局部治疗联合EGFR-TKIs在晚期耐药肺腺癌中的临床应用研究

目的探讨表皮细胞生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)使用后耐药进展的肺腺癌患者给予局部治疗(冷冻消融、支气管动脉栓塞)联合EGFR-TKIs的临床疗效。方法回顾性分析2012年3月至2018年10月应急总医院经病理证实并完成随访的原发性EGFR敏感突变型晚期肺腺癌患者,进展后再行EGFR基因检测为T790M阴性,继续应用EGFR-TKIs的同时联合局部治疗,分别统计PFS1(从使用EGFR-TKIs到疾病进展时间)、PFS2(从冷冻消融到疾病进展时间)、OS(总生存期)、OS1(冷冻消融后的生存期),及冷冻消融后的并发症情况。分析OS及PFS的统计学相关影响因素。结果32例符合入组标准的晚期肺腺癌患者,PFS1平均时间为(12.4±8.6)个月。其中14例患者冷冻消融前行支气管动脉栓塞治疗,共消融病灶38个。PFS2为(6.7±2.9)个月。OS为(31.5±13.5)个月,其中OS1为(15.5±7.6)个月。统计分析显示PFS1与PFS2与OS存在显著相关性(P<0.05),靶向治疗进展后至氩氦冷冻消融的时间与患者的OS及OS1存在相关性,支气管动脉栓塞联合氩氦消融治疗后并发症主要为气胸及肺内出血,对症处理后均可缓解。结论EGFR-TKIs耐药进展后晚期肺腺癌中,EGFR-TKIs继续使用并联合冷冻消融等局部治疗可延长患者生存,并发症少,取得临床获益。

Local therapy with continued EGFR-TKIs as a treatment in lung adenocarcinomas which have acquired drug resistance

Objective To investigate the clinical efficacy of cryoablation and bronchial artery embolization combined with epithelial growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)in the treatment of lung adenocarcinoma after drug resistance progression.Methods The study retrospectively analyzed 32 patients with sensitive EGFR mutations and showed a clinical benefit from initial EGFR-TKI and then advanced in Emergency General Hospital from March 2012 to December 2018.These patients(T790M negative)received cryoablation and continued on the same EGFR-TKI.Then calculated PFS1:from initial EGFR TKIs to first disease progression,PFS2:from cryoablation to second progression,OS:overall survival,OS1:the overall survival after cryoablation.Results The mean PFS1 of 32 patients with advanced lung adenocarcinoma was(12.4±8.6)months.Among them,14 patients were treated with bronchial artery embolization before cryoablation,and a total of 38 lesions were ablated.The mean PFS2 time was(6.7±2.9)months.The mean OS time was(31.5±13.5)months,in which OS1 was(15.5±7.6)months.Statistical analysis showed that there was a significant correlation between PFS1 and PFS2 with OS,and the time from cryoablation after the progress of targeted therapy was correlated with OS.A few of complications after bronchial artery embolization combined with cryoablation were pneumothorax and pulmonary hemorrhage,the symptoms could be gradually relieved after treatment.Conclusions This study shows that cryoablation combined with EGFR-TKIs can prolong the survival of patients after drug resistance progression and with less complications,and achieve clinical benefits.