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Systematic literature review of trials assessing recommended systemic treatments in hepatocellular carcinoma. 肝细胞癌推荐系统治疗试验的系统文献综述。
IF 5 Pub Date : 2021-08-26 DOI: 10.2217/hep-2021-0003
Sarah Ronnebaum, Abdalla Aly, Dipen Patel, Fernando Benavente, Juan-David Rueda

Aim: To identify and evaluate the similarity of all trials assessing recommended treatments for advanced hepatocellular carcinoma.

Materials & methods: Single arm and randomized trials from any phase and published any time up to February 2021 were systematically searched.

Results: From 5677 records reviewed, 50 trials were included in the review, and 24 for assessed for similarity. In the first-line (1L) setting, several trials assessing sorafenib were noted for enrolling patients with more severe disease and/or performance status than other 1L trials; trials within the second-line (2L) setting were generally similar. Median survival was <2 years in all trial arms.

Conclusions: Trials assessing recommended treatments are largely similar and appropriate for quantitative comparisons of several efficacy and safety outcomes.

目的:确定和评估所有评估晚期肝细胞癌推荐治疗方法的试验的相似性。材料和方法:系统检索截至2021年2月任何时候发表的任何阶段的单臂和随机试验。结果:在审查的5677份记录中,50项试验被纳入审查,24项用于评估相似性。在一线(1L)环境中,与其他1L试验相比,评估索拉非尼的几项试验被注意到招募了疾病和/或表现状态更严重的患者;在二线(2L)环境中的试验通常是相似的。中位生存率是结论:评估推荐治疗的试验在很大程度上相似,适合于对几种疗效和安全性结果进行定量比较。
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引用次数: 2
Evaluation of tumor mutational burden in small early hepatocellular carcinoma and progressed hepatocellular carcinoma. 早期小肝癌和进展性肝癌肿瘤突变负荷的评价。
IF 5 Pub Date : 2021-08-03 eCollection Date: 2021-12-01 DOI: 10.2217/hep-2020-0034
Mary Wong, Jong T Kim, Brian Cox, Brent K Larson, Stacey Kim, Kevin M Waters, Eric Vail, Maha Guindi

While researchers know that tumor mutational burden (TMB) is low in hepatocellular carcinoma (HCC), prior studies have not investigated TMB in cirrhosis, small early HCC and progressed HCC. HCC (n = 18) and cirrhosis (n = 6) cases were identified. TMB was determined by a 1.7 megabase, 409-gene next-generation sequencing panel. TMB values were defined as the number of nonsynonymous variants per megabase of sequence. There was no significant difference between cirrhosis versus small early HCC or between cohorts when stratified by size, early versus progressed, differentiation or morphology. There was a significant difference between cirrhosis and small early HCC versus progressed HCC (p = 0.045), suggesting TMB may be related to HCC progression. TMB similarities in small early HCC and background cirrhosis suggest TMB is not a useful tool for diagnosing small early HCC. Additional study is needed to address TMB in histological and molecular subsets of HCC.

虽然研究人员知道肝细胞癌(HCC)的肿瘤突变负担(tumor mutational burden, TMB)较低,但之前的研究尚未对肝硬化、早期小肝癌和进展期肝癌的TMB进行研究。肝细胞癌(18例)和肝硬化(6例)。TMB由1.7兆碱基、409个基因的下一代测序面板确定。TMB值被定义为每兆碱基序列的非同义变体的数量。肝硬化与小的早期HCC之间,或按大小、早期与进展、分化或形态分层的队列之间,没有显著差异。肝硬化、小早期HCC与进展性HCC的差异有统计学意义(p = 0.045),提示TMB可能与HCC进展有关。TMB在早期小肝癌和背景肝硬化中的相似性提示TMB不是诊断早期小肝癌的有用工具。需要进一步研究TMB在HCC的组织学和分子亚群中的作用。
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引用次数: 8
Transarterial chemoembolization alone or followed by bevacizumab for treatment of colorectal liver metastases. 经动脉化疗栓塞单独或随后贝伐单抗治疗结肠直肠癌肝转移。
IF 5 Pub Date : 2021-07-13 eCollection Date: 2022-03-01 DOI: 10.2217/hep-2020-0031
Giammaria Fiorentini, Donatella Sarti, Michele Nardella, Riccardo Inchingolo, Massimiliano Nestola, Alberto Rebonato, Caterina Fiorentini, Camillo Aliberti, Roberto Nani, Stefano Guadagni

Aims: Bevacizumab (B) in association with systemic chemotherapy is commonly used for the treatment of colorectal cancer liver metastases. The aim of this study was to monitor tumor response, overall survival (OS) and progression-free survival (PFS) of patients with colorectal cancer liver metastases treated with transarterial chemoembolization (TACE) + B compared with TACE alone and to correlate the results with KRAS mutational status.

Patients & methods: This was an observational multicentric case-control study (NCT03732235) on the efficacy and safety of B administered after TACE.

Results: The disease control rate was significantly higher for the TACE + B than the TACE alone group (p < 0.001). KRAS wild-type patients had a significantly better disease control rate than those with KRAS mutations in the TACE + B group. Median OS and PFS were similar for the TACE + B and TACE groups, whereas median time to progression was significantly higher for the TACE + B group (p < 0.01).

Conclusion: The combination of TACE with B may improve tumor response and delay disease progression.

目的:贝伐单抗(B)联合全身化疗是治疗结直肠癌癌症肝转移的常用药物。本研究的目的是监测经动脉化疗栓塞(TACE)+B与单纯TACE治疗的结直肠癌癌症肝转移患者的肿瘤反应、总生存率(OS)和无进展生存率(PFS),并将结果与KRAS突变状态相关联。患者和方法:这是一项关于TACE后使用B的疗效和安全性的观察性多中心病例对照研究(NCT03732235)。结果:TACE+B组的疾病控制率明显高于单纯TACE组(p KRAS野生型患者的疾病控制效率明显高于TACE+B组中有KRAS突变的患者(p结论:TACE与B联合应用可改善肿瘤反应,延缓疾病进展。
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引用次数: 2
Unresectable hepatocellular carcinoma treatment with doxorubicin-eluting polyethylene glycol microspheres: a single-center experience. 阿霉素洗脱聚乙二醇微球治疗不可切除的肝细胞癌:单中心经验。
IF 5 Pub Date : 2021-06-04 eCollection Date: 2021-09-01 DOI: 10.2217/hep-2020-0035
Gerardo Tovar-Felice, Andrés García-Gámez, Virgilio Benito-Santamaría, David Balaguer-Paniagua, Jordi Villalba-Auñón, Jaume Sampere-Moragues

Background: Transarterial chemoembolization (TACE) is indicated for unresectable hepatocellular carcinoma.

Methods: This was a retrospective study of 50 hepatocellular carcinoma patients treated with TACE using doxorubicin-loaded LifePearl™ to investigate the safety and efficacy of TACE.

Results: There was no 30-day mortality, and limited adverse events were reported. At best tumor response, complete response and disease control were 58% and 94%, respectively, with a median of 4.5 months of follow-up. Median overall survival was 33.8 months. Patients with Barcelona Clinic Liver Cancer stage 0 and stage A at best tumor response showed a higher complete response rate (83%) than patients with Barcelona Clinic Liver Cancer stage B (complete response: 50%; p = 0.0414).

Conclusion: Doxorubicin-loaded LifePearl™ TACE might be an effective treatment, with a good safety profile, for patients with early/intermediate-stage hepatocellular carcinoma. Further prospective data, especially with a small cohort of selected patients, are required to confirm these results.

背景:经动脉化疗栓塞(TACE)适用于不可切除的肝细胞癌。方法:回顾性研究50例接受TACE治疗的肝癌患者,采用负载多柔比星的LifePearl™,探讨TACE的安全性和有效性。结果:无30天死亡率,不良事件有限。最佳肿瘤缓解、完全缓解和疾病控制分别为58%和94%,中位随访时间为4.5个月。中位总生存期为33.8个月。在最佳肿瘤反应时,巴塞罗那临床肝癌0期和A期患者的完全缓解率(83%)高于巴塞罗那临床肝癌B期患者(完全缓解:50%;P = 0.0414)。结论:负载多柔比星的LifePearl™TACE可能是早期/中期肝细胞癌患者的有效治疗方法,具有良好的安全性。需要进一步的前瞻性数据,特别是选择的小队列患者,来证实这些结果。
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引用次数: 3
Locoregional therapy patterns and healthcare economic burden of patients with hepatocellular carcinoma in the USA. 美国肝细胞癌患者的局部治疗模式和医疗经济负担
IF 5 Pub Date : 2021-04-21 eCollection Date: 2021-09-01 DOI: 10.2217/hep-2021-0001
Abdalla Aly, Melissa Lingohr-Smith, Jay Lin, Brian Seal

Aim: To examine the locoregional therapy (LRT) patterns and the healthcare economic burden of patients with hepatocellular carcinoma (HCC) in the USA.

Patients & methods: Patients with newly diagnosed HCC were identified from the MarketScan® databases (1 July 2015-31 May 2018). The LRTs received and all-cause and HCC-related healthcare costs were measured.

Results: Among 2101 patients with HCC, most received embolization therapy as their first LRT treatment (57.8%, n = 1215); 17.1% (n = 360) received ablative therapy and 8.7% (n = 182) radiation therapy; 16.4% (n = 344) received multiple LRTs. After patients received their first LRT treatment, total all-cause healthcare costs averaged $20,316 per patient per month; 70.7% ($14,359) were HCC related.

Conclusion: Among newly diagnosed HCC patients treated with LRT in the USA, the economic burden is high.

目的:探讨美国肝细胞癌(HCC)患者的局部区域治疗(LRT)模式和医疗经济负担。患者和方法:从MarketScan®数据库(2015年7月1日- 2018年5月31日)中确定新诊断的HCC患者。接受的lrt和全因和hcc相关的医疗费用被测量。结果:在2101例HCC患者中,大多数接受栓塞治疗作为首次LRT治疗(57.8%,n = 1215);17.1% (n = 360)接受消融治疗,8.7% (n = 182)接受放射治疗;16.4% (n = 344)接受了多重lrt。在患者接受第一次LRT治疗后,每位患者每月的全因医疗费用平均为20,316美元;70.7%(14359美元)与HCC相关。结论:在美国接受LRT治疗的新诊断HCC患者中,经济负担较高。
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引用次数: 0
A rare histologic subtype of hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma: report of a case. 一种罕见的肝细胞癌的组织学亚型,肉瘤样肝细胞癌:报告1例。
IF 5 Pub Date : 2020-12-29 DOI: 10.2217/hep-2020-0027
Numbereye Numbere, Dongwei Zhang, Diana Agostini-Vulaj

Worldwide, primary liver cancer is the fourth leading cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of HCC with conventional HCC admixed with areas with sarcomatoid morphology. SHC is an aggressive, rapidly growing tumor with unfavorable prognosis. Pedunculated SHC is an uncommon presentation of SHC. Due to its rarity, much remains unknown about the etiopathogenesis, molecular underpinnings, and treatment of SHC. We present a case of an exophytic SHC arising in a background of cirrhosis in an older adult. A resection was performed, but the patient subsequently developed multiple additional intrahepatic metastatic lesions necessitating further treatment with chemotherapy.

在世界范围内,原发性肝癌是癌症死亡的第四大原因。肝细胞癌(HCC)是最常见的原发性肝癌类型。肉瘤样肝细胞癌(SHC)是一种罕见的HCC亚型,通常为常规HCC并伴有肉瘤样形态。SHC是一种侵袭性、快速生长的肿瘤,预后不良。带梗小细胞癌是小细胞癌的罕见表现。由于其罕见性,对SHC的发病机制、分子基础和治疗仍知之甚少。我们提出了一例外生性SHC在肝硬化背景下出现在一个老年人。手术切除,但患者随后出现多个额外的肝内转移性病变,需要进一步的化疗治疗。
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引用次数: 6
Characterizing the mechanism behind the progression of NAFLD to hepatocellular carcinoma. 确定非酒精性脂肪肝发展为肝细胞癌的机制。
IF 1.2 Q4 ONCOLOGY Pub Date : 2020-12-29 DOI: 10.2217/hep-2020-0017
Pierre Nahon, Manon Allaire, Jean-Charles Nault, Valérie Paradis

Hepatocellular carcinoma (HCC) developed in non-alcoholic fatty liver disease (NAFLD) individuals presents substantial clinical and biological characteristics, which remain to be elucidated. Its occurrence in noncirrhotic patients raises issues regarding surveillance strategies, which cannot be considered as cost-effective given the high prevalence of obesity and metabolic syndrome, and furthermore delineates specific oncogenic process that could be targeted in the setting of primary or secondary prevention. In this context, the identification of a genetic heterogeneity modulating HCC risk as well as specific biological pathways have been made possible through genome-wide association studies, development of animal models and in-depth analyses of human samples at the pathological and genomic levels. These advances must be confirmed and pursued to pave the way for personalized management of NAFLD-related HCC.

非酒精性脂肪肝(NAFLD)患者发生的肝细胞癌(HCC)具有重要的临床和生物学特征,这些特征仍有待阐明。由于肥胖和代谢综合征的发病率很高,因此在非肝硬化患者中发生 HCC 引起了有关监控策略的问题,而监控策略不能被视为具有成本效益,此外,它还描述了在一级或二级预防中可以针对的特定致癌过程。在此背景下,通过全基因组关联研究、动物模型的开发以及在病理和基因组水平上对人类样本的深入分析,确定了调节 HCC 风险的遗传异质性以及特定的生物通路。这些进展必须得到证实和继续推进,以便为非酒精性脂肪肝相关 HCC 的个性化管理铺平道路。
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引用次数: 0
Hepatitis B-related hepatocellular carcinoma and stress: untangling the host immune response from clinical outcomes. 乙型肝炎相关的肝细胞癌和应激:从临床结果解开宿主免疫反应
IF 5 Pub Date : 2020-12-29 DOI: 10.2217/hep-2020-0028
Peter D Block, Brianna Shinn, Jin Hyang Kim, Hie-Won Hann

Chronic hepatitis B virus (HBV) infection is a major public health challenge on the global scale. Affecting hundreds of millions worldwide, HBV is a leading risk factor for hepatocellular carcinoma (HCC). Clinical outcomes from chronic HBV infection are varied and appear to be influenced by a complex and dysregulated host immune response. In turn, much attention has been given to the immunologic response to HBV in an effort to identify host factors that lead to the development of HCC. However, the role of nonimmunologic host factors, such as chronic stress, in HBV-related HCC is poorly defined. Indeed, a growing appreciation for the effects of stress on chronic liver diseases raises the question of its role in chronic HBV infection. In this light, the present review will untangle the roles of key host factors in HBV-related HCC with an emphasis on chronic stress as a viable contributor. First discussed is the interplay of stress, inflammation and chronic liver disease. The host immune response's role as a driver of HBV-related HCC is then reviewed, allowing for a close exploration of the effects of stress on immune function in chronic hepatitis B and as a potential risk factor for HBV-related HCC.

慢性乙型肝炎病毒(HBV)感染是全球范围内的一项重大公共卫生挑战。HBV是肝细胞癌(HCC)的主要危险因素,影响着全球数亿人。慢性HBV感染的临床结果是多种多样的,似乎受到复杂和失调的宿主免疫反应的影响。反过来,为了确定导致HCC发展的宿主因素,人们对HBV的免疫反应给予了很大的关注。然而,非免疫性宿主因素(如慢性应激)在hbv相关HCC中的作用尚不明确。事实上,越来越多的人认识到压力对慢性肝病的影响,提出了它在慢性HBV感染中的作用的问题。鉴于此,本综述将阐明hbv相关HCC中关键宿主因子的作用,并强调慢性应激是一个可行的因素。首先讨论的是压力,炎症和慢性肝病的相互作用。然后回顾了宿主免疫反应作为hbv相关HCC驱动因素的作用,允许深入探索应激对慢性乙型肝炎免疫功能的影响,并作为hbv相关HCC的潜在危险因素。
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引用次数: 4
Endotrophin, a pro-peptide of Type VI collagen, is a biomarker of survival in cirrhotic patients with hepatocellular carcinoma. 内营养素是 VI 型胶原蛋白的一种原肽,是肝细胞癌肝硬化患者存活率的生物标志物。
IF 5 Pub Date : 2020-12-18 DOI: 10.2217/hep-2020-0030
Diana Julie Leeming, Signe Holm Nielsen, Roslyn Vongsuvanh, Pruthviraj Uchila, Mette Juul Nielsen, Alexander L Reese-Petersen, David van der Poorten, Mohammed Eslam, Detlef Schuppan, Morten Asser Karsdal, Jacob George

Aim: Type VI collagen, is emerging as a signaling collagen originating from different types of fibroblasts. A specific fragment of Type VI collagen, the pro-peptide, is also known as the hormone endotrophin. We hypothesized that this fibroblast hormone would be of particular relevance in cancer types with a high amount of fibrosis activity, namely for outcome in hepatocellular carcinoma (HCC) cirrhotic patients.

Patients & methods: Plasma C6M, PRO-C6 and alphafeto-protein (AFP) were assessed in 309 patients with mixed etiologies (hepatitis C, hepatitis B, alcohol and nonalcoholic fatty liver) diagnosed as cirrhotics, cirrhotics with HCC, noncirrhotics and healthy controls. Progression-free survival and overall survival (OS) data were collected up to 6120 days after diagnosis. The ability of each marker to predict survival was investigated.

Results & conclusion: The level of endotrophin assessed by PRO-C6 was able to separate healthy controls, noncirrhotics and cirrhotics from HCC (p < 0.05-0.0001). Both endotrophin and C6M provided value in the prediction of OS in cirrhotic patients with HCC. In the multivariate analysis for identifying HCC, in patients with high endotrophin (highest quartile) and that were positive for AFP (≥20 IU/ml), the hazard ratio for predicting OS was increased from 3.7 (p = 0.0006) to 14.4 (p = 0.0001) when comparing with AFP positive as a stand-alone marker. In conclusion, plasma levels for markers of Type VI collagen remodeling were associated with survival in cirrhotic patients with HCC. A combination of AFP with endotrophin improved the prognostic value compared with AFP alone for predicting OS in cirrhotic patients with HCC.

目的:Ⅵ型胶原蛋白作为一种信号胶原蛋白,正逐渐从不同类型的成纤维细胞中产生。VI 型胶原蛋白的一个特定片段,即原肽,也被称为激素内营养素。我们假设,这种成纤维细胞激素对具有高纤维化活性的癌症类型,即肝细胞癌(HCC)肝硬化患者的预后具有特殊意义:对309名被诊断为肝硬化的混合病因(丙型肝炎、乙型肝炎、酒精肝和非酒精性脂肪肝)患者、肝硬化合并HCC患者、非肝硬化患者和健康对照组的血浆C6M、PRO-C6和α-酮蛋白(AFP)进行了评估。无进展生存期和总生存期(OS)数据收集至确诊后6120天。研究了每种标记物预测生存期的能力:通过 PRO-C6 评估的内营养素水平能够将健康对照组、非肝癌患者和肝硬化患者与 HCC 区分开来(p
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引用次数: 0
Balloon-occluded chemoembolization for hepatocellular carcinoma: a prospective study of safety, feasibility and outcomes. 肝细胞癌球囊闭塞化疗栓塞:安全性、可行性和结果的前瞻性研究。
IF 5 Pub Date : 2020-10-13 DOI: 10.2217/hep-2020-0022
Ana-Maria Bucalau, Illario Tancredi, Martina Pezzullo, Raphael Leveque, Simona Picchia, Jean-Luc Van Laethem, Gontran Verset

Aim: Evaluation of safety and efficacy of selective balloon-occluded transarterial chemoembolization using polyethylene glycol embolizing microspheres in patients with hepatocellular carcinoma.

Materials & methods: Twenty-four consecutive patients were included in this monocentric prospective trial. Adverse events were evaluated at 24 h and 1 month. Imaging response according to modified response evaluation criteria in solid tumors was assessed at 1, 3 and 6 months.

Results: The median time of follow-up was of 22.8 months (interquartile range (IQR) 17.38-26.22). Clinical grade 1/2 toxicities (0% >grade 2) were reported in 25.7% of patients, with abdominal pain being the most frequent complication (17.1%). No 30-days mortalities or liver decompensation were observed. The 1-month follow-up MRI showed an overall response rate of 74.3%.

Conclusion: Balloon-occluded transarterial chemoembolization was shown to be safe and effective.

目的:评价聚乙二醇微球选择性球囊栓塞经动脉化疗栓塞治疗肝癌患者的安全性和有效性。材料与方法:这项单中心前瞻性试验纳入了24例连续患者。不良事件分别于24小时和1个月进行评估。分别在1个月、3个月和6个月时,根据改进的疗效评价标准评估实体瘤的影像学疗效。结果:中位随访时间为22.8个月(四分位间距(IQR) 17.38 ~ 26.22)。25.7%的患者报告了临床1/2级毒性(0% > 2级),腹痛是最常见的并发症(17.1%)。未见30天死亡或肝脏失代偿。1个月的随访MRI显示总有效率为74.3%。结论:球囊闭塞经动脉化疗栓塞是安全有效的。
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引用次数: 5
期刊
Hepatic Oncology
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