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


CONCLUSIONS
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.
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, The People's Republic of China.
An-an
AA
Yin
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, The People's Republic of China.
Lu-hua
LH
Zhang
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, The People's Republic of China.
Jin-xiang
JX
Cheng
Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, The People's Republic of China.
Yu
Y
Dong
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, The People's Republic of China.
Bo-lin
BL
Liu
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, The People's Republic of China.
Ning
N
Han
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, The People's Republic of China.
Xiang
X
Zhang
D000368:Aged; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D017594:Publication Bias; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes