Etiology of Hepatocellular Carcinoma May Influence the Pattern of Progression under Atezolizumab-Bevacizumab.

IF 11.6 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver Cancer Pub Date : 2025-05-26 DOI:10.1159/000545494

Bernardo Stefanini, Fabio Piscaglia, Fabio Marra, Massimo Iavarone, Caterina Vivaldi, Giuseppe Cabibbo, Andrea Palloni, Tiziana Pressiani, Andrea Dalbeni, Benedetta Stefanini, Leonardo Stella, Piera Federico, Gianluca Svegliati-Baroni, Sara Lonardi, Caterina Soldà, Luca Ielasi, Stefania De Lorenzo, Ingrid Garajova, Claudia Campani, Mariangela Bruccoleri, Gianluca Masi, Ciro Celsa, Giovanni Brandi, Alessandra Auriemma, Bruno Daniele, Francesca Romana Ponziani, Lorenzo Lani, Rusi Chen, Maria Boe, Alessandro Granito, Lorenza Rimassa, Francesco Tovoli

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引用次数: 0

Abstract

Background: Preclinical models have shown that metabolic dysfunction-associated steatotic liver disease (MASLD)-related hepatocellular carcinoma (HCC) may exhibit reduced responsiveness to immunotherapy, especially for intrahepatic lesions due to liver tumor microenvironment. Radiological pattern of progression has been validated in clinical studies as a useful tool for predicting outcomes in HCC undergoing systemic treatments.

Aims: The aim of this study was to determine whether MASLD influences the pattern of progression in patients treated with atezolizumab-bevacizumab.

Methods: This multicenter, prospective study included patients with unresectable HCC receiving atezolizumab-bevacizumab. Progression patterns were defined as previously proposed. Patients were categorized as either MASLD or controls based on a recent multisocietal Delphi consensus statement. Multivariable models analyzed the risk of specific progression patterns and their impacts on post-progression survival (PPS) and overall survival (OS). A historical cohort treated with sorafenib was also analyzed to determine whether observed patterns were specific for atezolizumab-bevacizumab.

Results: Four-hundred twenty patients were included (MASLD: n = 88, 21.0%). Time to progression (TTP) was shorter in MASLD compared to controls, due to an increased risk of intrahepatic growth (IHG - hazard ratio [HR] 1.739, 95% confidence interval [CI] 1.206-2.507, p = 0.003]). Neither etiology nor IHG predicted a different PPS. No differences between etiologies were found in OS. Etiology did not influence the pattern of progression under sorafenib in the historical cohort.

Conclusion: IHG was more frequently associated with MASLD-HCC compared to controls, confirming preclinical data and suggesting biological differences between tumors, with potential implications for future research. MASLD should not be seen as a contraindication to immunotherapy.

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肝细胞癌的病因可能影响阿特唑单抗-贝伐单抗治疗下的进展模式。

临床前模型显示，代谢功能障碍相关的脂肪变性肝病（MASLD）相关的肝细胞癌（HCC）对免疫治疗的反应性可能降低，特别是由于肝脏肿瘤微环境引起的肝内病变。放射学进展模式已在临床研究中被证实为预测肝细胞癌接受全身治疗的结果的有用工具。目的：本研究的目的是确定MASLD是否影响阿特唑单抗-贝伐单抗治疗患者的进展模式。方法：这项多中心前瞻性研究纳入了接受阿特唑单抗-贝伐单抗治疗的不可切除HCC患者。进度模式的定义与之前提出的一致。根据最近的多社会德尔福共识声明，患者被分类为MASLD或对照组。多变量模型分析特定进展模式的风险及其对进展后生存期（PPS）和总生存期（OS）的影响。还分析了使用索拉非尼治疗的历史队列，以确定观察到的模式是否对阿特唑单抗-贝伐单抗具有特异性。结果：共纳入420例患者（MASLD: n = 88, 21.0%）。与对照组相比，MASLD的进展时间（TTP）较短，这是由于肝内生长的风险增加（IHG -危险比[HR] 1.739, 95%可信区间[CI] 1.206-2.507, p = 0.003]）。病因学和IHG均未预测不同的PPS。OS患者的病因无差异。在历史队列中，病因不影响索拉非尼治疗的进展模式。结论：与对照组相比，IHG更频繁地与MASLD-HCC相关，证实了临床前数据，并提示肿瘤之间的生物学差异，对未来的研究具有潜在的意义。MASLD不应被视为免疫治疗的禁忌症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver Cancer Medicine-Oncology

CiteScore

20.80

自引率

7.20%

发文量

审稿时长

16 weeks

期刊介绍： Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.