Oncology Lecture Review

Non-Small Cell Lung Cancer (NSCLC)

• Environmental risk factors
• Primary: smoking (pack-years correlate with risk)
• Secondary: second-hand smoke, asbestos, radon gas, outdoor/indoor air-pollution particulates, occupational inhalants (e.g., silica, diesel exhaust).
• Take-home concept: risk ↑ whenever carcinogens contact bronchial epithelium → mutational burden → malignant transformation.

• Histologic sub-types
• Adenocarcinoma
• Most common subtype overall and in non-smokers.
• Origin: mucus-secreting glandular cells located peripherally.
• Often expresses driver mutations (e.g., EGFR, ALK, ROS1) → candidate for targeted therapy.
• Squamous Cell Carcinoma
• Strongly linked to smoking.
• Arises centrally in the bronchi; may cavitate; produces paraneoplastic hypercalcemia (PTHrP).
• Large Cell Carcinoma
• Undifferentiated, fast-growing; can arise anywhere in lung fields; early hematogenous spread.

• Targeted treatment snapshot (partial, see comprehensive section under "Cancer-Wide Treatments")
• TKIs against EGFR, ALK, ROS1, and monoclonal antibodies against HER2/ERBB2.
• Benefits: higher tumor specificity → fewer off-target cytotoxic effects.

Colorectal Cancer

• Risk factors
• Non-modifiable: age (>50\,\text{yr}), family history, hereditary syndromes (FAP, HNPCC).
• Modifiable: inflammatory bowel disease, low-fiber/high-fat diet, obesity & sedentary life, smoking, alcohol.

• Precancerous lesions
• Adenomatous polyps = benign epithelial proliferations that acquire mutations (APC → KRAS → p53) over time → adenoma-carcinoma sequence.
• Importance: colonoscopy with polypectomy interrupts this sequence, reducing incidence.

• Gastrointestinal bleeding complications
• Chronic microbleed → iron-deficiency anemia (fatigue, pallor, SOB).
• Acute brisk bleed → hypovolemia → compensated shock (tachycardia) → decompensated shock.

• Presenting symptoms (know med-terminology)
• Altered bowel habit: diarrhea ↔ constipation; narrowing caliber.
• Hematochezia = bright-red blood per rectum (left-sided lesions).
• Melena = black, tarry stool (right-sided lesions; upper GI bleed differential).
• Tenesmus = persistent urge / sense of incomplete evacuation.

• Signs of metastatic spread (commonly to liver via portal vein)
• Hepatomegaly, jaundice, ascites, RUQ pain, cachexia.

Primary Brain Cancer

• Most common primary malignancy: Glioblastoma Multiforme (GBM) (WHO grade IV astrocytoma)
• Highly invasive, crosses corpus callosum (“butterfly glioma” on MRI).
• Median survival (<2\,\text{yr}) despite maximal therapy.

• Clinical presentation
• Raised intracranial pressure: early-morning headache, nausea/vomiting.
• Focal cortical irritation: new-onset seizures.
• Local mass effect: visual field cuts, aphasia, hemiparesis depending on lobe.
• Frontal/temporal involvement: personality/cognitive shift (“quiet accountant becomes disinhibited”).

Leukemia

• Pathophysiology
• Clonal malignant transformation of hematopoietic stem/progenitor cell → uncontrolled proliferation of abnormal WBC lineage → marrow crowding → failure of normal hematopoiesis.

• Laboratory hallmark
• CBC: markedly elevated total WBC ((>50\times10^{9}/L)) with predominant blast cells (immature forms).
• Peripheral smear: large nuclei, scant cytoplasm, Auer rods if myeloid.

• Marrow dysfunction consequences
• \downarrow RBC → anemia → fatigue, dyspnea.
• \downarrow\,\text{functional WBC} → recurrent infections despite leukocytosis.
• \downarrow Platelets → petechiae, easy bruising, mucosal bleeding.

• Most common adult subtype
• Chronic Lymphocytic Leukemia (CLL)—malignancy of mature B cells; indolent course, often incidentally discovered.

• Splenic complications
• Splenomegaly → LUQ fullness.
• Hypersplenism → further cytopenias.
• Splenic infarct/rupture → acute abdomen, hemodynamic instability.

• Bone marrow biopsy
• Posterior iliac crest aspirate/core provides definitive cytogenetic & immunophenotypic diagnosis; blast fraction (>20\%) confirms acute leukemia.

• General symptom triad
• Anemia (fatigue)
• Infection (fever)
• Bleeding (gingival, epistaxis)

Lymphoma

• Key distinction
• Hodgkin Lymphoma (HL)
• Diagnostic Reed–Sternberg cell (bilobed nucleus, “owl eyes”).
• Bimodal age distribution (20s & 60s).
• Contiguous nodal spread (cervical → mediastinal).
• Non-Hodgkin Lymphoma (NHL)
• No RS cells; heterogeneous (B-cell > T-cell).
• Any age; often extranodal.
• Non-contiguous, unpredictable dissemination.

• Pathophysiology
• Malignant transformation of lymphocytes (≈85 % B-cell origin) → accumulation in lymph nodes, spleen, bone marrow.

• “B-symptoms” / presentation
• Painless lymphadenopathy (cervical, supraclavicular, axillary, inguinal, mediastinal).
• Intermittent fever, drenching night sweats, unexplained weight loss (>10\%\/6 mo).
• Pruritus, alcohol-induced node pain (HL classic board fact).

• Risk factors
• Immunosuppression (HIV, post-transplant).
• Viral: EBV, HTLV-1.
• Autoimmune diseases, family history, pesticide/chemical exposure.

Cancer-Wide Treatment Modalities (incomplete transcript reconstructed)

• Targeted therapy
• Small-molecule TKIs (e.g., EGFR, ALK inhibitors in NSCLC; ibrutinib for CLL).
• Monoclonal antibodies (e.g., trastuzumab vs HER2; rituximab vs CD20).
• Mechanism: bind specific oncoproteins → block downstream proliferation signals, trigger immune-mediated cytotoxicity.
• Advantages: tumor specificity → fewer systemic adverse effects compared with cytotoxic chemotherapy.

• Conventional chemotherapy
• Alkylators, antimetabolites, microtubule inhibitors attack all rapidly dividing cells (tumor + hair follicles, GI mucosa, marrow).
• Resultant toxicities: alopecia, mucositis, myelosuppression ((\rightarrow) neutropenic fever risk).

• Radiation therapy
• Local tumor control or symptomatic palliation (brain mets, bone pain).
• Radiosensitivity varies—GBM relatively radio-resistant.

• Surgery
• Curative in early-stage colon cancer (segmental colectomy) and NSCLC (lobectomy) if pre-op work-up shows no distant spread.

• Hematopoietic stem-cell transplant
• Option for select leukemias/lymphomas after myeloablative chemo ± total body irradiation.

Integrative & Ethical Considerations

• Screening saves lives
• Colonoscopy every 10 yr beginning at age 45 or earlier with risk factors.
• CT low-dose lung screening for adults 50–80 y with (\ge)20 pack-year history who currently smoke or quit <15 yr ago.

• Environmental justice
• Air-quality policies reduce NSCLC incidence; occupational safety (asbestos abatement) remains essential.

• Patient-centered care
• Discuss fertility preservation before chemo/radiation.
• Shared decision-making for aggressive GBM therapy vs quality-of-life hospice focus.

• Research frontiers
• CAR-T therapy for B-cell lymphomas & leukemias.
• CRISPR gene editing trials exploring repair of oncogenic driver mutations.