TY - JOUR
T1 - Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation
T2 - a Japanese Pediatric Molecular Neuro-Oncology Group study
AU - Fukuoka, Kohei
AU - Kurihara, Jun
AU - Shofuda, Tomoko
AU - Kagawa, Naoki
AU - Yamasaki, Kai
AU - Ando, Ryo
AU - Ishida, Joji
AU - Kanamori, Masayuki
AU - Kawamura, Atsufumi
AU - Park, Young Soo
AU - Kiyotani, Chikako
AU - Akai, Takuya
AU - Keino, Dai
AU - Miyairi, Yosuke
AU - Sasaki, Atsushi
AU - Hirato, Junko
AU - Inoue, Takeshi
AU - Nakazawa, Atsuko
AU - Koh, Katsuyoshi
AU - Nishikawa, Ryo
AU - Date, Isao
AU - Nagane, Motoo
AU - Ichimura, Koichi
AU - Kanemura, Yonehiro
N1 - Publisher Copyright:
© 2023, BioMed Central Ltd., part of Springer Nature.
PY - 2023/12
Y1 - 2023/12
N2 - Background: One 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. Methods: We 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. Results: Among 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). Conclusion: Although 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.
AB - Background: One 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. Methods: We 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. Results: Among 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). Conclusion: Although 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.
KW - Medulloblastoma
KW - Methylation analysis
KW - Prognostic stratification
UR - http://www.scopus.com/inward/record.url?scp=85172176238&partnerID=8YFLogxK
U2 - 10.1186/s40478-023-01652-4
DO - 10.1186/s40478-023-01652-4
M3 - 学術論文
C2 - 37749662
AN - SCOPUS:85172176238
SN - 2051-5960
VL - 11
JO - Acta neuropathologica communications
JF - Acta neuropathologica communications
IS - 1
M1 - 153
ER -