Effect of lenvatinib＋transarterial chemoembolization＋PD-1 antibody (LEN-TAP) on residual liver volume in patients with intermediate and advanced hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LÜ Haopeng ¹ , KANG Yuhang ¹ , LIU Qingsong ² , LIU Chang ¹ , LI Qiu ³ , CHEN Weixia ⁴ , LI Zhiping ⁵ , LUO Yan ⁶ , LU Qiang ⁶ , LU Wusheng ¹ ,  ZHANG Xiaoyun ¹ ,  WEN Tianfu ¹ , MDT of Liver Cancer in West China Hospital

1. Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
2. West China School of Medicine, Sichuan University, Chengdu 610041, P. R. China;
3. Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
4. Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
5. Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;
6. Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

ZHANG Xiaoyun, Email: zhangxiaoyun@wchscu.cn; WEN Tianfu, Email: wentianfu@scu.edu.cn

Keywords：

residual liver volume; intermediate and advanced hepatocellular carcinoma; conversional resection; lenvatinib; transarterial chemoembolization; programmed death protein-1 monoclonal antibody

DOI：

10.7507/1007-9424.202310052

Video：

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Objective To investigate the effects of lenvatinib combined with transarterial chemoembolization (TACE) and programmed death protein-1 (PD-1) monoclonal antibody (Abbreviated as LEN-TAP regimen) on residual liver volume and surgical safety in intermediate and advanced hepatocellular carcinoma (HCC). Methods The clinicopathologic data of patients with intermediate and advanced HCC were collected retrospectively, who underwent the LEN-TAP conversion therapy and surgical resection in the Department of Liver Surgery, West China Hospital, Sichuan University from October 2020 to December 2021. The total liver volume, tumor volume, and residual liver volume of the patients before and after conversion therapy were analyzed. Results A total of 48 patients were included, 26 of whom had partial remission and 22 had stable disease, the objective response rate was 54.2% (26/48) according to the Response Evaluation Criteria in Solid Tumours 1.1 after conversion therapy. Before and after conversion therapy, the total liver volumes including tumor were (1 607.15±712.22) mL and (1 558.03±573.89) mL [mean difference (MD) and 95% confidence interval (CI)=–57.42(–134.30, 19.46), t=–1.503, P=0.140], the total liver volumes excluding tumor tissue were (1 095.28±227.60) mL and (1 260.31±270.71) mL [MD(95%CI)=165.03(128.13, 201.93), t=8.997, P<0.001], the tumor volumes were 260.25(107.75, 699.50) mL and 121.73 (33.00, 332.88) mL [MD(95%CI)=–222.45(–296.46, –148.44), Z=–5.641, P<0.001], and the residual liver volumes were (493.62±154.51) mL and (567.83±172.23) mL [MD(95%CI)=74.21(54.64, 93.79), t=7.627, P<0.001], respectively. The increase rates of tumor volume and residual liver volume after conversion therapy were (–53.34±33.05)% and (16.34±15.16)%, respectively. The conversional resections were successfully completed in all patients, with 13 (27.1%) cases experiencing postoperative complications and without occurrence of postoperative liver failure. Conclusion The data analysis results of this study indicate that the LEN-TAP conversion therapy can shrink tumor volume and increase the residual liver volume for patients with intermediate and advanced HCC, which helps to improve the safety of conversion resection.

Citation： LÜ Haopeng, KANG Yuhang, LIU Qingsong, LIU Chang, LI Qiu, CHEN Weixia, LI Zhiping, LUO Yan, LU Qiang, LU Wusheng, ZHANG Xiaoyun, WEN Tianfu, MDT of Liver Cancer in West China Hospital. Effect of lenvatinib＋transarterial chemoembolization＋PD-1 antibody (LEN-TAP) on residual liver volume in patients with intermediate and advanced hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(1): 16-23. doi: 10.7507/1007-9424.202310052 Copy

1.	中国抗癌协会肝癌专业委员会转化治疗协作组. 肝癌转化治疗中国专家共识(2021版). 中国实用外科杂志, 2021, 41(6): 618-632.
2.	Zhang X, Zhu X, Liu C, et al. The safety and efficacy of transarterial chemoembolization (TACE) + lenvatinib + programmed cell death protein 1 (PD-1) antibody of advanced unresectable hepatocellular carcinoma. J Clin Oncol, 2022, 40(4_suppl): 453.
3.	中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版). 中国实用外科杂志, 2020, 40(2): 121-138.
4.	Peng W, Zhang X, Li C, et al. Programmed cell death protein 1 and tyrosine kinase inhibition plus transcatheter arterial chemoembolization of advanced hepatocellular carcinoma. Br J Surg, 2023, 110(7): 746-748.
5.	张晓赟, 李川, 彭伟, 等. 血小板/脾脏体积比预测肝硬化门静脉高压症的严重程度. 腹部外科, 2016, 29(3): 187-192.
6.	Park JW, 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.
7.	Lau WY, Lai EC. Salvage surgery following downstaging of unresectable hepatocellular carcinoma—a strategy to increase resectability. Ann Surg Oncol, 2007, 14(12): 3301-3309.
8.	Tang ZY, Zhou XD, Ma ZC, et al. Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int, 2004, 3(4): 495-498.
9.	Zhu XD, Huang C, Shen YH, et al. Hepatectomy after conversion therapy using tyrosine kinase inhibitors plus anti-PD-1 antibody therapy for patients with unresectable hepatocellular carcinoma. Ann Surg Oncol, 2023, 30(5): 2782-2790.
10.	Wang J, Zheng Z, Wu T, et al. Hepatic arterial infusion chemotherapy as a timing strategy for conversion surgery to treat hepatocellular carcinoma: a single-center real-world study. J Hepatocell Carcinoma, 2022, 9: 999-1010.
11.	Shimose S, Iwamoto H, Shirono T, et al. The impact of curative conversion therapy aimed at a cancer-free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Cancer Med, 2023, 12(11): 12325-12335.
12.	Yi Y, Sun BY, Weng JL, et al. Lenvatinib plus anti-PD-1 therapy represents a feasible conversion resection strategy for patients with initially unresectable hepatocellular carcinoma: a retrospective study. Front Oncol, 2022, 12: 1046584. doi: 10.3389/fonc.2022.1046584.
13.	Guiu B, Chevallier P, Denys A, et al. Simultaneous trans-hepatic portal and hepatic vein embolization before major hepatectomy: the liver venous deprivation technique. Eur Radiol, 2016, 26(12): 4259-4267.
14.	Makuuchi M, Thai BL, Takayasu K, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery, 1990, 107(5): 521-527.
15.	Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg, 2012, 255(3): 405-414.
16.	刘畅, 张晓赟, 金谌, 等. 肝静脉系统栓堵术在第二阶段根治性肝癌切除术中的应用. 中国普外基础与临床杂志, 2019, 26(7): 841-846.
17.	Botea F, Barcu A, Verdea C, et al. Regenerative liver surgery—ALPPS and associated techniques. Chirurgia (Bucur), 2021, 116(4): 387-398.
18.	Zhao HT, Cai JQ. Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma. World J Gastroenterol, 2021, 27(47): 8069-8080.
19.	Zhang JL, Zhang XH, Mu H, et al. Surgical conversion for initially unresectable locally advanced hepatocellular carcinoma using a triple combination of angiogenesis inhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy: a retrospective study. Front Oncol, 2021, 11: 729764.
20.	Zhu XD, Huang C, Shen YH, et al. Downstaging and resection of initially unresectable hepatocellular carcinoma with tyrosine kinase inhibitor and anti-PD-1 antibody combinations. Liver Cancer, 2021, 10(4): 320-329.
21.	He MK, Liang RB, Zhao Y, et al. Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma. Ther Adv Med Oncol, 2021, 13: 17588359211002720. doi: 10.1177/17588359211002720.
22.	中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版). 中国实用外科杂志, 2022, 42(3): 241-273.
23.	Sparrelid E, Olthof PB, Dasari BVM, et al. Current evidence on posthepatectomy liver failure: comprehensive review. BJS Open, 2022, 6(6): zrac142.
24.	van den Broek MA, Olde Damink SW, Dejong CH, et al. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment. Liver Int, 2008, 28(6): 767-780.
25.	Hammond JS, Guha IN, Beckingham IJ, et al. Prediction, prevention and management of postresection liver failure. Br J Surg, 2011, 98(9): 1188-1200.
26.	Kong QY, Li C, Wang MD, et al. A web-based prediction model for estimating the probability of post-hepatectomy major complications in patients with hepatocellular carcinoma: a multicenter study from a hepatitis B virus-endemic area. J Gastrointest Surg, 2022, 26(10): 2082-2092.

1. 中国抗癌协会肝癌专业委员会转化治疗协作组. 肝癌转化治疗中国专家共识(2021版). 中国实用外科杂志, 2021, 41(6): 618-632.
2. Zhang X, Zhu X, Liu C, et al. The safety and efficacy of transarterial chemoembolization (TACE) + lenvatinib + programmed cell death protein 1 (PD-1) antibody of advanced unresectable hepatocellular carcinoma. J Clin Oncol, 2022, 40(4_suppl): 453.
3. 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版). 中国实用外科杂志, 2020, 40(2): 121-138.
4. Peng W, Zhang X, Li C, et al. Programmed cell death protein 1 and tyrosine kinase inhibition plus transcatheter arterial chemoembolization of advanced hepatocellular carcinoma. Br J Surg, 2023, 110(7): 746-748.
5. 张晓赟, 李川, 彭伟, 等. 血小板/脾脏体积比预测肝硬化门静脉高压症的严重程度. 腹部外科, 2016, 29(3): 187-192.
6. Park JW, 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.
7. Lau WY, Lai EC. Salvage surgery following downstaging of unresectable hepatocellular carcinoma—a strategy to increase resectability. Ann Surg Oncol, 2007, 14(12): 3301-3309.
8. Tang ZY, Zhou XD, Ma ZC, et al. Downstaging followed by resection plays a role in improving prognosis of unresectable hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int, 2004, 3(4): 495-498.
9. Zhu XD, Huang C, Shen YH, et al. Hepatectomy after conversion therapy using tyrosine kinase inhibitors plus anti-PD-1 antibody therapy for patients with unresectable hepatocellular carcinoma. Ann Surg Oncol, 2023, 30(5): 2782-2790.
10. Wang J, Zheng Z, Wu T, et al. Hepatic arterial infusion chemotherapy as a timing strategy for conversion surgery to treat hepatocellular carcinoma: a single-center real-world study. J Hepatocell Carcinoma, 2022, 9: 999-1010.
11. Shimose S, Iwamoto H, Shirono T, et al. The impact of curative conversion therapy aimed at a cancer-free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Cancer Med, 2023, 12(11): 12325-12335.
12. Yi Y, Sun BY, Weng JL, et al. Lenvatinib plus anti-PD-1 therapy represents a feasible conversion resection strategy for patients with initially unresectable hepatocellular carcinoma: a retrospective study. Front Oncol, 2022, 12: 1046584. doi: 10.3389/fonc.2022.1046584.
13. Guiu B, Chevallier P, Denys A, et al. Simultaneous trans-hepatic portal and hepatic vein embolization before major hepatectomy: the liver venous deprivation technique. Eur Radiol, 2016, 26(12): 4259-4267.
14. Makuuchi M, Thai BL, Takayasu K, et al. Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report. Surgery, 1990, 107(5): 521-527.
15. Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg, 2012, 255(3): 405-414.
16. 刘畅, 张晓赟, 金谌, 等. 肝静脉系统栓堵术在第二阶段根治性肝癌切除术中的应用. 中国普外基础与临床杂志, 2019, 26(7): 841-846.
17. Botea F, Barcu A, Verdea C, et al. Regenerative liver surgery—ALPPS and associated techniques. Chirurgia (Bucur), 2021, 116(4): 387-398.
18. Zhao HT, Cai JQ. Chinese expert consensus on neoadjuvant and conversion therapies for hepatocellular carcinoma. World J Gastroenterol, 2021, 27(47): 8069-8080.
19. Zhang JL, Zhang XH, Mu H, et al. Surgical conversion for initially unresectable locally advanced hepatocellular carcinoma using a triple combination of angiogenesis inhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy: a retrospective study. Front Oncol, 2021, 11: 729764.
20. Zhu XD, Huang C, Shen YH, et al. Downstaging and resection of initially unresectable hepatocellular carcinoma with tyrosine kinase inhibitor and anti-PD-1 antibody combinations. Liver Cancer, 2021, 10(4): 320-329.
21. He MK, Liang RB, Zhao Y, et al. Lenvatinib, toripalimab, plus hepatic arterial infusion chemotherapy versus lenvatinib alone for advanced hepatocellular carcinoma. Ther Adv Med Oncol, 2021, 13: 17588359211002720. doi: 10.1177/17588359211002720.
22. 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗指南(2022年版). 中国实用外科杂志, 2022, 42(3): 241-273.
23. Sparrelid E, Olthof PB, Dasari BVM, et al. Current evidence on posthepatectomy liver failure: comprehensive review. BJS Open, 2022, 6(6): zrac142.
24. van den Broek MA, Olde Damink SW, Dejong CH, et al. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment. Liver Int, 2008, 28(6): 767-780.
25. Hammond JS, Guha IN, Beckingham IJ, et al. Prediction, prevention and management of postresection liver failure. Br J Surg, 2011, 98(9): 1188-1200.
26. Kong QY, Li C, Wang MD, et al. A web-based prediction model for estimating the probability of post-hepatectomy major complications in patients with hepatocellular carcinoma: a multicenter study from a hepatitis B virus-endemic area. J Gastrointest Surg, 2022, 26(10): 2082-2092.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of lenvatinib＋transarterial chemoembolization＋PD-1 antibody (LEN-TAP) on residual liver volume in patients with intermediate and advanced hepatocellular carcinoma

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