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

ABSTRACT: 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.

SUBMITTER: Eastman B

PROVIDER: S-EPMC8429726 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Eastman Brydon B Przedborski Michelle M Kohandel Mohammad M

Scientific reports 20210909 1

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 i ...[more]

PMID: 34504141

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Project description:BackgroundThe current guidelines for managing screen-detected pulmonary nodules offer rule-based recommendations for immediate diagnostic work-up or follow-up at intervals of 3, 6, or 12 months. Customized visit plans are lacking.PurposeTo develop individualized screening schedules using reinforcement learning (RL) and evaluate the effectiveness of RL-based policy models.MethodsUsing a nested case-control design, we retrospectively identified 308 patients with cancer who had positive screening results in at least two screening rounds in the National Lung Screening Trial. We established a control group that included cancer-free patients with nodules, matched (1:1) according to the year of cancer diagnosis. By generating 10,164 sequence decision episodes, we trained RL-based policy models, incorporating nodule diameter alone, combined with nodule appearance (attenuation and margin) and/or patient information (age, sex, smoking status, pack-years, and family history). We calculated rates of misdiagnosis, missed diagnosis, and delayed diagnosis, and compared the performance of RL-based policy models with rule-based follow-up protocols (National Comprehensive Cancer Network guideline; China Guideline for the Screening and Early Detection of Lung Cancer).ResultsWe identified significant interactions between certain variables (e.g., nodule shape and patient smoking pack-years, beyond those considered in guideline protocols) and the selection of follow-up testing intervals, thereby impacting the quality of the decision sequence. In validation, one RL-based policy model achieved rates of 12.3% for misdiagnosis, 9.7% for missed diagnosis, and 11.7% for delayed diagnosis. Compared with the two rule-based protocols, the three best-performing RL-based policy models consistently demonstrated optimal performance for specific patient subgroups based on disease characteristics (benign or malignant), nodule phenotypes (size, shape, and attenuation), and individual attributes.ConclusionsThis study highlights the potential of using an RL-based approach that is both clinically interpretable and performance-robust to develop personalized lung cancer screening schedules. Our findings present opportunities for enhancing the current cancer screening system.

Project description:BackgroundPsychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g., psychosis in bipolar disorder vs. schizophrenia). Computational modeling makes it possible to identify and mathematically differentiate behaviorally unobservable, specific reinforcement learning differences in patients with schizophrenia versus other disorders, likely owing to a higher reliance on prediction error-driven learning associated with basal ganglia and underreliance on explicit value representations associated with orbitofrontal cortex.MethodsWe used a well-established probabilistic reinforcement learning task to replicate those findings in individuals with schizophrenia both on (n = 120) and off (n = 44) antipsychotic medications and included a patient comparison group of bipolar patients with psychosis (n = 60) and healthy control subjects (n = 72).ResultsUsing accuracy, there was a main effect of group (F3,279 = 7.87, p < .001), such that all patient groups were less accurate than control subjects. Using computationally derived parameters, both medicated and unmediated individuals with schizophrenia, but not patients with bipolar disorder, demonstrated a reduced mixing parameter (F3,295 = 13.91, p < .001), indicating less dependence on learning explicit value representations as well as greater learning decay between training and test (F1,289 = 12.81, p < .001). Unmedicated patients with schizophrenia also showed greater decision noise (F3,295 = 2.67, p = .04).ConclusionsBoth medicated and unmedicated patients showed overreliance on prediction error-driven learning as well as significantly higher noise and value-related memory decay, compared with the healthy control subjects and the patients with bipolar disorder. Additionally, the computational model parameters capturing these processes can significantly improve patient/control classification, potentially providing useful diagnosis insight.

Dataset Information

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

Publications

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

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