{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T04:19:44Z","timestamp":1773029984126,"version":"3.50.1"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005760","name":"University of Gothenburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005760","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>A comparison of acute toxicity between photon and proton radiotherapy (RT) for children undergoing treatment for medulloblastoma.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This retrospective multi-institutional cohort study included 96 children\u2009&lt;\u200918 years treated for medulloblastoma in Sweden during 2008\u20132020. Patients treated with protons (<jats:italic>n<\/jats:italic>\u2009=\u200937) and photons (<jats:italic>n<\/jats:italic>\u2009=\u200959) were compared regarding acute side effects and radiation dose to intracerebral organs at risk (OARs). Data was collected from a prospectively maintained national database and was supplemented from a retrospective review of medical records. Acute symptoms were graded according to CTCAE (Common Terminology Criteria for Adverse Events), maximum grade occurring during RT and within 2 months after RT. Hematological toxicity was evaluated according to maximum grade and percentual reduction during RT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>No significant differences in incidence or severity of acute symptoms were observed between proton-RT and photon-RT; grade\u2009\u2265\u20092 fatigue (5.4 vs. 10.2%), headache (2.7 vs. 3.4%), nausea (43.2 vs. 42.4%), dermatitis (5.4 vs. 15.3%), gastrointestinal toxicity (0 vs. 0%), weight loss (10.8 vs. 8.5%). Median percentual reduction (0% vs. -11,25%) in hemoglobin was significantly smaller during proton-RT (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). No difference was observed for leucocytes, neutrophiles, or platelets. Absorbed mean dose to intracranial OARs was significantly lower with proton-RT.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This is one of the largest studies comparing acute side effects of proton-RT and photon-RT including only paediatric medulloblastoma patients. Proton-RT was safe and well tolerated regarding acute side effects. Absorbed dose to intracranial OARs was significantly lower with proton-RT. Further investigations of long-term side effects and cognitive evaluation is needed to show that this will translate into true clinical value for patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11060-025-05016-x","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T03:58:32Z","timestamp":1744689512000},"page":"559-569","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute side effects of proton and photon radiotherapy for medulloblastoma: a retrospective national multicenter study"],"prefix":"10.1007","volume":"173","author":[{"given":"Linn S\u00f6derlund","family":"Diaz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e5ns","family":"Agrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Asklid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Embring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Engellau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid Fagerstr\u00f6m","family":"Kristensen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Flejmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotta","family":"Fr\u00f6jd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin P","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maja","family":"Sv\u00e4rd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelica","family":"Walfridsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Blomstrand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"issue":"4","key":"5016_CR1","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1093\/neuonc\/not225","volume":"16","author":"NP Brodin","year":"2014","unstructured":"Brodin NP et al (2014) Hippocampal sparing radiotherapy for pediatric Medulloblastoma: impact of treatment margins and treatment technique. Neuro Oncol 16(4):594\u2013602","journal-title":"Neuro Oncol"},{"issue":"8","key":"5016_CR2","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1080\/0284186X.2017.1324207","volume":"56","author":"ESQ Ho","year":"2017","unstructured":"Ho ESQ, Barrett SA, Mullaney LM (2017) A review of dosimetric and toxicity modeling of proton versus photon craniospinal irradiation for pediatrics Medulloblastoma. Acta Oncol 56(8):1031\u20131042","journal-title":"Acta Oncol"},{"issue":"12","key":"5016_CR3","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1001\/jamaoncol.2016.2547","volume":"2","author":"BH Kann","year":"2016","unstructured":"Kann BH et al (2016) Postoperative radiotherapy patterns of care and survival implications for Medulloblastoma in young children. JAMA Oncol 2(12):1574\u20131581","journal-title":"JAMA Oncol"},{"issue":"1","key":"5016_CR4","doi-asserted-by":"publisher","first-page":"e28027","DOI":"10.1002\/pbc.28027","volume":"67","author":"S Tian","year":"2020","unstructured":"Tian S et al (2020) Reduced-volume tumor-bed boost is not associated with inferior local control and survival outcomes in high-risk Medulloblastoma. Pediatr Blood Cancer 67(1):e28027","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"5016_CR5","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/S1470-2045(15)00167-9","volume":"17","author":"TI Yock","year":"2016","unstructured":"Yock TI et al (2016) Long-term toxic effects of proton radiotherapy for paediatric Medulloblastoma: a phase 2 single-arm study. Lancet Oncol 17(3):287\u2013298","journal-title":"Lancet Oncol"},{"issue":"21","key":"5016_CR6","doi-asserted-by":"publisher","first-page":"5432","DOI":"10.1002\/cncr.27536","volume":"118","author":"NP Brodin","year":"2012","unstructured":"Brodin NP et al (2012) Life years lost\u2013comparing potentially fatal late complications after radiotherapy for pediatric Medulloblastoma on a common scale. Cancer 118(21):5432\u20135440","journal-title":"Cancer"},{"issue":"6","key":"5016_CR7","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1093\/neuonc\/nov302","volume":"18","author":"BR Eaton","year":"2016","unstructured":"Eaton BR et al (2016) Endocrine outcomes with proton and photon radiotherapy for standard risk Medulloblastoma. Neuro Oncol 18(6):881\u2013887","journal-title":"Neuro Oncol"},{"issue":"9","key":"5016_CR8","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1002\/pbc.24554","volume":"60","author":"G Suneja","year":"2013","unstructured":"Suneja G et al (2013) Acute toxicity of proton beam radiation for pediatric central nervous system malignancies. Pediatr Blood Cancer 60(9):1431\u20131436","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"5016_CR9","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1016\/j.ijrobp.2020.09.049","volume":"109","author":"KX Liu","year":"2021","unstructured":"Liu KX et al (2021) A Multi-institutional comparative analysis of proton and photon Therapy-Induced hematologic toxicity in patients with Medulloblastoma. Int J Radiat Oncol Biol Phys 109(3):726\u2013735","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"6","key":"5016_CR10","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1002\/cam4.4553","volume":"11","author":"S Uemura","year":"2022","unstructured":"Uemura S et al (2022) The comparison of acute toxicities associated with craniospinal irradiation between photon beam therapy and proton beam therapy in children with brain tumors. Cancer Med 11(6):1502\u20131510","journal-title":"Cancer Med"},{"key":"5016_CR11","doi-asserted-by":"publisher","first-page":"p5879723","DOI":"10.1155\/2019\/5879723","volume":"2019","author":"R Carbonara","year":"2019","unstructured":"Carbonara R et al (2019) Proton versus photon radiotherapy for pediatric central nervous system malignancies: A systematic review and Meta-Analysis of dosimetric comparison studies. J Oncol 2019:p5879723","journal-title":"J Oncol"},{"issue":"5","key":"5016_CR12","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1200\/JCO.19.01706","volume":"38","author":"LS Kahalley","year":"2020","unstructured":"Kahalley LS et al (2020) Superior intellectual outcomes after proton radiotherapy compared with photon radiotherapy for pediatric Medulloblastoma. J Clin Oncol 38(5):454\u2013461","journal-title":"J Clin Oncol"},{"issue":"10","key":"5016_CR13","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1200\/JCO.2015.62.1383","volume":"34","author":"LS Kahalley","year":"2016","unstructured":"Kahalley LS et al (2016) Comparing intelligence quotient change after treatment with proton versus photon radiation therapy for pediatric brain tumors. J Clin Oncol 34(10):1043\u20131049","journal-title":"J Clin Oncol"},{"key":"5016_CR14","doi-asserted-by":"crossref","unstructured":"Vennarini S et al (2022) Acute hematological toxicity during Cranio-Spinal proton therapy in pediatric brain embryonal tumors. Cancers (Basel), 14(7)","DOI":"10.3390\/cancers14071653"},{"issue":"1","key":"5016_CR15","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.ijrobp.2015.09.014","volume":"94","author":"BR Eaton","year":"2016","unstructured":"Eaton BR et al (2016) Clinical outcomes among children with Standard-Risk Medulloblastoma treated with proton and photon radiation therapy: A comparison of disease control and overall survival. Int J Radiat Oncol Biol Phys 94(1):133\u2013138","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"6","key":"5016_CR16","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1080\/02841860500218819","volume":"44","author":"X Mu","year":"2005","unstructured":"Mu X et al (2005) Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood Medulloblastoma?? A comparative treatment planning study. Acta Oncol 44(6):554\u2013562","journal-title":"Acta Oncol"},{"issue":"1","key":"5016_CR17","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.radonc.2014.07.003","volume":"113","author":"R Zhang","year":"2014","unstructured":"Zhang R et al (2014) A comparative study on the risks of radiogenic second cancers and cardiac mortality in a set of pediatric Medulloblastoma patients treated with photon or proton craniospinal irradiation. Radiother Oncol 113(1):84\u201388","journal-title":"Radiother Oncol"},{"issue":"2","key":"5016_CR18","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.ijrobp.2013.01.014","volume":"86","author":"AP Brown","year":"2013","unstructured":"Brown AP et al (2013) Proton beam craniospinal irradiation reduces acute toxicity for adults with Medulloblastoma. Int J Radiat Oncol Biol Phys 86(2):277\u2013284","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"10","key":"5016_CR19","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1080\/0284186X.2023.2260946","volume":"62","author":"U Martinsson","year":"2023","unstructured":"Martinsson U et al (2023) Complications after proton radiotherapy in children, focusing on severe late complications. A complete Swedish cohort 2008\u20132019. Acta Oncol 62(10):1348\u20131356","journal-title":"Acta Oncol"},{"issue":"5","key":"5016_CR20","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1016\/0360-3016(95)00060-C","volume":"31","author":"JD Cox","year":"1995","unstructured":"Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 31(5):1341\u20131346","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"5","key":"5016_CR21","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1182\/blood.V21.5.640.640","volume":"21","author":"PP CARBONE","year":"1963","unstructured":"CARBONE PP et al (1963) Clinical studies with vincristine. Blood 21(5):640\u2013647","journal-title":"Blood"},{"issue":"1","key":"5016_CR22","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/S0167-8140(98)00024-3","volume":"48","author":"S Jefferies","year":"1998","unstructured":"Jefferies S et al (1998) Haematological toxicity of cranio-spinal irradiation. Radiother Oncol 48(1):23\u201327","journal-title":"Radiother Oncol"},{"issue":"9","key":"5016_CR23","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.3109\/0284186X.2014.887225","volume":"53","author":"S Song","year":"2014","unstructured":"Song S et al (2014) Proton beam therapy reduces the incidence of acute haematological and Gastrointestinal toxicities associated with craniospinal irradiation in pediatric brain tumors. Acta Oncol 53(9):1158\u20131164","journal-title":"Acta Oncol"},{"issue":"3","key":"5016_CR24","doi-asserted-by":"publisher","first-page":"907","DOI":"10.4143\/crt.2021.332","volume":"54","author":"GS Yoo","year":"2022","unstructured":"Yoo GS et al (2022) Chronological analysis of acute hematological outcomes after proton and photon beam craniospinal irradiation in pediatric brain tumors. Cancer Res Treat 54(3):907\u2013916","journal-title":"Cancer Res Treat"},{"issue":"1","key":"5016_CR25","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.radonc.2007.05.018","volume":"84","author":"A Skowronska-Gardas","year":"2007","unstructured":"Skowronska-Gardas A et al (2007) Patterns of failure in children with Medulloblastoma treated with 3D conformal radiotherapy. Radiother Oncol 84(1):26\u201333","journal-title":"Radiother Oncol"}],"updated-by":[{"DOI":"10.1007\/s11060-025-05235-2","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000}}],"container-title":["Journal of Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-025-05016-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11060-025-05016-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11060-025-05016-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T05:34:32Z","timestamp":1759210472000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11060-025-05016-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,15]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["5016"],"URL":"https:\/\/doi.org\/10.1007\/s11060-025-05016-x","relation":{},"ISSN":["0167-594X","1573-7373"],"issn-type":[{"value":"0167-594X","type":"print"},{"value":"1573-7373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,15]]},"assertion":[{"value":"17 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s11060-025-05235-2","URL":"https:\/\/doi.org\/10.1007\/s11060-025-05235-2","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved be the Swedish Ethical Review Authority (Dnr 2021\u2009\u2212\u200900803).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from the parents.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}