title: Diffusion-weighted and multiphase contrast-enhanced MRI as surrogate markers of response to neoadjuvant sunitinib in metastatic renal cell carcinoma.
abstract: BACKGROUND
  Current imaging criteria for categorising disease response in metastatic renal cell carcinoma (mRCC) correlate poorly with overall survival (OS) in patients on anti-angiogenic therapies. We prospectively assess diffusion-weighted and multiphase contrast-enhanced (MCE) MR imaging (MRI) as markers of outcome.
  
  
  METHODS
  Treatment-naive mRCC patients on a phase II trial using sunitinib completed an MRI substudy. Whole-tumour apparent diffusion coefficient (ADC) maps and histograms were generated, and mean ADC and AUC(low) (proportion of the tumour with ADC values lying below the 25th percentile of the ADC histogram) recorded. On MCE-MRI, regions of interest were drawn around the most avidly enhancing components to analyse enhancement parameters. Baseline (n=26) and treatment-related changes in surviving patients (n=20) were correlated with OS. Imaged metastases were also analysed.
  
  
  RESULTS
  Forty-seven per cent of the patients showed significant changes in whole-tumour mean ADC following therapy, but there was no correlation with outcome. Patients with a high baseline AUC(low) and greater-than-median AUC(low) increase had reduced OS (HR=3.67 (95% confidence interval (CI)=1.23-10.9), P=0.012 and HR=3.72 (95% CI=0.98-14.21), P=0.038, respectively). There was no correlation between MCE-MRI parameters and OS. Twenty-eight metastases were analysed and showed positive correlation with primary tumour mean ADC for individual patients (r=0.607; P<0.001).
  
  
  CONCLUSIONS
  Primary RCC ADC histogram analysis shows dynamic changes with sunitinib. Patients in whom the tumour ADC histogram demonstrated high baseline AUC(low) or a greater-than-median increase in AUC(low) with treatment had reduced OS.
authors.affiliation: Department of Radiology, Barts Health NHS Trust, St Bartholomew's Hospital, King George V Building, West Smithfield, London EC1A 7BE, UK.
authors.forename: N
authors.initials: N
authors.lastname: Bharwani
authors.affiliation: 1] Department of Clinical Physics, Barts Health NHS Trust, St Bartholomew's Hospital, 4th Floor Dominion House, 60 St Bartholomew's Close, London EC1A 7BE, UK [2] Barts and the London NIHR Cardiovascular Biomedical Research Unit, Centre for Advanced Cardiovascular Imaging, Queen Mary University of London, Bonner Road, London E2 9JX, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Miquel
authors.affiliation: Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: T
authors.initials: T
authors.lastname: Powles
authors.affiliation: Department of Radiology, Barts Health NHS Trust, St Bartholomew's Hospital, King George V Building, West Smithfield, London EC1A 7BE, UK.
authors.forename: P
authors.initials: P
authors.lastname: Dilks
authors.affiliation: Department of Radiology, Barts Health NHS Trust, St Bartholomew's Hospital, King George V Building, West Smithfield, London EC1A 7BE, UK.
authors.forename: A
authors.initials: A
authors.lastname: Shawyer
authors.affiliation: Department of Radiology, Barts Health NHS Trust, St Bartholomew's Hospital, King George V Building, West Smithfield, London EC1A 7BE, UK.
authors.forename: A
authors.initials: A
authors.lastname: Sahdev
authors.affiliation: Department of Medical Oncology, St Bartholomew's Hospital, 7th Floor Gloucester House, London EC1A 7BE, UK.
authors.forename: P D
authors.initials: PD
authors.lastname: Wilson
authors.affiliation: Department of Medical Oncology, Guys and St Thomas' NHS Foundation Trust, Great Maze Pond, London SE1 9RT, UK.
authors.forename: S
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Barts Cancer Institute, Molecular Oncology and Cellular Pathology, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Berney
authors.affiliation: Department of Radiology, Barts Health NHS Trust, St Bartholomew's Hospital, King George V Building, West Smithfield, London EC1A 7BE, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Rockall
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis; D011758:Pyrroles / Q000008:administration & dosage; D011859:Radiography; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib