Prospective comparison of prognostic values of modified Response Evaluation Criteria in Solid Tumours with European Association for the Study of the Liver criteria in hepatocellular carcinoma following chemoembolisation
Introduction
World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumours (RECIST) guidelines have been universally accepted to evaluate solid tumour treatment responses.1, 2 However, these two conventional size-based criteria generally ignore tumour necrosis, and thus may underestimate treatment responses. Trans-arterial chemoembolisation (TACE), which is the fundamental locoregional therapy in patients with intrahepatic hepatocellular carcinoma (HCC) since HCC obtains most of the blood supply from hepatic artery, may induce acute tumour necrosis without decreasing tumour size. Thus, these two conventional size-based criteria could be improved to more accurately evaluate treatment responses.
Thus, to compensate for limitations of these size-based criteria, the HCC panel of European Association for the Study of the Liver (EASL) established the EASL criteria in 2001. In the EASL criteria, the arterially enhanced tumour burden, which indicated the remaining viable tumour after treatment, can be calculated bidimensionally.3 The EASL criteria have demonstrated superior efficacy for assessing treatment responses and predicting survival outcomes compared with the WHO and RECIST guidelines in patients with HCC, as EASL criteria can discriminate patients with better clinical outcomes by tumour necrosis, regardless of shrinkage of the entire tumour mass.4, 5, 6, 7 A complementary framework to assess therapeutic response was formally introduced in 2008 based on guidelines established by American Association for the Study of Liver Diseases–Journal of the National Cancer Institute.8 The revised guidelines, named the modified RECIST (mRECIST), consider both the concept of tumour viability based on arterial enhancement (i.e. from EASL criteria) and single linear summation (i.e. from RECIST), ultimately simplifying EASL criteria.8, 9 Similar to EASL criteria, the mRECIST criteria have also demonstrated superior efficacy compared with two conventional size-based criteria.4, 5, 10, 11
However, two major differences exist between these two enhancement-based criteria. First, the EASL criteria are based on a bidimensional calculation for target lesions, whereas the mRECIST criteria are based on a unidimensional calculation. Second, EASL criteria are designed to analyse all measurable target lesions, whereas the mRECIST criteria are designed to analyse up to two measurable target lesions. Thus, mRECIST is easier to use in a clinical setting. However, few investigations have compared the prognostic values of EASL and mRECIST guidelines for predicting overall survival (OS).11 Physicians and radiologists would benefit from the validation of the prognostic value of the EASL and mRECIST criteria through a comparative study in a homogeneous population in which the same treatment modality is applied. This validation would allow for an easier and more accurate determination of the efficacy of current treatment modalities and reduce unnecessary burden by recommending a more convenient assessment method.
In this study, we compared the prognostic value of mRECIST to predict OS in reference to the EASL criteria in treatment-naïve patients with HCC undergoing TACE as an initial treatment modality.
Section snippets
Patient eligibility
From the prospective database of the Liver Cancer Center at Severance Hospital of Yonsei University College of Medicine, treatment-naïve patients with intrahepatic HCC who received first-line therapy with TACE between June 2008 and December 2010 were included in this study. Exclusion criteria were: (1) inadequate target lesion (infiltrative pattern or largest lesion <1 cm); (2) presence of an additional primary malignancy in other organ; (3) presence of extrahepatic lesions; (4) Child–Pugh class
Baseline characteristics
The baseline demographic and clinical characteristics of the patients are shown in Table 2. Of the 292 patients (Fig. 1), 217 (74.3%) were male and the median age was 59 years (range, 30–75 years). All had Eastern Cooperative Oncology Group performance status of 0 or 1 and well preserved liver function with a Child–Pugh class A. The median diameter of the largest measurable lesion was 3.3 cm (range, 1.0–9.3 cm). The number of baseline measurable lesions was 1 in 39 patients (13.4%), 2 in 106
Discussion
Since two major differences exist between EASL and mRECIST guidelines, namely the method of calculating target area and the number of target lesions, we investigated whether the prognostic values for predicting OS differed between the two guidelines in a longitudinal setting. The overall response assessed by a simple new method, mRECIST, had excellent prognostic accuracy for predicting OS (C-index, 0.759), which was almost equivalent to that of EASL criteria (C-index, 0.753). The difference
Role of funding sources
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Conflict of interest statement
None declared.
Acknowledgements
The authors would like to thank the biostatisticians in the Department of Research Affairs, Yonsei University College of Medicine, for their assistance with the statistical analysis. This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065).
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Both authors equally contributed to this work.