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

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          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.

          Abstract

          A deep learning algorithm using electronic health records from two large cohorts of patients predicts the risk of pancreatic cancer from pre-cancer disease trajectories up to 3 years in advance, showing promising performance in retrospective validation.

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          Deep learning.

          Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
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            Dermatologist-level classification of skin cancer with deep neural networks

            Skin cancer, the most common human malignancy, is primarily diagnosed visually, beginning with an initial clinical screening and followed potentially by dermoscopic analysis, a biopsy and histopathological examination. Automated classification of skin lesions using images is a challenging task owing to the fine-grained variability in the appearance of skin lesions. Deep convolutional neural networks (CNNs) show potential for general and highly variable tasks across many fine-grained object categories. Here we demonstrate classification of skin lesions using a single CNN, trained end-to-end from images directly, using only pixels and disease labels as inputs. We train a CNN using a dataset of 129,450 clinical images—two orders of magnitude larger than previous datasets—consisting of 2,032 different diseases. We test its performance against 21 board-certified dermatologists on biopsy-proven clinical images with two critical binary classification use cases: keratinocyte carcinomas versus benign seborrheic keratoses; and malignant melanomas versus benign nevi. The first case represents the identification of the most common cancers, the second represents the identification of the deadliest skin cancer. The CNN achieves performance on par with all tested experts across both tasks, demonstrating an artificial intelligence capable of classifying skin cancer with a level of competence comparable to dermatologists. Outfitted with deep neural networks, mobile devices can potentially extend the reach of dermatologists outside of the clinic. It is projected that 6.3 billion smartphone subscriptions will exist by the year 2021 (ref. 13) and can therefore potentially provide low-cost universal access to vital diagnostic care.
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              Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.

              Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future. ©2014 American Association for Cancer Research.
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                Author and article information

                Contributors
                soren.brunak@cpr.ku.dk
                chris@sanderlab.org
                Journal
                Nat Med
                Nat Med
                Nature Medicine
                Nature Publishing Group US (New York )
                1078-8956
                1546-170X
                8 May 2023
                8 May 2023
                2023
                : 29
                : 5
                : 1113-1122
                Affiliations
                [1 ]GRID grid.5254.6, ISNI 0000 0001 0674 042X, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, , University of Copenhagen, ; Copenhagen, Denmark
                [2 ]GRID grid.38142.3c, ISNI 000000041936754X, Harvard Medical School, ; Boston, MA USA
                [3 ]GRID grid.65499.37, ISNI 0000 0001 2106 9910, Dana-Farber Cancer Institute, ; Boston, MA USA
                [4 ]GRID grid.66859.34, ISNI 0000 0004 0546 1623, Broad Institute of MIT and Harvard, ; Boston, MA USA
                [5 ]GRID grid.410370.1, ISNI 0000 0004 4657 1992, VA Boston Healthcare System, ; Boston, MA USA
                [6 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Boston University School of Medicine, ; Boston, MA USA
                [7 ]GRID grid.475435.4, Copenhagen University Hospital, , Rigshospitalet, ; Copenhagen, Denmark
                [8 ]GRID grid.38142.3c, ISNI 000000041936754X, Harvard T.H. Chan School of Public Health, ; Boston, MA USA
                [9 ]GRID grid.116068.8, ISNI 0000 0001 2341 2786, Massachusetts Institute of Technology, ; Cambridge, MA USA
                [10 ]GRID grid.5386.8, ISNI 000000041936877X, Weill Cornell Medicine, ; New York City, NY USA
                [11 ]GRID grid.62560.37, ISNI 0000 0004 0378 8294, Brigham and Women’s Hospital, ; Boston, MA USA
                [12 ]GRID grid.418158.1, ISNI 0000 0004 0534 4718, Present Address: Genentech, Inc., ; South San Francisco, CA USA
                Author information
                http://orcid.org/0000-0002-8327-8838
                http://orcid.org/0000-0002-9737-461X
                http://orcid.org/0000-0001-7656-7976
                http://orcid.org/0000-0002-9371-6918
                http://orcid.org/0000-0002-5561-6932
                http://orcid.org/0000-0001-9388-2281
                http://orcid.org/0000-0003-3293-3158
                http://orcid.org/0000-0001-6868-7011
                http://orcid.org/0000-0002-4472-8103
                http://orcid.org/0000-0002-0455-1032
                http://orcid.org/0000-0003-0316-5866
                http://orcid.org/0000-0001-6059-6270
                Article
                2332
                10.1038/s41591-023-02332-5
                10202814
                37156936
                5d8ffb66-2f43-4d39-b532-49b8e764767f
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 10 March 2022
                : 31 March 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/100009730, EIF | Stand Up To Cancer (SU2C);
                Award ID: SU2C#6180
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100000002, U.S. Department of Health & Human Services | National Institutes of Health (NIH);
                Award ID: U01 CA210171
                Award ID: P50 CA127003
                Award ID: U01 CA210171
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100009708, Novo Nordisk Fonden (Novo Nordisk Foundation);
                Award ID: NNF17OC0027594
                Award ID: NNF14CC0001
                Award Recipient :
                Categories
                Article
                Custom metadata
                © Springer Nature America, Inc. 2023

                Medicine
                cancer epidemiology,machine learning,cancer screening
                Medicine
                cancer epidemiology, machine learning, cancer screening

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