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Serine

High Risk Group 2 (familial pancreatic cancer relatives):

1. \> 55 years old or 10 years younger than the age of youngest relative with pancreatic cancer, and
2. come from a family with 2 or more members with a history of pancreatic cancer (2 of which have a first-degree relationship consistent with familial pancreatic cancer), and
3. have a first-degree relationship with at least one of the relatives with pancreatic cancer.

If there are 2 or more affected blood relatives, at least 1 must be a first-degree relative of the individual being screened

High Risk Group 3 (Group 1 germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of \~10% or higher):

a. \> 50 years old or 10 years younger than the age of the youngest relative affected, if pancreatic cancer is in family, and b. The Patient is a carrier of a confirmed BRCA2, ATM or PALB2 mutation, regardless of family history of pancreatic cancer. b.\> Individual is a carrier of a confirmed FAMMM (p16/CDKN2A) mutation, age 40 years or older, regardless of family history of pancreas cancer.

High Risk Group 4 (Group 2 germline mutation carriers with an associated with an estimated lifetime risk of pancreatic cancer of \~5%):

1. \> 50 years old or 10 years younger than the age of the youngest relative with pancreatic cancer, and
2. The patient is a carrier of a confirmed BRCA1 or HNPCC (hereditary non-polyposis colorectal cancer or Lynch syndrome, hMLH1, hMSH2, PMS1, hMSH6, EpCAM) gene mutation, and there is \> 1 pancreatic cancer in the family, one of whom is a first- or second-degree relative of the subject to be screened.

High risk group 5 (hereditary pancreatitis) with confirmed gene mutations that predispose to chronic pancreatitis, such as PRSS1, PRSS2, CTRC) and age 50 years or older (these patients have an estimated lifetime risk for pancreatic cancer of 40%) or twenty-years since their first attack of pancreatitis, whichever age is younger.

1. At least 30 years old, and
2. at least 2 of 3 criteria diagnostic of Peutz-Jeghers syndrome (characteristic intestinal hamartomatous polyps, mucocutaneous melanin deposition, or family history of Peutz-Jeghers syndrome), or,
3. known STK11 gene mutation carrier

1. are undergoing routine EGD or Colonoscopy; or Endoscopic Ultrasound (EUS) and/or Endoscopic Retrograde Cholangiopancreatography (ERCP) for non-pancreatic indications as part of their standard medical care, and
2. have no clinical or radiologic suspicion of pancreatic disease (chronic pancreatitis or pancreatic cancer)

1. are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven chronic pancreatitis as part of their standard medical care, and,
2. have no clinical or radiologic suspicion of pancreatic cancer

a. are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven pancreatic ductal adenocarcinoma (based on clinical and radiologic evidence)

are undergoing EUS and/or ERCP for evaluation and/or treatment of suspected or proven pancreatic cancer precursor, intraductal papillary mucinous neoplasm (based on clinical presentation and radiologic or prior EUS or radiologic evidence of a dilated main pancreatic duct and/or pancreatic cystic lesion communicating with the pancreatic ductal system).

inject Secretin to stimulate pancreatic digestive fluid, which is collected in duodenum near ampulla via endoscope suction port. This fluid will be assessed for biomarkers.

MRI abdomen with contrast (MRCP) will be clinically indicated for abnormal novel CA-19-9 lab results.

A tumor marker gene test that will be used to stratify individuals into one of several circulating tumor marker reference ranges for CA19-9. The variants in the genes FUT3 and FUT2 affect the levels of CA19-9.

Tumor marker gene test with CA19-9

Hilary Cosby, RN

Scott Merenda, BSN

James Farrell, MD

Hilary Cosby, RN, CGRN

Michael Goggins, MD

Marcia I Canto, MD

Emily Blair

Chinedu Ukaegbu

Sapna Syngal, MD

Erika Koeppe, MS

Elena Stoffel, MD

Tiffany Lam

Fay Kastrinos, MD

Barbara Heaton

Wendy Brock, RN

Amitabh Chak, MD

Maureen DeMarshall, RN

Daniel Clay

Bryson Katona, MD

Christine Decapite

Sara Booz

Randall Brand, MD

Johns Hopkins clinical research office quality assurance group will monitor and audit this study at Johns Hopkins. The Sub Investigator at each site will be responsible for internal monitoring at their site.

The Sub Investigator at each site will be responsible for internal monitoring at their site. The site sub Investigator and study team will report any serious adverse events to Principal Investigator and annually report adverse events.

Evaluation of the effect of diagnostic tests for pancreatic cancer

No masking of the diagnostic test results

The Cancer of the Pancreas Screening-5 CAPS5)Study

Aim #3: To determine the prevalence of pancreatic lesions, pancreatic fluid mutations and circulating pancreatic epithelial cells among a large cohort of high-risk individuals undergoing pancreatic screening and surveillance of a new cohort in which screening is begun at age \>55.

Aim #4 To evaluate the diagnostic performance of a tumor marker gene test to personalize the normal reference range of tumor markers such as CA19-9 for patients undergoing pancreatic surveillance.

Aim #1: To evaluate pancreatic fluid mutations and circulating pancreatic epithelial cells as accurate markers of neoplasia by comparing their prevalence in cases with sporadic pancreatic neoplasia to healthy and disease controls.

Aim #2: To compare the prevalence of pancreatic fluid mutations and circulating pancreatic epithelial cells among a prospective cohort of individuals with sporadic pancreatic cysts undergoing pancreatic surveillance.

ChiRhoClin, Inc.

National Cancer Institute (NCI)

National Institutes of Health (NIH)

Johns Hopkins University

Chronic Disease

Disease Attributes

Familial Pancreatic Cancer

Chronic Graft Versus Host Disease

Individual with ten fold higher risk to develop pancreatic cancer.

Matthias Löhr, Professor

Marco del Chiaro, Ass prof.

Marco del Chiaro, ass prof.

Matthias Lohr, Professor

Marco del Chiaro, ass. prof.

Early detection of pre-cancerous lesions or early stage pancreatic cancer seems to have a positive impact in survival for patients with an increased genetic risk to develop pancreas cancer.

In this study, following the indication of the swedish guidelines, consecutive patients with a family history for pancreas cancer underwent a clinical surveillance Magnetic Resonance Imaging (MRI) based. The results of this study were analyzed looking in the patients files collected during the screening period.

Pancreatic cancer is the 4th cause of cancer related deaths in USA and in many of the Western Countries. The incidence of the disease is almost corresponding to the mortality rate. For this reason pancreatic cancer can be considered a global lethal disease. Even if treatments have improved, the resection rate in patients suffering from ductal adenocarcinoma remain around 30% and the 5 years survival rates is below 20%. Because of the low incidence of pancreatic cancer in the general population, a population-based screening is not cost/effective. Anyway in the last two decades, data from literature demonstrate that pancreatic cancer can be the phenotypic expression of some know genetic syndromes and the existence of a familial risk to develop pancreatic cancer. In particular for this last condition, called familial pancreatic cancer (FPC), an increased risk is associated with the number of family member affected. In prospective epidemiological studies, is demonstrated that a positive family history of pancreatic cancer is present in about 10% of all consecutive probands. The identification of a population at risk, the suggestions that an early surgical treatment of pancreatic cancer can improve the prognosis and, in particular, the identifications of pre-neoplastic lesions as PanIN and IPMN associated to the natural history of FPC, contributed to the development on National and International guidelines for the surveillance of the individual at increased risk. Even do, today, no consensus is reached on inclusion criteria for a clinical surveillance program, screening modalities and target lesions. Traditionally individual with a 10 fold relative risk to develop pancreatic cancer were considered suitable for a screening program. However, more recently, the CAPS group suggested to include in a surveillance program individuals with a 5 fold higher relative risk. Early pancreatic cancer, IPMN and PanIN lesions are considered the target lesions of a clinical screening, however the concrete possibility to detect PanIN lesions during a surveillance program remain debatable and uncertain.The imaging modality technique used in the existing programs are, alone or in combination, magnetic resonance (MR), computed tomography (CT), endoscopic ultrasound (EUS), endoscopic retrograde cholagiopancreatography (ERCP). Anyway a tendency to use low aggressive modalities as MR and EUS is emerging by the recent recommendations. The results of the clinical studies are quite uncertain and difficult to compare due to different screening modalities and inclusion criteria. The yield of FPC screening programs published in literature range from 50 to 1.3%. The cost/effectiveness of a surveillance program for FPC is not already demonstrated.

The aim of this study is to analyze the preliminary result of a prospective clinical surveillance program for individuals at risk for pancreatic cancer using a low aggressive, MR based, screening.

Patients enrollment Patients with an increased "genetic" risk to develop pancreatic cancer will be enrolled in a MR surveillance program at Karolinska University Hospital.

The patients were enrolled in the study from 3 different ways: relative of probands treated for pancreas cancer at karolinska University Hospital and with a positive family history of pancreatic cancer or with a positive anamnesis of an associated genetic syndrome, subjects, with a "genetically" increased risk, referred to us from other swedish centers, subjects referred to us by general partitioners.

Inclusion criteria for the screening All the individuals with a 10 fold higher relative risk in respect to the general population to develop pancreatic cancer will be included in the study. In case of suspected known genetic syndromes, only patients with detected corresponding gene mutations will be enrolled.

Screening modalities All patients fulfilling the inclusion criteria will be enrolled in the clinical study after a specific informed consent. Basically a complete familial and personal anamensis (including the pedegree) and a clinical examination will be obtained from all the patients. A blood sample will be collected into a bio-bank at Karolinska University Hospital. An MR/MRCP with secretin will be performed for all the patients. If the result of the MR are negative (no findings detected) a one year screening, with the same modalities is recommended. Only patients with some anomaly at the MR will undergo EUS with or without FNA and/or MDCT scan. Patients with a positive anamnesis suggestive for a known genetic syndrome will be offered specific genetic tests (BRCA1/2, SPINK1, PRSS1, p16, STK11) and respective genetic counselling.

Target lesions of the screening Due to the low specificity and sensibility of the available technique in order to detect PanIN lesions, the lobulocentric atrophy areas are not considered a target of our screening. Macroscopic pre-neoplastic lesions (IPMN) or pancreatic solid mass are considered the only lesions suitable for detection and screening.

Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer.

Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer

MRI accuracy in detection precancerous pancreatic lesions.

Karolinska University Hospital

Professor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Cancer of the Pancreas Screening-5 CAPS5)Study	NCT02000089	Pancreas Cancer Peutz-Jeghers S... Gene Mutation Germline Mutati... Lynch Syndrome	Secretin MRI Tumor marker ge...	18 Years -	Johns Hopkins University
The Cancer of the Pancreas Screening-5 CAPS5)Study	NCT02000089	Pancreas Cancer Peutz-Jeghers S... Gene Mutation Germline Mutati... Lynch Syndrome	Secretin MRI Tumor marker ge...	18 Years -	Johns Hopkins University
Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer.	NCT02078245	Hereditary Panc... Hereditary Panc...	MRI	18 Years -	Karolinska University Hospital

Spots Global Cancer Trial Database for hereditary pancreatitis