title: Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. Part I. Identification and validation of volumetric functional response criteria.
abstract: OBJECTIVE
  To identify and validate the optimal thresholds for volumetric functional MR imaging response criteria to predict overall survival after intraarterial treatment (IAT) in patients with unresectable hepatocellular carcinoma (HCC).
  
  
  METHODS
  Institutional review board approval and waiver of informed consent were obtained. A total of 143 patients who had undergone MR imaging before and 3-4 weeks after the first cycle of IAT were included. MR imaging analysis of one representative HCC index lesion was performed with proprietary software after initial treatment. Subjects were randomly divided into training (n = 114 [79.7%]) and validation (n = 29 [20.3%]) data sets. Uni- and multivariate Cox models were used to determine the best cutoffs, as well as survival differences, between response groups in the validation data set.
  
  
  RESULTS
  Optimal cutoffs in the training data set were 23% increase in apparent diffusion coefficient (ADC) and 65% decrease in volumetric enhancement in the portal venous phase (VE). Subsequently, 25% increase in ADC and 65% decrease in VE were used to stratify patients in the validation data set. Comparison of ADC responders (n = 12 [58.6%]) with nonresponders (n = 17 [34.5%]) showed significant differences in survival (25th percentile survival, 11.2 vs 4.9 months, respectively; P = .008), as did VE responders (n = 9 [31.0%]) compared with nonresponders (n = 20 [69.0%]; 25th percentile survival, 11.5 vs 5.1 months, respectively; P = .01). Stratification of patients with a combination of the criteria resulted in significant differences in survival between patients with lesions that fulfilled both criteria (n = 6 [20.7%]; too few cases to determine 25th percentile), one criterion (n = 9 [31.0%]; 25th percentile survival, 6.0 months), and neither criterion (n = 14 [48.3%]; 25th percentile survival, 5.1 months; P = .01). The association between the two criteria and overall survival remained significant in a multivariate analysis that included age, sex, Barcelona Clinic for Liver Cancer stage, and number of follow-up treatments.
  
  
  CONCLUSIONS
  After IAT for unresectable HCC, patients can be stratified into significantly different survival categories based on responder versus nonresponder status according to MR imaging ADC and VE cutoffs.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science and Department of Surgery and Oncology, The Johns Hopkins Hospital, 600 N Wolfe St, MRI 143, Baltimore, MD 21287, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bonekamp
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Jean-François H
authors.initials: JF
authors.lastname: Geschwind
authors.forename: Vivek Gowdra
authors.initials: VG
authors.lastname: Halappa
authors.forename: Celia Pamela
authors.initials: CP
authors.lastname: Corona-Villalobos
authors.forename: Diane
authors.initials: D
authors.lastname: Reyes
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: David
authors.initials: D
authors.lastname: Bonekamp
authors.forename: John
authors.initials: J
authors.lastname: Eng
authors.forename: Ihab R
authors.initials: IR
authors.lastname: Kamel
mesh_terms: D000704:Analysis of Variance; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000628:therapy*; D016461:Chemoembolization, Therapeutic; D016009:Chi-Square Distribution; D003287:Contrast Media; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D004317:Doxorubicin; D019786:Gadolinium DTPA