Abstract
PURPOSE: Colorectal cancer is the third most common cancer globally, with a high mortality rate due to metastatic progression, particularly in the liver. Surgical resection remains the main curative treatment, but only a small subset of patients is eligible for surgery at diagnosis. For patients with initially unresectable colorectal liver metastases (CRLM), neoadjuvant chemotherapy can downstage tumors, potentially making surgery feasible. We investigate whether radiomic signatures-quantitative imaging biomarkers derived from baseline computed tomography (CT) scans-can noninvasively predict chemotherapy response in patients with unresectable CRLM, offering a pathway toward personalized treatment planning. APPROACH: We used radiomics combined with a stacking classifier (SC) to predict treatment outcome. Baseline CT imaging data from 355 patients with initially unresectable CRLM were analyzed using two regions of interest (ROIs) separately (all tumors in the liver and the largest tumor by volume). From each ROI, 107 radiomic features were extracted. The dataset was split into training and testing sets, and multiple machine learning models were trained and integrated via stacking to enhance prediction. Logistic regression coefficients were used to derive radiomic signatures. RESULTS: The SC achieved strong predictive performance, with an area under the receiver operating characteristic curve of up to 0.77 for response prediction. Logistic regression identified 12 and 7 predictive features for treatment response in all tumors and the largest tumor ROIs, respectively. CONCLUSION: Our findings demonstrate that radiomic features from baseline CT scans can serve as robust, interpretable biomarkers for predicting chemotherapy response, offering insights to guide personalized treatment in unresectable CRLM.