Abstract
Pancreatic cancer is an aggressive disease that typically presents late with poor patient outcomes. There is a pronounced medical need for early detection of pancreatic cancer, which can be facilitated by identifying high-risk populations. Here we apply artificial intelligence (AI) methods to a large corpus of more than 6 million patient records spanning 40 years with 24,000 pancreatic cancer cases in the Danish National Patient Registry. In contrast to existing methods that do not use temporal information, we explicitly train machine learning models on the time sequence of diseases in patient clinical histories. In addition, the models predict the risk of cancer occurrence in time intervals of 3 to 60 months duration after risk assessment. For cancer occurrence within 12 months, the performance of the best model trained on full trajectories (AUROC=0.91) substantially exceeds that of a model without time information (AUROC=0.81). For the best model, lower performance (AUROC=0.86) results when disease events within a 3 month window before cancer diagnosis are excluded from training, reflecting the decreasing information value of earlier disease events. These results raise the state-of-the-art level of performance of cancer risk prediction on real-world data sets and provide support for the design of real-world population-wide clinical screening trials, in which high risk patients are assigned to serial imaging and measurement of blood-based markers to facilitate earlier cancer detection. AI on real-world clinical records has the potential to shift focus from treatment of late- to early-stage cancer, benefiting patients by improving lifespan and quality of life.
Competing Interest Statement
S.B. has ownerships in Intomics A/S, Hoba Therapeutics Aps, Novo Nordisk A/S, Lundbeck A/S and managing board memberships in Proscion A/S and Intomics A/S. B.M.W. notes grant funding from Celgene and Eli Lilly; consulting fees from BioLineRx, Celgene, and GRAIL. A.R. is a co-founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas, and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics and Asimov until July 31, 2020. From August 1, 2020, A.R. is an employee of Genentech.