Management of HCC

Lope, Carlos Rodríguez de; Tremosini, Silvia; Forner, Alejandro; Reig, María; Bruix, Jordi

doi:10.1016/s0168-8278(12)60009-9

Cited by 543 publications

(506 citation statements)

References 174 publications

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“…1 Resection is still the main choice of treatment for patients with early stage HCC and well-compensated liver function. 2 Unfortunately, recurrence after resection occurs in up to 80% of patients within five years following surgery, which together with concomitant hepatic decompensation, are the main causes of death.…”

Section: Introductionmentioning

confidence: 99%

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

Xu¹,

Wang²,

Kim

et al. 2015

OncoImmunology

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Background & Aims: There is no generally accepted adjuvant therapy for hepatocellular carcinoma (HCC) after curative resection. Autologous cytokine-induced killer (CIK) cells therapy has been reported to improve outcomes of patients with HCC, but its role as an adjuvant therapy remains unclear. This study aimed to evaluate the efficacy and safety of CIK as an adjuvant therapy for HCC after curative resection.Methods: This is a single center, phase 3, open label, randomized controlled trial (RCT). Two hundred patients who were initially diagnosed with HCC of Barcelona Clinic Liver Cancer (BCLC) stage A or B, and underwent curative hepatectomy were randomly assigned to receive four cycles of CIK treatment (the CIK group, n D 100) or no treatment (the control group, n D 100). The primary outcome was time to recurrence. The secondary outcomes included disease-free survival (DFS), overall survival (OS) and adverse events.Results: All patients in the CIK group finished the treatment by protocol. The median time to recurrence (TTR) was 13.6 (IQR 6.5-25.2) mo in the CIK group and 7.8 (IQR 2.7-17.0) mo in the control group (p D 0.01). There were no significant differences between the groups in DFS and OS. All adverse events were grade 1 or 2. There were no significant differences in incidence between the two groups.Conclusions: Four cycles of CIK therapy were safe and effective to prolong the median TTR in patients with HCC after curative resection, but the treatment did not improve the DFS and OS.

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Section: Introductionmentioning

confidence: 99%

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

Xu¹,

Wang²,

Kim

et al. 2015

OncoImmunology

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“…This is partly due to a lack of effective chemotherapeutic options for patients with advanced-stage disease [3]. Various molecular profiling approaches have been used to identify potential therapeutic targets which are specifically activated in HCC [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

Nio

Yamashita

Okada

et al. 2015

Journal of Hepatology

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Background & Aims: Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM + liver cancer stem cells. Methods: Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of CHD4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. Results: CHD4 was abundantly expressed in EpCAM + hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of CHD4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM + liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model.Conclusions: CHD4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma. Ó

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“…Hepatocellular carcinoma (HCC) is a major health problem; it is the fifth most common type of cancer worldwide and the third most common cause of cancer-related mortality (1)(2)(3). The prognosis for untreated HCC is generally poor and the curative treatments for this disease consist of surgical resection, radiofrequency ablation and liver transplantation (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…The prognosis for untreated HCC is generally poor and the curative treatments for this disease consist of surgical resection, radiofrequency ablation and liver transplantation (1)(2)(3). Non-curative therapies for HCC include transcatheter arterial chemoembolization (TACE), transcatheter arterial chemotherapy infusion (TACI), continuous arterial chemoinfusion therapy, radioembolization, molecular targeting therapies such as sorafenib and radiation therapy (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Comparison of transcatheter arterial chemoembolization and transcatheter arterial chemotherapy infusion for patients with intermediate-stage hepatocellular carcinoma

et al. 2013

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Abstract. The aim of the present study was to compare clinical outcomes in patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent the following treatments: transcatheter arterial chemoembolization (TACE) using an epirubicin-mitomycin-lipiodol (EML) emulsion at initial therapy (TACE group; n=145), and transcatheter chemotherapy infusion (TACI) using an EML emulsion at initial therapy (TACI group; n=81). Overall survival (OS) and treatment efficacy in the TACE and TACI groups were retrospectively compared. Prognostic factors associated with OS were examined using univariate and multivariate analyses. Treatment-related mortality was also calculated. The median observation periods were 1.8 years (range, 0.2-9.0 years) in the TACE group and 2.0 years (range, 0.2-8.7 years) in the TACI group. The median survival time and the 1-, 2-, 3-and 5-year cumulative OS rates were 2.68 years and 81.5, 63.4, 43.9 and 32.7%, respectively, in the TACE group, and 2.64 years and 85.0, 60.0, 43.2 and 26.0%, respectively, in the TACI group (P=0.691). The objective response rate was significantly higher in the TACE group compared to the TACI group (80.0 vs. 66.7%; P=0.009). Using multivariate analysis, the Child-Pugh classification (P= 0.017), tumor number ≤5 (P= 0.045) and des-γ-carboxy prothrombin level >100 mAU/ml (P=0.002) were found to be significant predictors linked to OS. In all subgroup analyses involving Child-Pugh classification, maximum tumor size and tumor distribution, the differences in the two groups did not reach statistical significance in terms of OS. Treatment mortality was 0% in the two groups. In conclusion, patients with intermediate-stage HCC had a comparable prognosis when treated with TACI or TACE. IntroductionHepatocellular carcinoma (HCC) is a major health problem; it is the fifth most common type of cancer worldwide and the third most common cause of cancer-related mortality (1-3). The prognosis for untreated HCC is generally poor and the curative treatments for this disease consist of surgical resection, radiofrequency ablation and liver transplantation (1-3). Non-curative therapies for HCC include transcatheter arterial chemoembolization (TACE), transcatheter arterial chemotherapy infusion (TACI), continuous arterial chemoinfusion therapy, radioembolization, molecular targeting therapies such as sorafenib and radiation therapy (1-12).TACE is a procedure whereby an embolic agent is injected into the tumor feeding artery to deprive it of its major nutrient source by means of embolization; this results in ischemic necrosis of the targeted tumor (11,12). The survival benefit of TACE for unresectable HCC was established in two randomized controlled trials (RCTs) and in one meta-analysis (13-15). Thus, TACE plays an important role in treating unresectable HCC. It is clearly defined as a first-line therapy with an improved 2-year survival rate as compared with conservative therapy (16).The Barcelona Clinic Liver Cancer (BCLC) classification is regarded as one of the most reliable staging an...

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Management of HCC

Cited by 543 publications

References 174 publications

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

A randomized controlled trial on patients with or without adjuvant autologous cytokine-induced killer cells after curative resection for hepatocellular carcinoma

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

Comparison of transcatheter arterial chemoembolization and transcatheter arterial chemotherapy infusion for patients with intermediate-stage hepatocellular carcinoma

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