Chinese expert consensus on the clinical application of molecular diagnostics in hepatobiliary cancers (2024 edition)^☆

Abstract

Hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) are significant health challenges in China because of their high prevalence and mortality rates. Advances in molecular diagnostics have opened new avenues for personalized treatment strategies. This consensus provides a comprehensive update on the clinical applications of molecular diagnostics in HCC and BTC and addresses the urgent need for personalized treatment strategies tailored to the Chinese population, emphasizing the importance of molecular markers in guiding targeted therapies and immunotherapies. By employing the Delphi method and the Grading of Recommendations Assessment, Development, and Evaluation system, the expert panel formulated evidence-based recommendations for the use of molecular diagnostics in the clinical management of HCC and BTC. Key molecular markers, such as isocitrate dehydrogenase (IDH) 1 and 2, fibroblast growth factor receptor 2 (FGFR2), BRAF V600E, human epidermal growth factor receptor 2 (HER2), rearranged during transfection (RET), and neurotrophic tyrosine receptor kinase (NTRK), are highlighted for their roles in optimizing treatment regimens. The consensus also explores the significance of emerging biomarkers, such as tumor mutation burden and microsatellite instability, in predicting responses to immune checkpoint inhibitors. The recommendations aim to enhance precision medicine approaches, improve patient outcomes, and foster the integration of molecular diagnostics into routine clinical practice.

Keywords

Hepatocellular carcinoma (HCC) / Biliary tract cancer (BTC) / Targeted therapy / Immunotherapy / Molecular markers / Expert consensus

List of experts (arranged in alphabetical order by the last name)

Aizier Ainiwaer (Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China), Xinyu Bi (Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chi-nese Academy of Medical Sciences and Peking Union Medical Col-lege, Beijing, China), Jianqiang Cai (Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China), Jing Chen (Liver Failure Treatment and Research Center, The Fifth Medical Center of PLA General Hospital, Beijing, China), Minshan Chen (Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China), Jiamin Cheng (Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China), Jun Cheng (Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China), Jiuwei Cui (Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Cancer Center, First Hospital of Jilin University, Changchun, Jilin, China), Yingrong Du (Department of Hepatology, The Third People's Hospital of Kunming, Kunming, Yunnan, China), Zhixian Hong (Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General Hospital, Beijing, China), Zhiyong Huang (Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei China), Weidong Jia (Department of Hepatic Surgery, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Heifei, Anhui, China), Xiaodong Jia (Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China), Ming Kuang (Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China), Ren Lang (Department of Hepatobiliary and Pancreaticosplenic Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China), Wei Li (No.2 People's Hospital of Fuyang City, Fuyang, Anhui, China), Xiufeng Liu (Department of Medical Oncology, Bayi Hospital Affiliated to Nanjing Chinese Medical University, Nanjing, Jiangsu, China), Zhenwen Liu (Liver Transplantation Center, The Fifth Medical Center of PLA General Hospital, Beijing, China), Shichun Lu (Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, Key Laboratory of Digital Hepatobiliary Surgery, Chinese People's Liberation Army Medical School, Chinese People's Liberation Army General Hospital, Beijing, China), Yinying Lu (Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China), Li Luo (Department of Oncology, Guihang Guiyang Hospital, Guiyang, Guizhou, China), Jie Pan (Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China), Tao Peng (Depart-ment of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China), Liyong Pu (Liver Cancer Research Institute, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China), Honggang Qian (Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, China), Tianqiang Song (Department of Hepatobiliary, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China), Bin Sun (Center of Interventional Oncology and Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China), Xiaodong Tan (Depart-ment of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China), Bo Tu (Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China), Hongguang Wang (Depart-ment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China), Liming Wang (Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Dalian Medical Univer-sity, Dalian, Liaoning, China), Lu Wang (Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China), Nanya Wang (Department of Cancer, Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China), Qiong Wang (Department of Oncology, Jiangyin People's Hospital, Jian-gyin, Jiangsu, China), Feng Xia (Institute of Hepatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China), Song Yang (Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing, China), Hongfang Yin (Department of Pathology, Beijing Tsinghua Chang Gung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China), Chaohui Yu (Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China), Hongjiang Yu (Department of Medical Oncology, Tongliao City Hospital, Tongliao, Inner Mongolia, China), Lingxiang Yu (Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China), Yilan Zeng (Department of Clinical Nutrition, Clinical Medical Center of Public Health of Chengdu, Chengdu, Sichuan, China), Zhen Zeng (Department of Liver Disease Medicine, The Fifth Medical Center of PLA General Hospital, Beijing, China), Haoran Zha (Department of Oncology, Rocket Force Medical Center of PLA, Beijing, China), Jialin Zhang (Department of Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China), Meng Zhang (Department of Hepatobiliary Surgery, Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China), Ning Zhang (Translational Cancer Research Center, Peking Univer-sity First Hospital, Beijing, China), Ning Zhang (Senior Department of Liver Disease, The Fifth Medical Center of PLA General Hospital, Beijing, China), Qiang Zhang (Department of Oncology, Fourth People's Hospital of Zibo, Zibo, Shandong, China), Haitao Zhao (Department of Liver Surgery, Peking Union Medical College Hos-pital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China), Jingmin Zhao (Department of Pathology and Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing, China), Ming Zhao (Department of Minimally Invasive Interventional Therapy, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, Guangzhou, Guang-dong, China), Pan Zhao (Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, Beijing, China), Qiwen Zhao (Department of Pathology, The Sixth Medical Center of PLA General Hospital, Beijing, China), Xueke Zhao (Department of In-fectious Diseases, The Affiliated Hospital of Guizhou Medical Uni-versity, Guiyang, Guizhou, China), Yiming Zhao (Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China), Xuting Zhi (Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China), Guangde Zhou (Department of Pathology, The Fifth Medical Center of PLA General Hospital, Beijing, China), Zhenyu Zhu (Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General Hospital, Beijing, China), Shi Zuo (Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China).

Authors’ contributions

Aizier Ainiwaer and Jiamin Cheng contributed equally to the work. Aizier Ainiwaer: Writing e original draft, Visualization, Methodology, Investigation, Formal analysis. Jiamin Cheng: Writing e original draft, Investigation, Formal analysis, Data cura-tion. Ren Lang: Formal analysis, Data curation. Tao Peng: Formal analysis, Data curation. Xinyu Bi: Methodology, Investigation. Yinying Lu: Writing e review & editing, Supervision, Resources, Project administration, Funding acquisition, Conceptualization. Other experts participated in consensus discussion and sugges-tions. All authors read and approved the final manuscript.

Declaration of competing interest

The authors declare that there is no conflicts of interest.

Acknowledgements

This work was funded by the National Natural Science Foun-dation of China (No. 82272956).

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