Mains, Jill Rachel4; Donskov, Frede5; Pedersen, Erik Morre4; Madsen, Hans Henrik Torp4; Rasmussen, Finn4
1 Department of Clinical Medicine, Health, Aarhus University2 Diagnostic Radiology, Department of Clinical Medicine, Health, Aarhus University3 Department of Clinical Medicine - The Department of Oncology, Department of Clinical Medicine, Health, Aarhus University4 Department of Clinical Medicine, Health, Aarhus University5 Department of Clinical Medicine - The Department of Oncology, Department of Clinical Medicine, Health, Aarhus University
OBJECTIVES: The aim of this study was to explore the impact of dynamic contrast-enhanced (DCE) computer tomography (CT) as a biomarker in metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: Twelve patients with favorable or intermediate Memorial Sloan Kettering Cancer Center risk group and clear cell mRCC participating in an ongoing prospective randomized phase II trial comprising interleukin-2-based immunotherapy and bevacizumab were included in this preliminary analysis. All patients had a follow-up time of at least 2 years. Interpretation of DCE-CT (max slope method) was performed blinded to treatment group. The DCE-CT scans were performed at baseline, at weeks 5 and 10, and thereafter every third month. Blood flow (BF; mL/min/100 mL), peak enhancement (Hounsfield units), time to peak (seconds), and blood volume (BV; mL/100 g) were calculated. Parameters for DCE-CT were correlated with sum of diameters (defined by Response Evaluation Criteria in Solid Tumors 1.1), progression-free survival (PFS), and overall survival (OS) using Wilcoxon, Man-Whitney, Kaplan-Meier, and log rank statistics, as appropriate. RESULTS: Blood flow at baseline ranged from 4.9 to 148.1 mL/min/100 mL (median, 62.2; 25th percentile, 25.8; 75th percentile, 110.0). Patients with high baseline BF (using quartiles as cutoffs) had significantly longer OS (not reached vs 5.2 months, P = 0.011) and longer PFS (not reached vs 3.9 months, P = 0.026). Blood volume at baseline ranged from 8.8 to 74.1 mL/100 g tissue (median, 21.5), and at week 5, from 4.9 to 34.7 mL/100 g (median, 17.2). Relative changes in BV between baseline and week 5 ranged from -64% to +68% (median, -16%; 25th percentile, -41%; 75th percentile, +2%) and were significantly associated with OS using quartiles as cutoffs (5.2 months vs not reached, P = 0.038) and PFS using the median as cutoff (5.3 months vs not reached, P = 0.009), with larger reductions associated with longer survival. Using medians as cutoffs, relative changes in both BF and BV between baseline and week 10 were significantly associated with OS (for both, 8.6 months vs not reached, P = 0.031). CONCLUSIONS: Dynamic contrast-enhanced CT is a potential biomarker in patients with mRCC. High baseline BF and reductions in BF and BV during early treatment are associated with improved outcome. Large-scale studies are required.
Investigative Radiology, 2014, Vol 49, Issue 9, p. 601-7