377 CDKN2A Alterations Are Associated With Increased Postoperative Seizure Risk After Resection of Brain Metastases

Abstract

INTRODUCTION: Seizures are common and significantly disabling for patients with brain metastases (BMs). While surgical resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Molecular BM characteristics may influence which patients are at-risk for postoperative seizures. METHODS: All patients underwent BM resection at one institution with available clinical and sequencing data on > 500 oncogenes. Clinical seizures were documented preoperatively and postoperatively. Random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures using Cox proportional hazards models. RESULTS: There were 112 patients with BMs who underwent 114 surgeries and had at least one month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). Engel classification (EC) at six months achieved for those with preoperative seizures was EC I in 13 (50%); II in 6 (23.1%); III in 5 (19.2%), and IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively. Preoperative seizures were not a significant predictor of postoperative seizures (hazards ratio (HR) = 1.84; 95% confidence interval (CI) = 0.79 – 4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR = 3.22; 95% CI = 1.27–8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other malignancies (HR = 5.23; 95% CI = 1.37–19.98; p = 0.016). CONCLUSIONS: CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.