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Long-term outcome of the Milano-HART strategy for high-risk medulloblastoma, including the impact of molecular subtype.

Authors :
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
Barzanò 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
Source :
Neuro-oncology [Neuro Oncol] 2024 Sep 27. Date of Electronic Publication: 2024 Sep 27.
Publication Year :
2024
Publisher :
Ahead of Print

Abstract

Background: We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC/A histology, TP53 mutations, MYC/MYCN amplification.<br />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),high-dose-carboplatin(HD-Carbo).Hyperfractionated-accelerated-radiotherapy-craniospinal(HART-CSI),administered in 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 very young.Two courses of high-dose-thiotepa were delivered in case of not CR/PR after pre-radiotherapy(RT) phase and in all M0 patients either - pre/post HART.Subgrouping was performed where tissue was available.<br />Results: Eighy-nine patients were enrolled,median age 8.8 years,median follow up 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(three 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<0.001).Subgrouping in 66/89 patients' samples demonstrated a significantly worse EFS for patients with Sonic Hedgehog(SHH)-tumors(#15, 2 with constitutional TP53-mutations) vs. group 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.<br />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.<br /> (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Details

Language :
English
ISSN :
1523-5866
Database :
MEDLINE
Journal :
Neuro-oncology
Publication Type :
Academic Journal
Accession number :
39331528
Full Text :
https://doi.org/10.1093/neuonc/noae189