Combining
LiFraumini syn: Cowden syn: P-J syn:
P53. Multiple hamartoma PTEN gene. STK11.
Eosinophilia possibilities in genes
PDGFRA chrom4 or B chrom5 or FGFR1 rearrangement or PCM1-JAK2 fusion should be ruled out.
Durvalumab after Chemoradiotherapy in Stage III NSCLC:
PFS inc with durvalumab vs placebo. And safety was similar between the groups. AstraZeneca; PACIFIC.
CDK 4/6 Inhibitors
Palbociclib G 1+ S-phases. palpation first G spot for Sex
P substance Neurotransmitter/neuromodulator substance P(is part of mammalian tachykinin neurokinin-1 NK1 receptor involved in delayed phase of cisplatin related nausea, managed by aprepitant (Emend: selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors.), last from day 2-5 post chemo, There is also substance P in the GI tract secreted by enterochromaffin cells might help auxiliary role.
Peeing delayed in Imad.
In CMML mutation
Recurrent mts 90% of cases: SRSF2 30%, ASXL1 40% chrom 20, SETBP1, EZH2, TET2 60% chrom4, RUNX1, JAK2, (K+N)RAS, CBL.
PARP Inhibition Therapy
In BRCA1 or 2. Olaparib..
RTOG 85-31: what does it show?
Inc OS by ADT plus RTx.
Tumor suppressor gene as RB: neuroblastoma, retinoblastoma, osteosarcoma all related to RB.
Retinoblastoma Pt got RTx>>can get sarcoma anywhere because of Rb gene, not RT site alone.
Splicing factors: Cohesions: Transcription regulators also
SF3B1, SRSF2, ZRSF2, U2AF1. STAG2, SMC3, RAD21. are NMP1,TP53.
Lapatinib (Tykerb)
Tyrosine kinase inhibitor Inhibits EGFR and ErbB2 (HER2) tyrosine kinase SE :Hepatotoxicity, N/V, fatigue, rashes, QT-prolongation Dec left ventricular function when combined with cape, hypokalemia, hypomagnesemia Oral (1/day) EGFR and HER-2. crosses BBB.
CMML prognostic features
WBC>13k :more bad prognosis.
Bendamustine
bending a mustang so he GOT كللKALAL
CMML0: CMML1: CMML2:
blast<1% peripheral and<5% bone marrow, 2-4% blast PB or 5-9% blast in BMs, 5-19% PB blast or 10-19% bone marrow blast.
No sun damage>>more BRAF, sun damage>>KIT more, also KIT is more than BRAF and acral and mucosal.
bravo, you did not expose yourself to the sun, you deserve a KIT burning your mouth and limps :)
Stauffer syndrome
erythrocytosis, hypercalcemia, dysfibrinogenemia Paraneoplastic from cytokines, inc LFT.
High grade serous: Clear cell or endometrioid
from in fallopian tube as serous tubal intraepithelial ca comes with endometriosis.
The high-MSI, R or L colon?
goes with R>L colon.
faslodex fluvestrant
he finds fast/slow full of weed strains
Hercules study on colon
heraql wants trust her (la pati) هرقل و باتي
MDS and deletion 5 chromosome MDS.
hypolobated megakaryocytes in
More exposure to hormone>>
inc ov ca, so dec risk factor in : young age, pregnancy, OCP, breast feeding, early menopause.
PV
inc wbc, Jak2 V617F or exon 12 mt(pure erythrocytosis))major criteria, minor criteria(hypercellularity with trilineage proliferation, low EPO, endogenous erythroid colony formatioon in vitro): 18.5 in men, 16.5 in w, or 17 men, 15 w with inc of more than 2 of the baseline that is not related to iron deficiency, inc 99th percentile, inc red cell mass of 25% above NL. Phlebotomy, ASA, hydroxyurea, interferon, busulfan, Jak2 i Tx.
Risk factor:
Hx of sunburn, fair skin, Fx, painful sunburn intermittent, UV 290-320 nanometer.
Olaparib: a poly ADP-ribose polymerase inhibitor MOA? Used for what?
(PARP) inhibitor blocks enzymes involved in repairing damaged DNA. OC has BRCA1 and BRCA2 genes who have received 3 or more prior lines of CTx.
VHL percentage in RCC ? Medication used when unresectable then VEGF:
2/3 of RCC cases sutent, pazo (inc PFS) also we can use mTOR temsirolimus that inc OS.
Cell responsible for NET
NET rise from enterochromaffin cells.
PNH Tx
Transfusion, AC, eculizumab Solaris humanized anti-C5 ab
Prognosis of PV
Worse age >57, leukocytosis >15k, VTE, abnl karyo.
Insulinoma:
diazoxide, everolimus.
CTC-derived AR-V7 detection, is it prognostic or predictive? Androgen receptor splice variant 7 (AR-v7) is what? If positive, what does that mean?
prognostic and predictive bio-marker in advanced prostate cancer. it is considered truncated form of androgen receptor. if + pts>>is positive predictive and prognostic marker for response for docetaxel more than enzalutamide or Abiraterone. so it is positive for chemo.
Comes with SF3B1 is what ?
ring sideroblast
Type I uterine/ endometrial cancer:
- due to unopposed estrogen stimulation - leads to endometrial hyperplasia. :ER-dependent, young. II:ER independent, old, poorly differentiated, worse, needs LND. bev, temsiro, brivanib, cediranib(FGFR, VEGR), trials.
Sutent given for what?
: GIST, panc NET, renal ca(advanced and adj)
forgot : midgut: Hindgut:
:lung, stomach. :small intestine, appendix, prox large bowel. :distal large bowel and rectum.
spontaneous regression
Cancer cells revert back to normal Primary melanoma evading recognition before popping up as metastases.
Bone marrow failure
AA, PNH, MDS which all can lead to AML. Can be multilineage as above or single as pure red blood cell aplasia PRCA.
Anastrazole (Arimidex)
ANNA LOVE OF STREUSEL NEEDS REMEDY!
Fag-got cells
AP(promyelocytic )L wtih Auer rods
FAP
APC gene, 5q, 100% penetrance by age of 40. Tx is removed bowel total colectomy by age 19-20ys. FAP: hypertrophy of retinal pigment epithelium, desmoid tumor, osteoma, cysts. Screen first degree relative at age 10, check the APC gene with a genetic counselor. Tumor Suppressor (2 hit) gene, dinged in FAP and AFAP. inc brain medulloblastoma, liver hepatoblastoma, panc, small bowel, stomach, thyroid, skin growths, cysts fibroma, retinal pigment epithelium. FAP : AD(although some can be de novo), inc a lot adenoca, 100% CRC in 45, desmoid tumor, fundic gland tumor, duodenal/ ampullary adenoma, papillary thyroid ca, extra teeth (CHRPE). FAP is classic or attenuated. MAP(MYH-associated polyposis) is MYH associated with polyposis, AR so we need biallelic mutation. Has less adenoma before CRC diagnosis, inc thyroid ca, inc upper GI cancer, associated with (K-RAS G12C) mutation. Case of 26 f colon polyps more than 100, has also thyroid ca Fx in maternal grandmother, and desmoid tumor in mother, what is the genetic? APC gene mutation, from FAP, comes with hundred and thousand colon polyp, AD, located in chromo 5, also comes with fibroma, lipoma, epidermoid cyst sebaceous cyst, comes with follicular or papillary thyroid ca, childhood hepatoblastoma, CNS mainly medulloblastoma, supernumery teeth, juvenile nasopharyngeal angiofibroma, adrenal adenoma.
Aplastic anemia: if acquired, do we have LAP? Tx:
Acquired, no LAP, no splenomegaly, Cyclosporine, ATG, steroid, allo, majority respond 75%, 10-30 relapse, 10% change to PNH and 2-20% change to MDS and AML.
Adriamycin (Doxorubicin)
Adria doxo
ABCD rule
Asymmetry, border irregularity, color, diameter, dysplastic nevus syndrome 100% to be melanoma if there is family history of melanoma.
IMpower 131
Atezolizumab + CTx in Advanced Squam NSCLC: 29% of all patients, regardless of PD-L1 expression, had a reduced risk of ds vs CTx alone. And inc PFS and SE but manageable safety.
RANK ligand inhibitor
Denosumab (Prolia)
Pancreatic NET (30-40% hypersecretion, 60-70% non-functional) carcinoid (forgot :lung, stomach, midgut: small intestine, appendix, prox large bowel. Hindgut: distal large bowel and rectum).
For/mid/hind
CD41 and CD61
GPIIb-IIIa (fibrinogen receptor) seen in acute megakaryoblastic leukemia.
Risk factor for endometrial ca are B) HNPCCC) Cowden's syndromeD) Granulosa cell tumorE) PCOS F) Obesity, Unopposed estrogen exposure (i.e., no progestin), Nulliparity, Tamoxifen. Oral contraceptive use decreases the risk of endometrial cancer BRCA2 is not risk factor in it. it is for OC, BC. there is a talk that BRCA1 mt has inc slighty uterine ca, OC clear cell ca: seen more in stage I, large pelvic mass, rarley B/L, • comes more with endometriosis, thromboembolic vascular complications and hypercalcemia. Lynch (not Cowden syn)syndrome is predominantly associated with endometrioid carcinoma but is associated with clear cell carcinoma. • Stage IA, IB, IC disease: Carboplatin/Taxane 3-6 cycles Stage II - IV: Chemotherapy as per epithelial ovarian cancer (6 cycles) • Serous ovarian carcinoma is the predominant tumor type associated with BRCA mutations and nulliparity. • Smoking is a risk factor for mucinous carcinoma but is associated with a decreased risk of clear cell ovarian carcinoma. Germline p53 mt with LiFraumini syn, somatic. MMR mt with HNPCC or lynch less than 100 polyp, with uterine bladder bile duct, gastric ca. PTEN gene germline cowden syn with hamartoma polyp in GI tract.
Hamartomatous : 1- P-J syn is AD, STK11, small and large bowel, skin freckling, inc BC, panc, UG. 2- Cowden AD PTEN, facial papules, acral keratosis, neck and facial trichilemmomas. Cowden's syndrome: PTEN mutation, Autosomal dominant Predisposes to Endometrial cancer Look for macrocephaly and Trichilemmoma Thyroid cancer, Hamartoma 3- Juvenile polyposis: AD, SMAD4 or BMPR1A mt, HHT hereditary hemorrhagic telangiectasia and dysplastic hamartoma. Askenazi founder mutations: BRCA1,2 ,MSH2,6.
Herceptin trastuzumab
Her trust is all the time right.
GIST risk factors
High-risk EUS features include irregular border, cystic spaces, ulceration, echogenic foci, and heterogeneity.
FDA Approves Pembro as First-Line Combination with Pemetrexed and Carbo for Metastatic NSNSCLC
Irrespective of PD-L1 Expression. KEYNOTE-021
PV mutation
JAK2 or triple negative.
Ado-trastuzumab emtansine : Trastuzumab + TDM 1
Kadcyla: HER-2 positive MBC post progression on trastuzumab plus Taxane chemo, found to increase PFS and OS.
ATRX mutation comes with acquired alpha thalassemia.
MCV is low, but this pt MCV is high.
MDS has risk for what other health issues?
MDS has inc risk for DM, CAD.
HSM in MDS
MDS the HSM is rare.
OS in chemo regimen in chemo?
Mfolfirinox better than gem in resected panc ca in OS.
RTx usage in renal cell ca?:
No role for RTx, but we use ablation in small renal mass<4 cm.
dermatofibrosarcoma protuberans DFSP has no t(17;22) translocation
Not respond to imatinib
Endometrial ca: RF risk factor: RF decreased by: Histology:
Ob, age, hormon (tamo, infertility, POS), HNPCC, granulosa cell tumor, PCOS, Cowden syndrome. Smeneh w kbereh, 3m ta5ud hermonat w asmha couden a ra7mha bleeding. :Pregnancy or OCPs. :endometrioid PTEN, papillary, clear cell (more P53 than PTEN, also has KRAS, BRCA, MSI, ER, PR, beta catenin, MLH1, MSH2).
GIST 1.6 cm, R0, asking about Tx for KIT mt Exon 11, ECOG is 0. adj Tx?
Observation as favorable location stomach and the size less than 2 cm, no need for imatinib. Good factor: stomach, and less than 2 cm.
Prognostic features:
Thickness in millimeters, ulceration, mitosis, anatomical location [head and neck>>trunk>>extremities], histologic subtypes, lymphocytes infiltrate, LVI, microsatellites, LDH.
Eosinophilia
Tx: ASx >> observe, Hydroxyurea if inc in WBC or Sx splenomegaly. Curative by allo and directed to it when therapy initiated. If not candidate for allo then go aza/decita.
MDS risk factor
age, CTx, RTx, AA, PNH, Fanconi, Bloom, Ataxia T, FPD-AML (Familial platelet disorder with predisposition to AML(FPD/AML) (RUNX1), GATA2(warts, monocytopenia, pulm issue), ETV6, SRP72, ANKRD26, JAK2.
Auer rods
azurophilic granules, myeloid, +MPeroxidase.
Lynch: no BRAF mt {BRAF present = not Lynch}(or CIMP{ CIMP: CpG island methylator phenotype} as both are sporadic somatic MSI-h colonca). No for anti EGFR in RAS mt Cetuximab Panitumumab and we use it with wild type RAS mt, also in BRAF mt. MSI-h is 80% sporadic (serrated or sessile) as CIMP has BRAF V600E mt and somatic hyperethylation of MLH1 promotor, 20% {3% of all CRC} lynch (tubular pattern). FOLFOXIRI + bev vs FOLFIRI + bev as first-line Tx in met CRC: FOLFOXIRI plus bevacizumab is a feasible option for those patients who meet the inclusion criteria of the present study, irrespective of baseline clinical characteristics and RAS or BRAF mts status. If KRAS mutated then there is no benefit for cetuximab or panitumumab. Other genetics is peri-ampullar cancer as Gardner syn (Adenomatous Polyposis (FAP)), brain tumor in Turcot syn (usually meningioma. Muir-Torre syndrome (MTS), rare, hereditary, AD, thought to be a subtype of HNPCC, comes with colon, GU ca, and skin lesions, such as keratoacanthomas and sebaceous tumors.
bravo>> Right, if mutation then >>lives less, OS less. Lynch: germline mt, wild BRAF so it is negative for mt: high penetrance, GI colon, GYN endometrial ovary stromal, gastric hepatobiliary duct, UT, panc ca exocrine. MMR: MLH1, MSH2, MSH6, PMS2, EPCAM. Proximal R side, like Crohn tumor or infiltrates lymphocytes.
Myeloproliferative neoplasms
classifications of blood cancers which occur when body makes too much of WBC or RBC or platelets over production creates problems b/c of excess. Clonal over production of one or more cell line.
Triple negative seen where ?
could be in any of MPN.
Aplastic anemia treatment related
cytotoxic T cell Th1 profile, IF (gamma, alfa). But if drug related: gold, chloramphenicol, carbamazepine, sulfonamide, NSAIDs, cardiovascular drugs, PCN, allopurinol, Benzen, pesticides.
Zolendronic acid and tumor activity?>
does not have anti tumor activity.
CMML chronic myelomonocytic leukemia Dx?
dysplasia, overlap between MDS/MPN, both features as cytopenia one line and more, with leukocytosis/monocytosis/splenomegaly. Dx in monocytosis >1K, >10% of WBC, >3 months, no BCR-ABL, no PDGFRA,B. Blast are <20%in PB or BM, no reason. Dx after R/O CML or PV, or ET or PMF, or secondary cause.
myeloid blast
dysplastic and less or hypo-granular.
Abiraterone (Zytiga)
inhibits CYP17A1, an enzyme involved in androgen synthesis, given to castration-resistant prostate cancer patients. P450 CYP17 blocker Castration resistant prostate cancer CRPC: Abiraterone (Zytiga): block 17 alpha hydroxylase/C17,20 lyase CYP17 and block androgen biosynthesis>>dec androgen sensitive tumor growth. And inhibit androgen in tumor and adrenal, inc OS, PFS, LFTs (COU-AA-301 trial). Used CRMPC, CSPC high risk ds. 3beer
PNH acquired:
intravascular hemolysis, thrombosis, Budd-Chiari, somatic mutation in PIG-A gene>> block synthesis(decrease) of GPI glycosyl phosphatidylinositol anchor loss where still lack CD55(inhibited C3 convertase), 59(inhibitor assembly C5-C9 the membrane attack complex MAC), lack of CD55, 59 on RBCs which both CDs were as inhibitor of protein. PNH erythrocytes, lacking CD55, bind C3 convertase; moreover, because they lack CD59>>vulnerable to MAC attack>>lysis, NO level dec, esophageal spasm, ED, thrombosis, renal insuf. FLAER variant used for FCM to Dx PNH. PMH increase risk for AA-MDS-AML.
AML with eos
inv 16 : CBFB-MYH11
Coombs DAT in PNH?
is negative in PNH.
T1 in renal? T2 localized?
less than 7 cm. if more than 7 cm.
FOLFIRINOX and its side effect
leucovorin, 5-FU, irinotecan, oxaloplatin (tiredness, sick, diarrhea, hair loss, sore mouth and ulcer,)
If AA when inherited we see
macrocytosis (inc MCV), elevated HbF compared to acquired AA.
Ravulizumab
new agent with long half life.
When do we omit Irinotecan from chemo for abnl lab?
omitted for inc bili, around 1.5, So instead of FOLFIRINOX give FOLFOX, you can switch back whenever bili is down.
ADT Tx drugs are what?
orchiectomy, LHRL agonist, LHRL antagonist ( Degarelix Firmago which is LHRH antagonist), CYP17 inhibitor(abiraterone Zytiga blocks CYP17), anti-androgen.
MEN1:
panc NET. parathyroid gland, islet cells of the pancreas, and pituitary gland.
anti C5 MOA?
selectively binds/inhibits complement protein C5, dec hemolysis, and thrombotic microangiopathy(inc infection of encapsulated>> vaccine against Neisseria meningitides), allo.
Topotecan come swith SE of :
serious interstitial lung ds with fatalities, CBC requirement is =>1.5k neutrophil, eq or>100K plt, Hb =>9. Dose is no more than 4 mg IV, use full weight or actual body weight for obese pt.
Type II uterine/ endometrial cancer
serous, clear: I to III: CTx+ directed XRTx( if Ia, non invasion, no residual HYS, then possible no need for CTx but still chemo better to use, or RTx.) if IB then CTx for sure+RTx.
Clear cell sarcoma
t(12, 22); EWS, ATF1
Endocrine Tx in uterine not effective in:
type 2 tumor, if endometrioid and ER+.
Large neuroendocrine: Treat as small cell with etoposide. KI67 30% cut off.
• EGFR mt some non squam could change histology to small cell lung ca @_@. • Small cell cancer lung: • Atezolizumab (Tecentriq) it is first line NSCLC, and second line, also in small cell first line, met/advanced urothelial ca. it is PD-L1 monoclonal ab. • Recurrent SCLC: topotecan, nivo+- ipi :checkmate 032 • Chromogranin A, synaptophysin(neuronal presynaptic vesicles, + in neoroendocrine cells, carcinoid, paragangliomas, small cells. adrenal gland, CNS, adenoca well differentiated fetal type, medullary thyroid ca, Merkel cell ca, parathyroid ca of thymus.), NCAM neural cell adhesion molecule or CD56 are the SCC staining. • NLST tiral: smoker, 1ppd, for 30 ys, 55-74 ys, quit smoke 15 ys or less. • Stage I, II: check PFT, MRI brain if T2, stage II, bronchoscopy (possible medianistinocsopy same time), path eval for mediastinal LN, then go to surgery, should have brain RTx PCI inc OS in limited and extensive @_@. • Adj chemo post surgery. • In limited stage: no effusion, could has regional LN ipsi or contra hilar or mediastinal or supraclavicular all in one radiation field (extensive stage: any beyond that.) Tx surgery then chemo. • Extended disease: Eto+cis. • Alteration TP 53 and RB1 or loss. • Limited stage small cell lung Tx concurrent CRT X on cis + eto then PCI. • PS does not hold CTx here. • Endocrine Sx relate to cancer course vs neuro Sx does not relate to cancer course. • anti VGCC, VGKC, which are Lambert-Eaton, GAD65, CRMP4 which are neuropathy and encephalitis ,Ri opsoclonus(uncontrolled eye movement)and myoclonus, Recoverin retinal blindness, Amphipysin stiff person syndrome, Hu, Yo cerebral degeneration. • Limited disease LD: PCI, hyperfractionated, early RTx, E+P X 4Cs. • Extensive disease ED: Combo Tx 6Cs, remission with a 4 month, if we have pain, redness, vena cava: Start CTx before even RTx. • No role of maintenance, consolidation, dose dense, escalation, triplets. • Carbo in ED vs cis as tolerable, but use cis for LD. • In ED OS dec in PCI compared to observation @_@ • Don't order PDL1 in SCLC as there is no relation with PDL1 expression. • Irino (used in colon ca mets and it is off label ED, or SD) is contraindication in high bili, so give Eto +cis in this case though. UGT1A1-28 allele. Survival benefit in small cell ca in lung recurrent or resistant? Topotecan, either orally, vs IV, inc OS and inc QOL, esp if relapse happened within 2 months or less from first remission. • 66 f dysphagia, wt loss, CT chest showed enlarged hilar mass with bulky LN, pleural effusion with malignant cells, Small cell lung cancer of the lung. NS treatment? Eto and platin, he picked carbo over cis, as it is favorable SE vs cis, there is pleural effusion showing stage IV M1a. • 63 m hypokalemia, coughing, low wts, liver modular mets, and adrenal hyperplasia, what is the Dx? best option is small cell lung cancer with paraneoplastic ACTH production. Small cell ca goes to liver early, and able to produce ACTH inc mineral corticoid effect, low K, inc HTN, Cushing syndrome. Secretory diarrhea related to VIP. Conn syndrome for adrenocortical cancer, showing hyperplasia and not masses. • 55 f coughing, 5 cm RUL, 2 cm LUL, small lung ca, no distant mets, got carbo and eto 6 cycles, L lesion resolved, R is now 1 cm, NS? thoracic radiation therpay, as RTx consolidation: ES-SCLC OS is better with pt got RTx after CTx. Maintenance CTx is effective in non small not in small SCLCL. no role for surgery in SCLC except it is clinical trial. Limited small cell lung can:any T, any N, M0, treated with RTxd, except T3,4 of multiple lung nodules, so extensive is stage IV, M1a/b, or T3,4. • PTH related peptide inc and inc Ca not in SCLC, we see it in squam. • 68 m SCLC, what is Tx? it is Eto and Cis EP with concurrent RTx.? it is first line for limited disease, Carbo instead of cis is in more extensive ds ED.
