Quantitative Thermal Imaging Biomarkers to Detect Acute Skin Toxicity From Breast Radiation Therapy Using Supervised Machine Learning

Abstract

Radiation-induced dermatitis is a common side effect of breast radiation therapy (RT). Current methods to evaluate breast skin toxicity include clinical examination, visual inspection, and patient-reported symptoms. Physiological changes associated with radiation-induced dermatitis, such as inflammation, may also increase body-surface temperature, which can be detected by thermal imaging. Quantitative thermal imaging markers were identified and used in supervised machine learning to develop a predictive model for radiation dermatitis. Ninety patients treated for adjuvant whole-breast RT (4250 cGy/fx = 16) were recruited for the study. Thermal images of the treated breast were taken at 4 intervals: before RT, then weekly at fx = 5, fx = 10, and fx= 15. Parametric thermograms were analyzed and yielded 26 thermal-based features that included surface temperature (°C) and texture parameters obtained from (1) gray-level co-occurrence matrix, (2) gray-level run-length matrix, and (3) neighborhood gray-tone difference matrix. Skin toxicity was evaluated at the end of RT using the Common Terminology Criteria for Adverse Events (CTCAE) guidelines (Ver.5). Binary group classes were labeled according to a CTCAE cut-off score of ≥2, and thermal features obtained at fx = 5 were used for supervised machine learning to predict skin toxicity. The data set was partitioned for model training, independent testing, and validation. Fifteen patients (∼17% of the whole data set) were randomly selected as an unseen test data set, and 75 patients (∼83% of the whole data set) were used for training and validation of the model. A random forest classifier with leave-1-patient-out cross-validation was employed for modeling single and hybrid parameters. The model performance was reported using receiver operating characteristic analysis on patients from an independent test set. Thirty-seven patients presented with adverse skin effects, denoted by a CTCAE score ≥2, and had significantly higher local increases in skin temperature, reaching 36.06°C at fx = 10 (P = .029). However, machine-learning models demonstrated early thermal signals associated with skin toxicity after the fifth RT fraction. The cross-validated model showed high prediction accuracy on the independent test data (test accuracy = 0.87) at fx = 5 for predicting skin toxicity at the end of RT. Early thermal markers after 5 fractions of RT are predictive of radiation-induced skin toxicity in breast RT.