Robert J Lewandowski1, Jessica M Andreoli2, Ryan Hickey2, Joseph R Kallini2, Ahmed Gabr2, Talia Baker3, Sheetal Kircher4, Riad Salem5, Laura Kulik6. 1. Department of Radiology, Section of Interventional Radiology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611; Department of Medicine, Division of Hematology/Oncology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611. Electronic address: r-lewandowski@northwestern.edu. 2. Department of Radiology, Section of Interventional Radiology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611. 3. Department of Surgery, Division of Transplant Surgery, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611. 4. Department of Medicine, Division of Hematology/Oncology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611. 5. Department of Radiology, Section of Interventional Radiology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611; Department of Medicine, Division of Hepatology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611; Department of Surgery, Division of Transplant Surgery, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611. 6. Department of Medicine, Division of Hepatology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Abstract
PURPOSE: To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated withyttrium-90 ((90)Y) 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 ((90)Y alone, n = 6; (90)Y plus sorafenib, n = 7). RESULTS: In the (90)Y-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 (90)Y/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.
RCT Entities:
PURPOSE: To compare the regulation of serum angiogenic factors in patients with unresectable early hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) 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 ((90)Y alone, n = 6; (90)Y plus sorafenib, n = 7). RESULTS: In the (90)Y-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 (90)Y/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.
Authors: Joseph P Erinjeri; Gabriel C Fine; Gosse J Adema; Muneeb Ahmed; Julius Chapiro; Martijn den Brok; Rafael Duran; Stephen J Hunt; D Thor Johnson; Jens Ricke; Daniel Y Sze; Beau Bosko Toskich; Bradford J Wood; David Woodrum; S Nahum Goldberg Journal: Radiology Date: 2019-04-23 Impact factor: 11.105
Authors: Quirino Lai; Alessandro Vitale; Tommaso M Manzia; Francesco G Foschi; Giovanni B Levi Sandri; Martina Gambato; Fabio Melandro; Francesco P Russo; Luca Miele; Luca Viganò; Patrizia Burra; Edoardo G Giannini Journal: Cancers (Basel) Date: 2019-10-15 Impact factor: 6.639