MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951.

Details

Serval ID
serval:BIB_761A9BF97C5B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951.
Journal
Journal of Clinical Oncology
Author(s)
van den Bent M.J., Dubbink H.J., Sanson M., van der Lee-Haarloo C.R., Hegi M., Jeuken J.W., Ibdaih A., Brandes A.A., Taphoorn M.J., Frenay M., Lacombe D., Gorlia T., Dinjens W.N., Kros J.M.
ISSN
1527-7755[electronic]
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
27
Number
35
Pages
5881-6
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Randomized Controlled Trial Publication Status: ppublish
Abstract
PURPOSE: O6-methylguanine-methyltransferase (MGMT) promoter methylation has been shown to predict survival of patients with glioblastomas if temozolomide is added to radiotherapy (RT). It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT).
PATIENTS AND METHODS: In the European Organisation for the Research and Treatment of Cancer study 26951, 368 patients with AOT were randomly assigned to either RT alone or to RT followed by adjuvant PCV. From 165 patients of this study, formalin-fixed, paraffin-embedded tumor tissue was available for MGMT promoter methylation analysis. This was investigated with methylation specific multiplex ligation-dependent probe amplification.
RESULTS: In 152 cases, an MGMT result was obtained, in 121 (80%) cases MGMT promoter methylation was observed. Methylation strongly correlated with combined loss of chromosome 1p and 19q loss (P = .00043). In multivariate analysis, MGMT promoter methylation, 1p/19q codeletion, tumor necrosis, and extent of resection were independent prognostic factors. The prognostic significance of MGMT promoter methylation was equally strong in the RT arm and the RT/PCV arm for both progression-free survival and overall survival. In tumors diagnosed at central pathology review as glioblastoma, no prognostic effect of MGMT promoter methylation was observed.
CONCLUSION: In this study, on patients with AOT MGMT promoter methylation was of prognostic significance and did not have predictive significance for outcome to adjuvant PCV chemotherapy. The biologic effect of MGMT promoter methylation or pathogenetic features associated with MGMT promoter methylation may be different for AOT compared with glioblastoma.
Keywords
Antineoplastic Combined Chemotherapy Protocols/administration & dosage, Astrocytoma/drug therapy, Astrocytoma/genetics, Astrocytoma/</QualifierName> <QualifierName MajorTopicYN="N">, Brain Neoplasms/drug therapy, Brain Neoplasms/genetics, Chemotherapy, Adjuvant, Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, CpG Islands, DNA Methylation, DNA Modification Methylases/genetics, DNA Repair Enzymes/genetics, Disease-Free Survival, Europe/epidemiology, Gene Expression Regulation, Neoplastic, Humans, Kaplan-Meiers Estimate, Lomustine/administration & dosage, Middle Aged, Oligodendroglioma/drug therapy, Oligodendroglioma/genetics, Polymerase Chain Reaction/methods, Procarbazine/administration & dosage, Promoter Regions, Genetic, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Tumor Suppressor Proteins/genetics, Vincristine/administration & dosage
Pubmed
Web of science
Create date
11/11/2009 18:34
Last modification date
20/08/2019 14:33
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