Qin Bao-Dong, Jiao Xiao-Dong, Yuan Ling-Yan, Liu Ke, Wang Zhan, Qin Wen-Xing, Zang Yuan-Sheng
Department of Medical Oncology, Changzheng Hospital, Naval Medical University, Shanghai 200072, China,
Onco Targets Ther. 2018 Aug 10;11:4739-4745. doi: 10.2147/OTT.S167346. eCollection 2018.
In patients without tissue availability at presentation, the analysis of cell-free DNA derived from liquid biopsy samples, in particular from plasma, represents an established alternative for providing epidermal growth factor receptor (EGFR) mutational testing for treatment decision-making. Compared with quantitative polymerase chain reaction and digital polymerase chain reaction-targeted methods, next-generation sequencing can provide more information about tumor molecular alterations, especially EGFR mutations. Here, we present a case of a patient with non-small cell lung cancer (NSCLC) harboring 3 uncommon mutations of EGFR-R670W in exon 17 and H833V, and H835L in exon 21, as shown by next-generation sequencing of plasma cell-free DNA. To the best of our knowledge, this is the first case report of a patient harboring the R670W mutation. The patient responded well to second-generation tyrosine kinase inhibitors (TKIs). T790M is an acquired resistant mutation in patients with R670W, H833V, and H835L. This is also the first case of a patient harboring the H833V/H835L/T790M triple mutation; the patient had a good response to the third-generation TKI osimertinib. In this work, we also performed a literature review on the clinical characteristics of NSCLC patients with the H833V/H835L double mutation, together with a descriptive analysis about their response to EGFR TKI monotherapy as a first-line treatment, according to data from previous case reports. The results showed that the cohort of NSCLC patients with H833V/H835L responded well to EGFR TKIs; thus, before treatment in clinical practice, screening for EGFR mutations should be conducted and EGFR TKIs should be preferred in NSCLC patients with H833V/H835L mutations.
对于就诊时无法获取组织样本的患者，分析源自液体活检样本（尤其是血浆）的游离DNA，是为治疗决策提供表皮生长因子受体（EGFR）突变检测的既定替代方法。与定量聚合酶链反应和数字聚合酶链反应靶向方法相比，下一代测序可以提供更多关于肿瘤分子改变的信息，尤其是EGFR突变。在此，我们报告一例非小细胞肺癌（NSCLC）患者，通过血浆游离DNA的下一代测序显示，其在第17外显子存在3种罕见的EGFR-R670W突变以及第21外显子的H833V和H835L突变。据我们所知，这是首例报告的携带R670W突变的患者。该患者对第二代酪氨酸激酶抑制剂（TKIs）反应良好。T790M是携带R670W、H833V和H835L的患者中的一种获得性耐药突变。这也是首例携带H833V/H835L/T790M三重突变的患者；该患者对第三代TKI奥希替尼反应良好。在这项工作中，我们还根据既往病例报告的数据，对携带H833V/H835L双突变的NSCLC患者的临床特征进行了文献综述，并对其作为一线治疗对EGFR TKI单药治疗的反应进行了描述性分析。结果显示，携带H833V/H835L的NSCLC患者队列对EGFR TKIs反应良好；因此，在临床实践中治疗前，应进行EGFR突变筛查，对于携带H833V/H835L突变的NSCLC患者应优先选择EGFR TKIs。
