Prospective Screening for Pancreatic Ductal Adenocarcinoma in High-Risk Individuals

In this research study, investigators will combine blood-based tests and review of symptoms with standard-of-care pancreatic cancer screening procedures to see if pancreatic cancer can be detected early among individuals with increased risk. Pancreatic cancer screening procedures include Endoscopic Ultrasound (EUS), Magnetic Resonance Imaging (MRI), or Magnetic Resonance Cholangiopancreatography (MRCP).

The research study procedures include screening for eligibility, questionnaires, clinic visits, endoscopic ultrasound (EUS) or Magnetic Resonance (MRI)/Magnetic Resonance Cholangiopancreatography (MRCP), and collection of blood, stool, and saliva samples.

Participation in this research study will be a minimum of 30 months and up to 20 years via review of medical records and the annual collection of blood and stool samples.

It is expected that about 5,000 people will take part in this research study.

This study is supported by the Hale Family Research Center at Dana-Farber Cancer Institute.

Inclusion criteria

Participants must meet any of the following:

• Individuals with pathogenic/likely pathogenic germline variants in STK11, and age ≥30 years.
• Individuals with pathogenic/likely pathogenic germline variants in CDKN2A, and age ≥40 years (or 10 years younger than the earliest exocrine pancreatic cancer diagnosis in the family, whichever is earlier).
• Individuals with pathogenic/likely pathogenic germline variants in one of the other pancreatic cancer susceptibility genes (ATM, BRCA1, BRCA2, MLH1, MSH2, MSH6, EPCAM, PALB2, TP53), and age ≥50 years (or 10 years younger than the earliest exocrine pancreatic cancer diagnosis in the family, whichever is earlier) AND

• Exocrine pancreatic cancer in ≥1 first- or second-degree relative from the same side of (or presumed to be from the same side of) the family as the identified pathogenic/likely pathogenic germline variant.
• Individuals with pathogenic/likely pathogenic variants in PRSS1 AND a clinical phenotype consistent with hereditary pancreatitis, and age ≥40 years (or 20 years after onset of pancreatitis, whichever is earlier).
• Individuals with familial pancreatic cancer including:

• Family history of exocrine pancreatic cancer in ≥2 first-degree relatives from the same side of the family, even in the absence of a known pathogenic/likely pathogenic germline variant, OR
• Family history of exocrine pancreatic cancer in 1 affected first-degree relative and 1 second-degree relative, even in the absence of a known pathogenic/likely pathogenic germline variant, OR
• Family history of exocrine pancreatic cancer in ≥3 first- and/or second-degree relatives from the same side of the family, even in the absence of a known pathogenic/likely pathogenic germline variant.
• Individuals who are undergoing clinically recommended pancreatic cancer surveillance.

Exclusion criteria

• Individuals with active or prior pancreatic ductal adenocarcinoma diagnosis.
• Individuals with any active metastatic cancer.
• Individuals who are unable to give informed consent.
• Individuals who are under the age of 18 (infants, children, teenagers).
• Individuals unable to tolerate Magnetic Resonance Imaging/Magnetic Resonance Cholangiopancreatography and Endoscopic Ultrasound.
• Pregnant women are unlikely to be undergoing screening procedures and will not be considered eligible but can consent to the study at a later date.