转化序贯外科手术方案治疗不可手术切除肝细胞癌的安全性与有效性分析  

Safety and efficacy of a treatment protocol in converting initially unresectable to resectable hepatocellular carcinoma

作　　者：张泽 曹银彪 万涛[2] 张雯雯[2] 王湛博[3] 曹俊宁 胡丙洋 韩骏 唐浩文[2] 潘立茹[2] 卢实春[2] Zhang Ze;Cao Yinbiao;Wan Tao;Zhang Wenwen;Wang Zhanbo;Cao Junning;Hu Bingyang;Han Jun;Tang Haowen;Pan Liru;Lu Shichun(Medical School of Chinese People’s Liberation Army(PLA),Beijing 100853,China;Faculty of Hepato-Pancreato-Biliary Surgery,Chinese PLA General Hospital,Institute of Hepatobiliary Surgery,Chinese PLA General Hospital,Key Laboratory of Digital Hepatobiliary Surgery of PLA,Beijing 100853,China;Department of Pathology,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Organ Transplantation Center,Affiliated Hospital of Qingdao University,Qingdao 266100,China)

机构地区：[1]解放军总医院研究生院,北京100853 [2]解放军总医院肝胆胰外科医学部解放军总医院肝胆外科研究所全军数字肝胆外科重点实验室,北京100853 [3]解放军总医院第一医学中心病理科,北京100853 [4]青岛大学附属医院器官移植中心,青岛266100

出　　处：《中华肝胆外科杂志》2022年第1期15-20,共6页Chinese Journal of Hepatobiliary Surgery

基　　金：国家自然科学基金(81670590);国家重点科研计划(2017YFA0103003)。

摘　　要：目的:分析初始不可切除肝细胞癌患者接受免疫检查点抑制剂(ICIs)联合抗血管生成靶向药物(AATDs)治疗后行序贯外科切除的安全性及有效性。方法:回顾性分析2018年12月至2021年4月解放军总医院收治的免疫联合靶向治疗序贯外科手术的41例初始不可切除肝细胞癌患者资料,其中男性34例,女性7例,年龄(51.8±10.7)岁。分析患者临床特点、转化治疗效果、药物不良反应、手术情况及术后并发症情况,门诊复查或电话随访预后。结果:转化治疗前有5例中国肝癌分期(CNLC)-Ⅰb期,4例CNLC-Ⅱ期,28例CNLC-Ⅲa期,4例CNLC-Ⅲb期。其中28例患者存在门静脉癌栓,4例腹膜后淋巴结转移。转化治疗前所有患者肿瘤长径(9.16±4.43)cm,转化治疗后(肝切除前末次评估)肿瘤长径(6.49±4.69)cm。41例患者接受了3~15个周期(中位数5个周期)转化治疗后经改良的实体瘤临床疗效评价标准评估:完全缓解15例、部分缓解15例、疾病稳定6例、疾病进展5例。21例(51.2%)患者在药物治疗过程中发生药物相关不良反应,予以对症治疗或短暂停药后均有所缓解。41例患者均转化治疗成功行肝切除。术后发生Ⅱ级及以上并发症9例(22.0%)。41例患者确诊后6个月、1年及2年累积生存率为100.0%、92.6%与64.7%。手术后6个月、1年及2年累积生存率为95.1%、74.7%与60.8%,手术后6个月、1年及2年累积无复发生存率分别为87.8%、56.7%和48.6%。结论:本研究初步证实不可手术切除的肝细胞癌患者接受免疫联合靶向治疗后行外科手术切除是安全有效的,具有临床推广价值。Objective To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors(ICIs)and antiangiogenic targeted drugs(AATDs)in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma(HCC).Methods The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed.There were 34 males and 7 females,aged(51.8±10.7)years.The clinical characteristics,conversion to resectable HCC,adverse drug reactions,surgical data and postoperative complications were analysed.Patients were followed-up by outpatients clinics or telephone calls.Results There were 5 patients with Chinese Liver Cancer Staging(CNLC)-Ⅰb,4 with CNLC-Ⅱ,28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol.Among them,28 patients had portal vein tumor thrombosis(PVTT)and 4 had retroperitoneal lymph node metastases.All patients had a mean tumor diameter of(9.16±4.43)cm before and(6.49±4.69)cm after the treatment protocol.The latter was based on the last assessment before hepatectomy.The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles(median dose cycles,5)of protocal therapy:15 patients achieved a complete response;15 patients achieved a partial response;6 patients had a stable disease,and 5 patients had a progressive disease.21 patients(51.2%)experienced adverse reactions associated with drug treatment,which resolved with symptomatic treatment or brief discontinuation of the therapy.All patients underwent successful hepatectomy.Postoperative complications of gradeⅡor higher occurred in 9 patients(22.0%).The cumulative overall survival rates at 6 months,1 year and 2 years from diagnosis were 100.0%,92.6%and 64.7%respectively.The cumulative overall survival rates at 6 months,1 year and 2 years after surgery were 95.1%,74.7%and 60.8%,and th

关 键 词：癌 肝细胞 肝切除术 免疫检查点抑制剂 靶向治疗 转化治疗 

分 类 号：R735.7[医药卫生—肿瘤]