A multimodal fusion system predicting survival benefits of immune checkpoint inhibitors in unresectable hepatocellular carcinoma

Jun Xu; Tengfei Wang; Junjun Li; Yong Wang; Zhangxiang Zhu; Xiao Fu; Junjie Wang; Zhenglin Zhang; Wei Cai; Ruipeng Song; Changlong Hou; Li-Zhuang Yang; Hongzhi Wang; Stephen T C Wong; Hai Li

doi:10.1038/s41698-025-00979-6

A multimodal fusion system predicting survival benefits of immune checkpoint inhibitors in unresectable hepatocellular carcinoma

NPJ Precis Oncol. 2025 Jun 14;9(1):185. doi: 10.1038/s41698-025-00979-6.

Authors

Jun Xu^#^{1

2

3

4}, Tengfei Wang^#^{1

2

3}, Junjun Li⁵, Yong Wang⁶, Zhangxiang Zhu⁷, Xiao Fu^{1

3}, Junjie Wang^{1

2}, Zhenglin Zhang^{1

2}, Wei Cai⁸, Ruipeng Song⁸, Changlong Hou⁴, Li-Zhuang Yang^{1

2

3}, Hongzhi Wang^{1

2

3}, Stephen T C Wong^{9

10}, Hai Li^{11

12

13}

Affiliations

¹ Hefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, P. R. China.
² University of Science and Technology of China, Hefei, P. R. China.
³ Department of Oncology, Hefei Cancer Hospital; Chinese Academy of Sciences, Hefei, P. R. China.
⁴ Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, P. R. China.
⁵ Department of Radiology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, P. R. China.
⁶ Department of Radiology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, P. R. China.
⁷ Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, P. R. China.
⁸ Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, the University of Science and Technology of China, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei, P. R. China.
⁹ Department of Systems Medicine and Bioengineering, Houston Methodist Neal Cancer Center, Houston Methodist Hospital, Houston, TX, USA. stwong@houstonmethodist.org.
¹⁰ Department of Radiology, Weill Cornell Medical College, New York, NY, USA. stwong@houstonmethodist.org.
¹¹ Hefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, P. R. China. hli@cmpt.ac.cn.
¹² University of Science and Technology of China, Hefei, P. R. China. hli@cmpt.ac.cn.
¹³ Department of Oncology, Hefei Cancer Hospital; Chinese Academy of Sciences, Hefei, P. R. China. hli@cmpt.ac.cn.

^# Contributed equally.

Abstract

Early identification of unresectable hepatocellular carcinoma (HCC) patients who may benefit from immune checkpoint inhibitors (ICIs) is crucial for optimizing outcomes. Here, we developed a multimodal fusion (MMF) system integrating CT-derived deep learning features and clinical data to predict overall survival (OS) and progression-free survival (PFS). Using retrospective multicenter data (n = 859), the MMF combining an ensemble deep learning (Ensemble-DL) model with clinical variables achieved strong external validation performance (C-index: OS = 0.74, PFS = 0.69), outperforming radiomics (29.8% OS improvement), mRECIST (27.6% OS improvement), clinical benchmarks (C-index: OS = 0.67, p = 0.0011; PFS = 0.65, p = 0.033), and Ensemble-DL (C-index: OS = 0.69, p = 0.0028; PFS = 0.66, p = 0.044). The MMF system effectively stratified patients across clinical subgroups and demonstrated interpretability through activation maps and radiomic correlations. Differential gene expression analysis revealed enrichment of the PI3K/Akt pathway in patients identified by the MMF system. The MMF system provides an interpretable, clinically applicable approach to guide personalized ICI treatment in unresectable HCC.

Abstract

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