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Lookup NU author(s): Professor Simon BaileyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. Background. We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, and MYC/MYCN amplification. Methods. Patients over 3 years old received, after surgery, staging and histo-biological analysis, sequential high-dose-methotrexate(HD-MTX), high-dose-etoposide(HD-VP16), high-dose-cyclophosphamide(HD-Cyclo), and high-dose-carboplatin(HD-Carbo). Hyperfractionated-accelerated-radiotherapy–craniospinal(HART-CSI), administered twice daily 1.3 Gy-fractions reached a total dose tailored to the patients’ age and pre-radiation response to chemotherapy(CT): 31.2 Gy if under 10-years-old and complete response(CR) or partial response(PR) obtained or absence of metastatic disease, 39 Gy in other/older patients. Boosts to posterior fossa/residual metastatic(M+) deposits were given up to a total dose of 60 Gy/9 Gy, respectively, but avoided if metastatic nodules were very big or patients were very young. Two courses of high-dose-thiotepa were delivered in case of not CR/PR after the pre-radiotherapy (RT) phase and in all M0 patients either—pre/post-HART. Subgrouping was performed where the tissue was available. Results. Eighty-nine patients were enrolled, with a median age of 8.8 years, and a median follow-up of 136 months. Overall survival (OS) and event-free survival (EFS) at 5/15 years were 75.9/66.5% and 68.2/65.3%, respectively; 5/28 fatal events were not related to relapse(3 developed secondary malignancies). Sex, age less than 10 years, histological subtype, presence of MYC/MYCN amplification, reduction in CSI dose, omission of RT-boosts, implementation of myeloablative therapy, presence–absence of metastases did not impact prognosis.Patients progressing after pre-HART CT(14/89) and stable-disease(SD)+PD after HART(10/89) negatively affected outcome(P < .001).Subgrouping in 66/89 patients’ samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) versus groups 3 and 4(15 and 29 patients, respectively, group3/4 in 7).Patients younger than 10 received lower CSI doses if stratified according to CT response. Conclusions. This strategy, partly adopted in the ongoing SIOPE protocol, confirmed improved EFS and OS over previously reported outcomes in all high-risk categories; SHH tumors appeared the most aggressive.
Author(s): Massimino M, Barretta F, Dossena C, Minasi S, Buttarelli FR, Biassoni V, Oriani M, Schiavello E, Ficorilli M, Nigro O, Pollo B, Antonelli M, Donofrio V, Maggioni M, Kool M, Pecori E, Vennarini S, Giangaspero F, Gianno F, Erbetta A, Chiapparini L, Luksch R, Barzano E, Meazza C, Podda M, Spreafico F, Terenziani M, Bergamaschi L, Ferrari A, Casanova M, Chiaravalli S, Gattuso G, Modena P, Bailey S, De Cecco L
Publication type: Article
Publication status: Published
Journal: Neuro-Oncology
Year: 2025
Volume: 27
Issue: 1
Pages: 209-218
Print publication date: 01/01/2025
Online publication date: 27/09/2024
Acceptance date: 02/04/2018
Date deposited: 27/01/2025
ISSN (print): 1522-8517
ISSN (electronic): 1523-5866
Publisher: Oxford University Press
URL: https://doi.org/10.1093/neuonc/noae189
DOI: 10.1093/neuonc/noae189
Data Access Statement: The data will be made available upon reasonable request.
PubMed id: 39331528
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