326.2 🩺 國考版

326.2.1 高頻考點

326.2.1.1 SCLC Epidemiology

  • 15% of lung cancer

  • 95% smokers

  • Central, aggressive
  • 60-70% metastatic at diagnosis

326.2.1.2 Pathology

  • Neuroendocrine origin
  • Chromogranin, synaptophysin, CD56, INSM1
  • TP53 + RB1 mutations universal

326.2.1.3 Staging

  • Limited (LS-SCLC) vs extensive (ES-SCLC) — VALG
  • TNM 8th also applies

326.2.1.4 LS-SCLC Treatment

  • Concurrent chemoradiation (cisplatin + etoposide + 45 Gy BID)
  • PCI for complete response

326.2.1.5 ES-SCLC Treatment

  • IMpower133: carboplatin + etoposide + atezolizumab
  • CASPIAN: cisplatin/carboplatin + etoposide + durvalumab
  • Maintenance IO

326.2.1.6 Refractory SCLC (NEW 2024)

  • Tarlatamab (Imdelltra): DLL3-targeted BiTE
  • DeLLphi-301: 40% response
  • FDA approval 2024

326.2.1.7 Second-Line + Beyond

  • Lurbinectedin (2020 FDA)
  • Topotecan
  • Tarlatamab
  • Re-challenge with platinum if long platinum-free interval

326.2.1.8 Paraneoplastic Syndromes

  • SIADH (10% SCLC): hyponatremia
  • Cushing (5% SCLC): ectopic ACTH; severe rapid hypokalemia + hypertension
  • LEMS (3% SCLC): anti-VGCC; proximal weakness + autonomic; improves with repeated effort
  • Limbic encephalitis: anti-Hu, anti-CV2; memory + seizures
  • Cerebellar degeneration
  • Encephalomyelitis

326.2.1.9 Squamous + Adenocarcinoma Paraneoplastic

  • Squamous: PTHrP (hypercalcemia)
  • Adenocarcinoma: HPOA + clubbing
  • Trousseau syndrome (any cancer)

326.2.1.10 Carcinoid Tumors

  • Typical: well-differentiated, slow
  • Atypical: moderately differentiated
  • LCNEC: poorly differentiated
  • SCLC: most poorly differentiated

326.2.1.11 Key Trials

  • IMpower133 (2018): atezolizumab in ES-SCLC
  • CASPIAN (2019): durvalumab in ES-SCLC
  • DeLLphi-301 (2024): tarlatamab in pretreated SCLC

326.2.2 易混淆比范

Tumor Differentiation Mitoses/10 HPF Treatment
Typical carcinoid Well < 2 Surgery
Atypical carcinoid Moderate 2-10 Surgery + adjuvant
LCNEC Poor > 10 Chemo (SCLC-like or NSCLC-like)
SCLC Most poor > 11 Chemo + IO (extensive); chemo + RT + PCI (limited)

326.2.2.1 LEMS vs Myasthenia Gravis

Feature LEMS MG
Strength with effort Improves Worsens
Antibody Anti-VGCC Anti-AChR
Autonomic Common Rare
EMG Facilitation at high freq Decrement at low freq
Associated cancer SCLC Thymoma
Treatment 3,4-DAP, IVIG, treat cancer Pyridostigmine, IS, thymectomy

326.2.3 Special Topics

326.2.3.1 DLL3 (Delta-Like Ligand 3)

  • Notch pathway ligand
  • Aberrantly expressed in SCLC (85%+)
  • Target for tarlatamab (BiTE)
  • Tarlatamab connects DLL3 + CD3 → T-cell mediated killing

326.2.3.2 Brain Metastases in SCLC

  • 50%+ develop
  • Whole brain RT or SRS
  • Limited targeted therapy options

326.2.3.3 PCI in SCLC

  • LS-SCLC with complete response: PCI ↑ survival
  • ES-SCLC: PCI controversial (Slotman 2007 + 2017 negative)