Background

To analyze the role of circulating tumor cells (CTCs) as a confirmatory personalized biomarker for monitoring disease progression, disease burden, and minimal residual disease in epithelial origin cancers.

Methods

In this retrospective study, 127 patients with colorectal, breast, and ovarian cancer at stage III and IV were analyzed. The patients were at various stages of intensive chemo and radiotherapy while the CTCs were isolated and enumerated from 1.5 ml of blood. The decision to continue chemotherapy or change to oral metronomic therapy was based on the presence of circulating tumor cells in Stage III. While in stage IV, serial measurement of CTCs guided therapy. CTCs were isolated using the OncoDiscover platform possessing EpCAM antibody-based immunomagnetic targeting of magnetic nanoparticles after RBC lysis. CTCs were imaged and identified as CK18+ and CD45- cells showing a well-defined nucleus using a motorized fluorescence microscope operational with a monochrome camera. CTCs were enumerated using automated image analysis software and counts were expressed as the number per 1.5 ml of blood.

Results

In this retrospective study, we analyzed blood samples from 127 patients with advanced-stage epithelial cancers (breast: 50%, ovarian: 27%, colorectal: 23%) for the presence of CTCs. Amongst those, 52% showed the presence of CTCs (breast: 52%, ovarian: 46%, colorectal: 58%). The CTC count ranged between 1-5 / 1.5 ml of blood with mean and median values of 2 and 1. Among the CTC positive population, the majority had a CTC count of 1 (44.4%), while more than 2 CTCs were observed in 11% of the population. CTC clusters were detected in 13% of the population, which predominantly were stage IV patients. 67% among the follow-up patients showed a decrease in CTC count from the baseline due to the prescribed treatment, while 22% of patients showed an increase in CTC count from the baseline. 11% of patients did not show a change in CTC count from the baseline.

When CTC count was investigated as an independent variable to monitor the therapeutic response, it correlated well with positive or negative outcomes. In a few representative cases, the reduction of CTC numbers from the basal value was indicative of effective treatment. Exceptionally, in a representative colorectal cancer case, a PET scan showed no primary as well as secondary tumor burden, but the presence of CTCs in blood led to further investigating an abdominal MRI that indicated multiple liver lesions suggesting micro-metastasis. Subsequent to SIRT treatment, the patient showed complete tumor regression and the absence of CTCs in peripheral blood.

Conclusions

Our data suggest that CTCs can serve as a dynamic intermittent biomarker for monitoring disease progression in advanced stages and assessing the therapeutic response, thus emphasizing the role of CTCs in personalized cancer management.