Zhang Wei-Chen, Du Ke-Yi, Yu Song-Feng, Guo Xue-E, Yu Han-Xi, Wu Dong-Yan, Pan Cheng, Zhang Cheng, Wu Jian, Bian Li-Fang, Cao Lin-Ping, Yu Jun
Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Zhejiang University School of Medicine, Hangzhou 310000, China.
Hepatobiliary Pancreat Dis Int. 2025 Apr;24(2):157-163. doi: 10.1016/j.hbpd.2024.11.004. Epub 2024 Nov 16.
Transarterial chemoembolization (TACE) based neoadjuvant therapy was proven effective in hepatocellular carcinoma (HCC). Recently, tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) also showed promise in HCC treatment. However, the prognostic benefits associated with these treatments remain uncertain. This study aimed to explore the relationship between pathologic response and prognostic features in HCC patients who received neoadjuvant therapy.
HCC patients who received TACE either with or without TKIs/ICIs as neoadjuvant therapy before liver resection were retrospectively collected from the First Affiliated Hospital, Zhejiang University School of Medicine in China. Pathologic response was determined by calculating the proportion of non-viable area within the tumor. Major pathologic response (MPR) was defined as the presence of non-viable tumor cells reaching a minimum of 90%. Complete pathologic response (CPR) was characterized by the absence of viable cells observed in the tumor.
A total of 481 patients meeting the inclusion criteria were enrolled, with 76 patients (15.8%) achieving CPR and 179 (37.2%) reaching MPR. The median recurrence-free survival (mRFS) in the CPR + MPR group was significantly higher than the non-MPR group (31.3 vs. 25.1 months). The difference in 3-year overall survival (OS) rate was not significant. Multivariate Cox regression analysis identified failure to achieve MPR (hazard ratio = 1.548, 95% confidence interval: 1.122-2.134; P = 0.008), HBsAg positivity (HR = 1.818, 95% CI: 1.062-3.115, P = 0.030), multiple lesions (HR = 2.278, 95% CI: 1.621-3.195, P < 0.001), and baseline tumor size > 5 cm (HR = 1.712, 95% CI: 1.031-2.849, P = 0.038) were independent risk factors for RFS. Subgroup analysis showed that 67 of 93 (72.0%) patients who received the combination of TACE, TKIs, and ICIs achieved MPR + CPR.
In individuals who received TACE-based neoadjuvant therapy for HCC, failure to achieve MPR emerges as an independent risk factor for RFS. Notably, the combination of TACE, TKIs, and ICIs demonstrated the highest rate of MPR.
基于经动脉化疗栓塞（TACE）的新辅助治疗已被证实在肝细胞癌（HCC）中有效。近来，酪氨酸激酶抑制剂（TKIs）和免疫检查点抑制剂（ICIs）在HCC治疗中也显示出前景。然而，与这些治疗相关的预后益处仍不确定。本研究旨在探讨接受新辅助治疗的HCC患者病理反应与预后特征之间的关系。
回顾性收集中国浙江大学医学院附属第一医院接受TACE联合或不联合TKIs/ICIs作为肝切除术前新辅助治疗的HCC患者。通过计算肿瘤内无存活区域的比例来确定病理反应。主要病理反应（MPR）定义为无存活肿瘤细胞的比例至少达到90%。完全病理反应（CPR）的特征是肿瘤中未观察到存活细胞。
共纳入481例符合纳入标准的患者，其中76例（15.8%）达到CPR，179例（37.2%）达到MPR。CPR + MPR组的中位无复发生存期（mRFS）显著高于非MPR组（31.3个月对25.1个月）。3年总生存率（OS）率的差异无统计学意义。多因素Cox回归分析确定未达到MPR（风险比 = 1.548，95%置信区间：1.122 - 2.134；P = 0.008）、HBsAg阳性（HR = 1.818，95% CI：1.062 - 3.115，P = 0.030）、多发灶（HR = 2.278，95% CI：1.621 - 3.195，P < 0.001）和基线肿瘤大小>5 cm（HR = 1.712，95% CI：1.031 - 2.849，P = 0.038）是RFS的独立危险因素。亚组分析显示，93例接受TACE、TKIs和ICIs联合治疗的患者中有67例（72.0%）达到MPR + CPR。
在接受基于TACE的新辅助治疗的HCC患者中，未达到MPR是RFS的独立危险因素。值得注意的是，TACE、TKIs和ICIs联合治疗显示出最高的MPR率。
