Background: Anthracycline-induced cardiotoxicity is a major limitation of cancer therapy, highlighting the need for accurate and practical risk stratification. Although current guidelines recommend the HFA-ICOS score for baseline risk assessment, its complexity may limit routine clinical use.
Objectives: To develop and validate a simplified risk score based on readily available clinical and echocardiographic variables for predicting anthracycline-related cardiotoxicity, and to compare its performance with the HFA-ICOS model.
Methods: We retrospectively analyzed 2,612 adult cancer patients with baseline left ventricular ejection fraction (LVEF) ≥50% treated with anthracyclines. Echocardiography was performed at baseline, during therapy, and up to two years after treatment. Cardiotoxicity was defined as a decrease in LVEF >10 percentage points to a value <50% or the development of heart failure. The predictive performance of the HFA-ICOS score was assessed using the area under the receiver operating characteristic curve (AUC). A simplified model was derived using logistic regression with cross-validation and further validated with machine learning techniques. External validation was conducted in an independent cohort of 819 patients.
Results: Over the first two years, the likelihood of cardiotoxicity was higher in the moderate (HR 1.44, 95% CI 1.02-2.06) and high (HR 1.84, 95% CI 1.36-2.50) HFA-ICOS risk categories compared to the low-risk group. The cumulative incidence of cardiotoxicity was 8.3% (95% CI 7.1-9.1) at 12 months with only 5 additional events observed in patients still at risk through 2 years. The HFA-ICOS score showed good discrimination at 1 year (AUC 0.76, 95% CI 0.67-0.86). A simplified model including post-chemotherapy LVEF and cumulative anthracycline dose (RE-ACT score) demonstrated higher accuracy at 1 year (AUC 0.83, 95% CI 0.74-0.93) though not statistically different. Combining both scores in the derivation cohort further improved predictive performance (AUC 0.87, 95% CI 0.80-0.95; P<0.001 vs. HFA-ICOS score). In the validation cohort, the RE-ACT score achieved an AUC of 0.88 (95% CI 0.80-0.95) at 1 year.
Conclusions: HFA-ICOS score effectively stratifies baseline risk, while the RE-ACT score provides additional post-treatment prognostic value. Their integration supports a practical two-step strategy for personalized surveillance in cardio-oncology.
JACC CardioOncology Editor-in-Chief and CME Editor
Bonnie Ky, MD, MSCE, FACC
Authors
Daniela Cardinale, MD, MpD
GianCarlo Marenzi, MD
Important Dates
Date of Release: August 18, 2026
Term of Approval/Date of CME/MOC Expiration: August 17, 2027