Oncology Comprehensive Bullet-Note Guide

Background & Epidemiology

• Incidence & Mortality

  • >1.9\ \text{million} new cancer cases in the U.S. each year
  • Second leading cause of death (after heart disease)
  • Lifetime risk
  • Men: $\approx 1/2$; most common = prostate, lung, colorectal
  • Women: $\approx 1/3$; most common = breast, lung, colorectal

• What is Cancer?

  • Group of diseases characterized by uncontrolled cell division
  • Normal control mechanisms: DNA repair, apoptosis
  • Tumor types
  • Malignant (cancerous) vs. benign
  • Solid vs. hematologic (e.g., leukemia)
  • Metastasis
  • Spread via blood/lymph → secondary tumors (same cell type as primary)
  • Highest fatality; often treated palliatively

• Genetic Basis

  • Proto-oncogenes → oncogenes ("gas pedal stuck")
  • DNA-repair genes ("mechanic broken")
  • Tumor-suppressor genes ("brake pedal fails")
  • Multiple mutations usually required; some are drug-targetable (→ targeted therapy)

• Risk Factors

  • External (modifiable): benzene, formaldehyde, radiation/UV, tobacco, alcohol, HPV, etc.
  • Internal (non-modifiable): inherited mutations (e.g., BRCA1/2), hormones (estrogen), age

Prevention & Screening

• Lifestyle

  • No tobacco, limit alcohol, healthy weight, vaccinate (HPV, HBV), sun protection (shade, clothing, SPF $\ge 30$; reapply $q2h$)

• Skin Self-Check – ABCDE

  • Asymmetry, Border irregular, Color variegated, Diameter >6\,\text{mm}, Evolving

• ACS Screening (average risk)

  • Breast: mammogram yearly $\ge 45$; $\ge55$ q2y or continue yearly
  • Cervical: start $25$; Pap q3y OR HPV DNA q5y ± Pap
  • Colorectal: start $45$
  • Stool tests: FOBT yearly, stool DNA q3y
  • Visual: colonoscopy q10y, sigmoidoscopy q5y
  • Lung: low-dose CT yearly if $\ge50$ + $\ge20$ pack-yr & current/quit <15 yr
  • Prostate: shared decision; PSA ± DRE

Warning Signs – “CAUTION”

• C – change in bowel/bladder
• A – a sore that does not heal
• U – unusual bleeding/discharge
• T – thickening/lump
• I – indigestion/dysphagia
• O – obvious change in wart/mole
• N – nagging cough/hoarseness

Diagnosis & Staging

• Core elements
  • Biopsy (core needle, punch, bone marrow)
  • Imaging: X-ray/CT, US, MRI
  • Labs: CBC, CMP, tumor markers, mutation testing (e.g., EGFR)
• Classification: by tissue (adenocarcinoma, etc.)
• Staging – TNM
  • $T$ (tumor size), $N$ (nodes), $M$ (metastasis); higher number = advanced

Treatment Principles

• Factors: cancer type, stage, biomarkers (hormone, mutations), performance status, comorbidities, patient goals (curative vs palliative)
• Modalities
  • Surgery (local) – remove/debulk/relieve
  • Radiation (local DNA damage)
  • Chemotherapy (systemic cytotoxics)
  • Hormone therapy (block estrogen/testosterone)
  • Targeted therapy (TKI, mAb)
  • Immunotherapy (checkpoint inhibitors)
• Timing terms
  • Neoadjuvant – before primary (shrink)
  • Primary – definitive (often surgery)
  • Adjuvant – after (eradicate residual)

Chemotherapy Basics

• Cell-cycle specifics
  • Non-specific: alkylators, anthracyclines, platins
  • Specific phases
  • G1: PEG-asparaginase
  • S: antimetabolites (MTX, 5-FU), topoisomerase I (irinotecan)
  • G2: etoposide, bleomycin
  • M: taxanes, vinca alkaloids
• Common toxicities from rapid-dividing normal cells: diarrhea, mucositis, alopecia, myelosuppression
• Regimens given in cycles (e.g., AC q21d ×4)

Calculations

• Body Surface Area (BSA)
  • Mosteller: $\text{BSA}=\sqrt{\dfrac{\text{Ht(cm)}\times\text{Wt(kg)}}{3600}}$
  • Dubois & Dubois similar; both → same answer (round to $0.01\,m^2$)
• Carboplatin – Calvert Formula
  • $\text{Dose (mg)} = \text{Target AUC}\times(\text{GFR}+25)$
  • Cap GFR at $125\,mL/min$

Cytotoxic Drug Classes & Key Safety

Alkylating Agents

• Cyclophosphamide, Ifosfamide – hemorrhagic cystitis (acrolein)
  • Prevention: hydration + Mesna (mandatory for ifosfamide & high-dose cyclo >1\,g/m^2)
• Busulfan, Carmustine – pulmonary fibrosis; neurotoxicity (carmustine wafers)

Platinum Compounds – Cisplatin, Carboplatin, Oxaliplatin

• Boxed reactions: anaphylaxis (monitor 1st 15 min)
• Cisplatin
  • Nephrotoxicity → hydrate, $\text{dose}\le100\,mg/m^2$/cycle, amifostine
  • Ototoxicity (baseline audiogram)
• Class: peripheral neuropathy (cold-sensitive with oxaliplatin)

Anthracyclines – Doxorubicin (Ruby Red bodily fluids)

• Cardiotoxicity (CMP/HF)
  • Lifetime cumulative $450–550\,mg/m^2$; consider dexrazoxane ≥$300\,mg/m^2$

Topoisomerase Inhibitors

• Irinotecan – severe diarrhea
  • Acute (cholinergic) → atropine
  • Delayed → loperamide
• Etoposide – infusion-rate hypotension (≥30–60 min infusion)

Vinca Alkaloids (M-phase)

• Peripheral & autonomic neuropathy (constipation)
• Max vincristine single dose $2\,mg$
• Fatal if intrathecal – prepare in IV bag

Taxanes

• Peripheral neuropathy; hypersensitivity (premed: steroid + H1 + H2); docetaxel fluid retention (dex 3 days)
• Use non-PVC, 0.22 µm filter (paclitaxel, cabazitaxel)

Antimetabolites

• Pyrimidine analogs – 5-FU, Capecitabine
  • Hand-foot syndrome, diarrhea, mucositis
  • DPD deficiency ↑ toxicity; antidote = uridine triacetate ≤$96$ h
  • Warfarin interaction (↑INR; boxed for capecitabine)
• Folate analog – Methotrexate
  • High-dose $\ge500\,mg/m^2$ → nephrotoxicity, mucositis
  • Rescue: leucovorin (doses $\ge100$, mandatory $\ge500$)
  • Alkalinize urine (NaHCO3); glucarpidase for toxic levels/renal failure

Miscellaneous Highlights

• Bleomycin – pulmonary fibrosis (limit $\le400$ units; test dose for anaphylaxis)
• Tretinoin – differentiation syndrome (fever, effusions) → dexamethasone
• Arsenic trioxide – QT prolongation (keep K>4, Mg>1.8)
• Proteasome inhibitors (bortezomib) – herpes zoster reactivation (acyclovir ppx)
• Immunomodulators (lenalidomide) – teratogenic (REMS), VTE risk → anticoag ppx
• PEG-asparaginase – hypersensitivity (premed APAP, diphenhydramine, H2RA)

ChemoMan Toxicity Map (Mnemonic)

• N (brain) – carmustine neurotoxicity
• C (ears/mouth/kidneys) – cisplatin ototoxicity, highly emetogenic, nephrotoxicity
• M (mouth) – methotrexate mucositis (also 5-FU/capecitabine)
• P (lungs) – bleomycin, busulfan, carmustine pulmonary fibrosis
• D (heart) – doxorubicin cardiomyopathy
• IP (bladder) – ifosfamide & cyclophosphamide hemorrhagic cystitis
• I (butt) – irinotecan diarrhea
• PVT (hands/feet) – Platins, Vinca, Taxanes neuropathy
• BMS – Bone-Marrow Suppression (except bleomycin, vincristine, PEG-asparaginase)

Myelosuppression Management

• Nadir: WBC/plt day 7-14; RBC later
• ANC formula: $ANC=\frac{\text{WBC}\times(\%\text{segs} + \%\text{bands})}{100}$
  • <500 = severe; <100 profound
• CSF Prophylaxis
  • Filgrastim daily; Pegfilgrastim once/cycle (On-pro) – start $\ge24$ h post-chemo
  • AEs: bone pain, splenic rupture
• Febrile neutropenia (oncologic emergency)
  • Fever $\ge101$ once OR $\ge100.4$ >1 h + ANC criteria
  • High-risk → IV anti-pseudomonal β-lactam (cefepime, meropenem, piptazo)
  • Low-risk → PO (cipro + augmentin) outpatient
• Thrombocytopenia – bleed risk; transfuse plt <10,000
• Anemia – PRBC transfusion or ESA (only palliative; Hgb<10; need iron)

Chemotherapy-Induced Nausea & Vomiting (CINV)

• Types: anticipatory, acute (
• Risk category (IV chemo)
  • High (≥90%) – 3/4 drug prophylaxis (NK1 RA + 5-HT3 RA + Dex ± Olanzapine)
  • Moderate – 2/3 drugs
  • Low – 1 drug (5-HT3 RA, Dex, metoclopramide, or prochlorperazine)
• Key drug classes & pearls
  • NK1 RA – aprepitant, fosaprepitant (AEs: mild GI, dizzy)
  • 5-HT3 RA – ondansetron, palonosetron (QT prolongation; serotonin Sx)
  • Dopamine RA – prochlorperazine, promethazine, metoclopramide, olanzapine (EPS, QT)
  • Others – dexamethasone (insomnia), lorazepam (anticipatory), dronabinol (appetite)

Handling, Pregnancy, Extravasation, Vaccines

• Hazardous; PPE & negative-pressure hoods
• Avoid conception; barrier contraception; no breastfeeding
• Extravasation
  • Anthracyclines → cold compress + dexrazoxane
  • Vinca → warm compress + hyaluronidase; fatal intrathecal
• Vaccines: avoid live vaccines during chemo; give ≥2 wks before

Targeted Therapy

Monoclonal Antibodies (IV)

• Infusion reactions → premed (APAP + H1 ± steroid)
• Rituximab (CD20) – HBV reactivation (check panel)
• Cetuximab (EGFR) – acneiform rash (indicates efficacy); KRAS WT only
• Trastuzumab (HER2) – cardiomyopathy (monitor LVEF)
• Bevacizumab (VEGF) – impaired wound healing; VTE/bleed; GI perforation
• Checkpoint inhibitors
  • Pembrolizumab/Nivolumab (PD-1), Ipilimumab (CTLA-4)
  • Immune toxicities (colitis, hepatitis, endocrinopathies) → steroids

Tyrosine Kinase Inhibitors (oral, "-nib")

• BCR-ABL: imatinib, dasatinib, nilotinib – fluid retention, $QTc$ (esp nilotinib), CYP3A4 DDI; imatinib with food
• BRAF: vemurafenib, dabrafenib – new malignancies, $QTc$
• MEK: trametinib, cobimetinib – retinopathy, rhabdo
• EGFR: erlotinib, afatinib – rash (same skin care as cetuximab)

Hormone/Endocrine Therapy

Breast Cancer

• SERMs: Tamoxifen (pre & post meno)
  • Prodrug via CYP2D6 → avoid strong inhibitors (use venlafaxine for hot flashes)
  • Box: VTE, uterine cancer; ↓bone density → Ca/VitD
• SERD: Fulvestrant (IM) – ↑LFT, injection pain, hot flashes
• AIs: Anastrozole, Letrozole, Exemestane (post-meno or with ovarian suppression)
  • Osteoporosis (DEXA, Ca/VitD), arthralgia, hot flashes, ↑CV risk
• HER2 + → trastuzumab ± others

Prostate Cancer – Androgen Deprivation Therapy

• GnRH Agonists: Leuprolide, Goserelin
  • Tumor flare → start with anti-androgen
  • Osteoporosis, hot flashes, impotence, QT
• GnRH Antagonists: Degarelix, Relugolix – no flare
• Anti-androgens: Bicalutamide, Flutamide, Enzalutamide – hot flashes, gynecomastia, hepatotoxicity

Oncologic Emergencies

Tumor Lysis Syndrome (TLS)

• Electrolytes: ↑K, ↑PO4, ↓Ca, ↑uric acid → arrhythmia, renal failure
• Prevention/Treatment
  • Stop contributory drugs; vigorous IV hydration
  • Allopurinol (XO inhibitor) or febuxostat (if rash)
  • Rasburicase – converts uric acid → allantoin (G6PD-contra)
  • Correct electrolytes, monitor ECG

Hypercalcemia of Malignancy

• Corrected Ca: $Ca<em>{corr}=Ca</em>{serum}+0.8\times(4-albumin)$
• Severity
  • Mild <$12$ → hydration
  • Moderate $12–13.9$ → treat if symptomatic (IV bisphosphonate)
  • Severe ≥$14$ → aggressive: hydrate + IV bisphosphonate (zoledronic acid \text{Zometa} or pamidronate) ± calcitonin (≤48 h)
  • Refractory → Denosumab (XGEVA)
• Symptoms mnemonic "stones, bones, groans, moans"

END