Search

Objective: Cascade testing for hereditary cancer syndromes allows relatives to estimate cancer risk and pursue prevention and early detection strategies. The current paradigm relies on patient coordinated care, resulting in only one-third of relatives successfully completing testing. Studies suggest that team-based approaches, where clinicians facilitate testing, can increase uptake. As institutions consider implementing such programs, understanding patient characteristics associated with interest is crucial for resource allocation. We aim to assess interest in clinician-facilitated testing and evaluate barriers., Methods: Patients with cancer-associated pathogenic variants seen at a gynecologic oncology clinic were offered clinician-facilitated cascade testing. Patient interest and demographic variables were recorded and patients that declined were interviewed regarding the decision., Results: From 11/2023-4/2024, 139 patients were offered clinician-facilitated cascade testing. Median patient age was 43 years (IQR 17), 97 (69.8 %) self-identified as White and 101 (72.7 %) as non-Hispanic. Fifty-six (40.3 %) patients harbored a BRCA1 pathogenic variant, 37 (26.6 %) BRCA2, and 46 (33.1 %) other cancer-associated genes. Fifty-seven (41.0 %) patients expressed interest in the intervention. Interested patients were more likely to have been diagnosed in the prior year vs. patients who were not interested on univariate (OR 4.6, 95 % CI 2.0-10.2, P = 0.0002) and multivariable analyses (adjusted OR 3.8, 95 % CI 1.622-9.009, P = 0.0022)., Conclusions: Our study demonstrates that patients are almost five time more likely to be interested in cascade genetic testing within the first year of diagnosis of a pathogenic variant. Given the utility of such programs and their resource requirements, targeting this population could maximize effectiveness and uptake of cascade services., Competing Interests: Declaration of competing interest The authors have no financial or personal conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study compared Lynch syndrome universal tumor screening (UTS) across multiple health systems (some of which had 2 or more distinct UTS programs) to understand multilevel factors that may affect the successful implementation of complex programs., Methods: Data from 66 stakeholder interviews were used to conduct multivalue coincidence analysis and identify key factors that consistently make a difference in whether UTS programs were implemented and optimized at the system level., Results: The selected coincidence analysis model revealed combinations of conditions that distinguish 4 optimized UTS programs, 10 nonoptimized programs, and 4 systems with no program. Fully optimized UTS programs had both a maintenance champion and a positive inner setting. Two independent paths were unique to nonoptimized programs: (1) positive attitudes and a mixed inner setting or (2) limited planning and engaging among stakeholders. Negative views about UTS evidence or lack of knowledge about UTS led to a lack of planning and engaging, which subsequently prevented program implementation., Conclusion: The model improved our understanding of program implementation in health care systems and informed the creation of a toolkit to guide UTS implementation, optimization, and changes. Our findings and toolkit may serve as a use case to increase the successful implementation of other complex precision health programs., Competing Interests: Conflict of Interest No competing financial interests are reported by any authors in relation to the work described in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In the USA, up to 95% of individuals harbouring cancer-predisposing germline pathogenic variants have not been identified despite recommendations for screening at the primary care level., Methods and Analysis: Our primary objective is to use a two-arm, single-institution randomised controlled trial to compare the proportion of eligible patients that are recommended genetic testing for hereditary cancer syndromes using a digital tool versus clinician interview for genetic cancer risk assessment in an urban academic gynaecology clinic. New gynaecology patients will be consented and randomised 1:1 to either the intervention arm, in which a digital tool is used for genetic cancer risk assessment, or usual care, in which the clinician performs genetic cancer risk assessment. Individuals will be considered eligible for hereditary cancer syndrome genetic testing if criteria set forth by the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology are met. Eligible patients are 18 years or older, speak and read English, have not yet undergone hereditary cancer genetic testing and have access to a smartphone. The study aims to enrol 50 patients in each arm to allow for 80% power with two-tailed alpha of 5% to detect a 20% difference in proportion of eligible patients recommended for genetic testing. The primary outcome is the proportion of eligible individuals recommended genetic testing in the digital tool arm versus usual care arm, analysed using the χ 2 or Fisher's exact test as appropriate for sample size. The secondary outcome is completion of genetic testing, as well as exploration of patient factors, particularly social determinants of health, which may affect the receipt, utilisation and experience with genetic services., Ethics and Dissemination: This study has been approved by the Weill Cornell Institutional Review Board (Protocol No. 21-11024123). Participants will be informed of the benefits and risks of participation prior to consent. Dissemination of data will be deidentified and conducted through academic conferences and journals. Patients identified to be eligible for genetic testing who did not receive counselling from their providers will be contacted; participants will not receive direct notification of trial results., Registration Details: This trial is registered at clinicaltrials.gov (NCT05562778) in September 2022., Protocol Version: This is protocol version 1, as of 22 May 2024., Countries of Recruitment and Recruitment Status: USA, currently recruiting., Health Conditions/problems Studied: Genetic predisposition to cancers such as breast, ovarian, uterine and pancreatic. DEIDENTIFIED INDIVIDUAL CLINICAL TRIAL PARTICIPANT-LEVEL DATA IDP SHARING STATEMENT: IDP will not be shared., Trial Registration Number: NCT05562778., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial., Objective: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective., Study Design: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening., Results: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness., Conclusion: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This is a systematic review and meta-analysis evaluating the uptake of cascade genetic testing for hereditary breast and ovarian cancer syndrome. Among 30 studies included for meta-analysis, the uptake of cascade genetic testing was 33% (95% CI 25%-42%), with higher uptake rates among females compared with male relatives, and among first-degree compared with second-degree relatives. These findings indicate suboptimal uptake of cascade genetic testing among people at risk for hereditary breast and ovarian cancer syndrome, representing a missed opportunity for cancer prevention and early detection. There is a need for interventions to improve uptake rates., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Identification of those at risk of hereditary cancer syndromes using electronic health record (EHR) data sources is important for clinical care, quality improvement, and research. We describe diagnostic processes, previously seldom reported, for a common hereditary cancer syndrome, Lynch syndrome (LS), using EHR data within a community-based, multicenter, demographically diverse health system., Methods: Within a retrospective cohort enrolled between 2015 and 2020 at Kaiser Permanente Northern California, we assessed electronic diagnostic domains for LS including (1) family history of LS-associated cancer; (2) personal history of LS-associated cancer; (3) LS screening via mismatch repair deficiency (MMRD) testing of newly diagnosed malignancy; (4) germline genetic test results; and (5) clinician-entered diagnostic codes for LS. We calculated proportions and overlap for each diagnostic domain descriptively., Results: Among 5.8 million individuals, (1) 28,492 (0.49%) had a family history of LS-associated cancer of whom 3,635 (13%) underwent genetic testing; (2) 100,046 (1.7%) had a personal history of a LS-associated cancer; and (3) 8,711 (0.1%) were diagnosed with colorectal cancer of whom 7,533 (86%) underwent MMRD screening and of the positive screens (486), 130 (27%) underwent germline testing. One thousand seven hundred and fifty-seven (0.03%) were diagnosed with endometrial cancer of whom 1,613 (92%) underwent MMRD screening and of the 195 who screened positive, 55 (28%) underwent genetic testing. (4) 30,790 (0.05%) had LS germline genetic testing with 707 (0.01%) testing positive; and (5) 1,273 (0.02%) had a clinician-entered diagnosis of LS., Conclusion: It is feasible to electronically characterize the diagnostic processes of LS. No single data source comprehensively identifies all LS carriers. There is underutilization of LS genetic testing for those eligible and underdiagnosis of LS. Our work informs similar efforts in other settings for hereditary cancer syndromes.

Prostate cancer is a heritable disease with ancestry-biased incidence and mortality. Polygenic risk scores (PRSs) offer promising advancements in predicting disease risk, including prostate cancer. While their accuracy continues to improve, research aimed at enhancing their effectiveness within African and Asian populations remains key for equitable use. Recent algorithmic developments for PRS derivation have resulted in improved pan-ancestral risk prediction for several diseases. In this study, we benchmark the predictive power of six widely used PRS derivation algorithms, including four of which adjust for ancestry, against prostate cancer cases and controls from the UK Biobank and All of Us cohorts. We find modest improvement in discriminatory ability when compared with a simple method that prioritizes variants, clumping, and published polygenic risk scores. Our findings underscore the importance of improving upon risk prediction algorithms and the sampling of diverse cohorts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Patients with a personal or family history of cancer may have elevated risk of developing future cancers, which often remains unrecognized due to lapses in screening. This pilot study assessed the usability and clinical outcomes of a cancer risk stratification tool in a gynecologic oncology clinic., Methods: New gynecologic oncology patients were prompted to complete a commercially developed personal and family history-based risk stratification tool to assess eligibility for genetic testing using National Comprehensive Cancer Network criteria and estimated lifetime breast cancer risk using the Tyrer-Cuzick model. After use of the risk stratification tool, usability was assessed via completion rate and the System Usability Scale, and health literacy was assessed using the BRIEF Health Literacy Screening Tool., Results: 130 patients were prompted to complete the risk stratification tool; 93 (72%) completed the tool. Race and ethnicity and insurance type were not associated with tool completion. The median System Usability Scale score was 83 out of 100 (interquartile range, 60-95). Health literacy positively correlated with perceived usability. Public insurance and race or ethnicity other than non-Hispanic White was associated with lower perceived usability. Sixty (65%) patients met eligibility criteria for genetic testing, and 21 (38% of 56 eligible patients) were candidates for enhanced breast cancer screening based on an estimated lifetime breast cancer risk of ≥20%., Conclusions: A majority of patients completed the digital cancer risk stratification tool. Older age, lower health literacy, public insurance, and race or ethnicity other than non-Hispanic White were associated with lower perceived tool usability., Competing Interests: Declaration of competing interest The authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Gynecologic and breast cancers share several risk factors. Breast cancer risk assessment tools can identify those at elevated risk and allow for enhanced breast surveillance and chemoprevention, however such tools are underutilized. We aim to evaluate the use of routine breast cancer risk assessment in a gynecologic oncology clinic., Methods: A patient-facing web-based tool was used to collect personal and family history and run four validated breast cancer risk assessment models (Tyrer-Cuzick (TC), Gail, BRCAPRO, and Claus) in a gynecologic oncology clinic. We evaluated completion of the tools and identification of patients at elevated risk for breast cancer using the four validated models., Results: A total of 99 patients were included in this analysis. The BRCAPRO model had the highest completion rate (84.8%), followed by the TC model (74.7%), Gail model (74.7%), and the Claus model (52.1%). The TC model identified 21.6% of patients completing the model as having ≥20% lifetime risk of breast cancer, compared to 6.8% by the Gail model, and 0% for both the BRCAPRO and Claus models. The Gail model identified 52.5% of patients as having ≥1.67% 5-year risk of breast cancer. Among patients identified as high-risk for breast cancer and eligible for screening, 9/9 (100%) were referred to a high-risk breast clinic., Conclusion: Among patients that completed the TC breast cancer risk assessment in a gynecologic oncology clinic, approximately 1 in 5 were identified to be at significantly elevated lifetime risk for breast cancer. The gynecologic oncologist's office might offer a convenient and feasible setting to incorporate this risk assessment into routine patient care, as gynecologic oncologists often have long-term patient relationships and participate in survivorship care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Genetic counseling (GC) is standard of care in genetic cancer risk assessment (GCRA). A rigorous assessment of the data reported from published studies is crucial to ensure the evidence-based implementation of GC., Methods: We conducted a systematic review and meta-analysis of 17 patient-reported and health-services-related outcomes associated with pre- and post-test GC in GCRA in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology., Results: Twenty-five of 5393 screened articles met inclusion criteria. No articles reporting post-test GC outcomes met inclusion criteria. For patient-reported outcomes, pre-test GC significantly decreased worry, increased knowledge, and decreased perceived risk but did not significantly affect patient anxiety, depression, decisional conflict, satisfaction, or intent to pursue genetic testing. For health-services outcomes, pre-test GC increased correct genetic test ordering, reduced inappropriate services, increased spousal support for genetic testing, and expedited care delivery but did not consistently improve cancer prevention behaviors nor lead to accurate risk assessment. The GRADE certainty in the evidence was very low or low. No included studies elucidated GC effect on mortality, cascade testing, cost-effectiveness, care coordination, shared decision making, or patient time burden., Conclusion: The true impact of GC on relevant outcomes is not known low quality or absent evidence. Although a meta-analysis found that pre-test GC had beneficial effects on knowledge, worry, and risk perception, the certainty of this evidence was low according to GRADE methodology. Further studies are needed to support the evidence-based application of GC in GCRA., Competing Interests: Conflict of Interest Julie O. Culver, Nicole L. Bertsch, Raluca N. Kurz, Smita Rao, Shannon Stasi, Chris D. Stave, and Ravi N. Sharaf have no conflicts of interest to declare. At the time of the systematic review, Linda L. Cheng was an employee of Quest Diagnostics and received salary from Quest Diagnostics. Mary Pritzlaff is an employee and receives full time salary from Ambry Genetics and is an intellectual property owner and receives royalties for CancerGene Connect., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal tumor screening (UTS) of newly diagnosed CRC cases is recommended to aid in diagnosis of LS and reduce cancer-related morbidity and mortality. However, not all health systems have adopted UTS processes and implementation may be inconsistent due to system and patient-level complexities., Methods: To identify barriers, facilitators, and suggestions for improvements of the UTS process from the patient perspective, we conducted in-depth, semi-structured interviews with patients recently diagnosed with CRC, but not screened for or aware of LS. Patients were recruited from eight regionally diverse US health systems. Interviews were conducted by telephone, 60-minutes, audio-recorded, and transcribed. An inductive, constant comparative analysis approach was employed.  RESULTS: We completed 75 interviews across the eight systems. Most participants were white (79%), about half (52%) were men, and the mean age was 60 years. Most self-reported either no (60%) or minimal (40%) prior awareness of LS. Overall, 96% of patients stated UTS should be a routine standard of care for CRC tumors, consistently citing four primary motivations for wanting to know their LS status and engage in the process for LS identification: "knowledge is power"; "family knowledge"; "prevention and detection"; and "treatment and surveillance." Common concerns pertaining to the process of screening for and identifying LS included: creating anticipatory worry for patients, the potential cost and the accuracy of the genetic test, and possibly having one's health insurance coverage impacted by the LS diagnosis. Patients suggested health systems communicate LS results in-person or by phone from a trained expert in LS; offer proactive verbal and written education about LS, the screening steps, and any follow-up surveillance recommendations; and support patients in communicating their LS screening to any of their blood relatives., Conclusion: Our qualitative findings demonstrate patients with CRC have a strong desire for healthcare systems to regularly implement and offer UTS. Patients offer key insights for health systems to guide future implementation and optimization of UTS and other LS screening programs and maximize diagnosis of individuals with LS and improve cancer-related surveillance and outcomes., Trial Registration: Not available: not a clinical trial., (© 2023. The Author(s).)

Objective: Approximately 20% of ovarian cancers are due to an underlying germline pathogenic variant. While pathogenic variants in several genes have been well-established in the development of hereditary ovarian cancer (e.g. BRCA1/2, RAD51C, RAD51D, BRIP1, mismatch repair genes), the role of partner and localizer of BRCA2 (PALB2) remains uncertain. We sought to utilize meta-analysis to evaluate the association between PALB2 germline pathogenic variants and ovarian cancer., Methods: We conducted a systematic review and meta-analysis. We searched key electronic databases to identify studies evaluating multigene panel testing in people with ovarian cancer. Eligible trials were subjected to meta-analysis., Results: Fifty-five studies met inclusion criteria, including 48,194 people with ovarian cancer and information available on germline PALB2 pathogenic variant status. Among people with ovarian cancer and available PALB2 sequencing data, 0.4% [95% CI 0.3-0.4] harbored a germline pathogenic variant in the PALB2 gene. The pooled odds ratio (OR) for carrying a PALB2 pathogenic variant among the ovarian cancer population of 20,474 individuals who underwent germline testing was 2.48 [95% CI 1.57-3.90] relative to 123,883 controls., Conclusions: Our meta-analysis demonstrates that the pooled OR for harboring a PALB2 germline pathogenic variant among people with ovarian cancer compared to the general population is 2.48 [95% CI 1.57-3.90]. Prospective studies evaluating the role of germline PALB2 pathogenic variants in the development of ovarian cancer are warranted., Competing Interests: Declaration of Competing Interest The authors have no financial or personal conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Most individuals with a hereditary cancer syndrome are unaware of their genetic status to underutilization of hereditary cancer risk assessment. Chatbots, or programs that use artificial intelligence to simulate conversation, have emerged as a promising tool in health care and, more recently, as a potential tool for genetic cancer risk assessment and counseling. Here, we evaluated the existing literature on the use of chatbots in genetic cancer risk assessment and counseling., Methods: A systematic review was conducted using key electronic databases to identify studies which use chatbots for genetic cancer risk assessment and counseling. Eligible studies were further subjected to meta-analysis., Results: Seven studies met inclusion criteria, evaluating five distinct chatbots. Three studies evaluated a chatbot that could perform genetic cancer risk assessment, one study evaluated a chatbot that offered patient counseling, and three studies included both functions. The pooled estimated completion rate for the genetic cancer risk assessment was 36.7% (95% CI, 14.8 to 65.9). Two studies included comprehensive patient characteristics, and none involved a comparison group. Chatbots varied as to the involvement of a health care provider in the process of risk assessment and counseling., Conclusion: Chatbots have been used to streamline genetic cancer risk assessment and counseling and hold promise for reducing barriers to genetic services. Data regarding user and nonuser characteristics are lacking, as are data regarding comparative effectiveness to usual care. Future research may consider the impact of chatbots on equitable access to genetic services.

Objectives: Approximately 1% of individuals have a hereditary cancer predisposition syndrome, however, the majority are not aware. Collecting a cancer family history (CFH) can triage patients to receive genetic testing. To rigorously assess different methods of CFH collection, we compared a web-based tool (WBT) to usual care (clinician collects CFH) in a randomized controlled trial., Methods: New gynecologic oncology patients (seen 9/2019-9/2021) were randomized to one of three arms in a 2:2:1 allocation ratio: 1) usual care clinician CFH collection, 2) WBT completed at home, or 3) WBT completed in office. The WBT generated a cancer-focused pedigree and scores on eight validated cancer risk models. The primary outcome was collection of an adequate CFH (based on established guidelines) with usual care versus the WBT., Results: We enrolled 250 participants (usual care - 110; WBT home - 105; WBT office - 35 [closed early due to COVID-19]). Within WBT arms, 109 (78%) participants completed the tool, with higher completion for office versus home (33 [94%] vs. 76 [72%], P = 0.008). Among participants completing the WBT, 63 (58%) had an adequate CFH versus 5 (5%) for usual care (P < 0.001). Participants completing the WBT were significantly more likely to complete genetic counseling (34 [31%] vs. 15 [14%], P = 0.002) and genetic testing (20 [18%] vs. 9 [8%], P = 0.029). Participant and provider WBT experience was favorable., Conclusions: WBTs for CFH collection are a promising application of health information technology, resulting in more comprehensive CFH and a significantly greater percentage of participants completing genetic counseling and testing., Competing Interests: Declaration of Competing Interest Kevin Holcomb serves as a consultant for Johnson and Johnson and receives research support from Fujirebio Diagnostics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Identifying key determinants is crucial for improving program implementation and achieving long-term sustainment within healthcare organizations. Organizational-level complexity and heterogeneity across multiple stakeholders can complicate our understanding of program implementation. We describe two data visualization methods used to operationalize implementation success and to consolidate and select implementation factors for further analysis., Methods: We used a combination of process mapping and matrix heat mapping to systematically synthesize and visualize qualitative data from 66 stakeholder interviews across nine healthcare organizations, to characterize universal tumor screening programs of all newly diagnosed colorectal and endometrial cancers and understand the influence of contextual factors on implementation. We constructed visual representations of protocols to compare processes and score process optimization components. We also used color-coded matrices to systematically code, summarize, and consolidate contextual data using factors from the Consolidated Framework for Implementation Research (CFIR). Combined scores were visualized in a final data matrix heat map., Results: Nineteen process maps were created to visually represent each protocol. Process maps identified the following gaps and inefficiencies: inconsistent execution of the protocol, no routine reflex testing, inconsistent referrals after a positive screen, no evidence of data tracking, and a lack of quality assurance measures. These barriers in patient care helped us define five process optimization components and used these to quantify program optimization on a scale from 0 (no program) to 5 (optimized), representing the degree to which a program is implemented and optimally maintained. Combined scores within the final data matrix heat map revealed patterns of contextual factors across optimized programs, non-optimized programs, and organizations with no program., Conclusions: Process mapping provided an efficient method to visually compare processes including patient flow, provider interactions, and process gaps and inefficiencies across sites, thereby measuring implementation success via optimization scores. Matrix heat mapping proved useful for data visualization and consolidation, resulting in a summary matrix for cross-site comparisons and selection of relevant CFIR factors. Combining these tools enabled a systematic and transparent approach to understanding complex organizational heterogeneity prior to formal coincidence analysis, introducing a stepwise approach to data consolidation and factor selection., (© 2023. The Author(s).)

Cascade testing for familial cancer syndromes has historically been difficult to execute. As part of a facilitated cascade testing pathway, we evaluated barriers to completion of cascade testing. Our previously published study evaluated a facilitated cascade testing pathway whereby a genetics team facilitated at-risk relative (ARR) cascade testing through telephone genetic counseling and mailed saliva kit testing. This follow-up study evaluated barriers to completion of cascade genetic testing through six-month follow-up telephone interviews. Probands identified 114 ARRs, of whom 97 were successfully contacted by telephone. Among those contacted, 83 (86%) reported interest in genetic testing and 14 (14%) declined. Among those reporting interest in testing, 71% (69/83) completed testing. Follow-up telephone interviews revealed that 14 ARRs did not complete testing despite reporting interest for the following reasons: concern about genetic discrimination, fear of a positive result and belief that the pathogenic variant was not relevant to his/her health. Five ARRs reported that they remained interested in testing and the telephone call prompted completion of testing. Even when facilitated by a medical team with prioritization of relative convenience, significant barriers to cascade testing ARRs for hereditary breast and ovarian cancer syndrome persist due to concern about genetic discrimination, cost, and fear of positive test results., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To evaluate rates of familial disclosure of hereditary cancer syndrome information., Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO no.: CRD42020134276). Key electronic databases were searched to identify studies evaluating hereditary cancer syndrome cascade relative disclosure. Eligible studies were subjected to meta-analysis., Results: Thirty-four studies met inclusion criteria. Among 11,711 included relatives, 70% (95% CI 60 - 78%) were informed of their risk of carrying a cancer-associated pathogenic variant; of 2,875 relatives informed of their risk who were evaluated for uptake of cascade testing, 43% (95% CI 27 - 61%) completed testing. Rates of disclosure were higher among female vs male relatives (79% [95% CI 73% - 84%] vs 67% [95% CI 57% - 75%]) and first-degree vs second-degree relatives (83% [95% CI 77% - 88%] vs 58% [95% CI 45 - 69%])., Conclusion: Nearly one-third of at-risk relatives remain uninformed of their risk of carrying a cancer-associated pathogenic variant. Even among those informed, fewer than half subsequently complete genetic testing, representing a critical missed opportunity for precision cancer prevention., Innovation: Five studies evaluating interventions to improve disclosure rates were generally ineffective. Urgent work is needed to elucidate barriers to relative disclosure by probands to develop targeted interventions that can optimize proband-mediated cascade genetic testing rates., Competing Interests: Kevin Holcomb reports a relationship with Johnson & Johnson that includes: consulting or advisory., (© 2023 The Authors.)

Background: Cascade genetic testing for hereditary cancer syndromes offers affected relatives the opportunity to pursue cancer screening and risk-reducing surgery and thus reduces morbidity and mortality. The purpose of this study was to measure the long-term utilization of targeted cancer prevention and quality of life among at-risk relatives offered clinician-facilitated cascade genetic testing., Methods: In a pilot study, at-risk relatives of patients with a hereditary cancer syndrome were contacted directly by the clinical team and offered telephone genetic counseling and genetic testing via an at-home, mailed saliva kit. Two-year follow-up results evaluating the use of targeted cancer prevention strategies and the quality of life for enrolled relatives were reported. Quality-of-life was measured with validated surveys, and scores were compared to the time of initial contact by the Wilcoxon signed-rank test., Results: Ninety-five at-risk relatives were enrolled in the initial pilot study, and 72 (76%) participated in the 2-year follow-up; 57 of these (79%) had completed genetic testing. Twenty-five of those 57 relatives (44%) were found to harbor an inherited pathogenic variant. Guideline-based cancer surveillance was recommended to 18 relatives; 13 (72%) completed at least one recommended screening, and six (33%) completed all recommended screenings. Risk-reducing surgery was recommended to 10 relatives; four (40%) completed a total of eight procedures. Quality-of-life surveys demonstrated low levels of anxiety, depression, distress, and uncertainty., Conclusions: The 2-year follow-up of the original pilot study revealed that clinician-facilitated cascade testing resulted in genetically targeted cancer screening and prevention with preserved quality of life. These results, to be confirmed by larger randomized controlled trials, suggest that medical systems should consider supporting clinician-facilitated cascade testing programs., (© 2022 American Cancer Society.)

Purpose: Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic., Materials and Methods: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis., Results: Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50)., Conclusion: Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.

We conducted an updated economic evaluation, from a healthcare system perspective, to compare the relative effectiveness and efficiency of eight Lynch syndrome (LS) screening protocols among newly diagnosed colorectal cancer (CRC) patients. We developed decision analytic models for a hypothetical cohort of 1000 patients. Model assumptions and parameter values were based on literature and expert opinion. All costs were in 2018 USD. For identifying LS cases, the direct germline sequencing (DGS) protocol provided the best performance (sensitivity 99.90%, 99.57-99.93%; specificity 99.50%, 97.28-99.85%), followed by the tumor sequencing to germline sequencing (TSGS) protocol (sensitivity, 99.42%, 96.55-99.63%; specificity, 96.58%, 96.46-96.60%). The immunohistochemistry (IHC) protocol was most efficient at $20,082 per LS case identified, compared to microsatellite instability (MSI) ($22,988), DGS ($31,365), and TSGS ($104,394) protocols. Adding double-somatic testing to IHC and MSI protocols did not change sensitivity and specificity, increased costs by 6% and 3.5%, respectively, but reduced unexplained cases by 70% and 50%, respectively. DGS would be as efficient as the IHC protocol when the cost of germline sequencing declines under $368 indicating DGS could be an efficient option in the near future. Until then, IHC and MSI protocols with double-somatic testing would be the optimal choices.

Purpose: Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services., Methods: We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined., Results: A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27-53%] and 30% [CI 19-44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86-100%]), telemedicine (75% [CI 43-93%]), clinic-embedded genetic counselor (76% [CI 32-95%]), reflex tumor somatic genetic assessment (64% [CI 17-94%]), universal testing (57% [28-82%]), and referral forms (26% [CI 10-53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17-38%] vs. 40% [CI 25-57%]) as was being un-insured vs. insured (23% [CI 18-28%] vs. 38% [CI 26-53%])., Conclusions: Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status., Competing Interests: Declaration of Competing Interest Kevin Holcomb serves as a consultant for Johnson and Johnson and receives research support from Fujirebio Diagnostics, outside the submitted work. The other authors made no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Collection of family cancer histories (FCHs) can identify individuals at risk for familial cancer syndromes. The aim of this study is to evaluate the literature on existing strategies whereby providers use information technology to assemble FCH., Methods: A systematic search of online databases (Ovid MEDLINE, Cochrane, and Embase) between 1980 and 2020 was performed. Statistical heterogeneity was assessed through the chi-square test (ie, Cochrane Q test) and the inconsistency statistic (I 2 ). A random-effects analysis was used to calculate the pooled proportions and means., Results: The comprehensive search produced 4,005 publications. Twenty-eight studies met inclusion criteria. Twenty-seven information technology tools were evaluated. Eighteen out of 28 studies were electronic surveys administered before visits (18, 64.3%). Five studies administered tablet surveys in offices (5, 17.8%). Four studies collected electronic survey via kiosk before visits (4, 14.3%), and one study used animated virtual counselor during visits (1, 3.6%). Among the studies that use an FCH tool, the pooled estimate of the overall completion rate was 86% (CI, 72% to 96%), 84% (CI, 65% to 97%) for electronic surveys before visits, 89% (CI, 0.74 to 0.98) for tablet surveys, and 85% (CI, 0.66 to 0.98) for surveys via kiosk. Mean time required for completion was 31.0 minutes (CI, 26.1 to 35.9), and the pooled estimate of proportions of participants referred to genetic testing was 12% (CI, 4% to 23%)., Conclusion: Our review found that electronic FCH collection can be completed successfully by patients in a time-efficient manner with high rates of satisfaction., Competing Interests: Charlene ThomasTravel, Accommodations, Expenses: Inovio Pharmaceuticals, Nektar, Pfizer Kevin HolcombResearch Funding: Fujirebio DiagnosticsExpert Testimony: Johnson and Johnson Inc Melissa K. FreyResearch Funding: InvitaeNo other potential conflicts of interest were reported.

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus. Many new studies have been reported recently that describe EoE management. An expert panel was convened by the American Gastroenterological Association Institute and the Joint Task Force on Allergy-Immunology Practice Parameters to provide a technical review to be used as the basis for an updated clinical guideline. This technical review was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Eighteen focused EoE management questions were considered, with 15 answered using the GRADE framework and 3 with a narrative summary. There is moderate certainty in the evidence that topical glucocorticosteroids effectively reduce esophageal eosinophil counts to <15 per high-power field over a short-term treatment period of 4-12 weeks, but very low certainty about the effects of using topical glucocorticosteroids as maintenance therapy. Multiple dietary strategies may be effective in reducing esophageal eosinophil counts to <15 per high-power field over a short-term treatment period, with moderate certainty for elemental diets, low certainty for empiric 2-, 4-, and 6-food elimination diets, and very low certainty that allergy-based testing dietary eliminations have a higher failure rate compared to empiric diet elimination. There is very low certainty for the effect of proton pump inhibitors in patients with esophageal eosinophilia. Although esophageal dilation appears to be relatively safe, there is no evidence that it reduces esophageal eosinophil counts. There is very low certainty in the effects of multiple other medical treatments for EoE: anti-interleukin-5 therapy, anti-interleukin-13 therapy, anti-IgE therapy, montelukast, cromolyn, and anti-TNF therapy., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Patients and Methods: Probands with newly diagnosed cancer-associated pathogenic variants were offered facilitated cascade testing whereby the genetics team identified and contacted ARRs by telephone to disclose the familial pathogenic variant and offer telephone counseling and mailed saliva testing. Results and guideline-based recommendations were reviewed by telephone and shared with the primary care physician., Results: Thirty probands were enrolled, and 114 ARRs were identified. Twelve ARRs were excluded (lived outside of the United States, n = 5; proband did not approve of contact, n = 7). Among 102 ARRs telephoned, contact was established with 95 (93%). Among 114 identified ARRs, 66 (58%) completed genetic testing. Among those completing testing, 27 (41%) carried the familial pathogenic variant. Surveys of ARRs at the time of genetic testing and 6 months later demonstrated low levels of anxiety, depression, distress, and uncertainty and high levels of satisfaction with testing. At 6 months, 7 ARRs with pathogenic variants had undergone cancer surveillance interventions and 4 had undergone cancer risk-reducing surgery., Conclusion: Facilitated cascade testing with telephone genetic counseling and mailed saliva kits resulted in high testing uptake among ARRs. Positive genetic testing resulted in utilization of genetically targeted primary disease prevention at short-term follow-up. Facilitated cascade testing is a straightforward, low-cost, easily implemented strategy with significant potential to promote early detection for affected ARRs and reduce cancer mortality and should be evaluated in larger scale clinical trials.

Purpose: Despite advances in DNA sequencing technology and expanded medical guidelines, the vast majority of individuals carrying pathogenic variants of common cancer susceptibility genes have yet to be identified. An alternative to population-wide genetic screening of healthy individuals would exploit the trend for genetic testing at the time of cancer diagnosis to guide therapy and prevention, combined with augmented familial diffusion or "cascade" of genomic risk information., Methods: Using a multiple linear regression model, we derived the time interval to detect an estimated 3.9 million individuals in the United States with a pathogenic variant in 1 of 18 cancer susceptibility genes. We analyzed the impact of the proportion of incident patients sequenced, varying observed frequencies of pathogenic germline variants in patients with cancer, differential rates of diffusion of genetic information in families, and family size., Results: The time to detect inherited cancer predisposing variants in the population is affected by the extent of cascade to first-, second-, and third-degree relatives (FDR, SDR, TDR, respectively), family size, prevalence of mutations in patients with cancer, and the proportion of patients with cancer sequenced. In a representative scenario, assuming a 7% prevalence of pathogenic variants across cancer types, an average family size of 3 per generation, and 15% of incident patients with cancer in the United States undergoing germline testing, the time to detect all 3.9 million individuals with pathogenic variants in 18 cancer susceptibility genes would be 46.2, 22.3, 13.6, and 9.9 years if 10%, 25%, 50%, and 70%, respectively, of all FDR, SDR, and TDR were tested for familial mutations., Conclusion: Peridiagnostic and cascade cancer genetic testing offers an alternative strategy to achieve population-wide identification of cancer susceptibility mutations.

Purpose of Review: Next-generation sequencing is becoming more accessible. This review focuses on the clinical application of somatic and germline sequencing to genitourinary oncology., Recent Findings: Germline variants have been increasingly recognized as contributing to the development of genitourinary malignancies, particularly in patients with advanced disease. A variety of commercial and institutional technologies are in use to detect variants, with newer tools focused on integrating these results into the clinical workflow., Summary: DNA sequencing is becoming a valuable tool in caring for patients with genitourinary malignancies. Performing both somatic and germline sequencing will likely become standard practice. Interpretation and clinical application of these results can be challenging and often requires multidisciplinary expertise.

Cannabis is commonly used in cyclic vomiting syndrome (CVS) due to its antiemetic and anxiolytic properties. Paradoxically, chronic cannabis use in the context of cyclic vomiting has led to the recognition of a putative new disorder called cannabinoid hyperemesis syndrome (CHS). Since its first description in 2004, numerous case series and case reports have emerged describing this phenomenon. Although not pathognomonic, a patient behavior called "compulsive hot water bathing" has been associated with CHS. There is considerable controversy about how CHS is defined. Most of the data remain heterogenous with limited follow-up, making it difficult to ascertain whether chronic cannabis use is causal, merely a clinical association with CVS, or unmasks or triggers symptoms in patients inherently predisposed to develop CVS. This article will discuss the role of cannabis in the regulation of nausea and vomiting, specifically focusing on both CVS and CHS, in order to address controversies in this context. To this objective, we have collated and analyzed published case series and case reports on CHS in order to determine the number of reported cases that meet current Rome IV criteria for CHS. We have also identified limitations in the existing diagnostic framework and propose revised criteria to diagnose CHS. Future research in this area should improve our understanding of the role of cannabis use in cyclic vomiting and help us better understand and manage this disorder., (© 2019 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.)

Background: This evidence review was conducted to inform the accompanying clinical practice guideline on the management of cyclic vomiting syndrome (CVS) in adults., Methods: We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and focused on interventions aimed at prophylactic management and abortive treatment of adults with CVS. Specifically, this evidence review addresses the following clinical questions: (a) Should the following pharmacologic agents be used for prophylaxis of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, or mitochondrial supplements? (b) Should the following pharmacologic agents be used for abortive treatment: triptans or aprepitant?, Results: We found very low-quality evidence to support the use of the following agents for prophylactic and abortive treatment of CVS: amitriptyline, topiramate, aprepitant, zonisamide/levetiracetam, and mitochondrial supplements. We have moderate certainty of evidence for the use of triptans as abortive therapy. We found limited evidence to support the use of ondansetron and the treatment of co-morbid conditions and complementary therapies., Conclusions: This evidence review helps inform the accompanying guideline for the management of adults with CVS which is aimed at helping clinicians, patients, and policymakers, and should improve patient outcomes., (© 2019 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.)

Cyclic vomiting syndrome (CVS) is characterized by severe episodic emesis in adults and children. Cannabinoid hyperemesis syndrome is an increasingly recognized CVS-like illness that has been associated with chronic cannabis use. There are significant gaps in our understanding of the pathophysiology, clinical features, comorbidities, and effective management options of CVS. Recommendations for treating CVS are based on limited clinical data, as no placebo-controlled, randomized trials have yet been conducted. Diseases associated with CVS, including migraine, mitochondrial disorders, autonomic dysfunction, and psychiatric comorbidities, provide clues about pathophysiologic mechanisms and suggest potential therapies. We review our current understanding of CVS and propose future research directions with the aim of developing effective therapy. Establishing a multicenter, standardized registry of CVS patients could drive research on multiple fronts including developing CVS-specific outcome measures to broaden our understanding of clinical profiles, to serve as treatment end points in clinical trials, and to provide a platform for patient recruitment for randomized clinical trials. Such a robust database would also facilitate conduct of research that aims to determine the underlying pathophysiological mechanisms and genetic basis for CVS, as well as identifying potential biomarkers for the disorder. Soliciting government and industry support is crucial to establishing the necessary infrastructure and achieving these goals. Patient advocacy groups such as the Cyclic Vomiting Syndrome Association (CVSA), which partner with clinicians and researchers to disseminate new information, to promote ongoing interactions between patients, their families, clinicians, investigators, to support ongoing CVS research and education, must be an integral part of this endeavor., (© 2019 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.)

The increasing recognition of cyclic vomiting syndrome (CVS) in adults prompted the development of these evidence-based guidelines on the management of CVS in adults, which was sponsored by the American Neurogastroenterology and Motility Society (ANMS) and the Cyclic Vomiting Syndrome Association (CVSA). GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework was used and a professional librarian performed the literature search. The expert committee included the President of the CVSA who brought a patient perspective into the deliberations. The committee makes recommendations for the prophylaxis of CVS, treatment of acute attacks, diagnosis, and overall management of CVS. The committee strongly  recommends that adults with moderate-to-severe CVS receive a tricyclic antidepressant (TCA), such as amitriptyline, as a first-line prophylactic medication and receive topiramate or aprepitant as alternate prophylactic medications. Zonisamide or levetiracetam and mitochondrial supplements (Coenzyme Q10, L-carnitine, and riboflavin) are conditionally recommended as alternate prophylactic medications, either alone or concurrently with other prophylactic medications. For acute attacks, the committee conditionally recommends using serotonin antagonists, such as ondansetron, and/or triptans, such as sumatriptan or aprepitant to abort symptoms. Emergency department treatment is best achieved with the use of an individualized treatment protocol and shared with the care team (example provided). The committee recommended screening and treatment for comorbid conditions such as anxiety, depression, migraine headache, autonomic dysfunction, sleep disorders, and substance use with referral to appropriate allied health services as indicated. Techniques like meditation, relaxation, and biofeedback may be offered as complementary therapy to improve overall well-being and patient care outcomes., (© 2019 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.)

Background: Systematic screening of all colorectal tumors for Lynch Syndrome (LS) has been recommended since 2009. Currently, implementation of LS screening in healthcare systems remains variable, likely because LS screening involves the complex coordination of multiple departments and individuals across the healthcare system. Our specific aims are to (1) describe variation in LS screening implementation across multiple healthcare systems; (2) identify conditions associated with both practice variation and optimal implementation; (3) determine the relative effectiveness, efficiency, and costs of different LS screening protocols by healthcare system; and (4) develop and test in a real-world setting an organizational toolkit for LS screening program implementation and improvement. This toolkit will promote effective implementation of LS screening in various complex health systems., Methods: This study includes eight healthcare systems with 22 clinical sites at varied stages of implementing LS screening programs. Guided by the Consolidated Framework for Implementation Research (CFIR), we will conduct in-depth semi-structured interviews with patients and organizational stakeholders and perform economic evaluation of site-specific implementation costs. These processes will result in a comprehensive cross-case analysis of different organizational contexts. We will utilize qualitative data analysis and configurational comparative methodology to identify facilitators and barriers at the organizational level that are minimally sufficient and necessary for optimal LS screening implementation., Discussion: The overarching goal of this project is to combine our data with theories and tools from implementation science to create an organizational toolkit to facilitate implementation of LS screening in various real-world settings. Our organizational toolkit will account for issues of complex coordination of care involving multiple stakeholders to enhance implementation, sustainability, and ongoing improvement of evidence-based LS screening programs. Successful implementation of such programs will ultimately reduce suffering of patients and their family members from preventable cancers, decrease waste in healthcare system costs, and inform strategies to facilitate the promise of precision medicine., Trial Registration: N/A.

Objectives: This article introduces the rationale and methods for explicitly considering health equity in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology for development of clinical, public health, and health system guidelines., Study Design and Setting: We searched for guideline methodology articles, conceptual articles about health equity, and examples of guidelines that considered health equity explicitly. We held three meetings with GRADE Working Group members and invited comments from the GRADE Working Group listserve., Results: We developed three articles on incorporating equity considerations into the overall approach to guideline development, rating certainty, and assembling the evidence base and evidence to decision and/or recommendation., Conclusion: Clinical and public health guidelines have a role to play in promoting health equity by explicitly considering equity in the process of guideline development., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Screening of persons with newly diagnosed colorectal cancer for Lynch syndrome can yield substantial benefits at acceptable costs, presuming sufficient uptake of genetic testing by first-degree relatives of Lynch syndrome probands. We performed a systematic review of the literature to determine the frequency of and factors associated with genetic testing of first-degree relatives of Lynch syndrome probands., Methods: We searched 4 databases (CINAHL, PsycInfo, PUBMED, and SCOPUS) for articles published through May 2011 reporting uptake of genetic testing by relatives of Lynch syndrome probands. Two investigators independently screened articles to determine whether they met inclusion criteria; data were collected on study population, genetic counseling, and genetic testing. A narrative, qualitative systematic review was performed., Results: We identified 1258 potentially relevant articles; 533 underwent full-text review, and 8 were included in the final analysis. Of first-degree relatives of Lynch syndrome probands, 52% or less received genetic testing. For each proband, 3.6 or fewer relatives underwent genetic testing. Demographic factors (age <50 years, female sex, parenthood, level of education, employment, participation in medical studies), psychological factors (lack of depressive symptoms), and possibly family history (greater number of relatives with cancer) were associated with uptake of genetic testing., Conclusions: Genetic testing appears to be underutilized by first-degree relatives of patients with Lynch syndrome. The clinical benefit and economic feasibility of screening persons with colorectal cancer for Lynch syndrome depend on optimizing family-wide uptake of genetic testing. Future research and clinical efforts should focus on ways to overcome barriers to genetic testing., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: Fecal occult blood testing (FOBT) and sigmoidoscopy are proven to decrease colorectal cancer (CRC) incidence and mortality. Sigmoidoscopy's benefit is limited to the distal colon. Observational data are conflicting regarding the degree to which colonoscopy affords protection against proximal CRC. Our aim was to explore the comparative effectiveness and cost-effectiveness of colonoscopy vs. sigmoidoscopy and alternative CRC screening strategies in light of the latest published data., Methods: We performed a contemporary cost-utility analysis using a Markov model validated against data from randomized controlled trials of FOBT and sigmoidoscopy. Persons at average CRC risk within the general US population were modeled. Screening strategies included those recommended by the United States (US) Preventive Services Task Force, including colonoscopy every 10 years (COLO), flexible sigmoidoscopy every 5 years (FS), annual fecal occult blood testing, annual fecal immunochemical testing (FIT), and the combination FS/FIT. The main outcome measures were quality-adjusted life-years (QALYs) and costs., Results: In the base case, FIT dominated other strategies. The advantage of FIT over FS and COLO was contingent on rates of uptake and adherence that are well above current US rates. Compared with FIT, FS and COLO both cost <$50,000/QALY gained when FIT per-cycle adherence was <50%. COLO cost $56,800/QALY gained vs. FS in the base case. COLO cost <$100,000/QALY gained vs. FS when COLO yielded a relative risk of proximal CRC of <0.5 vs. no screening. In probabilistic analyses, COLO was cost-effective vs. FS at a willingness-to-pay threshold of $100,000/QALY gained in 84% of iterations., Conclusions: Screening colonoscopy may be cost-effective compared with FIT and sigmoidoscopy, depending on the relative rates of screening uptake and adherence and the protective benefit of colonoscopy in the proximal colon. Colonoscopy's cost-effectiveness compared with sigmoidoscopy is contingent on the ability to deliver ~50% protection against CRC in the proximal colon.