Abstract
Background
MGMT methylation may enhance the response to temozolomide and has been associated with improved survival in glioblastoma (GBM). Literature data do no clarify which is the clinical role of different grades of methylation in GBM patients with gross total resection (GTR) and concomitant chemio e radiotherapy.
The aim of our study is to analyze the relationship between MGMT methylation levels in tumors of patients diagnosed with GBM IDH wild type undergoing “gold standard therapy”, and the overall survival (OS).
Material and Methods
We collected data from 69 patients with GBM (WHO grade IV, IDH wild type, age 21–75 years old median 61, Karnoski >70) admitted in the Neurosurgical Unit, Ospedale Maggiore Policlinico, Milan, Italy and underwent GTR, from January 2005 to December 2016.MGMT promoter methylation status was analyzed by pyrosequencing technology.Patients were divided into 5 groups according to cut-off levels of MGMT methylation status: group 1 MGMT 5%, group 2 MGMT 10%, group 3 MGMT 15%, groups 4 MGMT 20%, group 5 MGMT 25%. Kaplan-Meier survival curves were obtained and compared between MGMT methylation status, through Log-rank test.
Results
A positive correlation between OS and increased level of MGMT methylation status was observed in all groups. Median OS was 16 month in patients with MGMT levels greater than 10% and 13 months in MGMT inferior to 10% (p=0,003).
Conclusion
Our study confirmed that MGMT methylation status has a prognostic value in patients undergoing “gold standard therapy” and with positive prognostic factors (KPS >70, Age > 70; GTR, concomitant chemio e radiotherapy and adjuvant cycles of temozolomide). A cut-off of 10% in the MGMT methylation could be used to stratify cases with MGMT methylation into two subclasses with different prognosis. Further studies are needed to establish further clinical role and cut-off values of MGMT levels in patients with primary GBM.