Lung cancer Study Guide

📖 Core Concepts Lung cancer – malignant tumor arising from lung tissue; divided into small‑cell (SCLC) 15 % and non‑small‑cell (NSCLC) 85 %. Major NSCLC subtypes – adenocarcinoma (≈40 %), squamous‑cell carcinoma (≈30 %), large‑cell carcinoma (<10 %). TNM staging – describes tumor size (T), nodal involvement (N), distant metastasis (M); determines overall stage (I–IV). Screening – low‑dose CT (LDCT) for high‑risk adults (55‑80 y, ≥30 pack‑years, current or quit ≤15 y). Driver mutations – EGFR, ALK, ROS1, MET, BRAF, RET, NTRK, KRAS; each tumor usually has one dominant driver. Paraneoplastic syndromes – hormone‑like effects (e.g., hyper‑calcemia, hyponatremia) and autoimmune phenomena (e.g., Lambert‑Eaton). 📌 Must Remember Smoking = 80‑90 % of cases; risk rises with pack‑years. Radon, asbestos, diesel exhaust, air pollution = notable environmental/occupational risks. LDCT reduces lung‑cancer‑specific mortality ≈20 % in screened high‑risk groups. SCLC staging: Limited (one hemithorax) vs Extensive (both sides or distant). NSCLC TNM highlights: T1 ≤1 cm; T2 3–5 cm or visceral pleura/main bronchus; T3 ≤7 cm or chest wall invasion; T4 >7 cm or mediastinal invasion. N0–N3 as defined by nodal stations. M0, M1a (pleura/contralateral lung), M1b (single organ), M1c (multiple organs). Targeted therapy choice follows detected driver mutation (e.g., EGFR → osimertinib; ALK → alectinib). Immune‑checkpoint inhibitors (pembrolizumab, atezolizumab, nivolumab + ipilimumab) improve outcomes in PD‑L1‑positive NSCLC. Prognosis: 5‑yr survival overall ≈19 %; Stage IA1 ≈92 %, Stage IV ≈0 %. 🔄 Key Processes Screening Workflow Verify age 55‑80 y + ≥30 pack‑years + current or quit ≤15 y → LDCT annually. Positive nodule → CT‑guided PET/CT → tissue biopsy if suspicious. Diagnostic Imaging Pathway Chest X‑ray → initial, may miss many tumors. Chest CT → size, location, mediastinal involvement. PET‑CT → metabolic activity, distant mets. Brain MRI/CT → if neurologic symptoms or high‑risk NSCLC. Biopsy Decision Tree Central lesion → bronchoscopy ± EBUS. Peripheral lesion → percutaneous core needle. Inaccessible lesion → liquid biopsy for circulating tumor DNA. Staging (NSCLC) Algorithm Determine T from CT. Assess N via mediastinal sampling (EBUS, mediastinoscopy). Evaluate M with PET‑CT ± brain MRI. Assign stage I‑IV based on combined TNM. Targeted‑Therapy Selection Perform broad molecular panel (EGFR, ALK, ROS1, MET, BRAF, KRAS, NTRK, RET). Match FDA‑approved inhibitor to detected driver. If no driver → consider immunotherapy ± chemotherapy. 🔍 Key Comparisons SCLC vs NSCLC Location: SCLC – central airways; NSCLC – peripheral (adenocarcinoma) or central (squamous). Staging: Limited vs Extensive (SCLC) vs TNM (NSCLC). Treatment: SCLC – chemo + radiation ± PCI; NSCLC – surgery ± radiation ± chemo ± targeted/immune. Adenocarcinoma vs Squamous‑Cell Carcinoma Growth pattern: Gland‑forming, mucin production vs keratinizing sheets with central necrosis. Immunostains: Napsin‑A & TTF‑1 (+) in adenocarcinoma; p63/p40 (+), Napsin‑A/TTF‑1 (–) in squamous. EGFR inhibitor vs ALK inhibitor EGFR mutations → osimertinib (3rd‑gen) preferred. ALK rearrangements → alectinib (2nd‑gen) preferred; lorlatinib for relapsed. ⚠️ Common Misunderstandings “All lung cancers are caused by smoking.” – Up to 15 % occur in never‑smokers (radon, occupational, genetic). “A negative chest X‑ray rules out cancer.” – Many early tumors are invisible; CT is required for high‑risk screening. “All NSCLC patients get immunotherapy.” – Only PD‑L1‑positive or after targeted‑therapy failure; histology guides chemo choice. “Stage IV is always fatal.” – Targeted therapies can yield prolonged survival in selected molecular subtypes. 🧠 Mental Models / Intuition “Pack‑year = exposure dose.” Think of cumulative risk like a radiation dose: more packs × more years → higher probability. “TNM = building a map.” T = house size, N = neighborhood (nodes), M = distant cities (metastasis). Stage is the overall city‑plan. “Driver mutation = key that opens a locked door.” Find the mutation → unlock a specific targeted drug; without it, the door stays closed. 🚩 Exceptions & Edge Cases Radon synergism – Even low‑level radon exposure dramatically raises risk when combined with smoking. Asbestos + smoking – Multiplicative risk; patients with both need aggressive surveillance. Small‑cell without classic driver mutations – Treat with chemotherapy ± immunotherapy; targeted agents not applicable. PD‑L1 testing – Low expression does not absolutely preclude benefit from checkpoint inhibitors in combination regimens. 📍 When to Use Which Screening: LDCT only in 55‑80 y, ≥30 pack‑years, current/quit ≤15 y. Surgery: Stage I–II NSCLC, adequate pulmonary reserve → lobectomy (standard). SBRT: Medically inoperable Stage I NSCLC or peripheral tumors ≤5 cm. Platinum‑based chemo + etoposide: First‑line for extensive‑stage SCLC. EGFR inhibitor: When EGFR exon 19 deletion or L858R mutation present. ALK inhibitor: When ALK rearrangement detected. Immunotherapy alone: PD‑L1 ≥50 % (first‑line); PD‑L1 1‑49 % (combo with chemo). Prophylactic cranial irradiation (PCI): Limited‑stage SCLC after good response to initial therapy. 👀 Patterns to Recognize Central mass + hemoptysis → think squamous or SCLC. Peripheral nodule in never‑smoker → consider adenocarcinoma, possible EGFR/ALK driver. Horner’s syndrome + apical mass → Pancoast tumor. Elevated calcium + lung mass → hypercalcemia of malignancy (PTHrP). Rapid weight loss + night sweats → systemic or metastatic disease. 🗂️ Exam Traps “All smokers develop lung cancer.” – Only 15 % of smokers get cancer; exam may test absolute vs relative risk. “PET‑CT positive always means cancer.” – Inflammatory lesions can be FDG‑avid; tissue confirmation still required. “Stage II NSCLC always needs adjuvant radiation.” – Radiation is added only for positive margins or nodal disease, not routinely. “KRAS mutation is targetable with EGFR inhibitors.” – KRAS is a distinct driver; EGFR TKIs are ineffective. “Low‑dose CT has no radiation risk.” – Small but present; over‑screening can cause unnecessary procedures. --- Study this guide in short bursts, focus on the bolded high‑yield facts, and test yourself with the “Pattern” and “Trap” sections before the exam.