Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma

Malin Blomstrand, N. Patrik Brodin, Per Munck Af Rosenschld, Ivan R. Vogelius, Gaspar Snchez Merino, Anne Kiil-Berthlesen, Klas Blomgren, Birgitta Lannering, Søren M. Bentzen, Thomas Bjrk-Eriksson

Research output: Contribution to journalArticle

47 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)882-889
Number of pages8
JournalNeuro-Oncology
Volume14
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • CNS
  • medulloblastoma
  • neurocognitive sparing
  • radiotherapy
  • risk modeling

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Blomstrand, M., Patrik Brodin, N., Munck Af Rosenschld, P., Vogelius, I. R., Snchez Merino, G., Kiil-Berthlesen, A., Blomgren, K., Lannering, B., Bentzen, S. M., & Bjrk-Eriksson, T. (2012). Estimated clinical benefit of protecting neurogenesis in the developing brain during radiation therapy for pediatric medulloblastoma. Neuro-Oncology, 14(7), 882-889. https://doi.org/10.1093/neuonc/nos120