title: Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma.
abstract: We sought to assess the feasibility and estimate the benefit of sparing the neurogenic niches when irradiating the brain of pediatric patients with medulloblastoma (MB) based on clinical outcome data. Pediatric MB survivors experience a high risk of neurocognitive adverse effects, often attributed to the whole-brain irradiation that is part of standard management. Neurogenesis is very sensitive to radiation, and limiting the radiation dose to the hippocampus and the subventricular zone (SVZ) may preserve neurocognitive function. Radiotherapy plans were created using 4 techniques: standard opposing fields, intensity-modulated radiotherapy (IMRT), intensity-modulated arc therapy (IMAT), and intensity-modulated proton therapy (IMPT). Mean dose to the hippocampus and SVZ (mean for both sites) could be limited to 88.3% (range, 83.6%-91.0%), 77.1% (range, 71.5%-81.3%), and 42.3% (range, 26.6%-51.2%) with IMAT, IMRT, and IMPT, respectively, while maintaining at least 95% of the prescribed dose in 95% of the whole-brain target volume. Estimated risks for developing memory impairment after a prescribed dose of 23.4 Gy were 47% (95% confidence interval [CI], 21%-69%), 44% (95% CI, 21%-65%), 41% (95% CI, 22%-60%), and 33% (95% CI, 23%-44%) with opposing fields, IMAT, IMRT, and IMPT, respectively. Neurogenic niche sparing during cranial irradiation of pediatric patients with MB is feasible and is estimated to lower the risks of long-term neurocognitive sequelae. Greatest sparing is achieved with intensity-modulated proton therapy, thus making this an attractive option to be tested in a prospective clinical trial.
authors.affiliation: Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Blomstrand
authors.forename: N Patrik
authors.initials: NP
authors.lastname: Brodin
authors.forename: Per
authors.initials: P
authors.lastname: Munck Af Rosenschöld
authors.forename: Ivan R
authors.initials: IR
authors.lastname: Vogelius
authors.forename: Gaspar
authors.initials: G
authors.lastname: Sánchez Merino
authors.forename: Anne
authors.initials: A
authors.lastname: Kiil-Berthlesen
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.forename: Birgitta
authors.initials: B
authors.lastname: Lannering
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.forename: Thomas
authors.initials: T
authors.lastname: Björk-Eriksson
mesh_terms: D001921:Brain / Q000528:radiation effects; D002528:Cerebellar Neoplasms / Q000532:radiotherapy*; D002648:Child; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000532:radiotherapy*; D055495:Neurogenesis / Q000528:radiation effects*; D058958:Organs at Risk / Q000528:radiation effects*; D011379:Prognosis; D061766:Proton Therapy; D011832:Radiation Injuries / Q000517:prevention & control*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies; D047368:Tumor Burden / Q000528:radiation effects*; D011522:Protons
chemical_list: D011522:Protons