Reinforcement learning derived chemotherapeutic schedules for robust patient-specific therapy.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
09 09 2021
Historique:
received: 10 05 2021
accepted: 09 08 2021
entrez: 10 9 2021
pubmed: 11 9 2021
medline: 10 11 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 34504141
doi: 10.1038/s41598-021-97028-6
pii: 10.1038/s41598-021-97028-6
pmc: PMC8429726
doi:

Substances chimiques

Antineoplastic Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

17882

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

© 2021. The Author(s).

Références

Biometrics. 1947 Sep;3(3):119-22
pubmed: 18903631
J Clin Med. 2020 May 02;9(5):
pubmed: 32370195
Math Biosci. 1997 Dec;146(2):89-113
pubmed: 9348741

Auteurs

Brydon Eastman (B)

Department of Applied Mathematics, University of Waterloo, Waterloo, N2L 3G1, Canada. b2eastma@uwaterloo.ca.

Michelle Przedborski (M)

Department of Applied Mathematics, University of Waterloo, Waterloo, N2L 3G1, Canada.

Mohammad Kohandel (M)

Department of Applied Mathematics, University of Waterloo, Waterloo, N2L 3G1, Canada.

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