title: The content of mutant EGFR DNA correlates with response to EGFR-TKIs in lung adenocarcinoma patients with common EGFR mutations.
abstract: This study aimed to elucidate the association of the content of mutant epidermal growth factor receptor (EGFR) deoxyribonucleic acid (DNA) with the treatment response to EGFR-tyrosine kinase inhibitor (TKI) and survival in patients with lung cancer.This retrospective cohort study included 77 lung adenocarcinoma patients with common EGFR mutations from December 2012 to February 2015. The content of mutant EGFR DNA in lung cancer tissues was determined using an Amplification Refractory Mutation System. The association of the amount of mutant EGFR DNA with treatment response, the clinical variables, and the progression-free survival (PFS) after EGFR-TKI therapy were evaluated.Using the amount of mutant EGR DNA above 4.77% as the cut-off value, the sensitivity to predict EGFR-TKI responder is 82.0% and the specificity is 75.0% (area under the curve [AUC]: 0.734, P = 0.003). The high content of mutant EGFR DNA is an independent factor associated with the response to EGFR-TKIs (odds ratio: 13.07, 95% confidence interval [CI]: 3.23-52.11, P = 0.0003). A significantly longer PFS was observed in the group with the high content of mutant EGFR DNA (26.3 months, 95% CI: 12.2-26.3) compared with the low content of mutant EGFR DNA groups (12.3 months, 95% CI: 5.7-14.8, P = 0.0155). A better predictive value of the content of mutant EGFR DNA was noted in patients with exon 19 deletions (AUC: 0.892, P < 0.0001) than exon 21 L858R mutations (AUC: 0.675, P = 0.0856).Our results show that the content of mutant EGFR DNA is associated with the clinical response to EGFR-TKIs, especially in patients with exon 19 deletions mutation.
authors.affiliation: aDivision of Thoracic Oncology, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Puzi City bDepartment of Medicine, College of Medicine, Chang Gung University, Taoyuan cDepartment of Respiratory Care, Chang Gung University of Science and Technology, Chiayi Campus, Chiayi dDepartment of Medical Research, Chang Gung Memorial Hospital, Chiayi Branch, Puzi City eDivision of Pulmonary Infection and Critical Care, Department of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Puzi City fDepartment of Respiratory Care, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Ming-Szu
authors.initials: MS
authors.lastname: Hung
authors.forename: Jr-Hau
authors.initials: JH
authors.lastname: Lung
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lin
authors.forename: Yu-Hung
authors.initials: YH
authors.lastname: Fang
authors.forename: Meng-Jer
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Ying-Huang
authors.initials: YH
authors.lastname: Tsai
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004273:DNA, Neoplasm; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C512478:EGFR protein, human; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases