S0025 Patients in Familial Pancreatic Cancer Kindreds Demonstrate Increased High-Risk Radiological Features Compared to Those With Deleterious Germline Variants in a High-Risk Pancreatic Surveillance Program

Abstract

INTRODUCTION: Recent literature has identified risk factors for neoplastic progression in patients at increased risk of pancreatic ductal adenocarcinoma (PDAC). Solid pancreatic masses, ≥ 3 cysts at baseline, main pancreatic duct dilation ≥ 5 mm at baseline, and the presence of pathogenic germline variants have been described as being associated with neoplastic progression. METHODS: We performed a retrospective study of high-risk individuals (HRIs) who underwent pancreatic surveillance at a tertiary referral center between May 2013 and April 2020. HRIs were included if they 1) had a pathogenic (P) or likely pathogenic (LP) germline variant that has been associated with PDAC, with at least one first- or second-degree relative with PDAC, or 2) were from familial pancreatic cancer (FPC) kindreds, defined as patients without an identifiable germline mutation but with two or more relatives with PDAC, at least one of whom is a first degree relative of the HRI. Initial surveillance imaging results and clinical data were reviewed. Univariable analyses were performed using Fisher’s exact test and multivariable analyses using logistic regression. RESULTS: A total of 117 patients met inclusion criteria: 39 with P/LP germline variants and 78 from FPC kindreds. Seventy-eight (66.7%) study subjects were female and median age was 63.3 ± 12.4. No other differences were noted in demographics. Of the 39 P/LP germline variants, 12 (30.8%) were in BRCA1, BRCA2 20 (51.3%), ATM 2 (5.1%), PALB2 1 (2.6%), and MSH2 4 (10.3%). Worrisome radiologic features included solid masses (n = 2), multifocal cysts (n = 26), or main pancreatic duct dilation ≥ 5 mm (n = 3) at baseline imaging with endoscopic ultrasound or magnetic resonance cholangiopancreatography. On initial surveillance, 27 (34.6%) patients from FPC kindreds exhibited worrisome radiologic findings compared to 4 (10.3%) of those with germline variants (p = 0.007). Multivariate logistic regression demonstrated that FPC (aOR 4.08, 95% CI 1.22–13.68) and age (aOR 1.10, 95% CI 1.04–1.17) were predictors of worrisome radiologic findings on initial surveillance when adjusting for confounders. CONCLUSION: In our study, patients in the FPC cohort exhibited a higher prevalence of worrisome radiologic features compared to patients with germline mutations. Further evaluation is needed to determine whether FPC patients with worrisome features are at increased risk of neoplastic progression compared to patients with P/LP germline variants in a high-risk cohort.Table 1.: Logistic Regression Analysis of Factors Associated with Worrisome Radiologic Features