Molecular Classification in Relation to Prevention of Endometrial Cancer Recurrence and Lifestyle Factors

Recruiting

• Conditions: Endometrial Cancer; Genetic Predisposition; Risk Behavior

• Registration Number: NCT06680791
• Lead Sponsor: Lukas Vanek

Brief Summary

Endometrial cancer (EC) is one of the most prevalent cancers in women worldwide with a significantly increasing incidence, especially in developed countries. One of the reasons for the increase in the incidence of this disease is the rising incidence of obesity as the biggest risk factor for the development of this disease. Other important risk factors are hypertension, diabetes mellitus and the general ageing of the population. These risk factors are not only associated with a higher risk of developing the disease, but also, for example, with post-operative complications affecting the quality of life of patients after surgery. The molecular classification of endometrial cancer, which has been introduced into clinical practice in recent years, is currently helping physicians to make treatment decisions for individual patients and predict prognosis. In this project, we would like to focus on the relationship of this molecular classification with genomic mutational signatures detected by whole-exome sequencing and their association with lifestyle risk factors for endometrial cancer (obesity - BMI, hypertension, diabetes mellitus), including the extent of staging lymphadenectomy. Identification and detailed analysis of dominant mutational profiles associated with a specific molecular subtype of EC and their influence on the presence of lifestyle risk factors may have a major impact on both disease development and prevention of disease recurrence. The possible relationship of the mutational profile with the extent of staging lymphadenectomy may help in deciding the extent of this surgical procedure, which subsequently affects the quality of life of patients, especially in patients with high BMI. Given the widespread prevalence of lifestyle risk factors in the developed world, a detailed understanding of the relationship between the genetic profile, its alterations and the prevalence of these risk factors, with potentially major implications for treatment success, is crutial.

Detailed Description

The main goal of the project is to define specific mutational signatures of endometrial cancer (EC) patients using whole-exome sequencing technology. The relationship between mutational profiles and molecular classification of endometrial cancer will be analyzed in order to improve the stratification of these patients, especially those classified as having a non-specific molecular profile or p53 mutations. At the same time, the association between the dominant mutational profiles of EC patients with the prevalence of lifestyle risk factors such as obesity/BMI, hypertension and diabetes mellitus will be investigated and their incidence is becoming more prevalent in the modern population. Associations between the occurrence of specific mutation profiles with risk factors will be sought and their role in influencing the genetic profile of EC patients will be analyzed. Another aim of the project is to find relationships between specific mutational profiles of patients with the extent of staging lymphadenectomy, which could help to decide the extent of this surgery, which subsequently affects the quality of life of patients, especially in patients with high BMI. The final aim of the project is to establish a methodology to detect mutations arising from dominant specific mutational profiles in circulating tumor DNA (ctDNA) to monitor potential recurrence in patients at high risk of developing and recurrent disease. Overall, the main contribution of the project will be a detailed understanding of the relationship of the genetic profile of EC patients with their molecular subtype, the extent of staging lymphadenectomy and, most importantly, their impact related to the presence of lifestyle risk factors. These factors may be related to the presence of specific dominant mutational profiles subsequently serving as a tool for prognosis, prevention, risk of recurrence but also potential therapeutic targets in women with the presence of any of the lifestyle risk factors.

Study Timeline

• Study First Submitted: 2024-06-10
• Study Start: 2024-07-15
• Status Verified: 2024-11
• Study First Submitted QC: 2024-11-06
• Last Update Submitted: 2024-11-06
• Study First Posted: 2024-11-08
• Last Update Posted: 2024-11-08
• Primary Completion: 2027-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 280

Inclusion Criteria

• Clinical diagnosis of endometrial cancer.
• Treated with uterine removal with adequate staging.

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Exclusion Criteria

• There are no exclusion criteria in this study.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Genetic variants/mutation signatures	Sampled during surgery	Association of dominant signatures with molecular subtype, staging lymphadenectomy, age and lifestyle risk factors as well as their role in recurrence prediction of high-risk patients (obese patients, patients with p53 abnormalities, NSMP patients) and for surgical treatment decisions.
Quality of life of EC patients using the EORTC QLQ-C30 questionnaire	Questionnaires filled before surgery, then after 6,12,24 months	Analysis of endometrial cancer patients' quality of life undergoing hysterectomy with adequate staging lymphadenectomy by questionary study, specifically questionnaire European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30).; The questionnaire is composed of both multi item scales and single item scales. These include five functional scales, three symptom scales, global health status/quality of life scale and six single items.; All scales and single item measures range in score from 0 to 100, high scale represents a higher response level - high score for a functional scale represents a high/healthy level of functioning, high score for the global health status/quality of life represents a high quality of life, high score for a symptom scale/item represents a high level of symptomatology/problems.
Quality of life of EC patients using the EORTC QLQ-EN24 questionnaire	Questionnaires filled before surgery, then after 6,12,24 months	Analysis of endometrial cancer patients' quality of life undergoing hysterectomy with adequate staging lymphadenectomy by questionary study, specifically questionnaire European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24).; The questionnaire is composed of three functional, single-item scales, and 10 symptom scales (both multi-item scales and single-item measures).; All scales and single item measures range in score from 0 to 100, high scale represents a higher response level - high score for a functional scale represents a high/healthy level of functioning, high score for a symptom scale/item represents a high level of symptomatology/problems.
Physical activity of EC patients	Questionnaires filled before surgery, then after 6,12,24 months	Analysis of physical activity of EC patients' undergoing hysterectomy with adequate staging lymphadenectomy by questionary study, specifically International Physical Activity Questionnaire - Short Form (IPAQ-SF) questionnaire. This questionnaire assesses the types of intensity of physical activity and sitting time that people do as part of their daily lives are considered to estimate total physical activity in MET-min/week and time spent sitting. MET (metabolic equivalent) minutes represent the amount of energy expended carrying out physical activity.; Results can be reported in categories (low activity levels, moderate activity levels or high activity levels) depending on MET-minutes (higher score means higher category) and sitting time (higher score means lower category).
Introduction of methodology of ctDNA detection by digital PCR of consecutive follow-up samples.	Collection of blood samples at the day of surgery, then after 6,12 and 24 months	Collection of follow-up blood samples at different time-points, at the day of surgery, and then during 6, 12 and 24 months after surgery, methodology optimization for genetic variant detection in ctDNA isolated from follow-up blood samples, analysis of somatic variants resulting from dominant molecular signatures in ctDNA with potential role in EC progress or recurrence, mainly for high-risk EC patients (patients with p53 abnormal expression and NSMP group).

Trial Locations

Locations (1)

Faculty Hospital Královské Vinohrady; 🇨🇿 Praha, Czechia