Title: Predicting patients at risk of developing gastrointestinal symptoms after treatment with pelvic radiotherapy.
Funder: Health Education England

Abstract: Background Annually, 17,000 British patients receive pelvic radiotherapy. Up to half of those patients develop chronic changes in their bowel function.Chronic diarrhoea, abdominal pain, increased bowel frequency, faecal incontinence, tenesmus and increased flatulence are most troublesome and impact levels of fatigue, psychological issues and socio-economic status. Being housebound due to toilet dependency has a devastating impact on the daily activity and quality of life of cancer survivors. Progress has been made in technical advances in the delivery of radiotherapy and understanding the personal parameters which change the risk of gastrointestinal (GI) side-effects for individuals. Mechanisms by which gastrointestinal symptoms occur after cancer treatment are starting to be understood and UK multi-professional guidance to manage those chronic GI problems has been published. However, the ability to predict and risk-stratify in advance those who might go on to develop serious problems as a result of radiotherapy has not yet been established. Normal gut flora produce gases from their metabolites (Volatile Organic Compounds or VOCs). Whilst the gold standard for analysing VOCs is gas chromatography/mass spectometry this is not a cost effective option in clinical practice. Two other techniques can be applied to analyse those VOCs: electronic sensing (e-nose) or High Field Asymmetric Ion Mobility Spectrometry (FAIMS). The e-nose and FAIMS techniques have been used successfully in small studies to diagnose lung disease, diabetes, bladder cancer, tuberculosis, cyanide poisoning, renal failure and schizophrenia. Focusing on gastrointestinal disorders, consistent changes in the VOCs produced by patients with inflammatory bowel disease, bile acid malabsorption, gastrointestinal cancer, coeliac disease, Clostridium difficile infection have been detected compared to healthy individuals. In 2012, our team conducted a retrospective blinded pilot study using the e-nose and FAIMS to analyse stool samples collected before the start of radiotherapy from 23 prostate cancer patients. Two completely distinct groups of patients could be identified from the samples taken before treatment: patients who would develop severe toxicity during treatment and those who would not. Aims of the work The primary aim of this study is to define a predictive marker of chronic radiation-induced GI toxicity using the olfactory signatures generated by the e-nose and FAIMS techniques. Research question Which are the volatile organic compounds in the olfactory signatures generated by the e-nose and FAIMS techniques analysing stool and urine samples predictive of radiation-induced GI toxicity in women with a gynaecological malignancy? Plan of investigation Newly diagnosed patients with a gynaecological cancer due to have curative pelvic radiotherapy will be invited into the study. There will be 5 time points of assessments: before treatment, 2 during treatment and 6 and 18 months after completion of treatment. Validated tools will be used to assess the symptom prevalence, severity and impact on quality of life. Stool and urine samples will be collected for analysis with the e-nose and FAIMS technique. Analysis of the VOCs will enable identification of which chemical gasses predict GI toxicity due to pelvic radiotherapy. Summary of the potential benefits to patients and the NHS Currently, there is no predictive marker for GI consequences and this research bridges that gap. This study will identify which VOCs are predictive and indicate which microbiota are involved in radiation-induced GI toxicity. The ability to predict this will lead to a non-invasive bench-to-patient application that can be used when discussing treatment options with the patient in clinic. This will have profound effects on the advice offered to patients in pre-treatment counseling, allow stratification of follow-up pathways for GI problems systematically according to the risk identified and ensure timely management. Long-term, it will inform care providers regarding the level of intervention and services needed in the NHS.

Lay abstract: The largest group of patients who experience problems after cancer treatment are those who are treated with pelvic radiotherapy. Up to half of all patients will develop major chronic changes in their bowel function and this currently cannot be predicted in advance. CHAR(13) + CHAR(10)Normal gut flora play an important role in radiation-induced side effects and produce gases that can be detected. This study will evaluate the use of 'sniffing' samples via electronic sensing and FAIMS to identify patients at risk of gastrointestinal problems before the start of radiotherapy. This will have profound effects on the advice and management offered to patients.

Research activity codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS