Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions
Large scale, prospective screening of EGFR mutations in the blood of advanced NSCLC patients to guide treatment decisions
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DOI：
10.1093/annonc/mdx288
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发表时间：
2017-09-01
影响因子：
50.5
通讯作者：
Molina-Vila, M. A.
中科院分区：
文献类型：
--
作者：
Mayo-de-las-Casas, C.;Jordana-Ariza, N.;Molina-Vila, M. A.
背景资料：在相当大比例的晚期非小细胞肺癌（NSCLC）患者中，肿瘤组织不可用或不足以进行遗传分析。我们前瞻性地分析了从血液中纯化的循环游离DNA（cfDNA）是否可以用作这种情况下选择表皮生长因子受体酪氨酸激酶抑制剂治疗患者的替代物患者和方法：在119家医院收集了1138例晚期NSCLC患者的血液样本（n = 1033）或进展为EGFR-TKI（n = 105），无活检或肿瘤组织不足。将血清和血浆送往中心实验室，纯化cfDNA，并使用实时PCR测定法分析和定量EGFR突变。从一个子集的患者（n = 18）的反应数据进行了回顾性collected.Results：1033 NSCLC患者在介绍，1026是可评估的，男性和以前或目前的吸烟者的患病率。在113名患者（11%）的cfDNA中发现了致敏突变;大多数为女性，从不吸烟，外显子19缺失。31例患者仅在血浆中呈阳性，11例仅在血清中呈阳性，血浆和外显子19缺失的病例中突变负荷较高。超过50%的样本
Background: In a significant percentage of advanced non-small-cell lung cancer (NSCLC) patients, tumor tissue is unavailable or insufficient for genetic analyses. We prospectively analyzed if circulating-free DNA (cfDNA) purified from blood can be used as a surrogate in this setting to select patients for treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).Patients and methods: Blood samples were collected in 119 hospitals from 1138 advanced NSCLC patients at presentation (n = 1033) or at progression to EGFR-TKIs (n = 105) with no biopsy or insufficient tumor tissue. Serum and plasma were sent to a central laboratory, cfDNA purified and EGFR mutations analyzed and quantified using a real-time PCR assay. Response data from a subset of patients (n = 18) were retrospectively collected.Results: Of 1033 NSCLC patients at presentation, 1026 were assessable; with a prevalence of males and former or current smokers. Sensitizing mutations were found in the cfDNA of 113 patients (11%); with a majority of females, never smokers and exon 19 deletions. Thirty-one patients were positive only in plasma and 11 in serum alone and mutation load was higher in plasma and in cases with exon 19 deletions. More than 50% of samples had