About this trial
Cancer treatments have improved substantially over the past decades, but some effective therapies such as anthracyclines and HER2-targeted agents are associated with severe cardiovascular adverse effects, including heart failure. Existing cardiovascular risk prediction scores have limited evidence in this setting.
The ML-CardioTox study is a prospective, multicenter, observational cohort conducted in 15 centers in France. The primary objective is to develop a one-year prediction score for cancer therapy-related cardiotoxicity using machine learning methods. A dedicated software platform will be used to standardize data collection and support integration of artificial intelligence tools.
A total of 600 patients treated with anthracyclines or HER2-targeted therapies in cardio-oncology clinics will be enrolled over a one-year inclusion period starting in December 2024, with a 12-month follow-up. The primary endpoint is the occurrence of cardiotoxicity as defined by the 2022 European Society of Cardiology guidelines (hospitalization for heart failure, initiation or escalation of diuretic therapy, decline in cardiac function on imaging, or increase in cardiac biomarkers such as troponin or natriuretic peptides).
Secondary objectives include comparison of the predictive performance of the machine learning-derived score with the established HFA-ICOS risk score. Patients will be managed according to routine clinical practice.
This study aims to improve prognostic stratification tools for patients receiving anthracyclines or HER2-targeted therapies, with the goal of better identifying those at high risk of developing cardiotoxicity during follow-up.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years
Planned follow-up in cardio-oncology clinic as part of a baseline pre-treatment evaluation before a sequence of anthracycline and/or HER2-targeted therapy, according to the 2022 ESC recommendations
Inclusion regardless of prior exposure to potentially cardiotoxic anticancer therapies or thoracic radiotherapy
Disqualifiers
Patients not covered by the French national health insurance system (Sécurité Sociale)
Patients for whom 12-month follow-up is planned outside the center performing the baseline pre-treatment evaluation
Trial population
Patients with cancer scheduled to receive anthracyclines and/or HER2-targeted therapy, referred to cardio-oncology clinics in 15 participating French centers for a baseline pre-treatment evaluation and planned follow-up. Consecutive eligible patients will be enrolled over a 12-month inclusion period, with a 12-month follow-up.
Trial design
Cohort
Prospective
Treatments tested in this trial
Not listed
Trial groups
Trial outcomes
Primary outcomes
Incidence of cardiotoxicity at 12 months
Cardiotoxicity defined as a composite outcome, according to the 2022 ESC guidelines: hospitalization for heart failure OR initiation or escalation of diuretic therapy for signs or symptoms of heart failure OR decrease in left ventricular ejection fraction (LVEF) by \>10 percentage points from baseline or to a value \<40% OR relative decrease in global longitudinal strain (GLS) ≥15% from baseline OR new increase in cardiac biomarkers (troponin or NT-proBNP/BNP). Events will be adjudicated by an independent committee.
Secondary outcomes
Predictive performance of machine learning-derived cardiotoxicity risk score
Performance assessed by AUC-ROC, AUC-PR, balanced accuracy, F1 score, PPV, NPV, McNemar's test, and Brier score. Unit of Measure: AUC values, accuracy (%), predictive values (%).
Comparison of predictive performance with HFA-ICOS risk score and traditional Cox model
Direct comparison of ML-derived risk score vs. HFA-ICOS and Cox model. Unit of Measure: Difference in AUC values (%), statistical comparison (DeLong test).
Correlation between baseline prognostic factors and cardiotoxicity at 12 months
Evaluation of demographic, clinical, biological (including biomarkers), and echocardiographic factors for correlation with cardiotoxicity occurrence. Unit of Measure: Odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals.
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