Case Presentation: William, a 76-Year-Old with HER2-Mutant NSCLC, Hepatic Impairment, and Rural Access Barriers

Dr. Evan Wu presents William, a 76-year-old Black man and former smoker (25 pack-year history, quit 15 years ago) who presents with 2 months of progressive fatigue, decreased appetite, and a 12-pound unintentional weight loss. William's medical history includes type 2 diabetes on metformin, hypertension on lisinopril and amlodipine, hyperlipidemia on atorvastatin, chronic hepatitis B on entecavir, cardiovascular prophylaxis with aspirin, and gastroesophageal reflux disease (GERD) on omeprazole—a total of 7 daily medications.

On baseline workup, William weighs 82 kg with aspartate aminotransferase (AST) elevated at 52 U/L (1.3× upper limit of normal [ULN]), total bilirubin 1.4 mg/dL (1.2× ULN), and a liver sonogram showing mild hepatic changes consistent with mild hepatic impairment. His Eastern Cooperative Oncology Group (ECOG) performance status is 1. Computed tomography (CT) of the chest, abdomen, and pelvis reveals a 3.8-cm right upper lobe mass, mediastinal lymphadenopathy, and 3 hepatic lesions (largest 2.1 cm). Magnetic resonance imaging (MRI) of the brain is negative for metastases. CT-guided biopsy confirms non-squamous non-small cell lung cancer (NSCLC), adenocarcinoma histology, with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) of 25%.

Socially, William lives alone in a rural area 50 miles from the cancer center; his son can attend some visits, and rideshare trips cost $80–$120 round trip. Comprehensive tissue next-generation sequencing (NGS) is ordered, but the sample is insufficient; a limited panel (EGFR, ALK, ROS1, KRAS, BRAF) returns negative. Plasma circulating tumor DNA (ctDNA) later identifies a HER2 A775_G776insYVMA mutation.

In the next episode, “Completing Biomarker Testing When Tissue Is Insufficient: Liquid Biopsy, Timing, and Patient Counseling,” Dr. Wu discusses how he approaches comprehensive molecular profiling when initial tissue is inadequate and how he counsels anxious patients about the value of waiting for complete results.