中晚期肝细胞癌局部区域和全身治疗的最佳序贯：一项网状Meta分析。
Optimal sequencing of locoregional and systemic therapies for intermediate and advanced hepatocellular carcinoma: a network meta-analysis.
作者信息
Lu Wei, Li Zhiyuan, Pan Chen, Chen Bingliang, Zhang Gang, Yang Zhiming, Hao Jingcheng
机构信息
Department of Hepatobiliary and Vascular Surgery, The First Affiliated Hospital of Chengdu Medical College, Baoguang Avenue 278, Xindu District, Chengdu, 610599, Sichuan Province, China.
出版信息
J Cancer Res Clin Oncol. 2025 Jun 25;151(6):196. doi: 10.1007/s00432-025-06233-7.
INTRODUCTION
Transarterial chemoembolization (TACE), anti-angiogenic drugs (AADs), and immune checkpoint inhibitors (ICIs) are common therapies for hepatocellular carcinoma (HCC). Despite proven benefits of combined regimens, optimal sequencing remains unclear. This network meta-analysis evaluates safety and efficacy of therapeutic sequences in intermediate-advanced HCC.
METHODS
We conducted a comprehensive search of multiple databases, including PubMed, Cochrane Library, Web of Science, and EMBASE, for studies published until February 1, 2025. Cochrane's tools and the Newcastle-Ottawa Scale were used to assess the evaluation of bias. We performed data compilation and conducted a network meta-analysis to compare the relative efficacy of different treatments.
RESULTS
A total of 56 studies (10,456 patients) evaluated 11 therapeutic sequences. Survival outcomes favored TACE-AADs-ICIs (TAI), which ranked highest for overall survival (OS: SUCRA 90.0%) and progression-free survival (PFS: SUCRA 91.3%). Tumor responses differed significantly across regimens: TACE-ICIs (TI) achieved the highest probability of complete response rate (CRR: SUCRA 83.9%), while AADs-ICIs-TACE (AIT) ranked first in objective response rate (ORR: SUCRA 85.8%). Notably, ICIs-AADs (IA) achieved superior disease control rate (DCR: SUCRA 88.1%). ICIs monotherapy (I) was associated with the lowest incidence of grade ≥ 3 adverse events (AEs: SUCRA 11.7%).
CONCLUSION
Our comprehensive network meta-analysis establishes a multidimensional efficacy-safety profile for sequential therapies in intermediate and advanced HCC management. TACE-initiated sequences (TAI/TIA) optimize survival (OS/PFS: SUCRA > 90%), while systemic-first regimens (AIT/IA) maximize tumor response (ORR/DCR: SUCRA > 85%). ICIs monotherapy exhibits the safest profile. Further clinical studies are warranted to determine optimal treatment sequencing for intermediate and advanced HCC.
引言
经动脉化疗栓塞术（TACE）、抗血管生成药物（AADs）和免疫检查点抑制剂（ICIs）是肝细胞癌（HCC）的常见治疗方法。尽管联合治疗方案已被证明有益，但最佳的治疗顺序仍不明确。这项网状Meta分析评估了中晚期HCC治疗顺序的安全性和有效性。
方法
我们对多个数据库进行了全面检索，包括PubMed、Cochrane图书馆、科学网和EMBASE，检索截至2025年2月1日发表的研究。使用Cochrane工具和纽卡斯尔-渥太华量表来评估偏倚。我们进行了数据汇总并进行了网状Meta分析，以比较不同治疗方法的相对疗效。
结果
共有56项研究（10456例患者）评估了11种治疗顺序。生存结果显示TACE-AADs-ICIs（TAI）最佳，其总生存期（OS：累积排序曲线下面积（SUCRA）90.0%）和无进展生存期（PFS：SUCRA 91.3%）排名最高。不同治疗方案的肿瘤反应差异显著：TACE-ICIs（TI）达到完全缓解率（CRR）的概率最高（SUCRA 83.9%），而AADs-ICIs-TACE（AIT）的客观缓解率（ORR）排名第一（SUCRA 85.8%）。值得注意的是，ICIs-AADs（IA）的疾病控制率（DCR）更高（SUCRA 88.1%）。ICIs单药治疗（I）的≥3级不良事件（AEs）发生率最低（SUCRA 11.7%）。
结论
我们全面的网状Meta分析为中晚期HCC治疗的序贯疗法建立了多维度的疗效-安全性概况。以TACE起始的治疗顺序（TAI/TIA）可优化生存（OS/PFS：SUCRA>90%），而以全身治疗优先的方案（AIT/IA）可使肿瘤反应最大化（ORR/DCR：SUCRA>85%）。ICIs单药治疗表现出最安全的概况。有必要进行进一步的临床研究以确定中晚期HCC的最佳治疗顺序。
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