Wang Yifan, Golesworthy Bryn, Cuggia Adeline, Domecq Celine, Chaudhury Prosanto, Barkun Jeffrey, Metrakos Peter, Asselah Jamil, Bouganim Nathaniel, Gao Zu-Hua, Chong George, Foulkes William D, Zogopoulos George
Department of Surgery, McGill University, Montreal, Québec, Canada.
Rosalind and Morris Goodman Cancer Institute, Montreal, Québec, Canada.
J Med Genet. 2022 Aug;59(8):793-800. doi: 10.1136/jmedgenet-2021-108054. Epub 2021 Sep 23.
Traditional medical genetics models are unable to meet the growing demand for germline genetic testing (GT) in patients with exocrine pancreatic cancer (PC). This study investigates the impact of an ambulatory oncology clinic-based GT model.
From 2012 to 2021, patients with PC were prospectively enrolled and considered for GT. Two chronological cohorts were compared: (1) the preuniversal genetic testing (pre-UGT) cohort, which received GT based on clinical criteria or family history; and (2) the post-UGT cohort, where an 86-gene panel was offered to all patients with PC.
Of 847 eligible patients, 735 (86.8%) were enrolled (pre-UGT, n=579; post-UGT, n=156). A higher proportion of the post-UGT cohort received prospective GT (97.4% vs 58.5%, p<0.001). The rate of pathogenic germline alterations (PGA) across both cohorts was 9.9%, with 8.0% of PGAs in PC susceptibility genes. The post-UGT cohort had a higher prevalence of overall PGAs (17.2% vs 6.6%, p<0.001) and PGAs in PC susceptibility genes (11.9% vs 6.3%, p<0.001). The median turnaround time from enrolment to GT report was shorter in the post-UGT cohort (13 days vs 42 days, p<0.001). Probands with a PGA disclosed their GT results to 84% of their first-degree relatives (FDRs). However, only 31% of informed FDRs underwent GT, and the number of new cases per index case was 0.52.
A point-of-care GT model is feasible and expedites access to GT for patients with PC. Strategies to increase the uptake of cascade testing are needed to maximise the clinical impact of an oncology clinic-based GT model.
传统医学遗传学模式无法满足外分泌型胰腺癌（PC）患者对种系基因检测（GT）日益增长的需求。本研究调查了基于门诊肿瘤诊所的GT模式的影响。
2012年至2021年，对PC患者进行前瞻性入组并考虑进行GT。比较了两个按时间顺序排列的队列：（1）普遍基因检测前（pre-UGT）队列，该队列根据临床标准或家族史接受GT；（2）UGT后队列，该队列向所有PC患者提供86基因检测 panel。
在847名符合条件的患者中，735名（86.8%）入组（pre-UGT，n = 579；UGT后，n = 156）。UGT后队列中接受前瞻性GT的比例更高（97.4%对58.5%，p < 0.001）。两个队列中致病种系改变（PGA）的发生率为9.9%，其中8.0%的PGA存在于PC易感基因中。UGT后队列中总体PGA（17.2%对6.6%，p < 0.001）和PC易感基因中PGA（11.9%对6.3%，p < 0.001）的患病率更高。UGT后队列中从入组到GT报告的中位周转时间更短（13天对42天） ，p < 0.001）。有PGA的先证者将其GT结果告知了84%的一级亲属（FDR）。然而，只有31%被告知的FDR接受了GT，每个索引病例的新病例数为0.52。
即时GT模式是可行的，并且加快了PC患者获得GT的速度。需要采取策略来提高级联检测的接受率，以最大限度地发挥基于肿瘤诊所的GT模式的临床影响。
