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Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival

Proton minibeam radiotherapy (pMBRT) is a spatial fractionation method using sub-millimeter beams at center-to-center (ctc) distances of a few millimeters to widen the therapeutic index by reduction of side effects in normal tissues. Interlaced minibeams from two opposing or four orthogonal directio...

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Autores principales: Sammer, Matthias, Girst, Stefanie, Dollinger, Günther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878903/
https://www.ncbi.nlm.nih.gov/pubmed/33574390
http://dx.doi.org/10.1038/s41598-021-81708-4
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author Sammer, Matthias
Girst, Stefanie
Dollinger, Günther
author_facet Sammer, Matthias
Girst, Stefanie
Dollinger, Günther
author_sort Sammer, Matthias
collection PubMed
description Proton minibeam radiotherapy (pMBRT) is a spatial fractionation method using sub-millimeter beams at center-to-center (ctc) distances of a few millimeters to widen the therapeutic index by reduction of side effects in normal tissues. Interlaced minibeams from two opposing or four orthogonal directions are calculated to minimize side effects. In particular, heterogeneous dose distributions applied to the tumor are investigated to evaluate optimized sparing capabilities of normal tissues at the close tumor surrounding. A 5 cm thick tumor is considered at 10 cm depth within a 25 cm thick water phantom. Pencil and planar minibeams are interlaced from two (opposing) directions as well as planar beams from four directions. An initial beam size of σ(0) = 0.2 mm (standard deviation) is assumed in all cases. Tissue sparing potential is evaluated by calculating mean clonogenic cell survival using a linear-quadratic model on the calculated dose distributions. Interlacing proton minibeams for homogeneous irradiation of the tumor has only minor benefits for the mean clonogenic cell survival compared to unidirectional minibeam irradiation modes. Enhanced mean cell survival, however, is obtained when a heterogeneous dose distribution within the tumor is permitted. The benefits hold true even for an elevated mean tumor dose, which is necessary to avoid cold spots within the tumor in concerns of a prescribed dose. The heterogeneous irradiation of the tumor allows for larger ctc distances. Thus, a high mean cell survival of up to 47% is maintained even close to the tumor edges for single fraction doses in the tumor of at least 10 Gy. Similar benefits would result for heavy ion minibeams with the advantage of smaller minibeams in deep tissue potentially offering even increased tissue sparing. The enhanced mean clonogenic cell survival through large ctc distances for interlaced pMBRT with heterogeneous tumor dose distribution results in optimum tissue sparing potential. The calculations show the largest enhancement of the mean cell survival in normal tissue for high-dose fractions. Thus, hypo-fractionation or even single dose fractions become possible for tumor irradiation. A widened therapeutic index at big cost reductions is offered by interlaced proton or heavy ion minibeam therapy.
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spelling pubmed-78789032021-02-12 Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival Sammer, Matthias Girst, Stefanie Dollinger, Günther Sci Rep Article Proton minibeam radiotherapy (pMBRT) is a spatial fractionation method using sub-millimeter beams at center-to-center (ctc) distances of a few millimeters to widen the therapeutic index by reduction of side effects in normal tissues. Interlaced minibeams from two opposing or four orthogonal directions are calculated to minimize side effects. In particular, heterogeneous dose distributions applied to the tumor are investigated to evaluate optimized sparing capabilities of normal tissues at the close tumor surrounding. A 5 cm thick tumor is considered at 10 cm depth within a 25 cm thick water phantom. Pencil and planar minibeams are interlaced from two (opposing) directions as well as planar beams from four directions. An initial beam size of σ(0) = 0.2 mm (standard deviation) is assumed in all cases. Tissue sparing potential is evaluated by calculating mean clonogenic cell survival using a linear-quadratic model on the calculated dose distributions. Interlacing proton minibeams for homogeneous irradiation of the tumor has only minor benefits for the mean clonogenic cell survival compared to unidirectional minibeam irradiation modes. Enhanced mean cell survival, however, is obtained when a heterogeneous dose distribution within the tumor is permitted. The benefits hold true even for an elevated mean tumor dose, which is necessary to avoid cold spots within the tumor in concerns of a prescribed dose. The heterogeneous irradiation of the tumor allows for larger ctc distances. Thus, a high mean cell survival of up to 47% is maintained even close to the tumor edges for single fraction doses in the tumor of at least 10 Gy. Similar benefits would result for heavy ion minibeams with the advantage of smaller minibeams in deep tissue potentially offering even increased tissue sparing. The enhanced mean clonogenic cell survival through large ctc distances for interlaced pMBRT with heterogeneous tumor dose distribution results in optimum tissue sparing potential. The calculations show the largest enhancement of the mean cell survival in normal tissue for high-dose fractions. Thus, hypo-fractionation or even single dose fractions become possible for tumor irradiation. A widened therapeutic index at big cost reductions is offered by interlaced proton or heavy ion minibeam therapy. Nature Publishing Group UK 2021-02-11 /pmc/articles/PMC7878903/ /pubmed/33574390 http://dx.doi.org/10.1038/s41598-021-81708-4 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sammer, Matthias
Girst, Stefanie
Dollinger, Günther
Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival
title Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival
title_full Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival
title_fullStr Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival
title_full_unstemmed Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival
title_short Optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival
title_sort optimizing proton minibeam radiotherapy by interlacing and heterogeneous tumor dose on the basis of calculated clonogenic cell survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878903/
https://www.ncbi.nlm.nih.gov/pubmed/33574390
http://dx.doi.org/10.1038/s41598-021-81708-4
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