Prediction of MGMT promotor methylation status in glioblastoma by contrast-enhanced T1-weighted intensity image

Takahiro Sanada; Manabu Kinoshita; Takahiro Sasaki; Shota Yamamoto; Seiya Fujikawa; Shusei Fukuyama; Nobuhide Hayashi; Junya Fukai; Yoshiko Okita; Masahiro Nonaka; Takehiro Uda; Hideyuki Arita; Kanji Mori; Kenichi Ishibashi; Koji Takano; Namiko Nishida; Tomoko Shofuda; Ema Yoshioka; Daisuke Kanematsu; Mishie Tanino; Yoshinori Kodama; Masayuki Mano; Yonehiro Kanemura

doi:10.1093/noajnl/vdae016

Prediction of MGMT promotor methylation status in glioblastoma by contrast-enhanced T1-weighted intensity image

Neurooncol Adv. 2024 Feb 1;6(1):vdae016. doi: 10.1093/noajnl/vdae016. eCollection 2024 Jan-Dec.

Authors

Takahiro Sanada¹, Manabu Kinoshita^{1

2}, Takahiro Sasaki^{3

4}, Shota Yamamoto^{1

5}, Seiya Fujikawa^{1

6}, Shusei Fukuyama¹, Nobuhide Hayashi⁴, Junya Fukai³, Yoshiko Okita^{7

8}, Masahiro Nonaka^{8

9}, Takehiro Uda¹⁰, Hideyuki Arita^{2

7}, Kanji Mori¹¹, Kenichi Ishibashi¹², Koji Takano^{2

13}, Namiko Nishida¹⁴, Tomoko Shofuda¹⁵, Ema Yoshioka¹⁵, Daisuke Kanematsu¹⁵, Mishie Tanino¹⁶, Yoshinori Kodama^{8

15

17}, Masayuki Mano¹⁸, Yonehiro Kanemura¹⁷

Affiliations

¹ Department of Neurosurgery, Asahikawa Medical University, Asahikawa, Japan.
² Department of Neurosurgery, Osaka International Cancer Institute, Osaka, Japan.
³ Department of Neurological Surgery, Wakayama Medical University School of Medicine, Wakayama, Japan.
⁴ Department of Neurosurgery, Wakayama Rosai Hospital, Wakayama, Japan.
⁵ Department of Neurosurgery, Osaka General Medical Center, Osaka, Japan.
⁶ Department of Neurosurgery, Japanese Red Cross Kitami Hospital, Kitami, Japan.
⁷ Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan.
⁸ Department of Neurosurgery, NHO Osaka National Hospital, Osaka, Japan.
⁹ Department of Neurosurgery, Kansai Medical University, Hirakata, Japan.
¹⁰ Department of Neurosurgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
¹¹ Department of Neurosurgery, Yao Municipal Hospital, Yao, Japan.
¹² Department of Neurosurgery, Osaka City General Hospital, Osaka, Japan.
¹³ Department of Neurosurgery, Toyonaka Municipal Hospital, Toyonaka, Japan.
¹⁴ Department of Neurosurgery, Tazuke Kofukai Foundation, Medical Research Institute, Kitano Hospital, Osaka, Japan.
¹⁵ Department of Biomedical Research and Innovation, Institute for Clinical Research, NHO Osaka National Hospital, Osaka, Japan.
¹⁶ Department of Diagnostic Pathology, Asahikawa Medical University Hospital, Asahikawa, Japan.
¹⁷ Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka, Japan.
¹⁸ Department of Central Laboratory and Surgical Pathology, NHO Osaka National Hospital, Osaka, Japan.

Abstract

Background: The study aims to explore MRI phenotypes that predict glioblastoma's (GBM) methylation status of the promoter region of MGMT gene (pMGMT) by qualitatively assessing contrast-enhanced T1-weighted intensity images.

Methods: A total of 193 histologically and molecularly confirmed GBMs at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KANSAI) were used as an exploratory cohort. From the Cancer Imaging Archive/Cancer Genome Atlas (TCGA) 93 patients were used as validation cohorts. "Thickened structure" was defined as the solid tumor component presenting circumferential extension or occupying >50% of the tumor volume. "Methylated contrast phenotype" was defined as indistinct enhancing circumferential border, heterogenous enhancement, or nodular enhancement. Inter-rater agreement was assessed, followed by an investigation of the relationship between radiological findings and pMGMT methylation status.

Results: Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the exploratory and 0.55 for the validation cohort, and for "Methylated contrast phenotype," 0.30 and 0.39, respectively. The imaging feature, the presence of "Thickened structure" and absence of "Methylated contrast phenotype," was significantly predictive of pMGMT unmethylation both for the exploratory (p = .015, odds ratio = 2.44) and for the validation cohort (p = .006, odds ratio = 7.83). The sensitivities and specificities of the imaging feature, the presence of "Thickened structure," and the absence of "Methylated contrast phenotype" for predicting pMGMT unmethylation were 0.29 and 0.86 for the exploratory and 0.25 and 0.96 for the validation cohort.

Conclusions: The present study showed that qualitative assessment of contrast-enhanced T1-weighted intensity images helps predict GBM's pMGMT methylation status.

Keywords: MGMT; MGMT promoter methylation; glioblastoma; magnetic resonance image; radiogenomics.