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

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• 作者：Robert J. Lewandowski ; MD^a ; ^b ; ^{r-lewandowski@northwestern.edu" class="auth_mail" title="E-mail the corresponding author} ; Jessica M. Andreoli ; MD^a ; Ryan Hickey ; MD^a ; Joseph R. Kallini ; MD^a ; Ahmed Gabr ; MD^a ; Talia Baker ; MD^d ; Sheetal Kircher ; MD^b ; Riad Salem ; MD ; MBA^a ; ^c ; ^d ; Laura Kulik ; MD^c
• 关键词：Ang-2 ; angiopoietin-2 ; HCC ; hepatocellular carcinoma ; IL ; interleukin ; OLT ; orthotopic liver transplantation ; PDGF ; platelet-derived growth factor ; VEGF ; vascular endothelial growth factor ; 90Y ; yttrium-90
• 刊名：Journal of Vascular and Interventional Radiology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：27
• 期：9
• 页码：1329-1336
• 全文大小：771 K

文摘

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.