Oral & Faecal Microbiota Analysis in Patients With Rectal Cancer Requiring Pre-operative Therapy Before Surgery, & Correlation With Response. (The MicrobRect Study).
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- 16s rRNA pyrosequencing analysis of microbial flora of rectal cancer patients
研究概览
简要总结
Rectal cancer is a common pathology which is treated by a multimodal approach. Those tumours in the rectum that are locally advanced are treated with neoadjuvant chemoradiotherapy before an operation. This aims to reduce the size of the tumour and increase the change of a complete resection. The degree of shrinkage of a rectal cancer to pre-operative treatment is influenced by the immune system. In some other cancers there is evidence that the bacteria living in our mouth & in the large bowel influence the way the body responds a cancer. In this study patients with rectal cancer requiring radiotherapy before surgery will be asked to give samples of saliva & bowel motions before chemoradiotherapy & again before surgery. These samples will have the type and number of bacteria analysed, as well as levels of key metabolic products of these bacteria. The results will be compared with the response, as assessed by the pathologist using standard criteria, of the rectal to the radiotherapy.
详细描述
Introduction:
Pelvic radiotherapy (VMAT) and chemotherapy are used in margin threatened rectal cancer to reduce the cancer and achieve a clear circumferential resection margin (CRM), facilitating potentially curative surgery. In 15 to 20% of cases, the pre-operative chemoradiotherapy potentially completely treats the cancer raising the possibility to avoid surgery altogether. Increasing the number of patients who are able to be cured without surgery is a research priority for the NCRI Colorectal Studies Group in UK. Other patients have some reduction in the size of the malignancy (a partial response) and others have a minimal response to the pre-operative therapy. As yet, it remains unclear as to the mechanism of response of the cancer to neoadjuvant therapy.
Understanding what biological factors influence response is important in order to improve the outcomes in rectal cancer. There is evidence that the innate immune system has a role in the degree of response. An increased degree of response (as measured by tumour regression grading) is associated with an increased abundance of natural killer (NK) CD56+ve cells. In mouse models the gut microbiome can modulate the tumour-immune microenvironment and T cell responses in colonic cancer. In addition some bacteria that are associated with colorectal cancer, such as F. nucleatum, are indigenous to the human oral cavity, and evidence that patients with colorectal cancer have a distinctive oral microbiota.
Clinical studies are needed to investigate the role of the oral & faecal microbiome in response to pre-operative treatment. If there is evidence of an association, the challenge will then be to explore if this can be modulated to increase response. Alternatively, the pre treatment microbiota profile may be able to be used as a predictor of response to neoadjuvant therapy.
This is a pilot study to assess the feasibility and acceptability to patients in providing faecal and saliva samples before cancer treatment. The investigators will also assess if there are any potential links between host microbial flora and chemoradiotherapy response
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with a locally advanced rectal cancer (defined as CRM threatening on MRI scans) in whom neoadjuvant chemoradiotherapy has been offered before consideration of curative resection
- •must be able to consent to inclusion in project
排除标准
- •Anyone who does not consent for inclusion
- •Any non rectal adenocarcinoma
- •Early rectal cancers that do not require neoadjuvant therapy
- •Patients presenting as an emergency with an obstructing rectal cancer requiring an early resection
- •Patients who are treated with short course radiotherapy alone rather than long course chemoradiotherapy
结局指标
主要结局
16s rRNA pyrosequencing analysis of microbial flora of rectal cancer patients
时间窗: 1 year
The microbial flora of the saliva and faeces of patients will be analysed at two time points. 1. before neoadjuvant chemoradiotherapy and 2. prior to surgery. This will be 16SrRNA pyrosequencing analysis to plot the microbial flora of each sample
次要结局
- Categorisation of microbial flora against response to neoadjuvant chemoradiotherapy(1 year)