载药脂微球配合肝动脉栓塞化疗治疗老年肝细胞癌的效果及对生存获益、PD-L1、PD-1水平影响

Drug-loaded lipid microspheres combined with transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma in elderly patients:Efficacy and impact on survival benefit and PD-L1 and PD-1 levels

背景传统肝动脉栓塞化疗在治疗肝癌时,肿瘤细胞仍会残留,患者预后不理想.载药脂质微球可以帮助进一步杀死残留的癌细胞并发挥重要作用.目的探讨载药脂微球结合肝动脉栓塞化疗治疗老年肝细胞癌的效果,并分析其对患者生存获益、程序性死亡配体1(programmed death ligand,PD-L1)、程序性死亡分子1(programmed death 1,PD-1)水平的影响.方法选取2015-10/2018-10我院老年肝细胞癌患者112例,根据对照设计试验原则,以随机抽签法分为观察组(n=56)、对照组(n=56).对照组采取传统肝动脉栓塞化疗,观察组采取HepaSphere载药脂微球结合肝动脉栓塞化疗.比较两组疗效、血清肿瘤标志物[甲胎蛋白(alpha-fetoprotein,AFP)、癌胚抗原(carcinoembryonic antigen,CEA)、糖类抗原199(carbohydrate antigen 199,CA199)、胸苷激酶1(thymidine kinase 1,TK-1)]、肿瘤血管生成有关指标[血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)、微血管密度(microvessel density,MVD)]、组织PD-L1、PD-1水平,并统计两组治疗期间不良反应、治疗后6 mo、1年及2年生存情况.结果观察组治疗总有效率为83.93%,高于对照组的67.86%(P<0.05);与治疗前相比,两组治疗后血清AFP、CEA、CA199、TK-1水平均明显降低,且观察组低于对照组(P<0.05);与治疗前相比,两组治疗后血清VEGF、bFGF水平及MVD均明显降低,且观察组低于对照组(P<0.05);与治疗前相比,两组治疗后组织PD-L1、PD-1水平均明显降低,且观察组低于对照组(P<0.05);治疗期间,观察组恶心、呕吐、腹痛、发热、乏力发生率与对照组比较差异无统计学意义(P>0.05);观察组治疗后1年、2年生存率高于对照组(P<0.05).结论载药脂微球结合肝动脉栓塞化疗治疗老年肝细胞癌的效果显著,可有效抑制癌组织中PD-L1、PD-1表达,有助于改善患者生存情况.

BACKGROUND Traditional hepatic artery embolization chemotherapy for treatment of liver cancer is often associated with an unsatisfactory prognosis since the tumor cells remain.Drug-loaded lipid microspheres can assist in further killing residual cancer cells and play an important role in the regulation of PD-1 and PD-L1 in the immune response.AIM To evaluate the efficacy of drug-loaded lipid microspheres combined with transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma in elderly patients,and to analyze its effect on the survival benefit and programmed death-1 ligand(PD-L1)and programmed death 1(PD-1)levels.METHODS From October 2015 to October 2018,112 elderly patients with hepatocellular carcinoma treated at our hospital were selected.According to the principle of controlled design,the patients were randomly divided into either an observation group(n=56)or a control group(n=56).The control group received traditional transcatheter arterial chemoembolization,and the observation group received HepaSphere drug-loaded lipid microspheres combined with transcatheter arterial chemoembolization.The efficacy and serum tumor markers[alpha-fetoprotein(AFP),carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199),thymidine kinase 1(TK-1)],tumor angiogenesis-related indicators[vascular endothelial cell growth factor(VEGF),basic fibroblast growth factor(bFGF),and microvessel density(MVD)],and tissue PD-L1 and PD-1 levels were compared between the two groups.The adverse reactions during the treatment period and the survival status of the two groups at 6 mo,1 year,and 2 years after treatment were also recorded.RESULTS The total effective rate in the observation group was 83.93%,which was higher than that(67.86%)of the control group(P<0.05).Compared with the values before treatment,serum AFP,CEA,CA199,and TK-1 levels in the two groups were significantly reduced after treatment;these tumor markers in the observation group were significantly lower than those of the control group after treatment(P<0.05).Compared with the values before treatment,the levels of serum VEGF,bFGF,and MVD in the two groups were significantly reduced after treatment;these tumor angiogenesis-related indicators in the observation group were significantly lower than those of the control group(P<0.05).Compared with the values before treatment,the levels of PD-L1 and PD-1 in the two groups were significantly reduced after treatment;they were also significantly lower in the observation group than in the control group(P<0.05).During treatment,there was no significant difference in the incidence of nausea,vomiting,abdominal pain,fever,or fatigue between the two groups(P>0.05).The 1-and 2-year survival rates of the observation group were significantly higher than those of the control group(P<0.05).CONCLUSION Drug-loaded lipid microspheres combined with transcatheter arterial chemoembolization have a significant effect in the treatment of hepatocellular carcinoma in elderly patients,and this combination therapy can effectively inhibit the expression of PD-L1 and PD-1 in cancer tissues and help improve the survival of patients.