Novel Functional Radiomics for Prediction of Cardiac PET Avidity in Lung Cancer Radiotherapy

Abstract

Traditional methods of evaluating cardiotoxicity focus solely on radiation doses to the heart and do not incorporate functional imaging information. Functional imaging has great potential to improve the ability to provide early prediction for cardiotoxicity for lung cancer patients undergoing radiotherapy. FDG-based PET/CT imaging is routinely obtained as part of standard staging work up for lung cancer patients. Although FDG PET/CT scans are typically used to evaluate the tumor, imaging guidelines note that FDG PET/CT scans are an FDA-approved method to image for cardiac inflammation, and studies have noted that the PET cardiac signal can be predictive of clinical outcomes. The purpose of this work was to develop a radiomics model to predict clinical cardiac assessment of standard of care FDG PET/CT scans. The study included 100 consecutive lung cancer patients treated with radiotherapy who underwent standard pre-treatment FDG-PET/CT staging scans. A clinician reviewed the PET/CT scans per clinical cardiac assessment guidelines and classified the cardiac uptake as: 0 = uniform diffuse, 1 = absent, 2 = heterogeneous, with event rates of 20%, 44%, and 35%, respectively. The heart was delineated and 200 novel functional radiomics features were selected to classify cardiac FDG uptake patterns. We divided the data into an 80% training set and a 20% test set to train and evaluate the classification models. Feature reduction was carried out using the Wilcoxon test (with Bonferroni adjusted p<0.05), hierarchical clustering, and Recursive Feature Elimination. Two automatic machine learning (AutoML) frameworks were used to determine classification models: a Random Forest Classifier (Tree-based Pipeline Optimization Tool, TPOT) and Linear Discriminant Analysis (AutoSklearn). 10-fold cross validation was carried out for training and the accuracy of the ability of the models to predict for clinical cardiac assessment is reported. Fifty-one independent radiomics features were reduced to 3 clinically pertinent features (PET 2D Skewness, PET Grey Level Co-occurrence Matrix Correlation, and PET Median) using feature reduction techniques. The model selected by TPOT showed 89.8% predictive accuracy in the cross validation of the training set and 85% predictive accuracy on the test set. The model selected by AutoSklearn showed 89.7% predictive accuracy in the cross validation of the training set and 80% predictive accuracy on the test set. The novelty of this work is that it is the first study to develop and evaluate functional cardiac radiomic features from standard of care FDG PET/CT scans with the data showing good predictive accuracy with clinical imaging evaluation. If validated, the current work provides automated methods to provide functional cardiac information using standard of care imaging that can be used as an imaging biomarker for early clinical toxicity prediction for lung cancer patients.