Cardiological adverse events in hepatocellular carcinoma patients receiving immunotherapy: Influence of comorbidities and clinical outcomes

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2025-04-12 DOI:10.1016/j.ejca.2025.115404

Marta Fortuny , Marta García-Calonge , Óscar Arrabal , Marco Sanduzzi-Zamparelli , Andrés Castaño-García , Enric Cascos , Alicia Mesa , Ana María Piedra-Cerezal , Neus Llarch , Gemma Iserte , Marta Campos , Melina González , Aida Marsal , Rebeca Lorca , Manuel Rodríguez , Ferran Torres , María Varela , María Reig

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Abstract

Introduction

Immunotherapy-based combinations have revolutionized the first-line treatment for advanced hepatocellular carcinoma (HCC), improving overall survival (OS). However, these therapies are associated with adverse events (AEs), particularly cardiological complications and major adverse cardiovascular events (MACE), which may adversely affect outcomes. The influence of comorbid conditions such as arterial hypertension (AHT) and type 2 diabetes mellitus (T2DM) on the incidence and prognosis of cardiological AEs in HCC patients remains understudied.

Methods

This retrospective study included 109 HCC patients treated with atezolizumab-bevacizumab, tremelimumab-durvalumab, or durvalumab as first-line therapy at two Spanish medical centers from 2017–2023. Patients were stratified by comorbidities, AE incidence, and cardiological risk (CARDIOSOR scale). The primary endpoints were the incidence of treatment-modifying AEs and MACE, and their association with survival.

Results

Among the cohort, 50.5 % experienced AEs of special interest (AESI), with 34 % considered immune-related (irAE). MACE occurred in 7.3 % of patients, including myocarditis (3.7 %). The CARDIOSOR scale identified a higher risk of MACE in patients with AHT, T2DM, or both (OR: 5.07, p = 0.034). Early cardiological AEs were independently associated with worse OS (HR: 3.38, p = 0.04). Patients with both AHT and T2DM exhibited higher rates of MACE (16.7 %) and treatment discontinuation (25.9 %). The CARDIOSOR scale effectively stratified patients into high-risk groups, correlating with increased MACE rates and poor survival outcomes.

Conclusions

Comorbid conditions, particularly AHT and T2DM, amplify the risk of MACE and influence treatment discontinuation. The CARDIOSOR scale is a valuable tool for personalized risk assessment, guiding tailored therapeutic strategies. Integrating cardiovascular risk management into HCC care is crucial for optimizing both oncological and cardiovascular outcomes.

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肝细胞癌患者接受免疫治疗的心血管不良事件：合并症和临床结果的影响

基于免疫治疗的联合治疗彻底改变了晚期肝细胞癌（HCC）的一线治疗，提高了总生存期（OS）。然而，这些疗法与不良事件（ae）相关，特别是心血管并发症和主要不良心血管事件（MACE），这可能会对结果产生不利影响。动脉高血压（AHT）和2型糖尿病（T2DM）等合并症对HCC患者心血管ae发生率和预后的影响尚不清楚。方法：本回顾性研究纳入了2017-2023年在西班牙两家医疗中心接受阿特唑单抗-贝伐单抗、tremelimumab-durvalumab或durvalumab作为一线治疗的109例HCC患者。根据合并症、AE发生率和心脏病风险（CARDIOSOR量表）对患者进行分层。主要终点是治疗改善性ae和MACE的发生率及其与生存率的关系。结果在队列中，50.5% %经历了特殊利益ae (AESI)， 34% %被认为是免疫相关ae （irAE）。MACE发生率为7.3 %，包括心肌炎（3.7 %）。CARDIOSOR量表显示，合并AHT、T2DM或两者的患者发生MACE的风险更高（or: 5.07, p = 0.034）。早期心脏病ae与较差的OS独立相关（HR: 3.38, p = 0.04）。同时患有AHT和T2DM的患者表现出更高的MACE发生率（16.7 %）和停药率（25.9 %）。CARDIOSOR量表有效地将患者分为高危组，与MACE率增加和生存结果差相关。结论合并症，尤其是AHT和T2DM，增加了MACE的风险并影响了治疗的终止。CARDIOSOR量表是个性化风险评估的宝贵工具，可指导量身定制的治疗策略。将心血管风险管理纳入HCC治疗对于优化肿瘤和心血管预后至关重要。

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

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

期刊介绍： The European Journal of Cancer (EJC) serves as a comprehensive platform integrating preclinical, digital, translational, and clinical research across the spectrum of cancer. From epidemiology, carcinogenesis, and biology to groundbreaking innovations in cancer treatment and patient care, the journal covers a wide array of topics. We publish original research, reviews, previews, editorial comments, and correspondence, fostering dialogue and advancement in the fight against cancer. Join us in our mission to drive progress and improve outcomes in cancer research and patient care.