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药物洗脱微球经动脉化疗栓塞术(DEB-TACE)联合酪氨酸激酶抑制剂(TKIs)治疗不可切除肝细胞癌(uHCC)患者的疗效和安全性:一项系统评价和荟萃分析

Efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC): A systematic review and meta-analysis.

作者信息

Ji Jun, Zhang Zhihong, Hou Ziqi, Qiu Guoteng, Mi Shizheng, Jin Zhaoxing, Huang Jiwei

机构信息

Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Clin Res Hepatol Gastroenterol. 2024 Apr;48(4):102313. doi: 10.1016/j.clinre.2024.102313. Epub 2024 Mar 5.

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.

CONCLUSION

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

不可切除肝细胞癌(uHCC)的最佳治疗方案仍是一个尚未解决的挑战。关于载药微球经动脉化疗栓塞术(DEB-TACE)联合酪氨酸激酶抑制剂(TKIs)的疗效和安全性,目前仍存在争议。

方法

我们在PubMed、Embase、Web of Science和Cochrane图书馆中检索符合条件的研究。主要研究终点为生存结局,包括总生存期(OS)、无进展生存期(PFS)和疾病进展时间(TTP)。次要结局包括肿瘤反应率和不良事件(AE)。两名研究人员独立进行数据提取并评估研究质量。在汇总和分析数据后,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

最终检索到8项研究,共1513例患者。与单一疗法相比,虽然双联疗法显示出更好的生存获益(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)和肿瘤反应(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),但结果的可靠性受到显著异质性的影响。在亚组分析中,与单纯DEB-TACE相比,双联疗法未显示出任何统计学差异。与TKIs相比,它在生存(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)和肿瘤反应(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)方面均显示出显著优势,而异质性较低。关于安全性,DEB-TACE不会导致更严重的AE,而与TKIs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可能是一种治疗uHCC的安全有效的方法,更适合晚期患者。

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