Systematic review and meta-analysis of the evidence for oral nutritional intervention on nutritional and clinical outcomes during chemo(radio)therapy: current evidence and guidance for design of future trials

Abstract

Background: Driven by reduced nutritional intakes and metabolic alterations, malnutrition in cancer patients adversely affects quality of life, treatment tolerance and survival. We examined evidence for oral nutritional interventions during chemo(radio)therapy.

Design: We carried out a systematic review of randomized controlled trials (RCT) with either dietary counseling (DC), high-energy oral nutritional supplements (ONS) aiming at improving intakes or ONS enriched with protein and n-3 polyunsaturated fatty acids (PUFA) additionally aiming for modulation of cancer-related metabolic alterations. Meta-analyses were carried out on body weight (BW) response to nutritional interventions, with subgroup analyses for DC and/or high-energy ONS or high-protein n-3 PUFA-enriched ONS.

Results: Eleven studies were identified. Meta-analysis showed overall benefit of interventions on BW during chemo(radio)therapy (+1.31 kg, 95% CI 0.24-2.38, P = 0.02, heterogeneity Q = 21.1, P = 0.007). Subgroup analysis showed no effect of DC and/or high-energy ONS (+0.80 kg, 95% CI -1.14 to 2.74, P = 0.32; Q = 10.5, P = 0.03), possibly due to limited compliance and intakes falling short of intake goals. A significant effect was observed for high-protein n-3 PUFA-enriched intervention compared with isocaloric controls (+1.89 kg, 95% CI 0.51-3.27, P = 0.02; Q = 3.1 P = 0.37). High-protein, n-3 PUFA-enriched ONS studies showed attenuation of lean body mass loss (N = 2 studies) and improvement of some quality of life domains (N = 3 studies). Overall, studies were limited in number, heterogeneous, and inadequately powered to show effects on treatment toxicity or survival.

Conclusion: This systematic review suggests an overall positive effect of nutritional interventions during chemo(radio)therapy on BW. Subgroup analyses showed effects were driven by high-protein n-3 PUFA-enriched ONS, suggesting the benefit of targeting metabolic alterations. DC and/or high-energy ONS were less effective, likely due to cumulative caloric deficits despite interventions. We highlight the need and provide recommendations for well-designed RCT to determine the effect of nutritional interventions on clinical outcomes, with specific focus on reaching nutritional goals and providing the right nutrients, as part of an integral supportive care approach.

Figure 1.

Search string and flow chart of screening and study selection ^areasons for exclusion from title/abstract included review articles, study not in cancer patients, not intervention study, not adult patients, inadequate intervention, not chemo(radio)therapy only and non RCT.

Figure 2.

Meta-analysis of the effects of oral nutritional intervention on body weight (BW) response. A random effect model was run on mean difference of BW response data from studies investigating the effect of oral nutritional intervention (A). Subgroup analysis were subsequently carried out for studies conducted with DC and ONS when required [26, 41, 30] (N = 3) or with high-energy ONS (N = 2) [36, 37] (B) and for studies conducted with high-protein, n-3 PUFA-enriched ONS (N = 4) [27, 28, 31, 34] (C). ^†Guarcello et al. [31] reported only per-protocol data. When excluding this study from the meta-analysis, results were MD 1.26 kg, 95% CI 0.01–2.52, P = 0.049 (A) and MD 1.91 kg, 95% CI −0.30 to 4.11, P = 0.065 (C). Limitations in the meta-analysis pertain to the limited amount of data available. Publication bias could not be assessed as there were not enough studies available to perform a funnel plot. In addition, there is heterogeneity in analyses A and B, and we cannot rule out the impact of the variety of cancer types and stages, nutritional status, length of intervention and variations in the intervention per se.