title: Pilot study of angiogenic response to yttrium-90 radioembolization with resin microspheres.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Biomedical and Health Sciences, New Brunswick, NJ 08903-0019.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Carpizo
authors.affiliation: Center for Biomedical Imaging & Informatics, Rutgers Cancer Institute of New Jersey, Rutgers Biomedical and Health Sciences, New Brunswick, NJ 08903-0019.
authors.forename: Rebekah H
authors.initials: RH
authors.lastname: Gensure
authors.affiliation: Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Biomedical and Health Sciences, New Brunswick, NJ 08903-0019.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Radiology, Rutgers Robert Wood Johnson Medical School, One Robert Wood Johnson Place MEB 404, PO Box 19, New Brunswick, NJ 08903-0019.
authors.forename: Vyacheslav M
authors.initials: VM
authors.lastname: Gendel
authors.affiliation: Department of Radiology, Rutgers Robert Wood Johnson Medical School, One Robert Wood Johnson Place MEB 404, PO Box 19, New Brunswick, NJ 08903-0019.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Greene
authors.affiliation: Department of Biostatistics, School of Public Health, Rutgers Biomedical and Health Sciences, New Brunswick, NJ 08903-0019.
authors.forename: Dirk F
authors.initials: DF
authors.lastname: Moore
authors.affiliation: Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Biomedical and Health Sciences, New Brunswick, NJ 08903-0019.
authors.forename: Salma K
authors.initials: SK
authors.lastname: Jabbour
authors.affiliation: Department of Radiology, Rutgers Robert Wood Johnson Medical School, One Robert Wood Johnson Place MEB 404, PO Box 19, New Brunswick, NJ 08903-0019. Electronic address: nosher@umdnj.edu.
authors.forename: John L
authors.initials: JL
authors.lastname: Nosher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042501:Angiogenic Proteins / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000098:blood supply / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000098:blood supply / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy*; D015179:Colorectal Neoplasms / Q000473:pathology*; D016207:Cytokines / Q000097:blood; D004621:Embolization, Therapeutic / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000098:blood supply / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary*; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010865:Pilot Projects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage*; D012117:Resins, Synthetic / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D042501:Angiogenic Proteins; D014408:Biomarkers, Tumor; D016207:Cytokines; D019275:Radiopharmaceuticals; D012117:Resins, Synthetic; D015021:Yttrium Radioisotopes
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