Evaluation and Prediction of Treatment Response for Hepatocellular Carcinoma

Abstract

The incidence of hepatocellular carcinoma (HCC) is still on the rise in North America and Europe and is the second leading cause of cancer-related mortality. The treatment of HCC varies, with surgery and locoregional therapy (LRT) such as radiofrequency ablation and transcatheter arterial chemoembolization, and radiation therapy being the primary treatment. Currently, systemic therapy with molecular-targeted agents and immune checkpoint inhibitors (ICIs) is becoming a major treatment option for the unresectable HCC. As the HCC after LRT or systemic therapy often remains unchanged in size and shows loss of contrast effect in contrast-enhanced CT or MRI, the response evaluation criteria in solid tumors (RECIST) and World Health Organization criteria, which are usually used to evaluate the treatment response of solid tumors, are not appropriate for HCC. The modified RECIST (mRECIST) and the European Association for the Study of the Liver (EASL) criteria were developed for HCC, with a focus on viable lesions. The latest 2018 edition of the Liver Imaging Reporting and Data System (LI-RADS) also includes a section on the evaluation of treatment response. The cancer microenvironment influences the therapeutic efficacy of ICIs. Several studies have examined the utility of gadoxetic acid-enhanced MRI for predicting the pathological and molecular genetic patterns of HCC. In the future, it may be possible to stratify prognosis and predict treatment response prior to systemic therapy by using pre-treatment imaging findings.

Keywords: hepatocellular carcinoma; locoregional therapy; magnetic resonance imaging; systemic therapy; treatment response.

Fig. 1

Current tumor response classification systems are used to report tumor response after treatment. A 77-year-old male with alcohol-related hepatocellular carcinoma who underwent TACE. The WHO criteria (a, arrows) and RECIST (b, arrow) are size-based classification systems, and enhancement is not considered. Enhancement-based classification systems include the EASL criteria (c, arrows) and mRECIST (d, arrow). The LR-TR evaluates each viable lesion (e, circles). EASL, European Association for the Study of the Liver; LR-TR, Liver Imaging Reporting and Data System Treatment Response; mRECIST, modified RECIST; RECIST, response evaluation criteria in solid tumors; TACE, transcatheter arterial chemoembolization; WHO, World Health Organization.

Fig. 2

A 72-year-old male patient with hepatocellular carcinoma who underwent RFA. Pre-treatment gadoxetic-acid-enhanced MRI showed the hypervascular tumor in the segment Ⅵ (a, arrow). Five months after RFA, the tumor showed hyperintensity on the pre-contrast T1 weighted image (b, arrow), a hypointense area on hepatobiliary phase surrounded the tumor (c, arrow), and the arterial phase hyperenhancement disappeared (d, arrow), consistent with complete response according to mRECIST. One year after the treatment, the size of the hypointense area in the hepatobiliary phase decreased (e, arrow). mRECIST, modified response evaluation criteria in solid tumors; RFA, radiofrequency ablation.

Fig. 3

A residual lesion of a hepatocellular carcinoma after TACE with lipiodol in a 71-year-old female with hepatitis B virus-related cirrhosis. A pre-treatment CT image obtained during the arterial phase showed a hyperenhanced lesion in the segment Ⅶ (a). After lipiodol TACE, the unenhanced CT image showed the lesion presenting with heterogenous lipiodol retention (b). Two months after the treatment, gadoxetic acid-enhanced MRI showed the viable lesion (consistent with partial response according to mRECIST) (c and d, arrow), unaffected by lipiodol, while the arterial phase hyperenhancement is difficult to detect in CT because of the beam hardening artifact (e). mRECIST, modified response evaluation criteria in solid tumors; TACE, transcatheter arterial chemoembolization.

Fig. 4

MR images from a 78-year-old male of multiple hepatocellular carcinomas treated with lenvatinib. The target lesion showed hyperenhancement in the arterial phase (a, arrows), and hypointensity in portal venous and hepatobiliary phases (b and c, arrows). Two months after the initiation of lenvatinib, the arterial phase hyperenhancement of these tumors decreased (d, arrows), but unchanged in size (e, arrows).

Fig. 5

MR images from a 70-year-old female of hepatocellular carcinoma with extrahepatic spread (lymph node metastasis) treated with atezolizumab plus bevacizumab. The hepatic lesion showed the arterial phase hyperenhancement (a, arrow), restricted diffusion (b, arrow), and hypointensity in hepatobiliary phase (c, arrow) before the treatment. After 5 cycles of atezolizumab plus bevacizumab, the lesion became hypovascular and decreased in size, consistent with partial response according to RECIST (d–f, arrow). RECIST, response evaluation criteria in solid tumors.

Fig. 6

MR images from a 76-year-old male of alcohol-related hepatocellular carcinoma with β-catenin mutation. The nodule in the segment VIII shows hyperenhancement on the arterial phase (a), hyperintensity on T2 weighted imaging (b) and diffusion weighted imaging (c), and hyperintensity on the hepatobiliary phase (d). The nodule includes the tumor capsule (a and d).

Fig. 7

MR images from a 70-year-old male of non-alcoholic steatohepatitis-related steatotic hepatocellular carcinoma. The nodule in the segment VIII shows hyperenhancement on the arterial phase (a), hypointensity on the portal venous phase (not shown), transitional phase (not shown), and hepatobiliary phases (b). In-phase T1-weighted gradient-echo MR image (c) shows a well-defined hyperintense and the opposed-phase T1-weighted gradient-echo MR image (d) reveals a drop in the signal intensity, which indicates the presence of fat.