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经动脉化疗栓塞-肝动脉灌注化疗-多靶点酪氨酸激酶抑制剂-免疫检查点抑制剂(TACE-HAIC-MTTs-ICIs)与经动脉化疗栓塞-多靶点酪氨酸激酶抑制剂-免疫检查点抑制剂(TACE-MTTs-ICIs)治疗肝细胞癌的疗效和安全性比较:基于血清甲胎蛋白动态变化的预后分析

Comparison of the efficacy and safety of TACE-HAIC-MTTs-ICIs and TACE-MTTs-ICIs in the hepatocellular carcinoma: a prognostic analysis based on the dynamic changes of serum AFP.

作者信息

Li Wenli, Lu Mingjian, Yuan Guosheng, Shi Feng, Zang Mengya, Hu Xiaoyun, Li Qi, Zhu Peilin, Chen Yongru, Zhao Jingyi, Su Kaiyan, Peng Yunheng, Chen Jinzhang

机构信息

Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangzhou, China.

Department of Interventional Radiology, Guangzhou Institute of Cancer Research, the Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, P.R. China.

出版信息

Int J Surg. 2025 Jun 20. doi: 10.1097/JS9.0000000000002818.

Abstract

BACKGROUND

To evaluate the efficacy and safety of 2 combination treatments for hepatocellular carcinoma (HCC): 1) transarterial chemoembolization (TACE) with hepatic arterial infusion chemotherapy (HAIC) combined with molecular targeted therapies (MTTs) and immune checkpoint inhibitors (ICIs) (TACE-HAIC-MI), and 2) TACE combined with MTTs and ICIs (TACE-MI). In addition, analysis of changes in serum AFP levels and patient survival was performed.

METHODS

A retrospective study of 459 HCC patients treated with one of the aforementioned treatments was performed: TACE-MI (N = 305) and TACE-HAIC-MI (N = 154). Inverse probability of treatment weighting (IPTW) was used to minimize confounding factors, and sensitivity analyses were conducted. The JLCM model was used to model AFP change trajectories, and Cox regression analysis was used to identify prognostic factors. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Tumor response and adverse events (AEs) were assessed using RECIST v1.1 and CTCAE v5.0, respectively.

RESULTS

After IPTW, the median OS of TACE-HAIC-MI group was 23.9 months, and for the TACE-MI group it was 21.7 months(P = 0.432). The median PFS of the 2 groups was 9.77 months versus 8.97 months (P = 0.45). Six optimal latent classes of AFP trajectories were identified. Class 1 demonstrated a median OS of 20.43 months, while class 2 did not reach the median OS. The median OS for class 3 was 43.87 months, for class 4 was 18.47 months, for class 5 was 8.13 months, and for class 6 was 11.37 months. Cox regression analyses showed that AFP trajectory independently predicted median OS and PFS, with HRs between 1.56 and 45.28. The most common AEs were elevated transaminase levels, electrolyte imbalances, anemia, and pain. Nausea and vomiting were more frequent in the TACE-HAIC-MI group, and elevated transaminase levels were less common than in the TACE-MI group.

CONCLUSION

TACE-HAIC-MI and TACE-MI treatments have no significant survival differences in patients with HCC. Patients with a favorable AFP response have significantly better survival outcomes than those with a poor response.

摘要

背景

评估两种肝细胞癌(HCC)联合治疗方案的疗效和安全性:1)经动脉化疗栓塞术(TACE)联合肝动脉灌注化疗(HAIC),并联合分子靶向治疗(MTT)和免疫检查点抑制剂(ICI)(TACE-HAIC-MI);2)TACE联合MTT和ICI(TACE-MI)。此外,还对血清甲胎蛋白(AFP)水平变化和患者生存率进行了分析。

方法

对459例接受上述治疗之一的HCC患者进行回顾性研究:TACE-MI组(N = 305)和TACE-HAIC-MI组(N = 154)。采用治疗权重逆概率法(IPTW)以尽量减少混杂因素,并进行敏感性分析。使用JLCM模型对AFP变化轨迹进行建模,并采用Cox回归分析确定预后因素。主要终点和次要终点分别为总生存期(OS)和无进展生存期(PFS)。分别使用RECIST v1.1和CTCAE v5.0评估肿瘤反应和不良事件(AE)。

结果

IPTW后,TACE-HAIC-MI组的中位OS为23.9个月,TACE-MI组为21.7个月(P = 0.432)。两组的中位PFS分别为9.77个月和8.97个月(P = 0.45)。确定了AFP轨迹的六个最佳潜在类别。第1类的中位OS为20.43个月,而第2类未达到中位OS。第3类的中位OS为43.87个月,第4类为18.47个月,第5类为8.13个月,第6类为11.37个月。Cox回归分析表明,AFP轨迹可独立预测中位OS和PFS,风险比在1.56至45.28之间。最常见的AE为转氨酶水平升高、电解质失衡、贫血和疼痛。TACE-HAIC-MI组恶心和呕吐更常见,转氨酶水平升高比TACE-MI组少见。

结论

TACE-HAIC-MI和TACE-MI治疗方案在HCC患者中的生存差异无统计学意义。AFP反应良好的患者生存结局明显优于反应较差的患者。

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