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


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.
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.
Robert J
RJ
Lewandowski
Department of Radiology, Section of Interventional Radiology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Jessica M
JM
Andreoli
Department of Radiology, Section of Interventional Radiology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Ryan
R
Hickey
Department of Radiology, Section of Interventional Radiology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Joseph R
JR
Kallini
Department of Radiology, Section of Interventional Radiology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Ahmed
A
Gabr
Department of Surgery, Division of Transplant Surgery, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Talia
T
Baker
Department of Medicine, Division of Hematology/Oncology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Sheetal
S
Kircher
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.
Riad
R
Salem
Department of Medicine, Division of Hepatology, Northwestern University, 676 N. St. Clair St., Suite 800, Chicago, IL 60611.
Laura
L
Kulik
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D002641:Chicago; D015536:Down-Regulation; D004621:Embolization, Therapeutic / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D010865:Pilot Projects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D010982:Platelet-Derived Growth Factor; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; D009536:Niacinamide; D000077157:Sorafenib