Surveillance of Pancreatic Health After Diabetes Diagnosis

Pancreatic cancer (PC) is one of the most lethal common cancers (five-year survival 5-7%). In more than 80% of patients the disease has spread before it is detected, ruling out potentially curative treatment options. Early detection offers the possibility of surgery leading to significantly improved overall survival.

There is currently no accepted screening test for pancreatic cancer. The Aventect test is designed to detect clues, or biomarkers for the presence or absence of pancreatic cancer signals in blood. The SAFE-D study will evaluate if the Avantect test can detect pancreatic cancer at an earlier more treatable stage.

People older than 50 years who have recently been diagnosed with type II diabetes have up to ten times higher-than-average risk of having pancreatic cancer without knowing.

The study will recruit 5,000 participants aged 50-84 years old diagnosed with type II diabetes or elevated Hb1Ac levels within the last 200 days from GP practices over 3 years.

Participants will have their blood samples analysed on the Avantect test as soon as possible. If a pancreatic biomarker is detected the participants will be informed and offered a standard of care diagnostic imaging scan (MRI or CT) to rule out pancreatic cancer. All participants will be followed remotely via cancer and mortality registry searches for 3 years from consent to assess any cancer diagnosed during this time.

• Avantect Pancreatic Cancer Test (Device): Avantect test

Primary outcomes

• Sensitivity of the Avantect test [The final analysis will be carried out after 3-year follow up data has been collected for all 5,000 participants.]: The proportion of individuals with one or more Avantect "detected" test result who have pancreatic cancer diagnosed via imaging in relation to all individuals in the study who had pancreatic cancer diagnosed.
• Specificity of the Avantect test [The final analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: The proportion of individuals with one or more Avantect "not detected" test results, and no Avantect "detected" results, who did not have a pancreatic cancer diagnosis in relation to all individuals in the study who did not have a pancreatic cancer diagnosis.

Secondary outcomes

• Stage shift [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: The proportion of pancreatic cancers cases diagnosed at stage I/II out of all participants diagnosed with pancreatic cancer between SAFE-D participants and point-estimate of the proportion from comparative data. Stage shift will be considered successful if the lower-bound of the 95% one-sided proportion in SAFE-D participants is higher than the proportion from comparative data.
• Positive Predictive Value (PPV) of Avantect test in detecting pancreatic cancer (PC) [The final analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: Percentage of participants with an Avantect "detected" result who have pancreatic cancer diagnosed. The analysis will be conducted with a sample size of 5,000, pancreatic cancer prevalence of 0.8%, and 5% lost from the per protocol population. There will be an expected 261 individuals with an Avantect "detected" result. 9.6% (25/261) are expected to have a PC. PPV will be considered successful if a null PPV of 5% can be ruled out at a one-sided p-value of 0.05.
• Negative Predictive Value (NPV) of Avantect test in ruling out pancreatic cancer (PC) [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: With a sample size of 5,000, PC prevalence of 0.8%, and 5% lost from the per protocol population, there will be an expected 4,489 individuals without an Avantect "detected" result. 99.6% (4,476/4,489) are expected to not have a diagnosis of PC. NPV will be considered successful if a null NPV of 99% can be ruled out at a one-sided p-value of 0.05.
• Resection rate of pancreatic cancer [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: Percentage of participants with pancreatic cancer who underwent resection. The analysis will be conducted by comparing the proportion of pancreati cancer cases that underwent resection as a treatment modality between SAFE-D participants and the point-estimate of the proportion from comparative data. Resection rate will be considered successful if the lower-bound of the 95% one-sided proportion in SAFE-D participants is higher than the proportion from comparative data.
• Resectability [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: Percentage of pancreatic cancers deemed resectable by the study MDST.

Other outcomes

• Time-to-event outcomes [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: To estimate the time from new onset diabetes diagnosis to pancreatic cancer diagnosis.
• Overall survival [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: To estimate the overall survival of study participants.
• Effect of the Avantect test on state anxiety over time [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: To assess the effect of the Avantect test on state anxiety over time.
• High-grade neoplasia [The analysis will be carried out after 3-year follow-up data has been collected for all 5,000 participants.]: To investigate the performance characteristics for high-grade neoplasia.

Sex: All, ages: 50 Years to 84 Years

Inclusion Criteria:

* 50 - 84 years of age at the time of enrolment (within year of birth, not month of birth)
* Confirmed type 2 DM diagnosis established within the last 200 days or an initial elevated HbA1c ≥ 48 mmol/mol or 6.5% obtained within the last 200 days. This includes people who have a first elevated HbA1c (≥ 48 mmol/mol or 6.5%) within the last 200 days, even if subsequent HbAc1 measurements return to the the normal range.
* Willing to provide up to 30 mL of blood for each study visit
* Willing and eligible to undergo MRI or CT scan
* Understands the study process and is willing to take part in the study and sign the informed consent form

Exclusion Criteria:

* Prior type I or type II DM diagnosis or an initial HbA1c ≥ 48 mmol/mol or 6.5% obtained prior to the 200-day inclusion window, except gestational elevated HbA1c.
* A history of pancreatic cancer, pancreatic neuroendocrine tumour (pNET) or Pancreatitis
* Under investigation for or confirmed pancreatic cancer
* Under investigation/surveillance for pancreatic cyst
* Any known pancreatic surgery (not including ERCP), or other major surgery requiring anaesthesia within 3 months
* Any invasive solid or haematological cancer in the past 3 years, including cancer recurrence after treatment in the last 3 years
* BMI > 40 at the time of consent
* Blood transfusion within 1 month
* Solid organ transplant recipient
* Currently pregnant
* Needing dialysis