血浆EGFR基因突变检测在晚期非小细胞肺癌患者EGFR-TKI疗效评估中的价值

Predictive value of EGFR mutation detection in plasma for the EGFR-TKI efficacy in advanced non-small-cell lung cancer patients

目的探讨血浆表皮生长因子受体(EGFR)突变状态检测在晚期非小细胞肺癌患者表皮生长因子受体酪氨酸酶抑制剂(EGFR-TKI)疗效评估中的价值。方法应用扩增阻滞突变系统(ARMS)法检测70例晚期非小细胞肺癌患者肿瘤组织及血浆的EGFR突变状态。以肿瘤组织中的EGFR突变状态检测为对照,计算血浆中EGFR突变状态检测的敏感性、特异性、一致性,并比较两种检测对患者EGFR-TKI疗效及预后评估的差异。结果以配对的肿瘤组织EGFR突变检测结果为对照,ARMS法检测血浆EGFR突变的敏感性、一致性及特异性分别为58.1%、72.9%、96.3%。在38例经过EGFR-TKI治疗的患者中,肿瘤组织EGFR突变型患者的有效率及中位无进展生存期均优于EGFR野生型患者(有效率:69%比11.1%,P=0.005;无进展生存期:10个月比3个月,P=0.003)。血浆EGFR突变型患者与肿瘤组织EGFR突变型患者的有效率及中位无进展生存期均相似(有效率:P=0.908;中位无进展生存期:P=0.593)。在血浆标本中,EGFR突变型患者的中位无进展生存期长于EGFR野生型患者(10个月比7个月,P=0.032)。EGFR突变型患者的有效率高于EGFR野生型患者,但差异无统计学意义(70.6%比42.9%,P=0.111)。结论血浆EGFR突变可预测晚期非小细胞肺癌患者EGFR-TKI疗效,但因较高的假阴性率,血浆EGFR野生型患者需应用肿瘤组织进一步检测。

To investigate the predictive value of epidermal growth factor receptor （EGFR） mutation detection in plasma for the EGFR tyrosine kinase inhibitor （EGFR-TKI） efficacy in advanced non-small-cell lung cancer （NSCLC） patients.Methods EGFR mutations in the tumor tissues and matched plasma samples from 70 advanced NSCLC patients were assessed using amplification refractory mutation system （ARMS）.The sensitivity, specificity and consistency of EGFR mutations in plasma were calculated by taking the EGFR mutations in tumor tissues as the control group.The differences of EGFR-TKI efficacy and prognosis were compared between the two detections.Results Compared with the EGFR mutation detection in the matched tumor tissues, the sensitivity, consistency and specificity of EGFR mutations in plasma detected by ARMS was 58.1%, 72.9% and 96.3%, respectively.For the 38 patients treated with EGFR-TKI, the response rate （ORR） and median progression-free survival （PFS） was significantly superior in the EGFR mutant group as compared with the wild-type group in tumor tissue samples （ORR： 69% vs.11.1%, P=0.005;PFS： 10 months vs.3 months, P=0.003）.ORR and PFS of patients with EGFR mutation in plasma was consistent to that of patients with EGFR mutation in tumor tissues （ORR： P=0.908;PFS： P=0.593）.In the plasma samples, PFS of patients with EGFR mutations was longer than that without EGFR mutations （10 months vs 7 months, P=0.032）.Patients with EGFR mutations had significantly higher ORR than those without mutations （70.6% vs 42.9%, P=0.111）.Conclusions The detection of EGFR mutations in plasma can predict the efficacy of EGFR-TKI.However, due to the high false negative rate in plasma samples, for the patients with wild-type EGFR in plasma, they need further confirmation in tumor tissues.