Epidermal Growth Factor Receptor Mutation Status Confers Survival Benefit in Patients with Non-Small-Cell Lung Cancer Undergoing Surgical Resection of Brain Metastases: A Retrospective Cohort Study

Background: Few prognostic markers are available for patients with non-small-cell lung cancer (NSCLC) undergoing neurosurgical resection of symptomatic brain metastases. Objective: We investigated whether tumor mutation status (EGFR, KRAS, ALK, ROS1, and BRAF) and treatment history were associated with survival after neurosurgery. Methods: We reviewed the electronic health records of 104 patients with NSCLC with genomic profiling who underwent neurosurgical resection for symptomatic brain metastases at an academic institution between January 2000 and January 2018. We used multivariate Cox proportional hazards regression models to evaluate the association between overall survival (OS) after neurosurgery and clinicopathologic factors, including mutation status. Results: Mean age of patients in this study was 61 (±12) years, and 44% were men. The median OS after neurosurgery was 24 months (95% confidence interval, 18–34 months). Our multivariate analysis showed that the presence of an EGFR mutation in the tumor was significantly associated with improved OS (hazard ratio [HR], 0.214; P = 0.029), independent of tyrosine kinase inhibitor use. Presence of KRAS, ALK, ROS1, and BRAF alterations was not associated with survival (all P > 0.05). Conversely, older age (HR, 1.039; P = 0.029), a history of multiple brain irradiation procedures (HR, 9.197; P < 0.001), and presence of extracranial metastasis (HR, 2.556; P = 0.016) resulted in increased risk of mortality. Conclusions: Patients requiring surgical resection of an epidermal growth factor receptor–mutated NSCLC brain metastasis had an associated improved survival compared with patients without this mutation, independent of tyrosine kinase inhibitor use. Decreased survival was associated with older age, multiple previous brain radiation therapies, and extracranial metastasis.