Abstract
Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision is the standard treatment for locally advanced rectal cancer. However, the response to nCRT varies significantly among patients, making it crucial to identify those unlikely to benefit to avoid unnecessary toxicities. Radiomics, a technique for extracting quantitative features from medical images like computed tomography (CT), offers a promising noninvasive approach to analyze disease characteristics and potentially improve treatment decision-making. This retrospective cohort study aimed to compare the performance of various machine learning models in predicting the response to nCRT in rectal cancer based on medical data, including radiomic features extracted from CT, and to investigate the contribution of radiomics to these models. Participants who had completed a long course of nCRT before undergoing surgery were retrospectively enrolled. The patients were categorized into 2 groups: nonresponders and responders based on pathological assessment using the Ryan tumor regression grade. Pretreatment contrast-enhanced CT scans were used to extract 101 radiomic features using the PyRadiomics library. Clinical data, including age, gender, tumor grade, presence of colostomy, carcinoembryonic antigen level, constipation status, albumin, and hemoglobin levels, were also collected. Fifteen machine learning models were trained and evaluated using 10-fold cross-validation on a training set (n = 112 patients). The performance of the trained models was then assessed on an internal test set (n = 35 patients) and an external test set (n = 40 patients) using accuracy, area under the ROC curve (AUC), recall, precision, and F1-score. Among the models, the gradient boosting classifier showed the best training performance (accuracy: 0.92, AUC: 0.95, recall: 0.96, precision: 0.93, F1-score: 0.94). On the internal test set, the extra trees classifier (ETC) achieved an accuracy of 0.84, AUC of 0.90, recall of 0.92, precision of 0.87, and F1-score of 0.90. In the external validation, the ETC model yielded an accuracy of 0.75, AUC of 0.79, recall of 0.91, precision of 0.76, and F1-score of 0.83. Patient-specific biomarkers were more influential than radiomic features in the ETC model. The ETC consistently showed strong performance in predicting nCRT response. Clinical biomarkers, particularly tumor grade, were more influential than radiomic features. The model's external validation performance suggests potential for generalization.