title: Seizure reduction is a prognostic marker in low-grade glioma patients treated with temozolomide.
abstract: We aimed to analyze the value of seizure reduction and radiological response as prognostic markers of survival in patients with low-grade glioma (LGG) treated with temozolomide (TMZ) chemotherapy. We retrospectively reviewed adult patients with a progressive LGG and uncontrolled epilepsy in two hospitals (VUmc Amsterdam; MCH The Hague), who received chemotherapy with TMZ between 2002 and 2014. End points were a ≥50 % seizure reduction and MRI response 6, 12 and 18 months (mo) after the start of TMZ, and their relation with progression-free survival (PFS) and overall survival (OS). We identified 53 patients who met the inclusion criteria. Seizure reduction was an independent prognostic factor for both PFS (HR 0.38; 95 % CI 0.19-0.73; p = 0.004) and OS (HR 0.39; 95 % CI 0.18-0.85; p = 0.018) after 6mo, adjusting for age and histopathological diagnosis, as well as after 12 and 18mo. Patients with an objective radiological response showed a better OS (median 87.5mo; 95 % CI 62.0-112.9) than patients without a response (median 34.4mo; 95 % CI 26.1-42.6; p = 0.046) after 12mo. However, after 6 and 18mo OS was similar in patients with and without a response on MRI. Seizure reduction is an early and consistent prognostic marker for survival after treatment with TMZ, that seems to precede the radiological response. Therefore, seizure reduction may serve as a surrogate marker for tumor response.
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. j.a.f.koekkoek@lumc.nl.|Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands. j.a.f.koekkoek@lumc.nl.|Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. j.a.f.koekkoek@lumc.nl.
authors.forename: Johan A F
authors.initials: JA
authors.lastname: Koekkoek
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Linda
authors.initials: L
authors.lastname: Dirven
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Heimans
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Tjeerd J
authors.initials: TJ
authors.lastname: Postma
authors.affiliation: Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands.
authors.forename: Maaike J
authors.initials: MJ
authors.lastname: Vos
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Reijneveld
authors.affiliation: Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Neurology, Medical Center Haaglanden, The Hague, The Netherlands.|Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Martin J B
authors.initials: MJ
authors.lastname: Taphoorn
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012640:Seizures / Q000209:etiology* / Q000517:prevention & control*; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Chemotherapy; Glioma; Primary brain tumor; Seizures; Temozolomide