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Abstract
Background and Objectives The association between levetiracetam and survival with isocitrate dehydrogenase (IDH) wild-type glioblastomas is controversial. We investigated whether the duration of levetiracetam use during the standard chemoradiation protocol affects overall survival (OS) of patients with IDH wild-type glioblastoma.
Methods In this observational single-institution cohort study (2010–2018), inclusion criteria were (1) age ≥18 years; (2) newly diagnosed supratentorial tumor; (3) histomolecular diagnosis of IDH wild-type glioblastoma; and (4) standard chemoradiation protocol. To assess the survival benefit of levetiracetam use during the standard chemoradiation protocol (whole duration, part time, and never subgroups), a Cox proportional hazard model was constructed. We performed a case-matched analysis (1:1) between patients with levetiracetam use during the whole duration of the standard chemoradiation protocol and patients with levetiracetam use part time or never according to the following criteria: sex, age, epileptic seizures at diagnosis, Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) class, tumor location, preoperative volume, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. Patients with unavailable O6-methylguanine-DNA methyltransferase promoter methylation status (48.5%) were excluded.
Results A total of 460 patients were included. The median OS was longer in the 116 patients with levetiracetam use during the whole duration of the standard chemoradiation protocol (21.0 months; 95% confidence interval [CI] 17.2–24.0) than in the 126 patients with part-time levetiracetam use (16.8 months; 95% CI 12.4–19.0) and in the 218 patients who never received levetiracetam (16.0 months; 95% CI 15.5–19.4; p = 0.027). Levetiracetam use during the whole duration of the standard chemoradiation protocol (adjusted hazard ratio [aHR] 0.69; 95% CI 0.52–0.93; p = 0.014), MGMT promoter methylation (aHR 0.53; 95% CI 0.39–0.71; p < 0.001), and gross total tumor resection (aHR 0.57; 95% CI 0.44–0.74; p < 0.001) were independent predictors of longer OS. After case matching (n = 54 per group), a longer OS was found for levetiracetam use during the whole duration of the standard chemoradiation protocol (hazard ratio 0.63; 95% CI 0.42–0.94; p = 0.023).
Discussion Levetiracetam use during the whole standard chemoradiation protocol possibly improves OS of patients with IDH wild-type glioblastoma. It should be considered in the antitumor strategy of future multicentric trials.
Classification of Evidence This study provides Class III evidence that in individuals with IDH wild-type glioblastoma, levetiracetam use throughout the duration of standard chemotherapy is associated with longer median OS.
Glossary
- AED=
- antiepileptic drug;
- aHR=
- adjusted hazard ratio;
- CI=
- confidence interval;
- HR=
- hazard ratio;
- IDH=
- isocitrate dehydrogenase;
- LevUse subgroup=
- levetiracetam use during the whole duration of the standard combined chemoradiation protocol (excluding the part time or never subgroups);
- MGMT=
- O6-methylguanine–DNA methyltransferase;
- OS=
- overall survival;
- RTOG-RPA=
- Radiation Therapy Oncology Group recursive partitioning analysis
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Class of Evidence: NPub.org/coe
- Received May 17, 2021.
- Accepted in final form October 15, 2021.
- © 2021 American Academy of Neurology
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- Author Response: Effect of Levetiracetam Use Duration on Overall Survival of Isocitrate Dehydrogenase Wild-Type Glioblastoma in Adults: An Observational Study
- Reader Response: Effect of Levetiracetam Use Duration on Overall Survival of Isocitrate Dehydrogenase Wild-Type Glioblastoma in Adults: An Observational Study
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