Abstract
OBJECTIVE: To test the hypothesis that subets of patients with brain metastases (BrM) without seizures at intracranial presentation are at increased risk for developing seizures, we characterized the incidence and risk factors for seizure development among seizure-naive patients with BrMs. METHODS: We identified 15,863 and 1,453 patients with BrM utilizing Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2008-2016) and Brigham and Women's Hospital/Dana Farber Cancer Institute (2000-2015) institutional data, respectively. Cumulative incidence curves and Fine/Gray competing risks regression were used to characterize seizure incidence and risk factors, respectively. RESULTS: Among SEER-Medicare and institutional patients, 1,588 (10.0%) and 169 (11.6%) developed seizures, respectively. On multivariable regression of the SEER-Medicare cohort, Black vs White race (hazard ratio [HR] 1.45 [95% confidence interval (CI), 1.22-1.73], p < 0.001), urban vs nonurban residence (HR 1.41 [95% CI, 1.17-1.70], p < 0.001), melanoma vs non-small cell lung cancer (NSCLC) as primary tumor type (HR 1.44 [95% CI, 1.20-1.73], p < 0.001), and receipt of brain-directed stereotactic radiation (HR 1.67 [95% CI, 1.44-1.94], p < 0.001) were associated with greater seizure risk. On multivariable regression of the institutional cohort, melanoma vs NSCLC (HR 1.70 [95% CI, 1.09-2.64], p = 0.02), >4 BrM at diagnosis (HR 1.60 [95% CI, 1.12-2.29], p = 0.01), presence of BrM in a high-risk location (HR 3.62 [95% CI, 1.60-8.18], p = 0.002), and lack of local brain-directed therapy (HR 3.08 [95% CI, 1.45-6.52], p = 0.003) were associated with greater risk of seizure development. CONCLUSIONS: The role of antiseizure medications among select patients with BrM should be re-explored, particularly for those with melanoma, a greater intracranial disease burden, or BrM in high-risk locations.