Background/objective: Pain is a challenging multifaceted symptom reported by most cancer patients, resulting in a substantial burden on both patients and healthcare systems. This systematic review aims to explore applications of artificial intelligence/machine learning (AI/ML) in predicting pain-related outcomes and supporting decision-making processes in pain management in cancer. Methods: A comprehensive search of Ovid MEDLINE, EMBASE and Web of Science databases was conducted using terms including Cancer, Pain, Pain Management, Analgesics, Opioids, Artificial Intelligence, Machine Learning, Deep Learning, and Neural Networks, published up to September 7, 2023. The screening process was performed using the Covidence screening tool. Only original studies conducted in human cohorts were included. AI/ML models, their validation and performance and adherence to TRIPOD guidelines were summarized from the final included studies. Results: This systematic review included 44 studies from 2006-2023. Most studies were prospective and uni-institutional. There was an increase in the trend of AI/ML studies in cancer pain in the last 4 years. Nineteen studies used AI/ML for classifying cancer patients pain development after cancer therapy, with median AUC 0.80 (range 0.76-0.94). Eighteen studies focused on cancer pain research with median AUC 0.86 (range 0.50-0.99), and 7 focused on applying AI/ML for cancer pain management decisions with median AUC 0.71 (range 0.47-0.89). Multiple ML models were investigated with. median AUC across all models in all studies (0.77). Random forest models demonstrated the highest performance (median AUC 0.81), lasso models had the highest median sensitivity (1), while Support Vector Machine had the highest median specificity (0.74). Overall adherence of included studies to TRIPOD guidelines was 70.7%. Lack of external validation (14%) and clinical application (23%) of most included studies was detected. Reporting of model calibration was also missing in the majority of studies (5%). Conclusion: Implementation of various novel AI/ML tools promises significant advances in the classification, risk stratification, and management decisions for cancer pain. These advanced tools will integrate big health-related data for personalized pain management in cancer patients. Further research focusing on model calibration and rigorous external clinical validation in real healthcare settings is imperative for ensuring its practical and reliable application in clinical practice.

The authors have declared no competing interest.

This study was funded by NIDCR (K01DE03052) and the National Cancer Institute (K12CA088084)

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