{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:53:37Z","timestamp":1791557617577,"version":"4.3.4"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Childs Nerv Syst"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Embryonal tumor with multilayered rosettes (ETMR) carries a median overall survival of approximately 10\u201312\u00a0months despite maximal-safe resection, high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT), and radiotherapy (RT). RT has historically been deferred or omitted in these predominantly infant-age patients owing to concerns over neurodevelopmental toxicity, with HDCT\/ASCT serving as the principal consolidation strategy. More recent data have called this approach into question. This narrative review synthesizes the evidence on the timing of RT relative to HDCT\/ASCT and its association with outcome in ETMR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A structured narrative review of PubMed, EMBASE, and the Cochrane Library (2000\u20132025) identified studies reporting ETMR-specific outcomes with extractable data on RT timing relative to ASCT. Major prospective trials (ACNS0334 and P-HIT\/HIT2000) and institutional or registry series (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009\u2265\u20094 molecularly or histopathologically confirmed ETMR patients) were considered.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine studies or study-level cohorts providing ETMR-specific RT-timing data were identified, including the Rare Brain Tumor Registry cohort of 159 molecularly confirmed patients. Across independent cohorts, early RT administered within approximately six weeks of surgery or before protracted HDCT\/ASCT is consistently overrepresented among long-term survivors (&gt;\u200936\u00a0months): 10 of 26 (38%) in one literature survey and near-universal RT (17\/18; 94%) in another. In the Rare Brain Tumor Registry, two-year event-free survival after gross total resection was 66% with HDCT plus RT versus 21% with HDCT and no RT, and 0% with conventional chemotherapy without RT. Radiation-sparing protocols (ACNS0334) showed predominantly local failure (88%), with salvage RT after progression providing no durable benefit. Tandem HDCT\/ASCT without upfront RT (P-HIT\/HIT2000) produced a five-year OS of 47% for the carboplatin\u2013etoposide plus tandem-HDCT backbone, superior to other chemotherapy regimens but with frequent on-treatment relapse and no independent prognostic benefit demonstrable for radiotherapy as delivered. Combined RT and HDCT\/ASCT was associated with improved survival in some series but, in a small series treated with tandem ASCT, with a high incidence of pseudoprogression and neurocognitive impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Current evidence indicates that RT deferral beyond the HDCT\/ASCT consolidation window is associated with inferior local control and worse long-term outcomes in ETMR. PNOC031, a prospective but nonrandomized trial that assigns RT-eligible patients to early focal RT and RT-ineligible patients to HDCT\/ASCT in parallel cohorts, together with future prospective studies, should help to resolve this. Pending those results, and recognizing that the supporting data are observational and subject to selection bias, early focal RT following gross-total resection appears a reasonable and defensible strategy in eligible patients. The relationship between RT timing, HDCT\/ASCT, pseudoprogression, and neurodevelopmental toxicity is not yet well understood and warrants further study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00381-026-07490-8","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:46:37Z","timestamp":1791557197000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Timing of radiotherapy and autologous stem cell transplantation in embryonal tumor with multilayered rosettes: a critical narrative review"],"prefix":"10.1007","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-6356","authenticated-orcid":false,"given":"Sudarshawn","family":"Damodharan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"7490_CR1","volume-title":"WHO Classification of Tumours of the Central Nervous System","author":"WHO Classification of Tumours Editorial Board","year":"2021","unstructured":"WHO Classification of Tumours Editorial Board (2021) WHO Classification of Tumours of the Central Nervous System, 5th edn. 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This narrative review synthesizes previously published, aggregate data and did not involve new studies of human participants or animals performed by any of the authors.","order":2,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":5,"name":"Ethics","label":"Use of AI-assisted tools","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"387"}}