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Meta-Analysis
. 2014 Jan 13;9(1):e85102.
doi: 10.1371/journal.pone.0085102. eCollection 2014.

The predictive but not prognostic value of MGMT promoter methylation status in elderly glioblastoma patients: a meta-analysis

An-an Yin  1 , Lu-hua Zhang  1 , Jin-xiang Cheng  1 , Yu Dong  2 , Bo-lin Liu  1 , Ning Han  1 , Xiang Zhang  1
Affiliations
Meta-Analysis

The predictive but not prognostic value of MGMT promoter methylation status in elderly glioblastoma patients: a meta-analysis

An-an Yin et al. PLoS One. .

Abstract

Background: The clinical implication of O6-methylguanine-DNA methyltransferase (MGMT) promoter status is ill-defined in elderly glioblastoma patients. Here we report a meta-analysis to seek valid evidence for its clinical relevance in this subpopulation.

Methods: Literature were searched and reviewed in a systematic manner using the PubMed, EMBASE and Cochrane databases. Studies investigating the association between MGMT promoter status and survival data of elderly patients (≥65 years) were eligible for inclusion.

Results: Totally 16 studies were identified, with 13 studies included in the final analyses. The aggregate proportion of MGMT promoter methylation in elderly patients was 47% (95% confidence interval [CI]: 42-52%), which was similar to the value for younger patients. The analyses showed differential effects of MGMT status on overall survival (OS) of elderly patients according to assigned treatments: methylated vs. unmethylated: (1) temozolomide (TMZ)-containing therapies: hazard ratio [HR] 0.49, 95% CI 0.41-0.58; (2) TMZ-free therapies: HR 0.97, 95% CI 0.77-1.21. More importantly, a useful predictive value was observed by an interaction analysis: TMZ-containing therapies vs. RT alone: (1) methylated tumors: HR 0.48, 95% CI 0.36-0.65; (2) unmethylated tumors: HR 1.14; 95% CI 0.90-1.44.

Conclusion: The meta-analysis reports an age-independent presence of MGMT promoter methylation. More importantly, the study encouraged routine testing of MGMT promoter status especially in elderly glioblastoma patients by indicating a direct linkage between biomarker test and individual treatment decision. Future studies are needed to justify the mandatory testing in younger patients.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Flow diagram of study selection.
Figure 2
Figure 2. The aggregate estimate for the frequency of MGMT promoter methylation in elderly glioblastoma patients.
Figure 3
Figure 3. Forest plot of comparison.
outcome: OS; comparison: methylated versus unmethylated: A. TMZ-free therapies; B. TMZ-containing therapies. (tmz = temozolomide; rt = radiotherapy; sc = supportive care; crt = chemoradiotherapy).
Figure 4
Figure 4. Forest plot of comparison.
outcome: OS; comparison: TMZ-containing therapies versus TMZ-free therapies: A. methylated tumors; B. unmethylated tumors.
See this image and copyright information in PMC

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