Arab Board Oncology Clinical cheat sheet

Hallmarks of cancer include sustained proliferative signaling, evasion of growth suppressors, resistance to apoptosis, replicative immortality, angiogenesis induction, invasion/metastasis, and immune evasion.

Oncogenes (e.g., RAS, MYC, HER2) are gain-of-function; tumor suppressors (e.g., TP53, RB1, APC) typically require biallelic loss (two-hit hypothesis).

Driver mutations confer selective growth advantage and are typically clonal and mutually exclusive; passenger mutations are neutral and subclonal.

Apoptosis is regulated by BCL-2 family balance: pro-apoptotic BAX/BAK versus anti-apoptotic BCL-2/BCL-xL; BH3 mimetics (venetoclax) inhibit BCL-2.

Synthetic lethality example: BRCA1/2 loss with PARP inhibition; HRD tumors are sensitive to PARP inhibitors.

Tumor heterogeneity arises from clonal evolution (Darwinian selection) and contributes to acquired drug resistance.

The Warburg effect describes preferential aerobic glycolysis in tumors, exploited by FDG-PET imaging.

Cell cycle checkpoints: G1/S (RB, p16, CDK4/6-cyclin D) and G2/M (CDK1-cyclin B); TP53 governs DNA damage response.

Incidence measures new cases per population-time; prevalence measures existing cases; mortality reflects both incidence and survival.

Age-standardized rates allow comparison across populations with different age structures.

Screening validity: sensitivity = TP/(TP+FN); specificity = TN/(TN+FP); PPV depends on prevalence.

Lead-time bias overestimates survival from screening; length-time bias favors detection of slow-growing tumors; overdiagnosis inflates apparent benefit.

Randomized trials with cancer-specific mortality endpoints are the strongest evidence for screening benefit.

HPV vaccination prevents cervical and HPV-associated cancers; hepatitis B vaccination reduces hepatocellular carcinoma.

Modifiable risk: tobacco (largest preventable cause), alcohol, obesity, physical inactivity, oncogenic infections (HPV, HBV, HCV, H. pylori).

Hereditary syndromes: BRCA1/2 (breast/ovarian), Lynch (MMR-deficient colorectal/endometrial), FAP (APC), Li-Fraumeni (TP53).

TNM classification: T = primary tumor extent, N = regional nodes, M = distant metastasis; stage grouping determines prognosis and therapy.

Tissue diagnosis with adequate sampling and immunohistochemistry is required before definitive systemic or radiation therapy in most solid tumors.

Grading describes differentiation; staging describes anatomic extent-both are independent prognostic factors.

Immunohistochemistry panels: cytokeratin (carcinoma), S100/SOX10 (melanoma), CD45 (lymphoma), desmin (sarcoma), TTF-1 (lung/thyroid).

Liquid biopsy (ctDNA) detects minimal residual disease and resistance mutations but has variable sensitivity.

Sentinel lymph node biopsy uses blue dye and/or radiolabeled colloid to stage regional nodes in breast cancer and melanoma.

Molecular profiling (NGS) identifies actionable alterations; report tier classification distinguishes clinical significance.

Restaging after neoadjuvant therapy uses ypTNM; pathologic complete response (ypT0N0) is a favorable prognostic marker.

Cytotoxic classes: alkylators (DNA crosslinking), antimetabolites (S-phase), topoisomerase inhibitors, taxanes (microtubule stabilization), vinca alkaloids (microtubule destabilization).

Cell kill follows first-order kinetics; log-kill and Norton-Simon hypotheses support dose density and sequential regimens.

Targeted agents: TKIs (imatinib, osimertinib), monoclonal antibodies (trastuzumab, rituximab), ADCs (T-DM1, trastuzumab deruxtecan), CDK4/6 inhibitors.

Checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4) require predictive biomarkers such as MSI-H/dMMR or PD-L1 expression depending on tumor type.

Immune-related adverse events (colitis, pneumonitis, thyroiditis, hypophysitis) are managed with corticosteroids and drug hold; grade 3-4 usually requires permanent discontinuation of CTLA-4 agents.

Pharmacogenomics: DPYD deficiency increases fluoropyrimidine toxicity; UGT1A1*28 increases irinotecan toxicity; TPMT/NUDT15 guide thiopurine dosing.

Response assessment uses RECIST 1.1 (target lesion sum, >=20% increase = progression) or iRECIST for immunotherapy pseudoprogression.

Drug resistance mechanisms include efflux pumps, target mutation (e.g., T790M, gatekeeper), bypass pathway activation, and apoptosis evasion.

Radiation biology 4 R's: repair, repopulation, redistribution (cell cycle), and reoxygenation; radiosensitivity is highest in M and G2 phases.

Fractionation exploits the alpha/beta ratio: tumors (high alpha/beta) respond to smaller fractions; late-responding normal tissue (low alpha/beta) is spared by smaller fractions.

Linear-quadratic model: surviving fraction = exp(-(alphad + betad^2)); BED = nd(1 + d/(alpha/beta)).

Stereotactic body radiotherapy (SBRT) delivers high dose per fraction with ablative effect; used in early NSCLC, oligometastases, and prostate cancer.

Organs at risk have tolerance doses (e.g., spinal cord ~45-50 Gy, whole-lung V20, mean heart dose); constraints are specified in treatment planning.

Acute toxicity occurs during or shortly after radiotherapy (mucositis, dermatitis, diarrhea); late toxicity occurs months to years later (fibrosis, xerostomia, radiation myelopathy).

Brachytherapy delivers dose by radioactive source placement; dose rate (LDR/HDR) and radiobiology differ from external beam.

Concurrent chemoradiation improves outcomes in head and neck, cervical, esophageal, and locally advanced NSCLC cancers by radiosensitization.

Tumor board (MDT) decisions integrate pathology, imaging, and patient factors to define resectability and sequence of therapy.

R0 resection (microscopically negative margins) is the surgical goal; R1 (microscopic) and R2 (macroscopic) residual disease worsen prognosis.

Neoadjuvant therapy downsizes tumors, tests in vivo response, and may increase sphincter-preserving or breast-conserving rates.

Sentinel node biopsy is standard for clinically node-negative breast cancer and melanoma; completion lymphadenectomy is selective in melanoma.

Cytoreductive surgery with HIPEC is used in selected peritoneal carcinomatosis (e.g., colorectal, appendiceal).

Metastasectomy can be curative in selected oligometastatic disease (colorectal liver, pulmonary metastases, sarcoma).

Enhanced recovery after surgery (ERAS) protocols reduce length of stay and complications.

Margin status, lymph node yield, and lymphovascular/perineural invasion are key pathology quality metrics.

Breast cancer subtypes: HR+/HER2- (endocrine therapy ± CDK4/6 inhibitors), HER2+ (trastuzumab/pertuzumab), triple-negative (chemotherapy ± immunotherapy).

NSCLC: EGFR/ALK/ROS1/KRAS/BRAF/MET/RET/NTRK alterations direct targeted therapy; PD-L1 and MSI guide immunotherapy; SCLC is treated with platinum-etoposide.

Colorectal cancer: RAS/BRAF wild-type predicts anti-EGFR benefit; MSI-H tumors respond to immunotherapy; HER2 amplification is targetable.

Gastric/esophageal cancer: HER2, PD-L1 (CPS), MSI, and Claudin 18.2 are actionable targets.

Renal cell carcinoma: clear cell histology; VEGF TKIs and immune checkpoint combinations; sarcomatoid features respond to immunotherapy.

Prostate cancer: PSA screening, Gleason/ISUP grading, androgen deprivation therapy; mCRPC uses AR pathway inhibitors, taxanes, PARP inhibitors (HRR mutations), and PSMA radioligand therapy.

Ovarian cancer: high-grade serous; BRCA/HRD testing guides PARP maintenance; CA-125 for monitoring.

Head and neck squamous cell carcinoma: HPV/p16 status in oropharynx; cisplatin chemoradiation; pembrolizumab for recurrent/metastatic disease.

Glioblastoma: IDH-wildtype, MGMT promoter methylation predicts temozolomide benefit; standard is maximal resection plus chemoradiation.

Melanoma: BRAF V600 mutation (~50%) targeted with BRAF/MEK inhibitors; immunotherapy first-line; SLNB for staging.

Sarcomas: grade and size determine risk; doxorubicin ± ifosfamide; GIST uses KIT/PDGFRA testing and imatinib.

AML: cytogenetics and molecular markers (NPM1, FLT3-ITD, CEBPA, TP53) define ELN risk; induction is anthracycline plus cytarabine (7+3).

APL (PML-RARA) is treated with ATRA plus arsenic trioxide; coagulopathy (DIC) is a major early complication.

CML: Philadelphia chromosome t(9;22) BCR-ABL1; TKIs (imatinib, dasatinib, nilotinib) achieve deep molecular response; TKI discontinuation is possible in sustained MR4.5.

CLL: del(17p)/TP53 and IGHV status are prognostic; targeted agents (BTK inhibitors, venetoclax) are preferred over chemoimmunotherapy.

DLBCL: R-CHOP; cell of origin and MYC/BCL2 double-hit status affect prognosis; IPI predicts outcome.

Hodgkin lymphoma: Reed-Sternberg cells (CD15+, CD30+); ABVD chemotherapy; PET-adapted therapy.

Multiple myeloma: CRAB criteria plus SLiM; treat with proteasome inhibitors, IMiDs, anti-CD38; autologous transplant is standard in eligible patients.

ALL: Philadelphia chromosome positivity adds TKI to chemotherapy; CNS prophylaxis is required.

MDS: IPSS-R risk stratification; hypomethylating agents for higher-risk disease; transplant is potentially curative.

Febrile neutropenia: fever >=38.3 C once or >=38.0 C sustained with ANC <500; empiric anti-pseudomonal beta-lactam within 60 minutes; MASCC score guides risk.

Tumor lysis syndrome: hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia; prevention with hydration and allopurinol/rasburicase in high-risk disease.

Spinal cord compression: back pain plus neurologic deficit; dexamethasone immediately and urgent MRI; definitive surgery or radiotherapy.

Superior vena cava syndrome: facial/upper extremity edema, distended neck veins; CT diagnosis; radiotherapy or stenting.

Hypercalcemia of malignancy: IV fluids, bisphosphonates or denosumab, calcitonin for rapid control.

Malignant pericardial tamponade and airway obstruction are oncologic emergencies requiring urgent intervention.

Antiemesis: 5-HT3 antagonists, NK1 antagonists, dexamethasone, olanzapine; match regimen to emetogenic risk.

Palliative care improves quality of life and survival when integrated early; opioid titration, bowel regimen, and advance care planning are core elements.

G-CSF primary prophylaxis when febrile neutropenia risk >=20%.

Phase I determines maximum tolerated dose and dose-limiting toxicity; phase II evaluates efficacy; phase III compares against standard; phase IV is post-marketing.

Randomization reduces selection bias; allocation concealment and blinding prevent confounding and detection bias.

Intention-to-treat analysis preserves randomization; per-protocol analysis can introduce bias.

Survival endpoints: overall survival is definitive; progression-free survival is a surrogate; hazard ratios from Cox regression quantify relative risk over time.

Kaplan-Meier estimates survival probability; log-rank test compares curves; Cox model adjusts for covariates.

Diagnostic test metrics: sensitivity, specificity, likelihood ratios, and area under the ROC curve.

Sample size depends on effect size, variance, alpha (type I error), power (1 - beta), and expected dropout.

p-value is the probability of observed data given the null hypothesis; it does not measure effect size or clinical importance.

Levels of evidence: systematic reviews/meta-analyses of RCTs rank highest; expert opinion ranks lowest.