Unbiased and automated identification of a circulating tumour cell definition that associates with overall survival

Circulating tumour cells (CTC) in patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. Classification of CTC however remains subjective, as they are morphologically heterogeneous. We acquired digital images, using the CellSearch™ system, from blood...

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Bibliographic Details
Published in:PloS one 2011-11, Vol.6 (11), p.e27419-e27419
Main Authors: Ligthart, Sjoerd T, Coumans, Frank A W, Attard, Gerhardt, Cassidy, Amy Mulick, de Bono, Johann S, Terstappen, Leon W M M
Format: Article
Language:English
Subjects:
Algorithms
Androgens
Antigens
Automation
Biology
Biophysics
Cancer metastasis
Cancer therapies
Carcinoma
Care and treatment
Case-Control Studies
Castration
Cell survival
Chemotherapy
Clinical trials
Cytotoxicity
Diagnosis, Computer-Assisted
Digital imaging
Health services
Humans
Image acquisition
Laboratories
Male
Medical prognosis
Medicine
Metastases
Metastasis
Neoplastic Cells, Circulating - classification
Neoplastic Cells, Circulating - pathology
Patient outcomes
Patients
Physics
Prostate
Prostate cancer
Prostatic Neoplasms - mortality
Prostatic Neoplasms - pathology
Studies
Survival
Survival Rate
Tumors
Working groups
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Summary:Circulating tumour cells (CTC) in patients with metastatic carcinomas are associated with poor survival and can be used to guide therapy. Classification of CTC however remains subjective, as they are morphologically heterogeneous. We acquired digital images, using the CellSearch™ system, from blood of 185 castration resistant prostate cancer (CRPC) patients and 68 healthy subjects to define CTC by computer algorithms. Patient survival data was used as the training parameter for the computer to define CTC. The computer-generated CTC definition was validated on a separate CRPC dataset comprising 100 patients. The optimal definition of the computer defined CTC (aCTC) was stricter as compared to the manual CellSearch CTC (mCTC) definition and as a consequence aCTC were less frequent. The computer-generated CTC definition resulted in hazard ratios (HRs) of 2.8 for baseline and 3.9 for follow-up samples, which is comparable to the mCTC definition (baseline HR 2.9, follow-up HR 4.5). Validation resulted in HRs at baseline/follow-up of 3.9/5.4 for computer and 4.8/5.8 for manual definitions. In conclusion, we have defined and validated CTC by clinical outcome using a perfectly reproducing automated algorithm.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0027419