Expert Review of Anticancer Therapy

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The role of nutrition in pediatric oncology

Ronald D. Barr & Elena J Ladas

To cite this article: Ronald D. Barr & Elena J Ladas (2020): The role of nutrition in pediatric
oncology, Expert Review of Anticancer Therapy, DOI: 10.1080/14737140.2020.1719834

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EXPERT REVIEW OF ANTICANCER THERAPY
https://doi.org/10.1080/14737140.2020.1719834

REVIEW

The role of nutrition in pediatric oncology

Ronald D. Barra and Elena J Ladasb
a
Division of Hematology and Oncology, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada; bDivision of Hematology-
Oncology/Stem Cell Transplant, Department of Pediatrics, Columbia University, Irving Medical Centre, New York, USA

ABSTRACT ARTICLE HISTORY

Introduction: Obesity compromises survival in children with cancer in high-income countries (HICs) and Received 25 July 2019
is accompanied often by sarcopenia. In low and middle-income countries (LMICs), where the great Accepted 20 January 2020
majority of children live, the prevalence of under-nutrition is as high as 95% in those with cancer. KEYWORDS
Nutritional support improves clinical outcomes, including survival. Anthropometry; cancer;
Areas covered: This narrative review describes the evolution of attention to nutrition in children with children; densitometry;
cancer and the increasing understanding of this relationship. An initial focus on obesity in children with malnutrition; metabolome;
acute leukemias in HICs has been matched more recently by a recognition of the negative effect of microbiome; morbidity;
under-nutrition on survival in children with cancer in LMICs. These observations have stimulated survival
explorations of underlying mechanisms, including dysbiosis of the gut microbiome, and structured
nutritional interventions to redress adverse outcomes.
Expert opinion: Studies of the gut microbiome and metabolome have yielded important information
on the pathogenesis of malnutrition in children, providing new avenues for interventions. Combinations
of plant products that are inexpensive and readily available in LMICs have been shown to ‘mature’ the
microbiome and the corresponding plasma proteome in children with acute malnutrition, offering the
prospect of cost-effective remedies that are tested in children with cancer.

1. Introduction Pediatric Oncology (SIOP) in 2013 [7]. At the COG meeting in

Some 20 years ago the first international workshop on nutrition
and cancer in children was held in Puebla, Mexico under the
auspices of UICC, the Union for International Cancer Control [1].
The workshop was entitled Nutritional Morbidity in Children with
Cancer: Mechanisms, Measures and Management and had three
objectives (Table 1). Three sets of outcomes resulted from the
workshop (Table 2–4). The second international workshop on
nutrition and cancer in children was convened almost a decade
later, again in Puebla [2]. The output included position statements
on Nutritional Status: Measurements and Outcomes; Energy
Balance and Body Composition; Bone Morbidity; Complementary
and Alternative Medicines; Dietary Manipulation and Vitamin
Supplementation; and Experience in Developing Countries.
The choice of Puebla for these events was made on two
counts; early contributions from investigators in Puebla to the
literature on the importance of nutrition in children with
cancer [3] and recognition of the influence of malnutrition
on clinical outcomes in children with cancer in developing
countries [4]. Support for these events came mainly from the
Office of International Affairs in the National Cancer Institute
(USA) and from the Public Health Agency of Canada.
In the years that have passed since the Puebla workshops,
there has been increasing interest in the challenges posed by
the inter-relationships of children, cancer and nutrition [5].
Nutrition committees were formed by the Children’s Oncology
Group (COG) in 2005 [6] and the International Society of
October 2018, there was a symposium on the State of the
Science in Nutrition [8] which has resulted in a set of published
manuscripts. The SIOP committee is a composite of two
streams; one focused on high-income countries (HICs) and the
other on low and middle-income countries (LMICs). The net-
work is united in its Terms of Reference that begin ‘Malnutrition
in its broadest sense poses serious challenges in the manage-
ment of children and adolescents throughout their cancer jour-
ney, from prior to diagnosis into long-term survivorship’.
2. In the beginning
Much of the focus in HICs has been on the impact of obesity in
children with malignant disease. While there are major con-
cerns about the increasing prevalence of obesity among chil-
dren in the general population, it poses particular risks in
those with cancer. However, the influence of weight appears
to begin early in life. Birth weight over 3.5 Kg has been
associated with an increased risk of ALL and AML [9], a risk
refined more recently as relating to ALL and high ‘proportion
of optimal birth weight’ [10]. Given the robust evidence that
leukemogenesis can begin ante-natally [11], there is an
obvious question about the effect of high birth weight on
this process. The relationship to ALL is more that of acceler-
ated fetal growth, leading to the suggestion that the biologi-
cal correlate with a heightened risk of ALL is mediated by

CONTACT Ronald D. Barr rbarr@mcmaster.ca Division of Hematology and Oncology, Department of Pediatrics, McMaster University, Hamilton, Ontario,
Canada
© 2020 Informa UK Limited, trading as Taylor & Francis Group
2 R. D. BARR AND E. J. LADAS
Article highlights
● In children with cancer both over- and under-nutrition compromise
clinical outcomes, including the prospects for survival.
● Metrics using body weight e.g. BMI are limited and often provide
inaccurate assessments of nutritional status in these children; arm
anthropometry is preferable.
● Measures of body composition, such as dual-energy X-ray absorptio-
metry, can provide accurate estimates of fat mass, lean body mass,
and bone mineral mass.
● Circumstances in low- and middle-income countries (LMICs), where
the great majority of children with cancer live and undernutrition is
prevalent, are especially challenging.
● In LMICs, the genetic, environmental, and dietary diversity offers
many opportunities for research on nutrition in children with cancer.
A major investment will be made in studies of the gut microbiome
in this population, which could lead to effective interventions and
improved clinical outcomes.
Table 1. Objectives of the first Puebla workshop, 1997.
1. To develop a consensus on the nature and magnitude of the challenges
2. To explore possible solutions
3. To set goals and priorities in research
Table 2. Key educational messages to health professionals.
● Malnutrition is an adverse prognostic factor in children with cancer
● Effective cancer therapy contributes to nutritional morbidity
● Serial monitoring of nutritional status is an essential component of care
● Early, effective nutritional support is a pre-requisite in the maintenance of
health and health-related quality of life in children with nutritional
deficiencies.
● The importance of the ‘rules of evidence’ in assessing both safety and
efficacy in the use of ‘alternative’ therapies must be explained and
stressed.
Table 3. Key educational messages for the families of children with cancer.
● Maintenance of adequate nutritional status makes an important
contribution to health and health-related quality of life.
● There is no evidence that nutritional support ‘feeds the tumor’
● When use of ‘alternative’ therapies is suggested, a framework of agreement
should be developed between the family and health-care professionals,
perhaps implementing a role for surrogates for health professionals and
other advocates for families.
Table 4. Research priorities.
● Design and evaluation of nutritional interventions during and following
cancer therapy, including ‘alternative’ holistic therapies, with the following
outcome measures: nutritional status, toxicity (by conventional criteria as
outlines by WHO), pharmacology, survival, monetary costs, and health-
related quality of life.
● Mechanisms of cachexia and anorexia of cancer
● Epidemiology of possible causes of neoplasia and sources of prevention in
the diet.
● Long-term consequences of late nutritional morbidity in survivors of
childhood cancer.
insulin-like growth factors (IGFs) [12] that are known to be
involved in normal and malignant hematopoiesis [12]. As
noted by Milne et al, ‘Associations observed between acceler-
ated fetal growth and risk of other childhood cancers suggest
that the proliferative and anti-apoptotic effects of IGFs may
also be involved in their development’ [10]. Obesity in later
childhood and early adolescence has been associated with the
development of pancreatic cancer in adult life [13].
3. More on obesity
The influence of obesity on clinical outcomes in children with
acute leukemias has been a major focus of attention. Lange et al
first described a higher rate of treatment-related mortality in
children with AML who were obese at diagnosis than in those
who were not [14]. Butturini et al then reported that, in children
with ALL who were obese at diagnosis, their event-free survival
(EFS) and overall survival (OS) rates were shorter than in non-
obese children [15]. The results from international consortia have
been inconsistent with respect to associations between obesity
and survival in children with acute leukemia. No studies have
shown an increased risk of infections in overweight or obese
children with ALL [16], except for two retrospective studies in
single institutions, one reporting that obesity was a risk factor for
urinary tract infections [17] and the other that obesity was asso-
ciated with admissions for fever and neutropenia during the pre-
maintenance phases of therapy in a univariate analysis [18].
A meta-analysis has been performed by Orgel et al [16]. This
revealed that a higher body mass index (BMI) was associated
with a significantly increased mortality rate, poorer EFS and
a statistically non-significant trend toward greater risk of relapse
in children with ALL [16]. Furthermore, obesity during remission
induction therapy is an independent predictor of minimal resi-
dual disease (MRD) in ALL [19]. In children with AML, a higher BMI
has been associated with poorer EFS and OS [20]. However,
a more recent report described a lack of association of BMI at
diagnosis with MRD, cumulative incidence of relapse/refractory
disease or EFS [21]. In that report, obesity was associated with
increased treatment-related mortality and less salvage after
refractory disease or bone marrow relapse.
High BMI has been linked to other treatment-related toxici-
ties, including high rates of fatal infections in children with
AML [22,23], osteonecrosis (especially in females) in ALL [23],
hypertension, hyperglycemia, infection, hepatotoxicity and pan-
creatitis in children with ALL [24], and thrombo-embolism in
those with solid tumors but not leukemias [25]. What can explain
these observations? With respect to disease refractoriness, pro-
gression and relapse limiting prospects for survival, the role of
IGFs again may play a role [26]. It is plausible that the pharma-
cokinetics of cancer chemotherapeutic agents are modified in
patients who are overweight/obese, but there have been no
adverse impacts on clinical outcomes in the setting of a formal
clinical trial [27]. The adverse effect of obesity at diagnosis on EFS
in ALL has been reported to persist in patients who remain obese
for more than 50% of the time between the end of induction and
the start of maintenance therapy, although this risk is eliminated
if obesity is reversed [28]. Conversely, children in a high-income
country who were malnourished at diagnosis with a variety of
cancers had poorer prospects for survival [29].
4. Limitations of BMI
Any measure based on body weight, including BMI, does not
distinguish muscle from adipose tissue [30]. In children with

Table 5. Methods for measurement of body composition.
Neutron activation
Total body potassium (body cell mass)
Deuterium dilution (total body water)
Air displacement plethysmography
Bioelectrical impedance assessment
Dual energy x-ray absorptiometry
Magnetic resonance imaging
Ellis K. Physiological Reviews 2000; 80: 649-680
cancer body weight may be influenced considerably by tumor
mass, so the use of such measures risks under-estimating under-
nutrition [31]. Among the numerous techniques used to
determine body composition (Table 5), dual-energy x-ray absorp-
tiometry (DXA) has found favor as a clinical gold standard [32].
Bioelectrical impedance analysis (BIA) has advantages in terms of
portability and lower cost but is compromised in the context of
fluid retention which is common in patients receiving corticos-
teroids [33]. BIA is not interchangeable with DXA in children with
cancer, notably as reported in an LMIC setting [34], although its
utility in that setting is recognized [34]. However, DXA has limited
availability in LMICs in which the use of arm anthropometry is
much more common. The relationships of mid-upper arm cir-
cumference (MUAC) to lean body mass (LBM which, together
with bone mineral mass, equates to fat-free mass) and of triceps
skin fold thickness (TSFT) to fat mass were described in a study of
newly diagnosed children with cancer at McMaster Children’s
Hospital comparing DXA with arm anthropometry [35].
Expanding studies of body composition to children with cancer
in LMICs is clearly a priority [36].
The advantage of using arm anthropometry over weight-
for-height (WFH), the measure of acute malnutrition recom-
mended by WHO [37], was recognized in children with cancer
more than 25 years ago [31]. Brinksma and colleagues under-
took a comprehensive review of malnutrition in children with
cancer, ‘restricted to studies in industrialized countries so as to
exclude other influencing factors such as poverty and lack of
health care facilities’. These authors noted prevalence rates of
under-nutrition at diagnosis ranging from 5% in children with
leukemia to 50% in those with neuroblastoma [38]. Rates were
higher with arm anthropometry than with BMI and WFH.
A subsequent review of 46 reports containing information
from both ‘developed’ and ‘developing’ countries, information
from the latter being especially limited, observed that most
studies were undertaken at diagnosis ‘with very few exploring
nutritional status during or at the end of therapy’ [39]. Arm
anthropometry was associated again with higher prevalence
rates of under-nutrition than BMI. However, the authors were
critical of the overall quality of evidence and concluded that
‘These limitations made it impossible to perform a meta-
analysis of the associations between malnutrition and clinical
outcomes’. Efforts are underway to close this scientific gap in
our knowledge through the SIOP PODC Nutrition Committee
and the International Initiative for Pediatrics and Nutrition
(IIPAN) at Columbia University Irving Medical Center [8].
5. Under-nutrition and changes in nutritional status
The great majority of children with cancer live in LMICs [40]
where under-nutrition is prevalent in the general population
EXPERT REVIEW OF ANTICANCER THERAPY 3
and even more so in those diagnosed with cancer [41]. As
revealed in Guatemala, this is associated with socio-economic
disadvantage [42]. In a large study in Central America under-
nutrition was related to a poor survival rate, a higher rate of
treatment abandonment and a trend toward a greater risk
of relapse [43]. Few studies have examined the relationship
of under-nutrition to outcomes in children with cancer in HICs.
In a report from the Netherlands, under-nutrition at diagnosis,
defined by BMI and present in only 5% of children, was
associated with a lower survival rate [29]. In the United
States, undernutrition has not been associated with poorer
outcomes in pediatric ALL; however, most of the studies
were likely underpowered to detect an effect due to the low
prevalence of under-nutrition at diagnosis.
There have been few studies of changes in body composi-
tion during treatment and most of them have been in children
with ALL in whom changes occur early with an increase in BMI
reported by the end of induction therapy [44,45]. In the US,
Hispanic children appear to be at particular risk of worsening
obesity during treatment [46]. However, a rise in BMI may mask
a loss of muscle mass (sarcopenia) that has been described in
children with ALL [47–50], occurring early in therapy with
incomplete recovery by the end of treatment [48]. Sarcopenia
appears to be a consequence of chemotherapy in these chil-
dren [50] and comes with significantly greater risk of severe
adverse events during remission induction, including invasive
fungal infection [50]. Long-term survivors of ALL in childhood
also exhibit sarcopenia [51].
Children with solid tumors treated with intensive che-
motherapy experience marked weight loss [52,53], and mal-
nutrition (under-nutrition) is especially common in children
with medulloblastoma [54]. It should be noted that these
studies did not undertake separate assessments of muscle
and adipose tissue. A recent systematic review highlights the
paucity of information on the relationship of nutritional status
to clinical outcomes in children with solid tumors [55].
6. A focus on bone mineral mass
Approximately 40% of bone mineral mass is accumulated in
childhood and adolescence and it is affected adversely by
cancer and its treatment in this age group [56]. Osteopenia
and osteoporosis have been defined in children as bone
mineral density (BMD) Z scores of −1.0 to −2.0 and less than
−2.0, respectively, [57]. Most studies in children with cancer
have been in those with ALL. Osteopenia is often evident at
diagnosis [58] and worsens with the onset of treatment [59].
Vertebral fractures are common and often unrecognized clini-
cally [60]. Orgel and colleagues have examined this loss of
bone mineral [61] using both quantitative computed tomo-
graphy (QCT) and DXA. QCT has the advantages of distinguish-
ing compact/cortical bone from the trabecular/cancellous
counterpart, which is much more active metabolically, and
determining volumetric (v) BMD instead of areal BMD available
from DXA. Loss of vBMD occurred during remission induction.
Compact/cortical bone mass was affected much less but
revealed thinning associated with the expansion of the medul-
lary cavity. Surrogate measures of bone modeling in children
with ALL have shown bone resorption exceeding bone
4 R. D. BARR AND E. J. LADAS
formation [62]. This imbalance, which results in loss of bone
mineral, is due mainly to corticosteroids and methotrex-
ate [56].
Osteopenia in children with cancer is not limited to those
with ALL, having been described in those with solid tumors [63]
as well as brain tumors. In the latter, it has been associated with
an adverse effect on health-related quality of life [64].
7. Nutritional status after completion of therapy
The literature on adverse sequelae (late effects) in children
with cancer who have completed therapy is dominated by
reports from HICs, many of which are focused on obesity
and the attendant risk of cardiovascular morbidity alone or
as part of the metabolic syndrome. In this regard, the impor-
tance of determining adiposity by studies of body composi-
tion has been emphasized [65]. However, there is a plethora of
late effects in such long-term survivors; these are, in numerous
instances, more common in those treated as adolescents and
young adults than as children [66]; and a case has been made
for the establishment of large international cohorts to enable
substantive studies [67]. Comprehensive models of care have
been proposed [66]. With respect to nutritional morbidity,
these emphasize not only the role of healthy diets but also
the importance of physical activity [68]. Clinical trials of appro-
priate interventions are essential [69].
8. Responding to the challenges in LMICs
The SIOP PODC Nutrition Working Group and IIPAN have
devoted attention to the prevalence and severity of under-
nutrition, as well as the prevalence of cancer, and the attendant
morbidity and mortality in children in LMICs [70–72]. It began
Figure 1. Participants in the workshop on nutrition and children with cancer at the post-graduate institute for medical education and research, Chandigarh, India.
with an examination of the nutritional practices in LMICs relat-
ing to the care of children with cancer [73] which highlighted
the need for enhanced education on nutrition and adoption of
tools for assessing nutritional status by dieticians, physicians,
and nurses. This prompted a framework for adapted nutritional
therapy [74] and a measure of the capacity to provide nutri-
tional care in pediatric oncology units in India [75]. In turn, an
algorithm was developed and tested at the Post Graduate
Institute of Medical Education and Research (PGIMER in
Chandigarh, India) [76,77] for delivery of nutritional support
(Figure 1); using the algorithm produced better nutritional out-
comes than the institutional standard of care [77].
The need for such an approach is exemplified in Malawi
where almost all children with cancer (95%) are severely mal-
nourished at diagnosis, as assessed by arm anthropometry [78].
Children in North America do not exhibit such malnutrition; for
example, fewer than 5% of those with Wilms tumor have a BMI
less than the 5th percentile [79].
In Guatemala children with ALL who were severely mal-
nourished at diagnosis and remained so after 6 months of
treatment had a 5-year OS rate of 56.9% [80]. The OS of
children who were adequately nourished throughout therapy
was 79.8%. For children who were severely under-nourished at
diagnosis, but became adequately nourished by 6 months
with nutritional supplementation, the 5-year OS was 77.5%.
A subsequent report from the COG provided confirmatory
evidence of the benefit of correcting nutritional depletion [28].
However, the prices of commercial nutritional supplements
make these products unaffordable in many LMICs. Non-
governmental organizations (NGOs) such as Childhood Cancer
International (CCI https://www.childhoodcancerinternational.org)
can help to fill this gap. The deficit has generated interest in ready-
to-use therapeutic foods (RUTFs). The beneficial impact of

a peanut-based RUTF (chiponde) was shown in children with
Wilms tumor in Malawi [81], with weight gain during pre-
operative chemotherapy and a better response to treatment. At
the SIOP meeting in Kyoto in 2018, the results of a randomized
clinical trial of RUTF in India were presented [82]. Children in the
RUTF arm had significantly greater weight gain and improvements
in body composition with fewer episodes of febrile neutropenia
than controls.
Building on success is an obvious way forward and will
include:
● Continuing and expanding the education of families and
health-care professionals.
● Promoting routine assessment and surveillance of nutri-
tional status, consistent with local resources, by estab-
lished methods.
● Increased availability of nutritional supplements that are
affordable and culturally appropriate, such as ready-to-
use therapeutic foods.
● Utilization of algorithms for nutritional interventions
commensurate with local realities.
● Maintenance of a registry with standardized elements to
record nutritional care and provide a platform for clinical
research.
● Ongoing program monitoring of established nutritional
programs.
Efforts to address undernutrition in children with cancer in
LMICs must be undertaken in randomized clinical trials. This is
exemplified by interventions to minimize sarcopenia during
and after treatment, such as with creatine, used in the treat-
ment of muscular dystrophy [83] and well-tolerated by chil-
dren with cancer [84]. It is essential to include important
clinical outcomes such as tolerance of chemotherapy, infec-
tions, relapse of disease, survival, health-related quality of life
and nutritional end points like obesity.
9. An investment in future biological enquiry
Understanding the human microbiome and metabolome using
stool, urine, saliva, and human milk samples is a promising area for
study in pediatric oncology [85]. The interaction of the gut micro-
biome and metabolome with nutritional status in children can
provide a basis for studies in children with cancer in LMICs [86]. As
reported by Bhatt and colleagues [87], the gut has a critical role to
play in modifying cancer susceptibility and progression through
several mechanisms, including DNA damage and inflammation as
well as metabolites contributing to carcinogenesis and tumor
suppression. A dysbiotic gut can influence the efficacy of che-
motherapy, leading to greater toxicity and poorer clinical out-
comes [87]. A recent systematic review [88] describes the lower
relative abundance of a healthy gut microbiome in children with
cancer during treatment, with a marked increase in Enterococcus
in those with ALL and AML. This dysbiosis may resolve after the
completion of therapy. Probiotics appear to improve the gut
microenvironment and may decrease clinical side effects such as
infection. Their incorporation into supportive care regimens is
exemplified by efforts underway in the COG among children
undergoing hematopoietic stem cell transplantation.
EXPERT REVIEW OF ANTICANCER THERAPY 5
An opportunity to explore a similar role for RUTFs is exem-
plified by a report on more than 100 pairs of Malawian twins
who were discordant for kwashiorkor [89]. With the adminis-
tration of a peanut-based RUTF, the gut microbiome and
metabolic functions in the malnourished children ‘matured’
transiently but regressed when the RUTF ceased. When fecal
samples from children with kwashiorkor were transplanted
into gnotobiotic mice this led to marked weight loss which
improved, again transiently, with the administration of the
RUTF [89]. Dr. Jeffrey Gordon’s group have also studied chil-
dren with severe acute malnutrition (SAM) and moderate
acute malnutrition (MAM) in an urban slum (Mirpur) in
Dhaka, the capital of Bangladesh. In a clinical trial of thera-
peutic foods the microbiota ‘immaturity’, which characterizes
SAM and MAM, was not repaired fully and there was no
impact on severe stunting [90]. The group then undertook
an exhaustive investigation based on a subset of 54 children
with SAM [91]. A combination of chickpea, soy, and peanut
flours with banana (code named MDCF 2) was most effective
in ‘maturing’ the gut microbiota of children with MAM as well
as of gnotobiotic mice and piglets which had been colonized
with microbiota of ‘immature’ phenotype derived from fecal
samples obtained from the children before treatment. The
4-component therapeutic food produced a significant increase
in the MUAC of the piglets. MDCF 2 also generated a striking
change in the plasma proteome of children with MAM from
that typical of SAM to that of healthy children, including
reduction in the levels of acute-phase proteins and anti-
inflammatory mediators. The scene is now set for a clinical
trial of MDCF 2 in children with SAM in Mirpur. Could these
findings lead to the use of healthy fecal microbiota transplants
to remediate under-nutrition, as has been accomplished with
Clostridium difficile infection [92] which is so common in
children with cancer during periods of prolonged neutrope-
nia? Experience in children is yet limited [93].
Metabolic profiling may be another area worthy of explora-
tion. Urinary metabolic phenotypes were shown to distinguish
under-nourished from well-nourished children in Brazil [94].
Again, the relationship between nutritional status, gingival
health, and the composition of oral microbiota were examined
in children from a poor region of Argentina [95]. Significant
differences in the main periodontal pathogen species were
identified between eutrophic and under-nourished children.
Findings such as these suggest that metabolic markers of
nutritional status may be useful in predicting clinical out-
comes in children with cancer.
10. Expert opinion
Measurement of nutritional status is accomplished best by
determination of body composition, allowing accurate assess-
ment of fat mass, lean mass and bone mineral mass, each of
which is altered during treatment, especially among children
with ALL. When aggregated from DXA, these components sum
almost exactly to total body weight measured directly. Simple
assessment of body composition can be accomplished by arm
anthropometry together with height and weight. The clinical
importance of accurate measurement of body composition is
6 R. D. BARR AND E. J. LADAS
not trivial, as exemplified by loss of skeletal muscle mass, the
dominant element of the sarcopenic phenotype, which results
in the frailty syndrome that presages premature aging and
susceptibility to intercurrent illnesses. Amelioration of sarco-
penia can improve health status and health-related quality of
life in adults with malignant disease. Furthermore, increased
fat confers a protective environment for leukemic cells leading
to reduced survival. Extending the availability of assessment of
body composition in LMICs will enable better understanding
of the perturbations which accompany non-communicable
diseases that are assuming increasing importance in countries
with limited resources. This is especially true among regions
with a high prevalence of malnutrition in the pediatric
population.
Malnutrition, in the forms of obesity and under-nutrition, is
well established as a cause of compromised clinical outcomes in
children with cancer. Risks to health associated with malnutrition
have been identified clearly, both during active treatment and in
long-term survivorship. However, the mechanisms responsible
for these adverse effects are as yet understood incompletely.
Nevertheless, the benefits of restoring normal nutritional status
are clear. This paradigm is being explored vigorously, with
a particular focus on the gut microbiome and the associated
metabolome and proteome. Under-nutrition in children has
been associated with increased proteolytic activity in the
gut microbiome as well as increased N-methylnicotinamide and
ß-aminoisobutyric acid in the urine, the latter reflecting meta-
bolic adaptation to reduce energy expenditure. Urinary metabo-
lite analysis may offer an easy and cost-effective tool to screen
children for under-nutrition where this problem is prevalent.
Modulation of the altered microbiome, even with simple mod-
ification of dietary composition and intake, offers the prospect of
not only correcting the aberrant microbiota but also reversing
the negative effects on health which result from the disturbed
composition of the microbial flora in the gut. These goals must
be tested in rigorously designed clinical trials.
Numerous areas of the world offer natural laboratories in
which to examine the influences of genetic, environmental,
and dietary diversities which impact the composition of the
healthy microbiome. Moreover, these variations provide
opportunities to gain insights into the changes in the micro-
biome which occur in ill-health and afford potential avenues
for remediation. Children with cancer residing in LMICs are
likely to be among the main beneficiaries of these investiga-
tions, with substantial life-years gained in improved health.
Success in this area may also correlate with reduced medical
costs over the long term.
Increasing awareness of the challenges and opportunities
in the nutritional care of children with cancer is a high prior-
ity. This demands engagement with a wide variety of stake-
holders – WHO, SIOP, IARC (International Agency for Research
on Cancer), CCI and other NGOs, and multiple levels of gov-
ernment – among them. Utilization of publications, presenta-
tions, social media, and conventional news outlets affords
obvious mechanisms. Nutrition in children with cancer, espe-
cially in LMICs, is encompassed in United Nations Sustainable
Development Goals, particularly number 2 (Zero Hunger), 10
(Reduced Inequalities) and 17 (Partnerships for the Goals). The
charge to our community of interested parties is to take
advantage of this framework in striving to achieve real pro-
gress in the nutritional care of children with cancer
worldwide.
Funding
This paper received no funding.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial conflict with
the subject matter or materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or options, expert
testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other
relationships to disclose.
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