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.
Medulloblastoma
Methylation analysis
Prognostic stratification
Journal
Acta neuropathologica communications
ISSN: 2051-5960
Titre abrégé: Acta Neuropathol Commun
Pays: England
ID NLM: 101610673
Informations de publication
Date de publication:
25 09 2023
25 09 2023
Historique:
received:
30
07
2023
accepted:
08
09
2023
medline:
27
9
2023
pubmed:
26
9
2023
entrez:
25
9
2023
Statut:
epublish
Résumé
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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 37749662
doi: 10.1186/s40478-023-01652-4
pii: 10.1186/s40478-023-01652-4
pmc: PMC10521425
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
153Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
Références
J Clin Oncol. 2005 Aug 20;23(24):5511-9
pubmed: 16110011
J Neuropathol Exp Neurol. 2021 Jun 4;80(6):552-557
pubmed: 33990838
J Clin Oncol. 2013 Dec 10;31(35):4407-15
pubmed: 24190124
Childs Nerv Syst. 2023 Sep;39(9):2505-2507
pubmed: 37185696
J Clin Oncol. 2021 Aug 20;39(24):2685-2697
pubmed: 34110925
Lancet Oncol. 2018 Dec;19(12):1602-1616
pubmed: 30392813
J Clin Oncol. 2001 Aug 1;19(15):3470-6
pubmed: 11481352
J Clin Oncol. 2020 Feb 10;38(5):454-461
pubmed: 31774710
Pediatr Blood Cancer. 2020 Nov;67(11):e28572
pubmed: 32710713
Brain Pathol. 2021 May;31(3):e12943
pubmed: 33576087
J Clin Oncol. 2023 May 1;41(13):2323-2325
pubmed: 36753694
Acta Neuropathol. 2019 Aug;138(2):309-326
pubmed: 31076851
Acta Neuropathol. 2012 Apr;123(4):501-13
pubmed: 22139329
J Clin Oncol. 2021 Mar 1;39(7):822-835
pubmed: 33405951
Acta Neuropathol. 2012 Apr;123(4):473-84
pubmed: 22358457
Nature. 2018 Mar 22;555(7697):469-474
pubmed: 29539639