Description:
<jats:title>Abstract</jats:title><jats:p>O<jats:sup>6</jats:sup>‐methylguanine‐DNA‐methyltransferase (<jats:italic>MGMT</jats:italic>) promoter methylation identifies a subpopulation of glioblastoma patients with more favorable prognosis and predicts a benefit from alkylating agent chemotherapy (CT). Little is known about its prevalence and clinical significance in older glioblastoma patients. We studied 233 glioblastoma patients aged 70 years or more (144 males, 89 females, median age: 74 years, range: 70.0–86.6 years), who were prospectively enrolled in the German Glioma Network, for <jats:italic>MGMT</jats:italic> promoter methylation by methylation‐specific PCR (MSP) in all patients and DNA pyrosequencing in 166 patients. <jats:italic>MGMT</jats:italic> data were correlated with patient outcome. Median progression‐free survival (PFS) was 4.8 months (95% CI: 4.3–5.3) and median overall survival (OS) was 7.7 months (95% CI: 6.3–9.0). <jats:italic>MGMT</jats:italic> promoter methylation was detected by MSP in 134 patients (57.5%). For the whole cohort, PFS was 5.2 <jats:italic>versus</jats:italic> 4.7 months (<jats:italic>p</jats:italic> = 0.207) and OS was 8.4 <jats:italic>versus</jats:italic> 6.4 months (<jats:italic>p</jats:italic> = 0.031) in patients with <jats:italic>versus</jats:italic> without <jats:italic>MGMT</jats:italic> promoter methylation. Patients with <jats:italic>MGMT</jats:italic> methylated tumors had longer PFS when treated with radiotherapy (RT) plus CT or CT alone compared to patients treated with RT alone. Patients with <jats:italic>MGMT</jats:italic> unmethylated tumors appeared to derive no survival benefit from CT, regardless of whether given at diagnosis together with RT or as a salvage treatment. Patients treated with RT plus CT or CT alone demonstrated longer OS when pyrosequencing revealed >25% <jats:italic>MGMT</jats:italic> methylated alleles. Taken together, <jats:italic>MGMT</jats:italic> promoter methylation may be a useful biomarker to stratify elderly glioblastoma patients for treatment with <jats:italic>versus</jats:italic> without alkylating agent CT.</jats:p>