Abstract
Pancreatic cancer (PC), a leading cause of cancer-related deaths in the United States, is typically diagnosed at an advanced stage. To improve survival, there is an unmet need to detect pre-malignant lesions and early invasive disease. Prime populations to study for early detection efforts include cohorts of high risk individuals (HRI): those with increased risk to develop pre-malignant pancreatic cysts and PC because of a familial or hereditary predisposition to the disease and those in the general population of sporadic cases who are incidentally found to harbor a pre-malignant pancreatic cyst. The objective of this study was to describe the characteristics and clinical outcomes of cohorts of HRI identified at Moffitt Cancer Center. We set out to determine the uptake of screening, the prevalence and characteristics of solid and cystic pancreatic lesions detected via screening or as incidental findings, and the age at which lesions were detected. Of a total of 329 HRI, roughly one-third were found to have pancreatic lesions, most of which constituted pre-malignant cysts known as intraductal papillary mucinous neoplasms. Individuals with the highest genetic risk for PC were found to have smaller cysts at a much earlier age than sporadic cases with incidental findings; however, many individuals at high genetic risk did not have abdominal imaging reports on file. We also identified a subset of HRI at moderate genetic risk for PC that were found to have cystic and solid pancreatic lesions as part of a diagnostic work-up rather than a screening protocol. These findings suggest the pancreatic research community should consider expanding criteria for who should be offered screening. We also emphasize the importance of continuity of care between cancer genetics and gastrointestinal oncology clinics so that HRI are made aware of the opportunities related to genetic counseling, genetic testing, and screening.
Highlights
Pancreatic ductal adenocarcinoma (PDAC), commonly known as Pancreatic cancer (PC), is currently the third leading cause of cancer-related deaths in the United States and has a 5-year relative survival rate of 8–9%, the lowest of any malignancy [1,2,3,4]
Individuals were classified into three groups of high risk individuals (HRI): (1) Those meeting the 5–10% lifetime risk of PC mentioned in Cancer of the Pancreas Screening (CAPS) guidelines (n = 105): including 45 mutation carriers who reported a first degree relatives (FDR) with PC and 60 individuals with familial PC and no known mutation; (2) those not meeting the CAPS guidelines threshold (n = 158): including 11 individuals who have one affected FDR and 147 individuals with a known deleterious mutation and no family history of PC; and (3) individuals with incidental findings of pancreatic lesions that had no known family history of PC or a hereditary syndrome (“sporadic cases”, n = 66) (Supplementary Figure S1)
We performed a descriptive analysis of the characteristics and clinical outcomes of three groups of high risk individuals (HRI) identified at our cancer center in order to better understand the uptake of screening, the prevalence and characteristics of solid and cystic pancreatic lesions detected via screening or as incidental findings, and the age at which lesions were detected
Summary
Pancreatic ductal adenocarcinoma (PDAC), commonly known as PC, is currently the third leading cause of cancer-related deaths in the United States and has a 5-year relative survival rate of 8–9%, the lowest of any malignancy [1,2,3,4]. In 2018, approximately 55,440 new cases of PC will be diagnosed and 44,330 patients will die from PC [1]. 80–85% of patients are diagnosed with late stage, inoperable disease because symptoms did not appear until the disease had metastasized [5]. Abdominal pain, and weight loss, whereas earlier stages are typically asymptomatic [6]. To improve PC survival, there is a dire need to develop screening approaches to detect early stage, operable malignancies. Given that the lifetime risk for developing PC is only 1.5% [7], screening the general population is impractical; selectively screening individuals at increased risk for PC can enable detection of early-stage malignancies and even pre-malignant lesions and prolong survival [8]
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