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Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma(Open Access)

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收录情况： ◇ SCIE

作者：
Tao Jiang[1] * ; Liyan Jiang[2] * ; Xiaorong Dong[3] * ; Kangsheng Gu[4] * ; Yueyin Pan[5] ; Qin Shi[6] ; Guojun Zhang[7] ; Huijuan[1] ; Wang[8] ; Xiaochun Zhang[9] ; Nong Yang[10] ; Yuping Li[11] ; Jianping Xiong[12] ; Tienan Yi[13] ; Min Peng[14] ; Yong Song[15] ; Yun Fan[16] ; Jiuwei Cui[17] ; Gongyan Chen[18] ; Wei Tan[19] ; Aimin Zang[20] ; Qisen Guo[21] ; Guangqiang Zhao[22] ; Ziping[1] ; Wang[23] ; Jianxing He[24] ; Wenxiu Yao[25] ; Xiaohong Wu[26] ; Kai Chen[27] ; Xiaohua Hu[28] ; Chunhong Hu[29] ; Lu Yue[30] ; Da[1] ; Jiang[31] ; Guangfa Wang[32] ; Junfeng Liu[33] ; Guohua Yu[34] ; Junling Li[35] ; Henghui Zhang[36] ; Lihong Wu[36] ; Lu Fang[36] ; Dandan Liang[36] ; Yi Zhao[36] ; Weihong Zhao[37] ; Wenmin Xie[37] ; Shengxiang Ren[1,*1] ; Caicun Zhou[1,*1] ;
机构： [1]Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China. [2]Department of Respiration, Shanghai Chest Hospital, Shanghai, China. [3]Cancer Center, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. [4]Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China. [5]Department of Chemotherapy, Anhui Provincial Hospital, Hefei, Anhui, China. [6]Department of Oncology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, Fujian, China. [7]Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. [8]Department of Respiration, Henan Cancer Hospital, Zhengzhou, Henan, China. [9]Medical Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. [10]Department of Medical Oncology, Hunan Cancer Hospital, Changsha, China. [11]Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China. [12]Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. [13]Department of Oncology, Xiang Yang Central Hospital, Xiangyang, Hubei, China. [14]Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. [15]Department of Respiration, General Hospital of Eastern Theater Command of Chinese People's Liberation Army, Nanjing, Jiangsu, China. [16]Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. [17]Cancer Center, The First Bethune Hospital of Jilin University, Changchun, Jilin, China. [18]Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China. [19]Department of Respiratory Medicine, Weifang People's Hospital, Weifang, Shandong, China. [20]Medical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei, China. [21]Department of Internal Medicine, Shandong Cancer Hospital & Institute, Jinan, Shandong, China. [22]Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China. [23]Medical Oncology, Beijing Cancer Hospital, Beijing, China. [24]Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. [25]Department of Chemotherapy, Sichuan Cancer Hospital & Institute, Chengdu, Sichuan, China. [26]Department of Oncology, The Fourth People's Hospital of Wuxi, Wuxi, Jiangsu, China. [27]Medical Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. [28]Department of Medical Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. [29]Department of Oncology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. [30]Department of Oncology, Qingdao Municipal Hospital, Qingdao, Shandong, China. [31]Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. [32]Department of Respiration, Peking University First Hospital, Beijing, China. [33]Department of Thoracic Surgery, 4th Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. [34]Department of Oncology, Weifang People's Hospital, Weifang, Shandong, China. [35]Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China. [36]Beijing Genecast Biotechnology Co., Beijing, China. [37]Nanjing Luye Pharmaceutical Co. Ltd, Nanjing, Jiangsu, China.
出处：
DOI： 10.7150/thno.51243
ISSN：

关键词： Cell-free DNA Chemotherapy Machine learning Non-small-cell lung cancer

摘要：
Rationale: Platinum-based chemotherapy is one of treatment mainstay for patients with advanced lung squamous cell carcinoma (LUSC) but it is still a “one-size fits all” approach. Here, we aimed to investigate the predictive and monitoring role of circulating cell-free DNA (cfDNA) profiling for the outcome of first-line chemotherapy in patients with advanced LUSC. Methods: Peripheral blood samples of 155 patients from a phase IV trial and 42 cases from an external real-world cohort were prospectively collected. We generated a copy number variations-based classifier via machine learning algorithm to integrate molecular profiling of cfDNA, named RESPONSE SCORE (RS) to predict the treatment outcome. To monitor the treatment efficacy, cfDNA samples collected at different time points were subjected to an ultra-deep sequencing platform. Results: The results showed that patients with high RS showed substantially higher objective response rate than those with low RS in training set (P < 0.001), validation set (P < 0.001) and real-world cohort (P = 0.019). Furthermore, a significant difference was observed in both progression-free survival (training set, P < 0.001; validation set: P < 0.001; real-world cohort: P = 0.019) and overall survival (training set, P < 0.001; validation set: P = 0.037) between high and low RS group. Notably, variant allele frequency (VAF) calculated from an ultra-deep sequencing platform significantly reduced in patients experienced a complete or partial response after 2 cycles of chemotherapy (P < 0.001), while it significantly increased in these of non-responder (P < 0.001). Moreover, VAF undetectable after 2 cycles of chemotherapy was correlated with markedly better objective response rate (P < 0.001) and progression-free survival (P < 0.001) than those with detectable VAF. Conclusions: These findings indicated that the RS, a circulating cfDNA sequencing–based stratification index, could help to guide first-line chemotherapy in advanced LUSC. The change of VAF is valuable to monitor the treatment response. © The author(s).

基金：
This study was sponsored by Nanjing Luye Pharmaceutical Co. Ltd, Nanjing, China, and supported in part by grants from the National Natural Science Foundation of China (No. 81772467, 81871865, 81874036 and 81972167). The Backbone Program of Shanghai Pulmonary Hospital (No. FKGG1802), “Shuguang Program” supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission (No. 16SG18), Shanghai Pujiang Talent Plan (No. 2019PJD048), Shanghai Key disciplines of Respiratory (No. 2017ZZ02012), and Shanghai Major Diseases Multidisciplinary Cooperation Diagnosis and Treatment Construction Project.
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 医学
小类 | 2 区 医学：研究与实验
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 医学：研究与实验
JCR分区：
出版当年[2020]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1 MEDICINE, RESEARCH & EXPERIMENTAL

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]Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
共同第一作者：
通讯作者：
通讯机构： [1]Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China. [*1]Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, No. 507, Zheng Min Road, Shanghai, 200433, P.R. China
推荐引用方式(GB/T 7714)：
Tao Jiang,Liyan Jiang,Xiaorong Dong,et al.Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma(Open Access)[J].THERANOSTICS.2021,11(1):257-267.doi:10.7150/thno.51243.
APA：
Tao Jiang,Liyan Jiang,Xiaorong Dong,Kangsheng Gu,Yueyin Pan...&Caicun Zhou.(2021).Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma(Open Access).THERANOSTICS,11,(1)
MLA：
Tao Jiang,et al."Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma(Open Access)".THERANOSTICS 11..1(2021):257-267

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