Teenage Male with Cough and Recurrent Bruit

A general pediatrician is skilled at continuity; through longitudinal evaluation, they serve as front-line providers in the recognition and referral of unusual pathology. The majority of arteriovenous malformations (AVM) are diagnosed with history and physical examination. AVM are inherently progressive by nature; their expansion is what creates the risk of morbidity. With higher-risk vascular lesions, relative risk is important when discussing management with observation versus with invasive intervention. Size, location, and expected course of progression of the lesion help generate a timeline for action. Collaboration of physicians with diverse expertise generates optimal plan of therapy, particularly when faced with an unusual clinical finding. Genetics referral may be beneficial, as the body of literature on AVM is growing, and databases on associated syndromes are evolving. Establishing concrete follow-up is imperative to assess for recurrence of AVM or development of additional symptoms. This can be with the interventionalist or with the generalist.

A Randomized Trial to Maximize Identification and Genetic Counseling Referral of Women at Risk for Hereditary Breast and Ovarian Cancer

Purpose: The Breast Cancer Genetics Referral Screening Tool (B-RST™) has been endorsed as one of several validated screening tools to identify women appropriate for cancer genetics referral. We conducted a randomized trial to determine the most effective means of follow-up for women who screened positive on B-RST™ 3.0. Methods: Women undergoing screening mammography at one of four Emory clinics were approached to complete the B-RST™. Participants who screened positive were randomized to one of three follow-up groups: self-referral (Group 1), electronic health record (EHR) clinician messaging (Group 2), or direct contact (Group 3). We compared genetic counseling appointment scheduling and completion rates by group. Results: Of 2,422 participants, 658 (27.2%) screened positive. Genetic counseling appointments were scheduled by 9.2%, 20.1% and 9.7% of Group 1, 2 and 3 participants respectively (p=0.001). Challenges to scheduling included lack of physician response to EHR messages and unsuccessful direct contact. Among those scheduled (n=78) 70.5% completed the appointment, with no difference between the three groups. Conclusion: B-RST™ can be used effectively in mammography settings to identify high-risk women for cancer genetics referral. Follow-up via EHR appears an acceptable and efficient approach, but additional strategies are needed to facilitate completion of the genetic counseling process.

Cancer specialists in the VA as early adopters of clinical genetic services.

11029 Background: Genetic testing has become essential to delivery of cancer treatment, risk assessment, surveillance, and prevention. We sought to understand the use of genetic tests by clinicians in the Department of Veterans Affairs (VA). Methods: We administered a web-based survey to clinicians at 20 VA facilities with precision oncology programs. We excluded respondents if they were: not at one of the 20 VA facilities; not seeing patients in VA; not a physician, nurse practitioner (NP), physician assistant (PA), or pharmacist; a medical geneticist or specialty was not reported; or if the survey was incomplete. Using multiple logistic regression, we assessed the association between genetic test ordering, genetics referral, and clinician characteristics. Results: There were 909 (909/11,442, 8%) eligible respondents with 61% women and 64% under age 55. There were 571 physicians (63%), 200 NPs (22%), 93 pharmacists (10%), and 45 PAs 5(%). There were 361 (40%) primary care providers (PCPs), 90 (10%) cancer specialists, and 458 (50%) non-cancer specialists. Only 21% of clinicians reported feeling prepared to use genetic tests in their practice. In the past year, only 8% had ordered at least one multi-gene cancer test (germline, tumor or both), 12% a pharmacogenetic test, and 0.2%, an exome. Compared to physicians, NPs were 60% less likely (OR = 0.42, 0.23-0.77, p = 0.005), pharmacists, 80% less likely (OR = 0.22, 0.08-0.62, p = 0.005), and PAs, 90% less likely (OR = 0.08, 0.01-0.58, p = 0.01) to have ordered a genetic test. Compared to PCPs, cancer specialists were almost 5 times more likely to order a genetic test (OR = 4.74, 2.57-8.73, p < 0.0001); there was no difference in genetic test ordering between PCPs and non-cancer specialists. Among clinicians (n = 72) who had ordered cancer genetic tests, only about two-thirds were confident in knowing the indications for testing; discussing the potential benefits, harms and limitations of testing; understanding the test report; and knowing implications of results on disease management and prevention. Clinicians (n = 106) who had ordered pharmacogenetic tests had lower frequencies of confidence in these tasks. About half (52%) of the cancer specialists had referred patients to genetics in the past year; they were 1.8 times more likely than PCPs to refer (OR = 1.82, 1.10-3.03, p = 0.02), and non-cancer specialists were about 50% less likely than PCPs to refer (OR = 0.46, 0.33-0.64, p < 0.0001). Conclusions: In the VA, cancer specialists are integrating genetic testing and genetics referral into their practice more than PCPs and other specialists. However, genetic testing is underutilized, and many clinicians remain unprepared to use genetic tests in their practice. These results will inform workforce planning, clinician education, and development of clinical decision support to facilitate genetic risk assessment, informed consent, and ordering of genetic tests.

Testing for mutations in BRCA1 and BRCA2 among ovarian cancer patients at a diverse academic medical center.

10588 Background: Testing for mutations in BRCA1 and BRCA2 is recommended for all women with ovarian cancer (OC), given important implications for treatment and prognosis. Despite this recommendation, studies show that only a small percentage of OC patients (pts) undergo genetic testing (GT). In this study, we evaluated rates of genetics referral, counseling and testing among OC pts at an academic medical center. Our goal was to identify factors associated with lower rates of GT. Given the large Black population at our center, we specifically wanted to evaluate the association between race and GT given limited existing data on this issue. Methods: Retrospective chart review was performed evaluating rates of referral and uptake for GT, and percentages of BRCA mutation carriers among pts with OC diagnosed and treated at Emory’s Winship Cancer Institute between 2008 and 2018. Associations between age, race, histology, family history (FH), performance status, provider characteristics and genetics referral and testing were evaluated using logistic regression models. Results: Of the 171 pts who met inclusion criteria, the majority were age 55 or older (62%) with high grade serous carcinoma (60.8%). Pts were predominantly Caucasian (59.4%), followed by Black (29.1%), Asian (10.3%) and Hispanic (1.2%). Overall, GT rates were low with 44.7% of pts referred for genetic counseling and 39.8% receiving testing. Among pts who did receive GT, the percentage of deleterious BRCA1 and BRCA2 mutations identified was 11% and 8.8% respectively. Variables correlating with higher likelihood of genetics discussion, referral and testing included serous histology (50% vs 23.9% non-serous, p < 0.001), Caucasian or Asian race (87.5% Asian, 58.8% Caucasian vs 42.2% Black, p = 0.003) and seeing a medical oncologist (67.5% vs 44.7% seeing gynecologic oncologist alone, p = 0.004). Notably, while fewer Black women were referred for GT (25.9% vs 74.1% Caucasian), those that did undergo GT were found to have higher rates of BRCA1 and BRCA2 mutations when compared to Caucasian pts (22.2% vs 8.2% BRCA1; 11.1% vs 6.0% BRCA2). Pts with a FH of OC were more likely to undergo GT (69.2% vs 37.9%, p = 0.027), and pts with a FH of breast cancer were more likely be referred for testing (57.1% vs 39.6%, p = 0.042), suggesting that FH impacted referral patterns. Conclusions: The rates of GT among OC pts at our institution were lower than expected despite the broad recommendation for GT in this population. It is imperative to improve access to GT for all OC pts regardless of FH, and in particular among Black pts given the higher rates of BRCA mutations in this population. Pts and providers must work together to overcome barriers to genetics referral and testing in order to improve GT rates and clinical outcomes. Further research is needed to design interventions that may help improve adherence to this important recommendation in the future.

BRCA testing in women with high-grade serous ovarian cancer: gynecologic oncologist-initiated testing compared with genetics referral

ObjectiveUp to 15% of patients with high-grade serous ovarian, tubal, or peritoneal carcinoma harbor a mutation in BRCA genes. Early notion of mutation status may facilitate counseling, predict prognosis, and increase access to Parp-inhibitors. The aim of this study was to examine the rate of germline genetic testing in a retrospective cohort of women with high-grade serous ovarian, tubal, or peritoneal carcinoma to determine if a new pilot project of gynecologic oncologist-initiated genetic testing improved the rate of testing, after 1 year of implementation.MethodsGynecologic oncology-initiated genetic testing was implemented at a single university hospital center with input and collaboration from gynecological oncologists, nurses, and genetic counselors. All patients diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma after August 2017 were offered gynecologic oncologist- initiated genetic testing for a panel of 13 hereditary breast and ovarian cancer susceptibility genes. Data from this group was then compared with a historic cohort of patients who received traditional genetic counseling between January 2014 and August 2017 (control group). Patients that had genetic testing through a clinical trial were excluded. The primary outcome was the uptake of genetic testing in both groups. Secondary outcomes included difference in time from diagnosis to genetic result between both cohorts. Data was analyzed using SPSS 25.0 and medians (ranges) were reported.ResultsA total of 152 women with high-grade serous ovarian, tubal, or peritoneal carcinoma were included in this study. Between January 2014 to July 2017 there were 108 patients with high-grade serous ovarian, tubal, or peritoneal carcinoma, among which 50.9% (n=54) underwent genetic testing following referral to genetics. The prevalence of BRCA pathogenic variants was 25.9% (14/54): 9.2% (5/54) in BRCA1 and 16.7% (9/54) in BRCA2. The median time from diagnosis to genetics referral was 53 days (range; 3–751), and median time from diagnosis to test result disclosure was 186 days (range; 15–938). After 1 year of implementation of the gynecologic oncologist-initiated genetic testing model, among 44 women diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma, 86.2% underwent genetic testing. The median time from diagnosis to result disclosure decreased to 58 days, representing a reduction of 128 days, or 4.27 months (P<0.001). Reasons for non-testing included refusal, death, and follow-up at another hospital. The prevalence of germline BRCA1/2 pathogenic variants was 21% (8/38).ConclusionGynecologic oncologist-initiated genetic testing at the time of high-grade serous ovarian, tubal, or peritoneal carcinoma diagnosis leads to increased uptake and decreased delays in testing compared with referral for traditional genetic counseling.

A prospective study of stress, anxiety and depression response to undergoing genetic assessment at the time of ovarian cancer diagnosis.

e13024 Background: Genetic assessment (GA) is recommended for all women with ovarian cancer however little is known about the psychological implications of this intervention. We sought to evaluate the psychological response to GA in newly diagnosed ovarian cancer patients as part of our facilitated genetics referral pathway. Methods: English-speaking patients with ovarian cancer undergoing GA at the time of cancer diagnosis completed three validated anxiety, stress and depression survey instruments immediately prior to and following GA and again 6-9 months after GA. Results: Forty-eight English-speaking patients underwent GA; 43 (90%) completed the pre-GA survey, 32 (67%) post-GA survey and 11 (23%) 6-9 months follow-up survey. Eight patients (17%) had documented psychiatric diagnoses (5 anxiety, 2 depression, 1 anxiety+depression) prior to cancer diagnosis. Overall, patients demonstrated mild to moderate stress, clinically significant anxiety and borderline depression (Table 1). There was no change in depression, anxiety or stress scores when comparing pre- to post-GA surveys. Age, stage, method of treatment, performance status at enrollment and history of psychiatric disorders were not associated with anxiety, stress or depression. Conclusions: A genetic testing pathway whereby GA is encouraged and facilitated at the time of diagnosis has not increased patient depression, anxiety or stress in our cohort. Concern about causing additional emotional distress should not deter clinicians from early genetics referral. [Table: see text]

Lynch Syndrome diagnosis in Ireland: The impact of universal mismatch repair protein testing.

532 Background: It is estimated that approximately 2-4% of colorectal cancers (CRCs) are attributable to Lynch Syndrome (LS). Immunohistochemical testing for mismatch repair proteins is increasingly being performed on CRC specimens. In some centres all incident cases undergo this testing. An abnormal result should initiate a cascade of testing to determine if the loss of mismatch repair protein expression is sporadic or hereditary. We examined the pattern of cancer genetics referral for hereditary CRC diagnosed in Ireland under the age of 70 years. Methods: The number of patients with CRC diagnosed under the age of 70 between 2005 and 2013 was obtained from the National Cancer Registry of Ireland. The number of patients referred for cancer genetics work-up with a diagnosis of CRC < 70 years of age was ascertained from the Department of Clinical Genetics, Our Lady’s Hospital, Crumlin (DCG), the only genetics laboratory in Ireland which processes such samples. The database of the DCG was searched for referrals for hereditary CRC syndromes; and the clinical reason for referral recorded. Results: Between 2005 and 2013, 10,334 patients were diagnosed with CRC less than 70 years of age. 85% were between 50 and 69 years of age (n = 8,736). 229 people under the age of 70 years were referred for cancer genetics work-up for LS with a diagnosis of CRC. Those referred for a non-CRC LS phenotypic manifestation and for predictive testing were excluded. For 41 individuals the reason for referral was not specified. Individuals with CRC were referred for one of the following reasons: diagnosis of CRC < 70 years in 76 patients (33%), diagnosis of CRC < 70 with a family history of LS-associated malignancy in 137 patients (60%), and diagnosis of CRC < 70 with known familial genetic mutation in 16 patients (7%).This represents a referral rate of approximately 0.02% for CRC diagnosed under 70 years of age. Conclusions: 0.2% of colorectal cancer cases diagnosed at < 70 years of age in Ireland over a nine year period were referred for cancer genetics opinion. Increased immunohistochemical testing for mismatch repair proteins should result in increased cancer genetics referral, which will require appropriate service provision within oncology management pathways.