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中华肝脏外科手术学电子杂志

中华肝脏外科手术学电子杂志 ›› 2021, Vol. 10 ›› Issue (03) : 269 -273. doi: 10.3877/cma.j.issn.2095-3232.2021.03.008

所属专题： 文献；

临床研究

靶向治疗在肝细胞癌合并门静脉癌栓术后辅助治疗中的应用
阎凯1, 卢文峰1, 付雍1, 陈佩钦1, 许朱定1, 张海斌1,†()   
  1. 1. 200438　上海东方肝胆外科医院肝外五科
  • 收稿日期:2021-02-22 出版日期:2021-06-10
  • 通信作者: 张海斌
  • 基金资助:
    上海市卫生和计划生育委员会面上项目(201840152)

Application of targeted therapy in postoperative adjuvant therapy for hepatocellular carcinoma complicated with portal vein tumor thrombus

Kai Yan1, Wenfeng Lu1, Yong Fu1, Peiqin Chen1, Zhuding Xu1, Haibin Zhang1,†()   

  1. 1. Department Ⅴ of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China
  • Received:2021-02-22 Published:2021-06-10
  • Corresponding author: Haibin Zhang
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引用本文：

阎凯, 卢文峰, 付雍, 陈佩钦, 许朱定, 张海斌. 靶向治疗在肝细胞癌合并门静脉癌栓术后辅助治疗中的应用[J]. 中华肝脏外科手术学电子杂志, 2021, 10(03): 269-273.

Kai Yan, Wenfeng Lu, Yong Fu, Peiqin Chen, Zhuding Xu, Haibin Zhang. Application of targeted therapy in postoperative adjuvant therapy for hepatocellular carcinoma complicated with portal vein tumor thrombus[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(03): 269-273.

目的

探讨靶向治疗在肝细胞癌（HCC）合并门静脉癌栓（PVTT）术后辅助治疗中的应用价值。

方法

回顾性分析2016年1月到2019年6月上海东方肝胆外科医院收治的35例HCC合并PVTT患者临床资料。患者均签署知情同意书，符合医学伦理学规定。其中男31例，女4例；年龄36～70岁，中位年龄为53岁。根据术后靶向药物使用情况，将患者分为靶向组（19例）和对照组（16例）。生存分析采用Kaplan-Meier法和Log-rank检验。采用Cox比例风险回归模型进行单因素和多因素分析。

结果

靶向组药物包括索拉非尼12例，仑伐替尼6例，阿帕替尼1例。靶向组术后1、2、3年生存率分别为73.3%、66.6%、53.3%，对照组相应为60.0%、10.9%、10.9%，靶向组术后总体生存率明显优于对照组（HR=0.32，P<0.05）。多因素分析显示，术后靶向治疗为HCC合并PVTT患者术后总体生存的独立保护因素（HR=0.35，95%CI：0.13～0.95；P<0.05）。

结论

术后靶向药物辅助治疗可明显改善HCC合并PVTT患者总体生存。

关键词: 肝细胞癌, 门静脉, 肿瘤细胞, 循环, 靶向治疗
Objective

To evaluate the application of targeted therapy in postoperative adjuvant therapy for hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombus (PVTT).

Methods

Clinical data of 35 HCC patients complicated with PVTT admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from January 2016 to June 2019 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 31 patients were male and 4 female, aged from 36 to 70 years, with a median age of 53 years. According to postoperative use of targeted drugs, all patients were divided into the targeted group (n=19) and control group (n=16). Survival analysis was performed by Kaplan-Meier method and Log-rank test. Cox's proportional hazards regression model was used for univariate and multivariate analyses.

Results

In the targeted group, sorafenib was given in 12 patients, lenvatinib in 6 cases and apatinib in 1 case. The postoperative 1-, 2- and 3-year survival rates in the targeted group were 73.3%, 66.6% and 53.3%, and were 60.0%, 10.9% and 10.9% accordingly in the control group. The postoperative overall survival rate in the targeted group was significantly better than that in the control group (HR=0.32, P<0.05). Multivariate analysis demonstrated that postoperative targeted therapy wasan independent protective factor affecting the postoperative overall survival of HCC patients complicated with PVTT (HR=0.35, 95%CI: 0.13-0.95; P<0.05).

Conclusion

Postoperative adjuvant therapy using targeted drug can significantly improve the overall survival of HCC patients complicated with PVTT.

Key words: Carcinoma, hepatocellular, Portal vein, Neoplastic cells, circulating, Targeted therapy
表1 靶向组与对照组肝细胞癌合并PVTT患者一般资料比较
组别 例数 年龄（岁，±s） 性别（例，男/女） HBsAg阳性（例） HBV-DNA阳性（例） 抗-HCV阳性（例） AFP≥400 μg/L（例） 异常凝血酶原>40 mAU/ml（例） Plt（×109/L，±s） 合并肝硬化（例）
靶向组 19 51±2 18/1 18 6 0 7 15 145±9 13
对照组 16 53±2 13/3 15 9 1 11 9 179±29 8
统计值   t=-1.414 χ2=2.594 χ2=0.016 χ2=2.159 - χ2=3.540 χ2=4.219 t=-1.196 χ2=1.228
P值   0.496 0.212 0.900 0.142 0.209 0.060 0.040 0.619 0.268
组别 肿瘤最大直径（cm，±s） 癌栓分型（例） 手术方式（例） 术后并发症（例） 随访时间[月，M（QR）]
vp1 vp2 vp3 vp4 区域性肝切除术 门静脉癌栓取出术 肝衰竭 胆漏
靶向组 7.2±0.7 3 7 8 1 5 14 0 1 20（13）
对照组 6.0±0.5 6 4 6 0 6 10 1 0 38（25）
统计值 t=1.351 - χ2=0.504 - - U=-85.5
P值 0.203 0.412 0.478 0.209 0.352 0.585
表2 靶向组与对照组肝细胞癌合并PVTT患者复发后治疗情况（例）
组别 例数 再手术 TACE 放疗 更换靶向药物或开始靶向治疗 PD-1单抗免疫治疗 局部消融
靶向组 17 0 14 4 2 4 0
对照组 14 2 12 1 2 1 2
图1 靶向组与对照组肝细胞癌合并PVTT患者Kaplan-Meier生存曲线
表3 肝细胞癌合并PVTT患者术后OS影响因素Cox分析
影响因素 单因素回归分析 多因素回归分析
HR值 95%CI P值 HR值 95%CI P值
年龄 0.99 0.93～1.04 0.762      
性别男性 1.78 0.58～5.46 0.339      
HBV-DNA阳性 0.85 0.32～2.22 0.751      
AFP≥400 μg/L 1.18 -2.99～0.46 0.721      
Plt 1.01 1.00～1.01 0.041 1.01 1.00～1.01 0.046
肝硬化 0.48 0.18～1.26 0.134      
PVTT分型 0.89 0.51～1.53 0.677      
术前辅助治疗（TACE、放疗） 0.67 0.08～5.20 0.686      
手术方式（PVTT取出术） 0.91 0.33～2.46 0.859      
术后靶向治疗 0.32 0.12～0.85 0.023 0.35 0.13～0.95 0.040
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