{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T20:59:56Z","timestamp":1780520396937,"version":"3.54.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>We applied the strategy for M+ medulloblastoma across all high-risk subgroups, including LC\/A histology, TP53 mutations, and MYC\/MYCN amplification.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2013craniospinal(HART-CSI), administered twice daily 1.3 Gy-fractions reached a total dose tailored to the patients\u2019 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\u2014pre\/post-HART. Subgrouping was performed where the tissue was available.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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\u2013absence 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 &amp;lt; .001).Subgrouping in 66\/89 patients\u2019 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/neuonc\/noae189","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T16:58:01Z","timestamp":1727456281000},"page":"209-218","source":"Crossref","is-referenced-by-count":7,"title":["Long-term outcome of the Milano-hyperfractionated accelerated radiotherapy strategy for high-risk medulloblastoma, including the impact of molecular subtype"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5506-2001","authenticated-orcid":false,"given":"Maura","family":"Massimino","sequence":"first","affiliation":[{"name":"Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7797-161X","authenticated-orcid":false,"given":"Francesco","family":"Barretta","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori Department of Clinical Epidemiology and Trial Organization, , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0260-8052","authenticated-orcid":false,"given":"Chiara","family":"Dossena","sequence":"additional","affiliation":[{"name":"Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Minasi","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-1281","authenticated-orcid":false,"given":"Francesca Romana","family":"Buttarelli","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Istituto Nazionale dei Tumori , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-1736","authenticated-orcid":false,"given":"Veronica","family":"Biassoni","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori , Milano ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Oriani","sequence":"additional","affiliation":[{"name":"Integrated Biology Platform, Department of Applied Research and Technology Development, Fondazione IRCCS Istituto Nazionale dei Tumori , Milano 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