MGMT methylation may benefit overall survival in patients with moderately vascularized glioblastomas

Objectives To assess the combined role of tumor vascularity, estimated from perfusion MRI, andMGMTmethylation status on overall survival (OS) in patients with glioblastoma. Methods A multicentric international dataset including 96 patients from NCT03439332 clinical study were used to study the prognostic relationships betweenMGMTand perfusion markers. Relative cerebral blood volume (rCBV) in the most vascularized tumor regions was automatically obtained from preoperative MRIs using ONCOhabitats online analysis service. Cox survival regression models and stratification strategies were conducted to define a subpopulation that is particularly favored byMGMTmethylation in terms of OS. Results rCBV distributions did not differ significantly (p > 0.05) in the methylated and the non-methylated subpopulations. In patients with moderately vascularized tumors (rCBV < 10.73),MGMTmethylation was a positive predictive factor for OS (HR = 2.73,p = 0.003, AUC = 0.70). In patients with highly vascularized tumors (rCBV > 10.73), however, there was no significant effect ofMGMTmethylation (HR = 1.72,p = 0.10, AUC = 0.56). Conclusions Our results indicate the existence of complementary prognostic information provided byMGMTmethylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most fromMGMTmethylation. Not considering this information may lead to bias in the interpretation of clinical studies.

Automated summary

The study found that MGMT methylation and rCBV provide complementary prognostic information, with MGMT methylation being a positive predictive factor for OS in patients with moderately vascularized tumors, but not showing significant effects in patients with highly vascularized tumors.