Implementation of a Video-Based Remote Germline Testing for Individuals with Pancreatic Ductal Adenocarcinoma

Up to 7–10% of patients with pancreatic ductal adenocarcinoma (PDAC) have germline mutations, but traditional genetics referral criteria (ex: PDAC family history) have not proven to be good predictors^1,2. In 2018, updated national guidelines recommended universal germline testing (GT) for PDAC patients³, but uptake remains dismally low, prompting the need for systematic approaches⁴. Given the aggressiveness of PDAC, the window of opportunity for GT is short and often overshadowed by treatment initiation. We designed a video-based care delivery model for universal GT in PDAC patients to streamline testing and make it rapidly available to a wider audience. This model was implemented from May 2019-July 2021, allowing us to capture genetic uptake preceding and during COVID-19 pandemic.

A seven minutes-long educational video featuring a genetic counselor describing the benefits, risks, and implications of GT was shown to a cohort of PDAC patients that presented to MD Anderson during a 2-year enrollment period. The video was shown in lieu of an initial consult with a genetic counselor and watched by patients on a mobile device in the clinic (before March 2020) or remotely after the start of the pandemic in the U.S. (March 2020 onwards). After watching the video, patients could elect to pursue GT and get tested on-site or remotely (at home), providing either a saliva or blood sample (see Supplementary Methods). Only patients who had not undergone GT or previously had not met with a genetic counselor were included. After patients consented to GT, research coordinators explained the study objectives and asked for consent to participate in a genetic registry. The Registry was approved by the Institutional Review Board at MD Anderson Cancer Center (PA19-0178). Genetic counselors disclosed results and provided post-test counseling by phone. Clinical and germline data were collected through medical records.

Two hundred eighty-six PDAC patients watched the educational video. From 175 patients who watched the video before the pandemic, 12 declined to test, whereas, during the pandemic period, none of the 111 patients declined testing (6.9% vs. 0%; p<0.004, Fisher’s exact test). Twenty-nine patients elected to undergo GT and consented for the registry. Of these 245 patients, 163 patients (66.6%) underwent GT before the pandemic, whereas 82 patients (33.4%) underwent GT during the pandemic (Figure 1A). We evaluated differences in demographic characteristics between these two groups and found no significant differences (Supplementary Table 1). From 245 samples collected, 4 of 87 saliva samples failed and prompted the team to switch to blood-based testing which achieved 100% successful analysis.

Figure 1.

A. CONSORT diagram. Number of patients exposed to video, enrolled into genetic testing (before and during the pandemic) and consented for germline registry. *One patient had both a pathogenic variant and a variant of uncertain significance. ¥ One Patient had 2 variants of uncertain significance. B. Germline genetic testing results. Frequency of individual pathogenic variants (PV) and variants of unknown significance (VUSs).

From the 241 patients with successfully collected samples, 21 patients (8.7%) had a pathogenic variant, 38 patients (15.8%) had a variant of uncertain significance, and 182 patients (75.5%) tested negative (Figure 1A). The pathogenic variants detected were BRCA2 (most frequent), ATM, BRCA1, CDKN2A, PALB2, and APC I1307K (Figure 1B).

The coronavirus disease 2019 pandemic spurred the use of effective remote video-based alternatives for medical care⁵, which may become a permanent approach in a post-pandemic world as telemedicine becomes increasingly popular. Comparing uptake of GT before the pandemic versus during the pandemic (Figure 1A) suggests that patients were more willing to trust information from a video platform during the pandemic, likely due to the global effect of living in a “virtual” society as a result of the pandemic.

GT can have tremendously beneficial effects, such as allowing patients to qualify for targeted treatment options⁶. Based on the results found through GT, 2 patients with BRCA2 mutations received targeted therapies, such as olaparib. Furthermore, a patient with an ATM pathogenic mutation and a patient with MSH6 variant of uncertain significance received immune checkpoint inhibitors (pembrolizumab). A recent study⁷ illustrated an increase of 1-year median overall survival for patients with PDAC with a somatic or germline mutation who received therapy matched to their mutations vs those who received standard-of-care unmatched treatment, highlighting the importance of GT in targeted treatment pipeline.

Furthermore, GT will facilitate cascade testing in probands’ at-risk family members, which may lead to early detection or prevention. Notably, because the established PDAC susceptibility genes are associated with risk of non-PDAC cancers for which there are established measures of prevention (such as mastectomy inpatient with BRCA1/2)⁸, the familial benefits of GT could be quite consequential. In summary, 2 major benefits conferred by GT include qualifying for targeted therapies and inciting cascade testing in family members.

We report here the feasibility of implementing video-based GT in patients with PDAC, which resulted in unexpectedly high uptake levels, particularly during the pandemic. Further extensive investigations are needed to explore the feasibility of a fully remote GT model in diverse populations to assess additional barriers to universal GT. This video-based pretesting education can easily be translated into several languages to enhance accessibility. In addition, this strategy can be applied to several other cancers in which genetic testing is increasingly relevant, such as ovarian cancer. Overall, this model of video-based pretesting education can reduce the burden on genetic counselors who could instead focus efforts on post-testing education and lead to greater uptake in GT, proving to be especially effective in a pandemic world.