Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation: a Japanese Pediatric Molecular Neuro-Oncology Group study

Acta Neuropathologica Communications

Research

Chikako Kiyotani¹  Tomoko Shofuda²  Yonehiro Kanemura²  Koichi Ichimura³  Atsuko Nakazawa⁴  Katsuyoshi Koh⁵  Kohei Fukuoka⁵  Ryo Nishikawa⁶  Isao Date⁷  Joji Ishida⁷  Ryo Ando⁸  Atsufumi Kawamura⁹  Motoo Nagane^1,10  Yosuke Miyairi^1,11  Young-Soo Park^1,12  Naoki Kagawa^1,13  Jun Kurihara^1,14  Masayuki Kanamori^1,15  Takeshi Inoue^1,16  Junko Hirato^1,17  Atsushi Sasaki^1,18  Kai Yamasaki^1,19  Takuya Akai^2,20  Dai Keino^2,21 

[1] Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan;Department of Biomedical Research and Innovation, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan;Department of Brain Disease Translational Research, Juntendo University Faculty of Medicine, Tokyo, Japan;Department of Clinical Research, Saitama Children’s Medical Center, Saitama, Japan;Department of Hematology/Oncology, Saitama Children’s Medical Center, 1-2, Shin-Toshin, 330-8777, Saitama, Japan;Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan;Department of Neurological Surgery, Okayama University Graduate School, Okayama, Japan;Department of Neurosurgery, Chiba Children’s Hospital, Chiba, Japan;Department of Neurosurgery, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan;Department of Neurosurgery, Kyorin University Faculty of Medicine, Mitaka, Japan;Department of Neurosurgery, Nagano Children’s Hospital, Azumino, Japan;Department of Neurosurgery, Nara Medical University, Kashihara, Japan;Department of Neurosurgery, Osaka University Graduate School of Medicine, Osaka, Japan;Department of Neurosurgery, Saitama Children’s Medical Center, Saitama, Japan;Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan;Department of Pathology, Osaka City General Hospital, Osaka, Japan;Department of Pathology, Public Tomioka General Hospital, Gunma, Japan;Department of Pathology, Saitama Medical University, Saitama, Japan;Department of Pediatric Hematology and Oncology, Osaka City General Hospital, Osaka, Japan;Departments of Neurosurgery, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan;Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Yokohama, Japan;

关键词: Medulloblastoma;    Methylation analysis;    Prognostic stratification;   

DOI  :  10.1186/s40478-023-01652-4

 received in 2023-07-30, accepted in 2023-09-08,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundOne of the most significant challenges in patients with medulloblastoma is reducing the dose of craniospinal irradiation (CSI) to minimize neurological sequelae in survivors. Molecular characterization of patients receiving lower than standard dose of CSI therapy is important to facilitate further reduction of treatment burden.MethodsWe conducted DNA methylation analysis using an Illumina Methylation EPIC array to investigate molecular prognostic markers in 38 patients with medulloblastoma who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with reduced-dose CSI.ResultsAmong the patients, 23 were classified as having a standard-risk and 15 as high-risk according to the classic classification based on tumor resection rate and presence of metastasis, respectively. The median follow-up period was 71.5 months (12.0–231.0). The median CSI dose was 18 Gy (15.0–24.0) in both groups, and 5 patients in the high-risk group received a CSI dose of 18.0 Gy. Molecular subgrouping revealed that the standard-risk cohort included 5 WNT, 2 SHH, and 16 Group 3/4 cases; all 15 patients in the high-risk cohort had Group 3/4 medulloblastoma. Among the patients with Group 3/4 medulloblastoma, 9 of the 31 Group 3/4 cases were subclassified as subclass II, III, and V, which were known to an association with poor prognosis according to the novel subtyping among the subgroups. Patients with poor prognostic subtype showed worse prognosis than that of others (5-year progression survival rate 90.4% vs. 22.2%; p < 0.0001). The result was replicated in the multivariate analysis (hazard ratio12.77, 95% confidence interval for hazard ratio 2.38–99.21, p value 0.0026 for progression-free survival, hazard ratio 5.02, 95% confidence interval for hazard ratio 1.03–29.11, p value 0.044 for overall survival).ConclusionAlthough these findings require validation in a larger cohort, the present findings suggest that novel subtyping of Group 3/4 medulloblastoma may be a promising prognostic biomarker even among patients treated with lower-dose CSI than standard treatment.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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