CLTR-01 SURGICAL SELECTION PATTERNS IN NSCLC BRAIN METASTASES: CLINICAL AND MOLECULAR CORRELATES IN THE TKI ERA

Abstract

First-line CNS-penetrant tyrosine kinase inhibitors (TKIs) permit deferral of local therapy in asymptomatic EGFR-mutant NSCLC brain metastases; however, real-world surgical selection patterns remain poorly characterized. We retrospectively analyzed 111 patients undergoing surgical resection to define the clinical and molecular phenotype of surgically selected patients in the current era of targeted systemic therapy. Clinical, radiographic, and molecular variables were compared between EGFR-mutant (EGFR+) and wild-type (WT) patients using Mann–Whitney U and Fisher’s exact tests. Median age was 65 years, 59% were female, and 84% were White. Median KPS was 80. Patients had a median of 2 brain metastases (range, 1–35) with a median dominant lesion size of 3.3 cm (range, 1.2–6.5), and extracranial metastases were present in 66%. Molecular profiling revealed EGFR mutations in 11%, ALK rearrangements in 1%, and PD-L1 expression ≥1% in 21%. Median Sperduto GPA was 1.5. No statistically significant differences were observed between EGFR-mutant and wild-type patients regarding age (69.5 vs 65.0 years, P = 0.07), KPS (P = 0.43), dominant lesion size (2.9 vs 3.4 cm, P = 0.41), number of brain metastases (P = 0.64), Sperduto GPA (2.0 vs 1.5, P = 0.44), smoking history (30.8 vs 36.5 pack-years, P = 0.07), or extracranial metastases (50.0% vs 67.7%, P = 0.33). ALK and PD-L1 expression rates were low and did not differ significantly between groups. Surgically resected NSCLC brain metastases were characterized by large lesions, frequent extracranial disease, and a low prevalence of actionable mutations. No statistically significant differences were observed between EGFR-mutant and wild-type patients across clinical and demographic variables, including extracranial metastases, smoking history, age, and lesion size, highlighting a distinct clinical profile of surgically treated patients and generating hypotheses for validation in larger, comparative cohorts with treatment and survival endpoints.