Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk
Preliminary Evaluation of Screening for Pancreatic Cancer in Patients With Inherited Genetic Risk
The study is a prospective, observational study evaluating the utility of endoscopic
 ultrasound or MRI for the identification of preneoplastic and neoplastic pancreatic lesions
 in patients at high risk for pancreatic cancer, specifically those with BRCA1/2, ATM, or
 PALB2 mutations.
Endoscopic Ultrasound (EUS) has emerged as a critical component in the imaging, staging, and
 diagnosis of pancreatic cancer. Not only can EUS delineate a mass utilizing sonography
 through the wall of the stomach or duodenum, but it also can obtain diagnostic fine needle
 aspiration of suspicious lesions. Especially in patients with incomplete visualization of a
 mass on cross-sectional imaging, EUS can provide valuable anatomic information prior to
 surgical exploration. While several studies have demonstrated that EUS has high sensitivity
 and specificity in diagnosing pancreatic masses, head-to-head comparisons with established
 modalities like CT have been often methodologically flawed. In a meta-analysis, it was found
 that of 4 studies that assessed resectability, 2 showed no difference and 1 favored each
 modality. As such, estimates of accuracy for assessing preoperative resectability have also
 ranged in several studies from 63-93%. As such it has been recognized as an accepted modality
 for the evaluation of potential pancreatic malignany.

 While screening in the general population is not feasible given the low incidence of PDAC,
 screening in high risk cohorts may allow for early detection of resectable, and potentially
 curable tumors. Clinical outcome of patients with smaller, non-metastasized tumors have a
 significantly improved 5-year survival. Generally the current recommendation is that patients
 who are first degree relatives of patients with PDAC from a familial PDAC kindred with at
 least 2 affected first-degree relatives, patients with Peutz-Jegher's syndrome, and patients
 with CDKN2A/BRCA1/BRCA2/ATM/PALB2/Lynch mutations with a first or second degree relative with
 pancreatic cancer would qualify for screening in the context of the CAPS5 trial. However,
 very recent evidence in a large Canadian study of pancreatic cancer patients demonstrated
 germline carrier status for BRCA1/2, and ATM in their cohort was associated with first degree
 relatives with breast and colorectal cancer but not pancreatic cancer, suggesting that we may
 have to re-evaluate criteria for pancreatic cancer screening in this population. Thus, the
 risk of pancreatic cancer development in this cohort of patients would not be addressed by
 the CAPS5 protocol, but would uniquely be addressed in our proposed study. In terms of
 modality, interval, and age to start/stop, there remains debate but generally annual EUS/MRI
 has been utilized. Therefore, amongst patients with increased risk of pancreatic cancer, like
 those with BRCA1/2, ATM, or PALB2 mutations, the successful identification of early
 neoplastic/preneoplastic lesions of the pancreas would allow for timely intervention and
 improved survival in this cohort and thus would be of high clinical relevance.

 Thus we propose to utilize the unique cohort of increased risk patients followed at the
 University of Pennsylvania, to identify patients with BRCA1, BRCA2, ATM, or PALB2 mutations,
 regardless of family history of pancreatic cancer, and enroll them on an annual prospective
 pancreatic screening program. The hypothesis is that through early screening interventions,
 morbidity and mortality from this under-recognized malignancy in this high-risk patient
 population will be reduced.
Inclusion Criteria

 -  Age >= 18

 -  Documented germline pathogenic or likely pathogenic BRCA1, BRCA2, ATM, or PALB2
 mutation

 -  If no history of PDAC in a first or second degree relative, age >= 50

 -  If there is a history of PDAC in a first or second degree relative, minimum age of
 eligibility is 10 years younger than the age of onset of the youngest relative with
 pancreatic cancer

 Exclusion Criteria

 • Pregnancy