Statistical considerations for enumeration of circulating tumor cells

A.G.J. Tibbe, M.C. Miller, L.W.M.M. Terstappen

Research output: Contribution to journalArticleAcademicpeer-review

184 Citations (Scopus)

Abstract

Background:
Circulating tumor cells (CTCs) in patients with carcinomas are extremely rare. In metastatic breast cancer, the presence of ≥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 CellSearch™ 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. © 2007 International Society for Analytical Cytology.
Original languageEnglish
Pages (from-to)154-162
JournalCytometry. Part A
Volume71A
Issue number3
DOIs
Publication statusPublished - 2007
Externally publishedYes

Keywords

  • n/a OA procedure

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