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

doi:10.1016/j.ejrad.2015.10.024

European Journal of Radiology

Volume 85, Issue 1, January 2016, Pages 103-112

https://doi.org/10.1016/j.ejrad.2015.10.024 Get rights and content

Highlights

•
Response or non-response as defined by the Choi criteria exhibited the highest predictive value for overall survival compared with the EASL, RECIST 1.1 and mRECIST criteria.
•
Patients with progression at the first follow-up examination are never downstaged.
•
Neither tumor necrosis nor tumor hypervascularization were independent predictors of tumor response.

Abstract

Purpose

The first aim was to compare Response Evaluation Criteria in Solid Tumor (RECIST) 1.1, modified Response Evaluation Criteria in Solid Tumor (mRECIST), Choi and European Association for the Study of the Liver (EASL) evaluations to assess the response to sorafenib for hepatocellular carcinoma (HCC).

The second aim was to describe the evolution of HCC and to identify whether some imaging features are predictive of the absence of response.

Materials and methods

This retrospective study included 60 patients with advanced HCC treated with sorafenib. Patients must have undergone a scan prior to treatment to identify the number of lesions, size, enhancement and endoportal invasions, and repeat scans thereafter. Computed tomography (CT) scans were analyzed using RECIST 1.1, mRECIST, Choi and EASL criteria. Overall survival was analyzed.

Results

The median overall survival was 10.5 months. On the first CT reevaluation, the sorafenib response rates were 20%, 5%, 7% and 3% according to Choi, EASL, mRECIST and RECIST 1.1. The responders based on Choi exhibited significantly better overall survival compared with non-responders (20.4 months; hazard ratio (HR) 0.042, 95% confidence interval (CI): 0.186–0.94, p = 0.035). A modification of imaging findings was observed in 48.3% of patients, and necrosis was present in 44.1% of patients.

Conclusion

This study found a significant difference between Choi versus RECIST 1.1, mRECIST and EASL when evaluating the response to sorafenib in HCC patients.

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:

-
Baseline thoracic and abdominopelvic imaging available within 6 weeks before sorafenib administration; and
-
Imaging available during sorafenib therapy (>4 weeks after initiation).

The exclusion criteria were as follows:

-
Concomitant specific treatment; or
-
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)

E.A. Eisenhauer et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)
Eur. J. Cancer Oxf. Engl. 1990
(2009)
A.-L. Cheng 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)
A.-L. Cheng 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)
J. Bruix 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)
S. Delumeau et al.
Aspects et évaluation post-thérapeutiques des lésions du foie après traitement non chirurgical
J. Radiol.
(2011)
D. Ippolito 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)
P. Therasse 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)
J.M. Llovet et al.
Sorafenib in advanced hepatocellular carcinoma
N. Engl. J. Med.
(2008)
J.M. Llovet et al.
Design and endpoints of clinical trials in hepatocellular carcinoma
J. Natl. Cancer Inst.
(2008)
M.B. Thomas et al.
Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting
J. Clin. Oncol.
(2010)

R. Lencioni et al.

Modified RECIST (mRECIST) assessment for hepatocellular carcinoma

Semin. Liver Dis.

(2010)

R. Lencioni

New data supporting modified RECIST (mRECIST) for Hepatocellular Carcinoma

Clin. Cancer Res.

(2013)

A.L. Keppke et al.

Imaging of hepatocellular carcinoma after treatment with yttrium-90 microspheres

Am. J. Roentgenol.

(2007)

Cited by (26)

Evaluation of liver tumour response by imaging
2020, JHEP Reports
Citation Excerpt :
Based on the validation in GIST tumours, the Choi criteria have also been studied for other hyperenhanced tumours, including metastatic renal cell carcinoma,68 non-GIST sarcomas, neuroendocrine tumours (Fig. 4), and finally HCC.7 Indeed, treatment response defined by the Choi criteria has been associated with longer survival in patients with advanced HCC treated with sorafenib,7,52 as well as in patients with intrahepatic cholangiocarcinoma treated with SIRT.69 However, the Choi criteria have certain limitations for the evaluation of HCC response.
The goal of assessing tumour response on imaging is to identify patients who are likely to benefit — or not — from anticancer treatment, especially in relation to survival. The World Health Organization was the first to develop assessment criteria. This early score, which assessed tumour burden by standardising lesion size measurements, laid the groundwork for many of the criteria that followed. This was then improved by the Response Evaluation Criteria in Solid Tumours (RECIST) which was quickly adopted by the oncology community. At the same time, many interventional oncology treatments were developed to target specific features of liver tumours that result in significant changes in tumours but have little effect on tumour size. New criteria focusing on the viable part of tumours were therefore designed to provide more appropriate feedback to guide patient management. Targeted therapy has resulted in a breakthrough that challenges conventional response criteria due to the non-linear relationship between response and tumour size, requiring the development of methods that emphasize the appearance of tumours. More recently, research into functional and quantitative imaging has created new opportunities in liver imaging. These results have suggested that certain parameters could serve as early predictors of response or could predict later tumour response at baseline. These approaches have now been extended by machine learning and deep learning. This clinical review focuses on the progress made in the evaluation of liver tumours on imaging, discussing the rationale for this approach, addressing challenges and controversies in the field, and suggesting possible future developments.
Multiparametric magnetic resonance imaging for hepatocellular carcinoma, part 1: Morphology and dynamic perfusion imaging in primary diagnostics and treatment monitoring
2024, Radiologie
Impact of radiological response and pattern of progression in patients with HCC treated by atezolizumab-bevacizumab
2024, Hepatology
Comparison of mRECIST and iRECIST criteria in evaluating the efficacy of immunotherapy for hepatocellular carcinoma
2023, China Journal of General Surgery
Evaluation and Prediction of Treatment Response for Hepatocellular Carcinoma
2023, Magnetic Resonance in Medical Sciences
Immunotherapy-Based Treatments of Hepatocellular Carcinoma: AJR Expert Panel Narrative Review
2022, American Journal of Roentgenology

View all citing articles on Scopus

View full text

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

Highlights

Abstract

Purpose

Materials and methods

Results

Conclusion

Introduction

Section snippets

Data collection

Results

Discussion

Conclusion

Conflict of interest

Eur. J. Cancer Oxf. Engl. 1990

Lancet Oncol.

Eur. J. Cancer Oxf. Engl. 1990

J. Hepatol.

J. Radiol.

Eur. J. Radiol.

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.

Sorafenib in advanced hepatocellular carcinoma

N. Engl. J. Med.

Design and endpoints of clinical trials in hepatocellular carcinoma

J. Natl. Cancer Inst.

Hepatocellular carcinoma: consensus recommendations of the National Cancer Institute Clinical Trials Planning Meeting

J. Clin. Oncol.

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.