Exploration and future prospects of clinical strategies for neoadjuvant therapy of hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

SU Yuhao ¹ , LIANG Yuxin ¹ , ZHONG Deyuan ¹ , SHANG Jin ² ,  HUANG Xiaolun ²

1. School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, P. R. China;
2. Department of Hepatobiliary and Pancreatic Surgery, Liver Transplantation Center, Sichuan Cancer Hospital, Affiliated Cancer Hospital, University of Electronic Science and Technology of China, Chengdu 610041, P. R. China;

Corresponding author：

HUANG Xiaolun, Email: huangxiaolun@med.uestc.edu.cn

Keywords：

hepatocellular carcinoma; neoadjuvant therapy; radiotherapy; immunotherapy

DOI：

10.7507/1007-9424.202407076

Video：

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Objective To explore the clinical protocols of neoadjuvant therapy for hepatocellular carcinoma and to provide a perspective on its future prospects. Method Literature search and review were conducted in CNKI, Wanfang, VIP, PubMed and other databases using keywords such as “hepatocellular carcinoma”, “neoadjuvant therapy”, “interventional therapy”, “radiotherapy”, “targeted therapy”, “immunotherapy”, etc in recent five years. Results Neoadjuvant therapy for hepatocellular carcinoma included neoadjuvant interventional therapy, radiotherapy, targeted therapy, and immunotherapy. Neoadjuvant interventional therapy and radiotherapy had significant advantages for hepatocellular carcinoma patients with portal vein tumor thrombus, while neoadjuvant targeted therapy and immunotherapy had achieved initial results in tumor pathological remission rate, providing more ideas for the diagnosis and treatment of patients with resectable hepatocellular carcinoma. Conclusions Neoadjuvant therapy is an emerging treatment for hepatocellular carcinoma, which has shown great potential in clinical applications and is moving towards individualization, precision, and systematization. We believe that with in-depth research on the mechanism of immunotherapy for hepatocellular carcinoma and continuous clinical practice, a comprehensive treatment strategy based on immunotherapy will become the key to neoadjuvant therapy for hepatocellular carcinoma in the future.

Citation： SU Yuhao, LIANG Yuxin, ZHONG Deyuan, SHANG Jin, HUANG Xiaolun. Exploration and future prospects of clinical strategies for neoadjuvant therapy of hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2025, 32(3): 389-396. doi: 10.7507/1007-9424.202407076 Copy

1.	Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2.	中华人民共和国国家卫生健康委员会医政司. 原发性肝癌诊疗指南 (2024年版). 协和医学杂志, 2024, 15(3): 532-559.
3.	郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
4.	宋天强. 肝癌新辅助治疗的热点与经验分享. 肝癌电子杂志, 2023, 10(1): 53-56.
5.	朱小东, 周俭. 原发性肝癌新辅助治疗的共识与争议. 中国实用外科杂志, 2023, 43(3): 286-290, 309.
6.	Frei E 3rd. Clinical cancer research: an embattled species. Cancer, 1982, 50(10): 1979-1992.Frei E 3rd. Clinical cancer research: an embattled species. Cancer, 1982, 50(10): 1979-1992.
7.	肝癌新辅助治疗中国专家共识协作组, 中国研究型医院学会消化外科专业委员会, 中国抗癌协会肝癌专业委员会. 肝癌新辅助治疗中国专家共识 (2023版). 中华外科杂志, 2023, 61(12): 1035-1045.
8.	中国医疗保健国际交流促进会肝脏肿瘤学分会, 中国抗癌协会肝癌专业委员会, 中国医师协会肝癌专业委员会, 等. 肝细胞癌新辅助及转化治疗中国专家共识(2023版). 肝癌电子杂志, 2023, 10(4): 1-14.
9.	叶定德. 肝细胞癌术前新辅助治疗的临床疗效研究. 南京: 东南大学, 2022.
10.	Shi HY, Wang SN, Wang SC, et al. Preoperative transarterial chemoembolization and resection for hepatocellular carcinoma: a nationwide Taiwan database analysis of long-term outcome predictors. J Surg Oncol, 2014, 109(5): 487-493.
11.	Jianyong L, Jinjing Z, Lunan Y, et al. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma. Sci Rep, 2017, 7: 41624. doi: 10.1038/srep41624.
12.	Amisaki M, Honjo S, Morimoto M, et al. The negative effect of preoperative transcatheter arterial chemoembolization on long-term outcomes for resectable hepatocellular carcinoma: a propensity score matching analysis. Yonago Acta Med, 2016, 59(4): 270-278.
13.	Chan KS, Tay WX, Cheo FY, et al. Preoperative transarterial chemoembolization (TACE) + liver resection versus upfront liver resection for large hepatocellular carcinoma (≥5 cm): a systematic review and meta-analysis. Acta Chir Belg, 2023, 123(6): 601-617.
14.	Zhang YF, Guo RP, Zou RH, et al. Efficacy and safety of preoperative chemoembolization for resectable hepatocellular carcinoma with portal vein invasion: a prospective comparative study. Eur Radiol, 2016, 26(7): 2078-2088.
15.	Mi S, Nie Y, Xie C. Efficacy and safety of preoperative transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis. Scand J Gastroenterol, 2022, 57(9): 1070-1079.
16.	Zhang CW, Dou CW, Zhang XL, et al. Simultaneous transcatheter arterial chemoembolization and portal vein embolization for patients with large hepatocellular carcinoma before major hepatectomy. World J Gastroenterol, 2020, 26(30): 4489-4500.
17.	魏博文, 陈凯, 侯一夫, 等. 辅助性肝动脉灌注化疗对原发性肝癌肝切除术后患者生存的影响. 实用医院临床杂志, 2023, 20(3): 62-66.
18.	Li B, Qiu J, Zheng Y, et al. Conversion to resectability using transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for initially unresectable hepatocellular carcinoma. Ann Surg Open, 2021, 2(2): e057. doi: 10.1097/AS9.0000000000000057.
19.	Hu Z, Yang Z, Wang J, et al. Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus. Front Pharmacol, 2023, 14: 1223632. doi: 10.3389/fphar.2023.1223632.
20.	Li S, Zhong C, Li Q, et al. Neoadjuvant transarterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: an interim analysis of a multi-center, phase 3, randomized, controlled clinical trial. J Clin Oncol, 2021, 39(15_suppl). doi: 10.1200/JCO.2021.39.15_suppl.4008.
21.	王恺悌, 巴登才仁·安蕊, 丛赟, 等. 肝细胞癌微血管侵犯术后早期复发的研究进展. 中国普外基础与临床杂志, 2024, 31(11): 1399-1405.
22.	Cheng S, Chen M, Cai J, et al. Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus (2018 edition). Liver Cancer, 2020, 9(1): 28-40.
23.	Schöniger-Hekele M, Müller C, Kutilek M, et al. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut, 2001, 48(1): 103-109.
24.	Kamiyama T, Nakanishi K, Yokoo H, et al. Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma. Int J Clin Oncol, 2007, 12(5): 363-368.
25.	Lee JH, Kim DH, Ki YK, et al. Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma. Radiat Oncol J, 2014, 32(3): 170-178.
26.	Li N, Feng S, Xue J, et al. Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy. HPB (Oxford), 2016, 18(6): 549-556.
27.	Wei X, Jiang Y, Zhang X, et al. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol, 2019, 37(24): 2141-2151.
28.	Wu F, Chen B, Dong D, et al. Phase 2 evaluation of neoadjuvant intensity-modulated radiotherapy in centrally located hepatocellular carcinoma: a nonrandomized controlled trial. JAMA Surg, 2022, 157(12): 1089-1096.
29.	刘智鹏. 新辅助放疗对肝细胞癌复发转移能力影响的初步研究. 南京: 东南大学, 2020.
30.	Wei X, Jiang Y, Feng S, et al. Neoadjuvant intensity modulated radiotherapy for a single and small (≤5 cm) hepatitis B virus-related hepatocellular carcinoma predicted to have high risks of microvascular invasion: a randomized clinical trial. Int J Surg, 2023, 109(10): 3052-3060.
31.	ShiC, LiY, GengL, et al. Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with micro vascular invasion: a randomised controlled trial. Eur J Cancer, 2022, 166: 176-184.
32.	Wang L, Wang W, Yao X, et al. Postoperative adjuvant radiotherapy is associated with improved survival in hepatocellular carcinoma with microvascular invasion. Oncotarget, 2017, 8(45): 79971-79981.
33.	刘千琳, 李秋. 肝细胞癌靶向治疗联合免疫治疗的研究剖析. 中国普外基础与临床杂志, 2023, 30(4): 392-396.
34.	Jin H, Qin S, He J, et al. New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials. Int J Biol Sci, 2022, 18(7): 2775-2794.
35.	Sangro B, Sarobe P, Hervás-Stubbs S, et al. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol, 2021, 18(8): 525-543.
36.	Ho WJ, Zhu Q, Durham J, et al. Neoadjuvant cabozantinib and nivolumab converts locally advanced HCC into resectable disease with enhanced antitumor immunity. Nat Cancer, 2021, 2(9): 891-903.
37.	Xia Y, Tang W, Qian X, et al. Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase Ⅱ clinical trial. J Immunother Cancer, 2022, 10(4): e004656. doi: 10.1136/jitc-2022-004656.
38.	Shi YH, Ji Y, Liu WR, et al. Abstract 486: a phase Ⅰb/Ⅱ, open-label study evaluating the efficacy and safety of Toripalimab injection (JS001) or combination with Lenvatinib as a neoadjuvant therapy for patients with resectable hepatocellular carcinoma (HCC). Cancer Res, 2021, 81(13_Suppl): 486.
39.	Markham MJ, Wachter K, Agarwal N, et al. Clinical cancer advances 2020: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol, 2020, 38(10): 1081. doi: 10.1200/JCO.19.03141.
40.	Sun HC, Zhu XD, Wang K, et al. Perioperative pembrolizumab and lenvatinib for resectable hepatocellular carcinoma: a single-arm, multi-center, phase Ⅱ trial (NeoLEAP-HCC). J Clin Oncol, 2024, 42(16_suppl): 4120. doi: 10.1200/JCO.2024.42.16_suppl.4120.
41.	Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol, 2020, 38(26): 2960-2970.
42.	Llovet JM, Kudo M, Merle P, et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol, 2023, 24(12): 1399-1410.
43.	Sun H, Zhu X, Gao Q, et al. Sintilimab combined with bevacizumab biosimilar as a conversion therapy in potentially resectable intermediate-stage hepatocellular carcinoma (HCC): updated results of a phase Ⅱ trial. J Clin Oncol, 2023, 41(16_suppl): e16220-e. doi: 10.1200/JCO.2023.41.16_suppl.e16220.
44.	Kaseb AO, Hasanov E, Cao HST, et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol, 2022, 7(3): 208-218.
45.	Su Y, Lin YJ, Hsiao CF, et al. P-124 Nivolumab plus ipilimumab as neoadjuvant therapy for potentially resectable hepatocellular carcinoma. Ann Oncol, 2021, 32(Suppl 3): S141.
46.	Pinato DJ, Cortellini A, Sukumaran A, et al. PRIME-HCC: phase Ⅰb study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma. BMC Cancer, 2021, 21(1): 301. doi: 10.1186/s12885-021-08033-x.
47.	Chen S, Wang Y, Xie W, et al. 7710P Neoadjuvant tislelizumab for resectable recurrent hepatocellular carcinoma: a non-randomized control, phase Ⅱ trial (TALENT). Ann Oncol, 2022, 33(Suppl 7): S867.
48.	Zhao M, Chen S, Li C, et al. Neoadjuvant immune checkpoint inhibitors for resectable hepatocellular carcinoma: a systematic review and meta-analysis. Cancers (Basel), 2023, 15(3): 600. doi: 10.3390/cancers15030600.
49.	Lai Z, He M, Bu X, et al. Lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy in patients with high-risk advanced hepatocellular carcinoma: a biomolecular exploratory, phase Ⅱ trial. Eur J Cancer, 2022, 174: 68-77.
50.	IMMUTACE: a phase 2 single-arm, open-label study of transarterial chemoembolization in combination with nivolumab performed for intermediate-stage hepatocellular carcinoma. Gastroenterol Hepatol (N Y), 2021, 17(11 Suppl 6): 16-17.
51.	Wei W, Li S, Zhao R, et al. Neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: a multi-center, phase 3, randomized, controlled clinical trial. J Clin Oncol, 2023, 41(16_suppl): 4023. doi: 10.1200/JCO.2023.41.16_suppl.4023.

1. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2024, 74(3): 229-263.
2. 中华人民共和国国家卫生健康委员会医政司. 原发性肝癌诊疗指南 (2024年版). 协和医学杂志, 2024, 15(3): 532-559.
3. 郝运, 李川, 文天夫, 等. 全球及中国的肝癌流行病学特征: 基于《2022全球癌症统计报告》解读. 中国普外基础与临床杂志, 2024, 31(7): 781-789.
4. 宋天强. 肝癌新辅助治疗的热点与经验分享. 肝癌电子杂志, 2023, 10(1): 53-56.
5. 朱小东, 周俭. 原发性肝癌新辅助治疗的共识与争议. 中国实用外科杂志, 2023, 43(3): 286-290, 309.
6. Frei E 3rd. Clinical cancer research: an embattled species. Cancer, 1982, 50(10): 1979-1992.Frei E 3rd. Clinical cancer research: an embattled species. Cancer, 1982, 50(10): 1979-1992.
7. 肝癌新辅助治疗中国专家共识协作组, 中国研究型医院学会消化外科专业委员会, 中国抗癌协会肝癌专业委员会. 肝癌新辅助治疗中国专家共识 (2023版). 中华外科杂志, 2023, 61(12): 1035-1045.
8. 中国医疗保健国际交流促进会肝脏肿瘤学分会, 中国抗癌协会肝癌专业委员会, 中国医师协会肝癌专业委员会, 等. 肝细胞癌新辅助及转化治疗中国专家共识(2023版). 肝癌电子杂志, 2023, 10(4): 1-14.
9. 叶定德. 肝细胞癌术前新辅助治疗的临床疗效研究. 南京: 东南大学, 2022.
10. Shi HY, Wang SN, Wang SC, et al. Preoperative transarterial chemoembolization and resection for hepatocellular carcinoma: a nationwide Taiwan database analysis of long-term outcome predictors. J Surg Oncol, 2014, 109(5): 487-493.
11. Jianyong L, Jinjing Z, Lunan Y, et al. Preoperative adjuvant transarterial chemoembolization cannot improve the long term outcome of radical therapies for hepatocellular carcinoma. Sci Rep, 2017, 7: 41624. doi: 10.1038/srep41624.
12. Amisaki M, Honjo S, Morimoto M, et al. The negative effect of preoperative transcatheter arterial chemoembolization on long-term outcomes for resectable hepatocellular carcinoma: a propensity score matching analysis. Yonago Acta Med, 2016, 59(4): 270-278.
13. Chan KS, Tay WX, Cheo FY, et al. Preoperative transarterial chemoembolization (TACE) + liver resection versus upfront liver resection for large hepatocellular carcinoma (≥5 cm): a systematic review and meta-analysis. Acta Chir Belg, 2023, 123(6): 601-617.
14. Zhang YF, Guo RP, Zou RH, et al. Efficacy and safety of preoperative chemoembolization for resectable hepatocellular carcinoma with portal vein invasion: a prospective comparative study. Eur Radiol, 2016, 26(7): 2078-2088.
15. Mi S, Nie Y, Xie C. Efficacy and safety of preoperative transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis. Scand J Gastroenterol, 2022, 57(9): 1070-1079.
16. Zhang CW, Dou CW, Zhang XL, et al. Simultaneous transcatheter arterial chemoembolization and portal vein embolization for patients with large hepatocellular carcinoma before major hepatectomy. World J Gastroenterol, 2020, 26(30): 4489-4500.
17. 魏博文, 陈凯, 侯一夫, 等. 辅助性肝动脉灌注化疗对原发性肝癌肝切除术后患者生存的影响. 实用医院临床杂志, 2023, 20(3): 62-66.
18. Li B, Qiu J, Zheng Y, et al. Conversion to resectability using transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for initially unresectable hepatocellular carcinoma. Ann Surg Open, 2021, 2(2): e057. doi: 10.1097/AS9.0000000000000057.
19. Hu Z, Yang Z, Wang J, et al. Survival benefit of neoadjuvant hepatic arterial infusion chemotherapy followed by hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus. Front Pharmacol, 2023, 14: 1223632. doi: 10.3389/fphar.2023.1223632.
20. Li S, Zhong C, Li Q, et al. Neoadjuvant transarterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: an interim analysis of a multi-center, phase 3, randomized, controlled clinical trial. J Clin Oncol, 2021, 39(15_suppl). doi: 10.1200/JCO.2021.39.15_suppl.4008.
21. 王恺悌, 巴登才仁·安蕊, 丛赟, 等. 肝细胞癌微血管侵犯术后早期复发的研究进展. 中国普外基础与临床杂志, 2024, 31(11): 1399-1405.
22. Cheng S, Chen M, Cai J, et al. Chinese expert consensus on multidisciplinary diagnosis and treatment of hepatocellular carcinoma with portal vein tumor thrombus (2018 edition). Liver Cancer, 2020, 9(1): 28-40.
23. Schöniger-Hekele M, Müller C, Kutilek M, et al. Hepatocellular carcinoma in Central Europe: prognostic features and survival. Gut, 2001, 48(1): 103-109.
24. Kamiyama T, Nakanishi K, Yokoo H, et al. Efficacy of preoperative radiotherapy to portal vein tumor thrombus in the main trunk or first branch in patients with hepatocellular carcinoma. Int J Clin Oncol, 2007, 12(5): 363-368.
25. Lee JH, Kim DH, Ki YK, et al. Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma. Radiat Oncol J, 2014, 32(3): 170-178.
26. Li N, Feng S, Xue J, et al. Hepatocellular carcinoma with main portal vein tumor thrombus: a comparative study comparing hepatectomy with or without neoadjuvant radiotherapy. HPB (Oxford), 2016, 18(6): 549-556.
27. Wei X, Jiang Y, Zhang X, et al. Neoadjuvant three-dimensional conformal radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a randomized, open-label, multicenter controlled study. J Clin Oncol, 2019, 37(24): 2141-2151.
28. Wu F, Chen B, Dong D, et al. Phase 2 evaluation of neoadjuvant intensity-modulated radiotherapy in centrally located hepatocellular carcinoma: a nonrandomized controlled trial. JAMA Surg, 2022, 157(12): 1089-1096.
29. 刘智鹏. 新辅助放疗对肝细胞癌复发转移能力影响的初步研究. 南京: 东南大学, 2020.
30. Wei X, Jiang Y, Feng S, et al. Neoadjuvant intensity modulated radiotherapy for a single and small (≤5 cm) hepatitis B virus-related hepatocellular carcinoma predicted to have high risks of microvascular invasion: a randomized clinical trial. Int J Surg, 2023, 109(10): 3052-3060.
31. ShiC, LiY, GengL, et al. Adjuvant stereotactic body radiotherapy after marginal resection for hepatocellular carcinoma with micro vascular invasion: a randomised controlled trial. Eur J Cancer, 2022, 166: 176-184.
32. Wang L, Wang W, Yao X, et al. Postoperative adjuvant radiotherapy is associated with improved survival in hepatocellular carcinoma with microvascular invasion. Oncotarget, 2017, 8(45): 79971-79981.
33. 刘千琳, 李秋. 肝细胞癌靶向治疗联合免疫治疗的研究剖析. 中国普外基础与临床杂志, 2023, 30(4): 392-396.
34. Jin H, Qin S, He J, et al. New insights into checkpoint inhibitor immunotherapy and its combined therapies in hepatocellular carcinoma: from mechanisms to clinical trials. Int J Biol Sci, 2022, 18(7): 2775-2794.
35. Sangro B, Sarobe P, Hervás-Stubbs S, et al. Advances in immunotherapy for hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol, 2021, 18(8): 525-543.
36. Ho WJ, Zhu Q, Durham J, et al. Neoadjuvant cabozantinib and nivolumab converts locally advanced HCC into resectable disease with enhanced antitumor immunity. Nat Cancer, 2021, 2(9): 891-903.
37. Xia Y, Tang W, Qian X, et al. Efficacy and safety of camrelizumab plus apatinib during the perioperative period in resectable hepatocellular carcinoma: a single-arm, open label, phase Ⅱ clinical trial. J Immunother Cancer, 2022, 10(4): e004656. doi: 10.1136/jitc-2022-004656.
38. Shi YH, Ji Y, Liu WR, et al. Abstract 486: a phase Ⅰb/Ⅱ, open-label study evaluating the efficacy and safety of Toripalimab injection (JS001) or combination with Lenvatinib as a neoadjuvant therapy for patients with resectable hepatocellular carcinoma (HCC). Cancer Res, 2021, 81(13_Suppl): 486.
39. Markham MJ, Wachter K, Agarwal N, et al. Clinical cancer advances 2020: annual report on progress against cancer from the American Society of Clinical Oncology. J Clin Oncol, 2020, 38(10): 1081. doi: 10.1200/JCO.19.03141.
40. Sun HC, Zhu XD, Wang K, et al. Perioperative pembrolizumab and lenvatinib for resectable hepatocellular carcinoma: a single-arm, multi-center, phase Ⅱ trial (NeoLEAP-HCC). J Clin Oncol, 2024, 42(16_suppl): 4120. doi: 10.1200/JCO.2024.42.16_suppl.4120.
41. Finn RS, Ikeda M, Zhu AX, et al. Phase Ⅰb study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol, 2020, 38(26): 2960-2970.
42. Llovet JM, Kudo M, Merle P, et al. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial. Lancet Oncol, 2023, 24(12): 1399-1410.
43. Sun H, Zhu X, Gao Q, et al. Sintilimab combined with bevacizumab biosimilar as a conversion therapy in potentially resectable intermediate-stage hepatocellular carcinoma (HCC): updated results of a phase Ⅱ trial. J Clin Oncol, 2023, 41(16_suppl): e16220-e. doi: 10.1200/JCO.2023.41.16_suppl.e16220.
44. Kaseb AO, Hasanov E, Cao HST, et al. Perioperative nivolumab monotherapy versus nivolumab plus ipilimumab in resectable hepatocellular carcinoma: a randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol, 2022, 7(3): 208-218.
45. Su Y, Lin YJ, Hsiao CF, et al. P-124 Nivolumab plus ipilimumab as neoadjuvant therapy for potentially resectable hepatocellular carcinoma. Ann Oncol, 2021, 32(Suppl 3): S141.
46. Pinato DJ, Cortellini A, Sukumaran A, et al. PRIME-HCC: phase Ⅰb study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma. BMC Cancer, 2021, 21(1): 301. doi: 10.1186/s12885-021-08033-x.
47. Chen S, Wang Y, Xie W, et al. 7710P Neoadjuvant tislelizumab for resectable recurrent hepatocellular carcinoma: a non-randomized control, phase Ⅱ trial (TALENT). Ann Oncol, 2022, 33(Suppl 7): S867.
48. Zhao M, Chen S, Li C, et al. Neoadjuvant immune checkpoint inhibitors for resectable hepatocellular carcinoma: a systematic review and meta-analysis. Cancers (Basel), 2023, 15(3): 600. doi: 10.3390/cancers15030600.
49. Lai Z, He M, Bu X, et al. Lenvatinib, toripalimab plus hepatic arterial infusion chemotherapy in patients with high-risk advanced hepatocellular carcinoma: a biomolecular exploratory, phase Ⅱ trial. Eur J Cancer, 2022, 174: 68-77.
50. IMMUTACE: a phase 2 single-arm, open-label study of transarterial chemoembolization in combination with nivolumab performed for intermediate-stage hepatocellular carcinoma. Gastroenterol Hepatol (N Y), 2021, 17(11 Suppl 6): 16-17.
51. Wei W, Li S, Zhao R, et al. Neoadjuvant hepatic arterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: a multi-center, phase 3, randomized, controlled clinical trial. J Clin Oncol, 2023, 41(16_suppl): 4023. doi: 10.1200/JCO.2023.41.16_suppl.4023.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Exploration and future prospects of clinical strategies for neoadjuvant therapy of hepatocellular carcinoma

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