Predicting treatment response and prognosis of immune checkpoint inhibitors-based combination therapy in advanced hepatocellular carcinoma using a longitudinal CT-based radiomics model: a multicenter study

Background: Identifying effective predictive strategies to assess the response of immune checkpoint inhibitors (ICIs)-based combination therapy in advanced hepatocellular carcinoma (HCC) is crucial. This study presents a new longitudinal CT-based radiomics model to predict treatment response and prognosis in advanced HCC patients undergoing ICIs-based combination therapy. Methods: Longitudinal CT images were collected before and during the treatment for HCC patients across three institutions from January 2019 to April 2022. A total of 1316 radiomic features were extracted from arterial and portal venous phase abdominal CT images for each patient. A model called Longitudinal Whole-liver CT-based Radiomics (LWCTR) was developed to categorize patients into responders or non-responders using radiomic features and clinical information through support vector machine (SVM) classifiers. The area under the curve (AUC) was used as the performance metric and subsequently applied for risk stratification and prognostic assessment. The Shapley Additive explanations (SHAP) method was used to calculate the Shapley value, which explains the contribution of each feature in the SVM model to the prediction. Results: This study included 395 eligible participants, with a median age of 57 years (IQR 51–66), comprising 344 males and 51 females. The LWCTR model performed well in predicting treatment response, achieving an AUC of 0.883 (95% confidence interval [CI] 0.881–0.888) in the training cohort, 0.876 (0.858–0.895) in the internal validation cohort, and 0.875 (0.860–0.887) in the external test cohort. The Rad-Nomo model, integrating the LWCTR model's prediction score (Rad-score) with the modified Response Evaluation Criteria in Solid Tumors (mRECIST), demonstrated strong prognostic performance. It achieved time-dependent AUC values of 0.902, 0.823, and 0.850 at 1, 2, and 3 years in the internal validation cohort and 0.893, 0.848, and 0.762 at the same intervals in the external test cohort. Conclusion: The proposed LWCTR model performs well in predicting treatment response and prognosis in patients with HCC receiving ICIs-based combination therapy, potentially contributing to personalized and timely treatment decisions.