Evolution from WHO to EASL and mRECIST for hepatocellular carcinoma: considerations for tumor response assessment

Abstract

Radiological response assessment criteria in hepatocellular carcinoma (HCC) have evolved to accurately evaluate tumor responses. The WHO criteria and the subsequent Response Evaluation Criteria in Solid Tumors (RECIST) evaluate change in tumor size; however, these criteria generally ignore tumor necrosis and therefore may underestimate treatment responses. Thus, a panel of experts of the European Association for the Study of Liver (EASL) amended the response criteria to take into account tumor necrosis. In 2010, the modified RECIST (mRECIST) was developed, which consider both the concept of tumor viability based on arterial enhancement and single linear summation, ultimately simplifying EASL criteria. Currently, the mRECIST represents the gold standard for radiologically evaluating tumor response during HCC treatment. Here, the authors review application and performance of mRECIST as well as other HCC response assessment criteria and discuss unmet and open issues regarding response evaluation for HCC treatments.

Keywords:

• EASL
• hepatocellular carcinoma
• mRECIST
• RECIST
• response assessment
• WHO

Acknowledgements

The authors are grateful to Dong-Su Jang (medical illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the figure.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• There has been an evolution of response assessment criteria toward optimizing universally adopted guidelines for evaluating accurate tumor response during hepatocellular carcinoma (HCC) therapies.

• The WHO and Response Evaluation Criteria in Solid Tumors (RECIST) criteria underestimate treatment response when applied to LRTs or molecular-targeted therapy, in which the primary target is to induce tumor necrosis.

• The European Association for the Study of the Liver introduced the key concept of considering the reduction of viable tissue, instead of decreased tumor load, as a more accurate indicator of HCC tumor response to treatment.

• In 2008, the modified RECIST was developed, which officially standardized the model previously approved by the European Association for the Study of the Liver and American Association for the Study of Liver Disease.

• Currently, the modified RECIST represents the gold standard for radiologically evaluating tumor response during HCC treatment.

• In the near future, the development of new therapeutic approaches with novel mechanisms of action will require further modifications to response assessment criteria.