Is Biannual Surveillance for Pancreatic Cancer Sufficient in Individuals With Genetic Syndromes or Familial Pancreatic Cancer?
Background: Individuals with a family history of pancreatic adenocarcinoma (PC) or with a germline mutation in a PC susceptibility gene are at increased risk of developing PC. These high-risk individuals (HRIs) may benefit from PC surveillance. Methods: A PC surveillance program was developed to evaluate the detection of premalignant lesions and early-stage PCs using biannual imaging and to determine whether locally advanced or metastatic PCs develop despite biannual surveillance. From January 2013 to April 2020, asymptomatic HRIs were enrolled and followed with alternating MRI and endoscopic ultrasound every 6 months. Results: Of 75 HRIs, 43 (57.3%) had a germline mutation in a PC susceptibility gene and 32 (42.7%) had a familial pancreatic cancer (FPC) pedigree. Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) were identified in 26 individuals (34.7%), but only 2 developed progressive lesions. One patient with Peutz-Jeghers syndrome (PJS) developed locally advanced PC arising from a BD-IPMN. Whole-genome sequencing of this patient’s PC and of a second patient with PJS-associated PC from the same kindred revealed biallelic inactivation of STK11 in a KRAS-independent manner. A review of 3,853 patients from 2 PC registries identified an additional patient with PJS-associated PC. All 3 patients with PJS developed advanced PC consistent with the malignant transformation of an underlying BD-IPMN in <6 months. The other surveillance patient with a progressive lesion had FPC and underwent resection of a mixed-type IPMN that harbored polyclonal KRAS mutations. Conclusions: PC surveillance identifies a high prevalence of BD-IPMNs in HRIs. Patients with PJS with BD-IPMNs may be at risk for accelerated malignant transformation.
Submitted May 4, 2021; final revision received October 25, 2021; accepted for publication October 26, 2021.
Author contributions: Study concept: Wang, Foulkes, Waschke, Zogopoulos. Data curation: Wang, Cuggia, Parent, Stanek, Denroche, Domecq, Golesworthy, Shwaartz, Borgida, Holter, Chong, O’Kane, Waschke. Formal analysis: Wang, Denroche, Domecq, Golesworthy, Zogopoulos. Funding acquisition: Wilson, Knox, Gallinger, Zogopoulos. Investigation: Wang, Cuggia, Parent, Stanek, Zhang, Grant, Domecq, Golesworthy, Shwaartz, Holter, Chong, O’Kane, Fischer, Gao, Foulkes, Waschke, Zogopoulos. Methodology: Wang, Cuggia, Parent, Stanek, Denroche, Zhang, Grant, Domecq, Golesworthy, Borgida, Chong, Fischer, Gao, Foulkes, Waschke, Zogopoulos. Project administration: Wilson. Resources: Cuggia, Parent, Stanek, Borgida, Holter, Wilson, Chong, O’Kane, Knox, Fischer, Gallinger, Gao, Foulkes, Waschke, Zogopoulos. Software: Denroche, Zhang. Supervision: Gallinger, Foulkes, Zogopoulos. Visualization: Wang, Denroche, Zhang, Shwaartz. Writing—original draft: Wang, Zogopoulos. Writing—review and editing: All authors.
Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: This work was supported through funding provided by the Terry Fox Research Institute (project 1078) and the Pancreatic Cancer Canada Foundation. This work was supported by the Quebec Cancer Consortium and the Ministère de l’Économie et de l’Innovation du Québec through the Fonds d’accélération des collaborations en santé. The Ontario Institute for Cancer Research (PanCuRx Translational Research Initiative) is supported through funding provided by the Government of Ontario, the Princess Margaret Cancer Foundation, and the Canadian Cancer Society Research Institute. Dr. Wang is supported by a Vanier Canada Graduate Scholarship, the Fonds de recherche du Québec—Santé/Ministère de la Santé et des Services sociaux training program, and the McGill University Surgical-Scientist Program. Dr. O’Kane is supported by the Lewitt Fellowship. Dr. Knox is the recipient of the Wilfred G. Lewitt Chair in Pancreatic Cancer Research. Dr. Gallinger is the recipient of an Investigator Award from the Ontario Institute for Cancer Research. Dr. Zogopoulos is a clinical research scholar of the Fonds de recherche du Québec—Santé and a recipient of the Michal and Renata Hornstein Career Award from McGill University.
Disclaimer: The funding agencies were not involved in the study design, collection, analysis, and interpretation of the data or in the writing of the manuscript.
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