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Quantum deep reinforcement learning for clinical decision support in oncology: application to adaptive radiotherapy.

ABSTRACT: Subtle differences in a patient's genetics and physiology may alter radiotherapy (RT) treatment responses, motivating the need for a more personalized treatment plan. Accordingly, we have developed a novel quantum deep reinforcement learning (qDRL) framework for clinical decision support that can estimate an individual patient's dose response mid-treatment and recommend an optimal dose adjustment. Our framework considers patients' specific information including biological, physical, genetic, clinical, and dosimetric factors. Recognizing that physicians must make decisions amidst uncertainty in RT treatment outcomes, we employed indeterministic quantum states to represent human decision making in a real-life scenario. We paired quantum decision states with a model-based deep q-learning algorithm to optimize the clinical decision-making process in RT. We trained our proposed qDRL framework on an institutional dataset of 67 stage III non-small cell lung cancer (NSCLC) patients treated on prospective adaptive protocols and independently validated our framework in an external multi-institutional dataset of 174 NSCLC patients. For a comprehensive evaluation, we compared three frameworks: DRL, qDRL trained in a Qiskit quantum computing simulator, and qDRL trained in an IBM quantum computer. Two metrics were considered to evaluate our framework: (1) similarity score, defined as the root mean square error between retrospective clinical decisions and the AI recommendations, and (2) self-evaluation scheme that compares retrospective clinical decisions and AI recommendations based on the improvement in the observed clinical outcomes. Our analysis shows that our framework, which takes into consideration individual patient dose response in its decision-making, can potentially improve clinical RT decision-making by at least about 10% compared to unaided clinical practice. Further validation of our novel quantitative approach in a prospective study will provide a necessary framework for improving the standard of care in personalized RT.

SUBMITTER: Niraula D

PROVIDER: S-EPMC8651664 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Involvement of many variables, uncertainty in treatment response, and inter-patient heterogeneity challenge objective decision-making in dynamic treatment regime (DTR) in oncology. Advanced machine learning analytics in conjunction with information-rich dense multi-omics data have the ability to overcome such challenges. We have developed a comprehensive artificial intelligence (AI)-based optimal decision-making framework for assisting oncologists in DTR. In this work, we demonstrate the proposed framework to Knowledge Based Response-Adaptive Radiotherapy (KBR-ART) applications by developing an interactive software tool entitled Adaptive Radiotherapy Clinical Decision Support (ARCliDS). ARCliDS is composed of two main components: Artifcial RT Environment (ARTE) and Optimal Decision Maker (ODM). ARTE is designed as a Markov decision process and modeled via supervised learning. Given a patient's pre- and during-treatment information, ARTE can estimate treatment outcomes for a selected daily dosage value (radiation fraction size). ODM is formulated using reinforcement learning and is trained on ARTE. ODM can recommend optimal daily dosage adjustments to maximize the tumor local control probability and minimize the side effects. Graph Neural Networks (GNN) are applied to exploit the inter-feature relationships for improved modeling performance and a novel double GNN architecture is designed to avoid nonphysical treatment response. Datasets of size 117 and 292 were available from two clinical trials on adaptive RT in non-small cell lung cancer (NSCLC) patients and adaptive stereotactic body RT (SBRT) in hepatocellular carcinoma (HCC) patients, respectively. For training and validation, dense data with 297 features were available for 67 NSCLC patients and 110 features for 71 HCC patients. To increase the sample size for ODM training, we applied Generative Adversarial Networks to generate 10,000 synthetic patients. The ODM was trained on the synthetic patients and validated on the original dataset. We found that, Double GNN architecture was able to correct the nonphysical dose-response trend and improve ARCliDS recommendation. The average root mean squared difference (RMSD) between ARCliDS recommendation and reported clinical decisions using double GNNs were 0.61 [0.03] Gy/frac (mean [sem]) for adaptive RT in NSCLC patients and 2.96 [0.42] Gy/frac for adaptive SBRT HCC compared to the single GNN's RMSDs of 0.97 [0.12] Gy/frac and 4.75 [0.16] Gy/frac, respectively. Overall, For NSCLC and HCC, ARCliDS with double GNNs was able to reproduce 36% and 50% of the good clinical decisions (local control and no side effects) and improve 74% and 30% of the bad clinical decisions, respectively. In conclusion, ARCliDS is the first web-based software dedicated to assist KBR-ART with multi-omics data. ARCliDS can learn from the reported clinical decisions and facilitate AI-assisted clinical decision-making for improving the outcomes in DTR.

Project description:BackgroundSurgical patients incur preventable harm from cognitive and judgment errors made under time constraints and uncertainty regarding patients' diagnoses and predicted response to treatment. Decision analysis and techniques of reinforcement learning theoretically can mitigate these challenges but are poorly understood and rarely used clinically. This review seeks to promote an understanding of decision analysis and reinforcement learning by describing their use in the context of surgical decision-making.MethodsCochrane, EMBASE, and PubMed databases were searched from their inception to June 2019. Included were 41 articles about cognitive and diagnostic errors, decision-making, decision analysis, and machine-learning. The articles were assimilated into relevant categories according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.ResultsRequirements for time-consuming manual data entry and crude representations of individual patients and clinical context compromise many traditional decision-support tools. Decision analysis methods for calculating probability thresholds can inform population-based recommendations that jointly consider risks, benefits, costs, and patient values but lack precision for individual patient-centered decisions. Reinforcement learning, a machine-learning method that mimics human learning, can use a large set of patient-specific input data to identify actions yielding the greatest probability of achieving a goal. This methodology follows a sequence of events with uncertain conditions, offering potential advantages for personalized, patient-centered decision-making. Clinical application would require secure integration of multiple data sources and attention to ethical considerations regarding liability for errors and individual patient preferences.ConclusionTraditional decision-support tools are ill-equipped to accommodate time constraints and uncertainty regarding diagnoses and the predicted response to treatment, both of which often impair surgical decision-making. Decision analysis and reinforcement learning have the potential to play complementary roles in delivering high-value surgical care through sound judgment and optimal decision-making.

Project description:PURPOSE:Precision oncology is hindered by the lack of decision support for determining the functional and therapeutic significance of genomic alterations in tumors and relevant clinically available options. To bridge this knowledge gap, we established a Precision Oncology Decision Support (PODS) team that provides annotations at the alteration-level and subsequently determined if clinical decision-making was influenced. METHODS:Genomic alterations were annotated to determine actionability based on a variant's known or potential functional and/or therapeutic significance. The medical records of a subset of patients annotated in 2015 were manually reviewed to assess trial enrollment. A web-based survey was implemented to capture the reasons why genotype-matched therapies were not pursued. RESULTS:PODS processed 1,669 requests for annotation of 4,084 alterations (2,254 unique) across 49 tumor types for 1,197 patients. 2,444 annotations for 669 patients included an actionable variant call: 32.5% actionable, 9.4% potentially, 29.7% unknown, 28.4% non-actionable. 66% of patients had at least one actionable/potentially actionable alteration. 20.6% (110/535) patients annotated enrolled on a genotype-matched trial. Trial enrolment was significantly higher for patients with actionable/potentially actionable alterations (92/333, 27.6%) than those with unknown (16/136, 11.8%) and non-actionable (2/66, 3%) alterations (p=0.00004). Actionable alterations in PTEN, PIK3CA, and ERBB2 most frequently led to enrollment on genotype-matched trials. Clinicians cited a variety of reasons why patients with actionable alterations did not enroll on trials. CONCLUSION:Over half of alterations annotated were of unknown significance or non-actionable. Physicians were more likely to enroll a patient on a genotype-matched trial when an annotation supported actionability. Future studies are needed to demonstrate the impact of decision support on trial enrollment and oncologic outcomes.

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Quantum deep reinforcement learning for clinical decision support in oncology: application to adaptive radiotherapy.

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