Radiomics-Based Machine Learning Models Can Detect Pancreatic Cancer on Prediagnostic CTs at a Substantial Lead Time Prior to Clinical Diagnosis

Our purpose was to detect pancreatic ductal adenocarcinoma (PDAC) at the prediagnostic stage (3-36 months before clinical diagnosis) using radiomics-based machine-learning (ML) models, and to compare performance against radiologists in a case-control study.Volumetric pancreas segmentation was performed on prediagnostic computed tomography scans (CTs) (median interval between CT and PDAC diagnosis: 398 days) of 155 patients and an age-matched cohort of 265 subjects with normal pancreas. A total of 88 first-order and gray-level radiomic features were extracted and 34 features were selected through the least absolute shrinkage and selection operator-based feature selection method. The dataset was randomly divided into training (292 CTs: 110 prediagnostic and 182 controls) and test subsets (128 CTs: 45 prediagnostic and 83 controls). Four ML classifiers, K-Nearest Neighbor, Support Vector Machine (SVM), Random Forest, and XGBoost, were evaluated. Specificity of model with highest accuracy was further validated on an independent internal dataset (n = 176) and the public National Institutes of Health dataset (n = 80). Two radiologists (R4 and R5) independently evaluated the pancreas on a 5-point diagnostic scale.Median (range) time between prediagnostic CTs of the test subset and PDAC diagnosis was 386 (97-1092) days. SVM had the highest sensitivity (mean; 95% confidence interval) (95.5; 85.5-100.0), specificity (90.3; 84.3-91.5), F1-score (89.5; 82.3-91.7), area under the curve (AUC) (0.98; 0.94-0.98), and accuracy (92.2%; 86.7-93.7) for classification of CTs into prediagnostic versus normal. All 3 other ML models, K-Nearest Neighbor, Random Forest, and XGBoost, had comparable AUCs (0.95, 0.95, and 0.96, respectively). The high specificity of SVM was generalizable to both the independent internal (92.6%) and the National Institutes of Health dataset (96.2%). In contrast, interreader radiologist agreement was only fair (Cohen's kappa 0.3) and their mean AUC (0.66; 0.46-0.86) was lower than each of the 4 ML models (AUCs: 0.95-0.98) (P < .001). Radiologists also recorded false positive indirect findings of PDAC in control subjects (n = 83) (7% R4, 18% R5).Radiomics-based ML models can detect PDAC from normal pancreas when it is beyond human interrogation capability at a substantial lead time before clinical diagnosis. Prospective validation and integration of such models with complementary fluid-based biomarkers has the potential for PDAC detection at a stage when surgical cure is a possibility.