Abstract

Abstract PURPOSE The study aims to explore MRI phenotypes that predict the methylation status of the promoter region of MGMT (pMGMT) in glioblastoma. MATERIALS AND METHODS 202 histologically and molecularly confirmed glioblastoma patients (pMGMT methylated: 103, unmethylated: 99) at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KNBTG) were used as a test cohort. 104 patients from the Cancer Imaging Archive (TCIA) / Cancer Genome Atlas (TCGA) dataset (pMGMT methylated: 103, unmethylated: 99) were used as a validation cohort. "Thickened structure" was defined when the solid component of the tumor had either a circumferential extension or occupied more than 50% of the entire volume of the tumor. "Methylated contrast phenotype" was defined by imaging findings with one of the following three features: indistinct enhancing circumferential border, heterogenous enhancement, and nodular enhancement. The inter-rater agreement between three independent blinded raters was first evaluated, and then the relationship between the image findings and pMGMT methylation status was investigated. RESULTS Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the KNBTG cohort and 0.56 for the TCIA cohort and for " Methylated contrast phenotype", 0.32 and 0.35, respectively. The odds ratio of "Methylated contrast phenotype" detecting pMGMT hypermethylation was 2.4 (p = 0.003) for the KNBTG cohort. The odds ratio of "Methylated contrast phenotype" associated with pMGMT methylation was 4.5 (p = 0.001) for those restricted to tumors presenting a "Thickened structure". The odds ratio for pMGMT methylation detected by "Methylated contrast phenotype" was 3.4 (p = 0.005) for the TCIA cohort. It was 7.1 (p = 0.009) when restricting to tumors presenting a "Thickened structure". CONCLUSION Glioblastoma showing both a "Thickened structure" structure and "Methylated contrast phenotype" is associated with pMGMT methylation, which may be a clinically useful imaging feature.

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