Faculty Opinions recommendation of Complete response under sorafenib in patients with hepatocellular carcinoma: Relationship with dermatologic adverse events.

Advanced hepatocellular carcinoma patients treated with sorafenib who develop early dermatologic adverse events (eDAEs) have a better prognosis. This may be linked to immune mechanisms, and thus, it is relevant to assess the association between peripheral immunity and the probability of developing eDAEs. Peripheral blood mononuclear cells of 52 HCC patients treated with sorafenib were analyzed at baseline and throughout the first eight weeks of therapy. T, B, Natural Killer cells, and their immune checkpoints expression data were characterized by flow cytometry. Cytokine release and immune-suppression assays were carried out ex vivo. Cox baseline and time-dependent regression models were applied to evaluate the probability of increased risk of eDAEs. DNAM-1, PD-1, CD69, and LAG-3 in T cells, plus CD16 and LAG-3 in NK cells, are significantly associated with the probability of developing eDAEs. While NK DNAM-1+ cells express activation markers, T DNAM-1+ cells induce immune suppression and show immune exhaustion. This is the first study to report an association between immune checkpoints expression in circulating immune cells and the increased incidence of eDAEs. Our results support the hypothesis for an off-target role of sorafenib in immune modulation. We also describe a novel association between DNAM-1 and immune exhaustion in T cells.

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Analysis of monitoring adverse events and problems in the treatment with sorafenib for hepatocellular carcinoma

Kanzo ◽

10.2957/kanzo.54.249 ◽

2013 ◽

Vol 54 (4) ◽

pp. 249-256

Author(s):

Keiko Komori ◽

Chie Mochizuki ◽

Yoshie Masu ◽

Noriko Hasegawa ◽

Akio Ishihara ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events

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Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211031141 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110311

Author(s):

Chiun Hsu ◽

Lorenza Rimassa ◽

Hui-Chuan Sun ◽

Arndt Vogel ◽

Ahmed O. Kaseb

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Kinase Inhibitor ◽

Treatment Options ◽

Healthcare Providers ◽

Safety Data ◽

Standard Of Care ◽

Antiangiogenic Agents ◽

Efficacy And Safety ◽

First Line

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

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Diaphragmatic weakness after transcatheter arterial chemoembolization of the right inferior phrenic artery for treatment of hepatocellular carcinoma: a comparison of outcomes after N-butyl cyanoacrylate versus gelatin sponge embolization

Acta Radiologica ◽

10.1177/0284185120981771 ◽

2020 ◽

pp. 028418512098177

Author(s):

Seung Yeon Noh ◽

Dong Il Gwon ◽

Suyoung Park ◽

Woo Jin Yang ◽

Hee Ho Chu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Complete Response ◽

Gelatin Sponge ◽

Inferior Phrenic Artery ◽

Gelatin Sponge Particles ◽

Phrenic Artery ◽

The Right ◽

Diaphragmatic Weakness ◽

Arterial Chemoembolization

Background The inferior phrenic artery (IPA) is the most common extrahepatic feeder for hepatocellular carcinoma (HCC) during transhepatic arterial chemoembolization (TACE). Purpose To compare the incidence of diaphragmatic weakness in patients with HCC after TACE of the right IPA conducted using either N-butyl cyanoacrylate (NBCA) or gelatin sponge particles. Material and Methods Medical records of 111 patients who underwent TACE of the right IPA using NBCA were retrospectively reviewed and compared with data from 135 patients with IPA embolization using gelatin sponge particles. Results The incidence of diaphragmatic weakness after the initial TACE procedure did not significantly differ between the groups (NBCA group 16.2%; gelatin sponge group 20.7%; P = 0.458). Five patients in the NBCA group and 11 in the gelatin sponge group showed spontaneous resolution of diaphragmatic weakness after a mean period of 3.5 months. Diaphragmatic weakness developed after the initial follow-up visit in 17 patients from the gelatin sponge group due to repeated TACE of the right IPA (mean 2.4 sessions; range 2–4 sessions), while it spontaneously developed without additional TACE procedures in one patient from the NBCA group. Permanent diaphragmatic weakness was less common in the NBCA than in the gelatin sponge group (12.6% and 25.2%, respectively; P = 0.017). The complete response rate did not significantly differ between the groups (NBCA group 16.2%; gelatin sponge group 25.9%; P = 0.065). Conclusion Use of NBCA rather than gelatin sponge particles for TACE of the right IPA resulted in a lower incidence of permanent diaphragmatic weakness.

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