Liver cancer international最新文献

英文中文

Impact of metformin on clinical outcomes in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors 二甲双胍对免疫检查点抑制剂治疗晚期肝细胞癌临床疗效的影响

Liver cancer international

Pub Date : 2023-03-08 DOI: 10.1002/lci2.71

Sandra Kang, Lana Khalil, Ashley McCook-Veal, Yuan Liu, John Galvin, Amber Draper, Nima Kokabi, Maria Diab, Walid Shaib, Olatunji Alese, Olumide Gbolahan, Bassel El-Rayes, Mehmet Akce

Background and Aims

Non-alcoholic steatohepatitis (NASH) is a common cause of hepatocellular carcinoma (HCC) worldwide. Emerging data suggests NASH-induced HCC could be associated with less response to immune checkpoint inhibitor (ICI)-based therapy. Metformin has been associated with improved outcomes in cancers like melanoma treated with ICIs, but its impact on HCC is not well defined. The purpose of this study was to examine the effect of metformin on clinical outcomes in patients with advanced HCC treated with ICIs.

Methods

We retrospectively analysed patients with advanced HCC treated with ICIs in first and later-line settings between 2015 and 2021. The primary endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) as assessed according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Patients were stratified based on their usage of metformin.

Results

Our study included 18 patients in the metformin group and 93 patients in the non-metformin group. The most common causes of HCC were viral hepatitis (52%), NASH (29%), and alcohol (8%). ORR was 5.6% in the metformin group vs 22.6% in the non-metformin group (P = .0987). Median OS was 10.8 months versus 45.9 months (HR = 1.99, 95% CI = 0.95–4.21, P = .065) and median PFS was 2.5 months versus 6.6 months (P = .077) in the metformin and non-metformin groups, respectively. Regardless of metformin usage, OS was significantly worse in patients with poor ECOG performance status, HCC aetiology of NASH, MELD score 10–23, AFP >= 400, and use of ICIs in later lines of therapy.

Conclusions

Metformin use was associated with a trend, although not statistically significant, toward a worse ORR, OS and PFS in advanced HCC patients treated with ICIs.

非酒精性脂肪性肝炎（NASH）是世界范围内肝细胞癌（HCC）的常见病因。新出现的数据表明，NASH诱导的HCC可能与对基于免疫检查点抑制剂（ICI）的治疗反应较少有关。二甲双胍与ICIs治疗的黑色素瘤等癌症的疗效改善有关，但其对HCC的影响尚不明确。本研究的目的是检验二甲双胍对ICIs治疗的晚期HCC患者临床结果的影响。

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引用次数: 0

Development of diagnostic and prognostic molecular biomarkers in hepatocellular carcinoma using machine learning: A systematic review 应用机器学习开发肝细胞癌诊断和预后分子生物标志物：系统综述

Liver cancer international

Pub Date : 2023-01-17 DOI: 10.1002/lci2.66

Amanpreet Brar, Alice Zhu, Cristina Baciu, Divya Sharma, Wei Xu, Ani Orchanian-Cheff, Bo Wang, Jüri Reimand, Robert Grant, Mamatha Bhat

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and morbidity worldwide. Machine learning (ML) tools have been developed in recent years to generate diagnostic and prognostic molecular biomarkers for this high-fatality cancer. To delineate the landscape of ML in HCC, we performed a systematic search of Ovid Medline, Ovid Embase, Cochrane Database of Systematic Reviews (Ovid) and Cochrane CENTRAL (Ovid) to identify studies of HCC molecular biomarkers using ML strategies. In total, 75 studies met our inclusion criteria, 53 of which were pertinent to diagnosis of HCC and 22 of which were pertinent to prognostication of HCC. Genomic, transcriptomic, epigenomic, proteomic and metabolomic signatures were derived using various ML techniques (supervised, unsupervised and deep learning approaches) using serum, urine and tissue samples of HCC. The ML algorithms achieved a sensitivity of up to 95% for the diagnosis of HCC. Through pathway analysis of the signatures derived by ML tools, we identified regulators of epithelial-mesenchymal transition and the cancer pathway Ras/Raf/MAPK as being particularly prognostic of HCC outcome. The application of ML to molecular data in HCC has thus far resulted in the generation of highly sensitive diagnostic and prognostic signatures. In future, development of ML algorithms that incorporate clinical, laboratory, alongside molecular features will be needed to fulfil the promise of personalized HCC diagnosis and treatment.

肝细胞癌（HCC）是全球癌症相关死亡率和发病率的主要原因。近年来开发了机器学习（ML）工具，以生成这种高致死率癌症的诊断和预后分子生物标志物。为了描述ML在HCC中的分布，我们对Ovid Medline、Ovid Embase、Cochrane系统评价数据库（Ovid）和Cochrane CENTRAL（Ovid）进行了系统搜索，以确定使用ML策略的HCC分子生物标志物的研究。总共有75项研究符合我们的纳入标准，其中53项与HCC的诊断有关，22项与肝癌的预后有关。使用各种ML技术（监督、无监督和深度学习方法），使用HCC的血清、尿液和组织样本，获得基因组、转录组、表观基因组、蛋白质组和代谢组特征。ML算法对HCC的诊断灵敏度高达95%。通过对ML工具得出的信号进行通路分析，我们确定上皮-间质转化的调节因子和癌症通路Ras/Raf/MAPK是HCC结果的特别预后因子。到目前为止，ML在HCC分子数据中的应用已经产生了高度敏感的诊断和预后特征。未来，需要开发结合临床、实验室和分子特征的ML算法，以实现个性化HCC诊断和治疗的前景。

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引用次数: 2

Very late local recurrences of hepatocellular carcinoma with macrovascular invasion treated with stereotactic body radiotherapy: Report of two cases 立体定向放射治疗侵袭大血管的肝癌晚期局部复发2例报告

Liver cancer international

Pub Date : 2022-12-30 DOI: 10.1002/lci2.69

Gordon E. Locke, Khalid Alrabiah, Tae Kyoung Kim, Jennifer Knox, Raymond Jang, Laura A. Dawson

Background and Aims

Stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) is becoming an accepted local therapy in patients who are not candidates for surgical intervention, ablation or transarterial chemo-embolization. In patients with HCC with macrovascular invasion, SBRT is sometimes the treatment of choice, especially when systemic therapies are contraindicated, not available or if the HCC is refractory to systemic therapy.

Methods

We present two cases of HCC with tumour macrovascular invasion treated with SBRT. Both tumours appeared to have a complete response to SBRT over the subsequent 5 years.

Results

Very late, in-field local recurrences of HCC were diagnosed 73 and 78 months following SBRT. One patient underwent re-irradiation, was started on Levatinib and remains alive at 12 months following his recurrence. The other patient experienced rapid hepatic and extra-hepatic HCC progression shortly after the local recurrence occurred, and they expired 6 months later.

Conclusions

We demonstrate that patients treated with SBRT for HCC, with or without vascular invasion, may have prolonged tumour control and overall survival beyond 5 years. As more HCC patients are living longer compared to historical cohorts, it has become apparent that very late local recurrences of HCC may occur highlighting the need for long-term surveillance.

立体定向体放疗(SBRT)治疗肝细胞癌(HCC)正在成为不需要手术干预、消融或经动脉化疗栓塞的患者接受的局部治疗方法。对于有大血管侵袭的HCC患者，SBRT有时是治疗的选择，特别是当全身治疗是禁忌的，不可用的或如果HCC对全身治疗是难治性的。

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引用次数: 0

Perspectives for novel therapeutic concepts in hepatocellular carcinoma targeting the stromal and innate immune microenvironment 靶向基质和先天免疫微环境的肝细胞癌新治疗理念展望

Liver cancer international

Pub Date : 2022-12-30 DOI: 10.1002/lci2.70

Charlotte Rennert, Julia Lang-Meli, Mikhail Gromak, Maike Hofmann, Robert Thimme, Natascha Roehlen

Hepatocellular carcinoma (HCC) is a major public health burden with increasing incidence and mortality worldwide. Arising almost exclusively on the background of chronic liver disease, the tumour microenvironment plays a tremendous role in the occurrence and progression of HCC. With the emergence of checkpoint inhibitor‐based combination therapies as first‐line therapy in advanced HCC, the tumour microenvironment has drawn increasing attention as a target for novel therapeutic approaches. In fact, checkpoint‐inhibitor‐based immunotherapies currently dominate clinical studies on HCC therapy. Importantly, whilst checkpoint‐inhibitor‐based immune‐oncology primarily targets T‐cells, the tumour microenvironment consists of a wide variety of different cell populations that show complex interactions with each other and the malignant tumour cells. Stromal cells and representatives of the innate immune system, such as macrophages, neutrophils and natural killer cells hereby orchestrate the initial immune response and thus appear as attractive targets for broad therapeutic effects, less susceptible to immune escape. In this review, we aim to discuss the current knowledge on the role of innate immune cells and stromal cell populations in HCC initiation and progression as well as related novel therapeutic concepts.

肝细胞癌（HCC）是全球范围内发病率和死亡率不断上升的主要公共卫生负担。肿瘤微环境几乎完全发生在慢性肝病的背景下，在HCC的发生和发展中发挥着巨大作用。随着基于检查点抑制剂的联合疗法作为晚期HCC的一线治疗方法的出现，肿瘤微环境作为新的治疗方法的靶点越来越受到关注。事实上，基于检查点抑制剂的免疫疗法目前主导着HCC治疗的临床研究。重要的是，尽管基于检查点抑制剂的免疫肿瘤学主要靶向T细胞，但肿瘤微环境由各种不同的细胞群组成，这些细胞群相互之间以及与恶性肿瘤细胞之间表现出复杂的相互作用。基质细胞和先天免疫系统的代表，如巨噬细胞、中性粒细胞和自然杀伤细胞，从而协调最初的免疫反应，从而成为具有广泛治疗效果的有吸引力的靶点，不太容易发生免疫逃逸。在这篇综述中，我们旨在讨论目前关于先天免疫细胞和基质细胞群在HCC发生和发展中的作用的知识，以及相关的新治疗概念。

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引用次数: 0

The regulation and functions of ACSL3 and ACSL4 in the liver and hepatocellular carcinoma ACSL3和ACSL4在肝癌和肝细胞癌中的调控及其作用

Liver cancer international

Pub Date : 2022-11-11 DOI: 10.1002/lci2.68

Jorlin Liu, Mark G. Waugh

Hepatocellular carcinoma (HCC) is a heterogeneous disease that often features dysregulated tumour lipid metabolism. ACSL3 and ACSL4 are two homologous long chain acyl-coenzyme A synthetases (ACSL) that preferentially catalyse the activation of monounsaturated and polyunsaturated fatty acids, respectively. Both enzymes are frequently overexpressed in HCC, and multiple reports have implicated ACSL4 in tumour progression. Increased expression of these isozymes in tumour cells can upregulate lipid metabolism through de novo lipogenesis, fatty acid β-oxidation and acyl chain remodelling of membrane phospholipids. We describe the subcellular functions of ACSL3 and ACSL4 in hepatocytes, and the transcriptional, epigenetic and post-translational mechanisms underpinning their regulation. We discuss the evidence that these enzymes can modulate hepatocarcinogenic signalling by oncoproteins, cell death by apoptosis or ferroptosis, and protein degradation through the ubiquitin-proteasome pathway. In addition, we survey how knowledge in this area may inform new approaches to the diagnosis and treatment of HCC and deepen our understanding of how lipid metabolic reprogramming can promote hepatic tumour growth.

肝细胞癌(HCC)是一种异质性疾病，通常以肿瘤脂质代谢失调为特征。ACSL3和ACSL4是两个同源的长链酰基辅酶A合成酶(ACSL)，分别优先催化单不饱和脂肪酸和多不饱和脂肪酸的活化。这两种酶在HCC中经常过表达，多个报告表明ACSL4与肿瘤进展有关。这些同工酶在肿瘤细胞中的表达增加，可以通过脂质新生、脂肪酸β氧化和膜磷脂酰基链重塑来上调脂质代谢。我们描述了ACSL3和ACSL4在肝细胞中的亚细胞功能，以及支持其调控的转录、表观遗传和翻译后机制。我们讨论了这些酶可以通过癌蛋白调节肝癌信号，通过凋亡或铁凋亡调节细胞死亡，以及通过泛素-蛋白酶体途径调节蛋白质降解的证据。此外，我们调查了这一领域的知识如何为HCC的诊断和治疗提供新方法，并加深了我们对脂质代谢重编程如何促进肝肿瘤生长的理解。

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引用次数: 0

Prognostic and predictive factors for locoregional and systemic therapies in hepatocellular carcinoma 肝细胞癌局部和全身治疗的预后和预测因素

Liver cancer international

Pub Date : 2022-11-11 DOI: 10.1002/lci2.62

Simon Gray, Angela Lamarca, Mairéad G. McNamara, Julien Edeline, Karen Piper-Hanley, Juan W. Valle, Richard A. Hubner

Hepatocellular carcinoma (HCC) is a growing health concern, with an estimated global incidence of over 1 million by 2025. In its intermediate and advanced stages, HCC remains a challenging condition to treat, despite a recently expanded array of systemic therapies, which continues to grow. Extensive efforts have accordingly been made to identify predictive factors to guide treatment decisions. However, currently, only one predictive biomarker is in widespread clinical use, namely elevated alpha-fetoprotein for second-line systemic therapy with ramucirumab. This article reviews known prognostic and predictive biomarkers for patients with HCC who are treated with locoregional and systemic therapies, including recent controversies around the potential impact of HCC aetiology on the efficacy of systemic therapies.

肝细胞癌（HCC）是一个日益严重的健康问题，预计到2025年，全球发病率将超过100万。在其中晚期，HCC仍然是一种具有挑战性的治疗条件，尽管最近扩大了一系列系统性治疗，而且还在继续增长。因此，已经做出了广泛的努力来确定预测因素，以指导治疗决策。然而，目前只有一种预测性生物标志物在临床上广泛使用，即甲胎蛋白升高，用于拉穆丘单抗的二线系统治疗。本文综述了接受局部和系统治疗的HCC患者的已知预后和预测生物标志物，包括最近关于HCC病因对系统治疗疗效的潜在影响的争议。

引用次数: 1

ALBI grade predicts suitability for further systemic therapy following sorafenib in patients with advanced hepatocellular carcinoma ALBI分级预测晚期肝细胞癌患者索拉非尼治疗后进一步全身治疗的适宜性

Liver cancer international

Pub Date : 2022-11-01 DOI: 10.1002/lci2.61

Omar Fakih, Suraiya S. Haddad, Sophie Walker, Julien Edeline, Florien Estrade, Xin Wang, Angela Lamarca, Mairéad G. McNamara, Juan W. Valle, Richard A. Hubner

Background & Aims

Preserved performance status (PS) and liver function are required for systemic therapy in patients with advanced hepatocellular carcinoma (aHCC). We investigated the frequency of suitability for further systemic therapies following sorafenib in aHCC.

Methods

Demographic, tumour and therapy-related data were collected retrospectively for patients with aHCC who received sorafenib at a UK tertiary referral centre (training cohort), and an independent French centre (validation cohort). The primary endpoint was percentage of patients with Child-Pugh class A (CP-A) liver disease and PS 0–1 after sorafenib discontinuation.

Results

Sorafenib was received by 182 patients. After sorafenib discontinuation, 93 patients (51%) were CP-A and 60 patients (33%) were PS 0–1; 43 patients (24%) were both CP-A and PS 0–1. On multivariable analysis, patients with Albumin-Bilirubin (ALBI) score of 1 at time of sorafenib commencement were more likely to be suitable for post-sorafenib therapy, (44% grade 1 vs 15% grade 2) (OR 3.76, 95%CI 1.72–8.25, P = .0009). In the validation cohort of 216 patients baseline ALBI grade was also significantly associated with suitability for further systemic therapy (P = .008).

Conclusions

Most patients with aHCC are not suitable for further systemic therapy after sorafenib, but those with ALBI grade 1 have a greater likelihood of suitability.

对晚期肝细胞癌（aHCC）患者进行系统治疗需要保留性能状态（PS）和肝功能。我们研究了索拉非尼治疗aHCC后进一步全身治疗的适用性频率。

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引用次数: 0

Clinical factors associated with early disease progression after radioembolization for hepatocellular carcinoma and feasibility of post-progression systemic therapy 肝细胞癌放射栓塞术后早期疾病进展的相关临床因素及进展后全身治疗的可行性

Liver cancer international

Pub Date : 2022-10-05 DOI: 10.1002/lci2.60

Charlotte Van Laeken, Thibault Taelman, Sarah Cappuyns, Geert Maleux, Vincent Vandecaveye, Chris Verslype, Christophe Deroose, Jeroen Dekervel

Background and Aims

Radioembolization (RE) for unresectable hepatocellular carcinoma (HCC) can provide clinical benefit for well-selected patients, whilst in others, rapid disease progression is observed. As an alternative for this patient population, new potent systemic treatment options are emerging. We aimed to identify the clinical factors associated with rapid progression following RE and assess the feasibility of starting a systemic treatment after progression.

Methods

A retrospective cohort study of patients with unresectable HCC undergoing RE at a single referral centre between January 2009 and December 2018. Progression-free and overall survival times were calculated. Uni- and multivariate cox regression analysis was used to assess factors associated with poor outcomes. Charts were reviewed for post-progression treatment strategies.

Results

Overall, 116 patients with unresectable HCC were included. Median PFS after RE was 6.7 months (95% CI 3.97–9.37), which varied significantly (P < .001) with Eastern Cooperative Oncology Group Performance Status (EGOC PS) (ECOG 0, 20.9 months [95% CI 8.6–33.2]; ECOG 1, 7.7 months [95% CI 3.1–12.1]; ECOG 2, 4.4 months [95% CI 1.7–7]). This association remained significant after multivariate testing, together with the number of HCC lesions (P = .017) and α-FP (P = .050). Progressive disease after RE occurred in 82 patients, of whom only 40 received subsequent systemic treatment. Again, ECOG PS at the time of progression was significantly better for patients who did receive systemic treatment versus those who did not (P = .002).

Conclusion

Patients with unresectable HCC, impaired general condition and multinodular disease have inferior outcomes after radioembolization. After RE, close monitoring of patient performance status, liver function and cancer control is warranted to allow timely initiation of systemic treatment when indicated.

背景与目的放射栓塞(RE)治疗不可切除的肝细胞癌(HCC)可以为选定的患者提供临床益处，而在其他患者中，观察到疾病的快速进展。作为这一患者群体的替代方案，新的有效的全身治疗方案正在出现。我们的目的是确定与RE后快速进展相关的临床因素，并评估进展后开始全身治疗的可行性。方法回顾性队列研究2009年1月至2018年12月在单个转诊中心接受RE治疗的不可切除HCC患者。计算无进展生存时间和总生存时间。采用单因素和多因素cox回归分析评估与不良预后相关的因素。回顾了进展后治疗策略的图表。结果共纳入116例不可切除HCC患者。RE后的中位PFS为6.7个月(95% CI 3.97-9.37)，与东部肿瘤合作组绩效状态(ECOG) (ECOG 0, 20.9个月[95% CI 8.6-33.2];ECOG 1,7.7个月[95% CI 3.1-12.1];ECOG 2, 4.4个月[95% CI 1.7-7])。在多变量检验后，这种关联仍然显著，包括HCC病变数量(P = 0.017)和α-FP (P = 0.050)。82例患者发生RE后的进展性疾病，其中只有40例接受了后续的全身治疗。同样，接受全身治疗的患者在进展时的ECOG PS明显优于未接受全身治疗的患者(P = 0.002)。结论不可切除的肝细胞癌、全身功能受损及多结节病变患者行放射栓塞治疗后预后较差。RE术后，应密切监测患者的身体状况、肝功能和癌症控制情况，以便在需要时及时开始全身治疗。

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引用次数: 0

Machine learning and biomarkers in hepatocellular carcinoma: The future is now 机器学习和肝细胞癌的生物标志物:未来就是现在

Liver cancer international

Pub Date : 2022-09-01 DOI: 10.1002/lci2.67

F. Ponziani, E. Giannini, Q. Lai

serum, urine, and tissue samples).

血清、尿液和组织样本)。

引用次数: 1

Issue Information 问题信息

Liver cancer international

Pub Date : 2022-09-01 DOI: 10.1002/lci2.30

引用次数: 0

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