Respiratory · Year 1 · from Respiratory

Case 1: Non-Small Cell Lung Cancer - Adenocarcinoma with EGFR Mutation

Clinical Image

Source: Wikimedia Commons - Lung cancer CT - CC BY-SA 3.0

Patient Presentation

A 58-year-old Asian woman, never-smoker, presents with a 2-month history of persistent dry cough and mild exertional dyspnea. She has no hemoptysis, fever, or weight loss. She initially thought it was allergies but the cough has not improved with antihistamines. A chest X-ray ordered by her primary care physician revealed a right lung mass.

Demographics

  • Age: 58 years
  • Sex: Female
  • Past Medical History: Hypothyroidism
  • Medications: Levothyroxine
  • Social History: Never smoker, works as an accountant
  • Family History: No lung cancer

Chief Complaint

Persistent cough and mild dyspnea for 2 months

Physical Examination

  • Blood pressure: 128/76 mmHg
  • Heart rate: 78 bpm
  • Respiratory rate: 16/min
  • Oxygen saturation: 97% on room air
  • General: Well-appearing, no distress
  • Respiratory: Decreased breath sounds at right base, no wheezing
  • Lymph nodes: No palpable cervical or supraclavicular adenopathy
  • Neurological: Normal

Workup

  • Chest X-ray: 4 cm right lower lobe mass
  • CT chest with contrast: 4.2 cm spiculated mass in right lower lobe with ipsilateral hilar lymphadenopathy (N1)
  • PET-CT: FDG-avid primary mass and hilar nodes; no distant metastases
  • Brain MRI: No metastases
  • CT-guided biopsy: Adenocarcinoma, TTF-1 positive
  • Molecular testing:
  • EGFR mutation: Exon 19 deletion (sensitizing mutation)
  • ALK: Negative
  • ROS1: Negative
  • PD-L1: 60%

Diagnosis

Stage IIB (T3N1M0) Non-Small Cell Lung Cancer - Adenocarcinoma with EGFR Exon 19 Deletion

Treatment

  1. Multidisciplinary tumor board review
  2. Surgical resection: Right lower lobectomy with mediastinal lymph node dissection
  3. Adjuvant therapy: Given positive EGFR mutation:
  • Adjuvant osimertinib (EGFR TKI) for 3 years (ADAURA trial)
  • Significant reduction in recurrence risk
  1. Surveillance: CT chest every 6 months for 2 years, then annually
  2. Genetic counseling if any family history of cancer

Physiological Principles Demonstrated

  • EGFR mutation epidemiology: EGFR mutations are more common in adenocarcinomas, never-smokers, women, and Asian patients. Up to 50% of Asian never-smokers with adenocarcinoma harbor EGFR mutations.
  • Driver mutation concept: Lung cancer with driver mutations (EGFR, ALK, ROS1) is "oncogene addicted" - tumor survival depends on the mutated pathway, making it exquisitely sensitive to targeted inhibitors.
  • Sensitizing vs. resistance mutations: Exon 19 deletions and exon 21 L858R are sensitizing mutations. T790M is a resistance mutation that develops on first/second-generation TKIs (osimertinib covers this).
  • Personalized medicine: Comprehensive molecular testing is standard of care to identify targetable mutations and guide therapy selection.

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