Implementation of a Population-Based Cancer Family History Screening Program for Lynch Syndrome.

OBJECTIVES: Lynch syndrome increases risks for colorectal and other cancers. Though published Lynch syndrome cancer risk-management guidelines are effective for risk-reduction, the condition remains under-recognized. The Cancer Genetics Program at an academic medical center implemented a population-based cancer family history screening program, Detecting Unaffected Individuals with Lynch syndrome, to aid in identification of individuals with Lynch syndrome. METHODS: In this retrospective cohort study, simple cancer family history screening questionnaires were used to identify those at risk for Lynch syndrome. Program navigators triaged and educated those who screened positive about hereditary cancer, and genetic counseling and testing services, offering genetic counseling if eligible. Genetic counseling was provided primarily via telephone. Genetic counselors performed hereditary cancer risk assessment and offered genetic testing via hereditary cancer panels to those eligible. Remote service delivery models via telephone genetic counseling and at-home saliva testing were used to increase access to medical genetics services. RESULTS: This program screened 212,827 individuals, over half of whom were considered underserved, and identified 133 clinically actionable genetic variants associated with hereditary cancer. Of these, 47 (35%) were associated with Lynch syndrome while notably, 70 (53%) were not associated with hereditary colorectal cancer. Of 3,344 patients offered genetic counseling after initial triage, 2,441 (73%) elected to schedule the appointment and 1,775 individuals (73%) completed genetic counseling. Among underserved patients, telephone genetic counseling completion rates were significantly higher than in-person appointment completion rates (P < .05). While remote service delivery improved appointment completion rates, challenges with genetic test completion using at-home saliva sample collection kits were observed, with 242 of 1592 individuals (15%) not completing testing. CONCLUSION: Population-based cancer family history screening and navigation can help identify individuals with hereditary cancer syndromes across diverse patient populations, but logistics of certain downstream service delivery models can impact outcomes.

Genetic variants with discordant classifications: An assessment of genetic counselor attitudes and practices.

Discordant variant classifications (DVCs) can impact patient care and pose challenges for clinicians. A survey-based study was conducted to examine genetic counselor (GC) attitudes and practices related to DVCs. Most GCs (202/229, 88%) in the study provide direct patient care across clinical specialties; review patients' genetic test results to determine if reported genetic variants have DVCs (176/202, 88%); and inform patients of known DVCs that impact medical management (165/202, 82%). DVC review, which takes 41 min (range: 5-240) on average per week, is typically prompted by the identification of a variant of uncertain significance (VUS) (160/176, 90%) and is primarily conducted using public databases (176/176, 100%). While most GCs felt it would not be ethical to knowingly provide different medical management recommendations to patients with the same genetic variant (152/229, 66%), they also stated they would rely on the variant classification on the test report (141/229, 61%) and/or the patient's personal/family history (188/229, 82%) to determine which classification to follow if a DVC is identified. Both factors are patient-specific and, inherently, could lead to differing recommendations. When posed with a hypothetical scenario in which two patients have the same genetic variant, but test reports show a DVC (pathogenic vs VUS), most GCs (179/229, 78.2%) stated they would make the same recommendation for both patients regardless of management guidelines. One-third (52/179, 29.1%) cited patient-specific factors, such as personal/family history, would impact their recommendations. Disagreements about whether the pathogenic or VUS classification should be used to make medical management recommendations were noted. Differing practices and opinions on how to manage patients with DVCs, as well as the fact that most GCs (209/229, 91.3%) have consulted with colleagues on this matter, highlight the need for more professional guidance to ensure equitable patient care.

Racial and Ethnic Disparities in Germline Genetic Testing of Patients With Young-Onset Colorectal Cancer.

BACKGROUND & AIMS: Up to 20% of younger patients (age <50 years) diagnosed with colorectal cancer (CRC) have germline mutations in cancer susceptibility genes. Germline genetic testing may guide clinical management and facilitate earlier intervention in affected relatives. Few studies have characterized differences in genetic testing by race/ethnicity. METHODS: We identified young adults (age 18-49 years) diagnosed with CRC between 2009 and 2017 in 2 health systems in Dallas, TX. We evaluated referral to genetic counseling, attendance at genetic counseling appointments, and receipt of germline genetic testing by race/ethnicity. RESULTS: Of 385 patients with young-onset CRC (median age at diagnosis 44.4 years), 176 (45.7%) were Hispanic, 98 (25.4%) non-Hispanic Black, and 111 (28.8%) non-Hispanic White. Most patients (76.9%) received immunohistochemistry (IHC) for mismatch repair proteins, and there was no difference in receipt of IHC by race/ethnicity. However, a lower proportion of Black patients were referred to genetic counseling (50.0% vs White patients 54.1% vs Hispanic patients 65.9%; P = .02) and attended genetic counseling appointments (61.2% vs 81.7% White patients vs 86.2% Hispanic patients; P < .01). Of 141 patients receiving genetic testing, 38 (27.0%) had a pathogenic or likely pathogenic variant in a cancer susceptibility gene. An additional 33 patients (23.4%) had variants of uncertain significance, of which 84.8% occurred in racial/ethnic minorities. CONCLUSIONS: In a diverse population of patients diagnosed with young-onset CRC, we observed racial/ethnic differences in referral to and receipt of germline genetic testing. Our findings underscore the importance of universal genetic testing to address racial/ethnic disparities in young-onset CRC.

Standardized applications for genetic counseling graduate programs: Opinions of program directors.

Genetic Counseling Graduate Programs (GCGPs) have progressively increased in number and class size, and implementation of the National Matching Services in 2018 was a major step toward streamlining the admissions process. Standardized applications (SAs), which have been incorporated into the admissions process for undergraduate studies as well as several professional graduate programs, could also be considered for GCGPs. In this study, we assessed the opinions of GCGP Program Directors (PDs) regarding the implementation of an SA for GCGP admissions processes. GCGP PDs participated in an anonymous online survey designed to evaluate interest in an SA and assess perceived implementation barriers. The survey collected GCGP and PD demographic information, data on current application components, and PD opinions of an SA. Thirty PDs were included in this study, and just over half (n = 16/30, 53.3%) reported their current application structure would allow for SA implementation. While 40% (n = 12/30) of respondents anticipated an SA would benefit GCGPs, an additional 23.3% (n = 7/30) anticipated no impact to GCGPs. Most respondents (n = 26/30, 86.6%) anticipated that an SA would be beneficial for GCGP applicants. The main perceived benefit to GCGPs was an efficient application process, while perceived benefits to applicants included decreased redundancy and increased application access. Perceived harms to GCGPs included more generic applications, while perceived harms to applicants included increased competition for admission to individual GCGPs. The most common SA implementation barrier cited by respondents was current administrative structures. This study demonstrates that while GCGP leadership largely perceives an SA to be beneficial for applicants, opinions on impact to GCGPs vary. While the majority of respondents perceive implementation of an SA to be feasible, there are implementation barriers that must be addressed. Interestingly, GCGP leadership had mixed perceptions about the structure of a hypothetical SA, and thus overall impact, demonstrating the need for further study.

Adapting genetic counseling operations amidst the COVID-19 pandemic.

The COVID-19 pandemic caused significant disruptions to the delivery of genetic counseling services and clinical operations. Understanding how these pivots in practice affected patient care across both a county hospital system and academic medical center can help provide models of clinical operations for other genetic counselors. Programmatic data were analyzed between March 18, 2020 and September 18, 2020, including visit completion rates and genetic testing completion outcomes for genetic counseling services during the COVID-19 pandemic. In addition to analyzing the effects on patient care, we provide commentary on technological adaptations that aided our operations, billing practices, onboarding and engaging new and existing staff, and coordination of education and outreach opportunities. Through this work, we highlight barriers encountered and successful adaptations that will influence future clinical practices and may guide other providers in the development of strategies to meet their clinical and operational needs.

Cascade genetic testing: an underutilized pathway to equitable cancer care?

The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the "cascade" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted primary disease prevention through intensive cancer surveillance, chemoprevention and risk-reducing surgery, reducing morbidity and preventing mortality. Cascade testing has been designated by the Centers for Disease Control and Prevention as a Tier 1 genomic application for hereditary breast and ovarian cancer. In this manuscript we describe a cascade genetic testing and in particular focus on its potential to provide necessary care to medically underserved and vulnerable populations.

Screening Families of North Texans to Identify Persons with an Increased Risk for Cancer Due to Lynch Syndrome.

In 2016, the UT Southwestern Medical Center's Cancer Genetics Program was awarded a grant (PP160103) by the Cancer Prevention and Research Institute of Texas (CPRIT) to increase awareness of hereditary cancer syndromes, particularly Lynch syndrome (LS), and implement a population-based genetic screening program to identify those at high genetic risk for cancer.