Modified RECIST (mRECIST) assessment for hepatocellular carcinoma

Abstract

The endpoint in cancer research is overall survival. Nonetheless, other potential surrogate endpoints, such as response rate and time to progression, are currently used. Measurement of response rate in hepatocellular carcinoma (HCC) has become a controversial issue. The World Health Organization (WHO) criteria underestimate the actual response rate; thus, they were amended in 2000 by a panel of experts convened by the European Association for the Study of the Liver (EASL) to take into account treatment-induced tumor necrosis. Applying these guidelines, there was an association between response rate and outcome prediction. More recently, the Response Evaluation Criteria in Solid Tumors (RECIST) guideline was proposed as a method for measuring treatment response based on tumor shrinkage, which is a valuable measure of antitumor activity of cytotoxic drugs. This method was initially adopted by regulatory agencies, such as the U.S. Food and Drug Administration (FDA), for drug approval. However, anatomic tumor response metrics can be misleading when applied to molecular-targeted therapies or locoregional therapies in HCC. In 2008, a group of experts convened by the American Association for the Study of Liver Diseases (AASLD) developed a set of guidelines aimed at providing a common framework for the design of clinical trials in HCC and adapted the concept of viable tumor-tumoral tissue showing uptake in arterial phase of contrast-enhanced radiologic imaging techniques-to formally amend RECIST. These amendments conformed the AASLD-JNCI (Journal of the National Cancer Institute) guidelines and are summarized and clarified in the current article. They are referred to herein as the modified RECIST assessment (mRECIST). Further studies are needed to confirm the accuracy of this measurement compared with conventional gold standards such as pathologic studies of explanted livers.

Figure 1

Application of mRECIST assessment for hepatocellular carcinoma (HCC). Target tumor response measurements on arterial-phase computed tomography (CT) scans. (A) Measurement of longest overall tumor diameter according to conventional RECIST, and (B) measurement of longest viable tumor diameter according to mRECIST for HCC.

Figure 2

Application of mRECIST assessment for hepatocellular carcinoma (HCC). New lesion. Computed tomography (CT) scans obtained in an HCC patient’s follow-up after treatment (main tumor not shown). On scans obtained at time point 1 (A, arterial phase; B, venous phase), a new lesion is identified (arrow). The tiny lesion is smaller than 1 cm; therefore, it must be considered equivocal. On CT scans obtained at time point 2 (C, arterial phase; D, venous phase), the tumor has become larger than 1 cm and shows the characteristic vascular pattern of HCC (arterial hypervascularization with venous washout). Although the criteria for diagnosing the lesion as HCC were fulfilled only at time point 2, progression must be declared in retrospect at time point 1, that is at the time the lesion was first detected.