Surgical and Locoregional Therapy of HCC: TACE

Tsurusaki, Masakatsu; Murakami, Takamichi

doi:10.1159/000367739

Cited by 173 publications

(141 citation statements)

References 48 publications

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“…There are unmet needs in HCC management in various settings, including neoadjuvant or adjuvant therapy with resection or ablation, combination of anti-PD-1 antibody with transcatheter arterial chemoembolization (TACE) [37,38], and first-and second-line treatment. The immune checkpoint-inhibiting anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies may prove useful for adjuvant therapy or combination therapy in all these settings.…”

Section: Future Perspectivesmentioning

confidence: 99%

Immune Checkpoint Blockade in Hepatocellular Carcinoma: 2017 Update

Kudo¹

2016

Liver Cancer

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releasing molecules such as perforin and granzymes (the effector phase) (fig 1) [10]. Moreover, recognition of TAAs by T cell receptors (TCR) triggers the release of interferon gamma (IFN-γ) and other cytokines by CD8-positive T cells in an attempt to attack the cancer. However, tumor cells protect themselves by expressing IFN-γ induced PD-L1 or PD-L2, which binds to PD-1. When this happens, PD-1/PD-L1 binding attenuate the antitumor immune response, thereby weakening the attacking power of the T cells. This is called immune escape or immune tolerance ( fig. 2). The anti-PD-1 antibody blocks PD-1 on activated T cells from binding to PD-L1 or PD-L2 on APCs or tumor cells. This removes the "brake" on the immune system and restores the ability of T cells to attack tumor cells ( fig. 3). Unlike conventional chemotherapy or molecular targeted therapy, anti-PD-1 antibody achieves its antitumor effect by restoring the original potential of the natural human immune system as a powerful and precise weapon against cancer cells [11][12][13][14][15][16][17][18][19][20][21][22]. Antibodies against PD-L1 expression in the cancer tissue are believed to have a similar effect [23]. The recognition of "immuno-oncology" using immune checkpoint inhibitors was considered the "Breakthrough of the Year" by the American journal Science in 2013, and immuno-oncology has been widely publicized. PD-L1 also serves as a biomarker that predicts the response to anti-PD-1 antibody [24]. In addition, Kupffer-phase Sonazoid contrast-enhanced ultrasonography is an effective imaging method for predicting the response to treatment with anti-PD-1 antibody [25]. Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma (HCC)Promising results from an interim analysis of a phase I/II trial of the anti-PD-1 antibody nivolumab (CheckMate-040 trial dose-escalation cohort) were presented at the

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Section: Future Perspectivesmentioning

confidence: 99%

Immune Checkpoint Blockade in Hepatocellular Carcinoma: 2017 Update

Kudo¹

2016

Liver Cancer

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“…According to this algorithm, sorafenib is indicated for patients diagnosed with Child-Pugh class A HCC with extrahepatic spread or vascular invasion. Sorafenib is also recommended for patients with Child-Pugh class A HCC where transcatheter arterial chemoembolization (TACE) [7][8][9][10][11] and hepatic arterial infusion chemotherapy [12,13] are not indicated. In the present study, we examined the efficacy of sorafenib treatment and the clinical outcome in 314 patients at 5 general hospitals in Kagawa Prefecture, Japan.…”

Section: Introductionmentioning

confidence: 99%

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study

et al. 2017

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87.3-170.7) and the median overall survival (OS) was 392 days (95% CI: 316.0-468.0). The OS of the patients with ChildPugh class A HCC was significantly better than that of the patients with Child-Pugh class B HCC ( p < 0.0001). The survival curves for Child-Pugh class A-5 points and class A-6 points were significantly different, with that for class A-5 points being better ( p < 0.0001). A significant difference was observed between the patients who exhibited HFS and those who did not, with the former exhibiting a better survival rate ( p < 0.001). In addition, the survival rate of the patients who received post-progression treatment after sorafenib therapy was significantly better than that of the patients who did not ( p < 0.001). Conclusion: In sorafenib therapy, patients with HFS and those who received post-progression treatment exhibited good OS. © 2017 S. Karger AG, BaselKeywords Hepatocellular carcinoma · Sorafenib · Hand-foot syndrome Abstract Objective: To determine the relationship between treatment outcomes and hand-foot syndrome (HFS), and the relationship between survival rate and post-progression treatment after sorafenib therapy. Methods: The study assessed 314 patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib at 5 general hospitals in Kagawa Prefecture, Japan. Results: At the start of sorafenib therapy, 23.6% of the patients had HCC of a Child-Pugh class other than A. The initial sorafenib dose was 800 mg in 9.2% of the patients and 400 mg in 64.3%. Time to progression was 129 days (95% CI:

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“…In 2007, sorafenib was approved in the EU and USA, where it became a first-line agent for unresectable advanced HCC. Transarterial chemoembolization (TACE) is the first-line treatment option for intermediate-stage HCC [3][4][5][6] ; however, repeated TACE sessions tend to impair liver functional reserve. Reducing the frequency of TACE, which is generally repeated upon tumor progression, is a challenging issue in the treatment of patients with intermediate-stage HCC.…”

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confidence: 99%

Transarterial Chemoembolization in Combination with a Molecular Targeted Agent: Lessons Learned from Negative Trials (Post-TACE, BRISK-TA, SPACE, ORIENTAL, and TACE-2)

Kudo

Arizumi²

2017

Oncology

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sessment Randomized Protocol (SHARP) and Asia-Pacific studies [1,2] . In 2007, sorafenib was approved in the EU and USA, where it became a first-line agent for unresectable advanced HCC. Transarterial chemoembolization (TACE) is the first-line treatment option for intermediate-stage HCC [3][4][5][6] ; however, repeated TACE sessions tend to impair liver functional reserve. Reducing the frequency of TACE, which is generally repeated upon tumor progression, is a challenging issue in the treatment of patients with intermediate-stage HCC. To address this issue, previous trials combined molecular targeted agents with TACE; however, the safety and efficacy of this combination could not be demonstrated, and none of the combination therapies is currently recommended.In the SHARP study, subanalysis showed that the hazard ratio (HR) for overall survival (OS) in patients with HCC with no vascular invasion or extrahepatic spread, which are regarded as good indications for TACE, was 0.52 and, thus, extremely good in the sorafenib group. The median survival of these patients was extended approximately 1.5-fold [7] , suggesting that the addition of sorafenib as adjuvant therapy to TACE improves prognosis. The combination of TACE with sorafenib does not simply represent the administration of 2 types of treatment; the combination is expected to extend the period during which TACE controls tumor progression because sorafenib strongly suppresses post-TACE tumor recur- AbstractThe multikinase inhibitor sorafenib is the first oral molecular targeted agent with proven prognostic benefit in unresectable advanced hepatocellular carcinoma (HCC). However, as with other drugs, sorafenib has its limitations, and various clinical trials have been conducted to develop novel molecular targeted agents for use alone or in combination with existing locoregional therapies. Despite this, clinical trials of molecular targeted agents combined with transarterial chemoembolization (TACE) have not reported major treatment outcomes to date. In this review, we describe previous clinical trials of combination therapy with TACE and a molecular targeted agent in patients with unresectable HCC.

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Surgical and Locoregional Therapy of HCC: TACE

Cited by 173 publications

References 48 publications

Immune Checkpoint Blockade in Hepatocellular Carcinoma: 2017 Update

Immune Checkpoint Blockade in Hepatocellular Carcinoma: 2017 Update

Hand-Foot Syndrome and Post-Progression Treatment Are the Good Predictors of Better Survival in Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Multicenter Study

Transarterial Chemoembolization in Combination with a Molecular Targeted Agent: Lessons Learned from Negative Trials (Post-TACE, BRISK-TA, SPACE, ORIENTAL, and TACE-2)

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