脾脏对BCLC B期和C期肝细胞癌患者靶向治疗联合免疫治疗效果影响的临床研究  

Impact of spleen on the efficacy of targeted therapy combined with immunotherapy in patients with BCLC stage B and C hepatocellular carcinoma

作　　者：余俊[1] 王金鹏 邵天胤 周洪浩[1] 吴俣[1] 申雪晗 董汉华[1] 程琪[1] 张志伟[1] 陈孝平[1] YU Jun;WANG Jinpeng;SHAO Tianyin;ZHOU Honghao;WU Yu;SHEN Xuehan;DONG Hanhua;CHENG Qi;ZHANG Zhiwei;CHEN Xiaoping(Department of Hepatic Surgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院肝脏外科,湖北武汉430060

出　　处：《肝胆胰外科杂志》2025年第3期171-178,共8页Journal of Hepatopancreatobiliary Surgery

基　　金：湖北陈孝平科技发展基金会肝胆胰恶性肿瘤研究基金多中心重大专项(CXPJJH11800001-2018104)。

摘　　要：目的探讨脾脏对接受免疫检查点抑制剂联合靶向治疗的BCLC B期和C期肝细胞癌(HCC)患者疗效的影响。方法回顾性分析2018年12月至2023年12月在华中科技大学同济医学院附属同济医院接受免疫检查点抑制剂联合酪氨酸激酶抑制剂治疗的BCLC B期和C期HCC患者临床资料。根据既往是否行脾切除术将患者分为既往脾切除组(n=57)和非脾切除组(n=70),通过随访记录患者的总生存期(OS)以及无进展生存期(PFS)。使用SPSS 26.0进行数据分析,Kaplan-Meier法进行生存分析,Cox比例风险回归模型进行预后影响因素分析。结果至2023年12月30日随访结束,中位随访时间为18.9个月。既往脾切除组死亡29例,非脾切除组死亡41例,既往脾切除组中位OS(24.9个月)与中位PFS(13.8个月)均长于非脾切除组的中位OS(18.1个月)和中位PFS(8.8个月),差异具有统计学意义(χ^(2)=8.77,P=0.003;χ^(2)=5.74,P=0.017)。既往脾切除组的客观缓解率(ORR,38.6%)高于非脾切除组(18.6%),且差异具有统计学意义(χ^(2)=6.31,P=0.012)。多因素Cox比例风险回归模型显示,既往未行脾切除(HR=2.86,95%CI 1.64-4.76,P<0.001)、BCLC分期C期(HR=1.83,95%CI 1.11-3.03,P=0.018)、Child-Pugh分级B级(HR=2.23,95%CI 1.24-4.01,P=0.007)、有门静脉侵犯(HR=5.93,95%CI 3.37-10.43,P=0.001)、肿瘤多发(>3个)(HR=2.96,95%CI 1.69-5.18,P=0.001)是HCC患者OS的独立危险因素(P<0.05);既往未行脾切除(HR=2.00,95%CI 1.23-3.23,P=0.005)、BCLC分期C期(HR=1.69,95%CI 1.06-1.69,P=0.001)、ALBI分级2级(HR=1.93,95%CI 1.19-3.12,P=0.007)、有门静脉侵犯(HR=1.95,95%CI 1.15-3.30,P=0.013)、肿瘤多发(>3个)(HR=2.20,95%CI 1.36-2.56,P=0.001)是HCC患者PFS的独立危险因素(P<0.05)。非脾切除组的不良事件发生率(94.29%)高于既往脾切除组(92.98%),但两组差异无统计学意义(χ^(2)=0.01,P=1.00)。结论既往行脾切除术可以显著延长BCLC B期和C期HCC患者使用靶向治疗联合免疫治疗的PFS和OS,改善预后;既往行�Objective To assess the impact of the spleen on the effi cacy of immune checkpoint inhibitors combined with targeted therapy in patients with BCLC stage B and C hepatocellular carcinoma(HCC).Methods A retrospective analysis was conducted on BCLC stage B and C HCC patients receiving immune checkpoint inhibitor and tyrosine kinase inhibitors at Tongji Hospital of Huazhong University of Science and Technology,between Dec.2018 and Dec.2023.Patients were divided into two groups based on whether they had undergone splenectomy:the prior splenectomy group(n=57)and the non-splenectomy group(n=70).The overall survival(OS)and progression-free survival(PFS)were collected by telephone follow-ups.Data analysis was performed with SPSS 26.0,the survival analysis was conducted with Kaplan-Meier analysis,and the prognostic factors was analyzed with Cox proportional hazards regression model.Results Till to Dec.30,2023,the median follow-up time was 18.9 months,29 patients died in the prior splenectomy group,while 41 died in the non-splenectomy group.The OS and PFS in the prior splenectomy group were significantly longer than those in the non-splenectomy group(mdeian OS:24.9 months vs 18.1 months,χ^(2)=8.77,P=0.003;mdeian PFS:13.8 months vs 8.8 months,χ^(2)=5.74,P=0.017).The objective response rate(ORR)in the prior splenectomy group was also significantly higher than that in the non-splenectomy group(38.6%vs 18.6%,χ^(2)=6.31,P=0.012).Multivariate Cox regression analysis demonstrated that,prior non-splenectomy(HR=2.86,95%CI 1.64 to 4.76,P<0.001),BCLC stage C(HR=1.83,95%CI 1.11 to 3.03,P=0.018),Child-Pugh class B(HR=2.23,95%CI 1.24 to 4.01,P=0.007),portal vein invasion(HR=5.93,95%CI 3.37 to 10.43,P=0.001),and multiple tumors(>3)(HR=2.96,95%CI 1.69 to 5.18,P=0.001)were independent prognostic risk factors for OS(P<0.05).Similarly,prior non-splenectomy(HR=2.00,95%CI 1.23 to 3.23,P=0.005),BCLC stage C(HR=1.69,95%CI 1.06 to 2.69,P=0.001),ALBI grade 2(HR=1.93,95%CI 1.19 to 3.12,P=0.007),portal vein invasion(HR=1.95,95%CI 1.15 to 3.30,P=0.

关 键 词：原发性肝细胞癌 巴塞罗那临床肝癌分期 脾切除术 靶向治疗 免疫治疗 COX回归分析 预后 

分 类 号：R735.7[医药卫生—肿瘤]