title: A radiotherapy technique to limit dose to neural progenitor cell niches without compromising tumor coverage.
abstract: Radiation therapy (RT) for brain tumors is associated with neurocognitive toxicity which may be a result of damage to neural progenitor cells (NPCs). We present a novel technique to limit the radiation dose to NPC without compromising tumor coverage. A study was performed in mice to examine the rationale and another was conducted in humans to determine its feasibility. C57BL/6 mice received localized radiation using a dedicated animal irradiation system with on-board CT imaging with either: (1) Radiation which spared NPC containing regions; (2) Radiation which did not spare these niches; or (3) Sham irradiation. Mice were sacrificed 24 h later and the brains were processed for immunohistochemical Ki-67 staining. For the human component of the study, 33 patients with primary brain tumors were evaluated. Two intensity modulated radiotherapy (IMRT) plans were retrospectively compared: a standard clinical plan and a plan which spares NPC regions while maintaining the same dose coverage of the tumor. The change in radiation dose to the contralateral NPC-containing regions was recorded. In the mouse model, non-NPC-sparing radiation treatment resulted in a significant decrease in the number of Ki67(+) cells in dentate gyrus (DG) (P = 0.008) and subventricular zone (SVZ) (P = 0.005) compared to NPC-sparing radiation treatment. In NPC-sparing clinical plans, NPC regions received significantly lower radiation dose with no clinically relevant changes in tumor coverage. This novel radiation technique should significantly reduce radiation doses to NPC containing regions of the brain which may reduce neurocognitive deficits following RT for brain tumors.
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Redmond
authors.forename: Pragathi
authors.initials: P
authors.lastname: Achanta
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
authors.forename: Michael
authors.initials: M
authors.lastname: Armour
authors.forename: Juvenal
authors.initials: J
authors.lastname: Reyes
authors.forename: Lawrence
authors.initials: L
authors.lastname: Kleinberg
authors.forename: Erik
authors.initials: E
authors.lastname: Tryggestad
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quinones-Hinojosa
authors.forename: Eric C
authors.initials: EC
authors.lastname: Ford
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000532:radiotherapy*; D016371:Cranial Irradiation / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005909:Glioblastoma / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D011881:Radiotherapy, Computer-Assisted / Q000379:methods; D012189:Retrospective Studies; D055153:Stem Cell Niche / Q000528:radiation effects*