Rui Wan1, Zhijie Wang2, J Jack Lee3, Shuhang Wang1, Qingqing Li4, Fuchou Tang4, Jin Wang5, Yu Sun6, Hua Bai2, Di Wang7, Jun Zhao1, Jianchun Duan2, Minglei Zhuo1, Tongtong An1, Meina Wu1, Zhaoli Chen8, Zhenlin Yang8, Jie Wang9. 1. Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China. 2. Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. 3. Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas. 4. Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, People's Republic of China. 5. Department of Respiratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. 6. Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China. 7. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, People's Republic of China. 8. Department of Thoracic Oncology Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. 9. Department of Thoracic Medical Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China; Department of Medical Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: wangjie_cc@yahoo.com.
Abstract
INTRODUCTION: This study aimed to address the underlying reasons for and clinical significance of the discordant EGFR mutation (EGFRm) status between tumor tissue (TT) and circulating tumor DNA (ctDNA). METHODS: Three groups of EGFR tyrosine kinase inhibitor (EGFR TKI)-treated patients whose EGFRm status was determined by the amplification refractory mutation system (ARMS) were included (group A, TT-positive/ctDNA-positive EGFRm status; group B, TT-negative/ctDNA-positive EGFRm status; and group C, TT-positive/ctDNA-negative EGFRm status). Patients with discordant EGFRm status were reevaluated by droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing. Meanwhile, surgical tumor specimens were microdissected for EGFRm detection by ddPCR. RESULTS: Of the 2463 patients with matched TT and ctDNA specimens, 1017 patients carried EGFRm in TT and/or ctDNA by the ARMS. Of these 1017 patients, 472 received EGFR TKIs, including 264, 28, and 180 in groups A, B, and C, respectively. The median progression-free survivals of those receiving EGFR TKIs across the three groups were similar (p = 0.062). Through ddPCR and next-generation sequencing of biopsy specimens (n = 22) and microdissected surgical specimens (n = 5), 27 patients in group B were identified as harboring EGFRm. After reevaluation by ddPCR, 64 patients in group C tested positive for EGFRm in their ctDNA. ctDNA as a screen for EGFRm then tissues as supplement (ctDNA→TT pattern) had similar detection efficiency and saved about 30% of TT compared with TT for initial EGFRm detection followed by ctDNA (TT→ctDNA pattern). CONCLUSIONS: Intratumor heterogeneity and the relatively low sensitivity of the ARMS contributed to discordant EGFRm status between TT specimens and ctDNA. The ctDNA→TT pattern might be a rational clinical procedure for EGFRm determination.
INTRODUCTION: This study aimed to address the underlying reasons for and clinical significance of the discordant EGFR mutation (EGFRm) status between tumor tissue (TT) and circulating tumor DNA (ctDNA). METHODS: Three groups of EGFR tyrosine kinase inhibitor (EGFR TKI)-treated patients whose EGFRm status was determined by the amplification refractory mutation system (ARMS) were included (group A, TT-positive/ctDNA-positive EGFRm status; group B, TT-negative/ctDNA-positive EGFRm status; and group C, TT-positive/ctDNA-negative EGFRm status). Patients with discordant EGFRm status were reevaluated by droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing. Meanwhile, surgical tumor specimens were microdissected for EGFRm detection by ddPCR. RESULTS: Of the 2463 patients with matched TT and ctDNA specimens, 1017 patients carried EGFRm in TT and/or ctDNA by the ARMS. Of these 1017 patients, 472 received EGFR TKIs, including 264, 28, and 180 in groups A, B, and C, respectively. The median progression-free survivals of those receiving EGFR TKIs across the three groups were similar (p = 0.062). Through ddPCR and next-generation sequencing of biopsy specimens (n = 22) and microdissected surgical specimens (n = 5), 27 patients in group B were identified as harboring EGFRm. After reevaluation by ddPCR, 64 patients in group C tested positive for EGFRm in their ctDNA. ctDNA as a screen for EGFRm then tissues as supplement (ctDNA→TT pattern) had similar detection efficiency and saved about 30% of TT compared with TT for initial EGFRm detection followed by ctDNA (TT→ctDNA pattern). CONCLUSIONS: Intratumor heterogeneity and the relatively low sensitivity of the ARMS contributed to discordant EGFRm status between TT specimens and ctDNA. The ctDNA→TT pattern might be a rational clinical procedure for EGFRm determination.
Authors: Joanna Przybyl; Jacob J Chabon; Lien Spans; Kristen N Ganjoo; Sujay Vennam; Aaron M Newman; Erna Forgó; Sushama Varma; Shirley Zhu; Maria Debiec-Rychter; Ash A Alizadeh; Maximilian Diehn; Matt van de Rijn Journal: Clin Cancer Res Date: 2018-02-20 Impact factor: 12.531
Authors: V F Bonazzi; L G Aoude; S Brosda; J M Lonie; K Patel; J J Bradford; L T Koufariotis; S Wood; B Mark Smithers; N Waddell; A P Barbour Journal: ESMO Open Date: 2022-03-23
Authors: T Stockley; C A Souza; P K Cheema; B Melosky; S Kamel-Reid; M S Tsao; A Spatz; A Karsan Journal: Curr Oncol Date: 2018-04-30 Impact factor: 3.677
Authors: Hanyan Xu; Adam Abdul Hakeem Baidoo; Shanshan Su; Junru Ye; Chengshui Chen; Yupeng Xie; Luca Bertolaccini; Mahmoud Ismail; Biagio Ricciuti; Calvin Sze Hang Ng; Raja M Flores; Yuping Li Journal: Transl Lung Cancer Res Date: 2019-04
Authors: Silvia Mola; Giulia Pinton; Marco Erreni; Marco Corazzari; Marco De Andrea; Ambra A Grolla; Veronica Martini; Laura Moro; Chiara Porta Journal: Int J Mol Sci Date: 2021-04-22 Impact factor: 5.923