外照射放疗联合酪氨酸激酶抑制剂治疗不可手术切除肝癌疗效的Meta分析

Efficacy of external beam radiation therapy combined with TKI in the treatment of non-resectable liver cancer:a Meta-analysis

目的:通过Meta分析对比外照射放疗(EBRT)联合酪氨酸激酶抑制剂(TKI)与EBRT或TKI单一治疗在不可手术切除肝癌中的有效性及安全性。方法:对Pubmed、Web of Science、Embase、Cochrane Library、CNKI、万方、维普、SinoMed等中英文数据库进行检索,检索时间截止至2023年4月1日。使用Revman5.4软件进行统计分析。结果:纳入12项研究共922例患者。结果表明,(1)有效性:联合治疗组的客观缓解率(ORR)、疾病控制率(DCR)高于单一治疗组(OR=2.33,95%CI 1.55~3.52,P<0.001;OR=5.09,95%CI 2.78~9.32,P<0.001);联合治疗组总生存期(OS)、无进展生存期(PFS)均长于单一治疗组(HR=0.67,95%CI 0.57~0.79,P<0.001;HR=0.58,95%CI 0.48~0.70,P<0.001)。(2)安全性:两组间总不良事件(AEs)未见统计学差异(OR=1.11,95%CI 0.93~1.31,P=0.25),但联合治疗组≥3级AEs发生率更高(OR=1.94,95%CI 1.11~3.38,P=0.02);对不限级AEs各分类分析发现,除了在胃区不适/腹痛、皮肤反应及白细胞减少方面联合治疗组的发生率更高,其他AEs两组间差异无统计学意义(P>0.05);(3)亚组分析:≥3级AEs在有远处转移及对照组干预措施为TKI时两组间差异无统计学意义,ORR、DCR在无远处转移时两组间差异无统计学意义,余各项与总体人群分析结果一致。结论:EBRT联合TKI较单一治疗可以显著改善不可手术切除肝癌患者的预后,AEs整体可控,但要警惕≥3级AEs的发生,需大样本高质量随机对照试验进一步验证本结论。

Objective:To conduct a Meta-analysis comparing the efficacy and safety of external beam radiation therapy(EBRT)combined with tyrosine kinase inhibitors(TKI)versus EBRT or TKI monotherapy in the treatment of non-resectable live cancer.Methods:Literature were searched in PubMed,Web of Science,Embase,and the Cochrane Library,CNKI,WanFang Data,Vip,and SinoMed until April 1st,2023.Statistical analyses were conducted using RevMan 5.4 software.Results:Twelve studies with a total of 922 patients were included.The results showed:(1)Effectiveness:the objective remission rate(ORR)and disease control rate(DCR)of the combination therapy group were higher than those of the monotherapy group(OR=2.33,95%CI 1.55-3.52,P<0.001;OR=5.09,95%CI 2.78-9.32,P<0.001).The overall survival(OS),disease-free survival(DFS),and progression-free survival(PFS)in the combination therapy group were significantly higher than those in the monotherapy group(HR=0.67,95%CI 0.57-0.79,P<0.001;HR=0.58,95%CI 0.48~0.70,P<0.001).(2)safety:no significant difference was observed in the total number of adverse events(AEs)between the two groups(OR=1.11,95%CI 0.93-1.31,P=0.25).However,the incidence of grade 3 or higher AEs was higher in the combination therapy group(OR=1.94,95%CI 1.11-3.38,P=0.02).Analysis of different classifications of AEs without limits revealed that,except for gastric discomfort/abdominal pain,skin reactions,and leukopenia,no significant difference was found between the two groups for other AEs(P>0.05).(3)Subgroup analysis:no significant difference was observed between the two groups in terms of grade≥3 AEs in the presence of distant metastasis and the control group when the intervention was TKI.Additionally,no significant difference was found between the two groups for ORR,DCR in the absence of distant metastasis,and the remaining results were consistent with the overall population analysis results.Conclusion:EBRT combined with TKI can significantly improve the prognosis of patients with non-resectable hepatocellular carcinoma compared with monotherapy,and the overall adverse events are controllable.However,we should be alert to the occurrence of grade≥3 AEs,which needs to be further verified by a large-sample,high-quality randomized controlled trial.