MPTH-03. SCREENING BIOMARKERS IN GLIAL TUMORS TO IDENTIFY PREDICTORS OF SEIZURE ACTIVITY: A PROOF OF CONCEPT USING ISOCITRATE DEHYDROGENASE 1 (IDH-1) MUTATION STATUS

Abstract

OBJECTIVE: This is a proof of concept to demonstrate whether screening pathological biomarkers, present in primary brain tumors, may be a useful strategy to identify epileptogenic tumor types. Using a single biomarker, isocitrate dehydrogenase gene (IDH-1), this study looks for an association between the presence or absence of IDH-1 and the risk of developing seizures. BACKGROUND: It has been established that tumor grade, location, necrosis, hemorrhage, and peri-tumoral tissue changes contribute to epileptogenesis. However, the precise mechanism is unknown. Seizures occur in up to 50% of patients with brain tumors. It is not understood why seizures occur more often in low-grade gliomas compared to high-grade gliomas, or metastases. DESIGN/METHODS: This is a retrospective case control study. Using “PennSeek”, a tool to search unstructured medical documents at the Hospital of the University of Pennsylvania, 551 patients with “IDH-1” (positive or negative) were identified. Patients with non-glial pathology were excluded. Using ICD-9 codes, the patients with known IDH-1 status were divided into seizure versus seizure-free groups. Comparisons between these two groups were made with t-tests and Chi-square. RESULTS: The odds of having seizures in the IDH-1 positive group was 1.4 times that of the IDH1-1 negative group (95% CI 0.782-2.536, p=0.22). The most common pathology in IDH-1 positive patients who had seizure activity was oligodendroglioma (27.8%) compared to IDH-1 negative patients with seizures, whose predominant pathology was glioblastoma multiforme (54.3%). Without statistical significance, further evaluation to adjust for tumor location, necrosis, and hemorrhage was not pursued. CONCLUSIONS: There was an increased odds of seizure in IDH-1 positive patients. This was not a statistically significant finding. The same methodology may be applied to additional molecular markers: EGFR, P53, 1p19q co-deletion. Subsequent statistical analysis will provide better understanding of tumor epileptogenesis after adjusting for tumor location, grade, degree of necrosis, and hemorrhagic changes.