Exploring Predictive Risk Factors for Myocardial Injury in Children Treated with Anthracyclines: A Pilot Study

Anthracycline-induced cardiotoxicity poses a threat to the long-term heart health of childhood cancer survivors; however, early risk assessment remains challenging due to limited predictive tools. While risk prediction models have been developed for chemotherapy-related hematological toxicity in pediatric cancer patients, research efforts addressing anthracycline-induced cardiotoxicity in this population remain limited. To fill this gap, we conducted a pilot study to develop a risk prediction model for anthracycline-induced cardiotoxicity in children. Using a paired-sample design, we analyzed data collected throughout treatment from 18 children receiving anthracycline-based chemotherapy. Patient demographics, clinical features, and treatment regimen served as input (explanatory) variables, while plasma concentration of high-sensitivity cardiac troponin T was used as the outcome (response), representing anthracycline-induced myocardial injury. Of the initial 33 potential variables, the top 18 were selected based on their importance scores in relation to myocardial injury. This set was further refined to 13 by removing redundancies using the caret package in R to develop a preliminary logistic regression model. A Leave-One-Patient-Out Cross-Validation identified four key predictors for the final model: sex, age at diagnosis, total cyclophosphamide dose (mg), and days since the first anthracycline dose. All were significantly associated with myocardial injury. The final logistic regression model achieved an accuracy of 85%, a sensitivity of 80%, a specificity of 88%, an area under the curve of 0.89, and a Youden's index of 0.68 for predicting myocardial injury risk. These preliminary findings suggest the potential of our predictive model to stratify risk of anthracycline-induced myocardial injury in the pediatric population.