Pancreatic Cancer Risk and Screening Outcomes in Li-Fraumeni Syndrome.

Objectives: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome that may confer increased pancreatic cancer (PC) risk. This study assesses PC risk and the rate of pancreatic imaging abnormalities in LFS.

Methods: PC prevalence in LFS was calculated for individuals with a known TP53 variant from the IARC/NCI database. Pancreatic imaging studies across three institutional LFS cohorts were reviewed and compared using Fisher's Exact test.

Results: Of 3043 individuals with LFS in the IARC/NCI database 46 (1.5%) had PC and 42/1243 (3.4%) LFS families had a member with PC. Amongst PCs with a known age of diagnosis, 2.6% and 43.2% were diagnosed prior to age 30 and 50 respectively. Across three institutional LFS cohorts, 32/329 (9.7%) individuals had a pancreatic imaging abnormality, including cysts in 20 (6.1%) and a mass in 4 (1.2%). Whole-body MRI (WBMRI) had the lowest detection rate of pancreatic abnormalities (6%) whereas endoscopic ultrasound (EUS)/MRI Abdomen (MRI Abd) had the highest (50%/20.8%, respectively). Cysts were detected more frequently with EUS/MRI Abd (33.1%/18.1%, respectively) compared to WBMRI (4.3%). Individuals older than age 50 were more likely to have a pancreatic abnormality (35.8% versus 4.7%, P<0.01) or pancreatic cyst (26.4% compared to 2.2%, P<0.001) compared to those younger than age 50.

Conclusions: PC may occur earlier in LFS compared to the general population. WBMRI identifies pancreatic abnormalities less frequently than other pancreatic cancer screening modalities in LFS. If dedicated PC screening is performed in LFS, screening should likely start prior to age 50 and use either EUS or MRI Abd.