胰腺癌基因组检测新方案的开发

Development of a Novel Protocol for Germline Testing in Pancreatic Cancer

ANNALS OF SURGICAL ONCOLOGY

影响因子:3.5

分区:医学2区 / 外科2区肿瘤学3区

发表日期:2024 Nov

作者: Hannah G McDonald, Andrew Kennedy, Angelica L Solomon, Chelsey M Williams, Anna M Reagan, Emily Cassim, Megan Harper, Erin Burke, Terra Armstrong, Michael Gosky, Michael Cavnar, Prakash K Pandalai, Mautin Barry-Hundeyin, Reema Patel, Snigdha Nutalapati, Jessica Moss, Pamela C Hull, Jill Kolesar, Justine C Pickarski, Joseph Kim

DOI: 10.1245/s10434-024-16011-3

摘要

指南现建议对所有胰腺导管腺癌（PDAC）患者进行普遍的遗传基因检测（GGT）。检测可提供可操作的病理变异信息，指导患者及家族的管理。鉴于传统遗传咨询（GC）模型耗时且资源有限，亟需新方法以在不超负荷现有资源的情况下遵循指南。本研究开发了由医生主导的GGT新方案。完成的检测样本由GC团队收取，建立前瞻性数据库并邮寄所有检测单。如检测结果显示具有病理变异，患者将接受全面的GC；阴性和变异不明（VUS）结果将通过简短电话告知。2020年1月至2022年12月期间，310例患者中有81.5%接受了GGT，医生遵从率为82.6%，患者遵从率为98.7%。在310例中，44例（14.2%）检测出病理变异，83例（26.8%）检测为VUS。病理变异包括BRCA1/BRCA2/PALB2（n=18，5.8%）、ATM（n=9，2.9%）、CFTR（n=4，1.3%）、EPCAM/MLH1/MSH2/MSH6/PMS2（n=3，1.0%）和CDKN2A（n=2，0.7%）。GC团队成功联系所有检测出病理变异的患者，讨论检测结果并提供全面咨询。本方案在资源有限的情况下实现了优良的遵从率，为高风险家族成员的级联检测提供了依据。未来将探索确保高风险家族成员遵从检测的方法。

Abstract

Guidelines now recommend universal germline genetic testing (GGT) for all pancreatic ductal adenocarcinoma (PDAC) patients. Testing provides information on actionable pathogenic variants and guides management of patients and family. Since traditional genetic counseling (GC) models are time-intensive and GC resources are sparse, new approaches are needed to comply with guidelines without overwhelming available resources.A novel protocol was developed for physician-led GGT. Completed test kits were delivered to the GC team, who maintained a prospective database and mailed all orders. If results revealed pathogenic variants for PDAC, patients were offered comprehensive GC, whereas negative and variant of uncertain significance (VUS) test results were reported to patients via brief calls.During protocol implementation between January 2020 and December 2022, 310 (81.5%) patients underwent GGT, with a physician compliance rate of 82.6% and patient compliance rate of 98.7%. Of 310 patients tested, 44 (14.2%) patients had detection of pathogenic variants, while 83 (26.8%) patients had VUS. Pathogenic variants included BRCA1/BRCA2/PALB2 (n = 18, 5.8%), ATM (n = 9, 2.9%), CFTR (n = 4, 1.3%), EPCAM/MLH1/MSH2/MSH6/PMS2 (n = 3, 1.0%), and CDKN2A (n = 2, 0.7%). The GC team successfully contacted all patients with pathogenic variants to discuss results and offer comprehensive GC.Our novel protocol facilitated GGT with excellent compliance despite limited GC resources. This framework for GGT allocates GC resources to those patients who would benefit most from GC. As we continue to expand the program, we seek to implement methods to ensure compliance with cascade testing of high-risk family members.