Microbubble ultrasound (DCE-US) compared to DCE-MRI and DCE-CT for the assessment of vascular response to sunitinib in renal cell carcinoma (RCC).

Abstract

4627 Background: DCE-MRI is widely accepted as a surrogate of vascular response. DCE-US uses microbubbles (MB) for contrast, which remain intravascular and allow direct assessment of tumor blood flow, blood flow velocity and blood volume (BV). DCE-US is repeatable and can be performed portably at the bedside. Methods: 25 treatment (Rx) naive patients (pts) with metastatic RCC and an abdominal tumor suitable for imaging received Sunitinib 50 mg on a 4W on /2W off schedule. DCE-US, DCE-CT, DCE-MRI and circulating endothelial cell counts (CEC’s) were done on the first course before therapy and after 2W and 4W on Rx (13 pts) or after 1W and 2W on Rx (12pts) and after 2W off Rx (21 pts). DCE-US included bolus and steady state infusions of MBs. Results: In 20 responding pts the median changes from baseline in BV by DCE-US and DCE-CT and Ktrans by DCE-MRI were -76%, -50%, and -70% respectively (p ≤ 0.002). With MB bolus, peak flow and AUC changed by -20% (p=0.042) and -44% (p=0.0040) respectively. Changes in Ktrans by MRI correlated with DCE-CT changes in BV (r=0.56, p=0.023) but not with DCE-US parameters. In 17 evaluable pts, progression free survival correlated with baseline measures of Ktrans (r=0.50, p=0.043) and Ve (r=0.52, p=0.031) by DCE-MRI, permeability surface area by DCE-CT (r=-0.52, p=0.032) and changes in apoptotic CECs (r=-0.61, p=0.016). Imaging parameters did not predict long-term assessment of best response by RECIST. Based on DCE-US flow velocity kinetics only 67% of the smallest tumor blood vessels responded to Rx. On DCE-US, BV decreased at 1W vs. baseline and again at 2W but remained similar or increased at 4W. A rebound was seen after 2W off Rx in 12/21 pts. These BV data suggest that a 2W on/1W off schedule may optimize the therapeutic index. Conclusions: This is the first study to contrast the utility of DCE-US, DCE-MRI and DCE-CT in RCC patients on TKI Rx. DCE-US may help select optimal scheduling for novel anti-angiogenic drugs.