肝细胞癌靶向联合免疫转化序贯肝切除术后辅助治疗预后分析的多中心研究  

Prognostic analysis of postoperative adjuvant therapy for hepatocellular carcinoma after con-version therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy:a multicenter study

作　　者：林孔英 林佳 赖子森 赖永平 王葵 陈进宏[3] 张志波[4] 李敬东[5] 邰升[6] 王石枫 郑四鸣 张建溪 郑璐 王恺[11] 张嘉成 吕嘉辉 黄理铭 曾永毅 Lin Kongying;Lin Jia;Lai Zisen;Lai Yongping;Wang Kui;Chen Jinhong;Zhang Zhibo;Li Jingdong;Tai Sheng;Wang Shifeng;Zheng Siming;Zhang Jianxi;Zheng Lu;Wang Kai;Zhang Jiacheng;Lyu Jiahui;Huang Liming;Zeng Yongyi(Department of Hepatobiliary Surgery,Mengchao Hepatobiliary Hospital of Fujian Medical University,Fuzhou 350001,China;Third Department of Hepatic Surgery,The Third Affiliated Hospital of Naval Medical University,Shanghai 200433,China;Department of General Surgery,Huashan Hospital,Fudan University,Shanghai 200031,China;Department of Hepatopancreatobiliary Surgery,The First Affiliated Hospital of Fujian Medical University,Fuzhou 350001,China;Department of Hepatopancreatobiliary Surgery,The Affiliated Hospital of North Sichuan Medical College,Nanchong 637503,China;Depart-ment of Hepatopancreatobiliary Surgery,The Second Affiliated Hospital of Harbin Medical University,Harbin 150001,China;Department of Hepatopancreatobiliary Surgery,Ganzhou Fifth People's Hospital,Ganzhou 341007,China;Department of Hepatopancreatobiliary Surgery,The First Affiliated Hospital of Ningbo University,Ningbo 315016,China;Department of Hepatopancreatobiliary Surgery,Xiamen Hospital,Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiamen 361015,China;Depart-ment of Hepatobiliary Surgery,The Second Affiliated Hospital of Army Medical University,Chongqing 400037,China;Department of Hepatopancreatobiliary Surgery,The Second Affiliated Hospital of Nanchang University,Nanchang 330000,China)

机构地区：[1]福建医科大学孟超肝胆医院肝胆外科,福州350001 [2]海军军医大学第三附属医院肝外三科,上海200433 [3]复旦大学附属华山医院普通外科,上海200031 [4]福建医科大学附属第一医院肝胆胰外科,福州350001 [5]川北医学院附属医院肝胆胰外科,南充637503 [6]哈尔滨医科大学附属第二医院肝胆胰外科,哈尔滨150001 [7]赣州市第五人民医院肝胆胰外科,赣州341007 [8]宁波大学附属第一医院肝胆胰外科,宁波315016 [9]北京中医药大学东直门医院厦门医院肝胆胰外科,厦门361015 [10]陆军军医大学第二附属医院肝胆外科,重庆400037 [11]南昌大学第二附属医院肝胆胰外科,南昌330000

出　　处：《中华消化外科杂志》2025年第1期103-112,共10页Chinese Journal of Digestive Surgery

基　　金：国家自然科学基金(62275050);福建省科技创新联合资金项目(2019Y9108);福建省卫健委中青年科研重大项目(2021ZQNZD013)。

摘　　要：目的分析肝细胞癌行靶向联合免疫转化序贯肝切除术后辅助治疗的预后。方法采用回顾性队列研究方法。收集2019年11月至2023年5月福建医科大学孟超肝胆医院等全国11家医学中心收治的103例初始不可切除肝细胞癌患者的临床病理资料;男83例,女20例;年龄为(54±12)岁。103例患者均行酪氨酸激酶抑制剂(TKIs)联合免疫检查点抑制剂(ICIs)成功转化治疗后序贯肝切除术,其中72例术后行辅助治疗设为辅助治疗组,31例术后行随访监测设为随访监测组。观察指标:(1)随访及预后情况。(2)患者无复发生存时间影响因素分析。(3)分层分析。计数资料组间比较采用χ^(2)检验或Fisher确切概率法。采用R软件绘制生存曲线,Log-rank检验进行生存分析。单因素和多因素分析采用Cox比例风险模型。结果(1)随访及预后情况。103例患者术后均获得随访,随访时间为21.0(1.9~47.2)个月,中位无复发生存时间为28.7个月,1、2、3年无复发生存率分别为68.6%、55.6%、41.2%;中位总生存时间未达到,1、2、3年总生存率分别为90.9%、82.1%、69.6%。辅助治疗组患者中位无复发生存时间为33.1个月,1、2年无复发生存率分别为77.2%、61.5%;随访监测组患者中位无复发生存时间为11.1个月,1、2年无复发生存率分别为46.6%、40.8%;两组患者无复发生存情况比较,差异有统计学意义(χ^(2)=5.492,P<0.05)。(2)患者无复发生存时间影响因素分析。多因素分析结果显示:病理学完全缓解和术后辅助治疗均是肝细胞癌患者行靶向联合免疫转化序贯肝切除术后无复发生存时间的独立影响因素(风险比=0.297、0.492,95%可信区间为0.137~0.647、0.268~0.903,P<0.05)。(3)分层分析。71例非病理学缓解患者中,48例辅助治疗组患者中位无复发生存时间为24.0个月,1、2年无复发生存率分别为67.4%、48.8%;23例随访监测组患者中位无复发生存时间为7.4个月,1、2年无复发生�Objective To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods The retrospective cohort study was conducted.The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma(HCC)who were admitted to 11 medical centers in China,including Mengchao Hepatobiliary Hospital of Fujian Medical University et al,from November 2019 to May 2023 were collected.There were 83 males and 20 females,aged(54±12)years.All 103 patients underwent conversion therapy of tyrosine kinase inhibitors(TKIs)and immune checkpoint inhibitors(ICIs)successfully followed by sequential hepatectomy,of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group,and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group.Observation indicators:(1)follow-up and postoperative condi-tions;(2)analysis of factors influencing recurrence-free survival time of patients;(3)stratified ana-lysis.Comparison of count data between group was conducted using the chi-square test or Fisher exact probability.The R software was used to draw survival curves,and the Log-rank test was used for survival analysis.Univariate and multivariate analyses were conducted using the Cox proportional hazard model.Results(1)Follow-up and postoperative conditions.All 103 patients were followed up for 21.0(range,1.9‒47.2)months,with the median recurrence-free survival time of 28.7 months and the 1-,2-,3-year recurrence-free survival rates of 68.6%,55.6%,41.2%.The median overall survival time of 103 patients was unreached,and the 1-,2-,3-year overall survival rates were 90.9%,82.1%,69.6%,respectively.The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group,with the 1-,2-year recurrence-free survival rates as 77.2%,61.5%.The median recurrence-free survival time was 11.1

关 键 词：肝肿瘤 酪氨酸激酶抑制剂 免疫检查点抑制剂 转化治疗 肝切除术 辅助治疗 预后 

分 类 号：R735.7[医药卫生—肿瘤]