Abstract
BACKGROUND: Previous studies have identified that the silencing of O6-methylguanine-DNA methyltransferase (MGMT) via methylation of its promoter region renders Glioblastoma Multiforme (GBM) more sensitive to Temozolomide, improving patients’ prognoses. In this study, we seek to explore and confirm this relationship in the patient population of NHS Tayside, as well as determine whether the level of MGMT methylation has a correlation with overall and progression free survival. PROCEDURE: A retrospective study involving 27 patients with GBM treated at NHS Tayside between 2012 and 2016 was carried out. Data regarding patient overall survival, progression free survival, treatment received, methylation status and percentage methylation was obtained through the patients’ case files. The relationship between MGMT status/percentage and patient outcomes was examined. RESULTS:14 patients out of 27 patients were MGMT methylation positive (defined as MGMT methylation status of 8.7% and above). Irrespective of MGMT methylation status, all patients were commenced on TMZ chemotherapy with the exception of 3 in the MGMT methylation negative arm and 1 in the MGMT methylation positive arm due to palliative reasons. The average overall survival time for patients with positive MGMT methylation was 17 months 24 days, as compared to 8 months 23 days for the 13 patients who were un-methylated. Average progression free survival was also significantly longer for MGMT methylation positive patients (15 months 13 days) compared to methylation negative patients (7 months and 6 days). Above the threshold for positive MGMT methylation (8.7%), there was no correlation between MGMT levels with patient overall survival and progression free survival. CONCLUSIONS: In this study, there is a clear benefit shown between MGMT methylation status and patient outcome, with no correlation between methylation levels and positive outcomes above the accepted threshold. These data further confirm the validity of MGMT methylation as a prognostic factor for survival in patients with GBM in a non-trial population. This study also further validates the current threshold set (8.7%) for positive methylation status to be significant for patient prognostication.