Functional MRI techniques demonstrate early vascular changes in renal cell cancer patients treated with sunitinib: a pilot study

Abstract

Objective: To assess the early vascular effects of sunitinib in patients with renal cell carcinoma (RCC) with diffusion-weighted magnetic resonance imaging (DWI), dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and T2* perfusion MRI.

Patients and methods: In 10 patients with abdominal RCC lesions, DWI, DCE-MRI and T2* perfusion MRI measurements at 3 Tesla were performed at baseline, 3 and 10 days after start of sunitinib. VEGF-A plasma levels were measured on days 0, 3 and 10.

Results: DWI showed a significant increase in the apparent diffusion coefficient (×10(-6) s/mm(2)) from baseline (mean 1158, range 814-2003) to day 3 (mean 1306, range 1008-2097, P = 0.015) followed by a decrease to baseline levels at day 10 (mean 1132, range 719-2005, P = 0.001). No significant changes were found in mean DCE-MRI parameters. T2* perfusion MRI showed a significant decrease in relative tumor blood volume (rBV) and relative tumor blood flow (rBF) at day 3 (rBV P = 0.037, rBF P = 0.018) and day 10 (rBV P = 0.006, rBF P = 0.009). VEGF-A plasma levels significantly increased after 10 days, but did not correlate with MRI parameters.

Conclusions: Sunitinib induces antiangiogenic effects as measured by DWI and T2*-perfusion MRI, 3 and 10 days after the start of the initial treatment. DCE-MRI did not show significant changes. In the near future, early functional MRI-based evaluation can play an important role in tailoring treatment to the individual patient with RCC. Further investigation is warranted.

Figure 1

DWI shows a significant increase of ADC (×10⁻⁶mm²/s) from baseline (mean 1158, range 814–2003) to day 3 (mean 1306, range 1008–2097, P = 0.015) followed by a decrease to baseline levels at day 10 (mean 1132, range 719–2005, P = 0.001).

Figure 2

Change in ADC over time. (A) Large tumor in the left kidney visualized by conventional T1 MRI. (B) Baseline ADC map projected on conventional T1 MRI image. Mean ADC value 814 × 10⁻⁶mm²/s. (C) Increase in ADC values after 3 days of treatment with sunitinib. Mean ADC value 1239 × 10⁻⁶mm²/s. (D) Recovery to baseline ADC values 10 days after starting sunitinib. Mean ADC value 719 × 10⁻⁶mm²/s.

Figure 3

Changes in perfusion parameters, rBV, rBF and MTT. (A) rBV significantly decreased from baseline (mean 1019.8, range 412.1–1944.0) to day 3 (mean 721.0, range 55.8–1996.7) (P = 0.044) and between baseline and day 10 (mean 573.5, range 99.7–1597.6) (P = 0.007). (B) The relative tumor blood flow (rBF) significantly decreased from baseline (mean 154.3, range 83.3–290.8) to day 10 (mean 69.2, range 12.4–148.1) (P = 0.002). This decrease was more pronounced between day 3 (mean 132.8, range 33.1–242.7) and day 10 (P = 0.003), not from baseline to day 3 (P > 0.1). (C) A decrease in mean transit time (MTT) from baseline (mean 9.15 s, range 1.5–17.6.0 s) to day 3 (mean 6.8 s, range 11.5 s) (P = 0.015) but not from baseline to day 10 (mean 11.5 s, range 4.0–18.4 s) (P > 0.1) was observed.