SDPS-45 PROGNOSTIC CHARACTERIZATION OF GENETIC MARKERS IN GLIOMA-ASSOCIATED EPILEPSY

Abstract

Abstract BACKGROUND High-grade gliomas are often associated with seizures, which impair quality of life and cause deleterious neurocognitive effects. Few molecular markers characterized in high-grade gliomas have prognostic capacity for glioma-associated epilepsy. Mutations in isocitrate-dehydrogenase 1 (IDH1) have been associated with glioma-associated epilepsy (Chen et al. Neurology 2017;88(19):1805–13), but other genetic and cell proliferation markers in glioma biopsies have inconclusive connections with glioma-associated epilepsy. Current AAN guidelines advise against prophylactic administration of anti-seizure medications in patients with newly diagnosed brain tumors. We sought to characterize common molecular markers in high-grade glioma-associated epilepsy. METHODS We retrospectively reviewed 241 patients diagnosed with grade IV gliomas between 2018 and 2021 at our institution. Analysis of genetic biomarkers in tumor biopsies included chromosome 1p/19q deletion, ki-67 expression, p53 expression, MGMT methylation, IDH1 mutation, and EGFR amplification. Multiple logistic regressions were utilized to examine the association between genetic biomarkers and seizure incidence at three intervals: preoperative, postoperative, and six months post-surgery. Other variables examined were age, tumor location (lobe, laterality, eloquence), and treatment type (radiation therapy, chemotherapy, immunotherapy). RESULTS Of 241 patients analyzed, 104 (43%) patients experienced seizures. EGFR amplification in high-grade gliomas was associated with preoperative seizures (β = .92, p = .013) but was not associated with postoperative seizures nor seizures six months post-surgery. Chromosome 1p/19q deletion, ki-67 expression, p53 expression, MGMT methylation, and IDH1 mutation were all not associated with seizure incidence. CONCLUSION The study results indicate that EGFR amplification is associated with preoperative seizures, suggesting EGFR to promote glioma epileptiform activity. As EGFR amplification is characteristic of the classical subtype of glioblastoma, these results further suggest that the pathogenesis of glioma-associated epilepsy is likely related to specific molecular tumor characteristics. These preliminary results will be expanded upon with further analyses that increase sample size and include next-generation sequencing RESULTS