Development of Machine Learning Models for Predicting Radiation Dermatitis in Breast Cancer Patients Using Clinical Risk Factors, Patient-Reported Outcomes, and Serum Cytokine Biomarkers.

Abstract

Background: Radiation dermatitis (RD) is a significant side effect of radiotherapy experienced by breast cancer patients. Severe symptoms include desquamation or ulceration of irradiated skin, which impacts quality of life and increases healthcare costs. Early identification of patients at risk for severe RD can facilitate preventive management and reduce severe symptoms. This study evaluated the utility of subjective and objective factors, such as patient-reported outcomes (PROs) and serum cytokines, for predicting RD in breast cancer patients. The performance of machine learning (ML) and logistic regression-based models were compared.

Patients and methods: Data from 147 breast cancer patients who underwent radiotherapy was analyzed to develop prognostic models. ML algorithms, including neural networks, random forest, XGBoost, and logistic regression, were employed to predict clinically significant Grade 2+ RD. Clinical factors, PROs, and cytokine biomarkers were incorporated into the risk models. Model performance was evaluated using nested cross-validation with separate loops for hyperparameter tuning and calculating performance metrics.

Results: Feature selection identified 18 predictors of Grade 2+ RD including smoking, radiotherapy boost, reduced motivation, and the cytokines interleukin-4, interleukin-17, interleukin-1RA, interferon-gamma, and stromal cell-derived factor-1a. Incorporating these predictors, the XGBoost model achieved the highest performance with an area under the curve (AUC) of 0.780 (95% CI: 0.701-0.854). This was not significantly improved over the logistic regression model, which demonstrated an AUC of 0.714 (95% CI: 0.629-0.798).

Conclusion: Clinical risk factors, PROs, and serum cytokine levels provide complementary prognostic information for predicting severe RD in breast cancer patients undergoing radiotherapy. ML and logistic regression models demonstrated comparable performance for predicting clinically significant RD with AUC>0.70.