Jeng-Sen Tseng1, Tsung-Ying Yang, Chi-Ren Tsai, Kun-Chieh Chen, Kuo-Hsuan Hsu, Meen-Hsin Tsai, Sung-Liang Yu, Kang-Yi Su, Jeremy J W Chen, Gee-Chen Chang. 1. *Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, ROC; †Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; ‡Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; §Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; ‖Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan, ROC; ¶Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; #Institute of Statistical Science, Academia Sinica, Taipei, Taiwan, ROC; **Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; ††Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; ‡‡Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC; §§Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan, ROC; ‖‖Center of Genomic Medicine, National Taiwan University, Taipei, Taiwan, ROC; and ¶¶Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Abstract
BACKGROUND: Epidermal growth factor receptor (EGFR) mutation status in lung cancer can effectively predict EGFR-tyrosine kinase inhibitor (TKI) efficacy. We evaluated the role of dynamic plasma cell-free DNA EGFR mutation status in outcome prediction. METHODS: Advanced lung adenocarcinoma patients were enrolled and prospectively observed for outcomes of EGFR-TKI treatment. Peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method was developed to assess EGFR mutations in matched tumor and serial plasma cell-free DNA specimens. RESULTS: A total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R). Pretreatment plasma used for EGFR mutation testing showed a sensitivity of 59.7% and a specificity of 100%. Detection sensitivity was significantly higher in stage IV-M1b patients compared with stage IIIb and IV-M1a patients (78.0% versus 23.8%, p < 0.001). All patients who presented with EGFR-mutant tumors received first-line EGFR-TKI therapy. The objective response rate and disease control rate were 74.2% and 82.3%, respectively. Median progression-free survival and overall survival were 8.8 months (95% CI: 6.6-11.0) and 20.5 months (95% CI 15.1-26.0), respectively. Failure to clear plasma EGFR mutations after EGFR-TKI treatment was an independent predictor of lower disease control rate (odds ratio 5.26 [95% CI: 1.13-24.44]; p = 0.034), shorter progression-free survival (hazard ratio: 1.97 [95% CI: 1.33-2.91]; p = 0.001), and shorter overall survival (hazard ratio: 1.82 [95% CI: 1.04-3.18], p = 0.036). CONCLUSION: Changes in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor.
BACKGROUND:Epidermal growth factor receptor (EGFR) mutation status in lung cancer can effectively predict EGFR-tyrosine kinase inhibitor (TKI) efficacy. We evaluated the role of dynamic plasma cell-free DNA EGFR mutation status in outcome prediction. METHODS: Advanced lung adenocarcinomapatients were enrolled and prospectively observed for outcomes of EGFR-TKI treatment. Peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method was developed to assess EGFR mutations in matched tumor and serial plasma cell-free DNA specimens. RESULTS: A total of 72 patients were enrolled in this study, of which 62 patients (86.1%) had EGFR-mutant tumors (34 patients with exon 19 deletions, and 28 patients with L858R). Pretreatment plasma used for EGFR mutation testing showed a sensitivity of 59.7% and a specificity of 100%. Detection sensitivity was significantly higher in stage IV-M1b patients compared with stage IIIb and IV-M1apatients (78.0% versus 23.8%, p < 0.001). All patients who presented with EGFR-mutant tumors received first-line EGFR-TKI therapy. The objective response rate and disease control rate were 74.2% and 82.3%, respectively. Median progression-free survival and overall survival were 8.8 months (95% CI: 6.6-11.0) and 20.5 months (95% CI 15.1-26.0), respectively. Failure to clear plasma EGFR mutations after EGFR-TKI treatment was an independent predictor of lower disease control rate (odds ratio 5.26 [95% CI: 1.13-24.44]; p = 0.034), shorter progression-free survival (hazard ratio: 1.97 [95% CI: 1.33-2.91]; p = 0.001), and shorter overall survival (hazard ratio: 1.82 [95% CI: 1.04-3.18], p = 0.036). CONCLUSION: Changes in plasma EGFR mutation status can be successfully assessed using the peptide nucleic acid-zip nucleic acid polymerase chain reaction clamp method and can serve as an independent outcome predictor.
Authors: Lee S Schwartzberg; Hidehito Horinouchi; David Chan; Sara Chernilo; Michaela L Tsai; Dolores Isla; Carles Escriu; John P Bennett; Kim Clark-Langone; Christer Svedman; Pascale Tomasini Journal: NPJ Precis Oncol Date: 2020-06-24
Authors: E Alegre; J P Fusco; P Restituto; D Salas-Benito; M E Rodríguez-Ruiz; M P Andueza; M J Pajares; A Patiño-García; R Pio; M D Lozano; A Gúrpide; J M Lopez-Picazo; I Gil-Bazo; J L Perez-Gracia; A Gonzalez Journal: Tumour Biol Date: 2016-07-29
Authors: Chris Karlovich; Jonathan W Goldman; Jong-Mu Sun; Elaina Mann; Lecia V Sequist; Krzysztof Konopa; Wei Wen; Philipp Angenendt; Leora Horn; David Spigel; Jean-Charles Soria; Benjamin Solomon; D Ross Camidge; Shirish Gadgeel; Cloud Paweletz; Lin Wu; Sean Chien; Patrick O'Donnell; Shannon Matheny; Darrin Despain; Lindsey Rolfe; Mitch Raponi; Andrew R Allen; Keunchil Park; Heather Wakelee Journal: Clin Cancer Res Date: 2016-01-08 Impact factor: 12.531