Effect of Levetiracetam use duration on overall survival of isocitrate dehydrogenase wildtype glioblastoma in adults: an observational study

Autor: Edouard Dezamis, Gilles Huberfeld, Johan Pallud, Alessandro Moiraghi, Martine Gavaret, Frédéric Dhermain, Fabrice Chrétien, Marc Zanello, Eléonore Guinard, Pascale Varlet, Alexandre Roux, Catherine Oppenheim, Sophie Peeters
Přispěvatelé: GHU Paris Psychiatrie et Neurosciences, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [Los Angeles] (UCLA), University of California (UC), Institut Gustave Roussy (IGR), Département de radiothérapie [Gustave Roussy], Martinez Rico, Clara, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Adult
Oncology
medicine.medical_specialty
Levetiracetam
Methyltransferase
Adolescent
medicine.medical_treatment
[SDV.CAN]Life Sciences [q-bio]/Cancer
Cohort Studies
03 medical and health sciences
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
Internal medicine
medicine
Humans
10. No inequality
DNA Modification Methylases
Retrospective Studies
Chemotherapy
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Brain Neoplasms
business.industry
Proportional hazards model
Hazard ratio
DNA Methylation
Prognosis
Isocitrate Dehydrogenase
3. Good health
Survival Rate
DNA Repair Enzymes
Isocitrate dehydrogenase
030220 oncology & carcinogenesis
Observational study
Neurology (clinical)
Glioblastoma
business
030217 neurology & neurosurgery
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
medicine.drug
Cohort study
Zdroj: Neurology
Neurology, 2021, pp.10.1212/WNL.0000000000013005. ⟨10.1212/WNL.0000000000013005⟩
Neurology, American Academy of Neurology, 2021, pp.10.1212/WNL.0000000000013005. ⟨10.1212/WNL.0000000000013005⟩
ISSN: 0028-3878
1526-632X
Popis: Background and ObjectivesThe 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.MethodsIn 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.ResultsA 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).DiscussionLevetiracetam 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 EvidenceThis 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.
Databáze: OpenAIRE
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