Utilization of circulating cell-free DNA profiling to guide first-line chemotherapy in advanced lung squamous cell carcinoma.

Journal: Theranostics
PMID: 33391473

Abstract

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. 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. The results showed that patients with high RS showed substantially higher objective response rate than those with low RS in training set ( < 0.001), validation set ( < 0.001) and real-world cohort ( = 0.019). Furthermore, a significant difference was observed in both progression-free survival (training set, < 0.001; validation set: < 0.001; real-world cohort: = 0.019) and overall survival (training set, < 0.001; validation set: = 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 ( < 0.001), while it significantly increased in these of non-responder ( < 0.001). Moreover, VAF undetectable after 2 cycles of chemotherapy was correlated with markedly better objective response rate ( < 0.001) and progression-free survival ( < 0.001) than those with detectable VAF. 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.

Authors

  • Tao Jiang
    Department of Respiratory and Critical Care Medicine, Center for Respiratory Medicine, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
  • Liyan Jiang
    Department of Respiration, Shanghai Chest Hospital, Shanghai, China.
  • Xiaorong Dong
    Cancer Center, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Kangsheng Gu
    Department of Medical Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
  • Yueyin Pan
    Department of Chemotherapy, Anhui Provincial Hospital, Hefei, Anhui, China.
  • Qin Shi
    Department of Oncology, Fuzhou Pulmonary Hospital of Fujian, Fuzhou, Fujian, China.
  • Guojun Zhang
    The department of Respiratory Medicine of The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: zlgj-001@126.com.
  • Huijuan Wang
    Faculty of Electrical Engineering, Mathematics, and Computer Science, Delft University of Technology, Delft, The Netherlands.
  • Xiaochun Zhang
    Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Fudan University, Shanghai, 200032, China.
  • Nong Yang
    Departement of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha 410013, China.
  • Yuping Li
    Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • Jianping Xiong
    Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • Tienan Yi
    Department of Oncology, Xiang Yang Central Hospital, Xiangyang, Hubei, China.
  • Min Peng
    Department of Dermatology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
  • Yong Song
    Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
  • Yun Fan
    Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
  • Jiuwei Cui
    Cancer Center, The First Bethune Hospital of Jilin University, Changchun, Jilin, China.
  • Gongyan Chen
    Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
  • Wei Tan
    Weifang People's Hospital, Guang Wen Road, Weifang 261000, China.
  • Aimin Zang
    Medical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei, China.
  • Qisen Guo
    Department of Internal Medicine, Shandong Cancer Hospital & Institute, Jinan, Shandong, China.
  • Guangqiang Zhao
    Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
  • Ziping Wang
    Medical Oncology, Beijing Cancer Hospital, Beijing, China.
  • Jianxing He
    Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou 510120, China.
  • Wenxiu Yao
    Department of Chemotherapy, Sichuan Cancer Hospital & Institute, Chengdu, Sichuan, China.
  • Xiaohong Wu
    Department of Oncology, The Fourth People's Hospital of Wuxi, Wuxi, Jiangsu, China.
  • Kai Chen
    Department of Critical Care Medicine, Fujian Provincial Key Laboratory of Critical Care Medicine, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian Provincial Center for Critical Care Medicine, Fuzhou, Fujian, China.
  • Xiaohua Hu
    Department of Information, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
  • Chunhong Hu
    Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • Lu Yue
    Department of oncology, Qingdao Municipal Hospital, Shandong, 266000, China.
  • Da Jiang
    Medical Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • Guangfa Wang
    Department of Respiratory and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China.
  • Junfeng Liu
    Indiana University-Purdue University, Indianapolis , 723 West Michigan St., SL 280, Indianapolis, Indiana 46202, United States.
  • Guohua Yu
    Department of Oncology, Weifang People's Hospital, Weifang, Shandong, China.
  • Junling Li
    Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China.
  • Henghui Zhang
    Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China shenlin@bjmu.edu.cn zhhbao@ccmu.edu.cn.
  • Lihong Wu
    Beijing Genecast Biotechnology Co., Beijing, China.
  • Lu Fang
  • Dandan Liang
    National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China.
  • Yi Zhao
    Department of Biostatistics and Health Data Science, Indiana University School of Medicine.
  • Weihong Zhao
    Division of Nephrology,Departmentof Geriatrics, The First Affiliated Hospital of Nanjing Medical University,300 Guangzhou Road, Nanjing, Jiangsu 210029, China.
  • Wenmin Xie
    Nanjing Luye Pharmaceutical Co. Ltd, Nanjing, Jiangsu, China.
  • Shengxiang Ren
    Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.
  • Caicun Zhou
    Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China.

Keywords

External Resources

Popular Topics
Recent Journals