PD-1抑制剂联合TKIs治疗中晚期肝细胞癌后实施肝移植的可行性探讨

Immune checkpoint inhibitors combined with TKIs as a bridge therapy for advanced HCC before liver transplantation

目的:探讨中晚期肝细胞癌患者接受程序性死亡蛋白-1(PD-1)抑制剂联合酪氨酸激酶抑制剂(TKIs)治疗后实施肝移植的安全性及有效性。方法:回顾性分析首都医科大学附属北京佑安医院与解放军总医院第一医学中心2019年1月至2020年12月中晚期肝细胞癌实施肝移植的6例患者资料,均为男性,年龄(57.5±4.3)岁。分析移植前肿瘤分期、PD-1抑制剂使用情况、移植时PD-1抑制剂停用时长,以及术后肝功能恢复、并发症等情况。门诊复查随访肿瘤复发、无瘤生存情况等。结果:6例中晚期肝细胞癌患者移植前接受了PD-1抑制剂联合TKIs治疗,其中4例肿瘤为巴塞罗那临床肝癌分期(BCLC)C期或中国肝癌分期(CNLC)Ⅲa期,2例为BCLC-B期或CNLC-Ⅱb期。6例患者使用PD-1抑制剂1~20个周期,平均5.5个周期,停用PD-1抑制剂至肝移植时间间隔12~45 d,平均19.5 d。6例患者经PD-1抑制剂联合TKIs治疗后达到肝移植标准,均成功实施了同种异体原位肝移植,术后肝功能恢复良好,无急性排斥反应和其他严重并发症发生。随访时间范围8.2~27.3个月,中位时间11.9个月。随访结束时无患者死亡,2例肿瘤复发。4例患者无肿瘤复发,无瘤生存期2.9~27.3个月,平均10.9个月。结论:肝移植前使用PD-1抑制剂联合TKIs治疗有可能使中晚期肝细胞癌患者获益,并且不会增加移植后急性排斥反应与其他并发症的发生。

Objective To investigate the safety and efficacy of combining programmed death-1(PD-1)with tyrosine kinase inhibitors(TKIs)in patients with advanced hepatocellular carcinoma(HCC)before liver transplantation(LT).Methods The data of six males with a mean±s.d.age of(57.5±4.3)years who were treated with PD-1 inhibitors combined with TKIs for advanced HCC before LT at Beijing You'an Hospital,Capital Medical University and the First Medical Center of Chinese PLA General Hospital were retrospectively analysed.The tumor stagings,the use of PD-1 inhibitors and TKIs with their discontinuation in pre-LT/post-LT liver function recovery durations,incidences of complication.The tumor recurrence and disease-free survival rates were determined on follow-up of these patients at outpatients clinics.Results For the 6 patients included in this study,four patients were classified by the Barcelona Clinic Liver Cancer Staging(BCLC)as C and the China Liver Cancer Staging(CNLC)asⅢa,and two patients were classified by the BCLC staging as B and the CNLC asⅡb.The mean cycle of PD-1 inhibitor used was 5.5(1-20),and the mean duration of PD-1 inhibitor discontinuation was 19.5(12-45)days pre-LT.All patients who were treated with PD-1 inhibitors combined with TKIs reached the liver transplantation standard,and all successfully underwent orthotopic liver transplantation.The liver function recovered well without any serious complications post-LT.All the patients survived without developing any acute rejection or other complications.The follow-up time ranged from 8.2 to 27.3 months,with a median of 11.9 months.No patients had died,and 2 patients developed tumor recurrence.The median(range)tumor-free survival time was 10.9(2.9-27.3)months.Conclusion Patients with advanced HCC could benefit from combined PD-1 inhibitors with TKIs therapy pre-LT.There were no increased incidences of acute rejection and other complications post-LT.