title: Magnetic resonance imaging biomarkers in hepatocellular carcinoma: association with response and circulating biomarkers after sunitinib therapy.
abstract: BACKGROUND
  To investigate the hypothesis that MRI derived diffusion-weighted imaging (DWI) and perfusion (MRP) parameters are sensitive image biomarkers for monitoring early antiangiogenic effects and predicting progression free survival (PFS) in advanced hepatocellular carcinoma (HCC).
  
  
  METHODS
  In this phase II clinical trial, 23 of 34 patients were included in the imaging and circulating biomarker study. DWI and MRP were performed at the baseline and at 2-weeks after initiation of sunitinib. The imaging protocol included an axial DWI sequence using b values of 50, 400 and 800 sec/mm2, and MRP using a series of coronal 3D-VIBE following 20 ml of Gd-DTPA at 2 ml/sec. These parameters were compared with clinical outcome and PFS at 6-months. Correlation between changes in MRI parameters and plasma biomarkers was also evaluated.
  
  
  RESULTS
  After 2-week of sunitinib, substantial Ktrans changes in HCC were observed from median baseline value 2.15 min⁻¹ to 0.94 min⁻¹ (P = 0.0001) with increases in median apparent diffusion coefficient (ADC) from 0.88 × 10⁻³ mm²/s to 0.98 × 10⁻³ mm²/s (P = 0.0001). Tumor size remained unchanged by RECIST and mRECIST (both P > 0.05). Patients who showed larger drop in Ktrans and Kep at 2 weeks correlated with favorable clinical outcome, and higher baseline Ktrans and larger drop in EVF correlated with longer PFS (all P < 0.05). There was a significant association between a decrease in sVEGFR2 and the drop in Ktrans and Kep (P = 0.044, P = 0.030), and a significant and borderline association between decrease in TNF-α and the drop in Ktrans and Kep, respectively (P = 0.051, P = 0.035).
  
  
  CONCLUSIONS
  In HCC, MRP may be a more sensitive biomarker in predicting early response and PFS following sunitinib than RECIST and mRECIST.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT00361309.
authors.affiliation: Division of Abdominal Imaging and Intervention, Harvard Medical School and Massachusetts General Hospital, 55 Fruit Street, White 270, Boston, MA 02114, USA. dsahani@partners.org
authors.forename: Dushyant V
authors.initials: DV
authors.lastname: Sahani
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Koichi
authors.initials: K
authors.lastname: Hayano
authors.forename: Dan G
authors.initials: DG
authors.lastname: Duda
authors.forename: Onofrio A
authors.initials: OA
authors.lastname: Catalano
authors.forename: Marek
authors.initials: M
authors.lastname: Ancukiewicz
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Jain
authors.forename: Andrew X
authors.initials: AX
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000097:blood / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib