Topographical Mapping of 436 Newly Diagnosed IDH Wildtype Glioblastoma With vs. Without MGMT Promoter Methylation.

Fatih Incekara,Stefan Klein,Geert Lycklama,Johan M Kros,Arnaud J P E Vincent,Peggy N Atmodimedjo,Sebastian R Van Der Voort,Rishi Nandoe Tewarie,Marion Smits,Martin Van Den Bent,Hendrikus J Dubbink

doi:10.3389/fonc.2020.00596

Abstract

Introduction: O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. There are conflicting reports about a differential topographical distribution of glioblastoma with vs. without MGMT promoter methylation, possibly caused by molecular heterogeneity in glioblastoma populations. We initiated this study to re-evaluate the topographical distribution of glioblastoma with vs. without MGMT promoter methylation in light of the updated WHO 2016 classification.Methods: Preoperative T2-weighted/FLAIR and postcontrast T1-weighted MRI scans of patients aged 18 year or older with IDH wildtype glioblastoma were collected. Tumors were semi-automatically segmented, and the topographical distribution between glioblastoma with vs. without MGMT promoter methylation was visualized using frequency heatmaps. Then, voxel-wise differences were analyzed using permutation testing with Threshold Free Cluster Enhancement.Results: Four hundred thirty-six IDH wildtype glioblastoma patients were included; 211 with and 225 without MGMT promoter methylation. Visual examination suggested that when compared with MGMT unmethylated glioblastoma, MGMT methylated glioblastoma were more frequently located near bifrontal and left occipital periventricular area and less frequently near the right occipital periventricular area. Statistical analyses, however, showed no significant difference in topographical distribution between MGMT methylated vs. MGMT unmethylated glioblastoma.Conclusions: This study re-evaluated the topographical distribution of MGMT promoter methylation in 436 newly diagnosed IDH wildtype glioblastoma, which is the largest homogenous IDH wildtype glioblastoma population to date. There was no statistically significant difference in anatomical localization between MGMT methylated vs. unmethylated IDH wildtype glioblastoma.

Highlights

O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma
This study voxel-wise analyzed postcontrast T1-weighted and T2-weighted/fluid-attenuated inversion recovery (FLAIR) heatmaps and showed that there was no statistically significant difference in anatomical localization between MGMT methylated vs. unmethylated IDH wildtype glioblastoma
In contrast to these findings, there are studies that found the reverse pattern of hemispheric lateralization, in which glioblastoma with MGMT methylation were located more frequently in the right hemisphere, while those without MGMT methylation lateralized to the left hemisphere [6]

Summary

Introduction

O6-methylguanine-methyltransferase (MGMT) promoter methylation and isocitrate dehydrogenase (IDH) mutation status are important prognostic factors for patients with glioblastoma. Patients with glioblastoma have a poor prognosis with a median overall survival of 15 months, despite standard of care consisting of safe, and maximal surgical resection followed by chemoand/or radiotherapy [1]. This prognosis varies based on factors such as age, Karnofsky Performance Status, extent of resection, and molecular markers, in particular isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-methyltransferase (MGMT) promoter methylation status [2]. MGMT is methylated in ∼50% of patients with newly diagnosed glioblastoma [3]

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Results

Conclusion