Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With <i>IDH</i> Wild-Type Glioblastoma.

Abstract

Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, <i>isocitrate dehydrogenase</i> (<i>IDH</i>)-wild-type is almost unexplored longitudinally during the whole course of the disease. We assessed tumor-related epilepsy and seizure control during tumor evolution and the prognostic significance of tumor-related epilepsy. We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, <i>IDH</i>-wild-type with available preoperative and postoperative MRI and with available epileptic seizure status at diagnosis. To determine factors associated with tumor-related epilepsy or seizure control, univariate analyses were performed using the χ² or Fisher exact tests for categorical variables and the unpaired <i>t</i> test or Mann-Whitney rank-sum test for continuous variables. Predictors associated with tumor-related epilepsy and seizure control in unadjusted analysis were entered into backward stepwise logistic regression models. One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; <i>p</i> < 0.001) independent of age, Karnofsky Performance Status score, tumor location and volume, extent of resection, standard combined chemoradiotherapy, levetiracetam use, and <i>MGMT</i> promoter methylation. The progression of tumor-related epilepsy with the evolution of glioblastoma, <i>IDH</i>-wild-type and the effects of surgery on seizure control argue for proper antiseizure medication and maximal safe resection. Tumor-related epilepsy is an independent predictor of a longer survival.