title: ERCC1 expression in circulating tumor cells (CTCs) using a novel detection platform correlates with progression-free survival (PFS) in patients with metastatic non-small-cell lung cancer (NSCLC) receiving platinum chemotherapy.
abstract: OBJECTIVE
  To utilize a novel circulating tumor cell (CTC) technology to quantify ERCC1 expression on CTCs and determine whether ERCC1 expression levels predict efficacy of platinum-based chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  ERCC1 expression was measured in 17 metastatic NSCLC patients who received platinum-based therapy and had ≥2 intact CTCs with acceptable ERCC1 expression assay results. ERCC1 levels were determined from average expression on individual CTCs in each sample. Progression-free survival (PFS) was calculated from the date of therapy initiation.
  
  
  RESULTS
  PFS decreased with increasing ERCC1 expression (p<0.04, F-test, linear regression). Lack of ERCC1 expression was associated with longer PFS (266 days versus 172 days, log-rank, p<0.02) in a Kaplan-Meier analysis using ERCC expression level of 1 as a cutoff (range 0-30). The difference in survival was statistically significant with a hazard ratio of 4.20 (95% CI 1.25-14.1, p<0.02, log-rank). PFS was also observed to decrease with increased cytokeratin (CK) expression (p<0.01 long-rank (Cox regression) and F-test (linear regression)). The hazard ratio is 4.38 (95% CI 1.76-10.9) for each log-change in CK value until progression was noted on imaging.
  
  
  CONCLUSIONS
  Low expression of ERCC1 on CTCs correlates with PFS in patients with metastatic NSCLC receiving platinum-based therapy.
authors.affiliation: Stanford University School of Medicine, Department of Medicine, Division of Oncology, Stanford, CA, USA.
authors.forename: Millie
authors.initials: M
authors.lastname: Das
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Riess
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.forename: Erich
authors.initials: E
authors.lastname: Schwartz
authors.forename: Robyn
authors.initials: R
authors.lastname: Bennis
authors.forename: H Ben
authors.initials: HB
authors.lastname: Hsieh
authors.forename: Xiaohe
authors.initials: X
authors.lastname: Liu
authors.forename: Janey C
authors.initials: JC
authors.lastname: Ly
authors.forename: Lisa
authors.initials: L
authors.lastname: Zhou
authors.forename: Jorge J
authors.initials: JJ
authors.lastname: Nieva
authors.forename: Heather A
authors.initials: HA
authors.lastname: Wakelee
authors.forename: Richard H
authors.initials: RH
authors.lastname: Bruce
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D010984:Platinum / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D010984:Platinum; C071447:ERCC1 protein, human; D004720:Endonucleases