A deep learning algorithm to predict risk of pancreatic cancer from disease trajectories.

Journal: Nature medicine
Published Date:

Abstract

Pancreatic cancer is an aggressive disease that typically presents late with poor outcomes, indicating a pronounced need for early detection. In this study, we applied artificial intelligence methods to clinical data from 6 million patients (24,000 pancreatic cancer cases) in Denmark (Danish National Patient Registry (DNPR)) and from 3 million patients (3,900 cases) in the United States (US Veterans Affairs (US-VA)). We trained machine learning models on the sequence of disease codes in clinical histories and tested prediction of cancer occurrence within incremental time windows (CancerRiskNet). For cancer occurrence within 36 months, the performance of the best DNPR model has area under the receiver operating characteristic (AUROC) curve = 0.88 and decreases to AUROC (3m) = 0.83 when disease events within 3 months before cancer diagnosis are excluded from training, with an estimated relative risk of 59 for 1,000 highest-risk patients older than age 50 years. Cross-application of the Danish model to US-VA data had lower performance (AUROC = 0.71), and retraining was needed to improve performance (AUROC = 0.78, AUROC (3m) = 0.76). These results improve the ability to design realistic surveillance programs for patients at elevated risk, potentially benefiting lifespan and quality of life by early detection of this aggressive cancer.

Authors

  • Davide Placido
    NNF Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
  • Bo Yuan
    New Use Agriculture and Natural Plant Products Program, Department of Plant Biology and Center for Agricultural Food Ecosystems, Institute of Food, Nutrition & Health, Rutgers University, 59 Dudley Road, New Brunswick, NJ, 08901, USA.
  • Jessica X Hjaltelin
    Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Chunlei Zheng
    Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
  • Amalie D Haue
    Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Piotr J Chmura
    Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Chen Yuan
    Group for Suicide Studies, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario M5T 1R8, Canada.
  • Jihye Kim
    Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Renato Umeton
    Dana-Farber Cancer Institute, Boston, MA, USA.
  • Gregory Antell
    Dana-Farber Cancer Institute, Boston, MA, USA.
  • Alexander Chowdhury
    Dana-Farber Cancer Institute, Boston, MA, USA.
  • Alexandra Franz
    Harvard Medical School, Boston, MA, USA.
  • Lauren Brais
    Dana-Farber Cancer Institute, Boston, MA, USA.
  • Elizabeth Andrews
    Dana-Farber Cancer Institute, Boston, MA, USA.
  • Debora S Marks
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02139, USA. Electronic address: debbie@hms.harvard.edu.
  • Aviv Regev
    Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Siamack Ayandeh
    VA Boston Healthcare System, Boston, MA, USA.
  • Mary T Brophy
    VA Boston Healthcare System, Boston, MA, USA.
  • Nhan V Do
    VA Boston Healthcare System, Boston, MA, USA.
  • Peter Kraft
    Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Brian M Wolpin
    From the Department of Radiology, Brigham and Women's Hospital, Boston, Mass (K.M., C.P. Bay, N.M., W.C.W., M.H.R.); MGH & BWH Center for Clinical Data Science, Boston, Mass (C.P. Bridge, K.P.A.); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Mass (A.B., L.K.B., B.M.W.); and Department of Radiology, Massachusetts General Hospital, Boston, Mass (F.J.F., F.M.T.).
  • Michael H Rosenthal
    Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (W.F.W., M.T.C., K.M., S.A.G., E.G., M.H.R., G.C.G., K.P.A.); and MGH & BWH Center for Clinical Data Science, Boston, Mass (W.F.W., M.T.C., K.M., K.P.A.).
  • Nathanael R Fillmore
    Harvard Medical School, Boston, MA, USA.
  • Søren Brunak
    NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
  • Chris Sander
    Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065 NY; and arne@bioinfo.se debbie@hms.harvard.edu cccsander@gmail.com.