NTRK突变肺癌患者的临床特征和预后分析

Characteristics and outcomes of lung cancer patients with NTRK mutations

目的:探讨NTRK基因突变肺癌患者的临床特征、治疗情况以及与预后的关系。方法:回顾性分析2016年10月至2019年11月就诊于华中科技大学同济医学院附属同济医院胸部肿瘤科且NGS检测伴有NTRK突变的原发性肺癌患者的临床资料,应用Kaplan-Meier法和Log-rank检验进行单因素生存分析。结果:研究共纳入28例患者,27例为Ⅳ期,基因检测结果均为NTRK点突变或拷贝数扩增;1例为ⅢC期,基因检测结果为AEN-NTRK3(A1:N18)融合。单因素分析结果显示,接受一线治疗的NTRK突变患者无进展生存期(progression-free survival,PFS)与肿瘤组织病理类型相关(腺癌vs.鳞癌:9.4个月vs. 2.5个月,P<0.05),而与年龄、性别、吸烟史、NTRK突变位点、突变类型、是否合并经典突变无关(均P>0.05)。一线接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗的NTRK1突变合并EGFR突变患者PFS明显长于NTRK3突变合并EGFR突变患者,中位PFS分别为12.4个月和3.0个月,差异具有统计学意义(P<0.05)。结论:接受一线治疗的NTRK突变肺腺癌患者PFS较鳞癌患者长。EGFR突变合并NTRK3突变肺癌患者接受EGFR-TKIs治疗的预后较差,合并NTRK3突变可能是EGFR突变肺癌预后不良的因素之一。

Objective:To analyze the clinical characteristics,treatments,and outcomes of lung cancer patients with NTRK mutations.Methods:The clinical data of patients with pathologically confirmed primary lung cancer and the NTRK mutation in next-generation sequencing(NGS)admitted to Tongji Hospital of Tongji Medical College,Huazhong University of Science and Technology between October 2016 and November 2019 were retrospectively analyzed.The Kaplan-Meier method and the Log-rank test were used for the univariate survival analysis.Results:A total of 28 patients were enrolled.27 patients were diagnosed as stageⅣwith point mutations or copy number amplifications of NTRK,and 1 patient was diagnosed as stageⅢC with AEN-NTRK3(A1:N18)fusion.The univariate analysis showed that the median progression-free survival(PFS)was related to the pathological pattern(adenocarcinoma vs.squamous carcinoma:9.4 months vs.2.5months,P<0.05).However,the PFS for first-line therapy was not related to age,gender,smoking history,site,and type of NTRK mutation or concomitant classical mutations(P>0.05,respectively).Contrastingly,the median PFS of EGFR-TKIs treatment for patients with EGFR mutant lung cancer and concomitant NTRK1 mutation was significantly longer than patients with concomitant NTRK3 mutation(12.4 months vs.3.0 months,P<0.05).Conclusions:Patients with NTRK mutant lung adenocarcinoma had a longer PFS than patients with lung squamous carcinoma when they received first-line therapy.EGFR mutant patients with concomitant NTRK3 mutation had a poorer prognosis than patients with concomitant NTRK1 mutation when they received EGFR-TKIs treatment.Therefore,concomitant NTRK3 mutation may be one of the poor prognostic factors of EGFR mutant lung cancer.