title: Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Pharmacodynamic Biomarker for Pazopanib in Metastatic Renal Carcinoma.
abstract: Traditional imaging assessment criteria might not correlate well with clinical benefit from vascular endothelial growth factor pathway-directed therapy in metastatic renal cancer. Preclinical data suggest tumor growth is preceded by a rise in Ktranslevel, a parameter derived from dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) that reflects vascular permeability. We thus hypothesized that Ktransmight be a predictive biomarker for pazopanib.
  
  
  
  Patients with metastatic renal cancer were treated with pazopanib at 800 mg oral daily until disease progression. MRI of the abdomen and pelvis with a DCE-MRI sequence was obtained at baseline and every 8 weeks.
  
  
  
  Seventy-three DCE-MRI scans were completed and 66 were technically assessable. Of the 17 patients with at least 1 DCE-MRI scan after the baseline scan, 16 (94%) had a decline in Ktranslevel. Changes in Ktranscompared with baseline after 1, 8, 16, and 24 weeks were -49%, -65%, -63%, and -53%, respectively (P = .0052, repeated measures analysis of variance). The median Ktransnadir occurred at 8 weeks. The median progression-free survival (PFS) was 32.1 weeks. PFS was longer in patients with higher baseline Ktransvalues (P = .036, log rank). Baseline Ktransdid not reach significance in a Cox proportional hazard model including clinical prognostic index and previous treatments (P = .083).
  
  
  
  We show that Ktransis a pharmacodynamic biomarker for pazopanib therapy in metastatic renal cancer. Because of the small sample size, the predictive capacity of Ktransrecovery could not be assessed, but baseline Ktranscorrelated with PFS.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, IL.
authors.forename: Randy F
authors.initials: RF
authors.lastname: Sweis
authors.affiliation: Department of Radiology, University of Chicago, Chicago, IL.
authors.forename: Milica
authors.initials: M
authors.lastname: Medved
authors.affiliation: Department of Radiology, University of Chicago, Chicago, IL.
authors.forename: Shannon
authors.initials: S
authors.lastname: Towey
authors.affiliation: Department of Radiology, University of Chicago, Chicago, IL.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Karczmar
authors.affiliation: Department of Radiology, University of Chicago, Chicago, IL.
authors.forename: Aytekin
authors.initials: A
authors.lastname: Oto
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, IL.
authors.forename: Russell Z
authors.initials: RZ
authors.lastname: Szmulewitz
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, IL.
authors.forename: Peter H
authors.initials: PH
authors.lastname: O'Donnell
authors.affiliation: Illinois Cancer Care, Peoria, IL.
authors.forename: Paul
authors.initials: P
authors.lastname: Fishkin
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, IL.
authors.forename: Theodore
authors.initials: T
authors.lastname: Karrison
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, Comprehensive Cancer Center, University of Chicago, Chicago, IL. Electronic address: wstadler@medicine.bsd.uchicago.edu.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D003287:Contrast Media / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011743:Pyrimidines / Q000008:administration & dosage* / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: DCE-MRI; K(trans); Progression; Renal cancer; VEGF receptor tyrosine kinase