Toward Precision Medicine: Development and Validation of A Machine Learning Based Decision Support System for Optimal Sequencing in Castration-Resistant Prostate Cancer.

INTRODUCTION: Selecting a patient-specific sequencing strategy to maximize survival outcomes is a clinically unmet need for patients with castration-resistant prostate cancer (CRPC). We developed and validated an artificial intelligence-based decision support system (DSS) to guide optimal sequencing strategy selection. PATIENTS AND METHODS: Clinicopathological data of 46 covariates were retrospectively collected from 801 patients diagnosed with CRPC at 2 high-volume institutions between February 2004 and March 2021. Cox-proportional hazards regression survival (Cox) modeling in extreme gradient boosting (XGB) was used to perform survival analysis for cancer-specific mortality (CSM) and overall mortality (OM) according to the use of abiraterone acetate, cabazitaxel, docetaxel, and enzalutamide. The models were further stratified into first-, second-, and third-line models that each provided CSM and OM estimates for each line of treatment. The performances of the XGB models were compared with those of the Cox models and random survival forest (RSF) models in terms of Harrell's C-index. RESULTS: The XGB models showed greater predictive performance for CSM and OM compared to the RSF and Cox models. C-indices of 0.827, 0.807, and 0.748 were achieved for CSM in the first-, second-, and third-lines of treatment, respectively, while C-indices of 0.822, 0.813, and 0.729 were achieved for OM regarding each line of treatment, respectively. An online DSS was developed to provide visualization of individualized survival outcomes according to each line of sequencing strategy. CONCLUSION: Our DSS can be used in clinical practice by physicians and patients as a visualized tool to guide the sequencing strategy of CRPC agents.

Optimal Triage for COVID-19 Patients Under Limited Health Care Resources With a Parsimonious Machine Learning Prediction Model and Threshold Optimization Using Discrete-Event Simulation: Development Study.

BACKGROUND: The COVID-19 pandemic has placed an unprecedented burden on health care systems. OBJECTIVE: We aimed to effectively triage COVID-19 patients within situations of limited data availability and explore optimal thresholds to minimize mortality rates while maintaining health care system capacity. METHODS: A nationwide sample of 5601 patients confirmed with COVID-19 until April 2020 was retrospectively reviewed. Extreme gradient boosting (XGBoost) and logistic regression analysis were used to develop prediction models for the maximum clinical severity during hospitalization, classified according to the World Health Organization Ordinal Scale for Clinical Improvement (OSCI). The recursive feature elimination technique was used to evaluate the maintenance of model performance when clinical and laboratory variables were eliminated. Using populations based on hypothetical patient influx scenarios, discrete-event simulation was performed to find an optimal threshold within limited resource environments that minimizes mortality rates. RESULTS: The cross-validated area under the receiver operating characteristic curve (AUROC) of the baseline XGBoost model that utilized all 37 variables was 0.965 for OSCI ≥6. Compared to the baseline model's performance, the AUROC of the feature-eliminated model that utilized 17 variables was maintained at 0.963 with statistical insignificance. Optimal thresholds were found to minimize mortality rates in a hypothetical patient influx scenario. The benefit of utilizing an optimal triage threshold was clear, reducing mortality up to 18.1%, compared with the conventional Youden index. CONCLUSIONS: Our adaptive triage model and its threshold optimization capability revealed that COVID-19 management can be achieved via the cooperation of both the medical and health care management sectors for maximum treatment efficacy. The model is available online for clinical implementation.