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Title: Dietary fibre in the prevention of gastrointestinal inflammation and toxicity in patients undergoing pelvic radiotherapy for cancer
Author: Wedlake, Linda Jane
ISNI:       0000 0004 5368 3853
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2015
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Introduction: Approximately 17,000 patients a year receive radiotherapy for the pelvic cancers. Acute radiation-induced damage to normal non-cancerous tissues (toxicity) is characterised by an inflammatory response which has many pathophysiological similarities to inflammatory bowel disease (IBD). Preventing or reducing the severity of treatment-induced toxicity is of increasing importance as the number of survivors of cancer treatment increases. Dietary fibre may be an attractive option through the anti-inflammatory action of its fermentation metabolites short chain fatty acids (SCFA) and its beneficial effect on stool frequency and form. Methods: A systematic review of the efficacy of dietary fibre in the management of IBD was undertaken. The aims were firstly to identify evidence for the manipulation of dietary fibre in this inflammatory condition of the bowel as it was anticipated that little evidence would be available in patients receiving pelvic radiotherapy and secondly to gain insight as to the nutritional interventional approaches employed. A further systematic review was undertaken to identify evidence for the efficacy of dietary fibre manipulation in patients receiving pelvic radiotherapy. A 3-arm randomised controlled trial (RCT) manipulating dietary fibre intake in pelvic radiotherapy patients was subsequently carried out, powered on the difference in the change in Inflammatory Bowel Disease Questionnaire - Bowel subset (IBDQ-B) score between study groups consuming a high fibre, low fibre or habitual dietary fibre intake measured as nonstarch polysaccharide (NSP) in g/day. Other measurements included concentration of faecal SCFA at start and end of radiotherapy, daily patient-reported bowel habit using the Bristol Stool Form scale and quality of life assessed using the IBDQ tool. Results: A total of 4232 original citations were identified in the systematic review of fibre in IBD, of which 23 articles (1296 patients) were included. Evidence for the efficacy of increased dietary fibre on disease outcomes was found in 4/23 RCTs, 3/10 in ulcerative colitis and 1/1 in pouchitis. Meta-analysis was not possible due to widely differing study designs. The systematic review of fibre during pelvic radiotherapy identified 4188 original citations of which 4 articles (264 patients) were included. Meta-analysis (2 studies) showed increased or modified dietary fibre to be of benefit as a prophylactic against new-onset diarrhoea with a risk ratio of 0.75 (95% CI: 0.56 – 1.01). However, this result was not statistically significant (p=0.06). A total of 166 patients were randomised to the ‘Fibre Study’ RCT with 159 providing evaluable data of the required 156 patients. A significant difference in the change in IBDQ-B score between baseline and end of radiotherapy was identified between the high fibre and no intervention (control) group of 7.7 points in favour or the high fibre group (p=0.007). A difference in the change in IBDQ-B score of 3.4 points was also found between the low fibre and control group in favour of the low fibre group although this difference was not significant (p=0.535). No significant differences between groups were found in the incidence of loose stool (Bristol Stool type 6/7) or stool frequency although there was a marked increase in the use of anti-diarrhoeal medication by the high fibre group during week 5 of radiotherapy treatment. Mean (sd) NSP consumption of the control, low and high fibre groups at the start of radiotherapy was 13.6 (5.3), 10.2 (3.4) and 17.1 (4.8) g / day and at the end of radiotherapy was 12.2 (5.2), 8.9 (2.9) and 15.7 (5.1) g / day. No significant difference between groups in the concentration of faecal SCFA was found (n=41 paired samples) between start and end of radiotherapy. There was a significant difference in the change in IBDQ quality of life scores between the high fibre and control groups between start and end of radiotherapy in favour of the high fibre group (p=0.010). Conclusion: Dietary advice to increase fibre during pelvic radiotherapy may protect against bowel symptoms compared to no dietary advice. However, advice to reduce fibre intake may also be of benefit compared to no dietary advice. High and low fibre intakes may have differing, independent benefits in comparison to ad-libitum intake. High fibre intake did not adversely affect stool frequency or type although use of anti-diarrhoeal medication may have masked these effects. The possible placebo effect of specific dietary advice versus no dietary advice is intriguing and merits further exploration.
Supervisor: Whelan, Kevin Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available