Editors' Note: Effect of Levetiracetam Use Duration on Overall Survival of Isocitrate Dehydrogenase Wild-Type Glioblastoma in Adults: An Observational Study

Dr. Pallud et al. investigated whether the duration of levetiracetam use during the standard chemoradiation protocol affected the overall survival of patients with IDH wild-type glioblastoma in an observational single-center cohort study of 460 patients. Levetiracetam use during the whole duration of the standard chemoradiation protocol independently predicted longer overall survival, and the authors concluded that levetiracetam should be considered in the antitumor strategy of future multicenter trials. In response, Dr. Mazzucchi et al. comment that because levetiracetam was likely initiated in these patients for new epilepsy or epilepsy resistant to other drugs, the study findings reinforce the hypothesis that uncontrolled epilepsy may be a risk factor for glioma progression. They also note that other antiseizure medications have been reported to display experimental antitumoral properties. Nevertheless, they caution against starting levetiracetam in patients without a prior history of seizures. Responding to these comments, the authors note that epilepsy was actually associated with improved survival in patients with glioblastomas and diffuse low-grade gliomas in their previous study. They emphasize that the discrepant findings among studies may relate to their focus on seizure control at the time of diagnosis rather than postoperatively. They also note that there were only a few patients without seizures who were on levetiracetam in their study. They agree that randomized controlled trials are needed to clarify the role of antiepileptic drugs in the treatment of diffuse gliomas. This exchange highlights both the promise and uncertainty presented by certain antiepileptic drugs such as levetiracetam in the treatment of patients with gliomas.