Decoding tumor heterogeneity with imaging biomarkers predicts response to TACE plus immunotherapy and targeted therapy in HCC (CHANCE2204)

作者：Zhi-Cheng Jin, Jingwei Wei, Yu‐Dong Xiao, Anfeng Si, Jian-Jian Chen, Xiaoli Zhu, Jinze Li, Fang Nie, Rong Ding, Haifeng Zhou, Wei Ding, Bin‐Yan Zhong, Yangyang Xie, Hong-Tao Hu, Guowen Yin, Jiansong Ji, Weihua Zhang, Hai‐Bin Shi, Jianbing Wu, Guohui Xu, Chunwang Yuan, Wei-Zhu Yang, Ruibao Liu, Ye-Ming Wu, Chuansheng Zheng, Aibing Xu, Mingsheng Huang, Jiaping Li, Li Chen, Shu-Wei Wen, Yu-Qing Wang, Shanzhi Gu, Dongrui Li, Duo Wang, Guan‐Hui Zhou, Weidong Wang, Zhenwei Peng, Xinying Wang, Haidong Zhu, Jie Tian, Gao-Jun Teng · 发表于：Hepatology · 年份：2025 · DOI：10.1097/hep.0000000000001593 · 被引用次数：9 · 研究领域：Cancer Immunotherapy and Biomarkers、Radiomics and Machine Learning in Medical Imaging、Radiopharmaceutical Chemistry and Applications

BACKGROUND AND AIMS: This study aims to quantify intratumoral heterogeneity (ITH) and identify prognostic imaging biomarkers in patients with HCC treated with transarterial chemoembolization combined with immune checkpoint inhibitor plus molecular targeted therapy (TACE-ICI-MTT). APPROACH AND RESULTS: This multicenter cohort study included 742 patients with unresectable HCC who received first-line TACE-ICI-MTT from January 2018 to December 2022. Radiomic features representing global tumor regions (GTRs) and ITH were extracted from pretreatment CT scans. A composite GTR-ITH score was generated using principal component analysis to integrate both GTR- and ITH-related features. Ensemble learning with multiple machine learning algorithms was employed to predict treatment response. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC). Following feature selection, 17 GTR- and 27 ITH-related radiomic features were retained to construct the GTR-ITH score. The model demonstrated high discriminative performance, with AUCs of 0.94 in the training set, 0.82 in the internal validation set, and 0.83 in the independent test set. The GTR-ITH score was strongly associated with treatment response (OR: 34.39; p<0.001) and independently predicted overall survival (HR: 0.63; p=0.004). Patients classified as GTR-ITH low-risk consistently showed significantly prolonged progression-free survival and overall survival. To reveal the biological relevance o...