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

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.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Progression-free survival for the patients randomly assigned to (A) radiotherapy and for the patients randomly assigned to radiotherapy followed by (B) adjuvant procarbazine, lomustine, and vincristine depending on methylation status (unmethylated: O6-methylguanine-methyltransferase averaged [MGMTav] ≤ 0.25, methylated: MGMTav > 0.25). O, number of observed events; N, sample size.

Fig 2.

Overall survival for the patients randomly assigned to (A) radiotherapy and for the patients randomly assigned to radiotherapy followed by (B) adjuvant procarbazine, lomustine, and vincristine depending on methylation status (unmethylated: O6-methylguanine-methyltransferase averaged [MGMTav] ≤ 0.25, methylated: MGMTav > 0.25). O, number of observed events; N, sample size.