324.3 🏥 內科專科考前版

324.3.1 Mechanistic Deep Dive

324.3.1.1 EGFR Pathway in Lung Adenocarcinoma

  • Exon 19 deletion (45%) + L858R (40%)
  • Other rare mutations (T790M acquired, exon 20 insertion)
  • TKI sensitive vs insensitive

324.3.1.2 ALK Rearrangement

  • EML4-ALK fusion most common
  • Echinoderm microtubule-associated protein-like 4
  • Multiple sensitive TKIs

324.3.1.3 KRAS G12C

  • Glycine to cysteine substitution
  • Allele-specific inhibitors
  • Sotorasib (CodeBreaK), adagrasib

324.3.1.4 Immunotherapy Mechanisms

  • PD-1/PD-L1 axis
  • CTLA-4
  • Pembrolizumab, nivolumab, atezolizumab, durvalumab
  • TMB, MSI predictive

324.3.2 Recent Trials & Updates

324.3.2.1 NLST + NELSON

  • Foundation of LDCT screening
  • Practice-changing

324.3.2.2 CheckMate-9LA (2021)

  • NSCLC: nivolumab + ipilimumab + 2 cycles chemo
  • Improved OS

324.3.2.3 ADAURA (2020) — Osimertinib Adjuvant

  • Resected EGFR+ NSCLC stage IB-IIIA
  • ↑ DFS dramatically

324.3.2.4 PACIFIC (2018) — Durvalumab Consolidation

  • Locally advanced NSCLC post-chemoradiation
  • ↑ OS

324.3.2.5 LAURA (2024) — Osimertinib + Chemoradiation

  • Unresectable stage III EGFR+ NSCLC
  • ↑ PFS dramatically

324.3.2.6 KEYNOTE-024 (2016) → Multiple

  • Pembrolizumab for PD-L1 ≥ 50%
  • Improved survival

324.3.2.7 CodeBreaK (2021) — Sotorasib for KRAS G12C

  • ~ 35% response rate
  • FDA approval

324.3.2.8 IMpower150 + IMpower110

  • Atezolizumab combinations

324.3.2.9 MRD (Molecular Residual Disease) Studies

  • ctDNA detection post-curative treatment
  • Emerging adjuvant decision tool
  • LUNGSCAPE, MERMAID-1 + 2

324.3.3 High-Yield Specialist Points

324.3.3.1 Lung Cancer Screening Implementation

  • Shared decision-making
  • Smoking cessation integration
  • Lung-RADS reporting
  • Follow-up of indeterminate nodules
  • Insurance coverage variable

324.3.3.2 Solitary Pulmonary Nodule (Ch326)

  • Risk stratification: age, smoking, size, morphology
  • Probability calculation (Brock, Mayo)
  • Fleischner Society follow-up guidelines

324.3.3.3 Comprehensive Molecular Testing

  • All advanced/metastatic NSCLC
  • Adenocarcinoma especially
  • Squamous limited but PD-L1 + selected mutations
  • Tissue + liquid biopsy combinations

324.3.3.4 Resistance Mechanisms

  • EGFR T790M (acquired resistance to 1st/2nd gen TKI) → osimertinib
  • C797S (acquired resistance to osimertinib) → trials
  • MET amplification (EGFR resistance) → MET inhibitor
  • ALK resistance → next-gen TKI

324.3.3.5 Bilateral Lung Surgery

  • Limited indications
  • Pleural mets contraindication
  • Performance + lung function matters

324.3.3.7 Pseudoprogression vs Hyperprogression

  • Pseudo: initial size increase before response (immunotherapy)
  • Hyperprogression: rapid worsening on immunotherapy

324.3.3.8 Brain Metastases

  • 30-50% of NSCLC develop
  • TKIs with CNS activity (osimertinib, alectinib, brigatinib, lorlatinib)
  • SRS + WBRT for symptomatic
  • Surgery for large solitary

324.3.3.9 Pleural Effusion + Lung Cancer

  • Malignant pleural effusion = Stage IVA (M1a)
  • Cytology + pleural biopsy
  • Pleurodesis vs PleurX (Ch311)

324.3.3.10 Adrenal Mass + Lung Cancer

  • Common metastasis site
  • Distinguish benign adenoma vs metastasis
  • Biopsy if uncertain

324.3.3.11 Future Directions

  • ctDNA for early detection (Grail, Galleri)
  • Tissue-of-origin profiling
  • AI-assisted image analysis
  • Personalized vaccines

324.3.4 Pearls

  • #1 cancer killer worldwide
  • Smoking #1, radon #2
  • NSCLC 85%, SCLC 15%
  • LDCT screening: USPSTF 2021 (age 50-80, ≥ 20 pack-years, current/quit < 15 yr)
  • NSCLC molecular: EGFR, ALK, ROS1, KRAS G12C, MET, HER2, BRAF, NTRK, RET, PD-L1, TMB
  • TNM 8th (2017)
  • EGFR + Asian women + adenocarcinoma: 50% prevalence
  • Pancoast: apical + Horner + arm pain
  • Paraneoplastic SCLC: SIADH, ACTH, LEMS
  • PACIFIC, ADAURA, LAURA: stage III + adjuvant osimertinib