Abstract
Simple SummaryMinibeam therapy spares certain normal tissues compared to conventional radiation therapy. Recently, minibeams applied with protons have shown efficacy in rodent models of glioblastoma. In consideration of translation to human therapy, heavier ions such as helium-4, lithium-7, carbon-12, or oxygen-16 would enable the method to reach deeper into the human brain, potentially sparing greater volumes of normal brain; however, biologic uncertainties and potential toxicities of the method are poorly understood, especially for heavy ions. This work explores the cognitive impairments and pathologic changes seen in normal rodent brain at late timepoints after partial-brain minibeam irradiation with heavy ions.The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium-7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of planar parallel minibeams having 300-micron width and 1-mm center-to-center spacing within a circular array. We followed animals for 6 months after treatment and utilized behavioral testing and immunohistochemical studies to investigate the resulting cognitive impairment and chronic pathologic changes. We found both solid-beam therapy and minibeam therapy to result in cognitive impairment compared with sham controls, with no apparent reduction in neurotoxicity using heavy ion minibeams instead of solid beams under the conditions of this study.
Highlights
Radiotherapy serves a critical role in the treatment of pediatric and adult brain cancers, especially for surgically inoperable sites or for subclinical disease intermingled with critical normal brain tissue
The findings of this work do not support our hypothesis and, instead, reveal cognitive impairment and chronic pathologic damage seen in normal rodent brain after minibeam therapy with lithium ions, which was not less severe than that seen after solid-beam therapy, when both methods provided an equivalent integral dose of 20 Gy
We performed a study of heavy ion minibeam therapy using lithium-7 ions in a rodent model of normal pediatric brain
Summary
Radiotherapy serves a critical role in the treatment of pediatric and adult brain cancers, especially for surgically inoperable sites or for subclinical disease intermingled with critical normal brain tissue. Cells directly hit by minibeams presumably die via mechanisms similar to that following conventional solid-beam irradiation, but the unirradiated cells either migrate or proliferate to compensate for this, offering a tissue sparing effect This effect has been demonstrated since 1959 [7], in a number of animal models using microbeams and minibeams in the size range of tens to hundreds of microns, and it has demonstrated tissue sparing at doses up to several hundreds of Gy in single fraction exposures [5,8,9,10,11]. Minibeam therapy has never been translated to human therapy, in part due to the still poorly understood mechanism and dose tolerances relevant for humans and in part due to the limitations of the radiation modalities used in the majority of these studies
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