Genetic testing to guide screening for pancreatic ductal adenocarcinoma: Results of a microsimulation model.

Autor: Peters MLB; Division of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, USA. Electronic address: mbpeters@bidmc.harvard.edu., Eckel A; Institute for Technology Assessment, Massachusetts General Hospital, USA., Lietz A; Institute for Technology Assessment, Massachusetts General Hospital, USA., Seguin C; Institute for Technology Assessment, Massachusetts General Hospital, USA., Mueller P; Institute for Technology Assessment, Massachusetts General Hospital, USA., Hur C; Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Current Affiliation: Division of Gastroenterology, Columbia University College of Physicians and Surgeons, USA., Pandharipande PV; Institute for Technology Assessment and Department of Radiology, Massachusetts General Hospital, USA.
Jazyk: angličtina
Zdroj: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] [Pancreatology] 2022 Sep; Vol. 22 (6), pp. 760-769. Date of Electronic Publication: 2022 May 31.
DOI: 10.1016/j.pan.2022.05.003
Abstrakt: Background: First-degree relatives (FDRs) of patients with pancreatic ductal adenocarcinoma (PDAC) have elevated PDAC risk, partially due to germline genetic variants. We evaluated the potential effectiveness of genetic testing to target MRI-based screening among FDRs.
Methods: We used a microsimulation model of PDAC, calibrated to Surveillance, Epidemiology, and End Results (SEER) data, to estimate the potential life expectancy (LE) gain of screening for each of the following groups of FDRs: individuals who test positive for each of eight variants associated with elevated PDAC risk (e.g., BRCA2, CDKN2A); individuals who test negative; and individuals who do not test. Screening was assumed to take place if LE gains were achievable. We simulated multiple screening approaches, defined by starting age and frequency. Sensitivity analysis evaluated changes in results given varying model assumptions.
Results: For women, 92% of mutation carriers had projected LE gains from screening for PDAC, if screening strategies (start age, frequency) were optimized. Among carriers, LE gains ranged from 0.1 days (ATM+ women screened once at age 70) to 510 days (STK11+ women screened annually from age 40). For men, LE gains were projected for all mutation carriers, ranging from 0.2 days (BRCA1+ men screened once at age 70) to 620 days (STK11+ men screened annually from age 40). For men and women who did not undergo genetic testing, or for whom testing showed no variant, screening yielded small LE benefit (0-2.1 days).
Conclusions: Genetic testing of FDRs can inform targeted PDAC screening by identifying which FDRs may benefit.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Peters: Outside the submitted work, institutional funding from Ambry Genetics, BeiGene, and Berg, honoraria and consulting fees from Agios and Exelixis, travel expenses from Halozyme, AstraZeneca, and Exelixis. Eckel: none; Lietz: none; Seguin: none; Mueller: none; Hur: none; Pandharipande: none.
(Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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