ML Score Prediction of Cardiotoxicity in Cancer Patients Receiving Anthracycline Chemotherapy or HER2-Targeted Therapies (ML-CardioTox)

Machine Learning Score Prediction of Cardiotoxicity in Cancer Patients Receiving Anthracycline Chemotherapy or HER-2-Targeted Therapies

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Neoplasms; Breast Neoplasms; Cardiotoxicity

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Damien Legallois, MD, PhD; Phone Number: 33231064418; Email: damien.legallois@unicaen.fr

Study Locations

• France
  • Caen, France
    • Recruiting
    • CHU de Caen
    • Contact: Damien Legallois, MD; Phone Number: +33231065118

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 months after initiation of anthracycline or HER2-targeted therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 (%).	12 months after initiation of anthracycline or HER2-targeted therapy.
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).	12 months after initiation of anthracycline or HER2-targeted therapy.
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.	12 months after initiation of anthracycline or HER2-targeted therapy.

Collaborators and Investigators

• Sponsor: University Hospital, Caen

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: August 25, 2025
• First Submitted That Met QC Criteria: September 22, 2025
• First Posted (Actual): September 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Anthracyclines; Machine Learning; Cardio-Oncology; Cancer Therapy-Related Cardiac Dysfunction; HER2-targeted Therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Neoplasms by Site; Heart Diseases; Chemically-Induced Disorders; Skin Diseases; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasms; Heart Failure; Breast Neoplasms; Cardiotoxicity
• Other Study ID Numbers: 23-0270

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No