Abstract
To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. EudraCtNo: 2005-004502-82.
Highlights
Renal Cell Carcinoma (RCC) is the most common malignant tumor of the kidney, with prognosis being highly stage-dependent
Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/ s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer Progression-free survival (PFS) (p = 0.03) on the log-rank test
The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in metastatic RCC (mRCC) undergoing nephrectomy, no parameter predicted overall survival (OS)
Summary
Renal Cell Carcinoma (RCC) is the most common malignant tumor of the kidney, with prognosis being highly stage-dependent. Expansion in the therapeutic options of mRCC requires a parallel improvement in methods of early detection of therapy response to optimize the time spent on effective therapy and reduce side-effects and costs in the absence of clinical benefit. Current guidelines suggest two to four-monthly follow-up of mRCC patients on systemic therapy with contrast-enhanced CT for response assessment according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [5]. These criteria have well-known limitations, and there is no clinical evidence that RECIST-defined disease progression is a clinically valid endpoint that requires treatment interruption or modification [3]. While survival is correlated with volumetric response in mRCC, even stabilization of the disease is a valuable achievement, which is, difficult to detect morphologically [7, 8]
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