes to pain -- not the case for cord compression

What were the risk factors included the enrollment criteria for high risk low-grade glioma per RTOG 04-24 (54 Gy + concurrent and adjuvant TMZ

Size >6 cm astrocytoma/mixed histology age >40 tumor crosses midline pre-operative neurologic deficit These are all the things that make LGG high risk (old "SATAN" risk factors -- newer studies really just used Age >40 or STR) Remember, 5 yr PFS for age <40 and GTR = ~50% Of note for RTOG 0424, 3 yr OS was 73.1% (SS improved compared to historical controls), 3 yr PFS was 59.2%

In RTOG 9508 of SRS + WBRT - what histologic subtype had an OS benefit? - pts w/ 1-3 brain mets - 333 pts, no prior cranial RT - MRI required - max diameter 5 cm w/ additional lesion not >3 cm -

Squamous cell or non-small cell tumors All comers med OS wasn't different. Slightly higher med OS if only 1 brain met (4.9 v 6.5 SS) LC was better w/ combined Stable or improved KPS better with combined On MVA, only RPA class 1 and type of tumor (squamous or non-small cell) had statistical effect on survival

What is the CSI and PF boost dose if a SR medulloblastoma is NOT able to receive chemo

Standard risk + chemo - CSI = 23.4 Gy - PF boost to 54 Gy (or really involved field these days) Standard risk without chemo - more like HR w/ chemo - CSI = 36 Gy - PF boost to 54-55.8 Gy

Quality Improvement BS - what is the PDSA cycle?

Stands for Plan Do Study Act

SALVAGE PROSTATE NOOMOGRAM Stephenson (retrospective) --> 3 papers --2004 - 2007 - Tendulkar 2016 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? NOTE: One is not intuitively obvious but makes sense when you think about it...

Stephenson (retrospective) RISK FACTORS FOR PROGRESSION: - PSA>2 prior to RT - Gleason 9-10 - negative margins (?) - fast PSA doubling times - SVI - lower SRT doses (66 Gy or higher is better) - lack of ADT - EPE 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) - 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.

What is a summary of what the oligomet trials showed - from the list know which ones showed PFS and OS benefit vs just PFS/ADT survival type things SABR COMET GOMEZ SINDAS EORTC 40004 STOMP ORIOLE IYENGAR RTOG 9508 PulMiCC (treasure)

Studies that showed improved PFS and OS SABR COMET (Palma; multiple histologies) Gomez (lung - SABR + surgery) SINDAS (lung - SABR) EORTC 40004 (Ruers; RFA-live) Studies that showed improved PFS/ADT free survival STOMP (Ost; prostate) - improved bRFS (not OS) - ADT free survival ORIOLE (Phillips; prostate) - improved PFS and bPFS (not OS) Iyengar (lung - SABR) - only PFS CNS people count RTOG 9508 - WBRT +/- SRS for single brain met - showed OS benefit for single mets PulMiCC (treasure) - colorectal + lung surgery = no benefit

NCI Canada - 190 pts with STS of extermity - randomized to pre-op RT (50 Gy - post op boost to 16-20 Gy if pos margin) VS post-op RT 66-70 Gy results?

Study was actually stopped early due to pre-op wound complications being higher than expected (35% pre vs 17% post, SS) - highest rate of complications in the thigh No difference in LR, locoregional recurrence or DM - OS was actually better however after 2.5 years in the preop group (study was not designed for survival however, so take with a grain of salt)

Current standard of care for GBM maximal therapy (with doses) and alternative escalation option?

Stupp Protocol (EORTC 26981) and EF-14 (NovoTTF; Stupp JAMA 2017) - max safe resection - post-op chemoRT to 46 Gy to T2 edema + cone down 60 Gy in 30 fractions to surgical cavity/residual enhancing tumor + 2cm) w/ concurrent TMZ (75 mg/m2 7 days per week) - adjuvant TMZ 150 mg/m2 5 days per 28 day cycles for 6 total cycles - +/- TTF Optune device worn >18 hrs per day for 6 months

What was the induction chemo in each of the RCT p3 studies looking at induction for NPX?

Sun - 3 cycles docetaxel, cisplatin, 5FU q 3 weeks --> followed by concurrent CRT w/ cis (100 mg, q3week) Zhang - 3 cycles gem/Cis --> followed by concurrent chemoRT with Cis

What are the two trials showing a benefit to induction chemo for advanced stage NPX cancer?

Sun et al 2016 Lancet - showed 3 yr FFS, OS, and distant failure free survival benefits with induction chemo Zhang et al NEJM - showed 3 yr DM and OS benefits Both had no difference in local failure which makes sense

Rectal field borders

Superior border: L5/S1 Posterior border: T4 tumors - cover entire sacrum, 1 cm posterior to sacrum/2 cm posterior to presacrum Inferior border: 3-5 cm from the inferior extent of the primary or the anal verge for the distal cancers as identified by a marker on simulation - sometimes written as the bottom of the obturator foramen Lateral borders for AP/PA: 2 cm lateral to the widest points of the bony pelvis Anterior on lateral = 1 cm anterior to the symphysis for anterior wall lesions and mid-symphysis for posterior wall lesions (we always say posterior to symphysis for T3 and anterior to symphysis for T4 to cover externals) -- another rad onc question didn't say anterior to symphysis for anterior wall - instead says anterior to symphysis only for T4 (not even T3)

Invasion of what arteries make a pancreatic cancer T4?

Superior mesenteric Celiac axis Common hepatic artery

What are the RTOG consensus borders of the prostate fossa?

Superiorly = 3-4 cm above the pubic symphysis (sometimes said the level of the cut end of the vas deferens) Anterior Border = depends if above or below the pubic symphysis - above the pubic symphysis the anterior border should encompass the posterior 1-2 cm of the bladder wall - below the PS, it is the posterior aspect of the pubis Posteriorly = to the anterior edge of the rectum, maybe concave at the level of the UVA Lateral = Levator ani and obturator internus (if above the pubic symphysis, the border is the sacrorectogenitopubic fascia) Inferiorly = >8-12 mm inferior to the vesicourethral anastomosis

what is removed in the different types of hysterectomy

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 - Class V - Ant. exent: Tubes, ovaries, vagina, bladder - Post. exent: Tubes, ovaries, rectosigmoid - Total exent: All pelvic organs

what is post-op RT dose for supratentorial anaplastic ependymoma sp GTR if <18 months vs >18 months?

Supratentorial is 59.4 Gy if >18 months if infratentorial OR supra and <18 months only go to 54 Gy

INT 0116 McDonald trial for gastric cancer - what was the 3 yr OS for both groups?

Surgery alone = 41% Surgery + ChemoRT (5fu/lv)= 50% SS OS benefit -- remember thought to be making up for inadequate D0-1 dissections in the majority of patients

Pt w/ nasopharynx cancer previously treated to 70 Gy has a local recurrence in the 65-70 Gy IDL, what is the best salvage?

Surgical resection Red Journal Ng 2021 nasopharynx re-RT guidelines - the idea is that excluding geographical miss/persistent tumor, a true local recurrence w/in the high dose target volume represents intrinsic radioresistance and re-RT is unlikely to work next time. NOTE: look for clues that they give a timeline of <6 months -- if you see this, don't pick re-RT. This is not enough time for adequate normal tissue recovery. Best answer here would be surgery with adjuvant re-RT considered for positive margins. Note: there was the 2023 Lancet You paper that claimed that twice daily was associated with improved OS in the re-RT setting (note, required a 12 month interval between RT and re-RT). The weird thing about this one was their standard fractionation group had 25% G5 toxicity and 7% G5 in hyperfrac. Makes it seem like G5 tox was driving OS difference. Their "standard fractionation" was also 60 Gy in 27 fractions....

High yield penile staging points?

T1 = superficial structures like lamina propria, dartos fascia, dermis T1a = no PNI/no LVI T1b = PNI/LVI T2 = spongiosium +/- urethra T3 = cavernosum +/- urethra T4 = adjacent structures Only inguinal nodes are regional; pelvic nodes (M1) stage IVB N3 = ENE/fixed/ulcerated = stage IV N1-2 = stage III

typical MRI findings for meningioma?

T1 iso-intense, T2 iso-hyperintense Also note T1+c = contrast enhancing

inclusion criteria for Z11

T1-2 (stage I-IIA) cN0 1-2 SLN + (NOT 3) No ENE allowed no neoadjuvant chemo allowed no positive margins no matted nodes 27.3% had additional nodes found on axillary dissection no diff in cancer outcomes (DFS, OS all equal) if they completion or RT (note RT was suppose to just be breast, but significant % used high tangents covering lvls I/II) This was shown in the Jagsi JCO 2014 paper - 15% of pts got a supraclav field, about 50% of those getting just whole breast got "high tangents"

NCCN guideline regarding who is appropriate for penile radiation (either EBRT or brachy - which is prefered?)

T1-2 G1-2 no nodes Brachy preferred <4 cm tumors max DOI <1 cm 4 cm is used as cutoff to reduce the risk of undertreating cavernosal lesions LF is as high as 50-60% if tumors is >4 cm.

what gallbladder cancer stage DOES NOT need further treatment if incidentally found at time of simple cholecystectomy?

T1a - only involving the lamina propria. If muscular layer involved the answer is to go back for radical surgery

vulvar SCC involving the anus is what T stage

T2

T stage for superficial (inner half) of bladder muscle involvement for MIBC?

T2a

a vulvar SCC involving the rectum is what T stage

T3

For a T4 rectal tumor, where should the posterior border of the lateral block be placed for a 3D field

T4 - 1 cm posterior to the entire sacrum T3 - 2 cm posterior to the pre-sacrum

treatment for a uterine carcinosarcoma?

TAH/BSO For stage IB-IV the next steps are: +chemotherapy +/- radiation therapy +/- vaginal brachytherapy this is based on NCCN of note, NCCN lumps together clear cell, serous, and carcinosarcoma into one group -- but there are difference - Bernardini 2016 showed a OS benefit for adjuvant RT in g3 endometrioid and clear cell but adjuvant chemotherapy was associated with OS benefit in serous and carcinosarcoma.

IntraOp RT - TARGIT trial and ELIOT trial - electrons via NOVAC7 as in ELIOT trial - photons (kV) via intrabeam as in TARGIT trial outcomes of these trials TARGIT - favorable, <2cm, grade 1/2, node negative, ER/PR pos - if surgical margins were <1 mm, or extensive in situ component, or unexpected lobular component - they had to get subsequent EBRT What led to non-uniform policy for this EBRT after IORT?

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. -- the statistically significant difference in LR also DID still technically meet the pre-specified non-inferiority margin of 2.5% meaning that intra-op was technically considered NON-inferior to whole breast (even tho worse control). -- in the long term data, the local recurrence rate was NOT actually reported, but local recurrence free survival was not statistically different. IMPORTANT POINT: There was non-uniformity in the post-intraop RT indications for additional EBRT because individual institutions were allowed to pre-specify additional factors that would mandate EBRT in pts treated at THEIR institution. 21.6% of pts overall that were randomized pre-operatively ended up receiving subsequent EBRT. 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

randomized study looking at 6711 women with intermediate risk oncotype score found what?

TAYLORX study - overall group didn't have SS benefit in DFS or OS with addition of chemo to endocrine therapy for oncotype 16-25 group - HOWEVER subgroup found women <50 yrs with intermediate score 16-25 in women <50 -- so thats why younger women may be offered chemo

NOA-08 trial (wick lancet 2012) looked at GBM or anaplastic astrocytoma pts >65 yrs and KPS >60. Compared TMZ alone vs 60/30 alone what was shown overall what group benefits more from TMZ what group benefits more from RT

TMZ 8.6 v EBRT 9.6 months (SS) OS TMZ was associated with longer EFS in pts with MGMT methylation RT was associated with longer EFS in pts with NON-MGMT methylated tumors

EORTC 26062 (Perry NEJM 2017) trial looked at hypofractionation 40.05 Gy in 15 fractions +/- TMZ for GBM pts >60-65 yrs with good PS (ECOG 0-2) and found what?

TMZ improved median PFS (3.9 vs 5.3 mo) and OS (7.6 v 9.3 mo).

breast genetics referral

TNBC <60 yrs all men breast ca diagnosis in pt with 1st degree relative of metastatic prostate breast ca diagnosis in pt with 1st/2nd degree relative with breast ca diagnosis <45 yrs

Management of adenocarcinoma of the anal canal?

TNT (chemo-chemoRT) followed by APR -- essentially follows rectal cancer approach cannot spare the anus with LAR -- never the right answer for anal canal.

What trial compared 23.4 and 36 Gy CSI for medulloblastoma?

TRICK QUESTION - there wasn't one There was a phase II single arm that treated standard risk medullo with 23.4 (CCG 9892 Packer et al JCO 1999) with excellent EFS (5 yr 79%). Made 23.4 Gy standard of care for standard risk

In the second Patchell study, which compared surgical resection +/- post-operative WBRT (50.4/28), what was the difference in the following metrics: - in brain tumor recurrence - median time from treatment to recurrence - tumor recurrence term at site of the original met - tumor recurrence at sites separate from the original met - death due to neurological causes - overall survival

Take home here is that post-op RT improves ALL metrics related to failure in the brain and significantly reduces the chances of dying from neurologic death but it DOES NOT improve OS All Statistically significant - Surgery+WBRT vs Surgery alone - in brain tumor recurrence = 18 vs 70% - median time from treatment to recurrence = 50 weeks vs 27 weeks - tumor recurrence at site of the original met = 10 vs 46% - tumor recurrence at sites separate from the original met = 14 vs 37% - death due to neurological causes = 14% vs 44% Overall survival = NOT SS different - 48 weeks vs 43 weeks

RTOG 9714 was a prospective RCT P3 - looked at prostate and breast patients and randomized to 30/10 vs 8/1 for painful bone mets - major findings?

Take home is that 30/10 had ~7% higher G2-4 toxicity (SS) but 8/1 had ~9% higher retx rates (SS; 18 v 9%). Subgroup analysis of painful vertebral mets showed essentially the same thing

What chemo class added to FAC (5FU, doxorubicin, and cyclophosphamide) for inflammatory breast cancer has a SS improvement in OS

Taxanes

RTOG 98-02 looked at LGG - observed "low risk" (GTR and age <40) - high risk (all others) -- randomized to RT +/- PCV - shows what?

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.

Bulk is part of what staging criteria for Hodgkin and where was it dropped?

The Cotswald modifications of the Ann Arbor system still counts size >10 cm or MMR >1/3 as X but AJCC 8th dropped bulk so doesn't count

Pagani trail NEJM 2014/18 demonstrated what with regard to adjuvant exemestane with ovarian suppression vs tamoxifen plus ovarian suppression for a period of 8 yrs in pre-menopausal women?

The adjuvant exemestane arm improved DFS and distant recurrence compared to tamoxifen alone at 8 yrs

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 Note - this is a good rule of thumb so that any thing more than this rule of thumb is >10% risk vs <10% risk if less than this. - keep in mind that generally DOI trumps grade per GOG33 so if you were comparing G2 deep third to G3 middle third, G2 deep third has the higher risk of nodal involvement because DOI wins.

What is the rationale behind TNT for rectal cancers?

The idea is to reduce the risk of distant progression by giving chemotherapy earlier and more consistently -- often when they go through CRT then surgery, they end up not getting all the chemo. Giving all therapy neoadjuvantly improves rates of getting all therapy in. Its not necessarily standardized as to how this is done - CRT followed by Chemo or Chemo followed by CRT - but tends to be chemoRT upfront if they are highly symptomatic

Where is the most common location for glomus tumors?

The skull base and neck region - carotid body tumors >50% of glomus tumors Jugulotympanic (middle ear) and vagal are less common

More recent data (Cao et al An Thoracic Surg 2018) was a SEER analysis looking at lobectomy vs wedge vs segmentectomy -- found what?

These were felt to be comparable oncologic procedures for small stage IA (1.0 cm or smaller) NSCLC. For tumors 1.1-2 cm - lobectomy and segmentectomy were equivalent -- wedge resection for this category had worse survival.

They might show imaging of an abdominal tumor and ask what to do first?

They are seeing if you want to start with chemo or do surgery first Wilms = surgery first Neuroblastoma = chemo first

Differences in toxicity for pre-op vs post-op RT for limb sarcoma? Which group had worse acute wound complications? Which group had worse late G2+ fibrosis? What were the expansions on this study?

Think O'Sullivan NCIC paper PRE-OP - preop had higher wound complications (35 v 17%) - preop had less edema (35 v 17%) - preop had less joint stiffness (18 v 23%) POST-OP - postop had bigger fields - postop had higher g2+ fibrosis (48% vs 32%) Expansion was 5 cm from tumor to block edge

Age >3 y GTR (<1.5 cm2 residual tumor) M0 CSF medulloblastoma with diffuse anaplasia on path how should this be treated?

This is standard risk by the major criteria, however diffuse anaplasia is treated per high risk regimen So 36 Gy CSI + 9 Gy boost to any spinal disease + 19.8 Gy to PF w concurrent vincristine and adjuvant cis/vcr chemo

Large mediastinal mass (mediastinal-thoracic ratio measured at T5-6 MTR >0.35) Age >50 ESR >50 if A >30 if B >3 nodal areas What group definition is this for unfavorable Hodgkins?

This is the EORTC definition EORTC adds age >50 and needs 1 more nodal site

Summary of the Big Rectal cancer trials - tell the major differences Swedish Rectal Cancer Trial (NEJM 1997) Dutch Rectal Trial (NEJM 2001) Polish rectal cancer trial (Bujko Rad onc 2004) German Rectal Cancer Trial (NEJM 2004)

This is the best way to keep these straight: They go in order as to when the trials were done and they sort of address the last question each time The Swedish, Dutch and Polish trial are all asking the question of benefit of short course RT pre-op (25/5). - ONLY Swedish (earliest) saw an OS benefit to pre-op - Dutch trial converted to SOC TME surgery and now OS benefit was lost. LR benefit still seen. - The polish trial then compared short course vs long course RT - 5x5 alone vs 50.4 w/ concurrent bolus 5FU. Swedish Rectal Cancer Trial (NEJM 1997) - 25/5 pre-op vs surgery alone (NOT TME - so NOT SOC surgery) - OS, LR, and CSS benefit to pre-op compared to nothing Dutch Rectal Trial (NEJM 2001) - 25/5 vs TME - No OS benefit - LR benefit still seen 2.4% vs 8.2% (SS) - biggest benefit seen in tumors with inferior margin <5 or <10 cm (5-10 biggest benefit) from the anal verge - no benefit if located 10-15 cm from the verge. So more benefit if lower lying Polish rectal cancer trial (Bujko Rad onc 2004) - 5x5 vs 50.4 + chemo. Sphincter preservation was the same, OS was the same, DFS and LR rates were the same. - Acute tox worse in chemoRT - pCR rate and CRM rate better in ChemoRT arm German Rectal Cancer Trial (NEJM 2004) - asked the question of pre-op vs post-op radiation - 50.4 Gy preop vs 55.8 Gy post-op both with chemo - sphincter preservation (39 v 19%) favored pre-op - 5 yr pelvic recurrence (6 v 13%) favored pre-op - less acute and late toxicity in pre-op (SS) - DM, DFS, and OS all the same though. - pCR rate for neoadjuvant chemoRT was 8% on this study - clinical T3 and or N1 downstaged to pT1-2N0 in 20% of cases SDPG - Swedish - Dutch - Polish - German - Sweds - Don't - Play - Games with the Rectum Interesting caveat about the sphincter preservation -- Overall there was no difference in Sphincter preservation on the German study. What the 39 v 19% thing is about is that in the subset of patients deterined by the surgeon before randomization to require an APR, a sphincter preserving surgery was done in 39% of them vs 19% in preop.

what factors were included in the stage adjusted IPI as defined in SWOG 8736

This specifically looked at LOWER stage people thus stage III-IV as in the typical IPI wasn't included, so stage II would have been high risk compared to stage I for the stage-adjusted Extranodal disease was excluded here so the factors were: - LDH > WNL - age >60 - PS >1 - stage I VS II Normal IPI is APLES including stage III-IV and extranodal >1 This was the classic CHOP x 8 vs CHOP x 3 + RT where CHOPx8 had worse cardiovascular outcomes and CHOPx3 + RT was the standard

Korean phase III RCT for T3-4 or N+ rectal cancer randomized to pre or post-operative chemoRT (capecitabine + RT to 50 Gy in 2 Gy fx) All pts had TME what was the result?

This was essentially a repeat of the German rectal cancer trial of pre/post op RT Result similar to German = For pts with low lying tumors, pre-operative chemoradiation arm had a higher rate of sphincter preservation (68% vs 42%, SS). - but remember, the german study only actually saw a difference in how often they were able to do sphincter preservation surgery when they thought they couldn't (39% pre-op v 19% post-op group). The actual overall rate of sphincter preservation wasn't really different. It was on the korean study. Differences = Acute and late complications were similar. 3, 5 yr DFS and OS and cumulative incidence of LR was similar. Note differences between Korean and German studies - pre vs post op doses for German 50.4 vs 55.8 compared to 50 Gy for everyone - German was 5FU instead of capecitabine - German showed lower risk of local recurrence (6% vs 13%) and lower G3-4 toxicity for acute (27 v 40%).

in RTOG 95-08, trial of WBRT +/- SBRT in pts with 1-3 brain mets, who were the only groups that had a survival advantage? What was the 1 yr LC difference? What specific classes were found to benefit from SRS boost on MVA?

Those with a single brain met (4.9 mo vs 6.5 mo, SS) -not significant for multiple brain mets other outcomes SRS assoc w/ improved PS at 6 months SRS assoc w/ improved LC 1 yr LC - WBRT = 71% - WBRT + SRS = 82% --- absolute 11% LC benefit at 1 yr OS no different all comers MVA -- RPA class 1 and squamous or non-small cell histology benefited from a boost

NSABP B04 trial design?

Three arms cN0 patients randomized to 1. radical mastectomy and axillary dissection 2. total mastectomy (w/ ALND if pos nodes) 3. total mastectomy (w/o ALND) + RT If cN+, either randomized to (1) or (3)

NSABP B06 design and outcomes?

Three arms stage I-II BC randomized to 1. total mastectomy vs 2. lumpectomy alone 3. lumpectomy + RT lumpectomy alone clear loser in terms of IBTR rates (39% lumpectomy alone vs 14% lumpectomy + RT) 20 yr DFS and OS were not different between the groups. Mastectomy = lumpectomy + RT

parameters of the Child Pugh score

Total bilirubin Serum albumin PT/INR Ascites Hepatic Encephalopathy

What is the primary therapy for non-secretory pituitary adenomas?

Trans-sphenoidal surgery Medical therapy should be used to manage symptoms caused by secretory tumors

What major risk factor should prompt bronchoscopy in esophageal cancer to r/o tracheoesophageal fistula?

Tumor above the level of the carina

Radiation planning how do you define tumor on preop volumes for extremity

Tumor defined on T1 + gad and/or T2 seq - fuse in MRI Generally you include any T1 enhancing disease as GTV + 3-4 cm for longitudinal expansions with 1.5 cm radial expansions (include with T2 hyperintense edema signal + biopsy tract) -- constrain anatomic boundaries (compartment fascia, bone, etc) PTV = 0.5 cm margin with daily IGRT - >1 cm if no daily IGRT - PTV trimmed 3-5 mm from skin typically don't use bolus unless concerned about skin involvement

Ultrahypofractionated prostate RT (SBRT) is delivered how?

Typically in WEEKLY fractions (not daily) - don't pick options that say daily Often doses are NOT >500 cGy if done in 5 fractions -- doses are more like 36/5

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? DLBCL - RICOVER-60 vs RICOVER-noRTH - RICOVER-60 was a 4 way randomization between 6 or 8 cycles of CHOP-14 with or without Rituximab. Pts w/ initial bulk or EN sites got RT. - pts 61-80 yrs - any stage or IPI - aggressive BCL RICOVER-noRTH - 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

UNFOLDER: 3 yr EFS significantly worse if RT was omitted so that arm was terminated RICOVER-60 Intention to treat analysis pts with bulky disease had better EFS with RT - trends for PFS and OS - R-CHOP x 6 + RT to sites of bulk was winner. 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

What anatomic structure allowed for cancers of the cervix to track posteriorly into the sacral fossa?

Uterosacral ligament

What was the IL bronchus constraint on RTOG 0813?

V18 Gy < 4 cc Goal to reduce fistula/stenosis Dmax <105% Rx is also acceptable

What is the lung constrain on RTOG 0813 PI/II dose escalation for 5 fraction SBRT for centrally located NSCLC?

V20 <10% CV12.5 Gy > 1500 cc This means you need to spare at least 1500 cc from getting more than 12.5 Gy Written another way D1500cc max 12.5 Gy D1000 cc max 13.5 Gy (CV 12.5 Gy >1000 cc) - volume of lung receiving 13.5 Gy or less should be >1000 cc

Best chest wall constraint to predict severe chest wall pain for 3-5 fraction lung SBRT for peripheral lung lesions (w/in 2.5 cm of the chestwall) Rate of chestwall pain above this?

V30 <30 cc Rate of severe chest wall pain as high as 30% if V30 = 35 cc In general, you should not compromise PTV coverage to meet chestwall metrics. MGH data did show that cropping PTV from the chestwall was associated with lower rates (0% G3/4 toxicity) of chestwall pain for tumors w/in 5 mm of the chestwall. No increase in LR was seen w/ this truncated TPV w/ 3 yr LC of 92.1% A more lax metric is often quoted at V30 <70 cc

RTOG small bowel dose constraint in cervical cancer treated with adjuvant RT?

V40 Gy <30%

What is the V60 heart constraint on RTOG 0617

V60 <1/3 V45 <2/3 V40 <100%

What is the V75 of the rectum to keep grade 2+ <15% and grade 3+ <10%?

V75 <15% Other metrics - V50 - <50% - V60 - <35% - V65 - <25% - V70 - <20% - V75 - <15% Per QUANTEC

What should be placed at sim for a endometrial sp TAH-BSO?

Vaginal opaque marker (we use a swab in a glove with radio-opaque gel)

What metric was found to be associated with developing esophagitis per Palma Red Journal meta-analysis in pts receiving chemoradiation?

Volume of esophagus receiving 60 Gy Keep in mind V60 Gy <17% - this was the best predictor Recursive partitioning identified: V60 Gy<0.07 -- Low risk group (G2 RE 29%, G3 4%) V60 Gy 0.07 - 16.99% = int risk group (G2 RE 41%, G3 10%) V60 Gy >17% -- High risk group (G2 RE 59%, G3 22%) Mean esophageal dose <34 Gy (memory aid 17 x 2)

Major two trials to think of that showed improvement in survival compared to gemcitabine/5FU for resected pancreas cancer?

Von Hoff 2013 - Gem monotherapy vs Gem + Abraxane (albumin bound paclitaxel) -- Gem+Abraxane improved PFS and OS (in metastatic pancreas cancer) + PRODIGE-24 - mFOLFIRINOX -- mFOLFIRINOX improved med OS 35 vs 54 months.

Wilms tumor, Aniridia, GU malformation, mental retardation

WAGR syndrome

Important factoids about medulloblastoma subgroups WNT SHH Group3 Group4

WNT = best prognosis, >90% survival. CTNNB1 mutations. b-cat staining SHH = intermediate prognosis. Mutations in PTCH1, SMO, SUFU. MYC-N amplification can occur. inverse relationship between age and prognosis, younger is better. - greatest frequency of this subgroup with infants and adults group 3 = typically MYC- amplified. Metastatic commonly. WORST prognosis. Group 4 - isochromosome 17q - intermediate prognosis.

What gene is associated with WAGR syndrome?

WT1 - 11p13

when is extend field radiation (inclusion of the para-aortics) done for cervical cancer?

When 1 or more pathologic node found at common iliac or above EMBRACE I data showed risk factors for failure above the radiation field - 3 or more pelvic nodes - common iliac nodes - degree of PET avidity - size of nodes >15 mm These are the criteria that EMBRACE I noted should make you consider extended para-aortic coverage EMBRACE II is ongoing and includes these factors as when to include para-aortics in the field. upper border goes to the level of the renal veins (usually L2 -- so we usually say L1/2) -- 3 cm cranial to any pathologic nodes

Treatment of Phyllodes tumor of the breast?

Wide excision without axillary staging good LC with surgery alone

should pre-operative radiation ever be considered for Ewing's sarcoma?

YES - tumors with poor radiographic/clinical response to neoadjuvant chemotherapy can be considered for pre-operative radiation

Does decadron prophylaxis improve rates of pain flare in patients receiving 8 Gy x 1 for painful bone mets?

YES - ~10% benefit Chow et al Lancet Oncol 2015 26% vs 35% Rate without steroids is ~30-40%

In the analyis of radiation induced endocrinopathy in pediatric/young adults - by Vatner et al JCO 2018, what factor was associated w/ increased risk of any hormone deficiency at 5 yrs after treatment? What was the most common endocrinopathy?

YOUNGER START OF RT GH was the most common endocrinopathy - remember measure with IGF1 All hormones showed a clear dose response to median pituitary and hypothalamic dose - 9% for <20 Gy - 55.5% for 20-40 Gy - 86.8% for >40 Gy children started on RT <10 yrs old were at highest risk.

Standard NCCN follow up for stage IA/B seminoma of the testis after radical inguinal orchiectomy for observation?

Year 1: - HP q3-6 months - CT scan 3 mo, 6 mo, 12 mo Year 2-3 - HP q6-12 months - CT scan q6-12 months Year 4-5 - HP q12 months - CT scan q12-24 months

multiple myeloma diagnostic criteria

active myeloma is defined as clonal marrow plasma cells 10% or higher or biopsy proven extramedullary plasmacytoma AND any one or more of the following: - calcium 1 mg/mL higher than the upper limit of normal or >11 - renal insufficiency - anemia - one or more osteolytic bone lesions - clonal bone marrow plasma cells >60% abnormal serum free light chain ratio >100 (involved kappy) or <0.01 (involved lambda) >1 focal lesion on MRI studies>5 mm if none of these myeloma defining events, it is termed "smoldering" myeloma if bone marrow has <10% plasma cells, M protein is <3 g/dL then the patient has MGUS

What bladder cancer histology is derived from the embryological remnant of the urachus

adenocarcinoma -- these tend to occur in the dome of the bladder Transitional cell makes up 92% of bladder cancers tho

what is in abvd

adriamycin Bleomycin vinBlastine Dacarbazine

risk features identified as intermediate high risk features on PORTEC 1

age >60 >1/2 myometrial invasion G3 disease RT reduced 5 yr LR when 2 of 3 were present (23% v 5%) For comparison GOG99 included the following - LVSI - outer 1/3 MMI - G2/3 Age >70 w/ 1 other risk factor Age >50 w/ 2 other risk factors any age with 3 risk factors dose was 46 Gy in 2 Gy fractions WBRT recurrence rate was 4% vs 14% observation 73% of recurrences were in the vaginal cuff LRR benefit only; OS was the same

where is the optimal match point between the cranial and spinal fields for CSI

as low as possible the optimal match point for the cranial and spinal fields is as low as possible. a lower match prevents dose from the PA field from exiting through the mouth - the inferior level of the match is limited by the shoulders blocking the lateral cranial levels

rates of g3+ GI toxicity for RP sarcoma pre-opRT?

based on the STRASS and Mak 2016 paper - rates of G3+ are actually very low ~5% or lower. G2+ ~85% of people tho

Chemotherapy in sarcoma -- which chemo has a benefit?

basically all i know is that doxorubicin and ifosfamide combination improves OS -- otherwise who cares Prior meta-analysis showed doxorubicin had improved DFS alone (trend for OS) Meta-analysis (Pervaiz et all Cancer 2008) - NO benefit to doxorubicin MONOTHERAPY - YES survival benefit if doxorubicin + ifosfamide (OR 0.56, SS) Neoadjuvant chemo has also been investigated - negative study for the most part - improvement in DFS/OS in favor of standard arm with epirubicin/ifosfamide compared to other random tailored chemotherapy

Major take home questions of Believers and Non-believers trails (both EORTC studies - 22844 and 22845 respectively) - believers study compared what and showed what? - non-believers study compared what and showed what? - both arms of non-believers study had what % transformation rate to HGG? - what potential benefit of early radiation did the non-believer's trial show?

believers study compared what and showed what? --> compared low dose (45 Gy) vs high dose (59.4 Gy) immediately after resection and showed no benefit to dose escalation in LGG non-believers study compared what and showed what? --> compared immediate RT vs salvage RT at time of progression (54 Gy either arm) and found better median and 5 yr PFS for early but the same OS regardless (also late group had longer survival AFTER progression) both arms of non-believers study had what % transformation rate to HGG --> 70% transformation rate in both arms (note 25% were actually HGG initially on central path review) what potential benefit of early radiation did the non-believer's trial show? --> reduced intractable seizures so that's a potential benefit to quote from this study for early RT. Can use this study also to argue to wait until progression to give RT.

CARMENA study showed what benefit in metastatic renal cell?

benefit of sunitinib (sunitinib alone was non-inferior to nephrectomy + sunitinib)

Matted axillary nodes with NO internal mammary nodes = what N stage for breast?

cN2a N1 = mobile axillary nodes N2a = Ipsilateral level I or II ax nodes that are fixed or mattered N2b = Clinically detected IM node WITHOUT axillary nodes. N3a = infraclav nodes N3b = IM nodes + axillary nodes N3c = supraclav nodes

Definitions of the distant from incisors for the following locations cervical esophagus upper thoracic esophagus middle thoracic esophagus lower thoracic esophagus

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 (30-40 cm) GEJ = divided into Siewart classification 15-20 - cervical esophagus 20-25 - upper T 25-30 - middle T 30-40 - lower T

t(12;22) = ?

clear cell sarcoma - ATF1-EWSR1 gene fusion

RTOG 911-11 -- what was the death not attributable to larynx cancer rate in the concurrent chemo vs sequential and rt alone?

concurrent = 30% sequential = 20% rt alone = 16%

what is the correct dosing of TMZ (used on RTOG 0825) What was "pre protocol" coverage of the PTV2 (high dose volume)

concurrent TMZ (75 mg/m2 7 days per week) with radiation - adjuvant TMZ 150 mg/m2 5 days per 28 day cycles for 6-12 total cycles -- the adjuvant starts 28 days after completion of chemoRT (if no G3 or greater adverse event) tmz could technically be dose escalated to 200 if no toxicity and continued good response Pre protocol = 95% PTV coverage by 60 Gy, 99% PTV2 covered by 54 Gy off protocol most people just say 95/95

inclusion criteria for SABR COMET

controlled primary disease 1-5 sites of metastasis randomized to SOC palliation vs SBRT to all sites

What is the most likely cause of vocal cord fixation in patients with hypopharynx cancer

cricoarytenoid joint/muscle invasion

Time interval for post-op SRS after resection of "less than 4 weeks" is associated with what outcome?

decreased local recurrence 2.3% local recurrence if <4 weeks 23.6% local recurrence if >4 weeks OS similar

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

what adjuvant tx should be recommended after WLE of a malig melanoma of the leg w/ 3 + LN, 2 of which have ENE?

discussion of adjuvant RT per TROG 02.01 and discussion of immunotherapy checkmate 238 also showed that in stage III/IV melanoma nivo vs ipi - nivo improved RFS and had reduced toxicity

identify the pterygomaxillary fissure

double red arrow in the pic connects the pterygopalatine fossa to the infratemporal fossa

Preop panc surgery followed by gem x 6 vs gem - gem-xrt - gem - surgery results?

doubled the R0 resection rate did not meet primary endpoint of improved OS initially -- updated follow up did show an improvement in OS unclear what to do with this in the context of

what is removed in an EPP

entire lung entire pleura IL half of pericardium hemi-diaphragm

what is the strongest predictor for LR recurrence after mastectomy (according to KATZ MDACC JCO 2000)

extent of axillary nodal involvement

Heart constraint for esophageal RT based on NRG GI006?

heart V40 <50% others V20 each kidney <30% Liver V30 <30%

what serology must be tested before started rituximab

hepb ag and antibody to core either active infection OR prior resolved infection are both associated with re-activation after rituxan

RTOG 1010 - looks at HER2 tx (herceptin) after carbo/taxol + RT --> surgery --> maintenance herceptin - chemo RT was pretty standard results?

herceptin didn't increase toxicity including cardiac No difference in DFS or OS so keep treating per checkmate 577 with nivolumab

What subgroup TECHNICALLY had inferior outcomes in Whelan for hypofrac?

high grade tumors actually had inferior 10 yr LR rates - 4.7 (CF) vs 15.6% (HF) All other outcomes essentially the same - 10 yr LR all comers - OS - cosmetic outcomes, etc Excluded from whelan - separation distance >25 cm - tumors >5 cm (T3 tumors) - positive margins (didn't have a boost on this study)

What is the primary concern when treating atypical meningiomas with SRS?

higher marginal failure rate with SRS compared to EBRT

What is the cumulative incidence of breast cancer in women treated for Hodgkin lymphoma at 30 years?

if >21 yrs old at time of RT = 19% if <21 yrs old at time of RT = 26% Size of the field also matters, mantle field 2.7x higher risk than ISRT mediastinal nodes

when do you need to do BMB in Hodgkin lymphoma

if no avid lesions, can presume negative, no BMB if >3 lesions, can presume positive and don't need to confirm with BMB If 1 hypermetabolic lesion -- you can biopsy to confirm that its actually involved. 99.9% NPV per the pooled analysis of the GHSG HD 16,17,18 trials

FIGO staging update for cervical cancer in 2018 allowed incorporation of what?

imaging studies like PET and MR

TROG 03.06 (TOAD) trial compared immediate vs delayed ADT in men with prior def therapy for prostate cancer and found what?

immediate ADT was associated with improved OS

RTOG 9410 Curran induction vs concurrent chemoRT for NSCLC showed what?

improved 5 yr OS in concurrent arms (technically there were two) sequential - 10% (cisplatin vinblastine) concurrent 1 - 16% (cisplatin vinblastine) concurrent 2 - 13% (chemotherapy and RT differed here - cis/etop (oral etop?), RT was 69.6 Gy in 58 BID fractions...)

NCDB analysis of care for sarcomas at high volume centers showed what

improvement in 2, 5 and 10 yr overall survival when these were treated at high volume centers

What considerations are important for the whole brain field for PCNSL

include posterior half of orbit intentionally inferior border goes to C2/3

EMRACE I study revealed that for cervical cancer, 50 Gy relative to 45 Gy for elective lymphatic coverage is associated with what toxicity?

increased Late GI toxicity G2+ late diarrhea increased from 9.5% --> 19.1% when comparing 45 Gy to 50 Gy

be able to identify lung LN levels based on axial slices - particularly for levels 5 and 6

keep in mind level 5 starts and inferior border of aortic arch lateral to ligamentum arteriosum level 6 starts at the lower border of the aortic arch station 5 = subaortic lymph nodes station 6 = para-aortic lymph nodes

What should be treated in whole ventricle radiation

lateral ventricles third ventricle fourth ventricle +/- pre-pontine cistern

who should receive bactrim PCP prophylaxis?

long term steroids (eqiv to 3 mg decadron for 1 month who have another immunocompromising condition) pts getting TMZ and RT (GBM, etc) solid organ transplant pts pts getting a purine analog (fludarabine ,etc) in combination with cyclophosphamide Situations where the risk of PCP is higher than 6%

medications for RT induced diarrhea

loperamide (imodium) --> followed by lomotil (Diphenoxylate / Atropine) if refractory

Benefits of pre-operative RT?

lower dose smaller treatment volumes hope to achieve R0 resection improved oxygenation of tumor cells with less disrupted vascular supply with surgery decreased fibrosis/joint stiffness Cons: - worse wound healing issues typically - tumor can progress through treatment requiring replanning

What vertebral level correlates with the origin of the superior mesenteric artery?

lower portion of L1

international germ cell cancer collaborative group risk categories for seminomatous and non-seminomatous tumors?

major things to remember - bad things: - mediastinal primary site - metastases NOT in the lung (lung mets ok) - elevated tumor markers remember S1 -2 -3 - S2 = LDH 1.5 -10x normal; AFP 1k-10k and b-HCG 5k-50k S1 is less and S3 is more in any of those categories Low risk = - RP or testicular site + - no mets or lung mets - S1 markers Intermediate risk = (only diff is S2) - RP or testicular site + - no mets or lung mets - S2 blood marks High risk = - MEDIASTINAL SITE OR - non-lung distant mets OR - S3 blood markers

what are the contents of the pterygopalatine fossa

maxillary division of the CNV (V2) infraorbital nerve (branch of V2) pterygopalatine ganglion vidian nerve, atery and vein (also known as nerve, etc of the pterygoid canal) This is a common route of spread of cancers via PNI -- classic skin cancers on the cheek.

standard breast field borders?

medial: mid sternal line (at midline) inferior: 1 cm below the inframammary fold (gunderson) or 2-3 cm below (Perez and Brady) superior: 1 cm superior on the palpable breast tissue (inferior edge of the sternoclavicular joint) lateral: 1 cm margin on all breast tissue - mid-axillary line to posterior axillary line anterior: flash skin by 2 cm

Checkmate 816 was a randomized phase III that took stage IB-IIIA resectable NSCLC and randomized to 3 cycles platinum chemo +/- nivolumab prior to surgery found what benefit? what group benefited the most?

median EFS was 31.6 months (chemo-IO) vs 20.8 months (Chemo alone) (SS) OS has not yet be reached in either group. toxicity the same pCR rate was 24% (chemo-IO) vs 2.2% (chemo alone) (SS) SUBGROUP ANALYSIS: - Stage IIIA had a comparatively greater EFS than patients with stage IB/II disease - pts w/ PDL1 expression of 1% or more had more benefit - pts with non-squamous histology had more benefit

what group has the highest rate of HPV oral infection per NHANES?

men 55-59 years old

Minniti radiother oncol 2010 showed what pattern of failure differences for MGMT methylated vs unmethylated tumors?

methylated tumors more likely to have out of field failures - only 64% were in field unmethylated tumors had 91% in field failures

Multicentric vs multifocal

multicentric = multiple lesions in different quadrants multifocal = multiple lesions in the same quadrant

What specific sarcoma is associated with a higher probability of volumetric change during pre-operative RT

myxoid liposarcoma note: initial size >10cm is also associated with high chance of change during treatment

t(12;16) is associated with what

myxoid/round cell liposarcoma

Rosenberg 1982 study of soft tissue sarcoma - amputation vs WLE and postop RT (45-50 Gy --> boost to 60-70 Gy) - patients got post-op AC - showed what results?

no difference in local failure, disease free survival or overall survival

benefit of TBI compared to chemo

no sanctuary sites is big one

who was eligible for EORTC 22931 Bernier study - think ENE/pos margins indications for chemoRT in HN cancer

note EORTC had better OS w/ CRT, RTOG 9501 did not.

posterior fossa syndrome?

occurs 1-2 days after resection of midline posterior fossa tumors SAME Swallowing dysfunction Ataxiaf Mutism Emotional lability

When should MRI of the brain be done post-op for medulloblastoma? how about of the spine?

of the brain w/in 48 hours due to post-op gliosis post-op MRI of the spine should be done on post-op day 10-14 if not done pre-operatively

What % of men have an elevated tumor marker at the time of relapse from seminoma

only 15%

swog 8794 showed what diff in adjvuant RT for post-prostectomy

only adj study to show OS benefit and improved metastatic free survival worse QOL that was worse earlier and better later

Anaplastic rhabdomyosarcoma associated with germline mutations in what?

p53 consider cancer predisposition syndromes (ie. Li Fraumeni syndrome)

Combined analysis of B18/B27 (Mamounas) showed what predictors of recurrence in mastectomy pts?

pCR to neoadjuvant chemotherapy nodal status prior to chemotherapy tumor size prior to chemotherapy

how is a micrometastasis defined for breast cancer and how does this affect anatomic staging ?

pN1mi is 0.2 mm - 2 mm (or >200 cells) micromets don't count as nodes exactly, makes prognostic anatomic stage IB

Salt and pepper appearance on MRI = ?

paragangiomas (glomus tumor)

what is the most common location of Ewings sarcoma

pelvis

Slotman CREST trial showed what benefit to chest consolidation after chemo?

primary endpoint was 1 yr OS -- wasn't met (no diff at 1 yr) BUT 2 yr showed OS benefit of 3-->13%

Seminoma treatment based on stage with doses?

radical inguinal orchiectomy followed by : Stage I = obs OR 20 Gy in 10 fractions to PA field (top of T12/bottom of L5) or carboplatin AUC 7 x1-2 cycles Stage II (nodes) - IIA - 20 Gy to PA + modified dog leg (PA + iliac down to top of acetabulum) - with boost to

what was rate of salvage TL in T4 vs <T4 on the VA larynx trial

rate of salvage TL was 56% in the T4 pts tho (so more than half it failed) vs 29% in <T4 tumors

follow up for checking blood markers for the first year in seminoma?

regardless think q2 months for 1st year q3 months for 2nd year q4 months for 3rd year q6 months for year 4 q12 months for year 5

p16 negative pathologic single node <3 cm with ENE makes what overall group stage

remember single node <3 cm with ENE downstages instead of N3b (any node with ENE clinically would be N3b), a single less than 3 cm is pN2a pN2a makes you automatically stage IVA (N3b is stage IVB) pT4a is also stage IVA pT4b is stage IVB stage IVC = metastatic

D1 nodal dissection = ?

removal of at least 15 lymph nodes from perigastric, celiac, left gastric, common hepatic, and splenic nodal regions

what areas are boosted for total skin electron beam therapy

scalp axilla perineum soles inframammary

What was the sensitivity and specificity of PET staging for NSCLC on the Cochrane meta-analysis?

sensitivity = 77.4% specificity = 90.1%

the esophagus lacks what lining

serosal lining has rich lymphatic drainage that allows for early local spread

workup for PCNSL in immunocompetent host should include what?

slit lamp exam should always be done

Giraud et al (red journal 2000) recommended what CTV margins for squamous vs adenocarcinoma in NSCLC?

squamous 6 mm adenocarcinoma 8 mm for some reason mean extent of pathologic microscopic extension was slightly higher for adenocarcinoma

Seminoma RT overview stage I stage IIA stage IIB

stage I - 20 Gy (para-aortic top of T12 --> bottom of L5) stage IIA - 30 Gy (para-aortic + IL iliac) stage IIB (nodes 2-5 cm) - 36 Gy (para-aortic + IL iliac) Note for stage II, its 20 Gy to the lymphatic chain and a boost of 10 or 16 Gy to the gross nodes. 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

nodes in extremity sarcoma = what clinical stage

stage IV T1 = <5 cm T2 = 5-10 cm T3 = 10-15 cm T4 = <15 cm

when can you consider no radiation?

superficial small T1 G1 tumors we generally consider size >5 cm and higher grade or positive margins to be post-op indications

management of primary testicular lymphoma

surgery (radical inguinal orchiectomy) chemo (R-CHOP-21 x 6 or DA-R-EPOCH) intrathecal chemotherapy (MTX) RT - 25-30 Gy (30.6 / 17 most common) - remaining testicle and scrotum pts usually >60 yrs old painless testicular mass Orchietomy required Brain MR and LP is necessary bilateral involvement in 10% of cases

what suspected thymomas can proceed directly to surgery without a biopsy

surgically resectable, well defined anterior mediastinal masses without adenopathy, negative serum tumor makers

TAX324 RCT P3 study looked at addition of a taxane to induction chemotherapy (TPF vs PF) prior to chemoradiation for stage III/IV SCC of the HN - found what? T= Docetaxel P= cisplatin F = 5-FU

survival advantage to taxane containing induction regimen 5 yr OS - 52% vs 42% (SS) med OS - 70.6 months vs 34.8 months (SS) med PFS - 38.1 months vs 13.2 months (SS) NOTE: Subsequent studies have compared induction chemo followed by CRT compared to induction chemoRT alone found no benefit to induction

Random translocation memorization t(11;18) t(9;22) t(11;22) t(15;17) t(8;14) t(11;14) t(10;14) t(12;21) t(2;13) t(14;18) t(12;22) t(12;16) t(x;17) t(x;18)

t(11;18) = gastric MALT assoc. w/ abx failure - MALT1 t(9;22) = Philadelphia chromosome (CML) - Gleevec (imatinib) - Bcr-Abl t(11;22) = Ewing's sarcoma t(15;17) = PML subtype AML M3 t(8;14) = Burkitt's lymphoma (C-MYC) t(11;14) = Mantle cell lymphoma (Cyclin-D1) t(10;14) = ALL t(12;21) = favorable prognosis AML t(2;13) = FOXO1 alveolar rhabdomyosarcoma - less common but t(1;13) also associated with RMS - t2;13 = PAX3-FOXO1 - t1;13 = PAX7-FOXO1 t(14;18) = follicular lymphoma (blc2 defect) t(12;16) = Myxoid liposarcoma - FUS-DDIT3 t(x;17) = Alveolar Soft part sarcoma - ASPL-TFE3 t(x;18) = Synovial sarcoma = SS18-SSX1 gene fusion

What was the subgroup of radiation fractionation patients on the Bonner trial that had the most improved survival with the addition of cetuximab to RT? Arms were all +/- cetuximab with different RT fractionations 1. 70/35 daily 2. 72-76.8 in 60-64 fx bid 3. 72 in 42 fractions - part daily part bid (concomitant boost)

the concomitant boost arm

If you have a plan created with 3 field 18x beams which results in 90% IDL over the pre-sacral space - what do you do

the explanation says make the energy 6x for the posterior beam

the probability of incorrectly rejecting the null hypothesis = ? Erroneously concluding that an effect doesn't exist when it does = ?

the probability of incorrectly rejecting the null hypothesis = type 1 error = alpha Erroneously concluding that an effect doesn't exist when it does = type II error = beta

worse prognostic factors for LGG

tumor >6 cm is bad

vaginal nodal drainage - upper 2/3 vs lower 1/3

upper 2/3 = pelvic nodes like iliacs and obturator lower 1/3 = inguinal/femoral

What vertebral level correlates with the origin of the celiac artery?

upper L1 or lower T12

Historically, when was RT initiated for ICE (intracranial extension) for RMS and when is it done now?

week 0 - immediately for symptoms if CN deficits or cord compression Currently we would initiate immediate chemotherapy with close monitoring and in the setting of symptomatic or radiographic progression we would then administer radiation emergently - otherwise RT should start at week 13 for low risk/int risk patients or 20 weeks for high risk In most cases, systemic chemo will relieve symptoms as quickly as RT. if done, the entire course of RT should be done in week 1 to avoid split treatment.

when should RT be used for kaposi sarcoma in AIDS

when not responding to HAART therapy and - pain - ulceration - bleeding - cosmesis - functional impairment doses 24/12 8/1 30/15 TSET also has been used

AC + T vs AC alone in NSABP B27 improved what?

ypT0 and ypN0 rates addition of docetaxel was more toxic (G4 tox 23.4% vs 10.%) cCR rates were 40.1 v 63.6% (w T) pCR rates were 13.7 v 26.1% (w T) Rates of breast conservation were similar with neoadjuvant vs adjuvant

superior border of the parotid gland

zygomatic arch

What is the typical dose rate at the prescription point for TBI?

~10 cGy/min You want <20 cGy/min to reduce the incidence of radiation pneumonitis (the dose limiting toxicity)

what % of people undergoing RT for pituitary adenoma will have a hormone deficit w/in 5 yrs?

~100%

what is the rate of subclinical level V involvement in pts with pathatologic lymphadenopathy in lvls II-IV? T1-2 oropharynx cancer

~3% according to Sanuineti 2009 red journal

What % of bFFF is lost for each 0.1 ng/mL increase in post-prostatectomy PSA?

~3% per 0.1 ng/mL Additionally an extra 2% improvement in DFS for each Gy above 60 Gy given. Data suggests a difference in control for dose < 66Gy and those of 66 Gy or higher (stephenson/tendulakar retrospective data). Per King systematic review of all salvage RT trials (41 studies, >5500 pts)

STMAPEDE 18 showed what benefit to treatment of the primary in all pts vs what benefit in low volume metastatic patients?

~4 month Biochemical FFS benefit in ALL PATIENTS OS benefit ~8% (3 yr) in low volume metastatic patients (CHAARTED def 3 or fewer bone mets - only axial, no visceral) - pelvic nodes do not count here

What is the approximate cure rate for extragonadal non-seminomatous germ cell tumors in the mediastinum?

~45%

In Timmerman et al 2006 JCO report of SBRT for early stage NSCLC, what was the incidence of G3-5 tox for central tumors? Phase II trial - 60-66 in 3 fractions for medically inoperable up to 7 cm in size

~45% 2 yr LC was 95% and 2 yr OS was 55% 20% overal G3+ tox 46% for central vs 17% for peripheral tumors This lead to RTOG 0813 which established the no fly zone around the 2cm around the proximal broncheal tree

What is the 5 yr OS advantage of any type of chemotherapy (neoadjuvant, concurrent or adjuvant) vs RT alone for LA-NPX cancer according to meta-analysis by Blanchard Lancet 2015? MAC-NPC meta-analysis

~5% (6.1% at 5 yrs to be exact) meta-analysis rule This study showed benefit of - concurrent followed by adjuvant or concurrent alone - did not see benefit to induction or adjuvant alone

EBCTCG meta-analysis for PMRT showed what benefit in node positive patients

~5% OS benefit (remember its a meta-analysis, its always 5%) This meta-analysis looked at all node positive and found ~5% OS benefit when dividing into subgroups 1-3 nodes = breast cancer specific mortality benefit and decreased local recurrence to PMRT 4+ nodes = BCSM and OS benefit 1-3 nodes had BCSM benefit but NOT OS benefit. The magnitude of the OS benefit is smaller in the meta-analysis than in the other 3 major trials (next cards) In the 1-3 node group -- LRF rate was 20% without radiation and 3.8% with radiation

What is the relapse rate if chemotherapy alone is used for intracranial germ cell tumor

~50% local relapse rate 10% mortality rate which is why chemo alone isn't an option options are chemo + RT or RT alone (higher dose) but never chemo alone

What did TAILORx trial look at?

~6700 women with HR+/HER2-, T1-2, node negative breast cancer with an intermediate oncotype DX score (11-25) comparing chemotherapy (mostly docetaxel + cyclophosphamide) endocrine therapy vs endocrine therapy alone Showed overall no benefit of the addition of chemo to the intermediate risk group Subgroup analysis showed for women <50 yrs (essentially pre-menopausal), there may be a chemo benefit in the interemediate risk group. Of note, the updated publication by Sparano NEJM 2019 suggested pathologic risk features which were further predictive of distant recurrence within this group and were (<3 cm AND low grade, <2 cm and intermediate grade or <1 cm and high grade - if didn't fall into these, were considered high risk)

approximate obliteration rate when treating a small (< 10 cc) AVM with SRS?

~85% ~69% if >10 cc