摘要目的 总结肝胆肿瘤术后难治性复发患者应用靶向与免疫联合精准治疗的初步临床效果,探讨精准医学时代多学科综合治疗在肝胆肿瘤术后难治性复发患者治疗中的价值.方法 前瞻性收集解放军总医院第一医学中心肝胆外科2016年6月至2019年1月门诊及住院诊治的52例肝胆肿瘤术后难治性复发患者资料,其中男性37例,女性15例,年龄(56.2±8.5)岁.基于二代基因测序和其他组学包括蛋白组学的结果,为患者制定最适的治疗方案.随访并使用修订的实体瘤疗效评价标准(mRECIST)评估疗效.结果 52例患者随访3～31个月,中位随访时间7个月.完全缓解(CR) 14例,部分缓解(PR)8例,稳定(SD) 14例,疾病进展(PD)16例(其中死亡4例),总的客观缓解率(ORR)为42.3％ (22/52),疾病控制率(DCR)为69.2％ (36/52).中位无进展生存期为7个月.6个月生存率、1年生存率分别为100.0％(48/48)和87.5％ (21/24).结论 精准医学理念在肝胆肿瘤术后难治性复发患者治疗中有良好的指导作用,多靶点酪氨酸激酶抑制剂合并免疫检查点阻断剂联合治疗方案可获得较好的疾病控制率,建议临床上进一步推广使用.

abstractsObjective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.