scholarly journals Treatment of Advanced Hepatocellular Carcinoma with Somatostatin Analogues: A Review of the Literature

2019 ◽  
Vol 20 (19) ◽  
pp. 4811
Author(s):  
Hendrik Reynaert ◽  
Isabelle Colle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Receptor Expression ◽  
Surrounding Tissue ◽  
Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by surgery or ablation techniques, but advanced hepatocellular carcinoma remains a challenge for clinicians. Most of these patients have underlying cirrhosis, which complicates or even precludes treatment. Therefore, efficacious treatments without major side effects are welcomed. Initial results of treatment of advanced hepatocellular carcinoma with somatostatin analogues were promising, but subsequent trials have resulted in conflicting outcomes. This might be explained by different patient populations, differences in dosage and type of treatment and differences in somatostatin receptor expression in the tumor or surrounding tissue. It has been shown that the expression of somatostatin receptors in the tumor might be of importance to select patients who could benefit from treatment with somatostatin analogues. Moreover, somatostatin receptor expression in hepatocellular carcinoma has been shown to correlate with recurrence, prognosis, and survival. In this review, we will summarize the available data on treatment of primary liver cancer with somatostatin analogues and analyze the current knowledge of somatostatin receptor expression in hepatocellular carcinoma and its possible clinical impact.

scholarly journals Somatostatin receptor expression in hepatocellular carcinoma: prognostic and therapeutic considerations

2014 ◽  
Vol 21 (6) ◽  
pp. R485-R493 ◽  
Author(s):  
Omar Abdel-Rahman ◽  
Angela Lamarca ◽  
Juan W Valle ◽  
Richard A Hubner
Keyword(s):  
Hepatocellular Carcinoma ◽  
Therapeutic Potential ◽  
Somatostatin Receptor ◽  
Molecular Targets ◽  
Predictive Biomarkers ◽  
Somatostatin Analogues ◽  
Receptor Expression ◽  
Advanced Hepatocellular Carcinoma ◽  
Significant Survival ◽  
Randomised Controlled

Sorafenib is the only systemic therapy to demonstrate a significant survival benefit over supportive care in robust randomised controlled trials for advanced hepatocellular carcinoma (HCC). In the context of an intense search for prognostic and predictive factors for response and efficacy of different systemic therapies (including sorafenib), a number of molecular targets have been identified, paving new avenues for potential therapeutic opportunities. Such molecular targets include somatostatin receptor (SSTR)-related alterations. In this review, we provide an overview of the various considerations relating to SSTRs as potentially novel prognostic and predictive biomarkers for HCC with special emphasis on the therapeutic potential of somatostatin analogues in HCC management.

scholarly journals Surgery for Intermediate and Advanced Hepatocellular Carcinoma: A Consensus Report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)

Liver Cancer ◽  
2016 ◽  
Vol 5 (4) ◽  
pp. 245-256 ◽  
Author(s):  
Ming-Chih Ho ◽  
Kiyoshi Hasegawa ◽  
Xiao-Ping Chen ◽  
Hiroaki Nagano ◽  
Young-Joo Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Primary Liver Cancer ◽  
Asia Pacific ◽  
Advanced Hepatocellular Carcinoma ◽  
Expert Meeting ◽  
Consensus Report

scholarly journals 452 Preliminary analysis of a real-world study (RWS) of camrelizumab treatment in primary liver cancer (PLC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A479-A480
Author(s):  
Zhendong Chen ◽  
Nianfei Wang ◽  
Dayong Luo ◽  
Bo Jiang ◽  
Mu Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Group Performance ◽  
Primary Liver Cancer ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Open Label ◽  
Patient Disposition ◽  
Ecog Ps

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the landscape of PLC management at all evolutionary stages.1 As an anti-programmed cell death-1 (PD-1) antibody, camrelizumab monotherapy and in combination with apatinib, an anti-angiogenetic tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-2, chemotherapy or locoregional therapy, have demonstrated their efficacy in advanced hepatocellular carcinoma (HCC).2 3 4 5MethodsThis prospective, open-label, multi-center, observational RWS was conducted to evaluate efficacy and safety of camrelizumab in treatment of PLC in clinical practice. Eligible patients were histopathologically or cytologically identified HCC or intrahepatic cholangiocarcinoma, who were going to receive camrelizumab treatment, with age ≥18 ages, Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0–2 and Child-Pugh score ≤ 9. Patients were treated at clinician discretion. Three hundred patients were planned to enroll, including advanced or peri-operative PLC. The primary endpoint was progress-free survival for advanced PLC, whose efficacy was available to analysis. Efficacy was assessed per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom March 29, 2020 to June 10, 2021,a total of 147 eligible patients of advanced PLC were enrolled and included in this interim analysis, with 128 (87.1%) men, 130 (94.9%) ECOG PS of 0–1, 139 (94.6%) HCC, 74 (50.4%) Barcelona Clinic Liver Cancer stage C, 98 (66.7%) Child-Pugh B, and 72 (49.0%) with extrahepatic metastases, shown in table 1. Of the 147 patients, 45 (30.1%) patients were treated with camrelizumab monotherapy, 79 (53.8%) patients with combination with angiogenesis inhibitors, of which 55 (37.4%) in combination with apatinib, 21 (14.3%) patients with camrelizumab and chemotherapy. Patients, who had at least one efficacy assessment, were included in the efficacy analyses. Up to July 19, 2021, with a median follow time of 6.2 months, 132 patients were available for efficacy analyses. Patient disposition was shown in figure 1. Objective response rate (ORR) and disease control rate (DCR) were 10%/30.8%/35.3% and 75.0%/86.5%/70.6% in camrelizumab monotherapy/combined with apatinib/combined with chemotherapy, respectively. (table 2) The most common camrelizumab-treatment related adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (12, 8.2%), ICI-induced pneumonia (2, 1.4%), enterocolitis (2, 1.4%), and nephritis (1, 0.7%), of which all these AEs recovered. Other AEs included increase of transaminase (5, 3.4%) and hypertension (4, 2.7%). All AEs were 1–2 grade and no treatment-related death occurred.Abstract 452 Table 1Baseline characteristicsAbstract 452 Figure 1Patient dispositionAbstract 452 Table 2Confirmed tumor response assessed by investigators per RECIST v1.1ConclusionsCamrelizumab, combined with anti-angiogenetic agents or chemotherapy, or monotherapy, demonstrated good efficacy and safety in treatment of PLC.Trial RegistrationChiCTR2000034264ReferencesLlovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7(1):6–28.Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol 2020;21(4):571–580.Xu J, Shen J, Gu S, et al. Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res 2021;27(4):1003–1011.Mei K, Qin S, Chen Z, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. J Immunother Cancer 2021;9(3).Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol 2013;31(28):3501–3508.Ethics ApprovalThis study was approved by China registered clinical trial ethics review committee with No.ChiECRCT20200042.

scholarly journals Outcome of Sorafenib Therapy in Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 15 (1) ◽  
pp. 16-18
Author(s):  
Md Niamul Gani Chowdhury ◽  
Md Azizul Islam
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Cancer ◽  
Median Overall Survival ◽  
Primary Liver Cancer ◽  
Armed Forces ◽  
Oral Drug ◽  
Advanced Hepatocellular Carcinoma ◽  
Hepatitis C Infection ◽  
Medical College

Introduction: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It occurs most often in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection. It is the fifth most common liver cancer globally and also a common cancer in Bangladesh. Treatment is difficult; however newer oral drug Sorafenib is available in our country which is promising. Objectives: To evaluate the efficacy of TKI Sorafenib on advanced and non-resect able primary HCC in Bangladeshi patients. Materials and Methods: This clinical trial was conducted on 38 diagnosed patients of advanced hepatocellular carcinoma (stage-3 and Child-Pugh Class-C) over a period of 3 years from May 2014 to July 2017 in the department of Oncology, CMH Dhaka. The patients receive Sorafenib 200-400 mg twice daily till disease progression ceases or increases and there are no unacceptable toxicities. Efficacy was observed in terms of overall survival, progressive free survival (PFS), drug compliance and common toxicities. Results: In 24 months of follow –up period from the date of Sorafenib taken, median overall survival was 7.73 months. The median overall survival was 8 months (range 8.13-27.43 months) in 42.4% patients. The median PFS is 3.5 months (range 1.2-5.8 months). Common toxicities found were anorexia, weakness, yellow colouration of skin and mucosa, HTN, rash and diarrhoea. Conclusion: In Sorafenib treated Bangladeshi advanced HCC patients, the median overall survival was found to be significant and compatible with some of the international publication. Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 16-18

scholarly journals Translational Considerations to Improve Response and Overcome Therapy Resistance in Immunotherapy for Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2495
Author(s):  
Sophia Heinrich ◽  
Darko Castven ◽  
Peter R. Galle ◽  
Jens U. Marquardt
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Objective Response ◽  
Response Rates ◽  
Therapy Resistance ◽  
Phase Iii ◽  
Treatment Modalities ◽  
Molecular Characteristics

Over the last decade, progress in systemic therapies significantly improved the outcome of primary liver cancer. More recently, precision oncological and immunotherapeutic approaches became the focus of intense scientific and clinical research. Herein, preclinical studies showed promising results with high response rates and improvement of overall survival. However, results of phase III clinical trials revealed that only a subfraction of hepatocellular carcinoma (HCC) patients respond to therapy and display only moderate objective response rates. Further, predictive molecular characteristics are largely missing. In consequence, suitable trial design has emerged as a crucial factor for the success of a novel compound. In addition, increasing knowledge from translational studies indicate the importance of targeting the tumor immune environment to overcome resistance to immunotherapy. Thus, combination of different immunotherapies with other treatment modalities including antibodies, tyrosine kinase inhibitors, or local therapies is highly promising. However, the mechanisms of failure to respond to immunotherapy in liver cancer are still not fully understood and the modulation of the immune system and cellular tumor composition is particularly relevant in this context. Altogether, it is increasingly clear that tailoring of immunotherapy and individualized approaches are required to improve efficacy and patient outcome in liver cancer. This review provides an overview of the current knowledge as well as translational considerations to overcome therapy resistance in immunotherapy of primary liver cancer.

scholarly journals Profiling of tumour-associated microbiota in human hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seiga Komiyama ◽  
Takahiro Yamada ◽  
Nobuyuki Takemura ◽  
Norihiro Kokudo ◽  
Koji Hase ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Fatty Liver Disease ◽  
Primary Liver Cancer ◽  
Epithelial Barrier ◽  
Sequence Variants ◽  
Alcoholic Fatty Liver ◽  
Uncultured Bacterium ◽  
Hepatitis C Viruses ◽  
Alcoholic Fatty Liver Disease

AbstractLiver cancer is the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is a primary liver cancer that results from chronic hepatitis caused by multiple predisposing factors such as viral infection, alcohol consumption, and non-alcoholic fatty liver disease. Accumulating studies have indicated that dysfunction of the gut epithelial barrier and hepatic translocation of gut microbes may be implicated in the pathogenesis of HCC. However, the translocated bacteria in HCC patients remains unclear. Here, we characterised tumour-associated microbiota in patients with liver cancer and focused on HCC. We observed that the number of amplicon sequence variants in tumour-associated microbiota was significantly higher compared with that in non-tumour regions of the liver. The tumour-associated microbiota consisted of Bacteroidetes, Firmicutes, and Proteobacteria as the dominant phyla. We identified an unclassified genus that belonged to the Bacteroides, Romboutsia, uncultured bacterium of Lachnospiraceae as a signature taxon for primary liver cancer. Additionally, we identified Ruminococcus gnavus as a signature taxon for HCC patients infected with hepatitis B and/or hepatitis C viruses. This study suggests that tumour microbiota may contribute to the pathology of HCC.

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