Risk Prediction of Pancreatic Cancer in Patients with Recent-onset Hyperglycemia: A Machine-learning Approach

Background: New-onset diabetes (NOD) has been suggested as an early indicator of pancreatic cancer. However, the definition of NOD by the American Diabetes Association requires 2 simultaneous or consecutive elevated glycemic measures. We aimed to apply a machine-learning approach using electronic health records to predict the risk in patients with recent-onset hyperglycemia. Materials and Methods: In this retrospective cohort study, health plan enrollees 50 to 84 years of age who had an elevated (6.5%+) glycated hemoglobin (HbA1c) tested in January 2010 to September 2018 with recent-onset hyperglycemia were identified. A total of 102 potential predictors were extracted. Ten imputation datasets were generated to handle missing data. The random survival forests approach was used to develop and validate risk models. Performance was evaluated by c-index, calibration plot, sensitivity, specificity, and positive predictive value. Results: The cohort consisted of 109,266 patients (mean age: 63.6 y). The 3-year incidence rate was 1.4 (95% confidence interval: 1.3-1.6)/1000 person-years of follow-up. The 3 models containing age, weight change in 1 year, HbA1c, and 1 of the 3 variables (HbA1c change in 1 y, HbA1c in the prior 6 mo, or HbA1c in the prior 18 mo) appeared most often out of the 50 training samples. The c-indexes were in the range of 0.81 to 0.82. The sensitivity, specificity, and positive predictive value in patients who had the top 20% of the predicted risks were 56% to 60%, 80%, and 2.5% to 2.6%, respectively. Conclusion: Targeting evaluation at the point of recent hyperglycemia based on elevated HbA1c could offer an opportunity to identify pancreatic cancer early and possibly impact survival in cancer patients.