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We investigated the relationship between radiation dose to brain substructures and HRQoL in children with brain tumors treated with proton beam therapy (PBT).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Data were obtained from children in the Pediatric Proton\/Photon Consortium Registry who received PBT for primary brain tumors between 2015 and 2021. HRQoL was assessed using PedsQL Generic Core questionnaires during the first week of PBT and annually thereafter. Standardized substructure segmentations and dosimetry data were correlated with parent-proxy reported HRQoL scores using Pearson correlations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Seventy-six patients were included, with median age 8.9 years (range 1.2\u201316.5) at diagnosis. Median follow-up was 5.0 years post-PBT and median prescribed dose was 54Gy<jats:sub>RBE<\/jats:sub>. HRQoL scores were lower than normative population values during PBT, particularly in those who received craniospinal irradiation (CSI) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). Across the total cohort, higher mean doses to the whole brain, supratentorial brain, corpus callosum, left hippocampus, hypothalamus, optic chiasm, pituitary and thalamus correlated with worse HRQoL (<jats:italic>r<\/jats:italic>= -0.24 to -0.39), <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). In the CSI subgroup (<jats:italic>n<\/jats:italic>\u2009=\u200917), moderate-to-strong associations between dose to these structures and physical functioning (<jats:italic>r<\/jats:italic>= -0.50 to -0.79, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) were observed. In children who received focal PBT (<jats:italic>n<\/jats:italic>\u2009=\u200959), weaker associations were observed between dose to the hypothalamus and pituitary, and HRQoL (<jats:italic>r<\/jats:italic> = -0.28 to -0.36, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Higher radiation doses to specific brain substructures were associated with poorer HRQoL outcomes after PBT. Minimizing dose to these areas during treatment planning may help preserve HRQoL in survivors.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11060-025-05211-w","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T12:21:37Z","timestamp":1757420497000},"page":"1443-1453","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Impact of substructure radiation dose on health-related quality of life in children with brain tumors: a Pediatric Proton\/Photon Consortium Registry (PPCR) study"],"prefix":"10.1007","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-4489","authenticated-orcid":false,"given":"Mikaela","family":"Doig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young","family":"Kwok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain","family":"MacEwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Wolden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Allison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Dennehy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bajaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michala","family":"Short","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gorayski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Bezak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torunn I.","family":"Yock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"5211_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26442","author":"F Schulte","year":"2017","unstructured":"Schulte F, Russell KB, Cullen P, Embry L, Fay-McClymont T, Johnston D et al (2017) Systematic review and meta-analysis of health-related quality of life in pediatric CNS tumor survivors. 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