Breast Neoplasms, Cardiotoxicity, Heart Failure, Neoplasms
Conditions
Keywords
Cancer Therapy-Related Cardiac Dysfunction, Anthracyclines, HER2-targeted Therapy, Cardio-Oncology, Machine Learning
Brief summary
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.
Interventions
None listed
Sponsors
University Hospital, Caen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of cardiotoxicity at 12 months | 12 months after initiation of anthracycline or HER2-targeted therapy. | 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
| Measure | Time frame | Description |
|---|---|---|
| Predictive performance of machine learning-derived cardiotoxicity risk score | 12 months after initiation of anthracycline or HER2-targeted therapy. | 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 | 12 months after initiation of anthracycline or HER2-targeted therapy. | 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 | 12 months after initiation of anthracycline or HER2-targeted therapy. | 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. |
Countries
France
Contacts
CONTACTDamien Legallois, MD, PhD
Outcome results
None listed