How I Treat Early-Stage Hepatocellular Cancer With Local Nonsurgical Approaches (Radiation)

2019 ◽  
Author(s):  
Jonathan B. Ashman
Keyword(s):  
Early Stage ◽  
Hepatocellular Cancer

scholarly journals Novel extracellular RNA biomarkers for early stage hepatocellular cancer

ExRNA ◽  
2021 ◽  
Vol 0 ◽  
pp. 0-0
Author(s):  
Piyush Gondaliya ◽  
Tushar Patel
Keyword(s):  
Early Stage ◽  
Hepatocellular Cancer ◽  
Extracellular Rna ◽  
Rna Biomarkers

scholarly journals PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
David J. Pinato ◽  
Alessio Cortellini ◽  
Ajithkumar Sukumaran ◽  
Tom Cole ◽  
Madhava Pai ◽  
...  
Keyword(s):  
Liver Resection ◽  
Early Stage ◽  
Objective Response ◽  
Hepatocellular Cancer ◽  
Preliminary Evidence ◽  
Primary Objective ◽  
Cancer Therapies ◽  
Clinical Trial Registry ◽  
Phase Ib ◽  
Link Type

Abstract Background After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC. Methods The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC. Discussion The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population. Trial registration EudraCT Number: 2018–000987-27 Clinical trial registry & ID: ClinicalTrials.gov: NCT03682276.

scholarly journals The Potential of Serum Exosomal hsa_circ_0028861 as the Novel Diagnostic Biomarker of HBV-Derived Hepatocellular Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuanxiao Wang ◽  
Lin Pei ◽  
Zhihong Yue ◽  
Mei Jia ◽  
Hui Wang ◽  
...  
Keyword(s):  
Early Stage ◽  
Hepatocellular Cancer ◽  
Circular Rnas ◽  
The Novel ◽  
Diagnostic Biomarker ◽  
Diagnostic Ability ◽  
Highly Sensitive ◽  
B Virus ◽  
Chronic Hbv ◽  
Serum Exosomes

Hepatitis B virus (HBV)-derived hepatocellular cancer (HCC) is a serious threat to human health, especially in China. There is no highly sensitive and specific HCC biomarker at present, which makes it difficult to detect HCC at the early stage. Serum exosomal circular RNAs (circRNAs) have been reported as novel diagnostic and prognostic biomarkers of cancers. In the present study, we aimed to explore the diagnostic performance of serum exosomal circRNAs for HBV-derived HCC screening. At first, many circRNAs were found to be differentially expressed in the serum exosomes of HCC individuals by microarray analysis. The validation of dysregulated circRNAs by qRT-PCR revealed that serum exosomal hsa_circ_0028861 was decreased in HCC compared to chronic HBV and cirrhosis. Then, hsa_circ_0028861 was identified as a novel biomarker for HCC diagnosis with an area under the ROC curve (AUC) of 0.79 for discriminating HCC from chronic HBV and cirrhosis individuals. Hsa_circ_0028861 was capable of detecting small (AUC = 0.81), early-stage (AUC = 0.82) and AFP-negative [AFP (−)] (AUC = 0.78) tumors as well. The combination of hsa_circ_0028861 and AFP exhibited better diagnostic ability (AUC = 0.86 for discriminating HCC from chronic HBV and cirrhosis). Moreover, bioinformatics prediction suggested that hsa_circ_0028861 might influence HCC progression by regulating its targeted microRNAs (miRNAs) and downstream tumor-related signaling pathways. Collectively, our study reveals a novel diagnostic tool for HBV-derived HCC.

Association of high histone H3K4 trimethylation level and prognosis of patients with low-TNM-stage hepatocellular carcinoma.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 171-171 ◽  
Author(s):  
Junyao Xu ◽  
Chuanchao He ◽  
Jianlong Zhang ◽  
Jie Wang
Keyword(s):  
Tumor Tissue ◽  
Early Stage ◽  
Prognostic Significance ◽  
Hepatocellular Cancer ◽  
Histone Methyltransferase ◽  
Epigenetic Alterations ◽  
Cellular Expression ◽  
Kaplan Meier ◽  
Enhanced Expression ◽  
Histone H3k4

171 Background: Along with genetic events, tumor associated epigenetic alterations including DNA methylation and post-translational histone modifications are important determinants in the initiation and progression of hepatocellular cancer (HCC) and represent promising biomarkers and therapeutic targets. Locus-specific trimethylation of histone H3 lysine 4 (H3K4me) is a well-known modification linked to the enhanced transcriptional expression of many genes activated in HCC. However its expression and association with prognosis of HCC patients remain unclear. Our aim was to assess the cellular expression pattern of H3K4me3 in HCC and its association with clinicopathologic variables and outcome. Methods: Expression of H3K4me3 and the histone methyltransferase SMYD3 was studied by western blotting and immunohistochemistry in human HCC cell lines and tumor tissue micmicroarray, which is from a well–characterized series of HCC patients(n=168). Tissue staining were assessed using blinded semiquantitative scoring. The optimal cut-point of H3K4me3 expression for prognosis was determined by the X-tile program. The prognostic significance was evaluated using Kaplan-Meier survival estimates and log-rank tests. Tumor tissue micmicroarray from another independent HCC patients cohort(n=147) was used for validation studies. Results: Expression of H3K4me3 and the histone methyltransferase SMYD3 were enhanced in HCC cell lines.In clinical tumor specimens, enhanced expression of H3K4me3 was correlated with reduced overall survival (P < 0.0001), especially in early-stage HCC patients(TNM I/II).Furthermore,both univariate and multivariate analysis revealed that H3K4me3 level was a significant and independent predictor of poor survival (hazard ratio,3.592; 95% CI, 2.302-5.605). In addition, H3K4m3 expression was positively correlated with SMYD3 expression in both testing and validation cohorts (P<0.0001). Conclusions: H3K4me3 level defines previously unrecognized subsets of HCC patients with distinct epigenetic phenotype and clinical outcome, thus can be a novel predictor for poor prognosis of HCC patients, especially within TNM I/IIstage.

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