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

Abstract

Objectives To assess the combined role of tumor vascularity, estimated from perfusion MRI, and MGMT methylation 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 between MGMT and 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 by MGMT methylation 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), MGMT methylation 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 of MGMT methylation (HR = 1.72, p = 0.10, AUC = 0.56). Conclusions Our results indicate the existence of complementary prognostic information provided by MGMT methylation and rCBV. Perfusion markers could identify a subpopulation of patients who will benefit the most from MGMT methylation. Not considering this information may lead to bias in the interpretation of clinical studies. Key Points • MRI perfusion provides complementary prognostic information to MGMT methylation. • MGMT methylation improves prognosis in glioblastoma patients with moderate vascular profile. • Failure to consider these relations may lead to bias in the interpretation of clinical studies.

The Prognostic Value of Preoperative Systemic Inflammatory Response Index (SIRI) in Patients With High-Grade Glioma and the Establishment of a Nomogram

“…Our results confirmed the known influencing factors for OS of high-grade gliomas, such as age, histological type, number of gliomas, extent of resection, MGMT methylation status, etc. (30)(31)(32)(33)(34)(35). For the IDH mutation status, we only observed trends related to OS benefits.…”

Lack of benefit of temozolomide for MGMT methylated patients with high vascular glioblastoma: a confirmatory study

“…With the present study we aimed to evaluate the lack of benefit of temozolomide for MGMT methylated patients with high vascular glioblastomas, since previous results published in [47] concluded that the combined effect of MGMT methylation and moderate vascularity of the tumor causes a benefit in glioblastoma patient overall survival. In addition, the previously proposed threshold has been validated and we propose an upload to be more generalizable in future studies, since it has been calculated with data from 214 patients.…”

“…To validate the combined effect of MGMT methylation and vascularity, we used the maximum relative cerebral blood volume (rCBVmax) calculated in the HAT habitat, since it is shown to be the most relevant prognostic marker calculated with the HTS method [50, 52, 53] and it was used in the previous study to define the vascular groups [47].…”

“…Table 2 includes the results of the Uniparametric cox regression analyses for the entire cohort and for the moderate-and high-vascular groups, generated with different proposed cut off thresholds: (I) the threshold proposed in the preliminary study [47], (II) the median HAT rCBVmax of the current study cohort and (III) the threshold calculated with the combination of both cohorts (n = 214 patients). The Uniparametric Cox results show a significant association between the MGMT methylation status and patient overall survival (OS) for the entire cohort of 123 patients.…”

Radiology in the lead: towards radiological profiling for precision medicine in glioblastoma patients? Editorial comment on Glioblastoma patients with a moderate vascular profile benefit the most from MGMT methylation

“…Published in this issue, a study by Fuster-Garcia and colleagues, however, has found that the prognostic impact of MGMT methylation might be influenced by the tumor's vascularity [5]. In their multicenter retrospective study among 96 GBM patients, the authors have demonstrated that there is a beneficial effect of MGMT methylation in tumors with moderately vascular status only.…”