Lung Cancer Approach

Intro & Risks - Genesis Glimpse

Lung cancer: leading malignancy. Two main groups:

• NSCLC (~85%):
  • Adenocarcinoma: Most common, esp. non-smokers.
  • Squamous Cell: Central, smoking.
  • Large Cell.
• SCLC (~15%): Very aggressive, smoking.

Major Risks:

• Smoking (paramount, 80-90%).
• Asbestos, Radon.
• Genetics, chronic lung disease.
• Air pollution (PM2.5). 📌 Risks: Smoking, Asbestos, Radon, Genetics (SARG). India: ↑ incidence, esp. males; Adenocarcinoma rising.

⭐ Adenocarcinoma is the most common lung cancer in non-smokers.

Clinical Clues - Symptom Spectrum

• Common Symptoms: Cough (persistent/changed), dyspnea, chest pain, hemoptysis, weight loss, fatigue.

• Local Invasion/Compression:

  • SVC Obstruction: Facial/arm swelling, plethora, dilated veins.
  • Horner's (Pancoast): Ptosis, miosis, anhydrosis.

• Paraneoplastic Syndromes:

  Syndrome	With	Mediator/Mechanism
  SIADH	SCLC	Ectopic ADH → Hyponatremia
  Cushing's	SCLC	Ectopic ACTH → ↑Cortisol
  Hypercalcemia	Squamous Cell	PTHrP
  Lambert-Eaton	SCLC	Anti-presynaptic Ca2+ channels

  📌 Small Cell Loves Creating Syndromes: SIADH, Cushing's, Lambert-Eaton.

⭐ Lambert-Eaton Myasthenic Syndrome (LEMS) is commonly associated with Small Cell Lung Cancer (SCLC) and presents with proximal muscle weakness that improves with activity.

Diagnosis & Staging - Unmasking & Mapping

• Initial Imaging:
  • CXR: Initial; shows nodule, mass, effusion.
  • CT Chest (contrast): Gold standard; details lesion, nodes, local invasion. Essential for T.
• Biopsy - Tissue is the Issue: (Confirms histology: NSCLC/SCLC, molecular markers)
  • Sputum cytology (central lesions)
  • Bronchoscopy: Central lesions, EBUS-FNA (mediastinal/hilar nodes).
  • EUS-FNA (posterior nodes/adrenal).
  • TTNA: CT-guided, peripheral lesions.
• Staging - Mapping the Spread:
  • PET-CT: For N & M staging (NSCLC focus).

    ⭐ PET-CT is crucial for detecting distant metastases in NSCLC staging, impacts resectability & treatment.

  • TNM (Simplified):
    • T: Size/local extent (T1 ≤3cm; T4 vital invasion). Impacts resectability.
    • N: Node spread (N0 none; N1-N3 ↑). Prognostic.
    • M: Mets (M0 none; M1 distant). M1 often palliative.
• Diagnostic Flow (SPN):

Treatment Toolkit - Therapy Tactics

Non-Small Cell Lung Cancer (NSCLC): Treatment guided by stage and molecular markers.

• Early Stages (I-II): Curative surgery. Adjuvant chemotherapy for high-risk (e.g., stage IB >4cm, II).
• Locally Advanced (Stage III): Concurrent Chemotherapy + Radiotherapy (CRT) for unresectable disease. Consider consolidation immunotherapy (e.g., Durvalumab).
• Metastatic (Stage IV): Systemic therapy.
  • Chemotherapy (platinum-doublets).
  • Targeted Therapy: For driver mutations (EGFR: Osimertinib; ALK: Alectinib; ROS1: Crizotinib).
  • Immunotherapy: PD-1/PD-L1 inhibitors (e.g., Pembrolizumab), alone or with chemo, based on PD-L1.

Small Cell Lung Cancer (SCLC): Highly chemo/radiosensitive.

• Limited Stage (LS-SCLC): Concurrent Chemotherapy (etoposide + platinum) + Thoracic Radiotherapy. Curative intent.
• Extensive Stage (ES-SCLC): Chemotherapy (etoposide + platinum) +/- Immunotherapy (e.g., Atezolizumab, Durvalumab).
• Prophylactic Cranial Irradiation (PCI): For LS-SCLC with good response; consider for ES-SCLC with good response to reduce brain mets.

⭐ Osimertinib is a key targeted therapy for EGFR T790M mutation-positive NSCLC.

High‑Yield Points - ⚡ Biggest Takeaways

• Adenocarcinoma: Most common overall, especially in non-smokers & women; peripheral.
• Squamous Cell Ca: Strong smoking link; central; hypercalcemia (PTHrP).
• SCLC: Central, aggressive; SIADH, Lambert-Eaton syndrome; chemo-sensitive.
• Pancoast Tumor: Apical (superior sulcus); causes Horner's syndrome, shoulder/arm pain.
• Screening: Low-Dose CT (LDCT) for high-risk (age 50-80, >20 pack-year history, current/quit <15 yrs).
• Paraneoplastic syndromes: Common, especially with SCLC (e.g., Cushing's, cerebellar degeneration).
• NSCLC Staging: TNM is crucial; PET-CT for mets. EGFR/ALK/ROS1 testing for targeted therapy in adenocarcinoma.