title: Dynamic contrast-enhanced computed tomography as a potential biomarker in patients with metastatic renal cell carcinoma: preliminary results from the Danish Renal Cancer Group Study-1.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: From the Departments of *Radiology and †Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jill Rachel
authors.initials: JR
authors.lastname: Mains
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.forename: Erik Morre
authors.initials: EM
authors.lastname: Pedersen
authors.forename: Hans Henrik Torp
authors.initials: HH
authors.lastname: Madsen
authors.forename: Finn
authors.initials: F
authors.lastname: Rasmussen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging* / Q000556:secondary*; D003287:Contrast Media; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016037:Single-Blind Method; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D015415:Biomarkers; D003287:Contrast Media