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Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes
The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442104/ https://www.ncbi.nlm.nih.gov/pubmed/28536438 http://dx.doi.org/10.1038/s41598-017-01757-6 |
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author | Paul-Gilloteaux, Perrine Potiron, Vincent Delpon, Grégory Supiot, Stéphane Chiavassa, Sophie Paris, François Costes, Sylvain V. |
author_facet | Paul-Gilloteaux, Perrine Potiron, Vincent Delpon, Grégory Supiot, Stéphane Chiavassa, Sophie Paris, François Costes, Sylvain V. |
author_sort | Paul-Gilloteaux, Perrine |
collection | PubMed |
description | The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy. |
format | Online Article Text |
id | pubmed-5442104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-54421042017-05-25 Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes Paul-Gilloteaux, Perrine Potiron, Vincent Delpon, Grégory Supiot, Stéphane Chiavassa, Sophie Paris, François Costes, Sylvain V. Sci Rep Article The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy. Nature Publishing Group UK 2017-05-23 /pmc/articles/PMC5442104/ /pubmed/28536438 http://dx.doi.org/10.1038/s41598-017-01757-6 Text en © The Author(s) 2017 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Paul-Gilloteaux, Perrine Potiron, Vincent Delpon, Grégory Supiot, Stéphane Chiavassa, Sophie Paris, François Costes, Sylvain V. Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes |
title | Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes |
title_full | Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes |
title_fullStr | Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes |
title_full_unstemmed | Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes |
title_short | Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes |
title_sort | optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442104/ https://www.ncbi.nlm.nih.gov/pubmed/28536438 http://dx.doi.org/10.1038/s41598-017-01757-6 |
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