经肝动脉化疗栓塞联合系统治疗对不可切肝细胞癌的疗效分析  

Analysis of the therapeutic efficacy of transcatheter arterial chemoembolization combined with systemic treatment in unresectable hepatocellular carcinoma

作　　者：李文利 杜阳峰[3] 袁国盛 臧梦雅 朱培琳 李榕[1] 陈泳如 苏开妍 李祺[1] 胡晓云[1] 庞桦进[2] 陈锦章[1] Wenli Li;Yangfeng Du;Guosheng Yuan;Mengya Zang;Peilin Zhu;Rong Li;Yongru Chen;Kaiyan Su;Qi Li;Xiaoyun Hu;Huajin Pang;Jinzhang Chen(Department of Infectious Diseases,Nanfang Hospital,Southern Medical University,State Key Laboratory of Organ Failure Research,Key Laboratory of Infectious Diseases Research in South China(Ministry of Education),Guangdong Provincial Key Laboratory of Viral Hepatitis Research,Guangdong Provincial Clinical Research Center for Viral Hepatitis,Guangdong Institute of Hepatology,Guangzhou 510515,China;Division of Vascular and Interventional Radiology,Department of General Surgery,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Department of Oncology,The First People′s Hospital of Changde City,Changde 415003,China)

机构地区：[1]南方医科大学南方医院感染内科,器官衰竭防治国家重点实验室,华南传染病防治教育部重点实验室,广东省病毒性肝炎研究重点实验室,广东省病毒性肝炎临床医学研究中心,广东省肝脏疾病研究所,广州市510515 [2]南方医科大学南方医院血管与介入科 [3]湖南省常德市第一人民医院肿瘤科

出　　处：《中国肿瘤临床》2023年第22期1135-1141,共7页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:82102879);广东省自然科学基金(编号:2022A1515010526,2021A1515012518);中国博士后科研基金(编号:2021M691468);广东省医学科研基金(编号:A2021343)资助。

摘　　要：目的:探索经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)为基础的不同方案治疗不可切除肝细胞癌(unresectable hepatocellular carcinoma,uHCC)患者的疗效和安全性,以及TACE联合酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)和免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的最佳时机。方法:回顾性分析2016年4月至2021年12月期间在南方医科大学南方医院接受基于TACE治疗的555例uHCC患者资料。根据不同治疗方案分为:TACE组(n=317)、TACE+TKIs组(n=66)、TACE+ICIs组(n=33)、TACE+TKIs+ICIs组(n=139)。在亚组分析中,根据不同的联合时间将TACE+TKIs+ICIs组分为“TACE前”和“TACE后”组。采用单因素、多因素Cox回归分析影响OS的预后因素。结果:TACE+TKIs+ICIs组获得最长的OS(21.9个月,95%CI:17.2~26.6,P=0.030)和PFS(8.3个月,95%CI:7.3~9.3,P=0.004)。在亚组分析中,“TACE后”组比“TACE前”组获得更长的OS(26.8个月vs.19.2个月,P=0.011)。TACE组、TACE+TKIs组、TACE+ICIs组、TACE+TKIs+ICIs组的ORR分别为32.8%、41.1%、42.4%、52.5%(P=0.001),DCR分别为59.6%、71.2%、69.7%、82.7%(P<0.001)。不良反应事件与既往研究相似。Cox回归分析提示肿瘤数量、肝外转移及治疗方案是患者OS的独立预后因素(均P<0.05)。结论:TKIs或ICIs可以提高TACE治疗uHCC患者的OS和PFS,TKIs+ICIs联合TACE生存获益更佳。首次TACE术后3个月内联合“TKIs+ICIs”治疗方案的总生存期获益更显著。Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibitors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The patients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into“pre-TACE”and“post-TACE”groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence interval[CI]:17.2−26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3−9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the“post-TACE”group had longer OS than the“pre-TACE”group(26.8 months vs.19.2 months,P=0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better bene

关 键 词：肝细胞癌 经动脉化疗栓塞 免疫检查点抑制剂 酪氨酸激酶抑制剂 总生存期 无进展生存期 

分 类 号：R735.7[医药卫生—肿瘤]