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.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuro-Oncology and Pathology, Daniel den Hoed Cancer Center and Erasmus University Medical Center, Rotterdam, the Netherlands. m.vandenbent@erasmusmc.nl
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
authors.forename: Hendrikus J
authors.initials: HJ
authors.lastname: Dubbink
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Cathleen R
authors.initials: CR
authors.lastname: van der Lee-Haarloo
authors.forename: Monika
authors.initials: M
authors.lastname: Hegi
authors.forename: Judith W M
authors.initials: JW
authors.lastname: Jeuken
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ibdaih
authors.forename: Alba A
authors.initials: AA
authors.lastname: Brandes
authors.forename: Martin J B
authors.initials: MJ
authors.lastname: Taphoorn
authors.forename: Marc
authors.initials: M
authors.lastname: Frenay
authors.forename: Denis
authors.initials: D
authors.lastname: Lacombe
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001254:Astrocytoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D018572:Disease-Free Survival; D005060:Europe / Q000453:epidemiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008130:Lomustine / Q000008:administration & dosage; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D016133:Polymerase Chain Reaction / Q000379:methods; D011344:Procarbazine / Q000008:administration & dosage; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D025521:Tumor Suppressor Proteins; D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes