Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy

Wedlake, Linda; Shaw, Clare; McNair, Helen; Lalji, Amyn; Mohammed, Kabir; Klopper, Tanya; Allan, Lindsey A.; Tait, Diana; Hawkins, M.; Somaiah, Navita; Lalondrelle, Susan; Taylor, Alexandra; VanAs, Nicholas; Stewart, Alexandra J.; Essapen, Sharadah; Gage, Heather; Whelan, Kevin; Andreyev, H. J. N.

doi:10.3945/ajcn.116.150565

Cited by 48 publications

(90 citation statements)

References 30 publications

(36 reference statements)

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“…Furthermore, it must be taken into consideration that the distinction between soluble and insoluble dietary fibres is complex [34]. A recent RCT found that a high-fibre dietreduced gastrointestinal toxicity compared with habitual fibre intake, both in the acute and late phases [35]. A higher fibre intake will also increase the intake of soluble fibres which may be beneficial due to the enhanced production of SCFA, which could potentially reduce inflammatory processes [16].…”

Section: Discussionmentioning

confidence: 99%

Effects of a nutrition intervention on acute and late bowel symptoms and health-related quality of life up to 24 months post radiotherapy in patients with prostate cancer: a multicentre randomised controlled trial

Forslund

Ottenblad

Ginman

et al. 2019

Support Care Cancer

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Purpose Radiotherapy to the prostate gland and pelvic lymph nodes may cause acute and late bowel symptoms and diminish quality of life. The aim was to study the effects of a nutrition intervention on bowel symptoms and health-related quality of life, compared with standard care. Methods Patients were randomised to a nutrition intervention (n = 92) aiming to replace insoluble fibres with soluble and reduce intake of lactose, or a standard care group (n = 88) who were recommended to maintain their habitual diet. Bowel symptoms, health-related quality of life and intake of fibre and lactose-containing foods were assessed up to 24 months after radiotherapy completion. Multiple linear regression was used to analyse the effects of the nutrition intervention on bowel symptoms during the acute (up to 2 months post radiotherapy) and the late (7 to 24 months post radiotherapy) phase. Results Most symptoms and functioning worsened during the acute phase, and improved during the late phase in both the intervention and standard care groups. The nutrition intervention was associated with less blood in stools (p = 0.047), flatulence (p = 0.014) and increased loss of appetite (p = 0.018) during the acute phase, and more bloated abdomen in the late phase (p = 0.029). However, these associations were clinically trivial or small. Conclusions The effect of the nutrition intervention related to dietary fibre and lactose on bowel symptoms from pelvic RT was small and inconclusive, although some minor and transient improvements were observed. The results do not support routine nutrition intervention of this type to reduce adverse effects from pelvic radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Effects of a nutrition intervention on acute and late bowel symptoms and health-related quality of life up to 24 months post radiotherapy in patients with prostate cancer: a multicentre randomised controlled trial

Forslund

Ottenblad

Ginman

et al. 2019

Support Care Cancer

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“…Eight studies (57)(58)(59)(60)(61)(62)(63)(64)(65) recruiting 639 patients, comprising six RCT (57,59,(61)(62)(63)(64)(65) (including one cross-over trial (57) ) and two cohort studies (58,60) have explored the benefit of manipulating dietary and/or supplemental fibre during pelvic irradiation. Of the interventional RCT, two manipulated dietary fibre alone (60,65) , three used a fibre supplement (59,63,64) (two of which included additional dietary restrictions (59,64) ) and a further study with long-term follow-up manipulated dietary fibre in combination with a low-lactose restriction (61,62) . Seven studies (58)(59)(60)(61)(62)(63)(64)(65) explored the role of fibre in preventing gastrointestinal toxicity (i.e.…”

Section: Dietary Fibrementioning

confidence: 99%

“…Of the interventional RCT, two manipulated dietary fibre alone (60,65) , three used a fibre supplement (59,63,64) (two of which included additional dietary restrictions (59,64) ) and a further study with long-term follow-up manipulated dietary fibre in combination with a low-lactose restriction (61,62) . Seven studies (58)(59)(60)(61)(62)(63)(64)(65) explored the role of fibre in preventing gastrointestinal toxicity (i.e. as a prophylactic agent) whilst one (57) explored the therapeutic efficacy of the psyllium v. codeine phosphate for the control of radiation-induced diarrhoea.…”

Section: Dietary Fibrementioning

confidence: 99%

Nutritional strategies to prevent gastrointestinal toxicity during pelvic radiotherapy

Wedlake

2018

Proc. Nutr. Soc.

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Radiotherapy-induced damage to non-cancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option with sound rationale for intervention. The aim of this review was to synthesise published evidence for the use of elemental formulae, low or modified fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the bowel from gastrointestinal side effects during long-course, radical pelvic radiotherapy. Thirty original studies (recruiting n 3197 patients) were identified comprising twenty-four randomised controlled trials, four cohort studies and two comparator trials. Endpoints varied and included symptom scales (Inflammatory Bowel Disease Questionnaire, Common Technology Criteria for Adverse Events, Radiation Therapy Oncology Group) and Bristol Stool Scale. Dietary and supplement interventions were employed with many studies using a combination of interventions. Evidence from RCT was weak for elemental, low or modified fat and low-lactose interventions and modestly positive for the manipulation of fibre during radiotherapy. Evidence for probiotics as prophylactic interventional agents was more promising with a number of trials reporting positive results but strength and strains of interventions vary, as do methodologies and endpoints making it difficult to arrive at firm conclusions with several studies lacking statistical power. This consolidated review concludes that there is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula could be effective in severe toxicity but this is unproven. Probiotics offer promise but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients.

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“…With an ageing population, new approaches to radiosensitisation are urgently required. One such approach might be to modify the intake of dietary fibre by supplements before and during radiotherapy or current standard chemoradiation schedules, which would be a very costeffective strategy, not expected to add to normal tissue toxicity (3,4).…”

Section: Introductionmentioning

confidence: 99%

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

Then

Paillas

Wang

et al. 2019

Preprint

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BackgroundPatients with pelvic malignancies often receive radiosensitising chemotherapy with radiotherapy to improve survival, however this is at the expense of increased normal tissue toxicity, particularly in elderly patients. Here we explore if an alternative, low-cost and non-toxic approach can achieve radiosensitisation in mice transplanted with human bladder cancer cells. Other investigators have shown slower growth of transplanted tumours in mice fed high-fibre diets. We hypothesised that mice fed a high-fibre diet would have improved tumour control following ionising radiation (IR) and that this would be mediated through the gut microbiota.ResultsWe investigated the effects of four different diets (low fibre, soluble high fibre, insoluble high fibre and mixed soluble/insoluble high fibre diets) on tumour growth in immunodeficient mice implanted with human bladder cancer flank xenografts and treated with ionising radiation, simultaneously investigating the composition of their gut microbiomes by 16S rRNA sequencing. A significantly higher relative abundance of Bacteroides acidifaciens was seen in the gut (faecal) microbiome of the soluble high fibre group, and the soluble high fibre diet resulted in delayed tumour growth after irradiation compared to the other groups. Within the soluble high fibre group, responders to irradiation had significantly higher abundance of B. acidifaciens than non-responders. When all mice fed with different diets were pooled, an association was found between the survival time of mice and relative abundance of B. acidifaciens. The gut microbiome in responders was predicted to be enriched for carbohydrate metabolism pathways and in vitro experiments on the transplanted human bladder cancer cell line suggested a role for microbial-generated short-chain fatty acids and/or other metabolites in the enhanced radiosensitivity of the tumour cells.ConclusionsSoluble high fibre diets sensitised tumour xenografts to irradiation and this phenotype was associated with modification of the microbiome and positively correlated with B. acidifaciens abundance. Our findings might be exploitable for improving radiotherapy response in human patients.

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Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy

Cited by 48 publications

References 30 publications

Effects of a nutrition intervention on acute and late bowel symptoms and health-related quality of life up to 24 months post radiotherapy in patients with prostate cancer: a multicentre randomised controlled trial

Effects of a nutrition intervention on acute and late bowel symptoms and health-related quality of life up to 24 months post radiotherapy in patients with prostate cancer: a multicentre randomised controlled trial

Nutritional strategies to prevent gastrointestinal toxicity during pelvic radiotherapy

Association of Bacteroides acidifaciens relative abundance with high-fibre diet-associated radiosensitisation

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