经导管动脉化疗栓塞联合抗血管生成药物治疗肝细胞癌最佳治疗顺序及时间间隔的研究
Study on the optimal treatment sequence and time interval of transcatheter arterial chemoembolization combined with Anti-angiogenic agents for hepatocellular carcinoma
蒋婷 1李培裴 2张杰 3蓝广芊4
作者信息
- 1. 成都医学院临床医学院;西南大学蚕桑纺织与生物质科学学院
- 2. 成都医学院药学院
- 3. 成都医学院临床医学院
- 4. 西南大学蚕桑纺织与生物质科学学院
- 折叠
摘要
背景 经导管动脉化疗栓塞（TACE）联合抗血管生成药物已成为肝细胞癌的重要治疗手段。但，两者联合的最佳治疗顺序与时间间隔尚不明确，临床决策缺乏参考依据，导致患者预后差异较大。目的 探讨TACE联合抗血管生成药物治疗肝细胞癌的最佳治疗顺序与时间间隔。方法 回顾性分析2020年1月—2025年5月于成都医学院第一附属医院接受TACE联合抗血管生成治疗的228例肝细胞癌患者为研究对象，根据治疗顺序分为抗血管先序组（166例）、同步组（15例）、TACE先序组（47例）。收集患者临床资料，包括年龄、性别、中国肝癌分期、体能状态评分、营养风险筛查评分、TACE次数、抗血管生成治疗方案、抗血管生成联合方案、合并症等。所有患者随访至2026-05-01，采用主分析与敏感性分析相结合的方法比较组间客观缓解率（ORR）、疾病控制率（DCR）、中位无进展生存期（mPFS）及不良事件发生率。采用Kaplan-Meier法进行生存分析，通过Log-rank检验进行组间比较；采用多因素Cox比例风险回归模型分析影响PFS的预后因素。结果 总体人群主分析显示，抗血管先序组、同步组、TACE先序组ORR、DCR及mPFS比较，差异均无统计学意义（P>0.05）。敏感性分析（乐观假设）显示，三组间mPFS差异有统计学意义（P=0.013），其中抗血管先序组mPFS显著优于TACE先序组（P0.05）；三亚组间mPFS差异有统计学意义（P=0.019），其中8~14 d亚组mPFS显著优于≥15 d亚组（P0.05）。结论 TACE联合抗血管生成治疗HCC具有一定疗效。尽管主分析未显示统计学差异，但敏感性分析提示抗血管生成先行策略在延长无进展生存期方面具有潜在优势，8~14 d可能是相对更优的治疗窗口。上述发现需前瞻性研究进一步验证。
Abstract
Background Transcatheter arterial chemoembolisation (TACE) combined with anti-angiogenic agents has become an important therapeutic modality for hepatocellular carcinoma (HCC). However, the optimal sequence and time interval for this combination remain undefined, and the absence of established reference standards in clinical practice has led to considerable disparities in patient outcomes. Objective To investigate the optimal treatment sequence and time interval between TACE and anti-angiogenic agents in patients with HCC. Methods A retrospective analysis was conducted on 228 HCC patients treated with TACE plus anti-angiogenic therapy at the First Affiliated Hospital of Chengdu Medical College from January 2020 to May 2025.Patients were divided into three groups based on treatment sequence: anti-angiogenic first group (n=166), concurrent group (n=15), and TACE first group (n=47). Clinical data collected included age, sex, china liver cancer staging, performance status score, china liver cancer staging score, number of TACE procedures, anti-angiogenic agents, combination therapy protocols, and comorbidities. All patients were followed up until May 1, 2026. The primary and sensitivity analysis were used to compare objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and adverse event rates across groups. mPFS was calculated using the Kaplan-Meier method, and inter-group comparisons were performed using the log-rank test. Multivariate Cox proportional hazards regression models were applied to identify independent prognostic factors. Results In the overall population, the primary analysis showed no statistically significant differences among the three groups in ORR, DCR, and mPFS (P>0.05). Sensitivity analysis (optimistic assumption) showed that there was a statistically significant difference in mPFS among the three groups (P=0.013). Pairwise comparisons indicated that the mPFS of the anti-angiogenic first group was significantly better than that of the TACE first group (P 0.05). There was a statistically significant difference in mPFS among the three subgroups (P=0.019). Pairwise comparisons showed that the mPFS in the 8-14 d group was significantly better than that in the 15 d group (P0.05). Conclusion TACE combined with anti-angiogenic therapy demonstrates therapeutic efficacy in HCC. Although the primary analysis did not reveal statistical differences, sensitivity analysis suggests that initiating anti-angiogenic therapy first may offer potential advantages in prolonging progression-free survival, with an interval of 8-14 days possibly representing a relatively optimal window. These findings require further validation through prospective studies.关键词
肝细胞癌/TACE/抗血管生成/治疗顺序/时间间隔Key words
Hepatocellular carcinoma/TACE/Anti-angiogenesis/Treatment sequence/Time interval引用本文复制引用
蒋婷,李培裴,张杰,蓝广芊.经导管动脉化疗栓塞联合抗血管生成药物治疗肝细胞癌最佳治疗顺序及时间间隔的研究[EB/OL].(2026-10-08)[2026-10-12].https://chinaxiv.org/abs/202610.00008.学科分类
临床医学
