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

Sandrine Faivre, Magaly Zappa, Valérie Vilgrain, Eveline Boucher, Jean Yves Douillard, Ho Y. Lim, Jun Suk Kim, Seock Ah Im, Yoon Koo Kang, Mohamed Bouattour, Safi Dokmak, Chantal Dreyer, Marie Paule Sablin, Camille Serrate, Ann Lii Cheng, Silvana Lanzalone, Xun Lin, Maria J. Lechuga, Eric Raymond

    Research output: Contribution to journalArticlepeer-review

    64 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)4504-4512
    Number of pages9
    JournalClinical Cancer Research
    Volume17
    Issue number13
    DOIs
    Publication statusPublished - 2011 Jul 1

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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