Recent Trends in the Management of Hepatocellular Carcinoma with Special Emphasis on Treatment with Regorafenib and Immune Checkpoint Inhibitors

Kudo, Masatoshi

doi:10.1159/000448864

Cited by 9 publications

(5 citation statements)

References 81 publications

(93 reference statements)

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“…Recently, it was also reported that PD-1 expression promotes tumor growth, where PD-1 binds the downstream effectors of mammalian target of rapamycin (mTOR) and promotes their phosphorylation; the combination of mTOR inhibition with anti-PD-1 antibody results in a synergic tumor regression [32] . Based on these findings, clinical trials of immunomodulation of tumor microenvironment through intervention of oncogenic signaling are ongoing [33][34][35][36][37][38][39] . These trials include immune checkpoint inhibition combined with tyrosine kinase inhibitors [40,41] and other types of immune checkpoint inhibitors such as CTLA-4 antibody as well as immune checkpoint therapy combined with locoregional therapy such as resection [42][43][44] , ablation [45,46] , transarterial chemoembolization [47,48] , and hepatic arterial infusion chemotherapy [49,50] .…”

Section: Resultsmentioning

confidence: 99%

Oncogenic Signal and Tumor Microenvironment in Hepatocellular Carcinoma

Nishida

Kudo²

2017

Oncology

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During tumor development, several immunosuppressive molecules are released from cancer cells and contribute to the establishment of immunosuppressive tumor environment. In tumor tissues, cytokines, chemokines, growth factors, and metabolites are present and could counter the effects of immune checkpoint inhibitors. From this point of view, monotherapy of anti-PD-1/PD-L1 antibody might not be enough to exert a sufficient antitumor effect; additional blockade of immunosuppressive molecules in tumor microenvironment could enhance the antitumor effect of anti-PD-1/PD-L1 antibody. Importantly, the production of immunosuppressive molecules in cancer cells is attributed to the activation of cellular signaling through genetic and epigenetic alterations and environmental stimulation, such as inflammation and hypoxia. In this review, we focus on the establishment of immunosuppressive microenvironment of hepatocellular carcinoma in the context of activation of oncogenic signals, and discuss how the immunosuppressive condition could be overcome using tyrosine kinase inhibitors.

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Section: Resultsmentioning

confidence: 99%

Oncogenic Signal and Tumor Microenvironment in Hepatocellular Carcinoma

Nishida

Kudo²

2017

Oncology

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“…Patients with a Child-Pugh score of 5-7 and meeting the up-to-7 criteria were classified as substage B1, those with a Child-Pugh score of 5-7 and exceeding the up-to-7 criteria were classified as substage B2, and those with a Child-Pugh score of 8-9 and any up-to-7 criteria status were classified as substage B3 [16,24] .…”

Section: Modified Bolondi Classification (Kinki Criteria)mentioning

confidence: 99%

Time to Transcatheter Arterial Chemoembolization Refractoriness in Patients with Hepatocellular Carcinoma in Kinki Criteria Stages B1 and B2

Arizumi

Minami²,

Chishina³

et al. 2017

Dig Dis

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Background: Transarterial chemoembolization (TACE) is recommended for patients with hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) stage B. However, because of the heterogeneity of HCC in BCLC stage B; various subclassification systems have been proposed to predict the prognosis of patients. Previously, we proposed the Kinki criteria for precise classification of HCC cases in BCLC stage B. In this study, we compared the time to TACE refractoriness in HCC patients with Kinki criteria substages B1 and B2-HCC. Summary: Between January 2006 and December 2013, 592 HCC patients (substage B1, n = 118; substage B2, n = 170) underwent TACE. Time to progression under TACE treatment was defined as the time to untreatable progression (TTUP). TTUP and changes in liver function were analyzed in patients with substages B1 and B2-HCC.The median TTUP was 25.7 months (95% CI 19.3-37.3) and 16.4 months (95% CI 13.1-20.2) in patients with substage B1-HCC and substage B2-HCC, respectively (p = 0.0050). In patients with substage B2-HCC, median Child-Pugh scores after the first TACE session was significantly different from those after third and fifth TACE sessions (first-third, p = 0.0020; first-fifth, p = 0.0008). Key Message: TACE refractoriness occurred earlier in patients with substage B2-HCC than those with substage B1-HCC; deterioration of liver function with repeated TACE was more obvious in HCC cases with stage-B1 tumor. Shorter TTUP and impaired liver function due to repeated TACE could be responsible for the shorter survival in patients with substage B2-HCC.

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“…Hepatocellular carcinoma (HCC) is one of aggressive tumors that usually arise on top of background of liver cirrhosis (1). It is the fifth most common cancer in the world (2). Also, it is the third most common cause of cancer related deaths (1).…”

Section: Introductionmentioning

confidence: 99%

Percutaneous radiofrequency versus microwave ablation for management of hepatocellular carcinoma: a randomized controlled trial

Kamal

Elmoety

Rostom

et al. 2019

J. Gastrointest. Oncol

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Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer related deaths. Radiofrequency ablation (RFA) and microwave ablation (MWA) are effective measures for HCC management. Although MWA is usually considered to be superior to RFA in the medical community, clinical studies showed contradictory results. We aimed to compare the efficacy of both techniques using a randomized controlled trial. Methods: We had assessed all patients with definite HCC who were referred to our unit during the period from mid-June 2017 to mid-December 2017 for inclusion in the study. After fulfilling the criteria, patients were randomized to either RFA or MWA. Achieving complete ablation was ensured. Patients were followed up every 3 months after the procedure to detect any tumor recurrence. Results: There were no statistically significant differences between both techniques regarding complications, local tumor recurrence, development of de novo HCC lesions and changes in the modified Child-Pugh score. Time of ablation using MWA was significantly shorter than RFA (P<0.001). Conclusions: RFA and MWA are comparable techniques for HCC treatment. Our group couldn't prove any superiority of MWA over RFA except for the shorter time needed for ablation.

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Recent Trends in the Management of Hepatocellular Carcinoma with Special Emphasis on Treatment with Regorafenib and Immune Checkpoint Inhibitors

Cited by 9 publications

References 81 publications

Oncogenic Signal and Tumor Microenvironment in Hepatocellular Carcinoma

Oncogenic Signal and Tumor Microenvironment in Hepatocellular Carcinoma

Time to Transcatheter Arterial Chemoembolization Refractoriness in Patients with Hepatocellular Carcinoma in Kinki Criteria Stages B1 and B2

Percutaneous radiofrequency versus microwave ablation for management of hepatocellular carcinoma: a randomized controlled trial

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