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Universal Screening for Lynch Syndrome in Women With Endometrial and Non-Serous Ovarian Cancer

Not Applicable
Active, not recruiting
Conditions
Lynch Syndrome
Ovarian Neoplasms
Colorectal Neoplasms
Endometrial Neoplasms
Interventions
Behavioral: Questionnaire, Educational Material
Registration Number
NCT02494791
Lead Sponsor
University Health Network, Toronto
Brief Summary

This study will maximize identification of women with Lynch Syndrome using an enhanced screening strategy to identify those at risk. These women will be referred to genetic counselling for testing and those found to have Lynch Syndrome will be asked to invite first degree relatives to participate and undergo genetic testing for Lynch Syndrome. Screening guidelines and risk reducing surgery options for participants found to have Lynch Syndrome will be reinforced by the study and adherence to these guidelines will be assessed annually for ten years following Lynch Syndrome diagnosis to assess the impact and cost-effectiveness of this enhanced screening approach.

Detailed Description

Lynch Syndrome increases an individual's risk for several cancers, such as colorectal, endometrial (EC) and certain types of ovarian cancer (OC). Lynch Syndrome is caused by inherited changes in mismatch repair (MMR) genes. In this study we will establish the proportion of EC and OC patients with Lynch Syndrome. We will screen all EC and OC patients by performing MMR immunohistochemistry (IHC) on their surgical specimen. These data will then be used along with family history data to determine which women are at high risk of Lynch Syndrome. We will facilitate the referral of all women at risk for Lynch Syndrome to genetic counselling on behalf of their treating physician. First degree relatives of those patients found to have Lynch Syndrome who consent to participate in the study will also be referred to genetics by the study PI. We will encourage all participants found to have Lynch Syndrome to attend regular colonoscopy screening to prevent colorectal cancer, and (for females with Lynch Syndrome) consideration of gynecologic risk reducing surgery to prevent endometrial and ovarian cancers. We will assess adherence to Lynch Syndrome screening guidelines in this population and will determine if our universal screening strategy is feasible and cost-effective for widespread implementation across Canada in an effort to prevent Lynch Syndrome associated cancers in women and their families. In addition to this, consenting patients may provide blood and tumour tissue samples for sequencing studies which will investigate the genetic basis for Lynch Syndrome and shed light on cases of MMR loss in the absence of germline mutation.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
886
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Endometrial and Ovarian Cancer ParticipantsQuestionnaire, Educational MaterialAll study subjects will be offered the same options for screening and follow-up.
Primary Outcome Measures
NameTimeMethod
Adherence to screening guidelines (colonoscopy and gynecologic risk-reducing surgery) in participants found to have Lynch Syndromeshort-term assessment at 1 year after diagnosis, long-term assessment for up to 10 years after diagnosis

Participants found to have Lynch Syndrome will be followed after diagnosis and asked to update the study annually with information about any colorectal cancer screening (colonoscopy) and/or gynecologic risk-reducing surgery they've undergone. This information will be used to assess the success of the enhanced universal screening protocol in helping treat pre-cancerous lesions and therefore prevent a possible cancer as well as aid in detection of early malignancies that otherwise may have gone undetected.

Cost-effectiveness of universal enhanced screening strategy to identify women with Lynch Syndrome and their family members via cascade testingshort-term assessment at 1 year after diagnosis, long-term assessment for up to 10 years after diagnosis

Data about adherence to screening guidelines and the outcome of screening procedures will be used to inform cost-effectiveness models assessing the feasibility of implementing this enhanced universal screening strategy for Lynch Syndrome in institutions across Canada.

Secondary Outcome Measures
NameTimeMethod
Incidence of Lynch Syndrome in an unselected group of women with endometrial and non-serous ovarian cancer3 years

This study will add data about the number of Lynch Syndrome cases among a large cohort of endometrial cancer patients in Canada, adding to previous work. This will be the first prospective study to assess Lynch Syndrome incidence in non-serous, non-mucinous ovarian cancer patients in Canada.

Discovery of novel genetic mutations and molecular events in unexplained MMR loss (Lynch-like Syndrome)3-5 years

This study will investigate tumour samples from women with unexplained MMR loss (MMR IHC deficient without a germline mutation) to probe what other factors may contribute to Lynch-like Syndrome. Currently these patients are believed to have an intermediate risk for Lynch-associated cancers and are counselled accordingly. Further investigation into the biology of this condition may yield more effective strategies for stratifying and managing risk for Lynch-like Syndrome patients.

Trial Locations

Locations (1)

University Health Network - Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

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