Oncology clinic-based germline genetic testing for exocrine pancreatic cancer enables timely return of results and unveils low uptake of cascade testing

Abstract

BackgroundTraditional 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.MethodsFrom 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.ResultsOf 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.ConclusionA 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.

Feasibility of a Traceback Approach for Using Pathology Specimens to Facilitate Genetic Testing in the Genetic Risk Analysis in Ovarian Cancer (GRACE) Study Protocol

“…The feasibility of implementing traceback programs to identify and recruit individuals with a prior diagnosis of ovarian cancer is currently unclear [42,43]. Feasibility could be impacted by multiple factors, such as patient interest and uptake, implementation approaches, and legal and regulatory guidelines at the federal, state, and health care system level [44][45][46]. Given contact may happen years after the cancer diagnosis, some patients may not have up-to-date contact information available, whereas others may not want to be identified and contacted for genetic testing [47].…”

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention

“…Studies in a UK model evaluating the effectiveness of registries in the facilitation of family contact confirm that registries provide long-term follow-up and proactive genetic counselling to relatives at risk, potentially an effective initiative in the Canadian context. The shift towards a formal provider-initiated, registry-based cascade testing is optimal, but important considerations must balance the concept of “duty to warn” with individual confidentiality and privacy [ 66 ].…”

“…Studies in a UK model evaluating the effectiveness of registries in the facilitation of family contact confirm that registries provide long-term follow-up and proactive genetic counselling to relatives at risk, potentially an effective initiative in the Canadian context. The shift towards a formal provider-initiated, registry-based cascade testing is optimal, but important considerations must balance the concept of "duty to warn" with individual confidentiality and privacy [66]. (2) Tumor-based referral and cascade testing: A tumor-first approach can be employed where samples from surgical specimens are sequenced, triggering a stepwise process whereby tumor genomic results are reported routinely and then patients with possible HCS are counselled regarding germline testing.…”

A systems approach to enhance Lynch syndrome diagnosis through tumor testing

“…It remains important to continue to evaluate the yield of universal tumor testing with respect to other approaches. Eventually, options that include more widespread germline genetic testing [17] and extending point-of-care genetic testing where cancer genetics is embedded into the oncology clinic [18] could end up identifying more individuals with LS and thus these need further consideration.…”