Abstract：
BACKGROUND: The optimal management of unresectable hepatocellular carcinoma (uHCC) remains an unresolved challenge. There is ongoing debate regarding the efficacy and safety of drug-eluting bead TACE (DEB-TACE) with tyrosine kinase inhibitors (TKIs).
METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library for eligible studies. The main endpoints under investigation were survival outcomes, including overall survival (OS), progression-free survival (PFS), and time to progression (TTP). Secondary outcomes encompassed tumor response rates and adverse events (AEs). Two researchers conducted the data extraction independently and assessed the quality of the studies. After pooling and analyzing the data, we assessed the heterogeneity and performed both subgroup analysis and sensitivity analysis. Additionally, we evaluated the potential for publication bias.
RESULTS: Eight studies with 1513 patients were finally retrieved. Compared to monotherapy, although bigeminal therapy exhibited improved survival benefits (OS: HR: 0.56, 95 % CI 0.41-0.76, p < 0.001; TTP: HR: 0.72, 95 % CI 0.59-0.87, p = 0.001) and tumor response (ORR: RR: 1.59; 95 % CI 1.19-2.13, p = 0.002; DCR: RR: 1.14; 95 % CI 1.03-1.26, p = 0.010), the reliability of results was affected by significant heterogeneity. In the subgroup analysis, compared to DEB-TACE alone, the bigeminal therapy failed to show any statistical differences. Compared to TKIs, it demonstrated significant advantages in both survival (OS: HR: 0.49, 95 % CI 0.40-0.61, p < 0.001; TTP: HR: 0.60, 95 % CI 0.48-0.75, p < 0.001) and tumor response (ORR: RR: 2.40, 95 % CI 1.86-3.09, p < 0.001; DCR: RR: 1.36, 95 % CI 1.20-1.54, p < 0.001) while low heterogeneity was observed. Concerning safety, DEB-TACE provides no more severe AEs while TKIs-related AEs require close monitoring.
CONCLUSIONS: Our findings suggest that DEB-TACE combined with TKIs may be a safe and effective treatment for uHCC, which is more suitable for patients in the advanced stage.
METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library for eligible studies. The main endpoints under investigation were survival outcomes, including overall survival (OS), progression-free survival (PFS), and time to progression (TTP). Secondary outcomes encompassed tumor response rates and adverse events (AEs). Two researchers conducted the data extraction independently and assessed the quality of the studies. After pooling and analyzing the data, we assessed the heterogeneity and performed both subgroup analysis and sensitivity analysis. Additionally, we evaluated the potential for publication bias.
RESULTS: Eight studies with 1513 patients were finally retrieved. Compared to monotherapy, although bigeminal therapy exhibited improved survival benefits (OS: HR: 0.56, 95 % CI 0.41-0.76, p < 0.001; TTP: HR: 0.72, 95 % CI 0.59-0.87, p = 0.001) and tumor response (ORR: RR: 1.59; 95 % CI 1.19-2.13, p = 0.002; DCR: RR: 1.14; 95 % CI 1.03-1.26, p = 0.010), the reliability of results was affected by significant heterogeneity. In the subgroup analysis, compared to DEB-TACE alone, the bigeminal therapy failed to show any statistical differences. Compared to TKIs, it demonstrated significant advantages in both survival (OS: HR: 0.49, 95 % CI 0.40-0.61, p < 0.001; TTP: HR: 0.60, 95 % CI 0.48-0.75, p < 0.001) and tumor response (ORR: RR: 2.40, 95 % CI 1.86-3.09, p < 0.001; DCR: RR: 1.36, 95 % CI 1.20-1.54, p < 0.001) while low heterogeneity was observed. Concerning safety, DEB-TACE provides no more severe AEs while TKIs-related AEs require close monitoring.
CONCLUSIONS: Our findings suggest that DEB-TACE combined with TKIs may be a safe and effective treatment for uHCC, which is more suitable for patients in the advanced stage.
摘要：
背景：不可切除的肝细胞癌（uHCC）的最佳管理仍然是一个尚未解决的挑战。关于药物洗脱珠TACE（DEB-TACE）与酪氨酸激酶抑制剂（TKIs）的疗效和安全性存在持续的争论。
方法：我们搜索了PubMed，Embase,WebofScience和Cochrane图书馆进行符合条件的研究。调查的主要终点是生存结果，包括总生存期(OS)，无进展生存期（PFS），和进展时间（TTP）。次要结果包括肿瘤缓解率和不良事件（AE）。两名研究人员独立进行了数据提取，并评估了研究的质量。在汇集和分析数据之后，我们评估了异质性,并进行了亚组分析和敏感性分析.此外,我们评估了发表偏倚的可能性.
结果：最终检索了8项1513例患者的研究。与单一疗法相比，尽管双药治疗改善了生存效益（OS：HR：0.56，95％CI0.41-0.76，p<0.001；TTP：HR：0.72，95％CI0.59-0.87，p=0.001）和肿瘤反应（ORR：1.59；95％CI1.19-2.13，p=0.002；DCR：RR：1.14；95％CI1.03-1.26，p=0.010），结果的可靠性受到显著异质性的影响。在亚组分析中，与单独的DEB-TACE相比，双重治疗未能显示任何统计学差异.与TKIs相比，在生存率(OS:HR:0.49,95%CI0.40-0.61,p<0.001;TTP:HR:0.60,95%CI0.48-0.75,p<0.001)和肿瘤反应(ORR:RR:2.40,95%CI1.86-3.09,p<0.001;DCR:RR:1.36,95%CI1.20-1.54,p<0.001)方面均有显著优势,同时观察到低异质性。关于安全，DEB-TACE不会提供更严重的AE，而与TKI相关的AE需要密切监测。
结论：我们的研究结果表明，DEB-TACE联合TKIs可能是一种安全有效的治疗uHCC的方法。更适合晚期患者。
方法：我们搜索了PubMed，Embase,WebofScience和Cochrane图书馆进行符合条件的研究。调查的主要终点是生存结果，包括总生存期(OS)，无进展生存期（PFS），和进展时间（TTP）。次要结果包括肿瘤缓解率和不良事件（AE）。两名研究人员独立进行了数据提取，并评估了研究的质量。在汇集和分析数据之后，我们评估了异质性,并进行了亚组分析和敏感性分析.此外,我们评估了发表偏倚的可能性.
结果：最终检索了8项1513例患者的研究。与单一疗法相比，尽管双药治疗改善了生存效益（OS：HR：0.56，95％CI0.41-0.76，p<0.001；TTP：HR：0.72，95％CI0.59-0.87，p=0.001）和肿瘤反应（ORR：1.59；95％CI1.19-2.13，p=0.002；DCR：RR：1.14；95％CI1.03-1.26，p=0.010），结果的可靠性受到显著异质性的影响。在亚组分析中，与单独的DEB-TACE相比，双重治疗未能显示任何统计学差异.与TKIs相比，在生存率(OS:HR:0.49,95%CI0.40-0.61,p<0.001;TTP:HR:0.60,95%CI0.48-0.75,p<0.001)和肿瘤反应(ORR:RR:2.40,95%CI1.86-3.09,p<0.001;DCR:RR:1.36,95%CI1.20-1.54,p<0.001)方面均有显著优势,同时观察到低异质性。关于安全，DEB-TACE不会提供更严重的AE，而与TKI相关的AE需要密切监测。
结论：我们的研究结果表明，DEB-TACE联合TKIs可能是一种安全有效的治疗uHCC的方法。更适合晚期患者。
