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免疫检查点抑制剂联合局部区域治疗和酪氨酸激酶抑制剂治疗不可切除肝细胞癌的疗效增强:一项单中心回顾性研究。

Enhanced efficacy of immune checkpoint inhibitors combined locoregional therapy and tyrosine kinase inhibitors in the treatment of unresectable hepatocellular carcinoma: A single - center retrospective study.

作者信息

Bu Junfeng, Li Zihan, Hu Die, Lan Ling, Huang Jiwei, Wang Xin, Li Qiu, Zhou Jin, Zeng Yong

机构信息

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

West China School of Medicine, Sichuan University, Chengdu, China.

出版信息

Front Oncol. 2025 Feb 25;15:1554711. doi: 10.3389/fonc.2025.1554711. eCollection 2025.

Abstract

BACKGROUND

Unresectable hepatocellular carcinoma (HCC) presents significant treatment challenges. While locoregional therapies (LT) and tyrosine kinase inhibitors (TKI) offer some benefits, prognosis remains poor. Immune checkpoint inhibitors (ICI) have shown promise in other oncological settings, suggesting potential benefits in HCC treatment regimens.

METHODS

This retrospective study analyzed 232 patients diagnosed with unresectable HCC at West China Hospital from January 2019 to December 2023. Patients were categorized into two treatment groups: LT+TKI and LT+TKI+ICI. All patients underwent standardized locoregional treatments and first-line TKIs, with the latter group also receiving ICIs. The primary endpoints measured were overall survival (OS) and progression-free survival (PFS). Survival analysis utilized Kaplan-Meier estimates and Cox regression models.

RESULTS

The LT+TKI+ICI group demonstrated significantly improved survival outcomes compared to the LT+TKI group. Median OS was 28 ± 3.9 months in the LT+TKI+ICI group versus 21 ± 3.0 months in the LT+TKI group, with corresponding 6-, 12-, and 24-month OS rates of 96.8%, 79.3%, and 59.4% versus 85.8%, 71.5%, and 44.1%, respectively (HR, 0.64; 95% CI, 0.449-0.913; P = 0.014). Median PFS also favored the LT+TKI+ICI group (11 ± 1.1 months vs. 7 ± 0.76 months; HR, 0.60; 95% CI, 0.452-0.805; P<0.001). Multivariable analysis identified LT+TKI, vascular invasion, and metastasis as independent risk factors for poorer survival outcomes.

CONCLUSIONS

Adding ICI to LT and TKI significantly extends both OS and PFS in patients with unresectable HCC. These findings suggest that integrating ICI into treatment protocols could be beneficial in managing unresectable HCC, particularly for patients with vascular invasion.

摘要

背景

无法切除的肝细胞癌(HCC)带来了重大的治疗挑战。虽然局部区域治疗(LT)和酪氨酸激酶抑制剂(TKI)有一定益处,但预后仍然很差。免疫检查点抑制剂(ICI)在其他肿瘤治疗领域已显示出前景,提示在HCC治疗方案中可能有益。

方法

这项回顾性研究分析了2019年1月至2023年12月在华西医院诊断为无法切除的HCC的232例患者。患者被分为两个治疗组:LT+TKI组和LT+TKI+ICI组。所有患者均接受标准化的局部区域治疗和一线TKI治疗,后一组还接受ICI治疗。测量的主要终点是总生存期(OS)和无进展生存期(PFS)。生存分析采用Kaplan-Meier估计和Cox回归模型。

结果

与LT+TKI组相比,LT+TKI+ICI组的生存结果有显著改善。LT+TKI+ICI组的中位OS为28±3.9个月,而LT+TKI组为21±3.0个月,相应的6个月、12个月和24个月OS率分别为96.8%、79.3%和59.4%,而LT+TKI组分别为85.8%、71.5%和44.1%(HR,0.64;95%CI,0.449-0.913;P=0.014)。中位PFS也有利于LT+TKI+ICI组(11±1.1个月对7±0.76个月;HR,0.60;95%CI,0.452-0.805;P<0.001)。多变量分析确定LT+TKI、血管侵犯和转移是生存结果较差的独立危险因素。

结论

在LT和TKI基础上加用ICI可显著延长无法切除的HCC患者的OS和PFS。这些发现表明,将ICI纳入治疗方案可能有利于管理无法切除的HCC,特别是对于有血管侵犯的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ec2/11893395/440ebe00e0b6/fonc-15-1554711-g001.jpg

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