Abstract
Simple SummaryHCC with alterations in CTNNB1 (which encodes β-catenin) is resistant to immune checkpoint inhibitors and is associated with HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI in resectable HCC. However, the prevalence, characteristics, mutation profile, and treatment response in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI are not well clarified. In this study, we showed that the prevalence was 13%, and the response to lenvatinib does not differ between HCC with and without iso-high intensity in the hepatobiliary phase of EOB-MRI. We analyzed CTNNB-1 mutations using cell-free DNA, providing support for their association with iso-high intensity in the hepatobiliary phase of EOB-MRI.In hepatocellular carcinoma (HCC), CTNNB-1 mutations, which cause resistance to immune checkpoint inhibitors, are associated with HCC with iso-high intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in resectable HCC; however, analyses on unresectable HCC are lacking. This study analyzed the prevalence, characteristics, response to lenvatinib, and CTNNB-1 mutation frequency in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI. In 52 patients with unresectable HCC treated with lenvatinib, the prevalence of iso-high intensity in the hepatobiliary phase of EOB-MRI was 13%. All patients had multiple HCCs, and 3 patients had multiple HCCs with iso-high intensity in the hepatobiliary phase of EOB-MRI. Lenvatinib response to progression-free survival and overall survival were similar between patients with or without iso-high intensity in the hepatobiliary phase of EOB-MRI. Seven patients (three and four patients who had unresectable HCC with or without iso-high intensity in the hepatobiliary phase of EOB-MRI, respectively) underwent genetic analyses. Among these, two (67%, 2/3) who had HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI carried a CTNNB-1 mutation, while all four patients who had HCC without iso-high intensity in the hepatobiliary phase of EOB-MRI did not carry the CTNNB-1 mutation. This study’s findings have clinical implications for the detection and treatment of HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI.
Highlights
Recent advances have dramatically changed the hepatocellular carcinoma (HCC)treatment landscape
Patients with unresectable HCC for whom lenvatinib treatment was initiated at Hokkaido University Hospital between April 2018 and April 2021 were screened in this retrospective study
Between April 2018 and April 2021, a total of 61 patients with unresectable HCC were treated with lenvatinib at Hokkaido
Summary
Recent advances have dramatically changed the hepatocellular carcinoma (HCC). The development of immune checkpoint inhibitors (ICIs), which target negative anti-cancer immune response regulators, has drastically improved anticancer therapy. Various clinical trials and real-world data have revealed the efficacy of ICIs, conferring a durable response, which is not observed in conventional anti-cancer therapy, in various malignancies [1,2,3,4,5]. A clinical trial on HCC has revealed that bevacizumab plus atezolizumab has been associated with better overall survival (OS) in patients with unresectable tumors than sorafenib, which was the standard therapy for patients with unresectable HCC [6]. Some patients did not experience sufficient treatment response.
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