晚期非小细胞肺癌外周血循环肿瘤DNAEGFR突变与TKI疗效的相关性

Correlation between peripheral blood circulating tumor DNA EGFR status and TKI efficacy in advanced non-small cell lung cancer

目的:探讨晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)外周血循环肿瘤DNA(circulating tumor DNA,ctDNA)表皮生长因子受体(epidermal growth factor receptor,EGFR)突变与EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)治疗疗效的相关性。方法:利用突变扩增阻滞系统(amplification refractory mutation system,ARMS)法检测50例NSCLC患者外周血ctDNA EGFR突变,其中27例进行组织与ctDNA配对检测。给予TKI治疗一月后进行疗效评价。对ctDNA EGFR突变与患者的临床因素、疗效相关性进行分析,并比较ctDNA与肿瘤组织EGFR突变的一致性。结果:患者性别、年龄、PS评分、病理类型、吸烟史与ctDNA EGFR突变无明显相关性(P>0.05)。ctDNA EGFR突变组客观缓解率(76.5%)、疾病控制率(100%)均高于野生型组(30.3%,60.6%)(P<0.05)。生存分析结果显示:ctDNA EGFR突变组无进展生存期(12个月)较野生型组长(4个月)(P<0.05)。27例配对检测结果显示:ctDNA与肿瘤组织EGFR突变一致率为66.7%(18/27,Kappa=0.400,P<0.05)。无进展生存期:ctDNA(23个月)/肿瘤组织(12个月)EGFR突变组均长于野生型组(2个月/1个月)(P<0.05)。结论:晚期NSCLC外周血ctDNA EGFR突变患者TKI治疗有效率高,ctDNA与肿瘤组织EGFR突变一致性好,作为肿瘤组织的替代检测标本是可行的。

Objective：To investigate the correlation between peripheral blood circulating tumor DNA（ctDNA） epidermal growth factor receptor（EGFR） status and tyrosine kinase inhibitor（TKI） efficacy in advanced non-small cell lung cancer（NSCLC）.Methods：The ctDNA EGFR status was detected by amplification refractory mutation system（ARMS） from 50 advanced NSCLC patients treated with epidermal growth factor receptor-tyrosine kinase inhibitor（EGFR-TKI）.27 patients of them had EGFR status detecting both in ctDNA and matched tumor tissue.Evaluate the therapeutic efficacy after 1 month.The association between ctDNA EGFR status and clinical characteristics,efficacy,progression free survival（PFS）were analyzed.The concordance ratio of EGFR mutation from 2 samples（ctDNA and tumor tissue） was compared.Results：There was no correlation between EGFR mutation with gender,age,PS score,smoking history and pathological type（P〉0.05）.Patients with ctDNA EGFR mutation had remarkably higher objective response rate（ORR） （76.5% vs 30.3%）,disease control rate（DCR）（100% vs 60.6%） and longer progression free survival （PFS）（12 months vs 4 months）（P〈0.05）.In the 27 patients,the consistent rate of the EGFR mutation from 2 samples was 66.7%（18/27,Kappa=0.400,P〈0.05）,patients who had EGFR mutation in ctDNA or tumor tissue had longer PFS（ctDNA：23 months vs 2 months;tumor tissue：12 months vs 1 month）（P〈0.05）.Conclusion：EGFR mutation can be reliably detected in ctDNA of patients with advanced NSCLC and can be used as a biomarker to predict tumor reponse to TKI when the tumor tissue sample was not obtained.