Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study

doi:10.1016/j.eclinm.2024.102622

. 2024 May 6:72:102622.

doi: 10.1016/j.eclinm.2024.102622. eCollection 2024 Jun.

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study

Zhi-Cheng Jin^{1

2}, Jian-Jian Chen^{1

2}, Xiao-Li Zhu³, Xu-Hua Duan⁴, Yu-Jing Xin⁵, Bin-Yan Zhong³, Jin-Zhang Chen⁶, Jun Tie⁷, Kang-Shun Zhu⁸, Lan Zhang^{9

10}, Ming Huang¹¹, Ming-Jian Piao¹², Xiao Li¹³, Hai-Bin Shi¹⁴, Rui-Bao Liu¹⁵, Ai-Bing Xu¹⁶, Fanpu Ji^{17

18}, Jian-Bing Wu¹⁹, Guo-Liang Shao²⁰, Hai-Liang Li²¹, Ming-Sheng Huang²², Zhi-Yi Peng²³, Jian-Song Ji²⁴, Chun-Wang Yuan²⁵, Xiu-Feng Liu²⁶, Zhou-Chao Hu²⁷, Wei-Zhu Yang²⁸, Guo-Wen Yin²⁹, Jin-Hua Huang³⁰, Nai-Jian Ge³¹, Xiaolong Qi³², Yang Zhao³³, Jia-Wei Zhou³³, Guo-Hui Xu³⁴, Qiang Tu³⁵, Hai-Lan Lin³⁶, Yao-Jun Zhang^{37

38}, Hua Jiang³⁹, Hai-Bo Shao⁴⁰, Yong-Jie Su⁴¹, Ting-Song Chen⁴², Bao-Qi Shi⁴³, Xiang Zhou¹³, Hai-Tao Zhao¹², Hai-Dong Zhu^{1

2}, Zheng-Gang Ren^{9

10}, Gao-Jun Teng^{1

2}; CHANCE2201 Investigators

Collaborators, Affiliations

Collaborators

CHANCE2201 Investigators:
Zhi-Cheng Jin, Jian-Jian Chen, Xiao-Li Zhu, Xu-Hua Duan, Yu-Jing Xin, Bin-Yan Zhong, Jin-Zhang Chen, Jun Tie, Kang-Shun Zhu, Lan Zhang, Ming Huang, Ming-Jian Piao, Xiao Li, Hai-Bin Shi, Rui-Bao Liu, Ai-Bing Xu, Fan-Pu Ji, Jian-Bing Wu, Guo-Liang Shao, Hai-Liang Li, Ming-Sheng Huang, Zhi-Yi Peng, Jian-Song Ji, Chun-Wang Yuan, Xiu-Feng Liu, Zhou-Chao Hu, Wei-Zhu Yang, Guo-Wen Yin, Jin-Hua Huang, Nai-Jian Ge, Xiao-Long Qi, Yang Zhao, Jia-Wei Zhou, Guo-Hui Xu, Qiang Tu, Hai-Lan Lin, Yao-Jun Zhang, Hua Jiang, Hai-Bo Shao, Yong-Jie Su, Ting-Song Chen, Bao-Qi Shi, Wen-Ge Xing, Shan-Zhi Gu, Wei-Dong Wang, Song Wang, Shu-Wei Wen, Wei-Fu Lv, Xu Zhu, Wei Mu, Wei-Xin Ren, Zai-Ming Lu, Yong Fan, Jia-Ping Li, Wei Zhao, Chuan-Sheng Zheng, Xu-Ya Zhao, Hui Zhao, Jian Xu, Wen-Hao Hu, Yan-Ming Lei, Qing-Hua Wu, Huan-Zhang Niu, Jia-Rui Li, Jian-Jun Han, Dui-Ping Feng, Zheng Cai, Qing-Dong Li, Zhen-Yu Dai, Rong-Shu Shi, Yong Chen, Wen-Jun Wang, Li-Nan Yin, Xiang Zhou, Hai-Tao Zhao, Hai-Dong Zhu, Zheng-Gang Ren, Gao-Jun Teng

Affiliations

¹ Center of Interventional Radiology & Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
² State Key Laboratory of Digital Medical Engineering, National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China.
³ Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
⁴ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
⁵ Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁶ State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁷ National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, China.
⁸ Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁹ Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
¹⁰ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
¹¹ Department of Minimally Invasive Interventional Therapy, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
¹² Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹³ Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹⁴ Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
¹⁵ Department of Interventional Radiology, The Tumor Hospital of Harbin Medical University, Harbin, China.
¹⁶ Department of Interventional Therapy, Nantong Tumor Hospital, Nantong, China.
¹⁷ Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁸ Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, China.
¹⁹ Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
²⁰ Intervention Department, Zhejiang Cancer Hospital, Hangzhou, China.
²¹ Department of Minimally Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
²² Department of Interventional Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
²³ Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
²⁴ Department of Radiology, Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, School of Medicine, Lishui Hospital of Zhejiang University, Lishui, China.
²⁵ Center of Interventional Oncology and Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
²⁶ Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, China.
²⁷ Interventional Diagnosis and Treatment Center, Zhoushan Hospital, Wenzhou Medical University, Wenzhou, China.
²⁸ Department of Interventional Radiology, Union Hospital of Fujian Medical University, Fuzhou, China.
²⁹ Department of Interventional Radiology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
³⁰ Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.
³¹ Department of Interventional Radiology, Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China.
³² Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
³³ Department of Biostatistics, Nanjing Medical University, Nanjing, China.
³⁴ Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Chengdu, China.
³⁵ Department of Hepatobiliary Oncology Surgery, Department of Interventional Oncology, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China.
³⁶ Department of Tumor Interventional Therapy, Fujian Cancer Hospital, Fuzhou, China.
³⁷ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
³⁸ Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
³⁹ Cancer Treatment Centers, Second Affiliated Hospital of Kunming Medical University, Kunming, China.
⁴⁰ Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang, China.
⁴¹ Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen Key Laboratory of Translational Medical of Digestive System Tumor, Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
⁴² Second Department of Oncology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴³ Department of Intervention, Inner Mongolia People's Hospital, Hohhot, China.

PMID: 38745965
PMCID: PMC11090892
DOI: 10.1016/j.eclinm.2024.102622

Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study

Zhi-Cheng Jin et al. EClinicalMedicine. 2024.

. 2024 May 6:72:102622.

doi: 10.1016/j.eclinm.2024.102622. eCollection 2024 Jun.

Authors

Collaborators

CHANCE2201 Investigators:
Zhi-Cheng Jin, Jian-Jian Chen, Xiao-Li Zhu, Xu-Hua Duan, Yu-Jing Xin, Bin-Yan Zhong, Jin-Zhang Chen, Jun Tie, Kang-Shun Zhu, Lan Zhang, Ming Huang, Ming-Jian Piao, Xiao Li, Hai-Bin Shi, Rui-Bao Liu, Ai-Bing Xu, Fan-Pu Ji, Jian-Bing Wu, Guo-Liang Shao, Hai-Liang Li, Ming-Sheng Huang, Zhi-Yi Peng, Jian-Song Ji, Chun-Wang Yuan, Xiu-Feng Liu, Zhou-Chao Hu, Wei-Zhu Yang, Guo-Wen Yin, Jin-Hua Huang, Nai-Jian Ge, Xiao-Long Qi, Yang Zhao, Jia-Wei Zhou, Guo-Hui Xu, Qiang Tu, Hai-Lan Lin, Yao-Jun Zhang, Hua Jiang, Hai-Bo Shao, Yong-Jie Su, Ting-Song Chen, Bao-Qi Shi, Wen-Ge Xing, Shan-Zhi Gu, Wei-Dong Wang, Song Wang, Shu-Wei Wen, Wei-Fu Lv, Xu Zhu, Wei Mu, Wei-Xin Ren, Zai-Ming Lu, Yong Fan, Jia-Ping Li, Wei Zhao, Chuan-Sheng Zheng, Xu-Ya Zhao, Hui Zhao, Jian Xu, Wen-Hao Hu, Yan-Ming Lei, Qing-Hua Wu, Huan-Zhang Niu, Jia-Rui Li, Jian-Jun Han, Dui-Ping Feng, Zheng Cai, Qing-Dong Li, Zhen-Yu Dai, Rong-Shu Shi, Yong Chen, Wen-Jun Wang, Li-Nan Yin, Xiang Zhou, Hai-Tao Zhao, Hai-Dong Zhu, Zheng-Gang Ren, Gao-Jun Teng

Affiliations

¹ Center of Interventional Radiology & Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
² State Key Laboratory of Digital Medical Engineering, National Innovation Platform for Integration of Medical Engineering Education (NMEE) (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing, China.
³ Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, China.
⁴ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
⁵ Department of Minimally Invasive Comprehensive Treatment of Cancer, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
⁶ State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.
⁷ National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, China.
⁸ Department of Minimally Invasive Interventional Radiology and Radiology Center, and Minimally Invasive and Interventional Cancer Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁹ Department of Hepatic Oncology, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
¹⁰ Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
¹¹ Department of Minimally Invasive Interventional Therapy, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
¹² Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹³ Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
¹⁴ Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
¹⁵ Department of Interventional Radiology, The Tumor Hospital of Harbin Medical University, Harbin, China.
¹⁶ Department of Interventional Therapy, Nantong Tumor Hospital, Nantong, China.
¹⁷ Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁸ Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, China.
¹⁹ Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
²⁰ Intervention Department, Zhejiang Cancer Hospital, Hangzhou, China.
²¹ Department of Minimally Invasive Intervention, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
²² Department of Interventional Radiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
²³ Hepatobiliary and Pancreatic Interventional Treatment Center, Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
²⁴ Department of Radiology, Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, School of Medicine, Lishui Hospital of Zhejiang University, Lishui, China.
²⁵ Center of Interventional Oncology and Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
²⁶ Department of Oncology, Nanjing Jinling Hospital of Nanjing University, Nanjing, China.
²⁷ Interventional Diagnosis and Treatment Center, Zhoushan Hospital, Wenzhou Medical University, Wenzhou, China.
²⁸ Department of Interventional Radiology, Union Hospital of Fujian Medical University, Fuzhou, China.
²⁹ Department of Interventional Radiology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.
³⁰ Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center, Guangzhou, China.
³¹ Department of Interventional Radiology, Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China.
³² Center of Portal Hypertension, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
³³ Department of Biostatistics, Nanjing Medical University, Nanjing, China.
³⁴ Department of Interventional Radiology, Sichuan Cancer Hospital and Institute, Chengdu, China.
³⁵ Department of Hepatobiliary Oncology Surgery, Department of Interventional Oncology, Jiangxi Cancer Hospital of Nanchang University, Nanchang, China.
³⁶ Department of Tumor Interventional Therapy, Fujian Cancer Hospital, Fuzhou, China.
³⁷ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
³⁸ Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
³⁹ Cancer Treatment Centers, Second Affiliated Hospital of Kunming Medical University, Kunming, China.
⁴⁰ Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang, China.
⁴¹ Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen Key Laboratory of Translational Medical of Digestive System Tumor, Department of Hepatobiliary Surgery, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
⁴² Second Department of Oncology, Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴³ Department of Intervention, Inner Mongolia People's Hospital, Hohhot, China.

PMID: 38745965
PMCID: PMC11090892
DOI: 10.1016/j.eclinm.2024.102622

Abstract

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC.

Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821.

Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group.

Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile.

Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Keywords: Hepatocellular carcinoma; Immune checkpoint inhibitors; Target trial emulation; Transarterial chemoembolization; Tyrosine kinase inhibitors; Vascular endothelial growth factor.

PubMed Disclaimer

Conflict of interest statement

We declare no competing interests.

Figures

**Fig. 1**
Study cohort. HCC, hepatocellular carcinoma; ICIs, immune checkpoint inhibitors; VEGF, vascular endothelial growth factor; TKIs, tyrosine kinase inhibitors; TACE, transarterial chemoembolization; BCLC, Barcelona Clinic Liver Cancer; TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs.

**Fig. 2**
Kaplan–Meier curves of (A) overall survival, (B) progression-free survival assessed by RECIST v1.1, and (C) progression-free survival assessed by mRECIST after sIPTW. TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; TACE, transarterial chemoembolization; ICIs, immune checkpoint inhibitors; VEGF, vascular endothelial growth factor; TKIs, tyrosine kinase inhibitors; CI, confidence interval; mRECIST, modified RECIST; sIPTW, stabilized inverse probability of treatment weighting.

**Fig. 3**
Subgroup analysis of overall survival. TACE-ICI-VEGF, TACE with ICIs plus anti-VEGF antibody/TKIs; ICI-VEGF, ICIs plus anti-VEGF antibody/TKIs; TACE, transarterial chemoembolization; ICIs, immune checkpoint inhibitors; VEGF, vascular endothelial growth factor; TKIs, tyrosine kinase inhibitors; HR, hazard ratio; CI, confidence interval; IPCW, inverse probability of censoring weight; FU, follow-up; PSM, propensity score matching; ECOG, Eastern Cooperative Oncology Group; ALBI, albumin-bilirubin; AFP, alpha-fetoprotein.

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[1] Sung H., Ferlay J., Siegel R.L., et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. - PubMed

[2] Sung H., Ferlay J., Siegel R.L., et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. - PubMed

[3] Rumgay H., Arnold M., Ferlay J., et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022;77(6):1598–1606. - PMC - PubMed

[4] Rumgay H., Arnold M., Ferlay J., et al. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol. 2022;77(6):1598–1606. - PMC - PubMed

[5] Reig M., Forner A., Rimola J., et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681–693. - PMC - PubMed

[6] Reig M., Forner A., Rimola J., et al. BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol. 2022;76(3):681–693. - PMC - PubMed

[7] Park J.W., Chen M., Colombo M., et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE study. Liver Int. 2015;35(9):2155–2166. - PMC - PubMed

[8] Park J.W., Chen M., Colombo M., et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE study. Liver Int. 2015;35(9):2155–2166. - PMC - PubMed

[9] Llovet J.M., De Baere T., Kulik L., et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18(5):293–313. - PubMed

[10] Llovet J.M., De Baere T., Kulik L., et al. Locoregional therapies in the era of molecular and immune treatments for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2021;18(5):293–313. - PubMed

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Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study

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Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study

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