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1
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Mittendorf KF, Bland HT, Andujar J, Celaya-Cobbs N, Edwards C, Gerhart M, Hooker G, Hubert M, Jones SH, Marshall DR, Myers RA, Pratap S, Rosenbloom ST, Sadeghpour A, Wu RR, Orlando LA, Wiesner GL. Family history and cancer risk study (FOREST): A clinical trial assessing electronic patient-directed family history input for identifying patients at risk of hereditary cancer. Contemp Clin Trials 2025; 148:107714. [PMID: 39395532 DOI: 10.1016/j.cct.2024.107714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 09/16/2024] [Accepted: 10/09/2024] [Indexed: 10/14/2024]
Abstract
BACKGROUND Hereditary cancer syndromes cause a high lifetime risk of early, aggressive cancers. Early recognition of individuals at risk can allow risk-reducing interventions that improve morbidity and mortality. Family health history applications that gather data directly from patients could alleviate barriers to risk assessment in the clinical appointment, such as lack of provider knowledge of genetics guidelines and limited time in the clinical appointment. New approaches allow linking these applications to patient health portals and their electronic health records (EHRs), offering an end-to-end solution for patient-input family history information and risk result clinical decision support for their provider. METHODS We describe the design of the first large-scale evaluation of an EHR-integrable, patient-facing family history software platform based on the Substitutable Medical Applications and Reusable Technologies on Fast Healthcare Interoperability Resources (SMART on FHIR) standard. In our study, we leverage an established implementation science framework to evaluate the success of our model to facilitate scalable, systematic risk assessment for hereditary cancers in diverse clinical environments in a large pragmatic study at two sites. We will also evaluate the success of the approach to improve the efficiency of downstream genetic counseling resulting from pre-counseling pedigree generation. CONCLUSIONS Our research study will provide evidence regarding a new care delivery model that is scalable and sustainable for a variety of medical centers and clinics. TRIAL REGISTRATION This study was registered on ClinicalTrials.gov under NCT05079334 on 15 October 2021.
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Affiliation(s)
- Kathleen F Mittendorf
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
| | - Harris T Bland
- Department of Biomedical Informatics, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Justin Andujar
- Division of Genetic Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Natasha Celaya-Cobbs
- Division of Genetic Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Clasherrol Edwards
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA
| | - Meredith Gerhart
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Gillian Hooker
- Division of Genetic Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA; Concert Genetics, Nashville, TN, USA
| | - Mryia Hubert
- Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sarah H Jones
- Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Dana R Marshall
- Department of Pathology, Anatomy and Cell Biology, Meharry Medical College, Nashville, TN, USA
| | - Rachel A Myers
- Department of Medicine Clinical Research Unit, Duke University School of Medicine, Durham, NC, 27705, USA
| | - Siddharth Pratap
- Department of Microbiology, Immunology and Physiology, Meharry Medical College, Nashville, TN 37208, USA
| | - S Trent Rosenbloom
- Department of Biomedical Informatics, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Azita Sadeghpour
- Duke Precision Medicine Program, Department of Medicine, Duke University, Durham, NC, USA
| | - R Ryanne Wu
- Duke Precision Medicine Program, Department of Medicine, Duke University, Durham, NC, USA; 23andMe, Sunnyvale, CA, USA
| | - Lori A Orlando
- Duke Precision Medicine Program, Department of Medicine, Duke University, Durham, NC, USA
| | - Georgia L Wiesner
- Division of Genetic Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
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2
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Mooney R, Wu YP, Kehoe K, Volkmar M, Kohlmann W, Koptiuch C, Kaphingst KA. Experiences of patients and family members with follow-up care, information needs and provider support after identification of Lynch Syndrome. Hered Cancer Clin Pract 2023; 21:28. [PMID: 38115072 PMCID: PMC10731879 DOI: 10.1186/s13053-023-00273-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 12/05/2023] [Indexed: 12/21/2023] Open
Abstract
BACKGROUND Lynch Syndrome is among the most common hereditary cancer syndromes and requires ongoing cancer surveillance, repeated screenings and potential risk-reducing surgeries. Despite the importance of continued surveillance, there is limited understanding of patient experiences after initial testing and counseling, the barriers or facilitators they experience adhering to recommendations, and how they want to receive information over time. METHODS A cross-sectional, observational study was conducted among 127 probands and family members who had received genetic testing for Lynch Syndrome. We conducted semi-structured interviews to determine proband and family member experiences after receiving genetic testing results including their surveillance and screening practices, information needs, and interactions with health care providers. Both closed-ended and open-ended data were collected and analyzed. RESULTS Both probands (96.9%) and family members (76.8%) received recommendations for follow-up screening and all probands (100%) and most family members (98.2%) who tested positive had completed at least one screening. Facilitators to screening included receiving screening procedure reminders and the ease of making screening and surveillance appointments. Insurance coverage to pay for screenings was a frequent concern especially for those under 50 years of age. Participants commented that their primary care providers were often not knowledgeable about Lynch Syndrome and surveillance recommendations; this presented a hardship in navigating ongoing surveillance and updated information. Participants preferred information from a knowledgeable health care provider or a trusted internet source over social media or support groups. CONCLUSIONS Probands and family members receiving genetic testing for Lynch Syndrome generally adhered to initial screening and surveillance recommendations. However, factors such as insurance coverage and difficulty finding a knowledgeable healthcare provider presented barriers to receiving recommended follow-up care. There is an opportunity to improve care through better transitions in care, procedures to keep primary care providers informed of surveillance guidelines, and practices so that patients receive reminders and facilitated appointment setting for ongoing screening and surveillance at the time they are due.
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Affiliation(s)
- Ryan Mooney
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
| | - Yelena P Wu
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
- Department of Dermatology, University of Utah, Salt Lake City, UT, USA
| | - Kelsey Kehoe
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
- Department of Psychology, University of Massachusetts Boston, Boston, MA, USA
| | - Molly Volkmar
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Wendy Kohlmann
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Cathryn Koptiuch
- VA Medical Center, National TeleOncology Service, Durham, NC, USA
| | - Kimberly A Kaphingst
- Department of Communication, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
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3
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Macrae F. Balancing the burden and benefits of colonoscopy in Lynch Syndrome. Fam Cancer 2023; 22:399-401. [PMID: 37713026 DOI: 10.1007/s10689-023-00347-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2023] [Indexed: 09/16/2023]
Affiliation(s)
- Finlay Macrae
- Department of Colorectal Medicine and Genetics, The Royal Melbourne Hospital, and Dept of Medicine, University of Melbourne, Melbourne, Australia, PO Box 2010 Royal Melbourne Hospital, 3050, Melbourne, Victoria, Australia.
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4
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Lau-Min KS, Bleznuck J, Wollack C, McKenna DB, Long JM, Hubert AP, Johnson M, Rochester SE, Constantino G, Dudzik C, Doucette A, Wangensteen K, Domchek SM, Landgraf J, Chen J, Nathanson KL, Katona BW. Development of an Electronic Health Record-Based Clinical Decision Support Tool for Patients With Lynch Syndrome. JCO Clin Cancer Inform 2023; 7:e2300024. [PMID: 37639653 PMCID: PMC10857752 DOI: 10.1200/cci.23.00024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/22/2023] [Accepted: 07/12/2023] [Indexed: 08/31/2023] Open
Abstract
PURPOSE To develop an electronic health record (EHR)-based clinical decision support (CDS) tool to promote guideline-recommended cancer risk management among patients with Lynch syndrome (LS), an inherited cancer syndrome that confers an increased risk of colorectal and other cancer types. MATERIALS AND METHODS We conducted a cross-sectional study to determine the baseline prevalence and predictors of guideline-recommended colonic surveillance and annual genetics program visits among patients with LS. Multivariable log-binomial regressions estimated prevalence ratios (PRs) of cancer risk management adherence by baseline sociodemographic and clinical characteristics. These analyses provided rationale for the development of an EHR-based CDS tool to support patients and clinicians with LS-related endoscopic surveillance and annual genetics program visits. The CDS leverages an EHR platform linking discrete genetic data to LS Genomic Indicators, in turn driving downstream clinician- and patient-facing CDS. RESULTS Among 323 patients with LS, cross-sectional adherence to colonic surveillance and annual genetics program visits was 69.3% and 55.4%, respectively. Patients with recent electronic patient portal use were more likely to be adherent to colonic surveillance (PR, 1.67; 95% CI, 1.11 to 2.52). Patients more recently diagnosed with LS were more likely to be adherent to annual genetics program visits (PR, 0.58; 95% CI, 0.44 to 0.76 for 2-4 years; PR, 0.62; 95% CI, 0.51 to 0.75 for ≥4 compared with <2 years). Our EHR-based CDS tool is now active for 421 patients with LS throughout our health system. CONCLUSION We have successfully developed an EHR-based CDS tool to promote guideline-recommended cancer risk management among patients with LS.
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Affiliation(s)
- Kelsey S. Lau-Min
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Joseph Bleznuck
- Information Services Applications, Penn Medicine, University of Pennsylvania, Philadelphia, PA
| | - Colin Wollack
- Information Services Applications, Penn Medicine, University of Pennsylvania, Philadelphia, PA
| | - Danielle B. McKenna
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Jessica M. Long
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Anna P. Hubert
- Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Mariah Johnson
- Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Shavon E. Rochester
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Gillain Constantino
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Christina Dudzik
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Abigail Doucette
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Kirk Wangensteen
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN
| | - Susan M. Domchek
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Jeffrey Landgraf
- Information Services Applications, Penn Medicine, University of Pennsylvania, Philadelphia, PA
| | - Jessica Chen
- Information Services Applications, Penn Medicine, University of Pennsylvania, Philadelphia, PA
| | - Katherine L. Nathanson
- Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Bryson W. Katona
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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D’Angelo V, Rega D, Marone P, Di Girolamo E, Civiletti C, Tatangelo F, Duraturo F, De Rosa M, de Bellis M, Delrio P. The Role of Colonoscopy in the Management of Individuals with Lynch Syndrome: A Narrative Review. Cancers (Basel) 2023; 15:3780. [PMID: 37568596 PMCID: PMC10417258 DOI: 10.3390/cancers15153780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 03/07/2023] [Accepted: 03/24/2023] [Indexed: 08/13/2023] Open
Abstract
The history of Lynch syndrome changed definitively in 2000, when a study published in Gastroenterology demonstrated a significant reduction in mortality among individuals with Lynch syndrome who undergo regular endoscopic surveillance. As a consequence of this clinical evidence, all scientific societies developed guidelines, which highlighted the role of colonoscopy in the management of Lynch syndrome, especially for individuals at high risk of colorectal cancer. Over the years, these guidelines were modified and updated. Specialized networks were developed in order to standardize endoscopic surveillance programs and evaluate all the clinical data retrieved by the results of colonoscopies performed for both the screening and the surveillance of individuals with Lynch syndrome. Recent data show that the impact of colonoscopy (with polypectomy) on the prevention of colorectal cancer in individuals with Lynch syndrome is less significant than previously thought. This narrative review summarizes the current discussion, the hypotheses elaborated and the algorithms depicted for the management of individuals with Lynch Syndrome on the basis of the recent data published in the literature.
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Affiliation(s)
- Valentina D’Angelo
- Division of Gastroenterology and Gastrointestinal Endoscopy, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy; (V.D.)
| | - Daniela Rega
- Colorectal Surgical Oncology, Department of Abdominal Oncology, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
| | - Pietro Marone
- Division of Gastroenterology and Gastrointestinal Endoscopy, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy; (V.D.)
| | - Elena Di Girolamo
- Division of Gastroenterology and Gastrointestinal Endoscopy, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy; (V.D.)
| | - Corrado Civiletti
- Division of Gastroenterology and Gastrointestinal Endoscopy, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy; (V.D.)
| | - Fabiana Tatangelo
- Division of AnatomicPathology and Cytopathology, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
| | - Francesca Duraturo
- Department of Molecular Medicine and Biomedical Technology, School of Medicine, University Federico II, 80138 Naples, Italy
| | - Marina De Rosa
- Department of Molecular Medicine and Biomedical Technology, School of Medicine, University Federico II, 80138 Naples, Italy
| | - Mario de Bellis
- Division of Gastroenterology and Gastrointestinal Endoscopy, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy; (V.D.)
| | - Paolo Delrio
- Colorectal Surgical Oncology, Department of Abdominal Oncology, Istituto Nazionale Tumori-IRCCS “Fondazione G. Pascale”, 80131 Naples, Italy
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6
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MyLynch: A Patient-Facing Clinical Decision Support Tool for Genetically-Guided Personalized Medicine in Lynch Syndrome. Cancers (Basel) 2023; 15:cancers15020391. [PMID: 36672340 PMCID: PMC9856567 DOI: 10.3390/cancers15020391] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 12/23/2022] [Accepted: 12/27/2022] [Indexed: 01/11/2023] Open
Abstract
Lynch syndrome (LS) is a hereditary cancer susceptibility condition associated with varying cancer risks depending on which of the five causative genes harbors a pathogenic variant; however, lifestyle and medical interventions provide options to lower those risks. We developed MyLynch, a patient-facing clinical decision support (CDS) web application that applies genetically-guided personalized medicine (GPM) for individuals with LS. The tool was developed in R Shiny through a patient-focused iterative design process. The knowledge base used to estimate patient-specific risk leveraged a rigorously curated literature review. MyLynch informs LS patients of their personal cancer risks, educates patients on relevant interventions, and provides patients with adjusted risk estimates, depending on the interventions they choose to pursue. MyLynch can improve risk communication between patients and providers while also encouraging communication among relatives with the goal of increasing cascade testing. As genetic panel testing becomes more widely available, GPM will play an increasingly important role in patient care, and CDS tools offer patients and providers tailored information to inform decision-making. MyLynch provides personalized cancer risk estimates and interventions to lower these risks for patients with LS.
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7
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Knerr S, Guo B, Mittendorf KF, Feigelson HS, Gilmore MJ, Jarvik GP, Kauffman TL, Keast E, Lynch FL, Muessig KR, Okuyama S, Veenstra DL, Zepp JM, Goddard KA, Devine B. Risk-reducing surgery in unaffected individuals receiving cancer genetic testing in an integrated health care system. Cancer 2022; 128:3090-3098. [PMID: 35679147 PMCID: PMC9308746 DOI: 10.1002/cncr.34349] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 05/03/2022] [Accepted: 05/19/2022] [Indexed: 12/17/2022]
Abstract
BACKGROUND Germline genetic testing enables primary cancer prevention, including through prophylactic surgery. We examined risk-reducing surgeries in unaffected individuals tested for hereditary cancer susceptibly between 2010 and 2018 in the Kaiser Permanente Northwest health system. METHODS We used an internal genetic testing database to create a cohort of individuals who received tests including one or more high-penetrance hereditary cancer susceptibility gene. We then identified, after testing, bilateral mastectomy, bilateral salpingo-oophorectomy (BSO), and total hysterectomy procedures in electronic health record and claims data through 2019. We describe surgery utilization by genetic test results and National Comprehensive Cancer Network (NCCN) guidelines. RESULTS The cohort included 1020 individuals, 16% with pathogenic/likely pathogenic (P/LP) variants in one or more of the following genes: BRCA1, BRCA2, CHEK2, APC, MUTYH, ATM, MSH2, PALB2, BRIP1, MLH1, MSH6, EPCAM, FLCN, RAD51C, RAD51D, or TP53. Among individuals with P/LP variants making them candidates for mastectomy, BSO, or hysterectomy per NCCN guidelines, 34% (33/97), 24% (23/94), and 8% (1/12), respectively, underwent surgery during follow-up. Fifty-three percent (18/37) of hysterectomies were among APC, BRCA1, and BRCA2 P/LP variant heterozygotes, typically concurrent with BSO. Three individuals with variants of uncertain significance (only) and 22 with negative results had prophylactic surgery after genetic testing. CONCLUSIONS Uptake of risk-reducing surgery following usual care genetic testing appears to be lower than in studies that actively recruit high-risk patients and provide testing and follow-up care in specialized settings. Factors in addition to genetic test results and NCCN guidelines motivate prophylactic surgery use and deserve further study.
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Affiliation(s)
- Sarah Knerr
- School of Public Health, University of Washington, Seattle, WA
| | - Boya Guo
- School of Public Health, University of Washington, Seattle, WA
| | - Kathleen F. Mittendorf
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | | | - Marian J. Gilmore
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Gail P. Jarvik
- School of Medicine, University of Washington, Seattle, WA
| | - Tia L. Kauffman
- Center for Health Research, Kaiser Permanente Northwest, Portland OR
| | - Erin Keast
- Center for Health Research, Kaiser Permanente Northwest, Portland OR
| | - Frances L. Lynch
- Center for Health Research, Kaiser Permanente Northwest, Portland OR
| | - Kristin R. Muessig
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Sonia Okuyama
- Division of Oncology, Denver Health and Hospital Authority, Denver, CO
| | - David L. Veenstra
- The Comparative Health Outcomes, Policy and Economics (CHOICE) Institute, School of Pharmacy, University of Washington, Seattle, WA
| | - Jamilyn M. Zepp
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Katrina A.B. Goddard
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Beth Devine
- The Comparative Health Outcomes, Policy and Economics (CHOICE) Institute, School of Pharmacy, University of Washington, Seattle, WA
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8
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Drogan C, Kupfer SS. Colorectal Cancer Screening Recommendations and Outcomes in Lynch Syndrome. Gastrointest Endosc Clin N Am 2022; 32:59-74. [PMID: 34798987 DOI: 10.1016/j.giec.2021.08.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Screening for colorectal cancer (CRC) in Lynch syndrome enables early detection and likely cancer prevention. CRC screening guidelines have evolved from universal to gene-specific recommendations based on lifetime neoplasia risks. Regular screening for Lynch syndrome reduces CRC-related mortality; however, high CRC incidence during regular colonoscopy screening suggests the possibility of nonpolypoid carcinogenesis. Colonoscopy is the primary modality for screening for Lynch syndrome with mixed and emerging data on quality metrics, chromoendoscopy, artificial intelligence, and nonendoscopic modalities. Screening adherence varies across studies. In this review, we present the current state of CRC screening recommendations, outcomes, and modalities in Lynch syndrome.
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Affiliation(s)
- Christine Drogan
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Sonia S Kupfer
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, Chicago, IL, USA.
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9
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Mittendorf KF, Knerr S, Kauffman TL, Lindberg NM, Anderson KP, Feigelson HS, Gilmore MJ, Hunter JE, Joseph G, Kraft SA, Zepp JM, Syngal S, Wilfond BS, Goddard KAB. Systemic Barriers to Risk-Reducing Interventions for Hereditary Cancer Syndromes: Implications for Health Care Inequities. JCO Precis Oncol 2021; 5:PO.21.00233. [PMID: 34778694 PMCID: PMC8585306 DOI: 10.1200/po.21.00233] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 09/21/2021] [Accepted: 09/28/2021] [Indexed: 11/20/2022] Open
Affiliation(s)
- Kathleen F. Mittendorf
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Sarah Knerr
- School of Public Health, University of Washington, Seattle, WA
| | - Tia L. Kauffman
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Nangel M. Lindberg
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | | | | | - Marian J. Gilmore
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Jessica Ezzell Hunter
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Galen Joseph
- Department of Humanities and Social Sciences, University of California, San Francisco, School of Medicine, San Francisco, CA
| | - Stephanie A. Kraft
- Treuman Katz Center for Pediatric Bioethics, Seattle Children's Hospital and Research Institute, Seattle, WA
- Department of Pediatrics, University of Washington School of Medicine, Seattle, WA
| | - Jamilyn M. Zepp
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
| | - Sapna Syngal
- Dana Farber Cancer Institute, Boston, MA
- Harvard Medical School, Boston, MA
- Brigham and Women's Hospital, Boston, MA
| | - Benjamin S. Wilfond
- Treuman Katz Center for Pediatric Bioethics, Seattle Children's Hospital and Research Institute, Seattle, WA
- Department of Pediatrics, University of Washington School of Medicine, Seattle, WA
| | - Katrina A. B. Goddard
- Department of Translational and Applied Genomics, Center for Health Research, Kaiser Permanente Northwest, Portland, OR
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10
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Vangala DB, Ladigan-Badura S, Engel C, Hüneburg R, Perne C, Bucksch K, Nattermann J, Steinke-Lange V, Rahner N, Weitz J, Kloor M, Tomann J, Canbay A, Nguyen HP, Strassburg C, Möslein G, Morak M, Holinski-Feder E, Büttner R, Aretz S, Löffler M, Schmiegel W, Pox C, Schulmann K. Early detection of duodenal cancer by upper gastrointestinal-endoscopy in Lynch syndrome. Int J Cancer 2021; 149:2052-2062. [PMID: 34331771 DOI: 10.1002/ijc.33753] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 06/30/2021] [Accepted: 07/05/2021] [Indexed: 11/06/2022]
Abstract
Small bowel cancer (SBC) is the malignancy with the highest standardized incidence ratio in Lynch syndrome (LS) patients. Of all SBCs, about 50% are duodenal cancers (DCs), therefore being accessible by esophago-gastro-duodenoscopy (EGD) for surveillance. We asked whether early detection of DC is possible for LS patients undergoing surveillance by EGD and if surveillance should be limited to specific subgroups. Data for LS patients with DC were retrieved from the registry of the German Consortium for Familial Intestinal Cancer. Patients undergoing active surveillance by EGDs (surveillance group) were compared to those who did not (nonsurveillance group) regarding tumor stage at diagnosis. Union for International Cancer Control stages I-IIA were defined as early stage disease and IIB-IV as advanced stage disease. Statistical analysis was performed using Fisher's exact test. Among 2015 patients with pathogenic variants in any mismatch-repair-gene, 47 patients with 49 DCs were identified. In 10% of cases, patients were under 35 years at diagnosis; family and personal tumor history did not correlate with DC diagnosis. Pathogenic germline variants in MSH6, PMS2 or EPCAM were present in 10% of patients. Statistical analysis could be performed on 13 DC patients in the surveillance group and 14 in the nonsurveillance group. Early detection was possible for 71% of patients in the surveillance group and 29% of patients in the nonsurveillance group (P = .021). Early detection of DC by EGD in LS patients is feasible regardless of family history, mutational status and should start no later than 25 years of age.
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Affiliation(s)
- Deepak B Vangala
- Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.,Molecular GI-Oncology, Ruhr-University Bochum, Bochum, Germany
| | - Swetlana Ladigan-Badura
- Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.,Molecular GI-Oncology, Ruhr-University Bochum, Bochum, Germany
| | - Christoph Engel
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - Robert Hüneburg
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.,National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
| | - Claudia Perne
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.,Institute of Human Genetics, University of Bonn, Bonn, Germany
| | - Karolin Bucksch
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.,National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
| | - Verena Steinke-Lange
- Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.,Medical Genetics Center Munich, Munich, Germany
| | - Nils Rahner
- Institute of Human Genetics, Medical School, Heinrich Heine University, Düsseldorf, Germany
| | - Jürgen Weitz
- Department of Surgery, Technische Universitaet Dresden, Dresden, Germany
| | - Matthias Kloor
- Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.,Cooperation Unit Applied Tumour Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Judith Tomann
- Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Ali Canbay
- Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Huu-Phuc Nguyen
- Department for Human Genetics, Ruhr-University Bochum, Bochum, Germany
| | - Christian Strassburg
- Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.,National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany
| | - Gabriele Möslein
- Surgical Center for Hereditary Tumors, Evangelisches Bethesda Krankenhaus, Duisburg, Germany
| | - Monika Morak
- Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.,Medical Genetics Center Munich, Munich, Germany
| | - Elke Holinski-Feder
- Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.,Medical Genetics Center Munich, Munich, Germany
| | | | - Stefan Aretz
- National Center for Hereditary Tumor Syndromes, University Hospital Bonn, Bonn, Germany.,Institute of Human Genetics, University of Bonn, Bonn, Germany
| | - Markus Löffler
- Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
| | - Wolff Schmiegel
- Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany
| | - Christian Pox
- Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.,Department of Medicine, St. Joseph-Stift Bremen, Bremen, Germany
| | - Karsten Schulmann
- Department of Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.,Praxis für Hämatologie und Onkologie, MVZ Arnsberg, Arnsberg, Germany
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11
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Bernstedt SW, Björk J, Fritzell K, Spigelman AD, Björck E, Backman AS. Room for improvement: One third of Lynch syndrome patients presenting for genetic testing in a highly specialised centre in Stockholm already have cancer. Hered Cancer Clin Pract 2021; 19:18. [PMID: 33579353 PMCID: PMC7881447 DOI: 10.1186/s13053-021-00171-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/19/2021] [Indexed: 11/13/2022] Open
Abstract
Background Lynch syndrome is caused by germline mutations in the mismatch repair genes and is characterised by a familial accumulation of colorectal and other cancers. Earlier identification of Lynch syndrome patients enables surveillance and might reduce the risk of cancer. It is important to explore whether today’s clinical care discovers patients with Lynch syndrome suitable for surveillance in time. This study aimed to describe what led to a diagnosis of Lynch syndrome in the cohort referred to the Hereditary Gastrointestinal Cancer Unit, Karolinska University Hospital, Solna, Sweden for gastrointestinal surveillance. Methods This was a descriptive study. Data from 1975 to 2018 were collected and compiled as a database. Age at diagnosis was calculated from the date when a pathogenic MMR gene mutation was confirmed, from the period June 1994–September 2018. Data were collected from patient protocols prospectively during patient consultations and medical records retrospectively. Criteria for inclusion were registration at the outpatient clinic and a confirmed mismatch repair gene mutation. Results A total of 305 patients were eligible for inclusion. Three major reasons for diagnosis were identified: 1. Predictive testing of a previously known mutation in the family (62%, mean age 37), 2. A family history of Lynch associated tumours (9%, mean age 37), 3. A diagnosis of cancer (29%, mean age 51). The proportion diagnosed due to cancer has not changed over time. Conclusion A high proportion of patients (29%) were identified with Lynch syndrome after they had been diagnosed with an associated cancer, which suggests that there is significant room for improvement in the diagnosis of patients with Lynch syndrome before cancer develops.
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Affiliation(s)
- Sophie Walton Bernstedt
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
| | - Jan Björk
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden.,Patient flow Hereditary Cancer, Cancer Theme, Karolinska University Hospital, Stockholm, Sweden
| | - Kaisa Fritzell
- Patient flow Hereditary Cancer, Cancer Theme, Karolinska University Hospital, Stockholm, Sweden.,Department of Neurobiology, Care Sciences and Society, Division of Nursing, Karolinska Institutet, Stockholm, Sweden
| | - Allan D Spigelman
- St Vincent's Genetics Clinic, The Kinghorn Cancer Centre, Sydney, Australia.,St Vincent's Clinical School, UNSW, Sydney, Australia
| | - Erik Björck
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.,Clinical Genetics, Karolinska University Laboratory, Karolinska University Hospital, Stockholm, Sweden
| | - Ann-Sofie Backman
- Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. .,Division of Gastroenterology, Medical Unit Gastroenterology, Dermatovenereology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden. .,Patient flow Hereditary Cancer, Cancer Theme, Karolinska University Hospital, Stockholm, Sweden.
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12
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Ibarvo Gracia HM, Saldaña Sanchez IG, Natour AK. On Hereditary Colorectal Cancer: What Is the Appropriate Surgical Technique? CURRENT COLORECTAL CANCER REPORTS 2020. [DOI: 10.1007/s11888-020-00457-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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