873 Next Generation Sequencing of Gliomas to Identify Predictors of Postoperative Seizures

Abstract

INTRODUCTION: Seizures are common in patients who have undergone resection of diffuse gliomas. As genetic characterization of gliomas has improved, how a tumors mutational profile influences the risk of postoperative epileptogenesis is currently unknown. METHODS: A retrospective review of patients who underwent resection of gliomas with next generation sequencing of tumors at a single institution was performed. Logistic regression, Fisher’s Exact Test, and linear regression were performed to identify factors associated with development of postoperative seizures, seizure frequency, seizure type, and number of antiepileptic drugs (AEDs). RESULTS: 140 patients with tumor tissue genotyped via next generation sequencing from 2017-2020 are included in this interim analysis (this cohort includes both newly diagnosed and recurrent tumors). Glioblastomas comprised the majority (59.3%) of tumors, followed by astrocytomas (18.6%), oligodendrogliomas (13,6%), and IDH-mutant diffuse gliomas (8.6%). Fifty-two (37.1%) patients had a seizure after tumor resection, median age at seizure onset was 56.5 years, and patients were on a median of 2 AEDs for their seizures. 75.0% of these patients experienced multiple seizures with 57.1% being simple partial seizures. Multivariate analysis of the most common mutations revealed that CDKN2B/CDKN2A mutation was significantly associated with postoperative seizures (OR 2.47, 95% CI 1.02 – 6.27, p = 0.0487), while NF1 mutation and 1p/19q codeletion were not. The common GBM copy number variant Polysomy 7/monosomy 10 was associated with use of fewer AEDs (β = -0.81, p <0.0001). Analysis of mutations most common in low grade tumor samples found no significant associations with seizure development. CONCLUSIONS: CDKN2B/CDKN2A mutations are associated with more postoperative seizures. Further analysis of this cohort may yield more relationships between genetic markers and seizures, including time to onset of seizures, which can inform operative planning and postoperative management.