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

https://doi.org/10.1016/j.ejca.2012.08.022Get rights and content

Abstract

Backgrounds

European Association for the Study of the Liver (EASL) and modified Response Evaluation Criteria in Solid Tumours (mRECIST) guidelines, which measure changes in arterialised hepatocellular carcinoma (HCC), differ in terms of number of target lesions (all versus ⩽2) and calculation method (bidimensional versus unidimensional). We compared prognostic values of mRECIST for predicting overall survival (OS) with reference to EASL criteria in treatment-naïve HCC undergoing trans-arterial chemoembolisation (TACE).

Methods

The ability to predict OS during longitudinal follow-up was expressed as C-index, and a sample size of 292 patients was required to validate its equivalence between each criteria. Treatment responses were assessed using both guidelines 4 weeks after the first TACE, using dynamic computed tomography or magnetic resonance imaging. Kaplan–Meier and Cox regression analyses were used to explore differences in OS between responders (complete or partial) and non-responders (stable or progressive disease), defined by each method.

Results

C-index for EASL and mRECIST guidelines was 0.753 and 0.759, respectively, demonstrating equivalence between two methods. Differences in median OS between responders and non-responders were statistically significant for both EASL (30.1 versus 18.7 months, p < 0.001) and mRECIST (33.8 versus 17.1 months, p < 0.001) guidelines. In addition to radiological response, α-fetoprotein (p < 0.001), tumour number (p < 0.001) and tumour size (p = 0.048) were significant predictors of OS. In multivariate analysis, radiological criteria, tumour number and α-fetoprotein were identified as independent predictors (all p < 0.05).

Conclusion

mRECIST, a simpler method, provided prognostic values for predicting OS equivalent to EASL criteria in patients with HCC undergoing TACE as an initial treatment modality.

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).

References (28)

  • R. Lencioni et al.

    Modified RECIST (mRECIST) assessment for hepatocellular carcinoma

    Semin Liver Dis

    (2010)
  • J. Edeline et al.

    Comparison of tumor response by response evaluation criteria in solid tumors (RECIST) and modified RECIST in patients treated with sorafenib for hepatocellular carcinoma

    Cancer

    (2012)
  • J.H. Shim et al.

    Which response criteria best help predict survival of patients with hepatocellular carcinoma following chemoembolization? A validation study of old and new models

    Radiology

    (2012)
  • Korean Liver Cancer Study Group and National Cancer Center

    Practice guidelines for management of hepatocellular carcinoma 2009

    Korean J Hepatol

    (2009)
  • Cited by (72)

    • Clinical Significance of the Initial and Best Responses after Chemoembolization in the Treatment of Intermediate-Stage Hepatocellular Carcinoma with Preserved Liver Function

      2020, Journal of Vascular and Interventional Radiology
      Citation Excerpt :

      Shim et al (3) also stated the importance of repeated transarterial chemoembolization for achieving a maximal tumor response and, thus, used the best response as a final response category. In contrast, other authors have preferred the assessment of treatment response at an early time point after transarterial chemoembolization because it did a good job of predicting the survival of HCC patients undergoing transarterial chemoembolization (1,4,21,22). For example, Kim et al (4) recently evaluated the prognostic significance of the initial and best response during repeated transarterial chemoembolization in 314 patients with preserved liver function (Child-Pugh class A).

    View all citing articles on Scopus
    f

    Both authors equally contributed to this work.

    View full text