Machine learning models for accurate pretreatment prediction of chemotherapy associated LV dysfunction in patients with breast cancer and lymphoma receiving chemotherapy (WF-98213 PREVENT and CCCWFU9912 DETECT IV).

Abstract

1553 Background: Cancer survivors receiving potentially cardiotoxic chemotherapy are at increased risk for developing left ventricular (LV) dysfunction. We implemented machine learning (ML) models to predict future LV dysfunction in patients with breast cancer or lymphoma scheduled to receive potentially cardiotoxic chemotherapy. Methods: We utilized prospectively collected data from NIH studies R01HL118740 (supported by the Wake Forest NCORP Research Base (UG1CA189824)) and R01CA167821. Data included measurements of LV function and demographic factors before, during, and 24 months after initiating potentially cardiotoxic chemotherapy. The two datasets were used both separately and collectively in the development of multiple ML models including penalized linear regression, support vector machine, and random forest (RF). A data preprocessing step properly handled missing information, data imbalance, and encoding. Hyperparameter tuning was performed using cross validation of training data. The final models were assessed with a 20% hold-out test dataset. Cardiotoxicity was defined as a pre- to 24-month post cancer treatment decline in LV ejection fraction (LVEF) of > 10% or to an absolute value of < 50%. Results: 276 patients were included in ML models (7% men, 93% women; age 52±13 years). The RF model based on the combined dataset had the best performance with a prediction accuracy, sensitivity, and specificity of 0.94, 0.81, and 0.98, respectively. The most important variables assessed pre-treatment as measured by the Gini impurity factor were in descending order, LVEF, global LV circumferential strain, LV end-systolic volume, body mass index, LV stroke volume, LV end-diastolic volume, and LV mass. Conclusions: Prior to cancer treatment, supervised ML methods such as RF models predicted declines in LVEF of > 10% and/or to absolute values below 50% would occur 24 months after initiating chemotherapy for breast cancer or lymphoma. With further improvement and validation using larger datasets, these models may play an important role in cardio-oncology care during and following cancer treatment.