EGFR敏感突变型非小细胞肺腺癌晚期患者EGFR-T790M原发性和继发性突变分析

Analysis of EGFR-T790M primary and secondary mutation in patients with EGFR-mutant advanced non-small cell lung adenocarcinoma

目的采用液体活检技术检测符合入组标准的EGFR敏感突变型非小细胞肺腺癌患者的外周血ctDNA样本中EGFR-T790M原发性和继发性突变情况,并结合临床病理特征进行分析。方法采用超级扩增阻碍突变系统(super ARMS)法对符合入组标准的样本进行EGFR基因检测,重点动态检测EGFR-T790M的突变情况。结果原发性EGFR-T790472000M突变率6.77%,明显低于继发性EGFR-T790M突变率50.9%,且在非吸烟(82.14%vs.18.51%)、脑转移(72.72%vs.45.45%)、EGFR-19del(73.77%vs.22.44%)患者中继发性EGFR-T790M突变率明显升高,差异均有统计学意义(P<0.05)。同时继发性EGFR-T790M突变主要集中在服用第1代或第2代EGFR-TKI药物超过6个月的患者中(64.55%vs.16.12%),差异有统计学意义(P<0.05)。而原发性EGFR-T790M突变率明显升高多见于有脑转移患者(20.83%vs.3.29%),差异有统计学意义(P<0.05)。第3代EGFR-TKI对原发性和继发性EGFR-T790M患者的疾病无进展生存期分别为14.2个月和9.3个月。结论在非吸烟、脑转移、EGFR-19del且TKI服药时间超过6个月患者易引起EGFR-T790M的突变,动态检测EGFR-T790M的突变状态可以有效指导临床用药。

Objective To investigate epidermal growth factor receptor(EGFR)gene T790M primary and secondary mutation in plasmatic ctDNA samples from patients with non-small cell lung adenocarcinoma and analyze the relationship between EGFR T790M mutation and the clinical factors.Methods The EGFR-T790M primary and secondary mutation was detected in eligible samples by super amplification refractory mutation system(Super ARMS)in this study.Results EGFR-T790M primary mutation rat which was 6.77%was significantly lower than the secondary mutation rate which was 50.9%,EGFR-T790M secondary mutation rat was higher in patients of non-smoking(82.14%vs.18.51%),brain metastases(72.72%vs.45.45%),EGFR-19 del(73.77%vs.22.44%),the difference had statistical significance(P<0.05).The EGFR-T790M mutation rate of patients who have received first or second generational EGFR-TKI for more than 6 months was higher(64.55%vs.16.12%),the difference had statistical significance(P<0.05).The EGFR-T790M primary mutation rate in patients with brain metastases was significantly increased(20.83%vs.3.29%),the difference was statistically significant(P<0.05).The third generation EGFR-TKI obviously improved progression-free survival of patients with EGFR-T790M primary and secondary mutation.The progress free Survival of patients with EGFR-T790M primary and secondary was 14.2 months and 9.3 months respecting.Conclusion EGFR-T790M mutation was more common in lately non-small cell lung adenocarcinoma patients of non-smoking,brain metastases,EGFR-19 del or have received EGFR-TKI treatment over 6 months.Dynamic detection of EGFR-T790M mutation status can effectively guide the clinical medication.