Predicting the risk of pancreatic cancer in adults with new-onset diabetes: development and internal–external validation of a clinical risk prediction model

Clift, Ash Kieran; Tan, Pui San; Patone, Martina; Liao, Weiqi; Coupland, Carol; Bashford-Rogers, Rachael; Sivakumar, Shivan; Hippisley-Cox, Julia

Abstract

Background: The National Institute for Health and Care Excellence (NICE) recommends that people aged 60+ years with newly diagnosed diabetes and weight loss undergo abdominal imaging to assess for pancreatic cancer. More nuanced stratification could lead to enrichment of these referral pathways. Methods: Population-based cohort study of adults aged 30–85 years at type 2 diabetes diagnosis (2010–2021) using the QResearch primary care database in England linked to secondary care data, the national cancer registry and mortality registers. Clinical prediction models were developed to estimate risks of pancreatic cancer diagnosis within 2 years and evaluated using internal–external cross-validation. Results: Seven hundred and sixty-seven of 253,766 individuals were diagnosed with pancreatic cancer within 2 years. Models included age, sex, BMI, prior venous thromboembolism, digoxin prescription, HbA1c, ALT, creatinine, haemoglobin, platelet count; and the presence of abdominal pain, weight loss, jaundice, heartburn, indigestion or nausea (previous 6 months). The Cox model had the highest discrimination (Harrell’s C-index 0.802 (95% CI: 0.797–0.817)), the highest clinical utility, and was well calibrated. The model’s highest 1% of predicted risks captured 12.51% of pancreatic cancer cases. NICE guidance had 3.95% sensitivity. Discussion: A new prediction model could have clinical utility in identifying individuals with recent onset diabetes suitable for fast-track abdominal imaging.

Citation

Clift, A. K., Tan, P. S., Patone, M., Liao, W., Coupland, C., Bashford-Rogers, R., Sivakumar, S., & Hippisley-Cox, J. (2024). Predicting the risk of pancreatic cancer in adults with new-onset diabetes: development and internal–external validation of a clinical risk prediction model. British Journal of Cancer, 130, 1969-1978. https://doi.org/10.1038/s41416-024-02693-9

• Journal Article Type: Article
• Acceptance Date: Apr 11, 2024
• Online Publication Date: May 3, 2024
• Publication Date: Jun 29, 2024
• Deposit Date: May 9, 2024
• Publicly Available Date: May 9, 2024
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 130
• Pages: 1969-1978
• DOI: https://doi.org/10.1038/s41416-024-02693-9
• Keywords: Epidemiology; Risk factors
• Public URL: https://nottingham-repository.worktribe.com/output/34628695
• Publisher URL: https://www.nature.com/articles/s41416-024-02693-9
• Additional Information: Received: 11 September 2023; Revised: 8 April 2024; Accepted: 11 April 2024; First Online: 3 May 2024; : JH-C is an unpaid director of QResearch, a not-for-profit organisation that is a partnership between the University of Oxford and EMIS Health who supply the QResearch database used for this work. JH-C has a 50% shareholding in ClinRisk Ltd, co-owning it with her husband, who is a director. As a shareholder and spouse of a director, she has a financial and family interest in the ongoing and future success of the company. The company licences software both to the private sector and to NHS bodies or bodies that provide services to the NHS (through GP electronic health record providers, pharmacies, hospital providers and other NHS providers). This software implements algorithms developed from access to the QResearch database during her time at the University of Nottingham. CC reports previous consultancy with ClinRisk Ltd outside the current work. PST reports previous consultation with AstraZeneca and Duke-NUS outside the current work. RB-R is a co-founder of Alchemab Therapeutics Ltd and consultant for Alchemab Therapeutics Ltd, Roche, GSK and UCB outside the current work. SS holds research funding from Bristol Myers Squibb, received fees for ad board for AstraZeneca, received speakers fees from AstraZeneca and received support from AstraZeneca and Novartis for online attendance at meetings. The other authors declare that they do not have any competing interests.; : This study was approved by the QResearch Scientific board (project reference OX153); ethical approval for the QResearch database is with the Derby Research Ethics Committee (reference: 18/EM/0400). Anonymised data sharing from general practices contributing to QResearch is on an individual ‘opt-out’ basis—individual patient consent was not required for this analysis of anonymised, routinely collected clinical data.