REVIEW

Important Aspects of Nutrition in

Children with Cancer1

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Jacqueline Bauer,2,4* Heribert Jürgens,3 and Michael C. Frühwald3,5
2
Department of Pediatrics and 3Department of Pediatric Hematology and Oncology of the University Children's Hospital Münster,
Münster 48149, Germany; 4New York Obesity Nutrition Research Center, St. Luke’s-Roosevelt Hospital Center, Columbia University, New York,
NY 10025; and 5Klinikum Augsburg, Pediatrics 1, Augsburg 86156, Germany

ABSTRACT

Adequate nutrition during cancer plays a decisive role in several clinical outcome measures, such as treatment response, quality of life, and cost
of care. However, the importance of nutrition in children and young adults with malignancies is still an underestimated topic within pediatric
oncology. The importance of our work is to reinforce and indicate that malnutrition in children with cancer should not be accepted at any stage
of the disease or tolerated as an inevitable process. Unique to our manuscript is the close collaboration, the exchange of knowledge and
expertise between pediatric oncologists and a nutritional specialist, as well as the comprehension of the mechanisms during cancer cachexia and
malnutrition. We provide a critical review of the current state of research and new knowledge related to nutritional management in childhood
cancer. Adv. Nutr. 2: 67–77, 2011.

Introduction a decisive role on several clinical outcome measures such as

The survival of children with cancer has substantially in- treatment response, quality of life, and cost of care (9,10).
creased over the last decades. Major reasons for this are, We provide a critical review of the current state of re-
among others, progress in the early detection, refined multi- search and knowledge related to the nutritional manage-
modality treatment, and enhancements of supportive care, ment in childhood cancer.
including prevention and efficient management of infec-
tions. Furthermore, multicenter trials guarantee a high de- Definition and prevalence of malnutrition in
gree of complete data and quality assurance (1). However, childhood cancer
despite continuous progress in the field, the disease itself Malnutrition is an unspecific term used to define an inade-
and associated therapies carry the burden of an array of ad- quate nutritional condition. It is characterized by either a
verse late effects (2). deficiency or an excess of energy with measurable adverse ef-
The literature suggests that up to 46% of children and fects on clinical outcome. Malnutrition describes the conse-
young adults with cancer experience malnutrition due to quences of insufficient protein-energy intake. An adequate
numerous tumor- and treatment-related factors (3–5). It is protein-energy balance is a prerequisite for age-appropriate
recognized that a diminished nutritional status may be a growth and maintenance. Malnutrition also comprises cir-
contributing factor for decreased immune function, delayed cumstances of elevated energy supply resulting in overnutri-
wound healing, and disturbed drug metabolism influencing tion with an increase in adipose tissue.
prognosis (6,7). Children with cancer are particularly vul- Even though malnutrition has been defined or described
nerable to malnutrition, because they exhibit elevated sub- in many ways, no consensus exists regarding a specific defi-
strate needs due to the disease and its treatment. At the nition to identify children at risk (11,12). The WHO recom-
same time, children have increased requirements of nutri- mends the weight-for-height index to assess the nutritional
ents to attain appropriate growth and neurodevelopment status of children and adolescents (13). However, it is pro-
(8). It has been demonstrated that adequate nutrition plays posed that a loss in body weight of $5% constitutes acute
malnutrition and a height-for-age value below the 5th per-
centile may reflect chronic undernourishment in children
1
Author disclosures: J. Bauer, J. Jürgens, and M. C. Frühwald, no conflicts of interest. (4). Ironically, many children suffering from cancer do not
* To whom correspondence should be addressed. E-mail: [email protected]. meet these criteria. Particularly those with large solid

ã2011 American Society for Nutrition. Adv. Nutr. 2: 67–77, 2011; doi:10.3945/an.110.000141. 67
abdominal masses (e.g. embryonal neoplasms such as neu- explains why the provision of apparently adequate calories
roblastoma, hepatoblastoma, or Wilms tumor) may present has often been disappointing in clinical studies, suggesting
with normal weight despite severe malnutrition. Nutritional a hypermetabolic state (16). In contrast to uncomplicated
depletion may furthermore be masked in children by edema starvation, cachexia in humans with cancer is an advanced
due to corticosteroid treatment. Even if no gold standard state of wasting marked by excess depletion of skeletal mus-
definition for undernourishment in children exists, concise cle mass and adipose tissue relative to total body weight (19).
definitions are needed for the institution of preventive Metabolic and body composition changes in cancer cachexia
policies. resemble those detected in individuals with polytrauma,
Current information regarding the prevalence of malnu- acute sepsis, burn injuries, and AIDS (22,23).
trition in childhood cancer is critically influenced by several
factors: 1) different diagnostic techniques to assess the nutri- Cancer and host factors mediating malnutrition
tional status; 2) histological type and stage of malignancy The role of cytokines. Food intake is regulated in the ven-
during assessment; 3) the child’s individual susceptibility to- tromedial nucleus of the hypothalamus. Animal models

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ward malnutrition and anticancer regimens during classifi- have demonstrated that neuropeptides such as proinflam-
cation; and finally 4) the rather nonspecific definition of matory cytokines (IL1a, IL-1b, IL-6) released by tumor tis-
malnutrition. sue, immune and stroma cells, TNFa, and INFg in
Thus, the frequency of undernourishment in children combination with other mediators affect food intake and en-
and adolescents with cancer is arbitrary reported as com- ergy expenditure, resulting in the clinical syndrome of can-
mon to not existent at diagnosis. Studies report a range cer cachexia (24,25). Cytokines are transported across the
from 0 to 50% depending on the type of cancer (4,9,14). blood-brain barrier and interact with the luminal surface
It must be stressed that body weight is not a sufficiently of brain endothelial cells to release compounds that affect
and adequately sensitive marker for the detection of nutri- appetite (26). In experimental models, many other media-
tional perturbations in children with cancer. It may be af- tors for cancer-induced anorexia have been proposed. These
fected by hydration during chemotherapy and does not include leptin levels, which depend on body fat stores and
identify any long-term changes in body cell mass (15). In are inversely related to the intensity of the inflammatory re-
children with adequate or excessive body weight, lean sponse and levels of inflammatory cytokines (24). Nevertheless,
body mass loss may be concealed as fat decreases or remains studies in humans demonstrate that leptin concentrations are
unchanged while skeletal muscle is wasting. Moreover, un- not elevated in weight-losing cancer patients, suggesting that
detectable nutritional depletion of 1 or more micronutrients leptin is not involved in the initiation of anorexia (27,28).
due to decreased food intake, excessive enteral losses, or
other factors occur in normal or overweight children Energy deficits and metabolic abnormalities. It is evident
(11,14,15). that energy deficits play an important role in the progress of
the wasting syndrome in children with neoplastic diseases
Etiology and pathophysiology related to: 1) increased nutrient requirements; 2) energy los-
A number of pathophysiological mechanisms contribute to ses caused by frequent gastrointestinal dysfunction due to to
the development of malnutrition and growth failure in cancer therapy induced toxicity; 3) an excess utilization of
childhood cancer. The causes are multifactorial, including: energy sources as a result of aggressive multimodal cancer
1) complex interactions between energy and substrate me- treatments; 4) metabolic and hormonal alterations; 5) un-
tabolism; 2) hormonal and inflammatory components; controlled pain or stress from inevitable procedures; and
and 3) alterations of metabolic compartments. These result 6) disorders in appetite sensation or changes in taste (e.g.
in accelerated mobilization, oxidation of energy substrates, due to xerostomia) (3,4,8,29).
and loss of body proteins (16,17). A number of factors interfere with enteral nutrient inges-
tion, some of which are directly related to the illness (e.g. re-
Mechanisms during simple starvation lapse) or immediate complications (e.g. infections or fever)
and cancer cachexia (30). However, all these cannot exclusively explain the pro-
Anorexia is defined as the loss of the desire to eat, which fre- gression of severe wasting and energy imbalance in childhood
quently leads to minimized intake of nutrients. Cachexia is malignancy. In simple starvation, wasting is reversible when
characterized by profound and progressive wasting of lean nutritional intervention is initiated. In contrast, an increase
tissue and body fat. In prolonged fasting or starvation, in nutrient ingestion alone is not sufficient to prevent, reverse,
weight loss occurs gradually, with a relative maintenance or retard cancer cachexia (31,32).
of lean body mass at the expense of body fat as an energy Previous studies have discussed a cancer-host rivalry for
source, whereas in cancer cachexia there is an equal loss of energy nutrients, suggesting tumor-induced host variances
fat and muscle (17,18). Compensatory mechanisms during in carbohydrate, lipid, and protein metabolism (33,34),
simple starvation consist of protein conservation and a de- whereas recent trials could not corroborate this competition
crease in energy expenditure allowing prolonged survival theory indicating that there is no positive correlation be-
in the chronic fasting state (19,20). These mechanisms tween tumor size or extension and the severity of host deple-
might be lost or inhibited in cancer (19,21). This most likely tion (3,4,8,35). In some patients, malnutrition often occurs

68 Bauer et al.
early in the course of the disease. Furthermore, manifestations Impact of energy metabolism
such as alterations in appetite and substrate metabolism cannot The metabolic turnover of a child is affected by factors such
easily be explained by a cancer-host competition for energy nu- as age, gender, nutritional status, energy intake, body com-
trients. This suggests that different utilization of exogenous en- position, hormones, physical activity, body and environ-
ergy substrates by host and tumor are present. In animal mental temperature, and pharmacotherapy as well as by
models, it has been demonstrated that deliberate dietary pro- pathological conditions such as surgical stress, infections,
tein depletion results in temporarily diminished tumor growth or trauma. There is a major controversy over whether the
rates, but also in severe host malnutrition (36,37). In addition, child with cancer has aberrations in energy expenditure dif-
in experimental models, the i.v. administration of nutrients in- ferent from a malnourished noncancer or healthy child
creases tumor volume and accelerates the mitotic activity of raised by limited energy balance studies using, among others
cancer cells (38–40). It must be emphasized that neither an in- ,different diagnostic techniques and diverse treatment strat-
fluence of nutritional deprivation (restricted diets) nor a direct egies. Studies have reported normal (50,51), reduced (52),
substrate-induced stimulation and modulation of tumor-cell and elevated energy expenditures (53) in children and adults

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proliferation has ever been documented in humans (41–43). with malignancies in contrast to control groups. Additional
Findings from experimental parabiotic designs are difficult to determinants such as cytostatic drugs, cancer type, stage, sta-
transfer to the clinical setting, because animal tumor models tus, and the time of investigation appear to play a significant
differ in size and proliferation from human neoplasms and rep- role in determining whether or not an alteration of energy ex-
resent substantially different patterns of energy metabolism penditure is observed in cancer patients. The metabolic turn-
(36). It is important to note that nutritional strategies for adults over is a function of several factors and it is not uniformly
with cancer, extrapolated from animal tumor systems, are not altered in patients with cancer. It has previously been pro-
practical and suitable for undernourished children. posed that sympathetic stimulation of brown adipose tissue
or skeletal muscle may lead to increased energy expenditure
The role of energy-consuming cycles and substrate me- in the cancer-bearing host in which the causes remain unclear
tabolism. Protein disturbances comprise an increased whole (17,54).
body protein turnover, likely mediated by cytokines, a re-
duction in muscle protein synthesis, and an increase in he- Changes in body composition
patic protein synthesis (17). Accelerated lipolysis with Body composition changes during normal infancy such as var-
iations in hydration and density of body tissues are influenced
increased production of glycerol and FFA contributes to
by gender, age, pubertal status, genetic factors, nutrition, dis-
the depletion of fat stores and subsequent weight loss (17).
eases, and physical activity (55,56). The determination of
It has been suggested that the main energy source for cancer
body composition includes direct or indirect measurements
cells is the aerobic metabolism of glucose, which signifi-
of body fat, lean body mass, bone mass, and in certain in-
cantly exceeds that of normal cells producing high levels
stances the distribution of fat between the visceral or subcuta-
of lactic acids (44). Lactic acids are transported to the liver
for renewed synthesis of glucose by the Cori cycle at a neous compartments. Fat tissue has relatively uniform physical
high energy cost. The use of muscle-derived proteins for properties during aging, whereas lean tissue exhibits over time
decreases in water content and increases in protein and mineral
gluconeogenesis contributes to an additional loss of energy
composition. This leads to a decline in the ratio of extracellular
and for a further increase in energy expenditure, resulting
to intracellular water with aging.
in a catabolic state (45).
In children with cancer, body weight can be influenced by
tumor mass and hydration, particularly during chemother-
The metabolic effects of cancer and apy, masking loss of fat and skeletal muscle. The measure-
chemotherapeutic agents ment of body compartments provides useful information
Changes of hormonal factors about the nutritional status at the time of diagnosis. It iden-
During adaptation to uncomplicated malnutrition, there is an tifies subsequent changes in the functional tissue during an-
increase in catecholamines, glucagon, cortisol, and growth tineoplastic therapy presenting additional information to
hormone levels, and a decreased insulin secretion (46). Endo- those obtained from anthropometry and subjective nutri-
crine disturbances in cancer patients present in contrast to tional assessments (57,58). Body compartments play an im-
uncomplicated malnourished humans in the form of insulin portant role in the pathophysiology of cancer cachexia
resistance and as elevated secretion of growth hormone contributing, e.g., to the fatigue syndrome (59).
(47,48). The production of thyroid hormones is reduced in The distribution, absorption, metabolism, and elimina-
malnourished humans with and without cancer due to activa- tion of cytostatic drugs are influenced by body composition.
tion of the sympathetic nervous system, decreased glandular Antineoplastic agents have narrow therapeutic indices; con-
secretion, and nutritional restriction (47). Thyroid dysfunc- sequently, minor changes in drug concentration or exposure
tion after total body or cranio-spinal irradiation is well known may have a profound impact on treatment efficacy and even
(49). The physiological benefits of hormonal depression are outcome. Previous studies have shown that the majority of
likely the reduction of energy expenditure and the preserva- children with malignancies exhibit alterations in body com-
tion of substrates in simple starvation and cancer cachexia. partments during chemotherapy, with a reduction in lean

Nutrition in children and young adults with cancer 69

mass and an increase in fat (57,58). Some anticancer agents differentiated understanding of body composition changes us-
are relatively lipid insoluble and may be poorly distributed ing new technologies. Cancer types and risk factors related to
in adipose tissue (59,60). On the other hand, for several hy- the development of malnutrition are presented in Table 1.
drophilic drugs, the excess of fat mass is not available for
compound distribution and the volume distribution ad- Risk factors relating to the modalities of
justed to weight or surface area might significantly decrease cancer therapies
(61). Examining body composition alterations in response The majority of childhood neoplasms are treated by com-
to chemotherapy and radiotherapy, attention should be bined modality therapy, including surgery, radiotherapy,
paid to several interactions of cancer drugs with the muscle and antineoplastic schedules commonly providing a variety
and adipose tissues. For most cytostatics, there are limited of side effects, which may lead a child into a state of nutri-
pediatric data on the potential relationship between body tional deprivation (73,74). Each of these treatment modali-
composition and pharmacokinetics. Dose calculations based ties may produce injuries to major organ systems (liver and
on true body size in obese adult patients can be 20–30% pancreas). Furthermore, their combination may cause a po-

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higher than the medication estimated for the same individ- tentiation or a synergism of adverse effects. Multimodality
ual based on normalized or ideal body weight (62). Antican- therapies combined with the effects of the malignancy itself
cer drugs are often applied in a reduced dose in very tall or/ affect nutritional status and damage rapidly growing cells, e.
and overweight children. Nevertheless, 2 investigations have g., in the gastrointestinal tract, inducing serious and unde-
demonstrated that obese patients receiving diminished anti- sirable symptoms. As a result of intense diarrhea, vomiting,
cancer therapy may have an inferior outcome (63,64). Other mucositis, and systemic effects of therapy, affected children
researchers have detected changes in drug clearance, half- often experience a prolonged period of minimal oral intake.
life, and significant differences in the metabolism of cyclo- This contributes to fluid loss, electrolyte and trace elements
phosphamide, ifosfamide, and doxorubicin in obese cancer imbalance, and alterations of their carrier proteins, as well as
patients (65–68). Corticosteroids, important components iron and vitamin deficiency that may result in acute and
of regimens for leukemias, lymphomas, and histiocytic dis- chronic malabsorption of micro- and macronutrients (74).
eases, promote fat mass, mainly via increased energy intake, Cancer survivor studies have demonstrated that treatment
induce insulin resistance and hyperinsulinemia, and may in- with alkylating agents or anthracyclines and total body irra-
duce loss of muscle mass affecting energy balance (69). It has diation are associated with underweight (75).
been reported that overweight at diagnosis is a poor prog-
nostic indicator for children with acute myeloid leukemia Consequences of starvation in
and for female adolescents with acute lymphoblastic leuke- childhood cancer
mia (70). It is currently being discussed whether this is an Morbidity and mortality
effect of disturbed chemotherapy distribution or increased One of the first publications, almost 30 y ago, reported that
drug toxicity. The timing of appearance and differences in nutritional depletion in humans with cancer causes debility,
body compartments is not clear, whereas increased fat depo- reduction in immunocompetence and wound healing, an
sition is recognized to increase the risk of developing meta- increase in drug toxicity, and changes in psychological
bolic syndrome later in life. Underweight has adverse well-being (76,77). Since that time, a wealth of research dis-
consequences for general health (71). cussed the consequences of starvation. These primarily con-
sider the impact of weight loss in adults with malignancies. It
Risk factors for malnutrition in children has been demonstrated that the prognosis of underweight hu-
with malignancies mans with and without cancer is inferior compared with well-
Risk factors concerning the type, stage, and nourished patients (78–80). Individuals with cancer exhibiting
metastatic status of cancer pronounced weight loss demonstrate decreased survival rates
Current data suggest that malnutrition is associated with the (79), diminished response to cytostatics (79,81), prolonged
type, stage, and metastatic status of the disease as well as the hospital stays, higher rates of readmissions (82,83), and a re-
toxicity of multimodal cancer therapies (10,72). In addition duced quality of life (84,85).
to the existing classification of patients into high and low In childhood cancer, undernourishment has a significant
risk groups for undernourishment, risk factors for obesity in- prognostic weight on survival rate, especially in children with
duced by cancer agents have to be considered to facilitate the solid tumors and metastatic diseases with a high risk of body
recognition and prevention of malnutrition at an early stage store depletion (10,85,86). Inferior survival rates in children
of the disease. High risk groups for starvation comprise pa- with newly diagnosed stage IV neuroblastoma (87), acute lym-
tients with body store depletion established at diagnosis, espe- phoblastic leukemia (88), and acute myeloid leukemia (89,90)
cially children with solid tumors and neoplastic diseases with are associated with the degree of an unfavorable weight loss
advanced stage, unfavorable biology, and localization of the tu- (90,91).
mor (30,73). Undernourishment occurs less frequently in chil-
dren diagnosed with nonmetastatic tumors or those with a Long-term consequences
favorable prognosis. The term malnutrition in childhood can- Children with malignancies tolerate the acute side effects of
cer is in the process of redefinition due to an increasingly antineoplastic agents better than adults, but the growing

70 Bauer et al.
Table 1. Tumor types associated with malnutrition for pediatric oncology patients
High risk factor Moderate risk factor High risk factor
for undernourishment for undernourishment for fat accumulation
Solid tumors with advanced stages Nonmetastatic solid tumors Acute lymphoblastic leukemia receiving cranial irradiation
Wilms tumors Uncomplicated acute lymphoblastic leukemia Craniopharyngeoma
Neuroblastoma stage III and IV Advanced diseases in remission during Malignancies with large and prolonged doses
rhabdomyosarcoma maintenance treatment of corticosteroid therapy or other drugs increasing
body fat stores
Ewing sarcoma Total body or abdominal or cranial irradiation
Medulloblastoma
Multiple relapsed leukemia and lymphoma
Head and neck tumors
Post stem cell transplantation
(graft vs. host-disease)
Diencephalic tumors

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child is more susceptible to long-term diseases that have im- cohort of survivors. Interestingly, visceral fat volume is an
plications for later life (92). The number of childhood can- important determinant that has been linked to increases in
cer survivors increases every year (93). Therefore, research the risk for cardiovascular diseases and some types of cancer
into the effects of long-term consequences of modern anti- (e.g. breast, colorectal cancer) (101–105) Table 2 demon-
neoplastic therapies is in the early stages, and chronic ill- strates the short- and long-term consequences of malnutri-
nesses are now observed and detected in this cohort tion on pediatric cancer survivors.
(65,75,94–96). Comparing the BMI of pediatric cancer sur-
vivors to the general population of similar age, it has been Methods to detect and analyze in depth poor
demonstrated that survivors of specific cancer types are nutritional status in children with cancer
more likely to be underweight (BMI # 18.5 kg/m2) (75). The objective is to detect children with preexisting malnutri-
This group includes children with soft tissue sarcoma, neu- tion with a risk of substrate depletion before cancer treat-
roblastoma, non-Hodgkin’s lymphoma, brain tumors, male ment starts and worsens the nutritional status over time.
survivors of leukemia, nonamputated females with bone Common anthropometric tests involve measurements of
cancer, Wilms tumors, and survivors of Hodgkin’s disease stature, body weight, and BMI that should be measured
(75). At the same time, it has been realized that survivors on admission and at follow-up points in all affected children
of common pediatric malignancies are at risk for adult-onset so that trends can be identified. To ascertain the head cir-
diseases such as obesity, which is associated with a high risk cumference is an important aspect of nutritional evaluation,
for cardiovascular and endocrine diseases (96–98). In- especially in the young ill child, to avoid disturbances in
creased BMI ($25 kg/m2) was found in pediatric survivors neurodevelopmental outcome throughout critical periods
of acute lymphoblastic leukemia with an age of fewer than 4 of brain growth. Currently, new noninvasive and inexpen-
y at diagnosis receiving cranial radiation therapy and in chil- sive methodologies to longitudinally and accurately analyze
dren with brain tumors, especially in craniopharyngeoma changes in body compartments are successfully applied in the
survivors (75,99,100). Obesity was analyzed in these studies pediatric clinical setting (Table 3). Selected complementary
by determining BMI. One may speculate that if employing biochemical markers such as plasma protein, pre-albumin,
other techniques to more accurately quantify body fat con- retinol-binding protein, transthyretin, and transferrin have
tent, the incidence of obesity could be much higher in this restricted usefulness in the recognition of malnutrition in

Table 2. Short- and long-term consequences of malnutrition on the pediatric cancer survivor
Short-term consequences Long-term consequences
Wasting of muscle and fat mass (3,15) Growth impairment, reduced final height (56,75)
Decreased tolerance of chemotherapy (30,67) Decreased long-term survival in several tumor types (78–80)
Unfavorable response to chemotherapy (29,30,76,77) Impact on motor, cognitive, and neurodevelopmental
impairment (95)
Treatment delays (76,77,81) Risk for metabolic syndrome (93,96)
Fatigue (29,59) Risk for secondary cancers (106–108)
Biochemical disturbances (anemia and Risk for aging (101–105)
hypoalbuminemia) (29)
Delayed recovery of normal marrow function (88–91) Increased mortality rate (79,68)
Changes in body composition (75,90,91) Retardation of skeletal maturation (109)
Drug dose alteration (65–68) Abnormal bone mineral density (109)
Decreased quality and productivity of life (84,85) Decreased quality of life (65,71)
Greater levels of psychological distress (90,91)
Higher susceptibility to infections (89,90)

Nutrition in children and young adults with cancer 71

Table 3. ethods to detect and analyze nutritional status and alterations in the pediatric oncology population
Methods Screening Comments
Body weight Daily, weekly Alone; no information of nutritional status
Height/length Daily, weekly Alone; no information of nutritional status
Head circumference Monthly Especially in infants under 3 y; brain development
BMI Biannually Body weight (kg) divided by height in meters squared;
inaccurate
Body composition tools Monthly
Bioelectrical impedance Rapid, easy, inexpensive, portable but sensitive to
hydration and temperature
Dual X-ray absorptiometry Accurate, but exposure to radiation
Isotope dilution method Expensive
Energy expenditure Weekly, monthly Determine noninvasive resting energy expenditure.
Indirect calorimetry Provide understanding of energy and
substrate requirements

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Stool analysis Weekly, monthly Analyses of carbohydrates and protein stool losses.
Determination of energy losses using bomb-calorimetry

children with cancer and in critically ill children due to the body composition tests, and evaluation of energy intake and
fact that these variables are influenced by fewer inflamma- losses are helpful in all children with cancer to prevent and
tions and infections (110,111). Chemotherapy and recurrent potentially treat malnutrition. These methods should be
episodes of sepsis may deplete the body of the essential used repeatedly for surveillance and for optimal dietary sup-
macro- and micronutrients needed for appropriate growth port during the entire duration of the disease (Fig. 1).
and metabolism, especially zinc (112). Recently developed
nutritional risk scores for adults and children should be a Nutritional support for children with cancer
part of the evaluation of malnutrition in patients with cancer Criteria for nutritional interventions
(113–115). The determination of individualized energy ex- At the present time, no universally agreed specific substrate
penditure provides an understanding of the precise energy requirements, criteria for, timing of, and duration of nutri-
and substrate requirements during cancer treatment, mini- tional interventions exist in pediatric oncology. There is an
mizing the risk for under- and overnutrition. Enteral analyses ample array of dissimilar approaches with limited efficacy
of substrate losses through stools for the calculation of energy for prevention and early treatment of growth failure in chil-
needs adapting nutritional support to individual intestinal dren with cancer (8,116,117). Several nutritional recom-
permeability are useful in children with marked intestinal mendations are based on ideal body weight, BMI, and
complications. A close link of anthropometric, laboratory, estimated energy needs without considering changes in

Figure 1 A screening schedule for nutritional status after diagnosis, including a classification in risk groups for undernutrition and fat
accumulation in children undergoing cancer therapies is demonstrated. We strongly recommend an adaptation of substrate intake
according to current requirements.

72 Bauer et al.
body compartments to capture muscle wasting and body of enteral absorption and no response to dietary supple-
mass depletion. Weight loss is a rather poor predictor of un- ment. However, emaciation should be anticipated early
dernourishment that reflects past rather than current nutri- and induce parenteral nutrition. The literature offers few
tional status. The primary objectives of nutritional clinical trials studying the optimal timing and efficacy of
interventions in pediatric oncology should be: the mainte- supplemental parenteral nutrition as well as the benefit
nance of body stores as close to the ideal as possible, mini- and outcome of children with malignancies (121,122).
mization of wasting, promotion of appropriate growth Most studies have been conducted in adults, presenting con-
development, and providing a good quality of life. troversial results and recommendations in the use of total
Nutrition strategies are indicated in all affected children, parenteral nutrition for patients undergoing hematopoietic
beginning with the diagnosis of cancer to prevent and/or re- stem cell transplantation (123,124). The potential complica-
store abnormalities in growth development before nutri- tions of parenteral nutrition include risks for infection, met-
tional and general status are severely compromised. These abolic disorders, hepatotoxicity, and reduction of oral intake
should be integrated into cancer treatment protocols start- (119). Exogenous glutamine application appears to play a

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ing directly after admission independent of the initial body role in diminishing the detrimental effects of anticancer
weight to establish the essential role of adequate nutrition drugs on the gastrointestinal mucosa. Furthermore carnitine
in the mind of the child and parents. The assessment of supplementation has been suggested to improve the cancer
the nutritional status is indispensable to stratify the child fatigue syndrome by influencing nutritional and immuno-
into nutritional risk groups in view of actual nutritional con- logical parameters (125,126).
dition and the extent of the disease, considering psycholog- Recently, the management of cancer cachexia has been
ical and socioeconomic aspects as well as the prescribed supplemented by new therapeutic strategies that may help
multimodal procedures for each tumor type. According to increase lean mass or treat the cytokine-induced catabolism
these factors, an individualized nutritional care plan may of skeletal muscle by distinguishing specific mediators of
be initiated. Absolutely desirable is the multidisciplinary muscle atrophy and the identification of sensitive bio-
management including close communication and collabora- markers of protein degradation (127). An interest for the
tion between the child, family, and the medical team to de- improvement of agents that promote muscle anabolism
termine together the expectations for dietary support as well has recently been verbalized (127). Several agents are under
as to develop further objectives. The expertise of a medical clinical investigation and some of them are in clinical trials
specialist in pediatric oncology nutrition is useful under for adult patients (127,128). Currently available therapeutic
these circumstances. We recommend monthly evaluation approaches are megestrol acetate, a synthetic derivate of pro-
to test the efficacy of the implemented nutritional tools us- gesterone; anabolic steroids, such as testosterone derivatives;
ing the methods described above. and the peptide hormones ghrelin and ghrelin agonists
(127–129). The use of these agents is critical in children con-
Nutritional strategies (parenteral and cerning the associated side effects on a growing and imma-
enteral nutrition) ture organism. However, there are currently no drugs
It is without doubt that the enteral route is the preferred and approved for the prevention or treatment of cancer cachexia.
safest way for the provision of nutrition in any child with an
undamaged and functional gastrointestinal tract, preventing Methods of enteral nutritional support (tube feeding
intestinal atrophy, toxicity, and complications of i.v. infusion and percutaneous endoscopic gastrostomy)
(118). Depending on gastric tolerance and pretenses of the Algorithms for nutritional strategies in children and adults
child depending on family participation, an individualized with malignancies have been proposed in the literature
nutritional schedule should be prepared. The selection of with the objective to treat rather than to anticipate weight
further means of support depends on the capability of oral loss (8,116,120,130,131). The application of nutritional pro-
intake, gut stability, absorption rate, and the possibility of tocols may be useful in advance for selecting those children
expected adverse effects induced by cytostatics (e.g. severe who are at high risk for malnutrition during antineoplastic
mucositis). Contraindications to enteral feeding in pediatric therapies. Energy requirements may be based on published
oncology are similar to those in other diseases or metabolic pediatric nutritional guidelines (117–119). Specific and sci-
disorders such as intestinal obstruction, permanent vomit- entifically based recommendations for children with cancer
ing, or acute hemorrhage (119). If oral or any kind of enteral are not yet available. High-energy protein formulas and liq-
tube feeding is not possible, parenteral nutrition is indicated uid supplements are offered to increase energy density in pe-
without delay. A latency of 3–7 d, as suggested by some re- diatric patients, but with less success and poor tolerance
ports (120), to initiate parenteral energy supply could be un- because of taste and smell perception. A balanced diet
favorable in children who have on preadmission evidence of with sufficient proteins and high energy levels is required
protein-energy depletion or/and a history of lower food in- to prevent an extreme overload of carbohydrate and fat con-
take. The aim of providing partial parenteral support is to sumption, as seen in many children with cancer. Children
meet nutrient requirements until the child tolerates oral in- with painful sequel (e.g. severe mucositis or vomiting)
take or tube feeding. Complete parenteral nutrition support may tolerate gastric or jejunal tube feeding better than
should be reserved for short periods in children with failure oral (e.g. via nasogastric tube) when the nasopharynx may

Nutrition in children and young adults with cancer 73

Table 4. Nutritional strategies for children with cancer illnesses for pediatric cancer
Nutritional strategies Indications survivors. Because cancer mal-
Enteral route In all patients with functional gastrointestinal tract nourishment is not unique to
Meeting .95–100% of estimated energy needs underweight children (96–98),
Tube feeding (nasogastric) Inability to ingest full energy requirements (.90%) through
an assessment of body compo-
oral diet for 3–5 d
Severe mucositis ,3 d sition is important for the char-
PEG jejunostomy Inability to meet full energy needs through tube diet for acterization of the severity of
3–5 d the condition. Furthermore,
Severe vomiting for 3–5 d the effects of malnutrition can
Weight loss despite tube feeding
be surveyed. In adults with can-
Parenteral nutrition Altered gastrointestinal absorption for 3–5 d
Severe vomiting and diarrhea cer, various agents are in devel-
Severe pancreatitis opment, including medications
Intestinal manifestation of graft vs. host disease that inhibit the mediators (in-

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Paralytic ileus flammatory cytokines) and tu-
mor-induced inflammation
be bypassed. A percutaneous endoscopic gastrostomy (PEG) that occur during cancer cachexia (17,18). Current treat-
is a successfully used method with high acceptance by oncol- ment options, including drugs (127–129) or anabolic agents,
ogists, children, and parents demonstrating somatic improve- for cancer malnutrition in pediatric oncologic patients are
ments and reduced family frustration due to eating problems limited due to adverse side effects in a growing and imma-
(132,133). The placement of a PEG tube is indicated when ture child.
oral ingestion is not sufficient to cover the daily energy needs.
Table 4 demonstrates nutritional strategies. Acknowledgments
J.B. was responsible for contact; J.B. and M.C.F. designed
Conclusions and conceived the study; J.B. and M.C.F. wrote the manu-
The importance of nutrition in children and young adults script; and H.J., J.B., and M.C.F. critically discussed and cor-
with cancer is an underestimated topic within pediatric on- rected the study. All authors read and approved the final
cology. There are new, inexpensive, and noninvasive tech- version of the paper.
niques for the evaluation of the nutritional status providing
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