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

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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 radiochemotherapy has proven its value in reducing local recurrences. Evaluation of the response to neoadjuvant treatment (essential for the subsequent therapeutic...

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 radiochemotherapy 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 radiochemotherapy in rectal cancer. This could lead to a better understanding and selection of patients for tailored treatment in rectal cancer.

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