title: Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib.
abstract: OBJECTIVE
  Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate the efficacy of targeted therapies. In hepatocellular carcinoma (HCC) studies with sunitinib, RECIST-defined response rates are low, although hypodensity on computed tomography (CT) scans occurs more frequently. This exploratory analysis investigated tumor density as a surrogate endpoint of sunitinib activity in a phase II HCC study.
  
  
  METHODS
  Patients received sunitinib 50 mg/d (4 weeks on/2 weeks off). Tumor size and density were assessed on CT scans by using RECIST and Choi criteria, the latter of which classify a partial response as a 15% or more reduction in tumor density or a 10% or more reduction in tumor size. The overall percentage volume of tumor necrosis was calculated with volumetric reconstruction. Tumor perfusion parameters were assessed by using perfusion CT scans with specific acquisition.
  
  
  RESULTS
  Among the 26 evaluable patients, 1 achieved a partial response and 22 had tumor stabilization by RECIST. In analysis of tumor density, 17 of 26 patients (65.4%) were responders by Choi criteria. Volumetric assessment showed major tumor necrosis (≥30% of tumor volume) in 10 of 21 patients (47.6%). Among four patients evaluated, tumor blood flow was reduced by 58.8% and blood volume by 68.4% after 4 weeks of treatment. The median time to progression (TTP) was 6.4 months. Patients with responses by Choi criteria had a significantly longer TTP (7.5 months) compared with nonresponders (4.8 months; HR = 0.33, two-sided P = 0.0182).
  
  
  CONCLUSIONS
  Tumor density assessment suggested that radiologic endpoints in addition to RECIST may be considered to capture sunitinib activity in HCC.
authors.affiliation: Beaujon University Hospital, Clichy, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Faivre
authors.forename: Magaly
authors.initials: M
authors.lastname: Zappa
authors.forename: Valérie
authors.initials: V
authors.lastname: Vilgrain
authors.forename: Eveline
authors.initials: E
authors.lastname: Boucher
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
authors.forename: Ho Y
authors.initials: HY
authors.lastname: Lim
authors.forename: Jun S
authors.initials: JS
authors.lastname: Kim
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
authors.forename: Yoon-Koo
authors.initials: YK
authors.lastname: Kang
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bouattour
authors.forename: Safi
authors.initials: S
authors.lastname: Dokmak
authors.forename: Chantal
authors.initials: C
authors.lastname: Dreyer
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Sablin
authors.forename: Camille
authors.initials: C
authors.lastname: Serrate
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Silvana
authors.initials: S
authors.lastname: Lanzalone
authors.forename: Xun
authors.initials: X
authors.lastname: Lin
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Lechuga
authors.forename: Eric
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D055420:Perfusion Imaging; D011758:Pyrroles / Q000627:therapeutic use*; D000077210:Sunitinib; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib