A machine learning based delta-radiomics process for early prediction of treatment response of pancreatic cancer

Changes of radiomic features over time in longitudinal images, delta radiomics, can potentially be used as a biomarker to predict treatment response. This study aims to develop a delta-radiomic process based on machine learning by (1) acquiring and registering longitudinal images, (2) segmenting and populating regions of interest (ROIs), (3) extracting radiomic features and calculating their changes (delta-radiomic features, DRFs), (4) reducing feature space and determining candidate DRFs showing treatment-induced changes, and (5) creating outcome prediction models using machine learning. This process was demonstrated by retrospectively analyzing daily non-contrast CTs acquired during routine CT-guided-chemoradiation therapy for 90 pancreatic cancer patients. A total of 2520 CT sets (28-daily-fractions-per-patient) along with their pathological response were analyzed. Over 1300 radiomic features were extracted from the segmented ROIs. Highly correlated DRFs were ruled out using Spearman correlations. Correlation between the selected DRFs and pathological response was established using linear-regression-models. T test and linear-mixed-effects-models were used to determine which DRFs changed significantly compared with first fraction. A Bayesian-regularization-neural-network was used to build a response prediction model. The model was trained using 50 patients and leave-one-out-cross-validation. Performance was judged using the area-under-ROC-curve. External independent validation was done using data from the remaining 40 patients. The results show that 13 DRFs passed the tests and demonstrated significant changes following 2-4 weeks of treatment. The best performing combination differentiating good versus bad responders (CV-AUC = 0.94) was obtained using normalized-entropy-to-standard-deviation-difference-(NESTD), kurtosis, and coarseness. With further studies using larger data sets, delta radiomics may develop into a biomarker for early prediction of treatment response.