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

Author:

Sanada Takahiro1,Kinoshita Manabu12ORCID,Sasaki Takahiro34,Yamamoto Shota15,Fujikawa Seiya16,Fukuyama Shusei1,Hayashi Nobuhide4,Fukai Junya3,Okita Yoshiko78,Nonaka Masahiro89,Uda Takehiro10,Arita Hideyuki27,Mori Kanji11,Ishibashi Kenichi12,Takano Koji213,Nishida Namiko14,Shofuda Tomoko15,Yoshioka Ema15,Kanematsu Daisuke15,Tanino Mishie16,Kodama Yoshinori81517,Mano Masayuki18,Kanemura Yonehiro17

Affiliation:

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

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.

Funder

Japan Society for the Promotion of Science

Japan Agency for Medical Research and Development

Takeda Science Foundation

Okawa Foundation for Information and Telecommunications

Akiyama Life Science Foundation

Publisher

Oxford University Press (OUP)

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