Prognostic value of circulating VEGFR2+ bone marrow-derived progenitor cells in patients with advanced cancer

Abstract

We hypothesised that host-related markers, possibly reflecting tumour aggressiveness, such as circulating endothelial cells (CEC) and circulating VEGFR2+ bone marrow-derived (BMD) progenitor cells, could have prognostic value in patients with advanced cancer enrolled in early anticancer drug development trials.Baseline CECs (CD45–CD31+CD146+7AAD– cells) and circulating VEGFR2+-BMD progenitor cells (defined as CD45dimCD34+VEGFR2+7AAD– cells) were measured by flow-cytometry in 71 and 58 patients included in phase 1 trials testing novel anti-vascular or anti-angiogenic agents. Correlations between levels of CECs, circulating VEGFR2+-BMD progenitor cells, clinical and biological prognostic factors (i.e. the Royal Marsden Hospital (RMH) score), and overall survival (OS) were studied.The median value of CECs was 12 CEC/ml (range 0–154/ml). The median level of VEGFR2+-BMD progenitor cells was 1.3% (range 0–32.5%) of circulating BMD-CD34+ progenitors. While OS was not correlated with CEC levels, it was significantly worse in patients with high VEGFR2+-BMD progenitor levels (>1%) (median OS 9.0 versus 17.0months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2months). The prognostic value of VEGFR2+-BMD progenitor levels remained significant (hazard ratio (HR)=2.3, 95% confidence interval (CI), 1.1–4.6, p=0.02) after multivariate analysis. A composite VEGFR2+-BMD progenitor level/RHM score ⩾2 was significantly associated with an increased risk of death compared to scores of 0 or 1 (median OS 9.0 versus 18.4months, HR=2.6 (95%CI, 1.2–5.8, p=0.02)).High circulating VEGFR2+-BMD progenitor levels are associated with poor prognostics and when combined to classical clinical and biological parameters could provide a new tool for patient selection in early anticancer drug trials.