Circulating endothelial cells, circulating tumour cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel.

PURPOSE: We investigated whether serum markers of angiogenesis endothelin-1 (ET-1) and tissue factor (TF), and/or markers of vascular damage such as circulating endothelial cells (CECs), or their relative changes during treatment, were prognostic for overall survival (OS) in castration resistant prostate cancer (CRPC) patients. Additionally, we combined these markers with circulating tumour cells (CTCs) to construct a predictive nomogram for treatment outcome. PATIENTS AND METHODS: One hundred and sixty two CRPC patients treated with a docetaxel containing regimen had blood drawn before and at 2-5 weeks and 6-8 weeks after treatment start. Prospectively determined CTC and CEC levels, and retrospectively measured serum concentrations of ET-1 (pg/mL) and TF (pg/mL) were evaluated to determine their prognostic value for OS. RESULTS: Baseline CEC, TF and ET-1 were not prognostic for OS. A > or = 3.8-fold increase in CEC 2-5 weeks after treatment initiation was associated with decreased OS (median 10.9 versus 16.8 months; P=0.015), as was any decrease in TF levels compared to baseline levels (median 11.9 versus 21.5 months; P=0.0005). As previously published, baseline and CTC counts > or = 5 at 2-5 weeks were also predictive of decreased OS. Combining CTC with changes in TF and CEC 2-5 weeks after treatment initiation yielded four groups differing in OS (median OS 24.2 versus 16.0 versus 11.4 versus 6.1 months; P<0.0001). CONCLUSION: CEC, CTC and TF levels alone and combined can predict early on OS in CRPC patients treated with docetaxel-based therapy. A prospective study to confirm the use of these markers for patient management is needed.

Circulating tumor cells and bone metastases as detected by FDG-PET/CT in patients with metastatic breast cancer.

BACKGROUND: We evaluated the relationship between the detection and prognostic significance of circulating tumor cells (CTCs) and sites of metastases detected by 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: From May 2004 to January 2008, 195 patients with relapsed/progressive MBC underwent whole-body FDG-PET/CT and provided blood samples for assessment of CTC count. RESULTS: Higher CTC numbers were detected in patients with bone metastases relative to those with no bone lesions (mean 65.7 versus 3.3, P = 0.0122) and in patients with multiple bone metastases relative to those with one or two bone lesions (mean 77.7 versus 2.6, P < 0.001). CTCs predicted overall survival (OS) in 108 patients with multiple sites of metastases including bone (P = 0.0008) but not in 58 without bone metastases (P = 0.4111) and in 29 with bone involvement only (P = 0.3552). All 15 patients but one with human epidermal growth factor receptor 2 (HER-2) positive tumors who were treated with trastuzumab-based regimens had <5 CTCs at progression. In multivariate analysis, CTCs, but not bone metastases, remained a significant predictor of OS. CONCLUSION: Presence of extensive bone metastases as detected by FDG-PET/CT is associated with increased CTC numbers in MBC.

Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer.

BACKGROUND: We demonstrated that circulating tumor cell (CTC) number at baseline and follow-up is an independent prognostic factor in metastatic colorectal cancer (mCRC). This analysis was undertaken to explore whether patient and treatment characteristics impact the prognostic value of CTCs. PATIENTS AND METHODS: CTCs were enumerated with immunomagnetic separation from the blood of 430 patients with mCRC at baseline and on therapy. Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of > or = 3 or <3 CTCs/7.5 ml, respectively. Subgroups were analyzed by line of treatment, liver involvement, receipt of oxaliplatin, irinotecan, or bevacizumab, age, and Eastern Cooperative Oncology Group performance status (ECOG PS). RESULTS: Seventy-one percent of deaths have occurred. Median follow-up for living patients is 25.8 months. For all patients, progression-free survival (PFS) and overall survival (OS) for unfavorable compared with favorable baseline CTCs is shorter (4.4 versus 7.8 m, P = 0.004 for PFS; 9.4 versus 20.6 m, P < 0.0001 for OS). In all patient subgroups, unfavorable baseline CTC was associated with inferior OS (P < 0.001). In patients receiving first- or second-line therapy (P = 0.003), irinotecan (P = 0.0001), having liver involvement (P = 0.002), >/=65 years (P = 0.0007), and ECOG PS of zero (P = 0.04), unfavorable baseline CTC was associated with inferior PFS. CONCLUSION: Baseline CTC count is an important prognostic factor within specific subgroups defined by treatment or patient characteristics.

Monitoring expression of HER-2 on circulating epithelial cells in patients with advanced breast cancer.

Nineteen breast cancer patients with measurable metastatic disease who were starting an initial or new line of therapy were evaluated for circulating epithelial cells (CECs) a minimum of 4 times over the course of treatment. In 7 of the 10 CEC+ patients, HER-2 expression was detected on the CECs. CECs expressing HER-2 varied among patients and in serial samples from the same patient including a shift from HER-2- to HER-2+ CECs. These results demonstrate that it is possible to quantify receptors essential for rationally designed therapy using CECs and that reliance on the immunophenotype of the primary tumor can be misleading.