免疫联合靶向序贯外科手术方案治疗初始不可切除肝细胞癌的临床疗效评估  

Clinical efficacy of sequential surgery after immune and targeted therapy in downstaging initially unresectable hepatocellular carcinoma

作　　者：李雪瑞 张雯雯[2] 胡丙洋 万涛[2] 刘哲[2] 唐浩文[2] 李俊锋 曹银彪 张泽 王湛博[3] 卢实春[2] Li Xuerui;Zhang Wenwen;Hu Bingyang;Wan Tao;Liu Zhe;Tang Haowen;Li Junfeng;Cao Yinbiao;Zhang Ze;Wang Zhanbo;Lu Shichun(School of Medicine,Nankai University,Tianjin 300071,China;Faculty of Hepato-Pancreato-Biliary Surgery,Chinese PLA General Hospital,Beijing 100853,China;Department of Pathology,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]南开大学医学院,天津300071 [2]解放军总医院肝胆胰外科医学部,北京100853 [3]解放军总医院病理科,北京100853

出　　处：《中华肝胆外科杂志》2023年第1期15-21,共7页Chinese Journal of Hepatobiliary Surgery

基　　金：国家重点研发计划(2017YFA0103003)。

摘　　要：目的评估初始不可切除肝细胞癌患者经免疫联合靶向治疗序贯外科根治性手术的临床疗效。方法前瞻性收集2018年12月至2022年7月在解放军总医院肝胆胰外科医学部接受免疫联合靶向治疗序贯外科手术的初始不可切除肝细胞癌患者资料。入组79例患者,其中男性69例,女性10例,年龄(53.0±10.9)岁。Kaplan-Meier法计算生存率,生存率比较采用log-rank检验。单因素及多因素Cox回归分析患者预后影响因素。结果初诊时有7例(8.9%)中国肝癌分期(CNLC)Ⅰb、Ⅱa、Ⅱb期因肿瘤破裂或剩余功能性肝体积不足行免疫联合靶向治疗,38例(48.1%)CNLCⅢa期,34例(43.0%)CNLCⅢb期。79例患者接受了3~20个周期(中位数5个周期)免疫联合靶向治疗,并序贯根治性外科手术。根据改良实体瘤临床疗效评价标准评估(免疫联合靶向治疗前后),肿瘤达到完全缓解12例(15.2%)、部分缓解50例(63.3%)、疾病稳定15例(19.0%)、疾病进展2例(2.5%)。79例患者1、2、3年累积生存率分别为96.1%、83.5%、76.6%,术后1、2、3年无复发生存率分别为62.1%、52.9%、34.7%。多因素Cox回归分析,术前甲胎蛋白>20μg/L(HR=2.816,95%CI:1.232~6.432,P=0.014)、病理残留肿瘤比例高(HR=1.015,95%CI:1.004~1.026,P=0.006)的患者有更高的术后复发风险,病理残留肿瘤比例高(HR=1.028,95%CI:1.007~1.049,P=0.007)、术前甲胎蛋白>400μg/L(HR=4.099,95%CI:1.193~14.076,P=0.025)的患者死亡风险更高。结论免疫联合靶向序贯外科手术方案治疗初始不可切除肝细胞癌患者可带来远期生存获益,术前甲胎蛋白升高、病理残留肿瘤比例高是患者无复发生存与总体生存的独立危险因素。Objective To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery,Chinese PLA General Hospital.There were 79 patients,with 69 men and 10 women,aged(53.0±10.9)years,being enrolled into this study.The Kaplan-Meier method was used to calculate the survival rate,and the log-rank test was used for survival rate comparison.Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results There were 7 patients(8.9%)with China Liver Cancer Staging(CNLC)Ⅰb,Ⅱa,Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy,and 38 patients(48.1%)with CNLCⅢa and 34 patients(43.0%)with CNLCⅢb.These 79 patients underwent R0 resection after 3-20 cycles(median 5 cycles)of immune and targeted therapy.Based on the modified response evaluation criteria in solid tumor,the results of preoperative imaging assessment were:complete remission in 12 patients(15.2%),partial remission in 50 patients(63.3%),stable disease in 15 patients(19.0%),and disease progression in 2 patients(2.5%).The overall survival rates of patients at 1,2,and 3 years after diagnosis were 96.1%,83.5%,and 76.6%;and the recurrence-free survival rates at 1,2,and 3 years after surgery were 62.1%,52.9%,and 34.7%,respectively.On multivariate Cox regression analysis,patients with a preoperative alpha-fetoprotein>20μg/L(HR=2.816,95%CI:1.232-6.432,P=0.014)and a high proportion of pathological residual tumors(HR=1.015,95%CI:1.004-1.026,P=0.006)had a higher risk of postoperative recurrence;and patients with a high proportion of pathological residual tumors(HR=1.028,95%CI:1.007-1.049,P=0.007)a

关 键 词：癌 肝细胞 肝切除术 免疫治疗 靶向治疗 转化治疗 

分 类 号：R735.7[医药卫生—肿瘤]