[HTML][HTML] The Predictive but Not Prognostic Value of MGMT Promoter Methylation Status in Elderly Glioblastoma Patients: A Meta-Analysis

A Yin, L Zhang, J Cheng, Y Dong, B Liu, N Han… - PLoS …, 2014 - journals.plos.org
A Yin, L Zhang, J Cheng, Y Dong, B Liu, N Han, X Zhang
PLoS One, 2014journals.plos.org
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 …
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.
PLOS