title: 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 CD45(dim)CD34(+)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 17.0 months), and with a RMH prognostic score >0 (median OS 9.0 versus 24.2 months). 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 18.4 months, 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.
authors.affiliation: Department of Medicine, Institut de Cancérologie Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Borget
authors.forename: Marie Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.forename: Melissa
authors.initials: M
authors.lastname: Taylor
authors.forename: Carlos
authors.initials: C
authors.lastname: Gomez-Roca
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Françoise
authors.initials: F
authors.lastname: Farace
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology*; D017321:Clinical Trials, Phase I as Topic; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology*; D013534:Survival; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D040301:Vascular Endothelial Growth Factor Receptor-2