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Refined Stratification Based on Baseline Concomitant Mutations and Longitudinal circulating tumor DNA Monitoring in Advanced EGFR-mutant Lung Adenocarcinoma under Gefitinib Treatment.

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收录情况： ◇ SCIE

作者：
Jianchun Duan[1] ; JiaChen Xu[1] ; Zhijie Wang[1] ; Hua Bai[1] ; Ying Cheng[2] ; Tongtong An[3] ; Hongjun Gao[4] ; Kai Wang[5] ; Qing Zhou[6] ; Yanping Hu[7] ; Yong Song[8] ; Cuimin Ding[9] ; Feng Peng[10] ; Li Liang[11] ; Yi Hu[12] ; Cheng Huang[13] ; Caicun Zhou[14] ; Yuankai Shi[1] ; Jiefei Han[1] ; Di Wang[1] ; Yanhua Tian[1] ; Zhenlin Yang[15] ; Li Zhang[16] ; Shaokun Chuai[17] ; Junyi Ye[17] ; Guanshan Zhu[18] ; Junhui Zhao[19] ; Yi-long Wu[6] ; Jie Wang[1,*1] ;
机构： [1]State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China. [2]Jilin Cancer Hospital, Division of Thoracic Oncology, Jilin Province Cancer Hospital, Changchun, China. [3]Department of Thoracic Medical Oncology, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China. [4]The 307th Hospital of Chinese People's Liberation Army, 1 Beijing, China. [5]Department of Respiratory Medicine, Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China. [6]Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China. [7]Department of Oncology, Hubei Cancer Hospital, Hubei, China. [8]Nanjing General Hospital of Nanjing Military Command and PLA Bayi Hospital, Nanjing, China. [9]Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University,Hebei, China. [10]Department of Thoracic Oncology, Cancer Center, West China Hospital, Medical School,Sichuan University, Chengdu, China. [11]Peking University Third Hospital, Beijing, China. [12]Chinese People's Liberation Army General Hospital, Beijing, China. [13]Department of Medical Oncology, Fujian Provincial Cancer Hospital, Teaching Hospital of Fujian Medical University, Teaching Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China. [14]Shanghai Pulmonary Hospital, Tongji University, Shanghai, China. [15]Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. [16]Sun Yat-sen University Cancer Center, Guangzhou, China. [17]Burning Rock Biotech, Guangdong, China. [18]Amoy Diagnostics, Xiamen, China. [19]Department of Medical Oncology, Affiliated Hospital of Qinghai University, Qinghai,China.
出处：
DOI： 10.1016/j.jtho.2020.08.020
ISSN：

关键词： Lung adenocarcinoma epidermal growth factor receptor co-mutations refined stratification ctDNA monitoring

摘要：
The optimal treatment for EGFR-mutant lung adenocarcinoma (LUAD) remains challenging due to intratumor heterogeneity. We aimed to explore a refined stratification mode based on the integrated analysis of ctDNA tracking. ctDNA was prospectively collected at baseline and every eight weeks in advanced treatment-naïve EGFR-mutant LUAD patients under gefitinib treatment enrolled in a phase II trial, and analyzed using next-generation sequencing of a 168-gene panel. Three subgroups categorized by baseline co-mutations: EGFR-sensitizing mutations (59, 32.8%), EGFR-sensitizing mutations with tumor suppressor mutations (97, 53.9%) and EGFR-sensitizing mutations with other driver mutations (24, 13.3%), exhibited distinct progression-free survival (PFS) and overall survival (OS) [PFS 13.2 (11.3-15.2) vs. 9.3 (7.6-10.5) vs. 4.0 (2.4-9.3) months; OS 32.0 (29.2-41.5) vs. 21.7 [(19.3-27.0) vs. 15.5 (10.5-33.7) months], providing evidence for initial stratification. 63.7% of the patients achieved week-8 ctDNA-clearance, with significant difference among three subgroups (74.5% vs. 64.0% vs. 29.4%, P=0.004, fisher's exact test). Patients without week-8 ctDNA-clearance had worse PFS [clearance vs. non-clearance 11.2 (9.9-13.2) vs. 7.4 (5.6-9.6) months, P=0.016, cox regression], especially in the second subgroup [5.8 (5.6-11.5) months], suggesting the necessity of adaptive stratification during treatment. During follow-up, 56.0% and 20.8% of the patients eventually harbored p.T790M and non-p.T790M mutations, with significant difference in non-p.T790M mutations among three subgroups (7.5% vs. 15.7% vs. 80.0%, P<0.001, fisher's exact test), giving clues to post-line treatment. The patients with baseline co-mutations and ctDNA non-clearance at first visit might require combined therapy due to limited survival benefit of EGFR-TKI monotherapy. We proposed a refined stratification mode for the whole-course management of EGFR-mutant LUAD. Copyright © 2020. Published by Elsevier Inc.

基金：
This work was supported by the National Natural Sciences Foundation Key Program [grant number 81630071]; CAMS Innovation Fund for Medical Sciences (CIFMS) [grant number 2016-I2M-3-008]; Aiyou Foundation [grant number KY201701], Ministry of Education Innovation Team development project [grant number IRT-17R10], CAMS Key lab of translational research on lung cancer [grant number 2018PT31035]; China National Natural Sciences Foundation [grant number 81871889]; Beijing Natural Science Foundation [grant number 7172045]; Beijing Novel Program Grants, cross-cooperation [grant number Z181100006218130]; CAMS Innovation Fund for Medical Sciences (CIFMS) [grant number 2017-I2M-1-005]; and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [grant number 2018RC320009].

基金编号： grant number KY201701 grant number 81871889 grant number 2018RC320009

语种：
外文
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中科院(CAS)分区：
出版当年[2020]版：
大类 | 1 区 医学
小类 | 1 区 肿瘤学 1 区 呼吸系统
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 肿瘤学 1 区 呼吸系统
JCR分区：
出版当年[2020]版：
Q1 RESPIRATORY SYSTEM Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY Q1 RESPIRATORY SYSTEM

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China.
共同第一作者：
通讯作者：
通讯机构： [1]State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P.R. China. [*1]State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College,NO. 17, Panjiayuannanli, Chaoyang District, Beijing 100021, P.R. China
推荐引用方式(GB/T 7714)：
Jianchun Duan,JiaChen Xu,Zhijie Wang,et al.Refined Stratification Based on Baseline Concomitant Mutations and Longitudinal circulating tumor DNA Monitoring in Advanced EGFR-mutant Lung Adenocarcinoma under Gefitinib Treatment.[J].JOURNAL OF THORACIC ONCOLOGY.2020,15(12):1857-1870.doi:10.1016/j.jtho.2020.08.020.
APA：
Jianchun Duan,JiaChen Xu,Zhijie Wang,Hua Bai,Ying Cheng...&Jie Wang.(2020).Refined Stratification Based on Baseline Concomitant Mutations and Longitudinal circulating tumor DNA Monitoring in Advanced EGFR-mutant Lung Adenocarcinoma under Gefitinib Treatment..JOURNAL OF THORACIC ONCOLOGY,15,(12)
MLA：
Jianchun Duan,et al."Refined Stratification Based on Baseline Concomitant Mutations and Longitudinal circulating tumor DNA Monitoring in Advanced EGFR-mutant Lung Adenocarcinoma under Gefitinib Treatment.".JOURNAL OF THORACIC ONCOLOGY 15..12(2020):1857-1870

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