CT imaging findings in patients with advanced hepatocellular carcinoma treated with sorafenib: Alternative response criteria (Choi, European Association for the Study of the Liver, and modified Response Evaluation Criteria in Solid Tumor (mRECIST)) versus RECIST 1.1
Introduction
The RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) criteria are considered to be the standard method for tumor responses assessment in clinical trials and are representative of survival outcome in patients with solid tumors [1], [2].
The Study of Heart and Renal Protection (SHARP) trial [3] demonstrated a significant improvement in overall survival (OS) (median 10.7 versus 7.9 months) and in the mean time to radiological progression (5.5 versus 2.8 months) in patients with advanced-stage hepatocellular carcinoma (HCC) treated with sorafenib (Nexavar®, Bayer Healthcare Pharmaceuticals). However, the response rate on follow-up examination was only 2% according to RECIST. Phase III trials also showed a low radiological response rate (3.3%) using the RECIST 1.1 criteria, despite an improvement in overall survival [4], [5]. Moreover, in the SHARP trial, no significant difference was noted between the sorafenib and placebo groups with respect to objective responses (complete plus partial) or stable disease based on RECIST 1.1 (2% and 71%, respectively, in the sorafenib group; 1% and 67%, respectively, in the placebo group) [3].
The European Association for the Study of the Liver (EASL) proposed a set of criteria that considers the antitumoral activity of local therapies used in HCC, such as radiofrequency ablation and chemoembolization [6].
The emergence and validation of systemic therapies called for new criteria to assess tumor responses [7], [8], giving rise to the modified RECIST criteria (mRECIST) [6], [9], [10], [11], [12]
Choi et al. developed a composite endpoint for gastrointestinal stromal tumors (GIST) treated with imatinib, including tumor size and enhancement [13]. This evaluation tool is also potentially relevant to HCC.
The main objective was to determine which criteria (RECIST 1.1, mRECIST, Choi or EASL) correlates best with OS among patients with HCC treated with sorafenib. The secondary objectives were to describe morphological changes in tumors treated with sorafenib and their correlation with pretreatment characteristics to identify predictors of non-response.
Section snippets
Data collection
This retrospective monocentric observational study was conducted from November 2007 to January 2014 in HCC patients treated with sorafenib.
The following inclusion criteria were utilized for this study:
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Baseline thoracic and abdominopelvic imaging available within 6 weeks before sorafenib administration; and
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Imaging available during sorafenib therapy (>4 weeks after initiation).
The exclusion criteria were as follows:
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Concomitant specific treatment; or
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Prior specific treatment of HCC ending less than
Results
In total, 84 patients were treated with sorafenib during the study period, of whom 60 were eligible for inclusion. The median follow-up was 10.3 months (1–45 months).
The female:male sex ratio was 1:9. The average age was 60 years (39–79 years) (Table 1).
In total, 40 patients received prior treatment: chemoembolization (n = 32), radioembolization (n = 6), radiofrequency ablation (n = 4), cyberknife (n = 1), surgical tumor resection (n = 6), and liver transplantation (n = 2).
Sorafenib treatment lasted a mean
Discussion
HCC is often diagnosed at an advanced stage based on the BCLC criteria [14], [15].
Evaluation of the HCC response to sorafenib, which is typically based on RECIST 1.1, seems inappropriate [3]. The largest diameter of target lesions is only slightly modified by this treatment. In clinical trials of sorafenib, the use of the RECIST 1.1 criteria suggested that only 2 to 3.3% of patients responded [3], [4], which is inconsistent with the observed improvement in OS. More accurate and reproducible
Conclusion
This study suggests that the Choi criteria are most suitable for assessing the response of advanced-stage HCC to sorafenib. Patients with disease progression at the first follow-up CT examination are never downstaged on subsequent examinations. Although sorafenib is an angiogenesis inhibitor, neither the occurrence of tumor necrosis nor a loss of tumor hypervascularization correlated with tumor response.
Conflict of interest
None.
References (26)
- et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eur. J. Cancer Oxf. Engl. 1990
(2009) - et al.
Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial
Lancet Oncol.
(2009) - et al.
Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial
Eur. J. Cancer Oxf. Engl. 1990
(2012) - et al.
Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver
J. Hepatol.
(2001) - et al.
Aspects et évaluation post-thérapeutiques des lésions du foie après traitement non chirurgical
J. Radiol.
(2011) - et al.
Quantitative evaluation of CT-perfusion map as indicator of tumor response to transarterial chemoembolization and radiofrequency ablation in HCC patients
Eur. J. Radiol.
(2014) - et al.
New guidelines to evaluate the response to treatment in solid tumors European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada
J. Natl. Cancer Inst.
(2000) - et al.
Sorafenib in advanced hepatocellular carcinoma
N. Engl. J. Med.
(2008) - et al.
Design and endpoints of clinical trials in hepatocellular carcinoma
J. Natl. Cancer Inst.
(2008) - et al.
Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting
J. Clin. Oncol.
(2010)
Modified RECIST (mRECIST) assessment for hepatocellular carcinoma
Semin. Liver Dis.
New data supporting modified RECIST (mRECIST) for Hepatocellular Carcinoma
Clin. Cancer Res.
Imaging of hepatocellular carcinoma after treatment with yttrium-90 microspheres
Am. J. Roentgenol.
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