Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study

doi:10.1007/s11523-019-00682-0

科研成果详情

题名	Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study
作者	Yang, Zhengquan1,2; Li, Jialu 1,2; Hu, Yujie 1,2; Chen, Meihua 1,2; Peng, Danli 1,2; Zong, Dan 1,2; Shang, Qingjuan 1,2; Tao, Lianqin 3; Zhao, Yanling1,2; Ni, Yiyun 1,2; Ye, Jinyan4; Xie, Yupeng4; Yang, Li4; Lin, Quan4; Cai, Chang4; Xu, Ning 5; Huang, Xiaoping 5; Dong, Xiaoting 6; Zhou, Zhonghui 7; Yu, Yali 7; Shangguan, Zongxiao8; Xu, Yangyang 9; Ying, Weiping 9; Weng, Meiling 10; Yuan, Zuguo 11; Dong, Zhijun 12; Li, Jifa 13; Zheng, Zhe 14; Pan, Jiongwei 15; Liu, Lu 16; Ye, Junhui 17; Zhang, Zhan18; Li, Wenfeng19; Zhu, Junfei 3; Jin, Shengnan1,2; Li, Yuping4; Ding, Chunming1,2
发表日期	2019-12
发表期刊	TARGETED ONCOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	CELL LUNG-CANCER ; DROPLET DIGITAL PCR ; LEADING TECHNOLOGIES ; LIQUID BIOPSIES ; FREE DNA ; RESISTANCE ; GEFITINIB ; CHEMOTHERAPY
摘要	BackgroundDroplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations.ObjectiveWe aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC).MethodsSpecificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples.ResultsWe set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency>0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression.ConclusionsWe developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC.Trial RegistrationClinical Trials.gov identifier: NCT02804100.
资助项目	Innovation Discipline of Zhejiang Province in Nucleic Acid Molecular Diagnostics [437201702G]; Key Discipline of Zhejiang Province in Medical Technology (First Class, Category A) [437601607]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LY18H200007]; Innovation Team in Zhejiang Province Universities
出版者	SPRINGER
出版地	DORDRECHT
ISSN	1776-2596
EISSN	1776-260X
卷号	14 期号:6 页码:719-728
DOI	10.1007/s11523-019-00682-0
页数	10
WOS类目	Oncology
WOS研究方向	Oncology
WOS记录号	WOS:000494787400001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	31691892
SCOPUSEID	2-s2.0-85074760784
通讯作者地址	[Jin, Shengnan]School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Oncology;Cancer Research;Pharmacology (medical)
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/20447
专题	检验医学院（生命科学学院、生物学实验教学中心）附属第一医院_放化疗科第一临床医学院（信息与工程学院）、附属第一医院_内科学_呼吸与危重症医学科其他_附属第三医院（瑞安市人民医院）其他_附属黄岩医院（台州市第一人民医院）
通讯作者	Jin, Shengnan
作者单位	1.School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Wenzhou,China; 2.Key Laboratory of Laboratory Medicine,Ministry of Education,Wenzhou Medical University,Wenzhou,China; 3.Department of Pulmonary Medicine,Taizhou Central Hospital,Taizhou,China; 4.Department of Pulmonary and Critical Care Medicine,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 5.Department of Respiratory Medicine,Ningbo First Hospital,Ningbo,China; 6.Wenzhou Hospital of Traditional Chinese Medicine,Wenzhou,China; 7.Ningbo Hospital of Traditional Chinese Medicine,Ningbo,China; 8.The Third Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 9.Zhejiang Jinhua Guangfu Hospital,Jinhua,China; 10.Department of Oncology,The People’s Hospital of Quzhou,Quzhou,China; 11.Department of Radiotherapy and Chemotherapy,Yinzhou Hospital Affiliated to Medical School of Ningbo University,Ningbo,China; 12.ChinacoHealthcare Corporation International Hospital,Ningbo,China; 13.Yue Qing General Hospital,Yue Qing,China; 14.The Ping Yang Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 15.Department of Respiratory and Critical Care Medicine,Lishui People’s Hospital,Lishui,China; 16.Department of Interventional Radiology,Zhejiang University Lishui Hospital,Lishui,China; 17.Department of Respiratory Medicine,Sanmen People’s Hospital of Zhejiang,Taizhou,China; 18.Huangyan Hospital of Wenzhou Medical University,Taizhou,China; 19.Department of Radiotherapy and Chemotherapy,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）; 温州医科大学
通讯作者单位	检验医学院（生命科学学院、生物学实验教学中心）
第一作者的第一单位	检验医学院（生命科学学院、生物学实验教学中心）
推荐引用方式 GB/T 7714	Yang, Zhengquan,Li, Jialu,Hu, Yujie,et al. Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study[J]. TARGETED ONCOLOGY,2019,14(6):719-728.
APA	Yang, Zhengquan., Li, Jialu., Hu, Yujie., Chen, Meihua., Peng, Danli., ... & Ding, Chunming. (2019). Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study. TARGETED ONCOLOGY, 14(6), 719-728.
MLA	Yang, Zhengquan,et al."Dynamics of Plasma EGFR T790M Mutation in Advanced NSCLC: A Multicenter Study".TARGETED ONCOLOGY 14.6(2019):719-728.