Risk Prediction Scores for Cardiotoxicity in Cancer Patients Treated With Cardiotoxic Anticancer Therapies in Europe

Overview

Cancer management has undergone major advances over the past 30 years. Several anticancer therapies are now highly effective, allowing many cancers to become chronic diseases through sequential lines of treatment. However, these therapies may be associated with severe cardiovascular adverse events. It is therefore essential to better understand the factors that determine, for a given patient and a given anticancer therapy, the occurrence of cardiovascular toxicity, and ideally to predict which patients are at highest risk. The 2022 ESC Cardio-Oncology Guidelines strongly recommend risk stratification prior to the initiation of cardiotoxic anticancer therapies. Current recommendations suggest the use of risk scores known as "HFA-ICOS" scores. However: Not all cardiotoxic anticancer therapies currently have an associated risk score; Existing scores are derived from small retrospective or prospective cohorts (typically fewer than 100 patients), and most have not undergone rigorous validation, leaving considerable room for improvement. The EU-CARTOX-SCORES protocol aims to develop new prediction scores for cardiotoxicity occurring within the first year after initiation of cardiotoxic anticancer therapies. This protocol is innovative through the integration of artificial intelligence and/or machine learning approaches alongside conventional statistical methods. These models will be interfaced with a dedicated cardio-oncology digital platform (CardioOncoPilot), currently being deployed across the European Union, ensuring standardized and high-quality data collection within routine clinical care. This is a prospective, multicenter, observational study designed as a European cardio-oncology registry, involving all European cardiologists using the platform in routine practice. The inclusion period will last 3 years, with a 12-month follow-up for each patient. At the time of data extraction, all available cases recorded in the CardioOncoPilot platform will be analyzed. Overall, it is anticipated that between 1,000 and 5,000 patients across Europe will be included by the end of 2027. These patients will be managed in cardio-oncology clinics as part of routine care during treatment with cardiotoxic anticancer therapies, with follow-up conducted at the same center throughout the study. The primary endpoint will be the occurrence of cardiotoxicity as defined by the 2022 ESC Guidelines. Additionally, the performance of newly developed prediction models will be compared with existing HFA-ICOS risk scores (when available) in the same patient population. Patients will be followed according to routine clinical practice and in accordance with the 2022 ESC Cardio-Oncology Guidelines, which recommend both a baseline pre-treatment assessment and a follow-up evaluation at 1 year, regardless of the type of cardiotoxic therapy. Patient management will not be modified by the study. This research will consist solely of secondary use of data collected during routine care. Investigators anticipate that this study will significantly improve prognostic risk stratification tools in patients treated with cardiotoxic anticancer therapies, thereby enhancing identification of those at highest risk of clinically relevant cardiovascular adverse events during follow-up. This project will be conducted in collaboration with the ESC Council of Cardio-Oncology, ensuring optimal dissemination through appropriate scientific channels. The developed scores will be shared with the scientific community, particularly the European Society of Cardiology (ESC), with the aim of informing future guideline updates.

Interventions

• Drug antineoplastic agents, endocrine therapy, immunostimulants drugs (ATC classification)
  Cancer patients in which an anticancer drug is planned after the baseline cardio-oncological evaluation

Primary outcome measures

• Occurrence of cardiotoxicity at 1-year follow-up, as defined by the 2022 ESC Guidelines. [Time frame: from the baseline cardio-oncological evaluation and up to 1 year]

Secondary outcome measures (2)

• Identification of baseline parameters obtained during the pre-treatment assessment (clinical, biological, ECG, or echocardiographic) associated with the occurrence of cardiotoxicity at 1 year, as defined by the 2022 ESC Guidelines. [Time frame: from the baseline cardio-oncological evaluation and up to 1 year]
• Comparison of the performance of newly developed prediction scores with existing risk stratification scores (HFA-ICOS scores proposed in the 2022 ESC Guidelines), for each anticancer drug with an available HFA-ICOS score. [Time frame: from the baseline cardio-oncological evaluation and up to 1 year]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Diagnosis of cancer
• Planned cardio-oncology follow-up as part of pre-treatment assessment prior to cardiotoxic anticancer therapy, as defined in the 2022 ESC Cardio-Oncology Guidelines

Exclusion criteria

• Patients for whom 12-month follow-up is planned to be conducted outside the center that performed the baseline pre-treatment evaluation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07621289 · Pharmaco2026_05_19

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗