Nutritional interventions for reducing gastrointestinal toxicity in adults undergoing radical pelvic radiotherapy

Across the developed world, an estimated 150,000 to 300,000 people are treated annually with pelvic radiotherapy and 80% will develop gastrointestinal (GI) symptoms during treatment. Acute GI symptoms are associated with a greater risk of chronic, often debilitating, GI symptoms. Up to one-third of patients are malnourished before pelvic radiotherapy and up to four-fifths of patients lose weight during treatment. Malnutrition is linked to a higher risk of GI toxicity, which can lead to breaks in radiotherapy and early cessation of chemotherapy, thus compromising the efficacy of the primary cancer treatment.

To assess the effects of nutritional interventions for reducing GI toxicity in adults undergoing radical pelvic radiotherapy.

We searched the Cochrane Gynaecological Cancer Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2012, MEDLINE and EMBASE to May 2012. We handsearched the citation lists of included studies and previous systematic reviews identified to identify further relevant trials.

We included studies if they were randomised controlled trials (RCTs) or non-randomised studies with concurrent comparison groups including quasi-randomised trials, cluster RCTs, non-randomised trials, prospective and retrospective cohort studies, and case series of 30 or more patients. We only included studies if they assessed the effect of a nutritional intervention in adults aged 18 years or over undergoing radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic malignancy. We excluded patients with stomas and a previous history of inflammatory bowel disease. Nutritional support interventions could be provided at any stage before or during pelvic radiotherapy and included dietary counselling; dietary modification of fibre, lactose or fat; supplementary foods or drinks or fortified foods; standard oral nutrition supplements including polymeric-, peptide- or amino acid-based supplements and those where novel substrates have been added; enteral tube feeds; or parenteral nutrition (partial or total). We excluded probiotics, prebiotics and synbiotics.

Two review authors independently assessed trial quality and extracted data. We contacted study authors to obtain missing data. We assessed bias for each of the included studies using the bias assessment tables in the Cochrane software Review Manager5. We performed meta-analysis, when indicated, using the Mantel-Haenszel fixed-effect method or inverse variance fixed-effect method displayed with heterogeneity. We undertook meta-analyses on trials evaluating dietary modification against standard treatment for diarrhoea at the end of radiotherapy and for change in weight from baseline to end of radiotherapy.

The searches identified 7558 titles, and we excluded 7513 during title and abstract searches. We reviewed 45 papers in full, and excluded 39. We identified four studies on handsearching of the references, which, along with the six eligible papers from the database search, led to 10 studies being included. Four studies, three of which were RCTs and one prospective study, investigated the effect of elemental diet on GI symptoms; one RCT investigated the effect of dietary modification and elemental diet; and five RCTs investigated dietary modification. Studies were varied in terms of risk of bias. Data were dichotomised for presence and absence of diarrhoea at the end of radiotherapy for four trials evaluating dietary modification comprising modified fat, lactose, fibre or combinations of these dietary changes. A reduction in diarrhoea was demonstrated with nutritional intervention (risk ratio (RR) 0.66; 95% confidence interval (CI) 0.51 to 0.87, four studies, 413 participants, moderate quality of evidence) with low heterogeneity (Chi(2) = 3.50, I(2) = 14%). Two trials evaluating dietary modification on weight change (comparing baseline and end of radiotherapy) showed no difference between intervention or control (mean difference (MD) -0.57 kg; 95% CI -1.22 to 0.09) with low heterogeneity (Chi(2) = 1.41, I(2) = 29%). Generally adverse effects were poorly reported in included studies. Elemental diet in particular was poorly tolerated. GI symptoms or toxicity > 6 months after radiotherapy was not reported in included studies

There have been benefits demonstrated with dietary modification during pelvic radiotherapy to reduce diarrhoea. Those diets included single interventions or combinations of modified fat, lactose-restriction, fat-restriction and fibre supplementation. We were unable to meta-analyse elemental diet, as data were not available. We considered some of the studies to be at high risk of bias. There have been recent advances in novel, more targeted radiotherapy techniques, such that the findings of older studies need to be interpreted with caution. In addition, there were problems with compliance and palatability with some of the interventions, particularly elemental diet, which limits its usefulness in clinical practice.