Improving Access to Hereditary Testing in Pancreatic Ductal Carcinoma.

PURPOSE: Approximately 5%-10% of patients with pancreatic ductal adenocarcinoma (PDAC) have an inherited basis, yet uptake of genetic testing remains low and subject to disparities. This study compared two genetic testing pathways available to patients referred to a provincial cancer center, BC Cancer: a traditional hereditary cancer clinic-initiated testing (HCT) pathway and a new oncology clinic-initiated testing (OCT) pathway. METHODS: Study subjects were patients with confirmed PDAC referred for genetic testing through the HCT or OCT pathway between June 1, 2020, and February 1, 2022. Charts were retrospectively reviewed for patient characteristics and testing outcomes. RESULTS: The study population was 397 patients (HCT, n = 279 and OCT, n = 118). OCT patients were more likely to have non-European ethnicity compared with HCT patients (41.9% v 25.6%, P = .004), to have earlier-stage disease (P = .012), and to have better Eastern Cooperative Oncology Group performance status than the HCT group (P = .001). A total of 306 patients completed testing (77%). OCT patients had higher test completion rates than HCT patients (odds ratio, 3.74 [95% CI, 1.66 to 9.62]). Median time for results was shorter in OCT than in HCT (53 days [IQR, 44-76] v 107 days [IQR, 63.8-158.3]). Pancreatic cancer susceptibility pathogenic gene variants were identified in 8.5% (26/306). CONCLUSION: The real-world observations in our study show that oncology clinic-initiated hereditary testing is more effective and faster than testing through hereditary cancer clinic referrals and reaches a more ethnically diverse population. This has important implications for publicly funded environments with limited resources for genetic counseling.

Correction: Gill et al. Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022. Curr. Oncol. 2023, 30, 7964-7983.

Karen Mulder was not included as an author in the original publication [...].

Report from the 24th Annual Western Canadian Gastrointestinal Cancer Consensus Conference on Colorectal Cancer, Richmond, British Columbia, 28-29, October 2022.

The 24th annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Richmond, British Columbia, on 28-29 October 2022. The WCGCCC is an interactive multidisciplinary conference attended by healthcare professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals such as dieticians, nurses and a genetic counsellor participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

Workforce Implications of Increased Referrals to Hereditary Cancer Services in Canada: A Scenario-Based Analysis.

Over the last decade, utilization of clinical genetics services has grown rapidly, putting increasing pressure on the workforce available to deliver genetic healthcare. To highlight the policy challenges facing Canadian health systems, a needs-based workforce requirements model was developed to determine the number of Canadian patients in 2030 for whom an assessment of hereditary cancer risk would be indicated according to current standards and the numbers of genetic counsellors, clinical geneticists and other physicians with expertise in genetics needed to provide care under a diverse set of scenarios. Our model projects that by 2030, a total of 90 specialist physicians and 326 genetic counsellors (1.7-fold and 1.6-fold increases from 2020, respectively) will be required to provide Canadians with indicated hereditary cancer services if current growth trends and care models remain unchanged. However, if the expansion in eligibility for hereditary cancer assessment accelerates, the need for healthcare providers with expertise in genetics would increase dramatically unless alternative care models are widely adopted. Increasing capacity through service delivery innovation, as well as mainstreaming of cancer genetics care, will be critical to Canadian health systems' ability to meet this challenge.

Genetic testing practices among specialist physicians who treat prostate cancer A Canadian, cross-sectional survey.

INTRODUCTION: In patients with prostate cancer (PCa), the identification of an alteration in genes associated with homologous recombination repair (HRR) has implications for prognostication, optimization of therapy, and familial risk mitigation. The aim of this study was to assess the genomic testing landscape of PCa in Canada and to recommend an approach to offering germline and tumor testing for HRR-associated genes. METHODS: The Canadian Genitourinary Research Consortium (GURC) administered a cross-sectional survey to a largely academic, multidisciplinary group of investigators across 22 GURC sites between January and June 2022. RESULTS: Thirty-eight investigators from all 22 sites responded to the survey. Germline genetic testing was initiated by 34%, while 45% required a referral to a genetic specialist. Most investigators (82%) reported that both germline and tumor testing were needed, with 92% currently offering germline and 72% offering tissue testing to patients with advanced PCa. The most cited reasons for not offering testing were an access gap (50%), uncertainties around who to test and which genes to test, (33%) and interpreting results (17%). A majority reported that patients with advanced PCa (74-80%) should be tested, with few investigators testing patients with localized disease except when there is a family history of PCa (45-55%). CONCLUSIONS: Canadian physicians with academic subspecialist backgrounds in genitourinary malignancies recognize the benefits of both germline and somatic testing in PCa; however, there are challenges in accessing testing across practices and specialties. An algorithm to reduce uncertainty for providers when ordering genetic testing for patients with PCa is proposed.

Development and early-stage evaluation of a patient portal to enhance familial communication about hereditary cancer susceptibility testing: A patient-driven approach.

INTRODUCTION: Genetic testing for hereditary cancer syndromes (HCSs) can improve health outcomes through cancer risk mitigation strategies. Effective communication between tested individuals and their family members is key to reducing the hereditary cancer burden. Our objective was to develop a patient portal to improve familial communication for patients undergoing HCS genetic testing, followed by an early-phase evaluation. METHODS: The portal was developed following the completion of 25 semistructured interviews with individuals having undergone HCS susceptibility testing at BC Cancer. Following initial development, we recruited patients and healthcare providers to provide critical feedback informing portal refinement. Quantitative feedback was summarized using descriptive statistics, and qualitative feedback was synthesized by two reviewers who engaged in iterative discussion within the research team to prioritize recommendations for integration. RESULTS: The patient portal includes four key components consisting of (a) targeted educational information about hereditary cancer and HBOC syndrome associated risks and testing process overview, (b) a general frequently asked questions 'FAQ' page informed by the qualitative interviews, patient partner feedback, and consultation with the HCP, (c) guidance to support familial communication including a video developed with a patient partner describing their lived experience navigating the communication process and (d) a series of lay summaries of genetic test findings to support information transfer among family members. Thirteen healthcare providers and seven patients participated in user testing. Domains within which participant recommendations were provided included presentation, educational content and process clarification. CONCLUSIONS: This investigation demonstrates the value of continual integration of patient and provider preferences through the development of tools endeavouring to assist with complex genomics-informed decision-making. Our work aims to broaden the population-wide impact of HCS testing programs by improving communication processes between probands and their potentially affected family members. PATIENT OR PUBLIC CONTRIBUTION: This work involved a patient partner who was actively engaged in all aspects of the research investigation including protocol development, review and editing of all study documentation (including that of the previously published qualitative investigation), interpretation of results, as well as reviewing and editing the manuscript. Patient partners and healthcare professionals were recruited as research participants to provide critical feedback on the patient portal.

Evaluation of out-of-pocket pay genetic testing in a publicly funded healthcare system.

When genetic tests are not funded publicly, out-of-pocket (OOP) pay options may be discussed with patients. We evaluated trends in genetic testing and OOP pay for two publicly funded British Columbia clinical programs serving >12 000 patients/year (The Hereditary Cancer Program [HCP] and Provincial Medical Genetics Program [PMGP]) between 2015-2019. Linear and regression models were used to explore the association of OOP pay with patient demographic variables at HCP. An interrupted time series and linear and logistic regression models were used on PMGP data to examine the effect of a change in the funding body. The total number of tests completed through PMGP, and HCP increased by 260% and 320%, respectively. OOP pay increased at HCP by 730%. The mean annual income of patients who paid OOP at HCP was ≥$3500 higher than in the group with funded testing (p < 0.0001). The likelihood of OOP pay increased at PMGP before the funding body change (OR per month: 1.07; 95% CI: 1.04, 1.10); while this likelihood had an immediate 87% drop when the change occurred (OR: 0.13; 95% CI: 0.06, 0.32). Patients with higher incomes are more likely to pay OOP. Financial barriers can create disparities in clinical outcomes. Funding decisions have a significant impact on rate of OOP pay.

Large-scale group genetic counseling: Evaluation of a novel service delivery model in a Canadian hereditary cancer clinic.

Increasing demand for genetic services has led to the development of streamlined genetic counseling (GC) models. We piloted large-scale group pre-test GC with up to 50 patients per group and compared this to a traditional one-on-one approach. Patients referred to the British Columbia (BC) Cancer Hereditary Cancer Program were eligible if they had: (a) family history meeting our program's referral criteria; (b) no relevant personal history of cancer; (c) no prior genetic testing in the family; and (d) no living testable relative in BC. Patient-reported outcome measures included: (a) Genetic Counselling Outcome Scale (GCOS) prior to pre-test GC (T1) and at 4 weeks post-test GC (T2); (b) Satisfaction Survey after pre-test GC; and (c) the Multidimensional Impact of Cancer Risk Assessment (MICRA) for patients undergoing testing (4 weeks after post-test GC). In total, 391 patients underwent GC, 184 by group and 207 by one-on-one appointments. Between May 2018 and May 2019, 6 pre-test group sessions were conducted (median number of patients per group = 28; range 15-48). 8% of patients (n = 32) declined large group GC due to personal preference for one-on-one GC. There were no statistically significant differences in MICRA and GCOS survey results when comparing the pre-test large group versus traditional pre-test one-on-one models (based on 3 MICRA subscales: p = 0.063, p = 0.612, p = 0.842; and GCOS p = 0.169). Overall, the large group pre-test counseling approach was more time-efficient with 15-48 patient group sessions conducted over a mean duration of 80 min as compared to 42 min per patient with the traditional one-on-one GC model. Large-scale group GC was feasible and acceptable to patients and represents a novel streamlined model for GC to enable timely access to cancer genetic services.

Patient ethnicity and cascade genetic testing: a descriptive study of a publicly funded hereditary cancer program.

Cascade genetic testing for hereditary cancer is highly accurate and cost-effective for identifying individuals at high risk for cancer; however, not all eligible people utilize this service. While sociodemographic factors related to the uptake of cascade genetic testing, such as age and sex, have been fairly well described in the literature, there is limited data available regarding patient ethnicity. We analyzed four years of testing data for this factor, as well as sex, age and genes tested. The patients were seen by the Hereditary Cancer Program of BC Cancer, which serves the entire population of British Columbia and Yukon, Canada. Patient ethnicity was compared to the 2016 Census data from the same region. Fisher's exact test was conducted to explore the cascade genetic testing uptakes. Chi-square test was used to compare the major ethnicity groups to Census data. There was significant variability in the uptake of cascade genetic testing in the three largest population groups (p < 0.05), with individuals of European ethnic origin overrepresented, individuals of Asian ethnic origin modestly underrepresented, and individuals of North American Indigenous origin considerably underrepresented for cascade genetic testing. The proportions represented compared to those expected from census data were significantly different for these three largest groups (p < 0.01). The majority of cascade genetic tests were for BRCA1/BRCA2 (58.8%), followed by 16.9% for Lynch syndrome genes. Most patients were female (70%), and the mean age of patients was 49 years old. This study provides further insight into uptake of cascade genetic testing by patient ethnicity. Examining patient ethnicity and cascade genetic testing rates helps to identify underserved populations. Our analysis highlights significant underrepresentation of North American Indigenous individuals for hereditary cancer cascade genetic testing, and helps recognize the need for development of culturally-safe alternatives to outreach and service promotion.

Integrating Tumor Sequencing Into Clinical Practice for Patients With Mismatch Repair-Deficient Lynch Syndrome Spectrum Cancers.

INTRODUCTION: Uninformative germline genetic testing presents a challenge to clinical management for patients suspected to have Lynch syndrome, a cancer predisposition syndrome caused by germline variants in the mismatch repair (MMR) genes or EPCAM. METHODS: Among a consecutive series of MMR-deficient Lynch syndrome spectrum cancers identified through immunohistochemistry-based tumor screening, we investigated the clinical utility of tumor sequencing for the molecular diagnosis and management of suspected Lynch syndrome families. MLH1-deficient colorectal cancers were prescreened for BRAF V600E before referral for genetic counseling. Microsatellite instability, MLH1 promoter hypermethylation, and somatic and germline genetic variants in the MMR genes were assessed according to an established clinical protocol. RESULTS: Eighty-four individuals with primarily colorectal (62%) and endometrial (31%) cancers received tumor-normal sequencing as part of routine clinical genetic assessment. Overall, 27% received a molecular diagnosis of Lynch syndrome. Most of the MLH1-deficient tumors were more likely of sporadic origin, mediated by MLH1 promoter hypermethylation in 54% and double somatic genetic alterations in MLH1 (17%). MSH2-deficient, MSH6-deficient, and/or PMS2-deficient tumors could be attributed to pathogenic germline variants in 37% and double somatic events in 28%. Notably, tumor sequencing could explain 49% of cases without causal germline variants, somatic MLH1 promoter hypermethylation, or somatic variants in BRAF. DISCUSSION: Our findings support the integration of tumor sequencing into current Lynch syndrome screening programs to improve clinical management for individuals whose germline testing is uninformative.