Predictive modeling of outcomes following definitive chemoradiotherapy for oropharyngeal cancer based on FDG-PET image characteristics

In this study, we investigate the use of imaging feature-based outcomes research ('radiomics') combined with machine learning techniques to develop robust predictive models for the risk of all-cause mortality (ACM), local failure (LF), and distant metastasis (DM) following definitive chemoradiation therapy (CRT). One hundred seventy four patients with stage III-IV oropharyngeal cancer (OC) treated at our institution with CRT with retrievable pre- and post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans were identified. From pre-treatment PET scans, 24 representative imaging features of FDG-avid disease regions were extracted. Using machine learning-based feature selection methods, multiparameter logistic regression models were built incorporating clinical factors and imaging features. All model building methods were tested by cross validation to avoid overfitting, and final outcome models were validated on an independent dataset from a collaborating institution. Multiparameter models were statistically significant on 5 fold cross validation with the area under the receiver operating characteristic curve (AUC) = 0.65 (p = 0.004), 0.73 (p = 0.026), and 0.66 (p = 0.015) for ACM, LF, and DM, respectively. The model for LF retained significance on the independent validation cohort with AUC = 0.68 (p = 0.029) whereas the models for ACM and DM did not reach statistical significance, but resulted in comparable predictive power to the 5 fold cross validation with AUC = 0.60 (p = 0.092) and 0.65 (p = 0.062), respectively. In the largest study of its kind to date, predictive features including increasing metabolic tumor volume, increasing image heterogeneity, and increasing tumor surface irregularity significantly correlated to mortality, LF, and DM on 5 fold cross validation in a relatively uniform single-institution cohort. The LF model also retained significance in an independent population.