Dana-Farber Cancer Institute, Boston, MA.
Harvard Medical School, Boston, MA.
JCO Oncol Pract. 2021 Feb;17(2):e236-e247. doi: 10.1200/OP.20.00678. Epub 2021 Jan 13.
National guidelines recommend genetic counseling and multigene germline testing (GC/MGT) for all patients with pancreatic ductal adenocarcinoma (PDAC). This study's aim was to assess real-world effectiveness of implementing systematic GC/MGT for all patients with PDAC at a high-volume academic institution.
An iterative process for systematizing GC/MGT was developed in which gastrointestinal oncology providers at the Dana-Farber Cancer Institute were recommended to refer all patients with PDAC for GC/MGT (clinician-directed referral). Workflows were subsequently changed such that patients with PDAC were automatically offered GC/MGT when scheduling their initial oncology consultation (automated referral). Clinical and germline data were collected on a consecutive cohort of patients with PDAC undergoing GC/MGT during a 25-month enrollment period (19-month clinician-directed referrals; 6-month automated referrals).
One thousand two hundred fourteen patients with PDAC were seen for initial oncologic evaluation, 266 (21.9%) of whom underwent GC/MGT. Compared with baseline clinician-directed referrals, implementation of automated referrals led to a significant increase in patients with PDAC undergoing GC/MGT (16.5% 38.0%, < .001), including those undergoing multigene germline testing (MGT) ≤ 7 days of initial oncology evaluation (14.7% 60.3%, < .001), with preserved pathogenic variant detection rates (10.0% 11.2%, = 0.84). 16 of 28 (57.1%) pathogenic variant carriers had relatives who pursued cascade germline testing, and 13 of 26 (50.0%) carriers with incurable disease received targeted therapy based on MGT results.
Implementation of systematic GC/MGT in patients with PDAC is feasible and leads to management changes for patients with PDAC and their families. GC/MGT workflows that bypass the need for clinician referral result in superior uptake and time to testing. Further investigation is needed to identify other barriers and facilitators of universal GC/MGT.
国家指南建议对所有胰腺导管腺癌（PDAC）患者进行遗传咨询和多基因种系检测（GC/MGT）。本研究旨在评估在高容量学术机构中对所有 PDAC 患者实施系统 GC/MGT 的实际效果。
我们制定了一个系统地进行 GC/MGT 的迭代过程，建议 Dana-Farber 癌症研究所的胃肠肿瘤学医生将所有 PDAC 患者转介进行 GC/MGT（医生主导的转介）。随后改变了工作流程，使 PDAC 患者在预约首次肿瘤学咨询时自动获得 GC/MGT（自动转介）。在 25 个月的入组期间（19 个月的医生主导的转介；6 个月的自动转介），对接受 GC/MGT 的连续队列的 PDAC 患者收集临床和种系数据。
共有 1214 例 PDAC 患者接受了初始肿瘤评估，其中 266 例（21.9%）接受了 GC/MGT。与基线医生主导的转介相比，实施自动转介显著增加了接受 GC/MGT 的 PDAC 患者数量（16.5% 38.0%，<.001），包括在首次肿瘤学评估后 7 天内接受多基因种系检测（MGT）的患者（14.7% 60.3%，<.001），同时保留了致病性变异检测率（10.0% 11.2%，=0.84）。28 个致病性变异携带者中有 16 个（57.1%）的亲属进行了级联种系检测，26 个（50.0%）不可治愈疾病的携带者根据 MGT 结果接受了靶向治疗。
在 PDAC 患者中实施系统的 GC/MGT 是可行的，并为 PDAC 患者及其家属带来了管理上的改变。绕过医生转介的 GC/MGT 工作流程可提高接受率并缩短检测时间。需要进一步研究以确定普遍进行 GC/MGT 的其他障碍和促进因素。
