放疗联合靶向、免疫治疗和化疗治疗不可手术切除的肝内胆管癌的疗效及安全性研究

Efficacy and safety of radiotherapy combined with targeted therapy,immunotherapy and chemotherapy for unresectable intrahepatic cholangiocarcinoma

目的观察放疗联合仑伐替尼、anti-PD-1抗体和吉西他滨+奥沙利铂(GEMOX)(四联疗法)在不可手术切除的肝内胆管癌(ICC)中的疗效及安全性。方法选取2018年9月至2022年5月在复旦大学附属中山医院接受四联疗法的复发、转移或不可手术切除的ICC患者。通过医院电子病历系统整理患者接受治疗后的疗效及安全性数据,并对患者进行定期随访获取生存数据,随访至2022年12月31日,分析患者的疗效、预后和不良反应。结果41例符合入组条件的ICC患者纳入分析。中位随访时间15个月时,36例患者发生疾病进展(18例已死亡),3例失访。死亡原因包括肝内肿瘤进展引起的肝衰竭(6例)、远处转移(肺或脑,6例),腹部淋巴结转移(3例)、癌症恶病质(2例)和不明原因(1例)。41例患者的中位无进展生存期为11个月(95%CI:9.2~12.8),中位总生存期为35个月(95%CI:17.0~52.0)。在治疗期间,所有患者都发生了与治疗相关的不良反应事件,13例患者至少发生1次≥3级治疗相关的不良事件,经保守支持治疗后均顺利康复。随访期间未观察到与治疗相关死亡事件的发生。结论放疗联合仑伐替尼、anti-PD-1抗体和GEMOX治疗不可手术切除的ICC患者,疗效显著、安全性耐受,值得临床进一步推广应用。

Objective To evaluate the efficacy and safety of quadruple therapy involving radiotherapy(RT),lenvatinib,anti-PD-1 antibody and GEMOX(oxaliplatin and gemcitabine)chemotherapy(quadruple therapy)in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma(ICC).Methods The patients with recurrent,metastatic,or unresectable ICC underwent quadruple therapy at Zhongshan Hospital,Fudan University between September 2018 and May 2022 were selected.The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system.All patients were followed up regularly to obtain the long-term prognostic data until December 31,2022.The efficacy,prognosis,and toxicity data were collected and analyzed.Results A total of 41 patients were included in the analysis.After a median follow-up period of 15 months,disease progression was diagnosed in 36 patients(18 patients died),while 3 patients were lost to follow-up.The causes of death included liver failure induced by intrahepatic tumor progression(n=6),distant metastases(lungs or brain,n=6),abdominal lymph node metastases(n=3),cancer cachexia(n=2),and unknown cause(n=1).The median progression-free survival(PFS)was 11 months(95%CI:9.2-12.8),and the median overall survival(OS)was 35 months(95%CI:17.0-52.0).All patients experienced treatment-related adverse events(AEs)during the study treatment period.Of the 41 patients,13 patients experienced at least once grade 3 or worse treatment-related AE,but all were manageable with symptomatic treatment.No treatment-related deaths were reported during the follow-up period.Conclusions Radiotherapy(RT),lenvatinib,anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety,which is worthy of clinical application.