Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib

Clin Cancer Res. 2011 Jul 1;17(13):4504-12. doi: 10.1158/1078-0432.CCR-10-1708. Epub 2011 Apr 29.


Purpose: 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.

Experimental design: 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.

Trial registration: NCT00247676.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Disease Progression
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Perfusion Imaging
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Tumor Burden


  • Antineoplastic Agents
  • Indoles
  • Pyrroles
  • Sunitinib

Associated data