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Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology

Radiotherapy is one of the major therapy forms in oncology, and combination therapies involving radiation and chemical compounds can yield highly effective tumor eradication. In this paper, we develop a tumor growth inhibition model for combination therapy with radiation and radiosensitizing agents....

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Autores principales: Cardilin, Tim, Almquist, Joachim, Jirstrand, Mats, Zimmermann, Astrid, El Bawab, Samer, Gabrielsson, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784742/
https://www.ncbi.nlm.nih.gov/pubmed/29218836
http://dx.doi.org/10.1002/psp4.12268
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author Cardilin, Tim
Almquist, Joachim
Jirstrand, Mats
Zimmermann, Astrid
El Bawab, Samer
Gabrielsson, Johan
author_facet Cardilin, Tim
Almquist, Joachim
Jirstrand, Mats
Zimmermann, Astrid
El Bawab, Samer
Gabrielsson, Johan
author_sort Cardilin, Tim
collection PubMed
description Radiotherapy is one of the major therapy forms in oncology, and combination therapies involving radiation and chemical compounds can yield highly effective tumor eradication. In this paper, we develop a tumor growth inhibition model for combination therapy with radiation and radiosensitizing agents. Moreover, we extend previous analyses of drug combinations by introducing the tumor static exposure (TSE) curve. The TSE curve for radiation and radiosensitizer visualizes exposure combinations sufficient for tumor regression. The model and TSE analysis are then tested on xenograft data. The calibrated model indicates that the highest dose of combination therapy increases the time until tumor regrowth 10‐fold. The TSE curve shows that with an average radiosensitizer concentration of [Formula: see text] the radiation dose can be decreased from [Formula: see text] to [Formula: see text]. Finally, we successfully predict the effect of a clinically relevant treatment schedule, which contributes to validating both the model and the TSE concept.
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spelling pubmed-57847422018-02-07 Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology Cardilin, Tim Almquist, Joachim Jirstrand, Mats Zimmermann, Astrid El Bawab, Samer Gabrielsson, Johan CPT Pharmacometrics Syst Pharmacol Original Articles Radiotherapy is one of the major therapy forms in oncology, and combination therapies involving radiation and chemical compounds can yield highly effective tumor eradication. In this paper, we develop a tumor growth inhibition model for combination therapy with radiation and radiosensitizing agents. Moreover, we extend previous analyses of drug combinations by introducing the tumor static exposure (TSE) curve. The TSE curve for radiation and radiosensitizer visualizes exposure combinations sufficient for tumor regression. The model and TSE analysis are then tested on xenograft data. The calibrated model indicates that the highest dose of combination therapy increases the time until tumor regrowth 10‐fold. The TSE curve shows that with an average radiosensitizer concentration of [Formula: see text] the radiation dose can be decreased from [Formula: see text] to [Formula: see text]. Finally, we successfully predict the effect of a clinically relevant treatment schedule, which contributes to validating both the model and the TSE concept. John Wiley and Sons Inc. 2017-12-14 2018-01 /pmc/articles/PMC5784742/ /pubmed/29218836 http://dx.doi.org/10.1002/psp4.12268 Text en © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Cardilin, Tim
Almquist, Joachim
Jirstrand, Mats
Zimmermann, Astrid
El Bawab, Samer
Gabrielsson, Johan
Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology
title Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology
title_full Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology
title_fullStr Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology
title_full_unstemmed Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology
title_short Model‐Based Evaluation of Radiation and Radiosensitizing Agents in Oncology
title_sort model‐based evaluation of radiation and radiosensitizing agents in oncology
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5784742/
https://www.ncbi.nlm.nih.gov/pubmed/29218836
http://dx.doi.org/10.1002/psp4.12268
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