title: Urinary circulating DNA detection for dynamic tracking of EGFR mutations for NSCLC patients treated with EGFR-TKIs.
abstract: OBJECTIVE
  Changes in EGFR profiles of non small cell lung cancer (NSCLC) patients correlates to clinical outcome. Extracting quality tumor tissue remains a challenge for molecular profiling. Our study aims to ascertain the clinical relevance of urinary cell free DNA as an alternative tumor material source.
  
  
  METHODS
  150 patients with activating EGFR mutation and received EGFR-TKIs were recruited to participate in the serial monitoring study. Matched primary tumor samples were taken together with blood and urine specimens before the initiation of TKIs. The EGFR mutation testing was performed and quantified using ddPCR. For serial time point measurements, urine and blood samples were extracted at 1-month intervals for duration of 9 months.
  
  
  RESULTS
  Urinary ctDNA yielded a close agreement of 88 % on EGFR mutation status when compared to primary tissue at baseline. Almost all samples detected via urine specimens were uncovered in plasma samples. Analysis of urinary cell free DNA at different time points showed a strong correlation to treatment efficacy. Interestingly, a secondary EGFR mutation T790M was detected for 53 % of the patients during monitoring. The results were corroborated with the plasma ctDNA analysis. The T790M+ group had a reduced median survival when compared to the wildtype group.
  
  
  CONCLUSIONS
  Urinary cell free DNA may be a potential alternative to conventional primary tissue based EGFR mutation testing. Our findings showed that the assay sensitivity was comparable to results from blood plasma. Urinary samples being noninvasive and readily available have clinical utility for monitoring of EGFR TKI treatment.
authors.affiliation: Department of Academic Affairs, Hubei University of Medicine, Shiyan, 442000, Hubei, China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Oncology, Xiangyang Central Hospital (The Affiliated Hospital of Hubei College of Arts and Science), Xiangyang, 441021, Hubei, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, Xiangyang Central Hospital (The Affiliated Hospital of Hubei College of Arts and Science), Xiangyang, 441021, Hubei, China.
authors.forename: L
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Oncology, Xiangyang Central Hospital (The Affiliated Hospital of Hubei College of Arts and Science), Xiangyang, 441021, Hubei, China. yyliuXYcentral@hotmail.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000652:urine; D014408:Biomarkers, Tumor / Q000652:urine*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000652:urine*; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000235:genetics / Q000652:urine*; D066246:ErbB Receptors / Q000235:genetics* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000652:urine; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cell free DNA; Drug resistance; EGFR mutations; Liquid biopsy; NSCLC; TKI treatment