title: Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer.
abstract: OBJECTIVE
  Lung cancer is the leading cause of cancer-related death worldwide. Non-small-cell lung cancer (NSCLC) lacks validated biomarkers to predict treatment response. This study investigated whether circulating tumor cells (CTCs) are detectable in patients with NSCLC and what their ability might be to provide prognostic information and/or early indication of patient response to conventional therapy.
  
  
  METHODS
  In this single-center prospective study, blood samples for CTC analysis were obtained from 101 patients with previously untreated, stage III or IV NSCLC both before and after administration of one cycle of standard chemotherapy. CTCs were measured using a semiautomated, epithelial cell adhesion molecule-based immunomagnetic technique.
  
  
  RESULTS
  The number of CTCs in 7.5 mL of blood was higher in patients with stage IV NSCLC (n = 60; range, 0 to 146) compared with patients with stage IIIB (n = 27; range, 0 to 3) or IIIA disease (n = 14; no CTCs detected). In univariate analysis, progression-free survival was 6.8 v 2.4 months with P < .001, and overall survival (OS) was 8.1 v 4.3 months with P < .001 for patients with fewer than five CTCs compared with five or more CTCs before chemotherapy, respectively. In multivariate analysis, CTC number was the strongest predictor of OS (hazard ratio [HR], 7.92; 95% CI, 2.85 to 22.01; P < .001), and the point estimate of the HR was increased with incorporation of a second CTC sample that was taken after one cycle of chemotherapy (HR, 15.65; 95% CI, 3.63 to 67.53; P < .001).
  
  
  CONCLUSIONS
  CTCs are detectable in patients with stage IV NSCLC and are a novel prognostic factor for this disease. Further validation is warranted before routine clinical application.
authors.affiliation: Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester, United Kingdom.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Krebs
authors.forename: Robert
authors.initials: R
authors.lastname: Sloane
authors.forename: Lynsey
authors.initials: L
authors.lastname: Priest
authors.forename: Lee
authors.initials: L
authors.lastname: Lancashire
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Hou
authors.forename: Alastair
authors.initials: A
authors.lastname: Greystoke
authors.forename: Tim H
authors.initials: TH
authors.lastname: Ward
authors.forename: Roberta
authors.initials: R
authors.lastname: Ferraldeschi
authors.forename: Andrew
authors.initials: A
authors.lastname: Hughes
authors.forename: Glen
authors.initials: G
authors.lastname: Clack
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ranson
authors.forename: Caroline
authors.initials: C
authors.lastname: Dive
authors.forename: Fiona H
authors.initials: FH
authors.lastname: Blackhall
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D018572:Disease-Free Survival; D004739:England; D005260:Female; D006801:Humans; D018189:Immunomagnetic Separation; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules