PD-1抗体联合治疗对肝切除术后难治性复发肝癌患者生存率及免疫功能的影响

Effects of PD-1 Antibody Combined Therapy on Survival Rate and Immune Function of Patients with Refractory Recurrent Liver Cancer after Hepatectomy

目的探讨局部治疗、酪氨酸激酶抑制剂(TKI)及抗程序性死亡蛋白-1(PD-1)抗体联合应用对肝切除术后难治性复发肝癌患者生存率及免疫功能的影响。方法收集2019年5月—2021年3月收治的肝切除术后难治性复发肝癌60例,按治疗方法分为研究组和对照组各30例。2组均给予局部治疗,对照组在此基础上给予TKI类药物口服,研究组在对照组基础上给予PD-1抗体静脉滴注。观察2组治疗后生存情况、临床疗效、免疫功能及不良事件发生情况。结果研究组治疗后6个月和1年总生存率及无进展生存率均高于对照组(P<0.01)。研究组治疗后临床获益率高于对照组(P<0.05)。2组任意级别及3/4级不良事件发生率比较差异无统计学意义(P>0.05)。2组治疗后1、3、6个月CD3+、CD4+水平均高于治疗前,CD8+低于治疗前(P<0.05)。研究组治疗后1、3、6个月CD3+、CD4+水平均高于对照组,CD8+水平低于对照组(P<0.01)。结论局部治疗、TKI及PD-1抗体联合可有效提高肝切除术后难治性复发肝癌患者的总生存率及无进展生存率,临床疗效较好,可增强患者免疫功能,且未明显增多不良事件发生,安全性较高。

Objective To explore effects of combined application of local therapy,tyrosine kinase inhibitor(TKI)and anti-programmed death protein-1(PD-1)antibody on survival rate and immune function of patients with refractory recurrent liver cancer after hepatectomy.Methods A total of 60 patients with refractory recurrent liver cancer after hepatectomy admitted between May 2019 and March 2021 were collected and divided into research group(n=30)and control group(n=30).Both groups were given local treatment.Control group was given TKI drugs orally,while research group was given intravenous infusion of PD-1 antibody on the basis of treatment for control group.Conditions of survival,clinical efficacy,immune function and adverse events were observed in two groups.Results The 6-month and 1-year overall survival(OS)and progression free survival(PFS)in research group were higher than those in control group(P<0.01).Clinical benefit rate in research group was higher than that in control group(P<0.05).There were no significant differences in incidence rates of any grade and grade 3/4 adverse events between two groups(P>0.05).After treatment,levels of CD3+and CD4+were higher,while levels of CD8+were lower after treatment for 1,3 and 6 months than those before treatment in two groups(P<0.05).In research group,levels of CD3+and CD4+were higher,while CD8+levels were lower after treatment for 1,3 and 6 months than those in control group(P<0.01).Conclusion Combined application of local therapy,TKI and PD-1 antibody may effectively improve the OS and PFS of patients with refractory recurrent liver cancer after hepatectomy,which has good clinical efficacy,may enhance the immune function of patients,and it does not significantly increase incidence rate of adverse reactions with good safety.