Prediction of Pancreatic Cancer Risk in Patients with New-onset Diabetes Using a Machine Learning Approach Based on Routine Biochemical Parameters

To develop a machine-learning model that can predict the risk of pancreatic ductal adenocarcinoma (PDAC) in people with new-onset diabetes (NOD). From a population-based sample of individuals with NOD aged >50 years, patients with pancreatic cancer-related diabetes (PCRD), defined as NOD followed by a PDAC diagnosis within 3 years, were included (n=716). These PCRD patients were randomly matched in a 1:1 ratio with individuals having NOD. Data from Danish national health registries were used to develop a random forest model to distinguish PCRD from Type 2 diabetes. The model was based on age, gender, and parameters derived from feature engineering on trajectories of routine biochemical variables. Model performance was evaluated using receiver operating characteristic curves (ROC) and relative risk scores. The most discriminative model included 20 features and achieved a ROC-AUC of 0.78 (CI:0.75-0.83). Compared to the general NOD population, the relative risk for PCRD was 20-fold increase for the 1% of patients predicted by the model to have the highest cancer risk (3-year cancer risk of 12% and sensitivity of 20%). Age was the most discriminative single feature, followed by the rate of change in haemoglobin A1c and the latest plasma triglyceride level. When the prediction model was restricted to patients with PDAC diagnosed six months after diabetes diagnosis, the ROC-AUC was 0.74 (CI:0.69-0.79). In a population-based setting, a machine-learning model utilising information on age, sex and trajectories of routine biochemical variables demonstrated good discriminative ability between PCRD and Type 2 diabetes.