title: Neuroendocrine liver metastasis treated by using intraarterial therapy: volumetric functional imaging biomarkers of early tumor response and survival.
abstract: OBJECTIVE
  To determine if volumetric changes of diffusion-weighted and contrast material-enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM).
  
  
  METHODS
  This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3-4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio.
  
  
  RESULTS
  There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (-25.3%, P < .0001) and the PVP (-22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02).
  
  
  CONCLUSIONS
  Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Sidney Kimmel Comprehensive Cancer Center, and Department of Surgery, Johns Hopkins Hospital, 600 N Wolfe St, Room 143, Baltimore, MD 21287, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gowdra Halappa
authors.forename: Celia Pamela
authors.initials: CP
authors.lastname: Corona-Villalobos
authors.forename: Susanne
authors.initials: S
authors.lastname: Bonekamp
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Diane
authors.initials: D
authors.lastname: Reyes
authors.forename: David
authors.initials: D
authors.lastname: Cosgrove
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: Diaz
authors.forename: Nikhil
authors.initials: N
authors.lastname: Bhagat
authors.forename: John
authors.initials: J
authors.lastname: Eng
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Geschwind
authors.forename: Ihab R
authors.initials: IR
authors.lastname: Kamel
mesh_terms: D016461:Chemoembolization, Therapeutic / Q000379:methods*; D003287:Contrast Media; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D021621:Imaging, Three-Dimensional; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000473:pathology*; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA