Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
AADN score: Predicting response to transarterial chemoembolization, sintilimab and lenvatinib in patients with hepatocellular carcinoma
Xue Zhang, Min-Jun Liao, Li-Ying Ren, Wan-Ying Qin, Shao-Wei Mu, Shao-Ping She, Ran Fei, Xu Cong, Yuan-Ping Zhou, Dong-Bo Chen, Hong-Song Chen
Xue Zhang, Min-Jun Liao, Li-Ying Ren, Shao-Ping She, Ran Fei, Xu Cong, Dong-Bo Chen, Hong-Song Chen, Peking University People’s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People’s Hospital, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing 100044, China
Min-Jun Liao, Yuan-Ping Zhou, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Wan-Ying Qin, Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541000, Guangxi Zhuang Autonomous Region, China
Shao-Wei Mu, Department of Hepatobiliary Surgery, Peking University People’s Hospital, Beijing 100044, China
Hong-Song Chen, Peking University Third Hospital, Beijing 100191, China
Co-first authors: Xue Zhang and Min-Jun Liao.
Co-corresponding authors: Dong-Bo Chen and Hong-Song Chen.
Author contributions: Zhang X and Liao MJ contributed to data analysis and manuscript writing; Ren LY, Qin WY, Mu SW, She SP, Fei R and Cong X were responsible for patient enrollment and data collection; Zhou YP provided patient care and study materials; Chen DB and Chen HS conceived and supervised the study; Zhang X and Liao MJ contributed equally to this manuscript and are co-first authors; Chen DB and Chen HS contributed equally to this manuscript and are co-corresponding authors. All authors reviewed and approved the final manuscript.
Supported by National Key Sci-Tech Special Project of China, No. 2018ZX10302207; Beijing Nova Program, No. 20250484965; Beijing Natural Science Foundation, No. 7222191 and No. 7244426; Fundamental Research Funds for the Central Universities, Peking University, No. PKU2024XGK005; Peking University Medicine Seed Fund for Interdisciplinary Research, No. BMU2021MX007 and No. BMU2022MX001; Fundamental Research Funds for the Central Universities, Peking University People’s Hospital Scientific Research Development Funds, No. RDX2020-06 and No. RDJ2022-14; and the Qi-Min Project.
Institutional review board statement: The study protocol, conducted in accordance with the principles of the Declaration of Helsinki, was approved by the Institutional Review Board of each participating center of Peking University People’s Hospital (Approval No. 2024PHB061-001), NanFang Hospital of Southern Medical University (Approval No. NFEC-202305-K32-01), and Affiliated Hospital of Guilin Medical University (Approval No. 2021WJWZC14).
Informed consent statement: Written informed consent was obtained from all participants prior to the initiation of combined therapy.
Conflict-of-interest statement: The authors declare no conflict of interest.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: If reasonably necessary, the datasets used and analyzed in this study can be obtained from the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Hong-Song Chen, Professor, Peking University People’s Hospital, Peking University Hepatology Institute, Infectious Disease and Hepatology Center of Peking University People’s Hospital, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China.
chenhongsong2999@163.com
Received: September 9, 2025
Revised: October 11, 2025
Accepted: November 10, 2025
Published online: December 28, 2025
Processing time: 110 Days and 2.6 Hours
BACKGROUND
Although the triple therapy of transarterial chemoembolization (TACE) combined with immune checkpoint inhibitors and tyrosine kinase inhibitors is becoming an effective treatment for unresectable hepatocellular carcinoma (uHCC). However, there is still a lack of effective tools for predicting therapeutic effects at present.
AIM
To develop a predictive tool for the prognosis of uHCC patients treated with TACE, sintilimab and lenvatinib.
METHODS
Based on multicenter data, this study constructed and validated an AADN score as variables to predict overall survival in patients treated with this combination therapy. This study included 188 uHCC cases (training cohort: n = 101, validation cohort: n = 87) from three different hospitals. Who were treated with TACE, sintilimab and lenvatinib.
RESULTS
In multivariate analysis, alpha-fetoprotein ≥ 100 ng/mL [hazard ratio (HR) = 2.579, P = 0.010], alkaline phosphatase > 120 U/L, (HR = 2.234, P = 0.021), direct bilirubin > 7.3 μmol/L (HR = 2.931, P = 0.007) and neutrophil to lymphocyte ratio > 2.5 (HR = 3.127, P = 0.006) were identified as independent prognostic factors and were used to establish the AADN score. Kaplan-Meier survival curves and time-dependent receiver operating characteristic curves were used to assess the accuracy of the AADN score, with area under receiver operating characteristic curve values of 0.827 (training cohort, 95% confidence interval: 0.743-0.911) and 0.832 (validation cohort, 95% confidence interval: 0.742-0.923). According to the score, the patients were divided into low-risk, intermediate-risk and high-risk groups. Overall survival and progression-free survival were significantly different between groups.
CONCLUSION
The AADN score can distinguish the prognostic risk of uHCC patients treated with TACE, sintilimab and lenvatinib, provides a basis for individualized treatment decision-making, and have clinical application prospect.
Core Tip: This multicenter study developed and validated a novel AADN score to predict survival in patients with unresectable hepatocellular carcinoma treated with triple therapy (transarterial chemoembolization, sintilimab, and lenvatinib). The AADN score effectively stratified patients into distinct low-risk, intermediate-risk, and high-risk groups with significantly different overall and progression-free survival outcomes, demonstrating high predictive accuracy. This tool provides a practical basis for prognostic assessment and individualized treatment decision-making in this patient population.
