A Focused Clinical Review of Lynch Syndrome

Georgiou, Demetra; Monje-Garcia, Laura; Miles, Tracie; Monahan, Kevin; Ryan, Neil

doi:10.2147/cmar.s283668

Cited by 8 publications

(3 citation statements)

References 116 publications

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“…26 27 30 31 Another approach to deliver effective diagnosis is to develop 'mainstreaming' models whereby patients are offered constitutional genetic testing by their cancer treating teams locally, rather than relying on referral of eligible patients to tertiary services such as clinical genetics. 32 This has many possible advantages including shorter timescale to diagnosis, effective communication provided through an existing relationship between patients and their clinical teams, and ensures that eligible patients access testing. 33 34 This model is associated with high levels of acceptability for patients and clinicians, 32 34 35 however, relies on the development of new skills by cancer teams.…”

Section: Tumour Testing and The Diagnosis Of Lsmentioning

confidence: 99%

The English National Lynch Syndrome transformation project: an NHS Genomic Medicine Service Alliance (GMSA) programme

Monahan,

Ryan,

Monje-Garcia

et al. 2023

bmjonc

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ObjectiveIn England, through the Genomic Medicine Service Alliances (GMSAs), a national transformation project aims to embed robust pathways to deliver universal Lynch syndrome (LS) testing for patients with colorectal and endometrial cancers. Prior to commencement of the project, there was evidence of variation and low testing levels in eligible patients which is consistent with other health systems; however, we believe this is amenable to systematic improvement with responsibility for testing delivery by local cancer teams supported by regional infrastructure.Methods and analysisA project team and national oversight group was formed in May 2021 with membership including 21×cancer alliances, 7×GMSAs, charities and other stakeholders who agreed key performance indicators. ‘LS champions’ within each cancer team were identified and surveyed. Workforce training focused on effective identification of eligible patients, overcoming barriers and mainstreamed constitutional genetic testing. Comprehensive pathway data analysis was performed in conjunction with the National Disease Registration Service.ResultsSurvey and baseline testing data illustrated variation, and a disparity between practice and perception, in levels of testing. The main reported barriers related to funding streams and systematic approaches. Multifaceted training programmes were produced to support workforce development. Champions responsible for testing delivery were appointed in >95% of cancer teams. We identified >9000 historically diagnosed LS patients to support ascertainment for a nationally coordinated screening programme.ConclusionThis ongoing transformational project is strongly supported by stakeholders in England. Significant quality improvement has been implemented, facilitating systematic delivery of universal testing for LS nationally and reduction in variation in care.

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Section: Tumour Testing and The Diagnosis Of Lsmentioning

confidence: 99%

The English National Lynch Syndrome transformation project: an NHS Genomic Medicine Service Alliance (GMSA) programme

Monahan,

Ryan,

Monje-Garcia

et al. 2023

bmjonc

Self Cite

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“…These bespoke workshops or tutorials aimed to provide the training needed to support the practical aspects of obtaining informed consent, and genetic counselling and testing for LS. They addressed key challenges for mainstreaming and examined practical examples of how these challenges can be overcome [12]. The training was delivered in 2-h sessions every 2 weeks.…”

Section: Phase 2 Training: Mainstreaming Germline Genetic Testing Bes...mentioning

confidence: 99%

From diagnosis of colorectal cancer to diagnosis of Lynch syndrome: The RM Partners quality improvement project

Monje‐Garcia,

Bill,

Farthing

et al. 2023

Colorectal Disease

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AimThe UK National Institute for Health and Care Excellence guideline DG27 recommends universal testing for Lynch syndrome (LS) in all newly diagnosed colorectal cancer (CRC) patients. However, DG27 guideline implementation varies significantly by geography. This quality improvement project (QIP) was developed to measure variation and deliver an effective diagnostic pathway from diagnosis of CRC to diagnosis of LS within the RM Partners (RMP) West London cancer alliance.MethodRM Partners includes a population of 4 million people and incorporates nine CRC multidisciplinary teams (MDTs), overseen by a Pathway Group, and three regional genetic services, managing approximately 1500 new CRC cases annually. A responsible LS champion was nominated within each MDT. A regional project manager and nurse practitioner were appointed to support the LS champions, to develop online training packages and patient consultation workshops. MDTs were supported to develop an ‘in‐house’ mainstreaming service to offer genetic testing in their routine oncology clinics. Baseline data were collected through completion of the LS pathway audit of the testing pathway in 30 consecutive CRC patients from each CRC MDT, with measurement of each step of the testing pathway. Areas for improvement in each MDT were identified, delivered by the local champion and supported by the project team.ResultsOverall, QIP measurables improved following the intervention. The Wilcoxon signed rank test revealed significant differences with strong effect sizes on the percentile of CRC cases undergoing mismatch repair (MMR) testing in endoscopic biopsies (p = 0.008), further testing with either methylation or BRAF V600E (p = 0/03) and in effective referral for genetic testing (from 10% to 74%; p = 0.02). During the QIP new mainstreaming services were developed, alongside the implementation of systematic and robust testing pathways. These pathways were tailored to the needs of each CRC team to ensure that patients with a diagnosis of CRC had access to testing for LS. Online training packages were produced which remain freely accessible for CRC teams across the UK.ConclusionThe LS project was completed by April 2022. We have implemented a systematic approach with workforce transformation to facilitate identification and ‘mainstreamed’ genetic diagnosis of LS. This work has contributed to the development of a National LS Transformation Project in England which recommends local leadership within cancer teams to ensure delivery of diagnosis of LS and integration of genomics into clinical practice.

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“…Muir Torre syndrome (MTS) is a rare genetic disease, considered a subtype of hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, an autosomal dominant disorder with variable penetrance (1)(2)(3)(4). The concerned genes (MSH2, MSH6, MLH1, MLH3, PMS2) are involved in DNA repair mechanisms (Mismatch Repair/ MMR) and their pathogenic variants lead to microsatellite instability (MSI) (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Muir-Torre Syndrome: a Long Way to Diagnosis

Turcas¹,

Fetică²,

Nagy³

2023

JMRO

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"Muir-Torre syndrome, a subtype of Lynch syndrome, is a rare genetic disorder. We present the case of a female patient with a long family and personal history who was diagnosed with numerous benign and malignant tumours of various histology, including some with sebaceous features, beginning at the age of 41. The majority were cutaneous tumours, treated with complete resection, but they frequently recurred. Visceral cancers included endocervical adenocarcinoma, vulvar squamous-cell carcinoma and urothelial carcinoma, treated surgically, followed by systemic oncological treatments and external beam radiotherapy. Following a 20-year evolution, extensive genetic blood testing revealed a pathogenic variant in the MSH2 gene, c.1861C>T (p.Arg621*), in heterozygous state. In light of this unusual clinical presentation and molecular profile, the patient was finally diagnosed with Muir-Torre syndrome. The prognosis was poor, with an inoperable recurrence of the urothelial carcinoma and extensive lymph node dissemination of a vulvar squamous cell carcinoma."

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A Focused Clinical Review of Lynch Syndrome

Cited by 8 publications

References 116 publications

The English National Lynch Syndrome transformation project: an NHS Genomic Medicine Service Alliance (GMSA) programme

The English National Lynch Syndrome transformation project: an NHS Genomic Medicine Service Alliance (GMSA) programme

From diagnosis of colorectal cancer to diagnosis of Lynch syndrome: The RM Partners quality improvement project

Muir-Torre Syndrome: a Long Way to Diagnosis

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