Assessing Survival in Non-Small Cell Lung Cancer Brain Metastases After Stereotactic Radiosurgery: Before and After the Start of the Targetable Mutation Era

Abstract Purpose Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BM) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations. Methods In this retrospective cross-sectional analysis, we reviewed patient charts from 2001–2021. We analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC with and without targetable mutations. We evaluated patient demographics, targetable mutations, and all treatments performed and their relationship on survival. Results Among the 235 patients included, 88 (37.5%) had targetable mutations—primarily EGFR (39.4%), KRAS (23.4%), and ALK (15.9%)—and 147 (62.5%) did not. Patients with targetable mutations were more often female (63.6%, p < .001) and nonsmokers (59.1%, p < .001) and received more systemic therapies (median 3 vs. 2, p < .001) and SRS courses (mean 1.56 vs. 1.32, p = .020). Patients with targetable mutations had lower mortality rates (72.7% vs. 90.5%, p < .001) and longer median overall survival (23.2 vs. 7.4 months, p < .001). Long-term survival was best predicted by SRS with resection in patients with non-targetable mutations (OR 3.284 [95% CI 1.075–10.03], p = .037), whereas systemic therapy with SRS appeared the best option for targetable mutation patients. Conclusion The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Long-term survival for patients without targetable mutations was greatest when SRS was used with surgical resection. These results inform best practices for managing NSCLC BM patients based on driver mutation status.