超声引导下微波消融联合^(125)Ⅰ粒子植入、靶向免疫治疗对不可切除巨块型肝癌的疗效观察

Clinical effect of ultrasound-guided microwave ablation combined with^(125)Ⅰ seed implantation and targeted immunotherapy on unresectable massive hepatocellular carcinoma

目的探讨超声引导下微波消融联合^(125)Ⅰ粒子植入、靶向免疫治疗对不可切除巨块型肝癌的疗效。方法回顾性抽取2019年12月至2022年5月徐州医科大学附属医院收治的不可切除巨块型肝癌患者58例,采用随机数字表法分为研究组(29例)与对照组(29例)。对照组接受超声引导下微波消融联合^(125)Ⅰ粒子植入治疗,研究组在对照组的基础上接受靶向免疫治疗。比较两组临床疗效,比较两组治疗前后血清肿瘤标志物[甲胎蛋白(AFP)、甲胎蛋白异质体-L3(AFP-L3)、异常凝血酶原(DCP)]、血清学指标[血管内皮生长因子(VEGF)、胸腺激酶1(TK1)]和免疫功能;比较两组不良反应发生情况;随访1年,记录两组无进展生存期(PFS)情况。结果研究组客观缓解率、临床控制率高于对照组(P<0.05)。治疗后,两组血清AFP、AFP-L3、DCP水平均较治疗前降低(P均<0.05),且研究组低于对照组(P<0.05)。治疗后,两组血清VEGF、TK1水平均较治疗前降低(P均<0.05),且研究组低于对照组(P<0.05)。治疗后,两组CD4^(+)、CD4^(+)/CD8^(+)、免疫球蛋白M水平均较治疗前升高(P均<0.05),且研究组高于对照组(P<0.05);治疗后,两组CD8^(+)水平均较治疗前降低(P均<0.05),且研究组低于对照组(P<0.05)。两组丙氨酸氨基转移酶(ALT)升高、天冬氨酸氨基转移酶(AST)升高、高血压、蛋白尿等Ⅰ~Ⅳ级不良反应总发生率比较差异未见统计学意义(P>0.05)。随访1年,对照组与研究组各失访1例,随访率为95.55%(28/29),研究组中位PFS为7.02个月(95%CI:5.20~11.14),对照组中位PFS为4.19个月(95%CI:3.98~10.87),研究组PFS曲线优于对照组(P<0.05)。结论超声引导下微波消融联合125Ⅰ粒子植入、靶向免疫治疗对不可切除巨块型肝癌的疗效确切,可降低肿瘤标志物水平,改善免疫功能,抑制血清VEGF、TK1表达,安全可靠,且可延长患者中位PFS。

Objective To investigate the clinical effect of ultrasound-guided microwave ablation combined with iodine-125(^(125)Ⅰ)seed implantation and targeted immunotherapy in the treatment of unresectable massive hepatocellular carcinoma.Methods A total of 58 patients with unresectable massive hepatocellular carcinoma admitted to the Affiliated Hospital of Xuzhou Medical University from December 2019 to May 2022 were retrospectively selected,and they were divided into study group(29 cases)and control group(29 cases)by random number table method.The control group received ultrasound-guided microwave ablation of liever neoplasms combined with ^(125)Ⅰ seed implantation,while the study group received targeted immunotherapy based on the treatment of the control group.The clinical efficacy of the two groups were compared.The levels of tumor markers,includingα-fetoprotein(AFP),α-fetoprotein anisoplast L3(AFP-L3)and disseminated intravascular coagulation profile(DCP),serological indicators,including vascular endothelial growth factor(VEGF)and thymokinase 1(TK1),and immune function were compared between the two groups before and after treatment.The incidence of adverse reactions of the two groups were compared.The progression-free survival(PFS)of the two groups were recorded after 1 year of follow-up.Results The objective remission rate and clinical control rate of the study group were higher than those of the control group(P<0.05).After treatment,the levels of serum AFP,AFP-L3 and DCP in the two groups decreased compared with preoperative levels(all P<0.05);and the levels of the above indicators in study group were lower than those in the control group after treatment(P<0.05).After treatment,levels of serum VEGF and TK1 of the two groups all decreased(all P<0.05),and the levels in the study group were lower compared with the control group(P<0.05).After treatment,the levels of cluster of differentiation 4^(+)(CD4^(+)),CD4^(+)/cluster of differentiation 8^(+)(CD8^(+)),and immunoglobulin M in the two groups increased(all P<0.05),and the levels in the study group were higher compared with the control group(P<0.05).After treatment,level of CD8^(+)in the two groups decreased(all P<0.05),and level of CD8^(+)in the study group was lower compared with the control group(P<0.05).There was no significant difference in the total incidence of Ⅰ-Ⅳ grade adverse reactions between the two groups,such as alanine aminotransferase increasing,aspartate aminotransferase increasing,hypertension and proteinuria(P>0.05).After 1 year of follow-up,both the control group and the study group had 1 case lost to follow-up,and the follow-up rate of the two groups were 95.55%(28/29).The median PFS of the study group was 7.02 months(95%CI 5.20-11.14),and the median PFS of the control group was 4.19 months(95%CI 3.98-10.87).The PFS curve of the study group was better than that of the control group(P<0.05).Conclusions Ultrasound-guided microwave ablation combined with ^(125)Ⅰ seed implantation and targeted immunotherapy,in the treatment of unresectable massive hepatocellular carcinoma,can effectively reduce the levels of tumor markers,improve immune function,inhibit the expression of serum VEGF and TK1.The treatment method is safe and reliable,and it can prolong the median PFS of patients.