Abstract
14003 Background: Evaluation of treatment response for cancer relies on application of criteria based on size such RECIST. However, changes in size are often delayed and small. An accurate and early evaluation of tumor vascular characteristics would allow selection of patients (pts) who would most likely benefit of these therapies and early detection of treatment response to tailor therapy on an individual basis. Changes in tumor vascular parameters were quantified using dynamic contrast-enhanced computed tomography (DCE-CT) as a biomarker for tumor angiogenesis. Methods: A total of 44 mRCC pts were enrolled in an imaging study corollary of two phase III trials evaluating efficacy of anti-angiogenic drugs: sorafenib (N=9) vs. placebo (N=13), or sunitinib (N=17) vs. interferon (N=5). Perfusion CT acquisitions after injection of 80 ml of iodinated contrast agent were performed on a single “functional metastatic target” before treatment and every 6 weeks for follow-up. Microvascular parameters of the functional target were calculated using a dedicated software based on compartmental models: tumor blood flow (TBF) (ml/min/100g), tumor blood volume (TBV) (%), vascular permeability (VP) (ml/min/100g) and mean transit time (MTT) (s). These parameters were correlated to the best treatment response as evaluated by the size variation of the RECIST targets. Results: Among the 26 treated pts, there was a statistically significant drop in TBF and TBV as early as the first cycle of treatment (respectively -50%, p=0.03 and -51%, p<0.01) compared to pre-treatment, showing the biological effect of the drug on tumor vascularity. There was a significantly higher drop in TBF and TBV in pts who would be later classified as responders (N=16) vs. non-responders (N=10) after the first cycle of treatment (-66% vs. -6%, p=0.02; -60% vs. -26.5%, p=0.04). The changes in MTT and VP were not correlated to the best response. Conclusions: The functional imaging biomarkers TBF and TBV quantified by DCE-CT detect the biological effect of anti-angiogenic drugs on tumor vessels. TBF appears as very early predictor of mRCC response to anti-angiogenic drugs supporting the hypothesis that DCE-CT may constitute a surrogate biomarker of angiogenesis inhibition. No significant financial relationships to disclose.
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