Determination of Microbiological Factors Associated With Poor Response to Neoadjuvant Treatment in Rectal Cancers

Study Overview
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Brief Summary
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The objective of this project is to determine in a non-invasive manner (fecal samples) the predictive value of the intestinal microbiota and the presence of genotoxin-producing bacteria on the response to neoadjuvant treatment in rectal cancer. This could lead to a better understanding and selection of patients for personalized treatment in rectal cancer.

Detailed Description
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Rectal cancer is the 8th leading cause of cancer in the world with more than 300,000 deaths in 2018. In addition to surgery, neoadjuvant treatment has proven its value in reducing local recurrences. Evaluation of the response to neoadjuvant treatment (essential for the subsequent therapeutic decision but also for the oncological prognosis. It is based on rectal magnetic resonance imaging, completed after surgery by anatomopathology. A personalised treatment with therapeutic de-escalation or intensification for aggressive tumours can be decided depending on the response to Neoadjuvant treatment. Thus, knowledge of the predictive factors of response to neoadjuvant treatment would permit to anticipate and adapt care. The intestinal microbiota is a true microbial organ, playing a major role in maintaining intestinal homeostasis. Some bacterial species have been identified and suspected of playing a role in colorectal carcinogenesis. Among these species, genotoxin-producing Escherichia coli (CPEC) strains such as colibactin (cyclomodulin encoded by the genomic islet pks) are preferentially detected in patients with colorectal cancer (CRC), especially the most aggressive forms. Recent studies show that the intestinal microbiota is a prognostic factor in the response to certain chemotherapies or immunotherapies, but little work has been done on its potential influence on the effectiveness of radiotherapy. This suggests the possibility of using these biomarkers associated with response to neoadjuvant treatment. The objective of this project is to determine in a non-invasive manner (fecal samples) the predictive value of the intestinal microbiota and the presence of genotoxin-producing bacteria on the response to neoadjuvant treatment in rectal cancer. This could lead to a better understanding and selection of patients for tailored treatment in rectal cancer.

Official Title
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Determination of Microbiological Factors Associated With Poor Response to Neoadjuvant Therapy in Rectal Cancers: Focus on Cyclomodulin-producing Escherichia Coli

Conditions
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Rectal Cancer

Intervention / Treatment
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* Other: Biological collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven lower and mid-rectal adenocarcinoma at clinical stage II and III Patient is to receive neoadjuvant treatment (radiochemotherapy or chemotherapy or radiotherapy). Induction chemotherapy such as folfox or folfirinox is allowed Patient who has signed the informed consent of the study Male or female ≥ 18 years old Appropriate contraceptive measures should be used by both men and non-menopausal women before entering the trial until at least 8 weeks after the last course of radiochemotherapy. The investigator should inform the patient about the contraceptive measures to be used. Exclusion Criteria: Antibiotic treatment at the time or in the month preceding stool sampling Presence of an ostomy Previous treatment for rectal cancer Patient not affiliated to a French social protection system Patient not in favour of good compliance with treatment for psychological, family, social or geographical reasons Legal incapacity (Patient under curatorship or guardianship) Prior radiation therapy or pelvic curia in the year prior to inclusion History of other cancers in the last 5 years (except for in-situ cervical carcinomas and non-melanoma skin carcinomas treated optimally) Pregnant or breastfeeding woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biological collection<br>Fecal samples collected at different times : During inclusion consultation with surgeon, after neoadjuvant treatment and before surgery, In parallel to this fecal collection, standardized clinical data will be entered into a database | Other: Biological collection<br>* Fecal samples collected at different times : during inclusion consultation with surgeon, after neoadjuvant treatment and before surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ratio between the proportions of poor response to neoadjuvant treatment in populations so-called exposed (patients colonized by bacteria producing toxins (cyclomodulin) and unexposed (patients not colonized by bacteria producing toxins) |  | About 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of cyclomodulin-Producing Escherichia Coli colonization rate before and after neoadjuvant treatment |  | About 1 years | 
| Change of cyclomodulin-Producing Escherichia Coli prevalence before and after neoadjuvant treatment |  | About 1 years | 
| Change of prevalence forming the overall bacterial composition before and after neoadjuvant treatment |  | About 1 years | 
| Change of colonization rate (in addition to cyclomodulin-Producing Escherichia Coli) forming the overall bacterial composition before and after neoadjuvant treatment |  | About 1 years | 
| Relative risk of poor response to neoadjuvant treatment in colonized patients with other bacteria (exposed) compared to non-colonized patients (unexposed) |  | About 1 years | 
| Proportion of patients colonized according to the modality of the clinical variable age |  | About 1 years | 
| Proportion of patients colonized according to the modality of the clinical variable gender |  | About 1 years | 
| Proportion of patients colonized according to the modality of the clinical variable body mass index |  | About 1 years | 
| Overall survival in colonized people by the different types of bacteria that form the overall bacterial composition (including cyclomodulin-Producing Escherichia Coli) compared to non-colonized people |  | About 1 years | 
| Disease-free survival in colonized people by the different types of bacteria that form the overall bacterial composition (including cyclomodulin-Producing Escherichia Coli) compared to non-colonized people |  | About 1 years | 
| Specific survival in colonized people by the different types of bacteria that form the overall bacterial composition (including cyclomodulin-Producing Escherichia Coli) compared to non-colonized people |  | About 1 years | 
| Types of other bacteria forming the overall bacterial composition before neoadjuvant treatment |  | About 1 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal, cancer, cyclomodulin, microbiological factors