Angiogenic Response following Radioembolization: Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib

Robert J Lewandowski*, Jessica M. Andreoli, Ryan M Hickey, Joseph R. Kallini, Ahmed Gabr, Talia Barzel Baker, Sheetal Mehta Kircher, Riad Salem, Laura M Kulik

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 (90Y) radioembolization alone vs with sorafenib. Materials and Methods In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c-reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization (90Y alone, n = 6; 90Y plus sorafenib, n = 7). Results In the 90Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36% vs baseline at 2 weeks and 22% at 4 weeks, and PDGF increased 24% at 2 weeks and 3% at 4 weeks. In the 90Y/sorafenib arm, Ang-2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49% at 2 weeks and 28% at 4 weeks, and PDGF decreased 31% at 2 weeks and 39% at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. Conclusions Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF.

Original languageEnglish (US)
Pages (from-to)1329-1336
Number of pages8
JournalJournal of Vascular and Interventional Radiology
Volume27
Issue number9
DOIs
StatePublished - Sep 1 2016

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Yttrium
Platelet-Derived Growth Factor
Vascular Endothelial Growth Factor A
Angiopoietin-2
Hepatocyte Growth Factor
Hepatocellular Carcinoma
Interleukin-6
sorafenib
Angiogenesis Inducing Agents
Interleukin-8
Liver Transplantation
Intercellular Signaling Peptides and Proteins
Down-Regulation
Biomarkers

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

@article{04934b29aa154a0eb93ee99775cbf36d,
title = "Angiogenic Response following Radioembolization: Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib",
abstract = "Purpose To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 (90Y) radioembolization alone vs with sorafenib. Materials and Methods In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c-reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization (90Y alone, n = 6; 90Y plus sorafenib, n = 7). Results In the 90Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36{\%} vs baseline at 2 weeks and 22{\%} at 4 weeks, and PDGF increased 24{\%} at 2 weeks and 3{\%} at 4 weeks. In the 90Y/sorafenib arm, Ang-2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49{\%} at 2 weeks and 28{\%} at 4 weeks, and PDGF decreased 31{\%} at 2 weeks and 39{\%} at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. Conclusions Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF.",
author = "Lewandowski, {Robert J} and Andreoli, {Jessica M.} and Hickey, {Ryan M} and Kallini, {Joseph R.} and Ahmed Gabr and Baker, {Talia Barzel} and Kircher, {Sheetal Mehta} and Riad Salem and Kulik, {Laura M}",
year = "2016",
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doi = "10.1016/j.jvir.2016.03.043",
language = "English (US)",
volume = "27",
pages = "1329--1336",
journal = "Journal of Vascular and Interventional Radiology",
issn = "1051-0443",
publisher = "Elsevier Inc.",
number = "9",

}

Angiogenic Response following Radioembolization : Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib. / Lewandowski, Robert J; Andreoli, Jessica M.; Hickey, Ryan M; Kallini, Joseph R.; Gabr, Ahmed; Baker, Talia Barzel; Kircher, Sheetal Mehta; Salem, Riad; Kulik, Laura M.

In: Journal of Vascular and Interventional Radiology, Vol. 27, No. 9, 01.09.2016, p. 1329-1336.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Angiogenic Response following Radioembolization

T2 - Results from a Randomized Pilot Study of Yttrium-90 with or without Sorafenib

AU - Lewandowski, Robert J

AU - Andreoli, Jessica M.

AU - Hickey, Ryan M

AU - Kallini, Joseph R.

AU - Gabr, Ahmed

AU - Baker, Talia Barzel

AU - Kircher, Sheetal Mehta

AU - Salem, Riad

AU - Kulik, Laura M

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Purpose To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 (90Y) radioembolization alone vs with sorafenib. Materials and Methods In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c-reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization (90Y alone, n = 6; 90Y plus sorafenib, n = 7). Results In the 90Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36% vs baseline at 2 weeks and 22% at 4 weeks, and PDGF increased 24% at 2 weeks and 3% at 4 weeks. In the 90Y/sorafenib arm, Ang-2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49% at 2 weeks and 28% at 4 weeks, and PDGF decreased 31% at 2 weeks and 39% at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. Conclusions Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF.

AB - Purpose To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 (90Y) radioembolization alone vs with sorafenib. Materials and Methods In a single-center pilot study, 23 patients with unresectable HCC awaiting orthotopic liver transplantation were prospectively randomized to receive radioembolization alone (n = 12) or radioembolization with sorafenib (n = 11). Serum angiogenic markers (angiopoietin-2 [Ang-2], hepatocyte growth factor, interleukin [IL]-6, IL-8, c-reactive protein, platelet-derived growth factor [PDGF], and vascular endothelial growth factor [VEGF]) were assayed at baseline and at 2 and 4 weeks after radioembolization (90Y alone, n = 6; 90Y plus sorafenib, n = 7). Results In the 90Y-alone group, all growth factors were elevated above baseline levels at 2 and 4 weeks: VEGF increased 36% vs baseline at 2 weeks and 22% at 4 weeks, and PDGF increased 24% at 2 weeks and 3% at 4 weeks. In the 90Y/sorafenib arm, Ang-2 and PDGF decreased at 2 weeks and the remainder increased. By 4 weeks, only PDGF remained below baseline levels. VEGF increased 49% at 2 weeks and 28% at 4 weeks, and PDGF decreased 31% at 2 weeks and 39% at 4 weeks. Differences were statistically significant for hepatocyte growth factor (P = .03) and PDGF (P = .02) at 2 weeks and for IL-6 (P = .05) at 4 weeks. Conclusions Radioembolization is associated with a mild increase in angiogenic markers. The addition of sorafenib blunts PDGF response; other factors such as VEGF remain unaffected. The predominant effect of sorafenib may be through downregulation of PDGF and not VEGF.

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