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.

Yttrium-90 Radioembolization of Hepatocellular Carcinoma–Performance, Technical Advances, and Future Concepts

“…30,31 A recent investigation identified increases in several angiogenic cytokines after hepatic resin radioembolization. 32 In this small cohort, cytokine changes including a transient increase in VEGF were associated with a worse overall survival rate.…”

Yttrium-90 radioembolization for colorectal cancer liver metastases: a prospective cohort study on circulating angiogenic factors and treatment response

“…Recently, Carpizo et al [28] have conducted a pilot study on angiogenic factors and 90 Y-RE. They included 15 patients with CRCLM and 7 patients with HCC and measured several angiogenic factors, including non-classical factors such as interleukin-8, at baseline and during follow-up until 120 days after treatment.…”

Immunotherapy and the Interventional Oncologist: Challenges and Opportunities—A Society of Interventional Oncology White Paper

“…pathways (84)(85)(86)(87). Increased tumor expression of vascular endothelial growth factor (VEGF), VEGF receptor, hypoxiainducible factor 1-α (HIF-1-α), matrix metalloproteinases (known as MMPs), cluster of differentiation 147 (CD147), and mammalian target of rapamycin (known as mTOR), and genes for cellular proliferation, tissue remodeling, and inflammation have all been reported after TACE (86)(87)(88)(89).…”

“…Increased tumor expression of vascular endothelial growth factor (VEGF), VEGF receptor, hypoxiainducible factor 1-α (HIF-1-α), matrix metalloproteinases (known as MMPs), cluster of differentiation 147 (CD147), and mammalian target of rapamycin (known as mTOR), and genes for cellular proliferation, tissue remodeling, and inflammation have all been reported after TACE (86)(87)(88)(89). Similarly, increased growth factor expression (VEGF and platelet derived growth factor-BB) and increased markers of inflammation (including IL-6 and IL-8), oxidative stress, and endothelial damage have been observed after TARE (84,85). Finally, there are also a number of studies that demonstrate the potential tumorigenic effects of tumor ablation, including ablation-induced local and systemic inflammation (including cytokines such as IL-6 and heat shock proteins), and upregulation of pro-oncogenic growth factors (such as HIF-1-α, VEGF, hepatocyte growth factor, and hepatocyte growth factor receptor [c-Met]) (71,74,80,90).…”