Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

Casadei-Gardini, Andrea; Scarpi, Emanuela; Faloppi, Luca; Scartozzi, Mario; Silvestris, Nicola; Santini, Daniele; Stefano, G. de; Marisi, Giorgia; Negri, Francesca; Foschi, Francesco Giuseppe; Valgiusti, Martina; Ercolani, Giorgio; Frassineti, Giovanni Luca

doi:10.18632/oncotarget.11565

Cited by 94 publications

(85 citation statements)

References 27 publications

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“…Unfortunately, specific inflammation markers, such as the systemic immune-inflammation index (SII) or neutrophil-to-lymphocyte ratio (NLR) [28], or adjuvant pharmacological treatments (such as antidiabetic drugs) [29] able to influence regorafenib outcomes have not been studied yet and this aspect should represent a further research field in the future.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Facciorusso

Aziz

Sacco

2019

Cancers

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Regorafenib showed promising results as a second-line agent after sorafenib failure in hepatocellular carcinoma patients. The aim of this meta-analysis was to evaluate the efficacy and safety of regorafenib in hepatocarcinoma patients. A computerized bibliographic search was performed on the main databases. The primary outcome was overall survival. Secondary outcomes were progression-free survival, tumor response, and the adverse events rate. Outcomes were pooled through a random-effects model and summary estimates were expressed in terms of median and 95% confidence interval or rates, as appropriate. One randomized-controlled trial and seven non-randomized studies with 809 patients were included. The great majority of recruited patients were in Child-Pugh A and ECOG 0 stage. Median overall survival was 11.08 months (9.46-12.71) and sensitivity analyses confirmed this finding, with a median survival ranging from 10.2 to 13.8 months. Duration of regorafenib therapy was 3.58 months, whereas median progression-free survival was 3.24 months (2.68-3.86). The pooled objective response rate was 10.1% (7.8-12.5%) while the disease control rate was 65.5% (61.3-69.7%) with no evidence of heterogeneity (I 2 = 0%; Diarrhea, fatigue, and hand-foot skin reaction were the most frequent adverse events. The current meta-analysis shows that regorafenib represents a valuable and relatively safe therapeutic option in intermediate/advanced hepatocellular carcinomapatients who progress on sorafenib.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Facciorusso

Aziz

Sacco

2019

Cancers

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“…However, it is known that these values may be treatment-dependent even in patients with the same disease. For example, SII > 330 × 10 9 /L was reported to be associated with poorer prognosis after curative resection of HCC [21], whereas Casadei et al [24] found that SII of 360 × 10 9 /L was the optimal cut-off value in patients with advanced HCC receiving sorafenib. ROC curve analysis in the present study identified the optimal cut-off value for SII as 230 × 10 9 /L after LT in patients with HCC.…”

Section: Discussionmentioning

confidence: 99%

Systemic Immune-Inflammation Index (SII) is Useful to Predict Survival Outcomes in Patients After Liver Transplantation for Hepatocellular Carcinoma within Hangzhou Criteria

Zheng

Cai

et al. 2018

Cell Physiol Biochem

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Background: There is growing evidence that the systemic immune-inflammation index (SII), a novel prognostic biomarker based on peripheral lymphocyte, neutrophil, and platelet counts, is associated with poor prognosis for several tumors. However, the prognostic value of SII in patients with hepatocellular carcinoma (HCC) who undergo liver transplantation (LT) remains unclear. The aim of this study was to determine the correlation between SII and prognosis in these patients. Methods: This retrospective study involved 150 patients with HCC who underwent LT within the Hangzhou criteria. The optimal cut-off value was determined by receiver-operating characteristic (ROC) curve analysis to stratify the patients into those with a high SII and those with low SII. The Kaplan-Meier method and the Cox proportional hazards model were used to evaluate the prognostic value of SII. Finally, we calculated the area under the ROC curve to compare the prognostic power of SII, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR). Results: Patients were divided into high SII (≥ 226) and low SII (< 226) groups. Five-year overall survival (OS) was lower in the high SII group than in the low SII group (56.1% vs. 82.4%, p = 0.002). SII ≥ 226 × 109/L, maximum tumor size> 5 cm, microvascular invasion, and poor differentiation were independent prognostic factors for OS. However, SII did not predict 5-year recurrence-free survival (high vs. low SII: 64.1% vs. 78.4%, p = 0.073). The area under the ROC curve was greater for SII than for PLR, NLR, and MLR. Conclusions: Preoperative SII may be a powerful prognostic biomarker in patients with HCC who undergo LT within the Hangzhou criteria. SII is superior to PLR, NLR, and MLR for prediction of OS in these patients.

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“…Indeed, it has been shown that CAFs and TGF-β signaling activation contribute to chemotherapy resistance in cancer [41]. Another study showed that HCC patients receiving sorafenib may benefit from immune modulation strategies [42]. Argentiero and colleagues reported that a specific WNT pathway inhibitor may instruct the immune system to increase cytotoxicity in tumor and re-establish the anti-PDAC immunity [43].…”

Section: Discussionmentioning

confidence: 99%

Utilizing Experimental Mouse Model to Identify Effectors of Hepatocellular Carcinoma Induced by HBx Antigen

Yang

Chen

et al. 2020

Cancers

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Hepatocellular carcinoma (HCC) is among the ten most commonly diagnosed cancers and the fourth leading cause of cancer-related death. Patients with hepatitis B virus (HBV) infection are prone to developing chronic liver diseases (i.e., fibrosis and cirrhosis), and the HBV X antigen plays an important role in the development of HCC. The difficulty in detecting HCC at the early stages is one of the main reasons that the death rate approximates the incidence rate. The regulators controlling the downstream liver protein expression from HBV infection are unclear. Mass spectrometric techniques and customized programs were used to identify differentially expressed proteins which may be involved in the development of liver fibrosis and HCC progression in hepatitis B virus X protein transgenic mice (HBx mice). FSTL1, CTSB, and TGF-β enhanced the signaling pathway proteins during the pathogenesis of HBx. Missing proteins can be essential in cell growth, differentiation, Cancers 2020, 12, 409 2 of 32 apoptosis, migration, metastasis or angiogenesis. We found that LHX2, BMP-5 and GDF11 had complex interactions with other missing proteins and BMP-5 had both tumor suppressing and tumorigenic roles. BMP-5 may be involved in fibrosis and tumorigenic processes in the liver. These results provide us an understanding of the mechanism of HBx-induced disorders, and may serve as molecular targets for liver treatment.

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Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

Cited by 94 publications

References 27 publications

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Efficacy of Regorafenib in Hepatocellular Carcinoma Patients: A Systematic Review and Meta-Analysis

Systemic Immune-Inflammation Index (SII) is Useful to Predict Survival Outcomes in Patients After Liver Transplantation for Hepatocellular Carcinoma within Hangzhou Criteria

Utilizing Experimental Mouse Model to Identify Effectors of Hepatocellular Carcinoma Induced by HBx Antigen

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