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Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy

The in-silico development of a chemotherapeutic dosing schedule for treating cancer relies upon a parameterization of a particular tumour growth model to describe the dynamics of the cancer in response to the dose of the drug. In practice, it is often prohibitively difficult to ensure the validity o...

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Autores principales: Eastman, Brydon, Przedborski, Michelle, Kohandel, Mohammad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429726/
https://www.ncbi.nlm.nih.gov/pubmed/34504141
http://dx.doi.org/10.1038/s41598-021-97028-6
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author Eastman, Brydon
Przedborski, Michelle
Kohandel, Mohammad
author_facet Eastman, Brydon
Przedborski, Michelle
Kohandel, Mohammad
author_sort Eastman, Brydon
collection PubMed
description The in-silico development of a chemotherapeutic dosing schedule for treating cancer relies upon a parameterization of a particular tumour growth model to describe the dynamics of the cancer in response to the dose of the drug. In practice, it is often prohibitively difficult to ensure the validity of patient-specific parameterizations of these models for any particular patient. As a result, sensitivities to these particular parameters can result in therapeutic dosing schedules that are optimal in principle not performing well on particular patients. In this study, we demonstrate that chemotherapeutic dosing strategies learned via reinforcement learning methods are more robust to perturbations in patient-specific parameter values than those learned via classical optimal control methods. By training a reinforcement learning agent on mean-value parameters and allowing the agent periodic access to a more easily measurable metric, relative bone marrow density, for the purpose of optimizing dose schedule while reducing drug toxicity, we are able to develop drug dosing schedules that outperform schedules learned via classical optimal control methods, even when such methods are allowed to leverage the same bone marrow measurements.
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spelling pubmed-84297262021-09-13 Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy Eastman, Brydon Przedborski, Michelle Kohandel, Mohammad Sci Rep Article The in-silico development of a chemotherapeutic dosing schedule for treating cancer relies upon a parameterization of a particular tumour growth model to describe the dynamics of the cancer in response to the dose of the drug. In practice, it is often prohibitively difficult to ensure the validity of patient-specific parameterizations of these models for any particular patient. As a result, sensitivities to these particular parameters can result in therapeutic dosing schedules that are optimal in principle not performing well on particular patients. In this study, we demonstrate that chemotherapeutic dosing strategies learned via reinforcement learning methods are more robust to perturbations in patient-specific parameter values than those learned via classical optimal control methods. By training a reinforcement learning agent on mean-value parameters and allowing the agent periodic access to a more easily measurable metric, relative bone marrow density, for the purpose of optimizing dose schedule while reducing drug toxicity, we are able to develop drug dosing schedules that outperform schedules learned via classical optimal control methods, even when such methods are allowed to leverage the same bone marrow measurements. Nature Publishing Group UK 2021-09-09 /pmc/articles/PMC8429726/ /pubmed/34504141 http://dx.doi.org/10.1038/s41598-021-97028-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Eastman, Brydon
Przedborski, Michelle
Kohandel, Mohammad
Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy
title Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy
title_full Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy
title_fullStr Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy
title_full_unstemmed Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy
title_short Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy
title_sort reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429726/
https://www.ncbi.nlm.nih.gov/pubmed/34504141
http://dx.doi.org/10.1038/s41598-021-97028-6
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