EC_ItaLynch: Mainstreaming the Diagnosis of Lynch Syndrome

NCT06501417 | Not Yet Recruiting

• 1 other identifier: 6511
• Study Type: observational
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

Lynch syndrome (LS) is the most common cause of hereditary endometrial cancer (EC) and is associated with an increased risk of colorectal (CRC), ovarian, gastric, small bowel and urinary tract cancer. LS is determined by germline pathogenic variants in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) or in EPCAM. Approximately 20-30% of ECs exhibit somatic MMR deficiency (dMMR), and among these patients approximately 10-30% are affected by LS. This estimate suggests that the prevalence of LS among all EC patients is roughly 3-5%. Prior to the introduction of Universal Screening, the diagnostic management of LS was mainly based on Selective Screening, which included clinical criteria based on the evaluation of family and personal history and the clinicopathological features of the tumor (Amsterdam criteria 1990, Bethesda criteria 1997). However, these have been limited in their application to clinical practice due to their complexity and the frequent lack of complete family history data. Therefore, Universal Screening for LS diagnosis by the identification of dMMR in the tumor tissue of all newly diagnosed CRC and EC cases has recently been proposed. Universal Screening for LS in tumor tissue includes an immunohistochemistry based (IHC) test to assess loss of MMR protein expression or a polymerase chain reaction (PCR) test for microsatellite instability. In the traditional diagnostic pathway for LS, genetic counseling and testing are always recommended for EC patients who are found to have loss of expression of any of the proteins encoded by the MSH2, MSH6, or PMS2. In case of MLH1 loss, genetic counseling and genetic testing are recommended for patients without hypermethylation of the MLH1 promoter. Recent findings suggest that incorporating genetic testing in an oncologist-driven diagnostic algorithm (mainstreaming of genetic testing) could enable increased diagnostic rates, offering the benefits of precision medicine and a streamlined pathway of care to patients and their families. The study consists of two parts:

1. 1.In the first part the aim of the current study is to compare the knowledge, experience and understanding of genetic testing among patients pursuing genetic testing using mainstreaming or standard genetic counseling through modified Modified Royal Marsden Patient Satisfaction Questionnaire.
2. 2.If the first aim will be achieved, a second part will be conducted, to evaluate the feasibility of the mainstreaming diagnostic pathway for LS.

Conditions

Lynch Syndrome; Endometrial Cancer

Outcome Measures

Primary Outcomes (2)

• Patients satisfaction

  The primary endpoint of this study is the rate of patients satisfied with the counseling measured by question n.15 of the Modified Royal Marsden Patient Satisfaction Questionnaire

  1 year

• LS diagnosis

  the proportion of LS diagnosis in dMMR EC patients

  3 years

Interventions

mainstreaming OTHER

mainstreaming in EC patients

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

popolazione: sesso, anni, che accesso fanno, che patologia hanno..

You may qualify if:

• Histologically confirmed diagnosis of stage I-IV EC with dMMR
• Only for part I presence of Lynch alert.
• Signed Informed consent to participate in the study.
• d. Patient must be ≥18 years

You may not qualify if:

• Histologically confirmed diagnosis of stage I-IV EC with pMMR.
• Significant psychiatric or clinical impairment compromising consent to the study.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, 00168, Italy

Location

MeSH Terms

Conditions

Colorectal Neoplasms, Hereditary Nonpolyposis; Endometrial Neoplasms

Interventions

Gender Equity

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Neoplastic Syndromes, Hereditary; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Health Inequities; Health Status; Demography; Population Characteristics

Study Officials

• Emanuela Lucci Cordisco

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emanuela Lucci Cordisco, dr

CONTACT

+390630154606; emanuela.luccicordisco@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 15, 2024
• Study Start: August 1, 2024
• Primary Completion: May 31, 2025
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 15, 2024

Record last verified: 2024-04

Locations

IT (1)