Cargando…
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....
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1783295510858170368 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5784742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT cardilintim modelbasedevaluationofradiationandradiosensitizingagentsinoncology AT almquistjoachim modelbasedevaluationofradiationandradiosensitizingagentsinoncology AT jirstrandmats modelbasedevaluationofradiationandradiosensitizingagentsinoncology AT zimmermannastrid modelbasedevaluationofradiationandradiosensitizingagentsinoncology AT elbawabsamer modelbasedevaluationofradiationandradiosensitizingagentsinoncology AT gabrielssonjohan modelbasedevaluationofradiationandradiosensitizingagentsinoncology |