Detection and enumeration of circulating tumor cells (CTC) in patients with metastatic cancer offers important prognostic information and may assist in patient management and therapy. CTC are cytokeratin-positive, CD45-negative nucleated >4 um diameter cells where identification with current methods relies on automated scanning for presumptive identification as hotspots followed by final identification by manual review of images of each hotspot randomly presented to the operator. Often hundreds to thousands of images are manually reviewed making the process time-consuming and laborious. As an alternative to random review of images of hotspots a concept for CTC rating of hotspots based on the scanning measurement to determine their likelihood of being CTC has been developed and in this study validated on clinical specimens.
29 blood samples from metastatic breast cancer patients (Erasmus Medical Ctr, Rotterdam, NL) were analyzed using the CytoTrack system. CTC were identified by random manual review of each hotspot. Subsequently, the CTC rating concept was applied and the number of CTC present among the CTC rated hotspots was determined.
29 blood samples had a total of 21129 hotspots ranging from 93 - 2246 per sample. 15 of 29 samples contained CTC ranging from 1 - 104 CTC per sample. Of the 15 CTC-positive samples, 100% had CTC among the CTC rated hotspots ranging from 50 - 100% of the total number of CTC. In summary, the negative predictive value of CTC rating is 100% whereas the presence of CTC correlates with 81% (50-100%) of the total number of CTC. In the present study CTC rating of hotspots could avoid imaging of a total of 14224 hotspots ranging from 43 - 2000 hotspots per sample.
The high negative predictive value using CTC rating of hotspots offers the potential for 67% (14224/21129) reduction in the number of images to be reviewed to determine the presence or absence of CTC. For samples with the presence of at least 1 CTC the remaining images may optionally be reviewed to detect all CTC in the sample.
Clinical trial identification
Legal entity responsible for the study
M.T. Nielsen, H. Stender, T. Glückstadt: Employed by CytoTrack. All other authors have declared no conflicts of interest.