Lung cancer

Definition
Lung cancer is a malignant tumor arising from the respiratory epithelium, characterized by uncontrolled cell proliferation within the lung tissue, often with the potential for local invasion and distant metastasis. It is broadly classified into two main categories:

• Non–small cell lung cancer (NSCLC) – accounts for about 85% of cases, includes adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

• Small cell lung cancer (SCLC) – accounts for about 15% of cases, more aggressive with earlier metastasis.

---

Epidemiology

• Lung cancer is the leading cause of cancer-related mortality worldwide.

• Most common in individuals aged 60 years and above.

• Strongly associated with smoking (over 80% of cases in high-prevalence countries).

• Higher risk in men, but the gender gap is narrowing due to changing smoking patterns.

---

Risk Factors

• Tobacco smoking: primary cause, risk increases with duration and intensity.

• Second-hand smoke exposure.

• Environmental exposures: radon gas, asbestos, silica, air pollution.

• Occupational hazards: arsenic, diesel exhaust.

• Genetic susceptibility: family history of lung cancer.

• Pre-existing lung disease: COPD, pulmonary fibrosis, tuberculosis scars.

---

Pathophysiology

1. Chronic exposure to carcinogens induces genetic mutations in oncogenes (e.g., KRAS, EGFR) and tumor suppressor genes (e.g., TP53).

2. Dysregulated cell proliferation, reduced apoptosis, and angiogenesis promote tumor growth.

3. Tumor progression leads to local invasion, lymphatic spread, and hematogenous metastases.

---

Clinical Features

Local Symptoms

• Persistent cough or change in cough character.

• Hemoptysis.

• Shortness of breath.

• Wheezing or stridor.

• Chest pain (pleuritic or dull).

Constitutional Symptoms

• Fatigue, weight loss, anorexia.

• Fever (paraneoplastic or secondary infection).

Local Invasion Signs

• Hoarseness (recurrent laryngeal nerve involvement).

• Superior vena cava obstruction: facial swelling, distended neck veins.

• Dysphagia (esophageal compression).

Metastatic Symptoms

• Bone pain, pathological fractures (bone metastases).

• Neurological deficits (brain metastases).

• Hepatomegaly, jaundice (liver metastases).

Paraneoplastic Syndromes

• SCLC: SIADH (hyponatremia), ectopic ACTH production (Cushing’s syndrome), Lambert–Eaton myasthenic syndrome.

• NSCLC (especially squamous cell): hypercalcemia from ectopic PTHrP secretion.

---

Diagnosis

Imaging

• Chest X-ray: initial detection.

• CT scan: detailed assessment of tumor size, location, lymph nodes.

• PET-CT: staging, detection of metastases.

Tissue Diagnosis

• Bronchoscopy with biopsy (central lesions).

• CT-guided transthoracic needle aspiration (peripheral lesions).

• Endobronchial ultrasound (EBUS) for mediastinal lymph node sampling.

Histological Classification

• NSCLC: adenocarcinoma, squamous cell carcinoma, large cell carcinoma.

• SCLC: high-grade neuroendocrine tumor.

Molecular Testing

• EGFR mutations, ALK and ROS1 rearrangements, PD-L1 expression, KRAS mutations – guides targeted therapy selection.

Staging

• TNM staging system for NSCLC.

• Limited vs extensive stage for SCLC.

---

Management

Treatment depends on type, stage, patient performance status, and molecular profile.

---

1. Non–Small Cell Lung Cancer (NSCLC)

Early Stage (I–II)

• Surgical resection (lobectomy or pneumonectomy) is preferred if operable.

• Adjuvant chemotherapy:

  • Cisplatin 75 mg/m² IV day 1 + vinorelbine 25 mg/m² IV days 1 and 8, every 21 days for 4 cycles.

Locally Advanced (Stage III)

• Concurrent chemoradiotherapy:

  • Cisplatin 50 mg/m² IV days 1 and 8 + etoposide 50 mg/m² IV days 1–5, every 28 days for 2 cycles with radiotherapy.

Advanced/Metastatic (Stage IV)

• Platinum-doublet chemotherapy:

  • Cisplatin or carboplatin + pemetrexed (for non-squamous histology) or gemcitabine/paclitaxel (for squamous histology).

Targeted Therapy (based on mutation testing)

• EGFR mutation: Osimertinib 80 mg orally once daily.

• ALK rearrangement: Alectinib 600 mg orally twice daily.

• ROS1 rearrangement: Crizotinib 250 mg orally twice daily.

• KRAS G12C mutation: Sotorasib 960 mg orally once daily.

Immunotherapy

• PD-L1 ≥50%: Pembrolizumab 200 mg IV every 3 weeks.

• PD-L1 1–49%: combined with chemotherapy.

---

2. Small Cell Lung Cancer (SCLC)

Limited Stage

• Concurrent chemoradiotherapy:

  • Cisplatin 75 mg/m² IV day 1 + etoposide 100 mg/m² IV days 1–3, every 21 days for 4–6 cycles.

Extensive Stage

• Chemotherapy: Carboplatin AUC 5 day 1 + etoposide 100 mg/m² IV days 1–3, every 21 days for 4–6 cycles.

• Addition of immunotherapy: Atezolizumab 1200 mg IV day 1 every 21 days with chemotherapy.

Prophylactic Cranial Irradiation (PCI)

• Recommended for patients with good response to initial therapy to reduce brain metastasis risk.

---

3. Palliative and Supportive Care

• Analgesia for pain control.

• Oxygen therapy for hypoxemia.

• Bisphosphonates (e.g., zoledronic acid 4 mg IV every 4 weeks) for bone metastases.

• Corticosteroids for symptomatic brain metastases.

• Nutritional support and psychological counseling.

---

Monitoring

• Regular imaging (CT/PET-CT) every 2–3 months during active treatment.

• Monitor for chemotherapy and targeted therapy toxicities (CBC, renal and liver function).

• Long-term follow-up for recurrence detection.

---

Prognosis

• Overall 5-year survival: ~20% for NSCLC, <10% for SCLC.

• Prognosis depends on stage at diagnosis, performance status, and molecular subtype.