Objective: To understand the evidence base for nutrition interventions delivered prior to or during cancer treatment for preventing and treating negative cancer and cancer treatment–related outcomes among individuals with or at risk for malnutrition. The primary purpose was to inform the National Institutes of Health (NIH) Pathways to Prevention workshop Nutrition as Prevention for Improved Cancer Health Outcomes, held July 26–28, 2022.
Data sources: We searched Ovid Medline®, Ovid Embase®, and Cochrane Central Register of Controlled Trials to identify studies from 2000 through July 2022. We conducted grey literature searches to identify additional resources relevant to the associated costs or value (e.g., cost-effectiveness, cost-benefit) of nutrition interventions.
Review methods: The review was guided by a set of Key Questions established by the NIH planning committee for the Nutrition as Prevention for Improved Cancer Health Outcomes workshop. We searched for studies that evaluated a broad range of nutrition interventions (e.g., dietary supplements, nutrition support, nutrition counseling) for preventing and treating negative outcomes of cancer and cancer-related treatment. Eligible studies included randomized controlled trials (RCTs) with enrollment ≥50 participants. We extracted basic study information from all eligible studies, then grouped studies by broad intervention and cancer types. We provide a detailed evidence map for all included studies, but conducted risk of bias and additional qualitative descriptions of outcomes for only those intervention and cancer types with a larger volume of literature.
Results: We identified 9,798 unique references, with 206 studies from 219 publications reporting RCTs of nutrition interventions to potentially improve negative outcomes of cancer and cancer-related treatment. Two decades of randomized trial evidence on nutrition interventions for adults prior to and/or during cancer treatment primarily focused on dietary supplements, nutrition support (including oral nutrition supplements), and the route or timing of nutrition interventions for gastrointestinal and head and neck cancers in the inpatient setting. Most studies evaluated changes in body weight/composition, adverse events, length of hospital stay, and quality of life. Few studies were conducted within the U.S. setting. Among intervention and cancer types with a high volume of literature (n=114), which predominantly included studies in dietary supplements and nutrition support in gastrointestinal and head and neck cancers, 11 percent (n=12) were rated as low risk of bias (higher quality), 40 percent (n=46) medium risk of bias, and 49 percent (n=56) high risk of bias (lower quality). Low and medium risk-of-bias studies reported mixed results on the effect of nutrition interventions across cancer and treatment-related outcomes. Although the evidence map shows a large volume of studies evaluating nutrition interventions and outcomes, these studies showed high heterogeneity across study populations, interventions, and outcomes (measure definitions, timing of measurements), even within nutrition intervention categories; as a result, we could not aggregate results. While studies enrolled individuals from multiple cancer types, treatments, and stages, across the lifespan, with varying degrees of muscle wasting, and in those with a range of comorbid conditions, no eligible studies specifically evaluated whether the effects of nutrition interventions on preventing negative outcomes varied across these characteristics.
Among studies included in our Key Questions, we found that few (4%, n=8) published cost or value (e.g., cost-effectiveness, cost-benefit) information related to the intervention. In our grey literature search of additional studies examining cost or value of nutrition interventions, we found few studies that conducted cost-effectiveness or cost-benefit analyses; among those that did, we found the studies were conducted in non-U.S. health systems and demonstrated mixed results on the value of nutrition interventions.
Conclusions: Although overall RCT evidence focused on a wide range of nutrition interventions, studies were concentrated in use of dietary supplements, nutrition support, and the route or timing of nutrition interventions within gastrointestinal and head and neck cancers in inpatient settings. Among interventions with the highest volume of literature, the majority of studies were rated as high risk of bias. Our findings point to the need for rigorous new research to bolster the evidence base. Specifically, the field needs a more detailed future evaluation of a subset of nutrition interventions contained in this evidence map that focuses on priorities most relevant to specific stakeholders (e.g., oncologists, patients, dietitians, researchers, policymakers). Further, studies should be specifically designed to evaluate the main outcomes of interest for clinical practice. Future research would also benefit from creation of standardized taxonomies for interventions and outcomes as well as more rigorous design and reporting of nutrition interventions. As mentioned, heterogeneity of populations, interventions, comparators, and outcomes precluded aggregation. Currently, the quality and heterogeneity of the studies limit translation of findings into clinical practice or guidelines. In order to inform development of these guidelines, coordinated efforts are required to develop detailed conceptual frameworks for mechanisms of nutrition interventions most relevant to clinical care providers and patients. Such frameworks would help inform priorities for future research as well as guide practice and policy.