Journal of Neuro-Oncology

, Volume 105, Issue 2, pp 325–335 | Cite as

Prognostic and predictive value of epigenetic silencing of MGMT in patients with high grade gliomas: a systematic review and meta-analysis

  • Robert A. Olson
  • Priscilla K. Brastianos
  • David A. Palma
Clinical Study – Patient Study

Abstract

Epigenetic silencing of the O6-methylguanine-DNA methyltransferase (MGMT) gene is associated with improved survival in patients with high-grade gliomas (HGG), with varying estimates of magnitude. The objective of this meta-analysis is to determine the prognostic value of MGMT silencing, and assess its predictive value by treatment type. MEDLINE and EMBASE databases were searched for studies relating to gliomas and MGMT. Studies reporting overall survival (OS) by MGMT status in patients with HGG were considered potentially eligible. We excluded studies that did not control for potential confounding variables. A meta-analysis of studies was performed via random-effects modelling. Subgroup meta-analyses by treatment were performed according to a priori hypotheses. Twenty studies were ultimately eligible, including 2,018 patients. In the pooled analysis, MGMT silencing was associated with improved OS (HR = 0.436; 95% CI: 0.333–0.571; P < 0.001). The prognostic utility of MGMT status varies significantly by treatment type (P = 0.001): the HR for OS for MGMT silenced tumors is 0.190 (0.047–0.770), 0.403 (0.282–0.576), 0.743 (0.579–0.954), and 1.070 (0.722–1.585) for studies using surgery plus the addition of either: chemotherapy (CT), chemoradiotherapy (CRT), radiotherapy (RT), and nothing (surgery alone), respectively. Epigenetic silencing of MGMT is associated with markedly improved survival in patients with HGG who receive adjuvant therapy. MGMT silencing serves as a predictive marker, with the largest benefit seen in patients receiving CT as a component of adjuvant treatment, an intermediate benefit in patients receiving adjuvant RT, and no evidence to support benefit in those receiving surgery alone.

Keywords

MGMT Meta-analysis Predictive markers Prognostic markers High-grade glioma 

Notes

Acknowledgments

The authors would like to thank Dr. Michael Stoto at the Harvard School of Public Health for his instruction and constructive feedback on this manuscript.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Robert A. Olson
    • 1
    • 2
  • Priscilla K. Brastianos
    • 2
    • 3
    • 4
  • David A. Palma
    • 2
    • 5
  1. 1.Centre for the North, Department of Radiation OncologyUniversity of British Columbia and British Columbia Cancer AgencyVancouverCanada
  2. 2.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  3. 3.Department of Medical OncologyHarvard Medical School and Dana Farber/Brigham and Women’s Cancer CenterBostonUSA
  4. 4.Department of Hematology and OncologyMassachusetts General Hospital Cancer CenterBostonUSA
  5. 5.Division of Radiation OncologyUniversity of Western Ontario and London Regional Cancer ProgramLondonCanada

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