MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel

Aug 8, 2015Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

MGMT gene inactivation and treatment response in new glioblastoma patients receiving Gliadel

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Abstract

MGMT promoter methylation was found in 32.7% of 122 newly diagnosed glioblastoma patients treated with Gliadel.

Patients with MGMT methylation had a median overall survival of 13.5 months.
The median recurrence-free survival for patients with MGMT methylation was 9.4 months.
Elderly patients (over 70 years) with MGMT methylation had a median overall survival of 13.5 months, compared to 7.6 months for unmethylated patients.
In older patients, the median recurrence-free survival was 13.1 months for those with methylated MGMT versus 7.6 months for unmethylated MGMT.
MGMT methylation is associated with a 15% reduced mortality risk, although this was not statistically significant.

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We examined the relationship between the O(6)-methylguanine-methyltransferase (MGMT) methylation status and clinical outcomes in newly diagnosed glioblastoma multiforme (GBM) patients who were treated with Gliadel wafers (Eisai, Tokyo, Japan). MGMT promoter methylation has been associated with increased survival among patients with GBM who are treated with various alkylating agents. MGMT promoter methylation, in DNA from 122 of 160 newly diagnosed GBM patients treated with Gliadel, was determined by a quantitative methylation-specific polymerase chain reaction, and was correlated with overall survival (OS) and recurrence-free survival (RFS). The MGMT promoter was methylated in 40 (32.7%) of 122 patients. The median OS was 13.5 months (95% confidence interval [CI] 11.0-14.5) and RFS was 9.4 months (95% CI 7.8-10.2). After adjusting for age, Karnofsky performance score, extent of resection, temozolomide (TMZ) and radiation therapy (RT), the newly diagnosed GBM patients with MGMT methylation had a 15% reduced mortality risk, compared to patients with unmethylated MGMT (hazard ratio 0.85; 95% CI 0.56-1.31; p=0.46). The patients aged over 70 years with MGMT methylation had a significantly longer median OS of 13.5 months, compared to 7.6 months in patients with unmethylated MGMT (p=0.027). A significant difference was also found in older patients, with a median RFS of 13.1 versus 7.6 months for methylated and unmethylated MGMT groups, respectively (p=0.01). Methylation of the MGMT promoter in newly diagnosed GBM patients treated with Gliadel, RT and TMZ, was associated with significantly improved OS compared to the unmethylated population. In elderly patients, methylation of the MGMT promoter was associated with significantly better OS and RFS.

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MGMT inactivation and clinical response in newly diagnosed GBM patients treated with Gliadel

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