1. MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma
- Author
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D Sartenaer, S Califice, Bart Neyns, J. De Greve, Peter In 'T Veld, Lionel D'Hondt, K. Bierau, Raphael Sciot, Theo Strauven, Eric Joossens, Johan Menten, Cristo Chaskis, C. Svensson, Alex Michotte, Jan Sadones, Supporting clinical sciences, Pathology, Anatomy, Pathological Anatomy, and Laboratory of Molecular and Medical Oncology
- Subjects
Male ,Cancer Research ,Pathology ,Methyltransferase ,Kaplan-Meier Estimate ,EXTENDED DOSING ,O-6-METHYLGUANINE-DNA ,RECURRENT ,Promoter Regions, Genetic ,Aged, 80 and over ,LOW-GRADE GLIOMAS ,DNA-repair ,Brain Neoplasms ,Methylation ,Middle Aged ,Prognosis ,MALIGNANT GLIOMA ,Dacarbazine ,Survival Rate ,1ST RELAPSE ,Oncology ,DNA methylation ,REPAIR GENE MGMT ,Female ,MGMT ,PHASE-II TRIAL ,high-grade glioma ,medicine.drug ,Adult ,medicine.medical_specialty ,DNA repair ,Astrocytoma ,O(6)-Methylguanine-DNA Methyltransferase ,Young Adult ,medicine ,Temozolomide ,Humans ,Survival rate ,neoplasms ,Antineoplastic Agents, Alkylating ,Aged ,Retrospective Studies ,business.industry ,O-6-methylguanine-DNA methyltransferase ,DNA Methylation ,medicine.disease ,digestive system diseases ,PROGOSTIC-FACTORS ,Cancer research ,METHYLTRANSFERASE ,Neoplasm Recurrence, Local ,business ,Glioblastoma ,Anaplastic astrocytoma - Abstract
To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma.A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence.A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p=0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma.MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.
- Published
- 2008