title: The emergence of T790M mutation in EGFR-mutant lung adenocarcinoma patients having a history of acquired resistance to EGFR-TKI: focus on rebiopsy timing and long-term existence of T790M.
abstract: Different growth kinetics occurring between the sensitive and T790M-containing cells may result in the repopulation of tumor cells over time. Little information has yet been uncovered on whether rebiopsy timing influences the T790M detection rate. We enrolled a total of 98 epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma patients, who had a history of acquired resistance to EGFR-tyrosine kinase inhibitor (TKI) and available rebiopsy tumor specimens for reassessment of EGFR mutations. Rebiopsy was performed at the time of first EGFR-TKI progression in 54 patients (55.1%); for the other 44 patients (44.9%), rebiopsy was done with an interval from first EGFR-TKI progression (median 470.5 days, range 46-1742 days). Our results indicated that rebiopsy timing did not influence the detection rate of T790M and that the mutation could be identified in patients with a long EGFR-TKI-free interval. For patients without suitable lesions for rebiopsy at the time of EGFR-TKI progression, an attempt to rebiopsy should be considered during the subsequent treatment courses.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jeng-Sen
authors.initials: JS
authors.lastname: Tseng
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Kang-Yi
authors.initials: KY
authors.lastname: Su
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tsung-Ying
authors.initials: TY
authors.lastname: Yang
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Kun-Chieh
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.|Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Kuo-Hsuan
authors.initials: KH
authors.lastname: Hsu
authors.affiliation: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.|College of Medicine, National Taiwan University, Taipei, Taiwan.|College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsuan-Yu
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan.|Institute of Molecular Biology, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Chi-Ren
authors.initials: CR
authors.lastname: Tsai
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.|Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.|Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*
chemical_list: D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: T790M; acquired resistance; epidermal growth factor receptor (EGFR); lung adenocarcinoma; rebiopsy