Integrated ultrasound radiomics and clinical data to predict PD-1 blockade efficacy in unresectable hepatocellular carcinoma.
Authors
Affiliations (10)
Affiliations (10)
- Department of Ultrasonography, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China.
- Department of Hepatic Surgery VI, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China.
- Department of Hepatobiliary Surgery, No. 971 Hospital of Chinese PLA Navy, Qingdao, 266071, China.
- Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing College, Jiaxing, 314001, China.
- Department of Hepatobiliary Surgery, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
- Department of General Surgery, Taiyuan People's Hospital, Taiyuan, 030001, China.
- School of Clinical Medicine, Tsinghua University, Beijing, 100084, China.
- School of Information Science and Technology, Fudan University, Shanghai, China.
- Department of Ultrasonography, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China. [email protected].
- Department of Hepatic Surgery VI, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, China. [email protected].
Abstract
PD-1 blockade therapy has emerged as a valuable treatment option for advanced hepatocellular carcinoma (HCC), but its therapeutic response and overall efficacy vary among patients. This study develops an automated framework for predicting response to PD-1 blockade with enhanced accuracy. A comprehensive two-phase investigation was conducted, comprising a retrospective multicenter cohort (n = 793) for model development and a prospective cohort (n = 60) for validation. We established an integrated predictive framework combining ultrasound radiomics with clinical indicators. Model performance was evaluated by ROC analyses, focusing on the area under the curve (AUC). Molecular analyses of liver tissues were performed to explore mechanisms underlying treatment response. The ultrasound radiomics model achieved AUCs of 0.714 (training) and 0.617 (validation). The ensemble model, integrating both modalities, demonstrated superior predictive capability, with AUCs of 0.743 (training) and 0.641 (validation). The ensemble learning model, integrating both imaging and clinical modalities, exhibited superior predictive capability, attaining an AUC of 0.743 in the training cohort and 0.641 in the validation cohort. The ensemble model demonstrated exceptional clinical utility in predicting pathological necrosis following PD-1 blockade before hepatectomy, achieving an AUC of 0.692. Notably, it exhibited strong clinical utility in predicting pathological necrosis post-therapy, achieving an AUC of 0.692. Subsequent KEGG/GO analyses implicated key genes in necroptosis and programmed cell death pathways. The proposed ultrasound-based ensemble model offers a non-invasive, reproducible method to predict PD-1 blockade response in HCC, effectively integrating imaging and clinical data to enhance predictive accuracy and reveal potential molecular mediators of therapeutic efficacy. We developed an advanced automated predictive model that synergistically integrates ultrasound imaging with clinical indicators through ensemble learning methodology. This innovative model employs state-of-the-art deep learning architectures, specifically optimized convolutional neural networks, to accurately predict therapeutic response to PD-1 blockade in patients with unresectable hepatocellular carcinoma.