Comprehensive Analysis of the Discordance of EGFR Mutation Status between Tumor Tissues and Matched Circulating Tumor DNA in Advanced Non–Small Cell Lung.

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Comprehensive Analysis of the Discordance of EGFR Mutation Status between Tumor Tissues and Matched Circulating Tumor DNA in Advanced Non–Small Cell Lung Cancer Rui Wan, MD, Zhijie Wang, MD, J. Jack Lee, PhD, Shuhang Wang, MD, Qingqing Li, PhD, Fuchou Tang, PhD, Jin Wang, MD, Yu Sun, MD, Hua Bai, MD, Di Wang, PhD, Jun Zhao, MD, Jianchun Duan, MD, Minglei Zhuo, MD, Tongtong An, MD, Meina Wu, MD, Zhaoli Chen, MD, Zhenlin Yang, MD, Jie Wang, MD, PhD Journal of Thoracic Oncology Volume 12, Issue 9, Pages 1376-1387 (September 2017) DOI: 10.1016/j.jtho.2017.05.011 Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 1 The schema for patient screening. EGFRm, EGFR mutation; ctDNA, circulating tumor DNA; TKI, tyrosine kinase inhibitor. Journal of Thoracic Oncology 2017 12, 1376-1387DOI: (10.1016/j.jtho.2017.05.011) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 2 The paradigm of comprehensive analysis in 28 patients with initial tumor tissue (TT)-negative/circulating tumor DNA (ctDNA)-positive EGFR mutation (EGFRm) status. ARMS, amplification refractory mutation system; ddPCR, digital droplet polymerase chain reaction; NGS, next-generation sequencing. Journal of Thoracic Oncology 2017 12, 1376-1387DOI: (10.1016/j.jtho.2017.05.011) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 3 Sensitivity of the next-generation sequencing assay for 19del mutation and the sequencing results of the three cases. (A) In a dilution of mutant to wild-type EGFR alleles up to 1:10,000, the mutant sequence could be detected by next-generation sequencing assay. (B) The fraction of the mutant sequence of the three cases (1, 8, and 25). (C) Sequencing results of cases 1, 8, and 25. EGFRm, EGFR mutant; UMI, unique molecular identifier; WT, wild-type allele; del, exon 19 deletion. Journal of Thoracic Oncology 2017 12, 1376-1387DOI: (10.1016/j.jtho.2017.05.011) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions

Figure 4 Survival curves. (A) Progression-free survival (PFS). (B) Overall survival of EGFR TKI therapy among patients in group A (tumor tissue [TT]-positive/circulating tumor DNA [ctDNA]-positive EGFR mutation [EGFRm] status), group B (TT-negative/ctDNA-positive EGFRm status), and group C (TT-positive/ctDNA-negative EGFRm status). Survival curves for PFS (C) and overall survival (D) of EGFR TKI therapy between patients with TT-positive and ctDNA-positive EGFRm status determined by the amplification refractory mutation system. Journal of Thoracic Oncology 2017 12, 1376-1387DOI: (10.1016/j.jtho.2017.05.011) Copyright © 2017 International Association for the Study of Lung Cancer Terms and Conditions