10.10.10

Circulating tumor cells (CTCs) became an interesting subject to researchers because of their predictive and prognostic potential; for example the presence of CTCs in peripheral blood of metastatic breast cancer patients seems to be an independent predictor of progression-free survival (PFS) and overall survival (OS). Another attraction is the possibility to sample tumor cells for 'omics analyses repetitively in a less invasive way than repeat biopsies.

A group of UK researchers (see abstract 172PD) evaluated the use of CTC counts to further improve the utility of the Royal Marsden Hospital prognostic score which has been validated in prospective analyses for patient selection in phase I clinical trials. Prognostic value of relevant baseline patients characteristics, including those in the Royal Marsden Hospital phase I Prognostic Score (albumin, lactate dehydrogenase and number of sites of metastases) were analyzed. The addition of baseline CTC counts enhanced the performance of the prognostic score and classified patients eligible to participate in phase I clinical trials into 3 prognostic groups: (1) Good prognosis (score 0-1; median OS 63.7 weeks); (2) Intermediate prognosis (score 2-3; median OS 37.3 weeks) and (3) Poor prognosis (score 4; median OS 13.4 weeks).

To date, all methods used to isolate CTCs facilitate the identification of epithelial circulating tumour cells, thus excluding other cell types, for instance those expressing mesenchymal traits. According to recent findings, more invasive CTCs may lose their epithelial antigens by the epithelial to mesenchymal transition (EMT) process. The aim of the study performed by researchers (see abstract 170PD) from Italy was to analyze the presence of EMT and stemness markers in CTCs isolated from breast cancer patients. Among those patients analyzed, 66% were found positive for CTCs. In a limited number of patients the authors found CTCs expressing both EMT (vimentin, fibronectin) and stemness markers (ALDH1). These patients were characterized by unfavorable classical prognostic factors (stage IV disease, a Ki 67 score >15; G2-3 grading of disease).

The objective of another CTC study (see abstract 171PD) was to compare the prognostic significance of lymphopenia, CTC count and extensive bone metastases (>2 lesions) in patients with metastatic breast cancer. In 195 assessable patients, the median OS time was 17 months and baseline lymphopenia, CTC counts, and bone metastases were found to be significantly associated with OS. In multivariate analysis, lymphopenia, more than five CTCs and estrogen receptor status remained as the only predictive factors for OS.

Enumeration of CTCs (see abstract 173PD) as a prognostic factor for PFS and OS in advanced colorectal cancer has recently been reported by Tol et al (Ann Oncol 2009). To confirm these results an ancillary study, with patients involved in the Spanish TTD MACRO study, treated with XELOX chemotherapy plus bevacizumab will be reported here. Blood samples for CTCs were collected at baseline in 180 patients out of 480 randomized into the trial and a second sample after 3 cycles of XELOX + bevacizumab given as first-line therapy in 149 patients. The investigators found that enumeration of CTCs at baseline and after several cycles of chemotherapy is a prognostic and predictive factor for PFS and OS in patients with metastatic colorectal cancer.

CTCs seem to be promising but need further validation and should not be measured outside clinical trials.