HAIC联合靶向和免疫治疗晚期肝癌伴门脉主干癌栓的研究

HAIC combined with targeted therapy and immunotherapy for advanced liver cancer complicated by main portal vein tumor thrombus:a clinical study

目的 评估以mFOLFOX为基础的肝动脉灌注化疗术(HAIC)联合酪氨酸激酶抑制剂(TKI)和免疫检查点抑制剂(ICI)治疗HCC伴门静脉癌栓(PVTT,Vp3,Vp4)的疗效及安全性。方法 本回顾性研究纳入2021年1月至2023年1月哈尔滨医科大学附属肿瘤医院介入科接受以mFOLFOX为基础的HAIC联合TKI和ICI治疗的37例患者进行分析,主要终点是PVTT反应的客观缓解率,次要终点是6个月、1年生存率和总生存期(OS),评估了相应的不良反应事件及并发症。使用ITK-SNAP软件评估PVTT反应,寿命表计算6个月及1年的生存率,Kaplan-Meier生存曲线评估总OS,logistic回归及Cox回归分析了与PVTT反应及OS相关的风险因素。结果 37例患者中7例(18.92%)PVTT体积完全消失(CR),21例(56.76%)患者PVTT体积减少超过50%(PR)。PVTT的客观缓解率(ORR)为75.68%。6个月生存率为89%,1年生存率为66%,中位OS为15.8个月。在单变量分析中,治疗中出现门静脉海绵样变(CTPV)(P=0.010)与PVTT反应相关,Child-Pugh评分(P=0.010)、治疗中出现PVTT反应(P=0.004)作为预测OS的重要因素;在多变量分析中,癌栓治疗前体积(P=0.033)、门静脉海绵样变(P=0.007)是预测PVTT反应的重要因素,Child-Pugh评分(P=0.035)、治疗中出现PVTT反应(P=0.015)作为预测OS的重要因素。在不良反应及并发症方面,与HAIC相关的最常见的不良反应为与奥沙利铂相关的疼痛(30.80%)和血小板减少症(22.59%),其中10例(27%)发生了3级的疼痛,4例(11%)出现了3级的血小板计数减少,在出现疼痛后通过减慢泵入速度及相应的止痛治疗后都可得到缓解;与靶向及免疫治疗相关的常见不良反应为手足反应(16.45%),其中6例(16%)发生了3级手足反应。结论 以FOLFOX为基础HAIC联合靶向及免疫治疗诱导了75.68%的PVTT客观缓解率,为肝内肿瘤提供了更多的治疗选择。

Objective To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy(HAIC)combined with tyrosine kinase inhibitors(TKIs)and immune checkpoint inhibitors(ICIs)in the treatment of advanced hepatocellular carcinoma(HCC)complicated by portal vein tumor thrombus(PVTT).Methods The clinical data of 37 patients with HCC complicated by PVTT,who received mFOLFOX-based HAIC combined with TKI and ICI at the Department of Intervention,Affiliated Cancer Hospital of Harbin Medical University of China between January 2021 and January 2023,were retrospective analyzed.The primary endpoint was the objective remission rate of PVTT response,and the secondary endpoints included the 6-month survival rate,one-year survival rate,and overall survival(OS).The treatment-related adverse events and complications were evaluated.PVTT response was assessed using ITK-SNAP software,life table was used to calculate 6-month and one-year survival,Kaplan-Meier survival curve was used to assess overall OS,and logistic regression analysis and Cox regression analysis were used to analyze the risk factors associated with PVTT response and OS.Results Of the 37 patients,complete resolution of PVTT volume(CR)was obtained in 7(18.92%),and reduction of PVTT volume over 50%was obtained in 21(56.76%).The objective remission rate(ORR)of PVTT was 75.68%.The 6-month survival rate was 89%,the one-year survival rate was 66%,and the median OS was 15.8 months.Univariate analysis indicated that cavernous degeneration of portal vein(CTPV)was correlated with PVTT response(P=0.010).The Child-Pugh score(P=0.010)and the presence of PVTT response(P=0.004)to treatment were the important factors for predicting OS.Multivariate analysis revealed that the preoperative volume of cancer thrombus(P=0.033),cavernous degeneration of portal vein(P=0.007)were the important factors for predicting the PVTT response,and the Child-Pugh score(P=0.035)and the presence of PVTT response during treatment(P=0.015)were the important factors for predicting OS.The most common adverse reactions related to HAIC were oxaliplatin-related pain(n=30,80%)and thrombocytopenia(n=22,59%),among them 10 patients(27%)developed gradeⅢpain and 4 patients(11%)developed gradeⅢthrombocytopenia.The pain could be alleviated by slowing down the pump velocity and corresponding pain relief treatment.The targeted therapy and immunotherapy-related common adverse reaction was hand and foot reactions(n=16,45%),among them 6 patients(16%)developed grade III hand and foot reactions.Conclusion FOLFOX-based HAIC combined with targeted therapy and immunotherapy can obtain a 75.68%ORR of PVTT,which provides more therapeutic options for intrahepatic tumors.