Pilot study of angiogenic response to yttrium-90 radioembolization with resin microspheres

Abstract

Purpose: To investigate the impact of radioembolization with yttrium-90 resin microspheres on the regulation of angiogenesis through observation of serial changes in a spectrum of angiogenic markers and other cytokines after therapy.

Materials and methods: This prospective pilot study enrolled 22 patients with liver-dominant disease deriving from biopsy-proven hepatocellular carcinoma (HCC) (n = 7) or metastatic colorectal carcinoma (mCRC) (n = 15). Circulating angiogenic markers were measured from serum samples drawn at baseline and at time points after therapy ranging from 6 hours to 120 days. Using multiplex enzyme-linked immunosorbent assay, several classic angiogenesis factors (vascular endothelial growth factor [VEGF], angiopoietin-2 [Ang-2], basic fibroblast growth factor [bFGF], platelet-derived growth factor subunit BB [PDGF-BB], thrombospondin-1 [Tsp-1]) and nonclassic factors (follistatin, leptin, interleukin [IL]-8) were evaluated.

Results: Increases in cytokine levels ≥ 50% over baseline were observed in more than half of all patients studied for many cytokines, including classic angiogenic factors such as VEGF, Ang-2, and Tsp-1 as well as nonclassic factors IL-8 and follistatin (range, 36%-82% for all cytokines). Baseline cytokine levels in patients with overall survival (OS) < 6 months differed significantly from patients with longer survival for Ang-2 (P = .033) and IL-8 (P = .041). Patients with OS ≤ 6 months exhibited transient increases in VEGF and PDGF-BB after therapy compared with patients with OS > 6 months.

Conclusions: Radioembolization is associated with early transient increases in many angiogenic cytokines. In this small sample size, some of these changes were associated with worse OS. This research has important implications for future studies of radioembolization with antiangiogenic therapy performed during and after the procedure.

Keywords: (90)Y; Ang-2; Conc; FGFR; G-CSF; GM-CSF; HCC; HGF; IFN; IL; IP; MCAF; MIP; OS; PDGF; PDGF-BB; PDGFR; PECAM-1; RANTES; TNF; Tsp-1; Tx; VEGF; VEGFR; aFGF; acidic fibroblast growth factor; angiopoietin-2; bFGF; basic fibroblast growth factor; concentration; fibroblast growth factor receptor; granulocyte colony-stimulating factor; granulocyte-macrophage colony-stimulating factor; hepatocellular carcinoma; hepatocyte growth factor; interferon; interferon-inducible protein; interleukin; mCRC; macrophage chemotactic and activating factor; macrophage inflammatory protein; metastatic colorectal carcinoma; overall survival; platelet endothelial cell adhesion molecule; platelet-derived growth factor; platelet-derived growth factor receptor; platelet-derived growth factor subunit BB; regulated on activation, normal T-cell expressed and secreted; thrombospondin 1; treatment; tumor necrosis factor; vascular endothelial growth factor; vascular endothelial growth factor receptor; yttrium-90.