Title: Detecting pancreatic cancer in the largest high-risk group for this disease: A top-down approach
Funder: Cancer Research UK

Abstract: Background Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common cancer (five-year survival is 5-7%). For ~80% of patients, PDAC is detected after disease spread, limiting treatment options. At the time of diagnosis, ~65% of PDAC patients have diabetes mellitus (DM). In ~15% of cases, DM is longstanding, however for 50% of PDAC patients DM is new–onset, with the DM diagnosis coming, on average, 13 months prior to PDAC being identified. Thus, new-onset DM (NOD) is an early warning sign of the presence of PDAC, and individuals with NOD are the largest high-risk group for PDAC. Approximately 1% of adults diagnosed with type 2 DM (T2DM) actually have PDAC-associated DM, a form of type3c DM (T3cDM). The scientific/medical community currently cannot distinguish PDAC-associated DM from T2DM and individuals with NOD are not screened. The US Consortium of Chronic Pancreatitis, Diabetes and Pancreatic Cancer is launching a collection of individuals with NOD. Similar initiatives in Europe are underway. Additional contributions are required; a UK component of the international NOD cohort will ensure that future biomarker-driven screening is relevant to the UK population/healthcare system, and will increase national awareness of the link between NOD and PDAC. Aim To develop a diagnostic test for use in individuals newly diagnosed with DM which will identify those most at risk of a diagnosis of PDAC, allowing them to be screened. Methods Individuals 50 years, newly diagnosed with DM will be recruited (target 2,500) from UK hospitals and general practice. Biosamples and questionnaire/clinical data will be collected to GCP and standardised to US and European collections. While recruitment is ongoing, further biomarker development for the high-risk NOD group will be undertaken. The specificity of biomarkers with potential to distinguish T3cDM (which harbours PDAC-associated DM) from T2DM will be tested in existing high-risk cohorts, including a pilot-scale collection of individuals with NOD (PANDIA) and the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Protocols for biomarker discovery using NOD will be developed/refined. The sensitivity/specificity for the detection of PDAC by combined biomarker and epidemiological/clinical feature analysis will be evaluated in the international NOD cohort. The cost-effectiveness of diagnosing PDAC earlier will be assessed. UK-NOD samples will be made available for research on early PDAC detection. Outcome Our work will enable stratification of individuals with new-onset DM for PDAC risk, making it feasible in future to screen for PDAC in individuals with new-onset DM.

Lay abstract: Background Pancreatic ductal adenocarcinoma (PDAC) is the most lethal common cancer (five-year survival is 5-7%). For ~80% of patients, PDAC is detected after disease spread, limiting treatment options. At the time of diagnosis, ~65% of PDAC patients have diabetes mellitus (DM). In ~15% of cases, DM is longstanding, however for 50% of PDAC patients DM is new–onset, with the DM diagnosis coming, on average, 13 months prior to PDAC being identified. Thus, new-onset DM (NOD) is an early warning sign of the presence of PDAC, and individuals with NOD are the largest high-risk group for PDAC. Approximately 1% of adults diagnosed with type 2 DM (T2DM) actually have PDAC-associated DM, a form of type3c DM (T3cDM). The scientific/medical community currently cannot distinguish PDAC-associated DM from T2DM and individuals with NOD are not screened. The US Consortium of Chronic Pancreatitis, Diabetes and Pancreatic Cancer is launching a collection of individuals with NOD. Similar initiatives in Europe are underway. Additional contributions are required; a UK component of the international NOD cohort will ensure that future biomarker-driven screening is relevant to the UK population/healthcare system, and will increase national awareness of the link between NOD and PDAC. Aim To develop a diagnostic test for use in individuals newly diagnosed with DM which will identify those most at risk of a diagnosis of PDAC, allowing them to be screened. Methods Individuals 50 years, newly diagnosed with DM will be recruited (target 2,500) from UK hospitals and general practice. Biosamples and questionnaire/clinical data will be collected to GCP and standardised to US and European collections. While recruitment is ongoing, further biomarker development for the high-risk NOD group will be undertaken. The specificity of biomarkers with potential to distinguish T3cDM (which harbours PDAC-associated DM) from T2DM will be tested in existing high-risk cohorts, including a pilot-scale collection of individuals with NOD (PANDIA) and the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Protocols for biomarker discovery using NOD will be developed/refined. The sensitivity/specificity for the detection of PDAC by combined biomarker and epidemiological/clinical feature analysis will be evaluated in the international NOD cohort. The cost-effectiveness of diagnosing PDAC earlier will be assessed. UK-NOD samples will be made available for research on early PDAC detection. Outcome Our work will enable stratification of individuals with new-onset DM for PDAC risk, making it feasible in future to screen for PDAC in individuals with new-onset DM.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: CANCER AND NEOPLASMS