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 journalArticle

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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

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Hepatocellular Carcinoma
Neoplasms
Tomography
Tumor Burden
Necrosis
Perfusion
sunitinib
Blood Volume
Research Design
Biomarkers
Response Evaluation Criteria in Solid Tumors
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Faivre, S., Zappa, M., Vilgrain, V., Boucher, E., Douillard, J. Y., Lim, H. Y., ... Raymond, E. (2011). Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. Clinical Cancer Research, 17(13), 4504-4512. https://doi.org/10.1158/1078-0432.CCR-10-1708

Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. / Faivre, Sandrine; Zappa, Magaly; Vilgrain, Valérie; Boucher, Eveline; Douillard, Jean Yves; Lim, Ho Y.; Kim, Jun Suk; Im, Seock Ah; Kang, Yoon Koo; Bouattour, Mohamed; Dokmak, Safi; Dreyer, Chantal; Sablin, Marie Paule; Serrate, Camille; Cheng, Ann Lii; Lanzalone, Silvana; Lin, Xun; Lechuga, Maria J.; Raymond, Eric.

In: Clinical Cancer Research, Vol. 17, No. 13, 01.07.2011, p. 4504-4512.

Research output: Contribution to journalArticle

Faivre, S, Zappa, M, Vilgrain, V, Boucher, E, Douillard, JY, Lim, HY, Kim, JS, Im, SA, Kang, YK, Bouattour, M, Dokmak, S, Dreyer, C, Sablin, MP, Serrate, C, Cheng, AL, Lanzalone, S, Lin, X, Lechuga, MJ & Raymond, E 2011, 'Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib', Clinical Cancer Research, vol. 17, no. 13, pp. 4504-4512. https://doi.org/10.1158/1078-0432.CCR-10-1708
Faivre, Sandrine ; Zappa, Magaly ; Vilgrain, Valérie ; Boucher, Eveline ; Douillard, Jean Yves ; Lim, Ho Y. ; Kim, Jun Suk ; Im, Seock Ah ; Kang, Yoon Koo ; Bouattour, Mohamed ; Dokmak, Safi ; Dreyer, Chantal ; Sablin, Marie Paule ; Serrate, Camille ; Cheng, Ann Lii ; Lanzalone, Silvana ; Lin, Xun ; Lechuga, Maria J. ; Raymond, Eric. / Changes in tumor density in patients with advanced hepatocellular carcinoma treated with sunitinib. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 13. pp. 4504-4512.
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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.",
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AU - Lim, Ho Y.

AU - Kim, Jun Suk

AU - Im, Seock Ah

AU - Kang, Yoon Koo

AU - Bouattour, Mohamed

AU - Dokmak, Safi

AU - Dreyer, Chantal

AU - Sablin, Marie Paule

AU - Serrate, Camille

AU - Cheng, Ann Lii

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AU - Lin, Xun

AU - Lechuga, Maria J.

AU - Raymond, Eric

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N2 - 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.

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