肝动脉化疗栓塞联合射频消融和免疫靶向治疗术后复发的肝细胞癌患者近远期疗效研究

Short-term efficacy of TACE, RFA, anti-PD-1 antibody and apatinib combination in the treatment of patients with postoperative recurrent hepatocellular carcinoma

目的探讨采用肝动脉化疗栓塞(TACE)联合射频消融(RFA)和免疫靶向治疗术后复发的肝细胞癌(HCC)患者的疗效。方法2014年8月~2018年4月我院诊治的术后复发性HCC患者150例,采用随机数字表法将患者分为对照组75例和观察组75例,分别给予TACE联合RFA治疗或在此基础上给予抗程序性细胞死亡蛋白-1(PD-1)抗体和阿帕替尼治疗,采用实体瘤mRESIST标准评估临床疗效,使用流式细胞仪测定外周血T细胞亚群,采用Kaplan-Meier法比较生存率。结果在治疗后3 m,观察组有效率为81.3%,显著高于对照组的53.3%(P<0.05);观察组外周血CD3^(+)、CD4^(+)细胞百分比和CD4^(+)/CD8^(+)细胞比值分别为(68.2±6.8)%、(45.9±4.7)%和(1.8±0.3),显著高于对照组【分别为(56.5±6.1)%、(33.3±4.5)%和(1.3±0.2),P<0.05】,而CD8^(+)细胞百分比为(22.5±1.8)%,显著低于对照组【(28.3±1.4)%,P<0.05】;观察组I/II级不良反应发生率为73.3%,显著高于对照组的32.0%(P<0.05);观察组1 a生存率为49.3%,显著高于对照组的30.7%(P<0.05)。结论采用TACE联合RFA和免疫靶向治疗能够有效提高复发性HCC患者的近期临床疗效,可能与提高了机体免疫功能,抑制了肿瘤血管生成有关。

Objective The purpose of this study was to explore the short-term efficacy of transcatheter arterial chemoembolization(TACE),radiofrequency ablation(RFA)and immune targeted therapy combination in the treatment of patients with postoperative recurrent hepatocellular carcinoma(HCC).Methods A total of 150 patients with postoperative recurrent HCC were enrolled in our hospital between August 2014 and April 2018,and were divided randomly into control and obserbation group,with 75 cases in each group.The patients in the control group underwent TACE and RFA,while those in the observation group were treated with anti-programmed cell death protein 1(PD-1)and angiogenesis inhibitors,apatinib,combination on the basis in control group.The clinical efficacy was evaluated by solid tumor mRESIST standards.The peripheral blood T cell subsets were detected by flow cytometry.The survival in the two groups after surgery was analyzed by Kaplan-Meier method.Results At the end of three months after treatment,the total response rate in the observation group was significantly higher than that in the control group(81.3%vs.53.3%,P<0.05);the percentages of peripheral blood CD3^(+)and CD4^(+)cells and CD4^(+)/CD8^(+)cell ratio were(68.2±6.8)%,(45.9±4.7)%and(1.8±0.3),significantly higher than[(56.5±6.1)%,(33.3±4.5)%and(1.3±0.2),respectively,P<0.05],while the percentage of CD8^(+)cells was(22.5±1.8)%,significantly lower than[(28.3±1.4)%,P<0.05]in the control;the incidence of untoward effects grade I/II in the observation group was 73.3%,significantly higher than 32.0%(P<0.05)in the control;the 1-year survival in the observation group was 49.3%,significantly higher than 30.7%(P<0.05)in the control.Conclusion The combination of TACE,RFA and immune targeted therapy could effectively improve short-term clinical efficacy in patients with postoperative recurrent HCC,which might be related to the up-regulation of cellular immune functions.