ARCliDS: A Clinical Decision Support System for AI-assisted Decision-Making in Response-Adaptive Radiotherapy

Abstract

Background: 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). Methods: ARCliDS is composed of two main components: Artificial 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 Network (GNN) is applied to exploit the inter-feature relationships for improved modeling performance and a novel double GNN architecture is designed to avoid unphysical 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 Network to generate 10,000 synthetic patients. The ODM was trained on the synthetic patients and validated on the original dataset. Results: Double GNN architecture was able to correct the unphysical 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. 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.

Competing Interest Statement

IEN is on the scientific advisory of Endectra, LLC., act as deputy editor for the journal of Medical Physics and receives funding from NIH and DoD. IDD acknowledges NIH grants R01-MH126137 and T32-GM141746. TSL and RKTH acknowledge NIH grant P01 CA59827 for funding the clinical trials that produced the datasets. A provisional patent was filed, titled "Adaptive Radiotherapy Clinical Decision Support Tool and Related Methods", Application Serial Number: 63/272,888, filed on 10/28/2021.

Funding Statement

This work was partly supported by National Institute of Health (NIH) grant R01-CA233487 and its supplement.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Moffitt Cancer Center and ethics committee/IRB of University of Michigan gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

The training data analyzed in this study are obtained from the University of Michigan. Restrictions apply to the availability of these data, which were used under the data sharing protocol for this study. ARCliDS is publicly available at https://arclids.shinyapps.io/ARCliDS for a limited time.

https://arclids.shinyapps.io/ARCliDS

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