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E. Orgel, J. Genkinger, D. Aggarwal, L. Sung, M. Nieder, E. Ladas (2016)Association of body mass index and survival in pediatric leukemia: a meta-analysis.
The American journal of clinical nutrition, 103 3
E. Holler, Peter Butzhammer, K. Schmid, C. Hundsrucker, J. Koestler, K. Peter, Wentao Zhu, Daniela Sporrer, T. Hehlgans, M. Kreutz, B. Holler, D. Wolff, M. Edinger, R. Andreesen, J. Levine, J. Ferrara, A. Gessner, R. Spang, P. Oefner (2014)Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 20 5
F. Antillon, E. Rossi, A. Molina, A. Sala, P. Pencharz, M. Valsecchi, R. Barr (2013)Nutritional status of children during treatment for acute lymphoblastic leukemia in Guatemala
Pediatric Blood & Cancer, 60
Laura Blanton, Michael Barratt, M. Charbonneau, T. Ahmed, J. Gordon (2016)Childhood undernutrition, the gut microbiota, and microbiota-directed therapeutics
E. Montassier, Gabriel Al-Ghalith, Tonya Ward, S. Corvec, T. Gastinne, G. Potel, P. Moreau, M. Cochetière, E. Batard, D. Knights (2016)Pretreatment gut microbiome predicts chemotherapy-related bloodstream infection
Genome Medicine, 8
S. Rajagopala, Shibu Yooseph, D. Harkins, K. Moncera, Keri Zabokrtsky, M. Torralba, A. Tovchigrechko, S. Highlander, R. Pieper, L. Sender, K. Nelson (2016)Gastrointestinal microbial populations can distinguish pediatric and adolescent Acute Lymphoblastic Leukemia (ALL) at the time of disease diagnosis
BMC Genomics, 17
Allison Pribnow, R. Ortiz, L. Báez, L. Mendieta, S. Luna-Fineman (2017)Effects of malnutrition on treatment‐related morbidity and survival of children with cancer in Nicaragua
Pediatric Blood & Cancer, 64
Trijn Israëls, M. Wetering, P. Hesseling, N. Geloven, H. Caron, E. Molyneux (2009)Malnutrition and neutropenia in children treated for Burkitt lymphoma in Malawi
Pediatric Blood & Cancer, 53
Shalini Jatia, M. Prasad, Ameya Paradkar, A. Bhatia, G. Narula, G. Chinnaswamy, T. Vora, Sanjay Gomle, H. Sankaran, S. Banavali (2019)Holistic support coupled with prospective tracking reduces abandonment in childhood cancers: A report from India
Pediatric Blood & Cancer, 66
E. Orgel, R. Sposto, J. Malvar, N. Seibel, E. Ladas, P. Gaynon, D. Freyer (2014)Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: A report from the Children's Oncology Group.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 32 13
M. Smith, Tanya Yatsunenko, M. Manary, Indi Trehan, R. Mkakosya, Jiye Cheng, A. Kau, S. Rich, P. Concannon, J. Mychaleckyj, Jieng-Lung Liu, E. Houpt, Jia Li, E. Holmes, J. Nicholson, D. Knights, L. Ursell, R. Knight, J. Gordon (2013)Gut Microbiomes of Malawian Twin Pairs Discordant for Kwashiorkor
P. Hesseling, M. Tamannai, E. Ladas, G. Afungchwi, E. Katayi, F. Kouya (2018)Burkitt lymphoma – Nutritional support during induction treatment: Effect on anthropometric parameters and morbidity of treatment
South African Journal of Oncology
Faith Ihekweazu, J. Versalovic (2018)Development of the Pediatric Gut Microbiome: Impact on Health and Disease
The American Journal of the Medical Sciences, 356
M. Testa, S. Erbiti, A. Delgado, I. Cardenas (2016)Evaluation of oral microbiota in undernourished and eutrophic children using checkerboard DNA-DNA hybridization.
Z. Ward, J. Yeh, J. Yeh, N. Bhakta, A. Frazier, R. Atun (2019)Estimating the total incidence of global childhood cancer: a simulation-based analysis.
The Lancet. Oncology, 20 4
A. Sala, E. Rossi, F. Antillon, A. Molina, Tania Maselli, M. Bonilla, Angélica Hernández, R. Ortiz, C. Pacheco, R. Nieves, M. Navarrete, M. Barrantes, P. Pencharz, M. Valsecchi, R. Barr (2012)Nutritional status at diagnosis is related to clinical outcomes in children and adolescents with cancer: a perspective from Central America.
European journal of cancer, 48 2
HesselingBurkitt Lymphoma - nutritional support during induction treatment: effect on anthropometric parameters and morbidity of treatment
SA J Oncol
Béatrice Lauby-Secretan, C. Scoccianti, D. Loomis, Y. Grosse, Franca Bianchini, K. Straif (2016)Body Fatness and Cancer--Viewpoint of the IARC Working Group.
The New England journal of medicine, 375 8
J. Mayneris‐Perxachs, A. Lima, R. Guerrant, Á. Leite, Alessandra Moura, N. Lima, A. Soares, A. Havt, S. Moore, R. Pinkerton, J. Swann (2016)Urinary N-methylnicotinamide and β-aminoisobutyric acid predict catch-up growth in undernourished Brazilian children
Scientific Reports, 6
Abstract Cancer is one of the prominent noncommunicable diseases and is responsible for more than 8 million deaths each year worldwide. It is expected to impact up to 22 million people annually by 2030, and more than 60% of new patient cases will be in Asia, Africa, and Central and South America. Despite improvements in the delivery of care to children in low- and middle-income countries, survival of those with cancer is as low as 10%; a figure that is in stark contrast to overall childhood cancer survival rates in North America and Western Europe. Although many factors are contributing to this disparity, access to well-educated health-care workers, knowledgeable in both antineoplastic and supportive care, particularly nutritional assessment and therapy, is necessary for effective treatment and reduced morbidities of children with cancer. To this end, we identify approaches for advancing nutritional care such as building nutritional capacity and education as well as advancing rigorous nutritional science through the establishment of multicountry research groups among pediatric oncology units located in low- and middle-income countries. The global burden of cancer in children is expected to rise with recent projections estimating that 6.7 million incident cases will be diagnosed between 2015 and 2030 (1). The great majority of these patient cases (at least 90%) will be in low- and middle-income countries (LMICs) where improvements in access to care, training of health-care professionals, and elements of supportive care have led to clinically significant gains in survival for children with cancer in several regions across the globe. However, in many of these regions, endemic rates of undernutrition remain at high levels, and several micronutrient deficiencies are prevalent. At the same time, the rapid increase of obesity in LMICs leaves clinicians faced with managing the double burden of malnutrition and initiating treatment for cancer. A broader definition of malnutrition was established by the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations to address the coexistence of undernutrition (inclusive of wasting, stunting, and micronutrient deficiencies) and overweight and obesity (imbalance of energy, proteins, and micronutrients) and their implications with the growing global challenge of noncommunicable diseases. Nutritional status is a measurable and modifiable factor that is often not considered during treatment and its clinical impact undervalued because in part to the competing demands on clinicians in LMICs. Addressing poor nutrition in LMICs is complex because of its multifactorial nature. In most cases, remediating undernutrition is a straightforward task; however, food insecurity, low socioeconomic status, and restricted availability of trained nutritionists and medical nutrition therapy often limits the initiation and effectiveness of clinical interventions. Resource allocation is further constrained because of poorly established nutritional monitoring systems, which preclude clinicians and investigators from determining the true prevalence of malnutrition throughout the spectrum of cancer care. Refining our understanding of nutritional status in children in LMICs and its clinical impact is an essential component of cancer care especially as an increasing number of pediatric cancer units are established in resource-limited settings. Clinical Impact of Malnutrition and Barriers in LMICs The prevalence of undernutrition at diagnosis has been reported to be as high as 75% among children in LMICs. Undernutrition is associated with greater abandonment of therapy (2) and increased treatment-related toxicity and mortality (3–5). Studies conducted in high-income countries (HICs) indicate that overnutrition (overweight and obesity) is associated with poorer outcomes in children with cancer, although there is currently a paucity of equivalent data in LMICs (6). Improving the nutritional status of children with cancer in LMICs enhances their prospects for survival (7) as has been demonstrated also in the HIC setting (8). Therefore, monitoring the nutritional status of children undergoing treatment for cancer is crucial for delivering optimal care. Nutritional monitoring data can be used as a basis for developing research in pediatric oncology aimed at disentangling relationships between nutritional status, therapeutic efficacy, prognosis, and survival. However, a barrier facing clinicians and investigators in LMICs, exemplified by Central America and India, is that global growth charts may not reflect the growth patterns of children because of genetic differences or a lack of appropriate normative data for children greater than 5 years of age, such as for arm anthropometry. Assessing nutritional status accurately and cost-effectively poses challenges in LMICs where simple measures such as arm anthropometry are used when more sophisticated methods, like analysis of body composition by dual-energy x-ray absorptiometry, are unavailable. Likewise, successful strategies for redressing malnutrition should be culturally appropriate and should take advantage of local resources in the form of ready-to-use therapeutic foods (RUTF). Screening for malnutrition, assessment of nutritional status, and the adequacy of interventions should be subject to rigorous analysis in the form of clinical trials. Cancer treatment needs to be adapted to the nutritional status of the child (eg, multimicronutrient supplementation for obese children and lipid-based multimicronutrient supplements for undernourished children). Models to Advance Nutritional Capacity, Education, and Research in LMICs A multitiered approach is necessary to comprehensively address the role of nutrition in pediatric cancer. Increasing capacity and education of clinicians in LMICs is an essential first step in moving forward in nutrition for pediatric cancer care and research. In September 2018, the WHO established a global initiative for childhood cancer. With support from St Jude Children’s Research Hospital, this initiative is advancing the establishment of pediatric cancer units in LMICs to ensure access to high-quality care and financing and stable drug supply for children in these regions. Specific to building nutritional capacity, the International Initiative for Pediatrics and Nutrition has been established at the Columbia University Irving Medical Center to increase the availability of well-trained clinicians in nutritional care related to pediatric cancer as well as to create a global platform for advancing high-quality research in nutritional science and pediatric oncology. These efforts are complemented by leading global organizations, such as the International Society of Pediatric Oncology, which have provided an effective forum through their annual and regional meetings to host workshops on nutrition, thereby expanding attendees’ clinical knowledge, fostering collaborations, and advancing scientific exchange on compelling research questions. Taken together, these represent illustrative examples and opportunities to improve outcomes for children with cancer in LMICs while advancing nutritional science with pioneering research. Regional and local nongovernmental agencies are key partners in advancing nutritional initiatives in LMICs, particularly as these relate to securing access to food and medical devices essential for the nutritional management of a child with cancer. For example, providing lunches and rations to children with cancer and their families in India reduced the incidence of abandonment of therapy, thus improving outcomes for children undergoing treatment at Tata Memorial Center, one of the largest cancer centers in Asia (9). Similar activities have been instituted in Tegucigalpa, Honduras, through the support of the International Initiative for Pediatrics and Nutrition and local nongovernmental agencies. Comparable models are under development in several pediatric cancer units located in sub-Saharan Africa. Such activities can be scaled up through the agency of Childhood Cancer International, a consortium of more than 170 organizations devoted to supporting children with cancer and their families worldwide. Global Opportunities for Advancing Nutritional Science High-quality scientific data on the impact of nutrition on children with cancer is relatively limited in LMICs. Data derived from dietary assessments and blood samples taken for monitoring and assessing nutritional status can be used to investigate the metabolic effects of all forms of malnutrition and its impact on treatment efficacy and prognosis. Advances in understanding the impact of the human metabolome and microbiome assessed via noninvasive techniques using stool, urine, saliva, and human milk collections is a promising yet understudied area in pediatric oncology (10). Obesity is a growing epidemic with a total of 640 million adults (a sixfold increase since 1975) and 110 million children and adolescents now estimated to be obese worldwide (11). The role of obesity and metabolic dysfunction on cancer outcomes is an area of growing interest in adult oncology and is gaining increased attention with respect to pediatric oncology. An expert panel convened by the International Agency for Research on Cancer and the WHO concluded recently that there is “sufficient” evidence of a causal relationship between obesity and tumors of the gastric cardia, colon, liver, gallbladder, pancreas, postmenopausal breast, corpus uteri, ovary, and kidney, as well as multiple myeloma, esophageal adenocarcinoma, and meningioma (11). It is estimated that obesity accounts directly for at least 15% of these tumors, and this attributable fraction is expected to increase significantly in the coming decades. There are currently limited data on the impact of obesity and metabolic health on childhood cancer outcomes, but given the now established link between obesity and cancers in adults, as well as the impact of obesity on the metabolic milieu, it is plausible that obesity and metabolic dysfunction could be important determinants of prognosis in children with cancer (6). The microbiome and metabolome have been identified as priority areas of inquiry with respect to oncology and stem cell transplant (12–14). Some intriguing studies have already been conducted on the interaction of the gut microbiome and metabolome with nutritional status in children, and these can serve as a basis for initiating studies in children with cancer in LMICs (15). For example, in more than 100 Malawian twin pairs who were discordant for kwashiorkor, the gut microbiomes and metabolic functions in the malnourished children “matured” transiently with the administration of a peanut-based RUTF but regressed when the RUTF ceased. Further, the fecal samples from children with kwashiorkor led to marked weight loss when transplanted into gnotobiotic mice, and this was ameliorated transiently with RUTF (16). These observations support a potential causal role for the gut microbiome in the malnutrition of kwashiorkor and suggest that, when studying the impact of malnutrition on cancer outcomes in children, the intestinal microbiome should be considered as an important effect modifier. Another area of opportunity for global collaboration is that of the metabolome. Metabolic profiling may also represent an important future research area in the application of nutrition to pediatric oncology. A number of small-scale studies have been performed within this domain. For example, the utility of urinary metabolic phenotypes was demonstrated in a case-control study that compared nourished and undernourished children in Brazil. This study reported that urinary N-methyl-nicotinamide and β-aminoisobutyric acid represent promising biomarkers for predicting short-term growth outcomes in undernourished children and for identifying children destined for further growth shortfalls (17). Further, Testa and colleagues (18) evaluated the relationship between nutritional status, gingival health, and the composition of oral microbiota in children from a deprived area of Argentina and found statistically significant differences in some of the main periodontal pathogen species between eutrophic and undernourished children. These studies demonstrate that markers of nutritional status may have utility for the prediction of phenotypes relevant to clinical outcomes in childhood cancer patients. The assembly of high-quality patient cohorts with the collection of biological specimens (blood, urine, stool, and saliva) and longitudinal outcome data could serve as a platform for establishing innovative new studies on the role of nutrition and metabolic health on cancer in childhood. To advance any of these fields, large, diverse datasets are necessary. The aforementioned initiatives present a unique opportunity to advance these understudied areas and offer real potential for the creation of new knowledge that will lead directly to additional strategies in the effective therapeutic armamentarium available for children with cancer. Nutritional status has proven to be a risk factor and potential prognostic indicator for clinical outcomes in children with cancer. Based on the existing literature, it is evident that nutritional programs are an essential component of pediatric cancer units. This is of utmost importance in LMICs where malnutrition is notably more prevalent and the clinician to patient ratio is considerably lower than is observed in HICs. Effective models have been established to advance both nutritional clinical care and research in pediatric oncology. Efforts made in this arena will undoubtedly improve outcomes for children with cancer in LMICs while also increasing our understanding of the epidemiology and biological mechanisms essential to both nutritional science and pediatric oncology. Funding This work was supported by the Tamarind Foundation (EJL) and American Cancer Society (grant number 127000-MRSG-14–157-01-CCE to EJL). Notes Affiliations of authors: Department of Pediatrics and Epidemiology, Institute of Human Nutrition, Columbia University Medical Center, New York, NY (EJL); Nutrition and Metabolism Section, International Agency for Research on Cancer, Lyon, France (GM, IH); Department of Pediatrics, McMaster University, Hamilton, ON (RB). 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Google Scholar Crossref Search ADS PubMed WorldCat © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: email@example.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
JNCI Monographs – Oxford University Press
Published: Sep 1, 2019
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