Pretest Risk Research Articles

Qualitative coronary artery calcium assessment on CT lung screening exam helps predict first cardiac events.

A total of 1,513 individuals underwent CTLS. Downstream data, pre-test cardiac risk factors and CAC scores were available for 88.3% (1,336/1,513). The average length of follow-up was 2.64 (SD ±0.72) years. There were a total of 43 events, occurring in 1.55% (6/386) of patients with mild CAC, 3.24% (11/339) of patients with moderate CAC, and 8.90% (26/292) of patients with marked CAC. There were no events among patients with no reported CAC (0/319). Using multivariable logistic modeling, the increased odds of an initial cardiac event was 2.56 (95% CI, 1.76-3.92, P<0.001) for mild CAC, 6.57 (95% CI, 3.10-15.4, P<0.001) for moderate CAC, and 16.8 (95% CI, 5.46-60.3, P<0.001) for marked CAC, as compared to individuals with no CAC. Time to event analysis showed distinct differences among the four CAC categories (P<0.001). Qualitative coronary artery calcification scoring of CTLS exams may provide a novel method to help select individuals at elevated risk for an initial cardiac event.

Prediction of Extensive Myocardial Fibrosis in Nonhigh Risk Patients With Hypertrophic Cardiomyopathy

In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGEext) at cardiovascular magnetic resonance (CMR) imaging has been proposed as a risk modifier in the decision process for implantable cardioverter defibrillator implantation. With a pretest risk of about 10%, a strategy that alters the likelihood of LGEext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGEext. In 98 HC patients without any clear indication for implantable cardioverter defibrillator implantation, we determined the discriminative values of a set of clinical variables and a panel of biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGEext, that is, LGE ≥15% of the left ventricular mass. LGEext was present in 10% (10/98) of patients. The clinical prediction model contained a history of nonsustained ventricular tachycardia, maximal wall thickness and reduced systolic function (c-statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with LGEext, in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGEext in half of the cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh risk HC cohort, the pretest likelihood of LGEext can be altered using clinical variables and the addition of hs-cTnT. The promising findings with the use of hs-cTnT only call for new initiatives to study its impact on efficacious CMR imaging in a larger HC population, either with or without additional use of clinical variables.

PRM67 - Creating a Flexible Continuous Procedure Distribution Model Based on Pre-Test Risk Level for Lung Cancer in Patients with Incidentally Detected Pulmonary Nodules

After initial diagnostic procedures, including imaging, for patients with indeterminate incidentally detected nodules, the multi-disciplinary team has three initial patient management options: Serial computed tomography (CT) observations, nodule biopsy or surgery. We needed to create a sub-model of a broader cost-effectiveness model, which would reflect real-world physician behavior driven distribution of initial management procedures based on a patient’s probability of having lung cancer. We developed parametric regression formulas for calculating the procedure distribution for any pre-test probability for malignancy. Procedure distribution and population data from the Tanner 2017 referral center study was used as the basis for the model. The data set had three risk groups: Low (2.5% malignancy rate); intermediate (26%) and high risk (78.9%). We anchored the regression at two hypothetical extreme risk levels: Very low (0.5%) and very high risk (95%) and made logical clinical considerations regarding how the procedure distribution would change for these extreme risk groups based on discussions with experts. We fit separate mathematical functions to describe the relationship between risk of malignancy and procedure utilization. Based on our approach we arrived at a set of polynomial formulas that calculated the percentage of patients undergoing each of the three procedure options. Serial-CT: 4th degree polynomial with square-root transformation of independent variable; Biopsy: 4th degree polynomial with square-root transformation of independent variable; Surgery: 3rd degree polynomial with no transformation of independent variable. The model calibrated well to the (expected) Tanner 2017 procedure utilization percentages for serial-CTs/biopsy/surgery: Low risk: 74%/21%/5% (72%/20%/8%); Intermediate: 57%/25%/17% (58%/26%/17%); High risk: 8%/54%/38% (8%/54%/38%). The results, when running the procedure utilization sub-model, matched closely with the real-world results from Tanner 2017. The method will allow the main cost-effectiveness model to be used with additional scenarios, different patient populations and new diagnostic modalities like biomarkers reflecting real-world physician behavior.

Circulating inflammatory proteins and gallbladder cancer: Potential for risk stratification to improve prioritization for cholecystectomy in high-risk regions

BackgroundInflammatory proteins could help identify individuals most likely to have gallbladder cancer (GBC) among those waiting for cholecystectomy. MethodsWe analyzed 49 circulating inflammation-related proteins in 144 patients with GBC and 150 patients with gallstones. We calculated age- and sex-adjusted odds ratios (ORs) and 95% CIs for protein quantiles and GBC versus gallstones. Using proteins associated with early GBC (stage 1–2) that were selected in stepwise logistic regression, we created an inflammation score and explored the potential utility for risk stratification. Results26 proteins (53%) had P values for the trend across categories ≤0.001, with associations for a one category increase ranging from 1.52 (95% CI: 1.20–1.94) for CC motif ligand 4 to 4.00 (95% CI: 2.76–5.79) for interleukin (IL)-8. Soluble tumor necrosis factor receptor 2 (sTNFR2), IL-6, sTNFR1, CC motif ligand 20 (CCL20), vascular cell adhesion molecule 1, IL-16, and granulocyte colony-stimulating factor had P values ≤0.001 for early GBC. Of those, IL-6, IL-16, CCL20, and STNFR1 were included in the inflammation score. In a high-risk setting with a pre-test disease risk of 10% (e.g., elderly patients) and using an inflammation score cutoff that provides 90% sensitivity, 39% of patients on the waiting list would be predicted to be positive, and 23% of those would be predicted to have GBC. ConclusionThese results highlight the strong associations of inflammatory proteins with GBC risk and their potential clinical utility. Larger studies are needed to identify the most effective combinations of inflammatory proteins for detecting early GBC and precursor lesions.

Abstract P4-06-07: Trends and results of BRCA1/2 and multigene panel testing in newly diagnosed breast cancer patients

Abstract Background: Next-generation sequencing technology, reduced costs and public interest have fueled a surge in more expansive germline genetic testing of breast cancer patients. However, there are no population-based data on trends in use of different test types or the distribution of results. Methods: In the iCanCare study, we surveyed 7,303 women diagnosed in 2013-15 with early-stage breast cancer and reported to the Georgia and Los Angeles County SEER registries. Of 5,080 respondents (response rate 70%), 5,050 were linked to SEER clinical data and to test results from four commercial laboratories that performed nearly all germline genetic testing for breast cancer patients in the regions. We examined trends in test type (two genes, BRCA1/2 only, vs. more cancer susceptibility genes, multigene panel) and patterns of results (positive for a pathogenic mutation; variant of uncertain significance (VUS); negative) by clinical and sociodemographic subgroups. Pre-test risk of having a pathogenic mutation was categorized as higher vs. average based on patient report of age at diagnosis, family cancer history, ancestry (Ashkenazi Jewish vs. not) and breast cancer subtype (triple-negative vs. not), according to practice guidelines criteria for genetic testing. Results: The mean age was 62 years; 26%, 49% and 25% had stage 0, I, and II cancer, respectively; 78% had estrogen receptor-positive, HER2-negative disease, and 9% had triple-negative; 28% had higher pre-test risk of having a pathogenic mutation; 56% were non-Hispanic white, 18% African American, 14% Hispanic, and 10% Asian. Genetic testing use did not change over time (p=0.695), with one-quarter of patients receiving any test (either BRCA1/2 only or multigene panel) according to clinical laboratory data. However, testing included more genes over time: multigene panels comprised 19% of tests in 2013 vs. 66% in 2015 (p&amp;lt;0.001). Among all patients, 14% received BRCA1/2 only and 12% multigene panel testing, with no differences in test type by pre-test risk or race/ethnicity. Among all patients, 7% had a pathogenic mutation and 14% had a VUS in any gene. Patients at high pre-test risk had a lower ratio of uninformative VUS to informative pathogenic mutations (14%/10%) than average risk patients (15%/4%, p&amp;lt;0.001). There was a substantially higher ratio of VUS to pathogenic mutation among African Americans (22%/7%) and Asians (23%/3%) than other racial/ethnic groups (12%/8%, p&amp;lt;0.001). Conclusions: In a large, diverse, contemporary sample of early-stage breast cancer patients accrued from population-based registries and linked to clinical laboratory data, one-quarter had genetic testing, with multigene panels markedly replacing BRCA1/2-only tests over time. The ratio of uninformative VUS to informative pathogenic mutation results was lowest in women at high pre-test risk and highest among racial/ethnic minorities. These findings can inform genetic counseling and they emphasize the urgent need to re-classify VUS results in racial/ethnic minorities. More research is needed to determine the impact of this marked increased in multigene panel testing on patient experiences, and the impact of test results on treatment decision-making and outcomes. Citation Format: Kurian AW, Katz SJ. Trends and results of BRCA1/2 and multigene panel testing in newly diagnosed breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-06-07.

Perivascular Epicardial Fat Stranding at Coronary CT Angiography: A Marker of Acute Plaque Rupture and Spontaneous Coronary Artery Dissection.

Purpose To evaluate the frequency and implications of perivascular fat stranding on coronary computed tomography (CT) angiograms obtained for suspected acute coronary syndrome (ACS). Materials and Methods This retrospective registry study was approved by the institutional review board. The authors reviewed the medical records and images of 1403 consecutive patients (796 men, 607 women; mean age, 52.8 years) who underwent coronary CT angiography at the emergency department from February 2012 to March 2016. Fat attenuation, length and number of circumferential quadrants of the affected segment, and attenuation values in the unaffected epicardial and subcutaneous fat were measured. "Cases" were defined as patients with perivascular fat stranding. Patients with significant stenosis but without fat stranding were considered control subjects. Baseline imaging characteristics, ACS frequency, and results of subsequent downstream testing were compared between cases and control subjects by using two-sample t, Mann-Whitney U, and Fisher tests. Results Perivascular fat stranding was seen in 11 subjects, nine with atherosclerotic lesions and two with spontaneous coronary artery dissections, with a mean fat stranding length of 19.2 mm and circumferential extent averaging 2.9 quadrants. The mean attenuation of perivascular fat stranding, normal epicardial fat, and normal subcutaneous fat was 17, -93.2, and -109.3 HU, respectively (P < .001). Significant differences (P < .05) between cases and control subjects included lower Agatston score, presence of wall motion abnormality, and initial elevation of serum troponin level. ACS frequency was 45.4% in cases and 3.8% in control subjects (P = .001). Conclusion Recognition of perivascular fat stranding may be a helpful additional predictor of culprit lesion and marker of risk for ACS in patients with significant stenosis or spontaneous coronary artery dissection. © RSNA, 2018 Online supplemental material is available for this article.

Factors Associated with Vitamin D Testing, Deficiency, Intake, and Supplementation in Patients with Chronic Pain

ABSTRACTVitamin D deficiency is a public health issue, with reports of six- to twenty-five–fold rise in vitamin D testing. Vitamin D deficiency has been linked to many chronic diseases such as diabetes mellitus, cardiovascular disease, depression, and chronic pain. Identifying factors associated with risk of deficiency in individuals with chronic pain will help minimize time and cost. This study aims to examine the factors associated with vitamin D testing, intake, and physician-advised supplementation in individuals with chronic pain. Using a cross-sectional design, data were collected from 465 individuals with chronic pain. These data were analyzed using penalized logistic regression with the LASSO technique. Fifty-seven percent reported being tested for vitamin D, about 40% reported being diagnosed with vitamin D deficiency, and of those who had been tested, 60% reported taking vitamin D supplementation. The findings suggest older age (OR 3.12, CI [1.02, 9.50]) and higher mean pain intensity score (OR 2.02, CI [1.13, 3.59]) increased an individual's chance of being vitamin D deficient. Unemployment or on leave due to pain (OR 1.79, [CI 1.03, 3.11]), part-time employment (OR 1.86, CI [1.02, 3.39]), and being a resident of Australia (OR 2.32, CI [1.13, 4.72]) increased chances of being tested for vitamin D. Being diagnosed with vitamin D deficiency (OR 6.67, CI [2.75, 16.19]), unemployed or on leave due to pain (OR 3.71, CI [1.25, 11.00]), and in part-time employment (OR 2.69, CI [0.86, 8.38]) were associated with physician-advised vitamin D supplementation. Our results may have practical implications, as identifying pretest risk factors may assist in identifying who is at risk of vitamin D deficiency, whom to test, and when to treat.

Long-term effects of a parenting preventive intervention on young adults' painful feelings about divorce.

This study examined whether the New Beginnings Program (NBP), a parenting preventive intervention for divorced mothers that was designed to reduce children's postdivorce mental health problems, reduced painful feelings about divorce in young adults whose families had participated 15 years earlier. This study also explored whether NBP participation reduced the relations between young adults' painful feelings about divorce and their concurrent internalizing, externalizing, and substance use problems. Participants (M = 25.6 years; 50% female; 88% Caucasian) were from 240 families that had been recruited into a randomized experimental trial (NBP vs. literature control). Data from the pretest and 15-year follow-up were used. NBP participants reported less feelings of seeing life through a filter of divorce (e.g., thinking about how the divorce causes continued struggles for them) than those in the control condition. Program effects on maternal blame and acceptance of the divorce were moderated by pretest risk, a composite of divorce-related stressors and externalizing problems. NBP participants with elevated risk at program entry had lower levels of maternal blame. Program participation was associated with higher acceptance for those with elevated risk at program entry but lower acceptance for those with low risk at program entry. Program participation decreased the relations between maternal blame, acceptance of the divorce and filter of divorce and some, but not all, of the adjustment outcomes. These findings suggest that programs designed to help families after divorce have benefits in terms of long-term feelings about parental divorce as well as their relations with adjustment problems. (PsycINFO Database Record

Prospective Utility of a Bronchial Genomic Classifier for Lung Cancer Detection: Interim Results From a Multicenter Prospective Registry

SESSION TITLE: Advances in Lung Cancer SESSION TYPE: Original Investigation Slide PRESENTED ON: Wednesday, November 1, 2017 at 08:45 AM - 10:00 AM PURPOSE: The Bronchial Genomic Classifier (BGC) improves the sensitivity and negative predictive value (NPV) of bronchoscopy for lung cancer detection. The BGC identifies patients who, with a pre-test intermediate (10-60%) risk of malignancy, and an inconclusive diagnostic bronchoscopy result, are at low risk of malignancy (<10%) and may be considered for radiographic monitoring instead of an additional invasive procedure. We report a planned interim utility analysis from a prospective, multi-center registry study of the BGC, designed to observe patient selection, classifier performance, clinical utility and safety across varied clinical settings. METHODS: The BGC Registry enrolls patients at 43 medical centers who have had an inconclusive diagnostic bronchoscopy for suspected lung cancer, and for whom the BGC was ordered. The BGC sample is obtained by brushing the normal appearing mucosa of the central airway during bronchoscopy. The BGC is measured in those samples after cytology on biospecimens collected at bronchoscopy are confirmed inconclusive. Pre- and post- BGC clinical management recommendations are recorded and follow-up clinical and imaging data are collected at regular time points up to 36 months. RESULTS: 665 eligible patients underwent a diagnostic bronchoscopy for evaluation of lung cancer. A diagnosis was made in 259 (39%) patients at index bronchoscopy: 182 (27%) with lung cancer and 77 (12%) with a benign condition. The BGC was not ordered in 39 (6%) patients and 13 (2%) were not consented, leaving 354 patients meeting enrollment criteria. Of these, 315 patients are evaluable with exclusions of 17 (2%) patients with a BGC ‘no-result’, and 22 patients with insufficient data. Demographics showed 60% ≥ 65 y/o; 50% female, with a median 40 pack-year smoking history. This interim analysis focuses on 209 (66%) patients with an intermediate pre-test risk of malignancy where CT scans showed 76% of index lesions were ≤ 30 mm, 69% were peripherally located, 60% were solid and 50% were in the upper lobe. Advanced bronchoscopic technologies were used in 68% of cases. The BGC test results reclassified 74 (35%) pre-test intermediate risk patients to post-test low risk. At 10-months median follow-up, the reclassified low risk group showed a 17% absolute (40% to 23%), or 40% relative reduction in the use of invasive procedures compared to their pre-test diagnostic management plan. Patients who remained intermediate post-test risk showed no increase in invasive procedures. Five (2%) reclassified low risk patients have, at a median of 10-months follow-up, been diagnosed with lung cancer, well within the NPV of the test (91%). Four of five patients have undergone successful resection without evidence of a stage shift. CONCLUSIONS: This interim analysis from this prospective registry confirms the performance of the BGC reported in the AEGIS I and II studies.The emerging safety of reclassified low risk patients is encouraging. Additional follow-up is required to evaluate the full impact of clinical utility. CLINICAL IMPLICATIONS: The BGC improves the sensitivity of diagnostic bronchoscopy for patients undergoing evaluation for lung cancer and can reduce the number of unnecessary invasive procedures that are performed following an inconclusive procedure. DISCLOSURE: Douglas Hogarth: Grant monies (from industry related sources): Industry funded research, Consultant fee, speaker bureau, advisory committee, etc.: Advisor Board Joshiah Gordon: Other: Paid for time it takes to enroll patients Kate Smith: Employee: I receive a salary and hold stock options from Veracyte. Pauline Bianchi: Employee: Employed by Veracyte Marc Lenburg: Consultant fee, speaker bureau, advisory committee, etc.: Veracyte, Grant monies (from sources other than industry): NIH Avrum Spira: Consultant fee, speaker bureau, advisory committee, etc.: Advisor The following authors have nothing to disclose: Hans Lee, Patrick Whitten, Krish Bhadra, Travis Dotson, Sadia Benzaquen, Michael Pritchett, Ajay Bedekar, Mark Esterle No Product/Research Disclosure Information

Coronary CT Angiography Derived Fractional Flow Reserve: The Game Changer in Noninvasive Testing.

To summarize the scientific basis of CT derived fractional flow reserve (FFRCT) and present an updated review on the evidence from clinical trials and real-world observational data RECENT FINDINGS: In prospective multicenter studies of patients with stable coronary artery disease (CAD), FFRCT showed high diagnostic performance. More recently, FFRCT has advanced to the realm of clinical utility and real-world clinical practice with emerging data showing that FFRCT when compared to standard care is efficient in safely reducing downstream utilization of invasive coronary angiography (ICA), and costs, as well as improving the diagnostic yield of ICA. Moreover, FFRCT may broaden applicability of frontline coronary CTA testing to patients with high pre-test risk of CAD. Introducing FFRCT into clinical practice has the potential to significantly improve the management of patients with stable CAD. The optimal FFRCT testing interpretation strategy, as well as the relative cost-efficiency of FFRCT against standard noninvasive functional testing, need further investigation.

The risk is never zero: experience with rare recessive disease diagnosis in the era of expanded carrier screening

Expanded carrier screening (ECS) was launched in 2008 and involves testing for significantly more recessively inherited disorders than are recommended by professional guidelines. Several laboratories have since developed large ECS disease panels. The differences in the number of diseases or genes evaluated, and the methodologies used, are known to vary among these panels, which presents challenges for reproductive risk counseling. Here we document our experience with rare recessive disease diagnoses in donor-conceived offspring to detail additional ECS counseling considerations. At California Cryobank, all reports of medical issues in fetuses or offspring conceived using donor sperm are documented in an Adverse Outcome Report (AOR) and investigated to assess the etiology and risks to other offspring, the donor and his family. If a diagnosis is attributed to a genetic mutation from the donor, distribution of the donor’s specimens is restricted and relevant individuals are informed. AORs received between January 2010 and April 2017 were reviewed to identify all offspring diagnosed with recessively inherited disorders. Cases were further evaluated to determine which diagnoses could have been detected by currently available ECS panels. Six donors were identified as carriers or presumed carriers for recessively inherited disorders based on diagnoses or tests performed on donor-conceived individuals. Carrier screening for each of these conditions is not known to be available on any major ECS panel (Table 1).Tabled 1TABLE 1CaseConditionGene1Friedreich’s AtaxiaFXN2GMPPB-related Muscular DystrophyGMPPB3Adenosine Monophosphate Deaminase 1 DeficiencyAMPD14Adenosine Deaminase 2 DeficiencyCECR15NephronophthisisNPHP16POMT1-related disordersPOMT1 Open table in a new tab Pre-test risk counseling may help to manage patient expectations while planning a pregnancy and assist in the decision-making process for screening prior to, during, and after a pregnancy. In particular, providers should be cautious in informing their patients that ECS involves carrier screening for “all of the most common” or “most severe” recessively inherited disorders. For example, Friedrich’s ataxia has a carrier frequency in the general population of 1/60-1/100[1]. This is a higher carrier frequency than many of the diseases included on ECS panels that have carrier frequencies of less than 1/500. Carrier screening has evolved and improved greatly over the past several decades; however, there is still a background risk for every pregnancy to be affected with a recessively inherited disorder regardless of the carrier screening that was performed on one or both reproductive partners. Addressing the other conditions and background risks that ECS cannot reduce is particularly important for patients using gamete donors since additional screening may not be readily available.

Why transition risk to psychosis is not declining at the OASIS ultra high risk service: The hidden role of stable pretest risk enrichment

BackgroundThe reason for declining risk to psychosis across individuals assessed and meeting Ultra High Risk (UHR) criteria is still unclear. No studies have investigated the potential substantial role of the underlying risk enrichment across all the individuals undergoing an UHR assessment. MethodsCohort study including all non-psychotic subjects who were assessed on suspicion of psychosis risk by the OASIS UHR service in the period 2001 to 2015. Posttest (after UHR assessment) and pretest risk (before UHR assessment) of psychosis were stratified and compared across three time periods (2001–2005, 2006–2010, 2011–2015) with Cox analysis and modulating factors were investigated. ResultsThe posttest risk of psychosis at the OASIS service has increased from the initial pilot years of the service (2001–2005) and then stabilised and not declined over the following decade (2006–2010 and 2011–2015). This was paralleled by a similar course of pretest risk for psychosis. Stability of pretest risk for psychosis over the past decade was associated with a lack of change in ethnicity and to counterweighting changes in the type of referral sources over different time periods. ConclusionsThe time course of transition risk to psychosis in UHR services is strictly associated with the time course of pretest risk enrichment. If the latter remains stable over time, as for the OASIS service, no declining transition risk is observed over the most recent years. Pretest risk enrichment is determined by recruitment and sampling strategies. This study confirms the need to control these factors in the UHR field.

Clinical imaging in patients experiencing chest pain.

Non-invasive imaging modalities integrate the clinical and laboratory diagnostic work-up of patients admitted in emergency department for chest pain. Transthoracic echocardiography is the first-line imaging tool because it is rapidly and widely available, bedside feasible and cost-effective. Even when a comprensive exam is not feasible, a fast focused ultrasound exam should be performed. Contrast enhanced computed tomography is an easily accessible tool with specific application in patients suspected for pulmonary embolism (PE) and acute coronary syndrome (ACS) according to the pre-test risk assessment and to the clinical status. Cardiac magnetic resonance is not yet very widespread, takes a long time and requires quite stable hemodynamic and clinical condition. It provides accurate information on ventricular systolic function in patients with inadequate echocardiographic windows and gives the unique opportunity to obtain myocardial tissue characterization data that may be diriment in diseases such as ACS, myocarditis and Takotsubo syndrome. Nuclear imaging modalities are generally not available on 24 h service but can be useful in doubtful cases of ACS and PE. Shared diagnostic protocols are the cornerstone of a good practice in emergency rooms and chest pain units. Physician should be familiar with the indication for urgent non-invasive imaging exams in patients admitted for chest pain, in order to achieve rapid diagnosis and start a prompt and proper therapy. Moreover, they should balance identification of critical patients with the safe and early discharge, directly from the emergency room, of low-risk subjects with no evidence of disease.

Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer.

Purpose Genetic testing for breast cancer risk is evolving rapidly, with growing use of multiple-gene panels that can yield uncertain results. However, little is known about the context of such testing or its impact on treatment. Methods A population-based sample of patients with breast cancer diagnosed in 2014 to 2015 and identified by two SEER registries (Georgia and Los Angeles) were surveyed about genetic testing experiences (N = 3,672; response rate, 68%). Responses were merged with SEER data. A patient subgroup at higher pretest risk of pathogenic mutation carriage was defined according to genetic testing guidelines. Patients' attending surgeons were surveyed about genetic testing and results management. We examined patterns and correlates of genetic counseling and testing and the impact of results on bilateral mastectomy (BLM) use. Results Six hundred sixty-six patients reported genetic testing. Although two thirds of patients were tested before surgical treatment, patients without private insurance more often experienced delays. Approximately half of patients (57% at higher pretest risk, 42% at average risk) discussed results with a genetic counselor. Patients with pathogenic mutations in BRCA1/2 or another gene had the highest rates of BLM (higher risk, 80%; average risk, 85%); however, BLM was also common among patients with genetic variants of uncertain significance (VUS; higher risk, 43%; average risk, 51%). Surgeons' confidence in discussing testing increased with volume of patients with breast cancer, but many surgeons (higher volume, 24%; lower volume, 50%) managed patients with BRCA1/2 VUS the same as patients with BRCA1/2 pathogenic mutations. Conclusion Many patients with breast cancer are tested without ever seeing a genetic counselor. Half of average-risk patients with VUS undergo BLM, suggesting a limited understanding of results that some surgeons share. These findings emphasize the need to address challenges in personalized communication about genetic testing.

Silent coronary heart disease in patients with type 2 diabetes: application of a screening approach in a follow-up study

AimsThe cost-effectiveness of screening for silent coronary heart disease (CHD) in type 2 diabetes (DM2) is still debated. MethodsWe applied a diagnostic algorithm for silent CHD detection, in a cohort of 102 asymptomatic DM2 subjects (57±7years), attending 5 Italian outpatient clinics, to verify its predictive value. The risk of silent CHD was calculated considering classical risk factors, and presence of microangiopathy/macroangiopathy. Patients were divided in 3 groups, i.e. group 1: normal ECG and low silent CHD risk; group 2: abnormal ECG, irrespective of silent CHD risk; group 3: high silent CHD risk, irrespective of ECG. To group 2 and 3, a functional test was recommended and performed in 78% of patients. ResultsSilent CHD prevalence was similar in group 2 and 3 (25 vs. 17% respectively; p=0.495). However, evaluating the entire cohort, a significant higher prevalence of silent CHD was observed in subjects with abnormal vs. normal ECG (23 vs. 4%; P=0.004), but not in subjects with high vs. low pre-test silent CHD risk (14 vs. 9%; p=0.472). ConclusionsAn abnormal ECG was a strong, independent predictor of silent CHD (OR 8.9; CI 1.27–62.5; p=0.028) in DM2. Therefore, a functional stress testing should be considered in DM2 patients with ECG abnormalities.

Gaps in integrating genetic testing into management of breast cancer.

160 Background: Genetic testing for breast cancer risk is evolving rapidly, with surging use of multiple-gene panels. However, little is known about the extent to which testing is effectively integrated into management after diagnosis of breast cancer. Methods: A population-based sample of 3930 patients diagnosed with breast cancer in 2014-15 and identified by two SEER registries (Georgia and Los Angeles) were sent surveys 2 months after surgery and responses merged to SEER data. A subgroup at higher pre-test risk of pathogenic mutation carriage (vs average risk) was defined according to testing guidelines. Results: Among 2502 eligible patients with unilateral breast cancer (response rate 70%), 666 (27%) reported genetic testing. The Table shows wide variability in patient report of which professional ordered the test and discussed the results. Few (18-21%) patients had testing ordered by a genetic counselor and approximately half (57% high-risk, 42% average-risk) discussed results with one. One third of patient received testing after they had surgery. In a multivariable model adjusted for age, race, education, pre-test risk of mutation carriage, stage, co-morbidities and study site, the only factor significantly associated with delayed testing was insurance status: Compared to private insurance, patients were more likely to be tested after surgery if they had Medicare (OR 2.1, 95% CI 1.1-4.2) or no insurance (OR 3.0, CI 1.6-5.3). Conclusions: There is wide variability in which professionals order genetic testing and discuss results. Many breast cancer patients who receive genetic testing never see a genetic counselor. Many patients do not get tested early enough to consider the results in surgery management. These findings suggest enormous challenges in personalizing communication about genetic testing after diagnosis of breast cancer. [Table: see text]

Diagnostic Performance of Wells Score Combined With Point-of-care Lung and Venous Ultrasound in Suspected Pulmonary Embolism.

Lung and venous ultrasound are bedside diagnostic tools increasingly used in the early diagnostic approach of suspected pulmonary embolism (PE). However, the possibility of improving the conventional prediction rule for PE by integrating ultrasound has never been investigated. We performed lung and venous ultrasound in consecutive patients suspected of PE in four emergency departments. Conventional Wells score (Ws) was adjudicated by the attending physician, and ultrasound was performed by one of 20 investigators. Signs of deep venous thrombosis (DVT) at venous ultrasound and signs of pulmonary infarcts or alternative diagnoses at lung ultrasound were considered to recalculate two items of the Ws: signs and symptoms of DVT and alternative diagnosis less likely than PE. The diagnostic performances of the ultrasound-enhanced Ws (USWs) and Ws were then compared after confirmation of the final diagnosis. A total of 446 patients were studied. PE was confirmed in 125 patients (28%). USWs performed significantly better than Ws, with a sensitivity of 69.6% versus 57.6% and a specificity of 88.2% versus 68.2%. In combination with D-dimer, USWs showed an optimal failure rate (0.8%) and a significantly superior efficiency than Ws (32.3% vs. 27.2%). A strategy based on lung and venous ultrasound combined with D-dimer would allow to avoid CT pulmonary angiography in 50.5% of patients with suspected PE, compared to 27.2% when the rule without ultrasound is applied. A pretest risk stratification enhanced by ultrasound of lung and venous performs better than Ws in the early diagnostic process of PE.

Utility of home sleep apnea testing in high-risk veterans.

Many Veterans Affairs Medical Centers (VAMCs) have implemented home sleep apnea testing (HSAT) in lieu of traditional in-lab testing to establish a timely and cost-sensitive diagnosis of obstructive sleep apnea (OSA). However, concern remains for the sensitivity and specificity of said technology in this population as many veterans are at increased risk for many of the comorbid conditions that can limit the accuracy of HSAT results. Hence, the purpose of this study is to evaluate rate of incongruent outcomes (e.g., negative HSAT results despite high clinical symptomology) as well as differences in study quality metrics and predictors of OSA between veteran sleep patients and general sleep patients being evaluated by a home sleep test. A random sample of HSAT outcomes from 1500 veterans and 1500 general sleep clinic patients was retrieved from a repository of anonymized HSAT outcomes from 2009 to 2013. General sleep clinic data were from patients referred for home sleep testing from a variety of clinical practices across North America, whereas VAMC patients were tested using a central dissemination process. All patients were tested for OSA using the Apnea Risk and Evaluation System (ARES), an HSAT that simultaneously records airflow, pulse oximetry, snoring, accelerometry, and EEG. Sample differences and rates of comorbidities, HSAT outcomes, predictors of OSA, and pretest OSA risk information were evaluated between groups. The presence of OSA was defined as an apnea-hypopnea index (AHI; using 4% desaturation criterion) of ≥5 and ≥15 events per hour. Sample differences in predictors of OSA were evaluated using logistic multiple regression. Veterans (91.3% male) were more likely to report comorbidities, especially depression, insomnia, hypertension, diabetes, restless legs syndrome (RLS), and use of sleep and pain medications compared to general sleep clinic patients (57.1% male). Despite differences in the rate of medical comorbidities, no differences were observed between groups with regard to rates of positive studies, study integrity indicators, or predictors of OSA. Veterans, on average, had 30min less recording time compared to those in the general clinic sample (p<.01). However, these differences did not impact the amount of the record that was deemed valid nor were veterans more likely to have wakefulness after sleep onset. Predictors of OSA for both groups included advancing age, and increased measures of adiposity (neck circumference and BMI). Mean AHI and respiratory disturbance index (RDI) were statistically similar for both groups and were similar for sleep stage and position. Home sleep apnea testing for the diagnosis of OSA appears to yield similar results for VAMC patients deemed at high risk for OSA as it does with general sleep clinic patients.

Abstract P2-02-06: Genetic counseling, germline genetic testing, and impact of results in patients with newly diagnosed breast cancer

Abstract The surge in BRCA1/2 and multiple-gene panel testing after a diagnosis of breast cancer has fueled concerns about how genetic testing results will be integrated into patient management. However, there is virtually no research about the timing or extent of genetic counseling before or after testing or the impact of genetic results on bilateral mastectomy (BLM) use since the advent of more widespread testing. Methods: A population-based sample of 3600 patients newly diagnosed with breast cancer identified by two SEER registries (Georgia and Los Angeles County) were sent surveys two months after surgery (Dx dates 2014-15) about their genetic testing and treatment experiences. Survey information was merged with SEER data. We examined patterns and correlates of counseling and genetic testing and the impact of results on patient preferences for BLM and receipt of BLM. Results: Among 2388 patients with unilateral breast cancer (response 70%), 697 (29.2%) had elevated pre-test risk of a germline mutation (based on age, family cancer history, ancestry, and tumor subtype). One-quarter of these higher risk patients (25.6%) did not discuss whether to have testing with any provider, 26.1% discussed it with clinicians only, and 48.3% had a visit with a genetic counselor. Half of patients with elevated pre-test risk (51.2%) were tested: 6.6% before diagnosis, 65.4% after diagnosis but before surgery and 28.0% after surgery. Higher risk patients who underwent testing were younger (p&amp;lt;.001) and had higher income (p=.029) but rates did not differ significantly by race, education, insurance, marital status, cancer stage, comorbidities, or geographic site after controlling for all covariates. There was wide variation in the type of professional who discussed test results with patients: discussed with surgeon only (17.8%), medical oncologist only (19.7%), both physicians but no counselor (4.8%), or genetic counselors (56.8%). Among all testers in the total sample (n=667), 54 (9.4%) reported a pathogenic mutation (12.1% of higher risk patients vs 5.7% of low risk patients) and 59 (10.0%) reported a variant of unknown significance (VUS) (10.2% of higher risk patients vs 9.9% of lower risk patients), p=.027 for differences between groups. Two-thirds (60.4%) of patients with pathogenic mutations reported that the test made them more interested in BLM vs 8.8% of those with a VUS, and 11.4% of those with negative tests, p&amp;lt;.001. Two-thirds (69.2%) of those with pathogenic mutations received BLM vs 21.9% of those with VUS and 27.9% of those with negative tests, p&amp;lt;.001. Conclusions: Many patients newly diagnosed with breast cancer at higher risk of carrying a pathogenic mutation do not receive pre-test counseling or genetic testing and disparities are observed. There is wide variability in the timing of genetic testing after diagnosis and with which clinician the findings are discussed. Taken together, these results suggest that germline genetic testing after a diagnosis of breast cancer is poorly integrated into practice. However, the impact of genetic test results on patient attitudes and receipt of bilateral mastectomy suggests that genetic testing does help target prevention to a patient's future risk for a new primary breast cancer. Citation Format: Katz SJ, Morrow M, Jagsi R, Kurian A. Genetic counseling, germline genetic testing, and impact of results in patients with newly diagnosed breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-02-06.

Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminate cytology.

ThyroSeq v2 claims high positive (PPV) and negative (NPV) predictive values in a wide range of pretest risks of malignancy in indeterminate thyroid nodules (ITNs) (categories B-III and B-IV of the Bethesda system). We evaluated ThyroSeq v2 performance in a cohort of patients with ITNs seen at our Academic Cancer Center from September 2014 to April 2016, in light of the new diagnostic criteria for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Our study included 182 patients (76% female) with 190 ITNs consecutively tested with ThyroSeq v2. Patient treatment followed our institutional thyroid nodule clinical pathway. Histologies of nodules with follicular variant papillary thyroid carcinoma or NIFTP diagnoses were reviewed, with reviewers blinded to molecular results. ThyroSeq v2 performance was calculated in nodules with histological confirmation. We identified a mutation in 24% (n = 45) of the nodules. Mutations in RAS were the most prevalent (n = 21), but the positive predictive value of this mutation was much lower (31%) than that in prior reports. In 102 resected ITNs, ThyroSeq v2 performance was as follows: sensitivity 70% (46-88), specificity 77% (66-85), PPV 42% (25-61) and NPV 91% (82-97). The performance in B-IV nodules was significantly better than that in B-III nodules (area under the curve 0.84 vs 0.57, respectively; P = 0.03), where it was uninformative. Further studies evaluating ThyroSeq v2 performance are needed, particularly in B-III.