Early responses of EGFR circulating tumor DNA to EGFR tyrosine kinase inhibitors in lung cancer treatment.
Early responses of EGFR circulating tumor DNA to EGFR tyrosine kinase inhibitors in lung cancer treatment.
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DOI：
10.18632/oncotarget.12373
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发表时间：
2016-11-01
期刊：
影响因子：
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通讯作者：
Kato K
中科院分区：
文献类型：
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作者：
Imamura F;Uchida J;Kukita Y;Kumagai T;Nishino K;Inoue T;Kimura M;Kato K
早期评估治疗效果有助于癌症患者的管理。如果循环生物标志物对肿瘤具有高度特异性并对肿瘤体积变化迅速反应，则它们是理想的工具。循环肿瘤DNA（ctDNA）就是其中之一。我们进行了一项前瞻性研究，以测试EGFR ctDNA在EGFR-TKI效应早期评估中的效用。入组了21例未经EGFR-TKI治疗的EGFR突变型肺癌患者。具有激活突变的EGFR ctDNA的PM评分在EGFR-TKI应答中迅速降低。在治疗前PM评分阳性的14例患者中，在第2 - 4、8和15天分别观察到14.3%、42.9%和57.1%的主要EGFR ctDNA完全消失。EGFR ctDNA的这些缓解在用于评价缓解的指标中最为突出，并且与通过胸部X线评价的早期放射学缓解相关。扩增系列血浆样本中的EGFR ctDNA，并使用下一代测序仪对105个拷贝进行测序。血浆突变（PM）评分定义为105个EGFR无细胞DNA（cfDNA）中含有缺失/置换的读数数量。当ctDNA中的EGFR突变与癌组织中检测到的EGFR突变相同时，将ctDNA定义为主要EGFR ctDNA。结果表明ctDNA作为高度特异性的生物标志物用于预测对治疗的早期反应的有用性，并且它可以应用于各种类型的癌症。
Early evaluation of the effect of treatment is helpful in the management of cancer patients. Circulating biomarkers are an ideal tool for this if they are highly specific to tumors and respond rapidly to tumor volume changes. Circulating tumor DNA (ctDNA) is one such candidate. We conducted a prospective study to test the utility of EGFR ctDNA in early evaluation of EGFR-TKI effects. Twenty-one patients with EGFR-mutant lung cancer who were naïve to EGFR-TKI were enrolled. PM scores of EGFR ctDNA with activating mutations decreased rapidly in response to EGFR-TKI. Of the 14 patients with positive pretreatment PM scores, complete disappearance of major EGFR ctDNA was observed in 14.3%, 42.9%, and 57.1% on days 2 – 4, 8, and 15, respectively. These responses of EGFR ctDNA were most prominent among the measures used to evaluate responses, and correlated with early radiologic responses evaluated by chest X-rays. EGFR ctDNA in serial plasma samples was amplified and 105 copies were sequenced with a next-generation sequencer. Plasma mutation (PM) score was defined as the number of reads containing deletions/substitutions in 105 EGFR cell free DNA (cfDNA). When EGFR mutation in ctDNA was the same as that detected in cancer tissue, the ctDNA was defined as major EGFR ctDNA. The results indicate the usefulness of ctDNA as a highly specific biomarker for prediction of early response to treatment and that it can be applied to various types of cancer.