324.1 🎓 醫孞生版

324.1.0.1 📌 䞀頁重點

324.1.0.1.1 Epidemiology
  • Lung cancer = #1 cancer killer globally (~ 1.8 million deaths/year)
  • ~ 2.2 million new cases/year
  • 5-year survival: ~ 25% overall (highly stage-dependent)
  • Survival has improved (immunotherapy, targeted therapy)
324.1.0.1.1.1 Risk Factors

Smoking (80-85% in US): - Active smoking 15-30x risk - Secondhand smoke 20-30% increase - E-cigarettes: long-term data emerging - Dose-response (pack-years) - Cessation reduces risk over 10-15 years

Other: - Radon (2nd cause; ~ 10-15%) - Asbestos (multiplicative with smoking, 50-90x) - Air pollution (PM2.5) - Occupational (silica, chromium, arsenic, nickel, beryllium, diesel exhaust) - Chronic lung disease (COPD, IPF) - Family history - Genetic syndromes (Li-Fraumeni, retinoblastoma) - Prior radiation - HIV (1.5-2x) - TB scar carcinoma (rare)

324.1.0.1.1.2 Demographics
  • Increasing in women (smoking + lung cancer in non-smokers)
  • Adenocarcinoma in Asian women (EGFR mutation high prevalence)
  • Decreasing in men (smoking decline)
  • Aging population
324.1.0.1.2 Pathology
324.1.0.1.2.1 NSCLC (~ 85%)

Adenocarcinoma (~ 40% of all lung cancer): - Most common in non-smokers - Often peripheral, smaller - TTF-1, napsin A positive - Driver mutations common (EGFR, ALK, ROS1, KRAS, MET, etc.)

Squamous Cell Carcinoma (~ 20-25%): - Smokers - Central, large bronchi - p40, p63 positive - Less driver mutations; more PD-L1 expression

Large Cell Carcinoma (~ 5-10%): - Undifferentiated - Increasingly reclassified as adenocarcinoma or squamous with IHC - Aggressive

Other: - Adenosquamous (mixed) - Sarcomatoid (rare) - NUT carcinoma (rare) - Pleomorphic

324.1.0.1.2.2 SCLC (~ 15%)
  • Almost always smokers
  • Central, fast-growing
  • Neuroendocrine markers: chromogranin, synaptophysin, CD56, INSM1
  • Highly aggressive
  • Paraneoplastic syndromes
  • TP53 + RB1 mutations universal
324.1.0.1.2.3 Other Pulmonary Malignancies
  • Carcinoid (typical + atypical) — well-differentiated NE
  • Large cell neuroendocrine carcinoma (LCNEC) — between SCLC and NSCLC
  • Mesothelioma (pleural; Ch311) — asbestos
  • Salivary gland-type tumors (adenoid cystic, mucoepidermoid)
  • Pulmonary lymphoma (MALT, DLBCL)
  • Sarcoma (rare)
324.1.0.1.3 Screening — Low-Dose CT (LDCT)

324.1.1 NLST (National Lung Screening Trial, 2011)

  • LDCT vs CXR
  • ↓ Lung cancer mortality 20%, ↓ all-cause 6.7%
  • Practice-changing

324.1.2 NELSON (2020)

  • European trial
  • LDCT vs no screening
  • ↓ Lung cancer mortality 24% in men, 33% in women
  • Confirmed NLST

324.1.3 USPSTF 2021

  • Age 50-80 (lowered from 55)
  • ≥ 20 pack-years (lowered from 30)
  • Current smoker OR quit < 15 years
  • Annual LDCT
  • Class B recommendation

324.1.4 Taiwan 2022 LDCT Screening Program

  • Men 50-74 + women 45-74
  • Heavy smokers (≥ 30 pack-years + current or quit < 15 years)
  • OR family history of lung cancer
  • Government subsidized

324.1.5 Lung-RADS (American College of Radiology)

  • Standardized reporting for LDCT
  • 1-4X categories
  • Guides follow-up

324.1.6 Pros + Cons of Screening

Pros: - ↓ Mortality - Early detection - Increased cure rate

Cons: - False positives (high) - Overdiagnosis - Radiation exposure (cumulative) - Incidental findings - Cost

324.1.6.0.1 Clinical Presentation

324.1.7 Symptoms (Often Late)

  • Cough (most common)
  • Hemoptysis
  • Dyspnea
  • Chest pain
  • Weight loss
  • Fatigue, anorexia
  • Wheezing (localized — obstruction)
  • Hoarseness (recurrent laryngeal nerve)
  • Dysphagia
  • SVC syndrome (mediastinal mass)
  • Pancoast syndrome (apical)
  • Bone pain (mets)
  • Neurologic (brain mets, paraneoplastic)
  • Pleural effusion (malignant)

324.1.8 Pancoast Syndrome

  • Apical (superior sulcus) tumor
  • Shoulder + arm pain (C8, T1, T2)
  • Horner syndrome (sympathetic chain)
  • Hand weakness + atrophy
  • Treatment: neoadjuvant chemoradiation + surgery

324.1.9 Paraneoplastic Syndromes

Common in SCLC: - SIADH (hyponatremia) - Cushing syndrome (ectopic ACTH) - Lambert-Eaton myasthenic syndrome (LEMS) — anti-VGCC - Limbic encephalitis

Adenocarcinoma: - Hypertrophic osteoarthropathy - Clubbing - DIC + Trousseau syndrome

Squamous: - PTHrP (hypercalcemia)

General: - Anorexia, cachexia - Anemia - Hypercoagulability

324.1.9.0.1 Diagnosis

324.1.10 Imaging

Chest X-Ray: - Initial screening - Mass, infiltrate, atelectasis - Limited sensitivity for small lesions

CT Chest with Contrast: - Better characterization - Lymph nodes, mediastinum - Extension assessment

PET-CT (FDG): - Metabolic activity - Distant staging - NSCLC standard for staging - SUVmax > 2.5 concerning

Brain MRI: - For NSCLC staging (especially stages III-IV) - SCLC routinely - Brain metastases (common)

MRI Thoracic (selected): - Pancoast - Vascular involvement - Spinal involvement

324.1.11 Tissue Diagnosis

Sputum Cytology (limited): - Central tumors only - Sensitivity 60-70% if central

Bronchoscopy: - For central, hilar, mediastinal lesions - Endobronchial biopsy - Transbronchial biopsy - EBUS-TBNA (endobronchial ultrasound) - Navigational / robotic bronchoscopy for peripheral

Percutaneous CT-Guided Biopsy: - Peripheral lesions - Pneumothorax risk (10-30%)

Thoracoscopic (VATS) Biopsy: - Definitive - Pleural lesions

Open Surgical Biopsy: - Rarely; for diagnosis or definitive treatment

Mediastinoscopy: - For mediastinal LN - Largely replaced by EBUS

324.1.12 Liquid Biopsy (ctDNA)

  • Plasma cell-free DNA
  • Useful for: molecular profiling when tissue insufficient
  • Monitoring resistance
  • Less sensitive than tissue (especially early-stage)
  • Emerging for MRD

324.1.13 Molecular + Immunohistochemistry

NSCLC Workup (Comprehensive Molecular Testing — MANDATORY for advanced/metastatic): - EGFR mutation (exon 19 deletion, L858R most common — 50% Asian adenocarcinoma) - ALK rearrangement (5%) - ROS1 rearrangement (1-2%) - KRAS G12C mutation (~ 13% adenocarcinoma) - MET exon 14 skipping (3%) - MET amplification - HER2 mutation (3%) - BRAF V600E mutation (2%) - NTRK fusion (1%) - RET fusion (1-2%) - PD-L1 expression (immunohistochemistry; TPS score) - TMB (tumor mutational burden) - MSI (microsatellite instability) — uncommon in lung

SCLC: limited targeted therapies; TP53 + RB1 universal; no routine driver mutation profiling

324.1.13.0.1 Staging — 8th TNM (AJCC/UICC 2017)

324.1.14 NSCLC Staging Concept

T (Primary Tumor): - T1 ≀ 3 cm - T2 3-5 cm or main bronchus or atelectasis - T3 5-7 cm or invasion local structures or separate nodules same lobe - T4 > 7 cm or invasion mediastinum or separate nodules different lobe of same lung

N (Lymph Nodes): - N0 no nodes - N1 ipsilateral peribronchial or hilar - N2 ipsilateral mediastinal or subcarinal - N3 contralateral mediastinal/hilar or supraclavicular/scalene

M (Metastases): - M0 no distant mets - M1a separate nodule contralateral lung, pleural/pericardial nodules, malignant effusion - M1b single extrathoracic met - M1c multiple extrathoracic mets

324.1.15 Stages (NSCLC)

  • Stage I (IA, IB): T1-T2a, N0
  • Stage II (IIA, IIB): limited disease, N1 or larger T
  • Stage IIIA, IIIB, IIIC: locally advanced, N2-N3
  • Stage IV (IVA, IVB, IVC): metastatic

324.1.16 SCLC Staging

  • Traditionally “limited” vs “extensive”
  • Now also TNM applies

324.1.17 Staging Workup

  • History + physical
  • CT chest with contrast + abdomen (adrenals, liver)
  • PET-CT (whole body except brain)
  • Brain MRI
  • Mediastinal staging (EBUS or mediastinoscopy if PET+ nodes)
  • Bone scan if symptoms
  • Labs (CBC, comprehensive, LDH for SCLC)

324.1.17.1 🩺 床邊速查

  • #1 cancer killer: lung cancer ~ 1.8 M deaths/yr
  • Smoking: 80-85% of US lung cancer
  • NSCLC: 85%; adenocarcinoma (most), squamous, large cell
  • SCLC: 15%; smokers, aggressive, neuroendocrine
  • LDCT screening (USPSTF 2021): age 50-80, ≥ 20 pack-years, current/quit < 15 yr
  • NSCLC molecular testing (advanced): EGFR, ALK, ROS1, KRAS G12C, MET, HER2, BRAF, NTRK, RET, PD-L1, TMB
  • Staging: TNM 8th, PET-CT + brain MRI + EBUS for mediastinum
  • Pancoast: apical + Horner + arm pain
  • Paraneoplastic SCLC: SIADH, ACTH (Cushing), LEMS