Journal of neurologyDec 7, 2016

Survival in untreatable glioblastoma varies with MGMT gene methylation

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

Methylation of the MGMT promoter was found in 30 out of 56 patients and is associated with better survival outcomes.

MGMT promoter methylation was linked to a median overall survival of 20.3 months compared to 7.3 months for unmethylated patients.
Patients with methylated MGMT promoters had a median progression-free survival of 15.0 months versus 6.1 months for those without methylation.
Methylation status correlated with higher treatment response rates and prolonged post-recurrence survival, with a median of 4.5 months compared to 1.4 months for unmethylated patients.
The findings indicate that MGMT promoter methylation status is a crucial factor for risk stratification in patients with unresectable glioblastoma.

Simplified

In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ → TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008. Last follow-up was performed in June 2016. MGMT promoter methylation was determined using methylation-specific PCR (MSP) and sodium bisulfite sequencing. Analyses were done by intention to treat. Prognostic factors were obtained from proportional hazard models. At the time of the final analysis 55 patients showed progressive disease and 53 patients had died. MGMT promoter was methylated (unmethylated) in 30 (26) patients. Methylation of the MGMT promoter was the strongest favorable predictor for overall survival (OS, median: 20.3 vs. 7.3 months, p < 0.001, HR 0.30, 95% CI 0.16-0.55), and PFS (median: 15.0 vs. 6.1 months, p < 0.001, HR 0.31, 95% CI 0.17-0.57) and was also associated with higher frequencies of treatment response and prolonged post-recurrence survival (PRS, median: 4.5 vs. 1.4 months, p < 0.002, HR 0.39, 95% CI 0.21-0.71). Knowledge of MGMT promoter methylation status is essential for patients' counseling, prognostic evaluation, and for the design of future trials dealing with unresectable glioblastomas.

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Survival in untreatable glioblastoma varies with MGMT gene methylation

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