title: Nutritional interventions for survivors of childhood cancer.
abstract: BACKGROUND
  Childhood cancer survivors are at a higher risk of developing health conditions such as osteoporosis, and cardiovascular disease than their peers. Health-promoting behaviour, such as consuming a healthy diet, could lessen the impact of these chronic issues, yet the prevalence rate of health-protecting behaviour amongst survivors of childhood cancer is similar to that of the general population. Targeted nutritional interventions may prevent or reduce the incidence of these chronic diseases.
  
  
  OBJECTIVE
  The primary aim of this review was to assess the efficacy of a range of nutritional interventions designed to improve the nutritional intake of childhood cancer survivors, as compared to a control group of childhood cancer survivors who did not receive the intervention. Secondary objectives were to assess metabolic and cardiovascular risk factors, measures of weight and body fat distribution, behavioural change, changes in knowledge regarding disease risk and nutritional intake, participants' views of the intervention, measures of health status and quality of life, measures of harm associated with the process or outcomes of the intervention, and cost-effectiveness of the intervention
  
  
  METHODS
  We searched the electronic databases of the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 3), MEDLINE/PubMed (from 1945 to April 2013), and Embase/Ovid (from 1980 to April 2013). We ran the search again in August 2015; we have not yet fully assessed these results, but we have identified one ongoing trial. We conducted additional searching of ongoing trial registers - the International Standard Randomised Controlled Trial Number register and the National Institutes of Health register (both screened in the first half of 2013) - reference lists of relevant articles and reviews, and conference proceedings of the International Society for Paediatric Oncology and the International Conference on Long-Term Complications of Treatment of Children and Adolescents for Cancer (both 2008 to 2012).
  
  
  METHODS
  We included all randomised controlled trials (RCTs) that compared the effects of a nutritional intervention with a control group which did not receive the intervention in this review. Participants were childhood cancer survivors of any age, diagnosed with any type of cancer when less than 18 years of age. Participating childhood cancer survivors had completed their treatment with curative intent prior to the intervention.
  
  
  METHODS
  Two review authors independently selected and extracted data from each identified study, using a standardised form. We assessed the validity of each identified study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE criteria to assess the quality of each trial.
  
  
  RESULTS
  Three RCTs were eligible for review. A total of 616 participants were included in the analysis. One study included participants who had been treated for acute lymphoblastic leukaemia (ALL) (275 participants). Two studies included participants who had all forms of paediatric malignancies (266 and 75 participants). All participants were less than 21 years of age at study entry. The follow-up ranged from one month to 36 months from the initial assessment. All intended outcomes were not evaluated by each included study. All studies looked at different interventions, and so we were unable to pool results. We could not rule out the presence of bias in any of the studies.There was no clear evidence of a difference in calcium intake at one month between those who received the single, half-day, group-based education that focused on bone health, and those who received standard care (mean difference (MD) 111.60, 95% confidence interval (CI) -258.97 to 482.17; P = 0.56, low quality evidence). A regression analysis, adjusting for baseline calcium intake and changes in knowledge and self-efficacy, showed a significantly greater calcium intake for the intervention as compared with the control group at the one-month follow-up (beta coefficient 4.92, 95% CI 0.33 to 9.52; P = 0.04). There was statistically significant higher, self-reported milk consumption (MD 0.43, 95% CI 0.07 to 0.79; P = 0.02, low quality evidence), number of days on calcium supplementation (MD 11.42, 95% CI 7.11 to 15.73; P < 0.00001, low quality evidence), and use of any calcium supplementation (risk ratio (RR) 3.35, 95% CI 1.86 to 6.04; P < 0.0001, low quality evidence), with those who received this single, face-to-face, group-based, health behaviour session.There was no clear evidence of a difference in bone density Z-scores measured with a dual-energy X-ray absorptiometry (DEXA) scan at 36 months follow-up (MD -0.05, 95% CI -0.26 to 0.16; P = 0.64, moderate quality evidence) between those who received calcium and vitamin D supplementation combined with nutrition education and those who received nutrition education alone. There was also no clear evidence of a difference in bone mineral density between the intervention and the control group at the 12-month (median difference -0.17, P = 0.99) and 24-month follow-up (median difference -0.04, P = 0.54).A single multi-component health behaviour change intervention, focusing on general healthy eating principles, with two telephone follow-ups brought about a 0.17 lower score on the four-point Likert scale of self-reported junk food intake compared with the control group (MD -0.17, 95% CI -0.33 to -0.01; P = 0.04, low quality evidence); this result was statistically significant. There was no clear evidence of a difference between the groups in the self-reported use of nutrition as a health protective behaviour (MD -0.05, 95% CI -0.24 to 0.14; P = 0.60, low quality evidence).
  
  
  CONCLUSIONS
  Due to a paucity of studies, and the heterogeneity of the studies included in this review, we are unable to draw conclusions regarding the effectiveness of nutritional interventions for use with childhood cancer survivors. Although there is low quality evidence for the improvement in health behaviours using health behaviour change interventions, there remains no evidence as to whether this translates into an improvement in dietary intake. There was also no evidence that the studies reduced the risk of cardiovascular and metabolic disorders in childhood cancer survivors, although no evidence of effect is not the same as evidence of no effect. This review highlights the need for further well designed trials to be implemented in this population.
authors.affiliation: Department of Nutrition and Dietetics, Kids Cancer Centre, Sydney Children's Hospital, Randwick NSW, Australia.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Cohen
authors.forename: Claire E
authors.initials: CE
authors.lastname: Wakefield
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cohn
mesh_terms: D000293:Adolescent; D000818:Animals; D015519:Bone Density; D002136:Calcium, Dietary / Q000008:administration & dosage*; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002648:Child; D004700:Endocrine System Diseases / Q000517:prevention & control; D057140:Fast Foods; D015438:Health Behavior; D006801:Humans; D057194:Intention to Treat Analysis; D024821:Metabolic Syndrome / Q000517:prevention & control; D008892:Milk; D009369:Neoplasms / Q000628:therapy; D044623:Nutrition Therapy / Q000379:methods*; D010024:Osteoporosis / Q000517:prevention & control; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D017741:Survivors; D014807:Vitamin D / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D002136:Calcium, Dietary; D014815:Vitamins; D014807:Vitamin D