Hyunseon C. Kang MD, Presenter: Nothing to Disclose

Kay See Tan BA, Abstract Co-Author: Nothing to Disclose

Daniel F. Heitjan PhD, Abstract Co-Author: Nothing to Disclose

Keith Flaherty MD, Abstract Co-Author: Nothing to Disclose

Stephen M. Keefe MD, Abstract Co-Author: Nothing to Disclose

Mark Alan Rosen MD, PhD, Abstract Co-Author: Nothing to Disclose

Peter J. O'Dwyer MD, Abstract Co-Author: Nothing to Disclose

Evan Spencer Siegelman MD, Abstract Co-Author: Consultant, Bio-Imaging Technologies, Inc Consultant, ICON plc

Traditional radiologic assessment of oncologic response depends on tumor size measurements (e.g., RECIST, or WHO criteria). However, these methods may be less sensitive to the effects of newer molecularly targeted antiangiogenic therapies, associated with inhibition of tumor vasculature and growth rather than marked tumor shrinkage. Here, we examine whether static MR imaging findings may be used as biomarkers of oncologic response to sorafenib, a broad spectrum VEGFR (vascular endothelial growth factor receptor) inhibitor.

Sixteen patients with metastatic renal cell carcinoma (RCC) and 16 patients with metastatic melanoma were studied. A total of 88 tumors (53 RCC and 35 melanoma) were identified. All patients had MRI scans at baseline, and 3-12 weeks after treatment with sorafenib. Tumor signal intensity on T1-weighted, T2-weighted, and delayed gadolinium contrast-enhanced images was compared before and after therapy, and across the two groups, using the proportional odds logistic regression model. Tumor size measurements were also performed for each patient.

Signal intensity on T1-weighted images increased (p=.039) following sorafenib therapy in patients with metastatic RCC, but not in those with metastatic melanoma. T2-weighted signal intensity showed a trend decrease in RCC, but not in melanoma. Post-gadolinium enhancing tumor appearance decreased after therapy in patients with RCC (p=.035), but not in melanoma patients. Although changes in tumor size differed significantly (p = .0001) between the groups (-13% change in RCC and +3% change in melanoma), the vast majority of patients in each group had stable disease at this time.

Following sorafenib therapy, RCC tumors demonstrated T1 shortening and decreased enhancement, while melanoma tumors did not change significantly. These findings are in line with results of clinical trials which demonstrate efficacy of sorafenib for RCC but less so for melanoma. Such changes assessed on routine MR images precede response by RECIST and may be useful biomarkers of tumor response to angiogenesis inhibitors.

Signal intensity changes on routine clinical MRI may represent early treatment effects of anti-angiogenic therapy.

Kang, H, Tan, K, Heitjan, D, Flaherty, K, Keefe, S, Rosen, M, O'Dwyer, P, Siegelman, E, Static MR Biomarkers of Tumor Response to VEGF Receptor Inhibition.  Radiological Society of North America 2010 Scientific Assembly and Annual Meeting, November 28 - December 3, 2010 ,Chicago IL. http://archive.rsna.org/2010/9003403.html