Dynamics of EGFR mutations in plasma recapitulates the clinical response to EGFR-TKIs in NSCLC patients.
Dynamics of EGFR mutations in plasma recapitulates the clinical response to EGFR-TKIs in NSCLC patients.
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血浆中 EGFR 突变的动态概括了 NSCLC 患者对 EGFR-TKI 的临床反应
DOI：
10.18632/oncotarget.19139
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Jiang L
中科院分区：
文献类型：
--
作者：
Xiong L;Cui S;Ding J;Sun Y;Zhang L;Zhao Y;Gu A;Chu T;Wang H;Zhong H;Ye X;Gu Y;Zhang X;Hu M;Jiang L
目的利用无浆细胞DNA （cfDNA）进行基因组分析是肿瘤再活检的一种非侵入性替代方法，这在临床实践中具有挑战性。研究了应用酪氨酸激酶抑制剂（TKIs）治疗的非小细胞肺癌（NSCLC）患者血浆样品动态监测表皮生长因子受体（EGFR）突变状态的可行性及其在临床疗效跟踪和耐药性检测中的应用。患者和方法本研究招募了45例tki前血浆EGFR突变阳性和至少2例tki后血浆采集的NSCLC患者。采用液滴数字PCR （ddPCR）对纵向采集的血浆样本进行L858R、外显子19缺失（19-del）和T790M等EGFR突变分析。结果：在TKI治疗的前两个月，我们观察到血浆EGFR突变丰度显著降低。获得继发性T790M看门人突变或EGFR突变完全“丢失”代表了两大类耐药谱。此外，我们证明血浆EGFR突变水平与肿瘤直径的变化高度相关，这是由放射成像确定的，或者是新病变的发展。在一部分患者中，我们进一步发现EGFR突变可在进展性疾病（PD）发生前5个月在血浆中检测到，提示早期发现耐药性。结论使用血浆cfDNA进行基因组分析可能是监测临床反应和耐药性出现的有效方法。
Objectives Genomic profiling using plasma cell-free DNA (cfDNA) represents a non-invasive alternative to tumor re-biopsy, which is challenging in clinical practice. The feasibility of dynamically monitoring epidermal growth factor receptor (EGFR) mutation status using serial plasma samples from non-small cell lung cancer (NSCLC) patients treated by tyrosine kinase inhibitors (TKIs) and its application in tracking clinical response and detection of resistance were investigated. Patients and methods Forty-five NSCLC patients with EGFR mutation-positive pre-TKI plasma and at least two post-TKI plasma collections were recruited to this study. EGFR mutations including L858R, exon 19 deletion (19-del) and T790M were analyzed using droplet digital PCR (ddPCR) in longitudinally collected plasma samples. Results We observed a significant reduction in plasma EGFR mutation abundance during the first two-month of TKI treatment. Acquiring of secondary T790M gatekeeper mutation or completed “loss” of EGFR mutations represented two major categories of resistance profiles. Moreover, we demonstrated that levels of plasma EGFR mutations highly correlated with changes of tumor diameter as determined by radiographic imaging, or development of new lesions. In a subset of patients, we further showed that reappearance of EGFR mutations could be detected in plasma up to 5 months ahead of progressive disease (PD), suggesting an early detection of drug resistance. Conclusions Our findings suggest that genomic analysis using plasma cfDNA may offer an effective approach to monitor clinical response and emergence of resistance.
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影响因子：
158.5
作者：
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通讯作者：
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Sequist LV