混合型肝癌免疫治疗疗效及安全性的初步观察

摘要/Abstract

摘要： 目的：初步观察免疫检查点抑制剂在混合型肝癌治疗中的疗效及安全性。
方法：收集2018年1月至2023年12月在中山大学肿瘤防治中心收治的接受免疫检查点抑制剂治疗的患者的临床资料,包括基本信息、治疗方案、实验室指标和生存情况等。采用实体瘤疗效评价标准1.1版进行疗效评估,用Kaplan-Meier曲线进行生存分析,用Cox回归模型单因素和多因素预后分析。
结果：共收集到有完整资料的混合型肝癌患者21例,中位年龄55岁。客观缓解率为28.6%,疾病控制率为52.4%,中位无进展生存时间为12.4个月（95%CI为6.7~18.1个月）,中位总生存时间为 14.4个月（95%CI为10.4~18.4个月）。多因素分析显示癌栓（HR=3.95,95%CI为1.09~14.28,P=0.036）、癌胚抗原水平升高（>5 μg/L）（HR=5.46,95%CI为1.14~26.17,P=0.034）与较短的无进展生存时间相关。任何级别不良事件均可控,无不良事件相关死亡。
结论：初步观察显示免疫检查点抑制剂在混合型肝癌治疗中的疗效肯定、安全性好,癌栓、癌胚抗原水平升高（>5 μg/L）可能是较短的无进展生存时间的不良因素。

关键词: 混合型肝癌, 免疫检查点抑制剂, 预后

Abstract: Objective: To observe preliminary the efficacy and safety of immune checkpoint inhibitors in the treatment of mixed liver cancer.
Methods: From January 2018 to December 2023, clinical data of patients admitted to the Cancer Prevention Center of Sun Yat-sen University were collected, including basic information, treatment plan, laboratory indicators and survival status. Efficacy was assessed by response evaluation criteria in solid tumors v1.1 for solid tumors. The survival analysis with Kaplan-Meier curve. The univariate and multivariate analysis with Cox regression model.
Results: A total of 21 patients with mixed liver cancer were collected. The median age was 55 years. The objective response rate was 28.6%. The disease control rate was 52.4%. The median progression-free survival time was 12.4 months (95%CI : 6.7-18.1 months). The median overall survival time was 14.4 months (95%CI: 10.4-18.4 months). Multivariate analysis showed that cancer thrombus (HR=3.95, 95%CI: 1.09-14.28, P=0.036) and increased carcinoembryonic antigen levels (>5 μg/L) (HR=5.46, 95%CI: 1.14-26.17, P=0.034) were associated with poor progression-free survival time. Adverse events of any level were controllable and no adverse event-related deaths.
Conclusion: Preliminary observe shows that the immune checkpoint inhibitors have good efficacy and safety in the treatment of mixed liver cancer, and the increased thrombus and increased antigen level (> 5 μg/L) may be adverse factors to shorten the progression-free survival time.

Key words: Mixed liver cancer, Immune checkpoint inhibitor, Prognosis

梁骏, 杨振云, 张耀军, 陈敏山, 胡丹旦. 混合型肝癌免疫治疗疗效及安全性的初步观察[J]. 肝癌电子杂志, 2024, 11(3): 20-24.

Liang Jun, Yang Zhenyun, Zhang Yaojun, Chen Minshan, Hu Dandan. Preliminary observe of the efficacy and safety of mixed liver cancer immunotherapy[J]. Electronic Journal of Liver Tumor, 2024, 11(3): 20-24.

参考文献

[1] 胡进晗,蔡玲燕,曾欣.混合型肝癌研究进展[J].肝脏,2023,28(7):861-865.
[2] KIM S H, PARK Y N, LIM J H,et al.Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma[J]. Eur J Surg Oncol, 2014, 40(8): 976-981.
[3] TIAN M X, HE W J, LIU W R, et al.A novel risk prediction model for patients with combined hepatocellular-cholangiocarcinoma[J]. J Cancer, 2018, 9(6): 1025-1032.
[4] STAVRAKA C, RUSH H, ROSS P.Combined hepatocellular cholangiocarcinoma (cHCC-CC): an update of genetics, molecular biology, and therapeutic interventions[J]. J Hepatocell Carcinoma, 2018, 6: 11-21.
[5] ESCHRICH J, KOBUS Z, GEISEL D, et al.The diagnostic approach towards combined hepatocellular-cholangiocarcinoma-state of the art and future perspectives[J]. Cancers (Basel), 2023, 15(1): 301.
[6] AUER T A, COLLETTINI F, SEGGER L, et al.Interventional treatment strategies in intrahepatic cholangiocarcinoma and perspectives for combined hepatocellular-cholangiocarcinoma[J]. Cancers (Basel), 2023, 15(9): 2655.
[7] WANG J, WANG F, KESSINGER A.Outcome of combined hepatocellular and cholangiocarcinoma of the liver[J]. J Oncol, 2010, 2010: 917356.
[8] AZIZI A A, HADJINICOLAOU A V, GONCALVES C, et al.Update on the genetics of and systemic therapy options for combined hepatocellular cholangiocarcinoma[J]. Front Oncol, 2020, 10: 570958.
[9] WAIDMANN O.Recent developments with immunotherapy for hepatocellular carcinoma[J]. Expert Opin Biol Ther, 2018, 18(8): 905-910.
[10] RUFF S M, MANNE A, CLOYD J M, et al.Current landscape of immune checkpoint inhibitor therapy for hepatocellular carcinoma[J]. Curr Oncol, 2023, 30(6): p. 5863-5875.
[11] LI Q, HAN J J, YANG Y L, et al.PD-1/PD-L1 checkpoint inhibitors in advanced hepatocellular carcinoma immunotherapy[J]. Front Immunol, 2022, 13: 1070961.
[12] JOERGER M, GÜLLER U, BASTIAN A, et al. Prolonged tumor response associated with sequential immune checkpoint inhibitor combination treatment and regorafenib in a patient with advanced pretreated hepatocellular carcinoma[J]. J Gastrointest Oncol, 2019, 10(2): 373-378.
[13] KUDO M, FINN R S, QIN S K, et al.Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126): 1163-1173.
[14] XIE L L, HUANG J Z, WANG L L, et al.Lenvatinib combined with a PD-1 inhibitor as effective therapy for advanced intrahepatic cholangiocarcinoma[J]. Front Pharmacol, 2022. 13: 894407.
[15] 谢炎,黄亚北,蒋文涛.免疫检查点抑制剂在肝癌中的应用现状及进展[J/CD].肝癌电子杂志,2022,9(1):65-70.
[16] CHU K J, KAWAGUCHI Y, WANG H, et al.Update on the diagnosis and treatment of combined hepatocellular cholangiocarcinoma[J]. J Clin Transl Hepatol, 2024, 12(2): 210-217.
[17] YE L T, SCHNEIDER J S, KHALED N B, et al.Combined hepatocellular-cholangiocarcinoma: biology,diagnosis,and management[J]. Liver Cancer, 2024, 13(1): 6-28.
[18] BEAUFRÈRE A, CALDERARO J, PARADIS V. Combined hepatocellular-cholangiocarcinoma: an update[J]. J Hepatol, 2021, 74(5): 1212-1224.
[19] FOWLER K, SAAD N E, BRUNT E, et al.Biphenotypic primary liver carcinomas: assessing outcomes of hepatic directed therapy[J]. Ann Surg Oncol, 2015, 22(13): 4130-4137.
[20] YIN X, ZHANG B H, QIU S J, et al.Combined hepatocellular carcinoma and cholangiocarcinoma: clinical features, treatment modalities, and prognosis[J]. Ann Surg Oncol, 2012, 19(9): 2869-2876.
[21] RIZELL M, ÅBERG F, PERMAN M, et al.Checkpoint inhibition causing complete remission of metastatic combined hepatocellular-cholangiocarcinoma after hepatic resection[J]. Case Rep Oncol, 2020, 13(1): 478-484.