TY - JOUR
T1 - Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma
AU - Blomstrand, Malin
AU - Brodin, N Patrik
AU - Munck Af Rosenschöld, Per
AU - Vogelius, Ivan R
AU - Sánchez Merino, Gaspar
AU - Kiil-Berthlesen, Anne
AU - Blomgren, Klas
AU - Lannering, Birgitta
AU - Bentzen, Søren M
AU - Björk-Eriksson, Thomas
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Brain
KW - Cerebellar Neoplasms
KW - Child
KW - Cranial Irradiation
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Male
KW - Medulloblastoma
KW - Neurogenesis
KW - Organs at Risk
KW - Prognosis
KW - Protons
KW - Radiation Injuries
KW - Radiotherapy Dosage
KW - Radiotherapy Planning, Computer-Assisted
KW - Radiotherapy, Intensity-Modulated
KW - Retrospective Studies
KW - Tumor Burden
U2 - 10.1093/neuonc/nos120
DO - 10.1093/neuonc/nos120
M3 - Journal article
C2 - 22611031
SN - 1522-8517
VL - 14
SP - 882
EP - 889
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 7
ER -