Vessels That Encapsulate Tumor Cluster+ Unresectable Hepatocellular Carcinomas Benefit of Antiangiogenic Therapy
Year: 2025
Type: article
Abstract: Introduction: Two distinct molecular groups of HCC have been recently associated with a better response to atezolizumab-bevacizumab. One of these, “angiogenesis-driven,” is related to HCC vascularization. Vessels that encapsulate tumor clusters (VETCs) is a morphological form of angiogenesis associated with worse prognosis in resected and transplanted HCC. The aim of this study was to explore if VETC can be used, at morphological level, to potentially surrogate the angiogenesis-driven molecular subgroup to identify HCC patients who might benefit of antiangiogenic treatments. Methods: The significance of VETC was first explored in a retrospective, single institution series of 75 patients with unresectable HCC (study cohort) and later validated in an external, retrospective series of 82 patients (validation cohort). The VETC phenotype was identified in the liver biopsy obtained just before the onset of systemic treatment. Results: Patients with VETC+ HCC experienced a significant survival benefit from antiangiogenic drugs, as tyrosine kinase inhibitors and/or bevacizumab (TKI/BEVA), across the study, validation, and overall cohorts. In the whole series of 157 patients, those with VETC+ HCC (n = 70, 45%) treated with TKI/BEVA had a significantly longer overall survival (OS) as compared to those receiving immune checkpoint inhibitors (19.8 months vs. 8.8 months; HR: 0.34; 95% CI: 0.20–0.59; p = 0.0001). The significant treatment-by-biomarker interaction test (p = 0.002) demonstrated that treatment effect varies by VETC status. Case with higher extent of VETC+ or with VETC+ detected before the onset of 1st-line treatment showed even longer survival. Conclusion: VETC+ predicts a significantly longer OS in patients with unresectable HCC treated with TKI/BEVA and can be used as surrogate marker on liver biopsy of angiogenesis-driven molecular class.
Source: Liver Cancer
DOI: 10.1159/000547669
Authors: Camilla De Carlo, Reha Akpinar, Barbara Durante, Tiziana Pressiani, Julien Calderaro, Salvatore Lorenzo Renne, Angelo Pirozzi, Elena Valenzi, Irene Oi-lin Ng, Tan To Cheung, Albino Eccher, Pamela Sighinolfi, Erica Villa, Massimo Iavarone, Marco Maggioni, Yu-Yun Shao, Sara Lonardi, Mario Domenico Rizzato, Antonio De Rosa, Matteo Fassan, Valentina Angerilli, Federica Pedica, Margherita Rimini, Andrea Casadei Gardini, Armando Santoro, Young Nyun Park, Massimo Roncalli, Luigi Terracciano, Salvatore Piscuoglio, Lorenza Rimassa, Luca Di Tommaso
Institutions: Humanitas University, IRCCS Humanitas Research Hospital, Assistance Publique – Hôpitaux de Paris, Hôpitaux Universitaires Henri-Mondor, University of Hong Kong, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, National Taiwan University, National Taiwan University Hospital, Istituto Oncologico Veneto, University of Padua, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Yonsei University, Yonsei University Health System
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,590
Funders: Bristol-Myers Squibb, Fondation de l'Avenir pour la Recherche Médicale Appliquée, National Research Foundation, National Science Council, Ministero della Salute, Innovation and Technology Commission, National Research Foundation of Korea, Fondation ARC pour la Recherche sur le Cancer, Ministry of Science and Technology, Taiwan, Associazione Italiana per la Ricerca sul Cancro, Ministry of Science and ICT, South Korea, Ipsen, National Science and Technology Council, Agenzia Italiana del Farmaco, Ministero della Salute
Awards: G1258458633, G1364224112, G1960857032, G2076520454, G3387545348, G4213487846, G4456767593, Enhancing Treatment Efficacy of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma through Modulation of Checkpoint Expression Vi a Cyclin Dependent Kinase 9 Inhibition( I ), G6813035927, G7774124784
OpenAlex ID: W7082267349