title: Statistical considerations for enumeration of circulating tumor cells.
abstract: BACKGROUND
  Circulating tumor cells (CTCs) in patients with carcinomas are extremely rare. In metastatic breast cancer, the presence of >or=5 CTCs in 7.5 ml of blood has been associated with short survival. As this threshold has clinical implications, it is important to recognize the limitations associated with the detection and enumeration of CTCs.
  
  
  METHODS
  Statistical analyses were performed on data generated from a multi-center clinical trial that utilized the CellSearchtrade mark System to isolate and enumerate CTCs in 7.5 ml blood samples. The statistical issues associated with each step of the process, from blood collection to final image analysis and CTC enumeration, were determined and implemented into a model.
  
  
  RESULTS
  A model describing the statistics of the different process steps that are needed for the isolation and detection of CTCs was developed. The model uses the Poisson distribution for blood collection and empirically determined distributions for the isolation and identification of CTCs. The variability between readers was identified as one of the main sources of errors responsible for the current threshold level of five CTCs.
  
  
  CONCLUSIONS
  Elimination of the errors made in the identification of tumor cells isolated from 7.5 ml of blood could potentially reduce the CTC threshold for the identification of patients with a poor prognosis from the current value of five CTCs to one CTC per 7.5 ml of blood.
authors.affiliation: Immunicon Corporation, Huntingdon Valley, Pennsylvania, USA.
authors.forename: Arjan G J
authors.initials: AG
authors.lastname: Tibbe
authors.forename: M Craig
authors.initials: MC
authors.lastname: Miller
authors.forename: Leon W M M
authors.initials: LW
authors.lastname: Terstappen
mesh_terms: D001943:Breast Neoplasms / Q000401:mortality; D005260:Female; D006801:Humans; D015233:Models, Statistical; D009360:Neoplastic Cells, Circulating