Currently, there is a dearth of nutrition-based studies in pediatric oncology patients. Existing studies are primarily retrospective and secondary analyses nested within larger or therapeutic studies. We were able to identify nine prospective, interventional nutrition-focused studies. Of these, six included prospective, nutrition-based interventional studies and three involved validation or outcomes related to nutritional screening. Despite variation in study design and outcomes of interest, the overall findings suggest nutritional interventions increase weight and decrease complication during pediatric oncology treatment while nutritional screening decreases risk for malnutrition and potentially improves weight gain.
Of the studies reviewed for nutritional intervention, five of the six examined the addition of nutrition supplementation including appetite stimulants and various formula compositions. Only one study aimed at proactive enteral tube placement as an intervention. This significant variability in the research surrounding nutrition in children with cancer mirrors the inconsistency in nutritional screening and intervention in clinical practice(10). While all the studies demonstrated improved weight, there was no significant difference seen in isocaloric versus hypercaloric formulas or ready-to-use therapeutic food versus traditional formulas. This potentially supports the notion that early and appropriate correction of malnutrition can have health benefits, including weight gain or decreased weight loss, regardless of the type of nutritional supplementation used. Similarly, Couluris et al. and Curvelier et al. both observed that cyproheptadine hydrochloride and megestrol acetate both have the potential to lead to improved weight gain compared to placebo(17, 19). Current literature lacks a systematic, evidence-based and patient-centered approach into how and which appetite stimulants or nutrition support tools should be utilized in specific patients, diseases, or treatments. Additionally, the complexity of nutritional intervention to prevent malnutrition is hard to distinguish from support following a diagnosis of malnutrition. Regardless, proactive nutritional intervention including nasogastric tube placement, has been shown to be safe, feasible, and effective(18). This study suggests pre-empting malnutrition is more effective than treating malnutrition once it has developed.
Previous literature has suggested there are treatment- and disease-specific risk factors for malnutrition, and our study identified interesting findings based on the type of pediatric cancer. Couluris et al. found that patients with hematologic malignancy had improved weight gain on cyproheptadine hydrochloride compared to patients with non-hematologic malignancy also on cyproheptadine hydrochloride(19). Also, Prasad et al. found greater response to ready-to-use therapy food by patients with ALL compared to standard nutritional therapy(20). These two observations suggest appropriate interventions may be disease- and treatment-specific. Existing pediatric oncology literature emphasizes the importance of risk-based monitoring for toxicity including increased rates of ototoxocity and hematologic toxicity in teenagers with brain tumors along with more nausea, vomiting, and anorexia in different aged patients treated for lymphoma and rhabdomyosarcoma(24, 25). Age and treatment intensity have also been shown to impact the risk of developing malnutrition, but we continue to lack prospective interventional studies or widely utilized tools for nutrition screening and intervention in pediatric oncology(26, 27). Furthermore, in the development of novel therapeutics, documentation shows that changes in weight, specifically body composition, can alter the pharmacokinetics and pharmacodynamics of chemotherapy metabolism(6). Specific and dedicated study of nutritional interventions directed towards age, disease, and treatment are essential and require further evaluation.
Examining nutrition screening tools in pediatric oncology yielded even fewer studies. Despite multiple professional societies advocating for systematic and consistent nutritional screening, it remains underutilized in clinical practice and fails to account for the unique medical needs and physiologies of children and adolescents compared to adults(28–30). Gallo et al. used implementation of a nutritional support team to decrease the risk for malnutrition and the length of cancer treatment(21). Nutritional support team implementation also increased 4-year survival rates in patients, specifically with CNS tumor diagnoses. Han et al. found that the SCAN system improves dietician referral and increased weight gain(22). Totadri et al. studied SIOP-PODC algorithm, which did not increase weight gain(23). However, it did increase MUAC and supplement usage while decreasing platelet transfusions, but it did not decrease other complications. Overall, the addition of a screening tool benefits patients by preventing weight loss or causing weight gain; but there are several important factors that have not been included in prospective studies. Data demonstrates that nutrition and feeding create significant anxiety in parents and caregivers(31, 32). It also stands to reason that failure to lose weight or failure to gain weight may reflect earlier intervention and proper nutrition maintenance throughout. Additionally, inclusion of an improved study on nutrition screening could have impacts on quality of life and cancer survivorship. Adult oncologists have better incorporated appetite, body measurements, and function into “cancer cachexia,” but we have even less classification of the cancer cachexia phenotype in children(33, 34).
Limitations
This systematic review focuses on finding malnutrition interventions and screening tools that adequately treat or prevent cancer-related cachexia. The following limitations should be acknowledged when reviewing the results. First, the frequency of cancer within the pediatric population is far less than the frequency within the adult population. This yields fewer studies regarding cancer cachexia for this systematic review. Second, due to the small number of articles present at the time of this study, the variables reported amongst each study were heterogeneous in comparison to one other. The heterogeneity of variables prevented an accurate meta-analysis to be conducted causing the findings to be conceptual instead of statistical. This is similar to previous cancer related nutritional reviews amongst pediatric patient care. Lastly, there is variability in treatment appropriateness within the pediatric population due to the vast developmental differences between the youngest and oldest patients within this population. The variability of needs within the pediatric population should not be neglected when looking at these results because developmental variability caused varying intervention and screening results based on age. This review intended to be as inclusive as possible amongst the pediatric population with cancer and cancer related cachexia without widening the scope past the review’s purpose.