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Chapter 16
Paediatric oncology
Evelyn Ward
Introduction
With continued improvement in the treatment of childhood cancers, the role of nutrition
has become increasingly important in terms of treatment, supportive care and treatmentrelated morbidity. Childhood cancers generally refer up to the age of 15 years; however,
older adolescents and young adults up to the age of 24 years who develop paediatrictype malignancies tend to be treated on the same protocols. Advances in treatment have
achieved an overall cure rate for paediatric malignancies that now exceeds 70% in developed countries, with figures up to 80% now being quoted (Landier & Bhatia, 2008;
O?Leary et al., 2008). As survival rates increase, the need to maintain growth and development for normal life is paramount. Advances in use of intensive multimodal therapy
and combination chemotherapy and/or the primary diagnosis frequently result in nutritional depletion. It is well documented that malnutrition is a common complication of
paediatric malignancy and its treatment (Mauer et al., 1990; Andrassey & Chwals, 1998).
Studies have highlighted malnutrition contributing to a reduced tolerance to treatment,
and protein calorie intake may affect the sensitivity to chemotherapy agents (Charland
et al., 1994; Gomez-Almaguer et al., 1995; Ladas et al., 2005). Malnutrition is associated
with a reduced immunity and a higher risk of infectious complications in children receiving anticancer therapy (van Eys et al., 1980; Taj et al., 1993). However, the evidence
of malnutrition at diagnosis or during treatment on overall survival is controversial and
may depend on the disease and its extent (Weir et al., 1998; Yaris et al., 2002; Sala et al.,
2004).
The importance of providing safe, appropriate and effective nutritional support for
the child undergoing treatment for paediatric malignancy is now well recognised as an
important part of supportive care to enhance therapy, decrease complications and improve
immunological status.
Nutrition and Cancer, First Edition, edited by Clare Shaw
C 2011 Blackwell Publishing Ltd
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Types of childhood cancers
The types of cancers seen in children can be divided into three main groups:
1. Leukaemias
2. Lymphomas
3. Solid tumours
Leukaemias
Leukaemia is the most common malignant disease in infancy and childhood and accounts
for one-third of all childhood cancers. Acute lymphoblastic leukaemia (ALL) is the most
common form of the disease in childhood, with its incidence highest at 3?7 years of age,
falling off by 10 years (Hoffbrand et al., 2006). Males are affected more than females.
Approximately 80% of ALL in children is the precursor B-cell origin, about 15% is T-cell
and 5% is more mature B-cell derived. Acute myeloid leukaemia (AML) is the second
most common leukaemia in childhood and accounts for 10?15% of the leukaemias in
childhood, with 15?20% of the cases occurring in patients with predisposing conditions
that include certain congenital syndromes such as Down?s syndrome or DNA instability
syndromes such as Fanconi anaemia (Forestier & Schmiegelow, 2005). Although rare,
accounting for 15% of leukaemias, chronic myeloid leukaemia can occur in older children.
Five-year survival rates are around 87% in children with ALL and 65% for those with
AML (CCLG, 2008). It should be noted however that prognosis in infants with ALL is
poor.
The leukaemias are fatal unless treated, and clinical features at presentation include
bone marrow failure ? anaemia (pallor, lethargy), neutropenia (fever, malaise), thrombocytopenia (bruising, purpura, bleeding gums, nose bleeds) and organ infiltration ? tender
bones, lymphadenopathy, splenomegaly and hepatomegaly.
The current treatment protocol for children in the United Kingdom includes initial
induction chemotherapy aimed at achieving remission. The protocol is graded as regimen
A, for those children with standard risk disease; regimen B, for those children with
intermediate risk disease; and regimen C, for those children with high-risk disease, which
are children who have not responded to initial treatment or those with poor cytogenetics
(Philadelphia chromosome t(9;22), near haploidy (?44 chromosomes), iAMP21,t(17;19)
and MLL gene arrangement). All these are rare. Following induction, the next phase of
treatment is consolidation (intensification) and central nervous system (CNS) treatment
aimed to completely reduce or eliminate the tumour burden and to prevent or treat CNS
disease. The number of intensification blocks is one to two in children depending on
treatment regimen and randomisation. Maintenance chemotherapy is then given for up to
2 years in girls and up to 3 years in boys. Bone marrow transplantation is used in children
with ALL that is likely to recur following standard treatment or those with relapsed disease.
Treatment for AML is primarily with the use of intensive chemotherapy, generally
given as four blocks, 3 weeks apart or on blood count recovery. Similarly, bone marrow
transplant is used for children with AML, which is likely to recur or for those who have
relapsed disease.
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Lymphomas
Lymphomas encompass approximately 10% of all childhood cancers and can be divided
into two main groups: non-Hodgkin?s lymphomas (NHL) and Hodgkin?s lymphomas.
r Non-Hodgkin?s lymphomas account for 60% of lymphomas and are a large group of
lymphoid tumours. Those most commonly seen in children include B-cell NHL and
T-cell NHL. The majority of patients present with asymmetric enlargement of lymph
nodes in one or more peripheral lymph node regions. Those with diffuse bone marrow
disease present with anaemia, neutropenia or thrombocytopenia. Five-year survival
rates are around 85% (CCLG, 2008). Chemotherapy is the most important treatment
for children with NHL. High-dose chemotherapy and autologous stem cell transplant
are sometimes used in relapsed disease.
r Hodgkin?s lymphoma accounts for 40% of lymphomas. Presenting symptoms are usually painless cervical and/or mediastinal adenopathy. Symptoms also generally include
fever, night sweats, weight loss, fatigue and anorexia. Hodgkin?s disease is more common in adolescents than younger children. Five-year survival rates are around 95%
(CCLG, 2008). Treatment is by chemotherapy, with radiotherapy restricted to those
with extended disease or lack of response to chemotherapy. Some relapsed patients
may require high-dose chemotherapy and autologous stem cell transplant.
Solid tumours
Solid tumours account for approximately 45% of all malignant disease in children. The
most common solid tumours seen in children are as follows:
r Brain tumours: Brain and spinal CNS tumours are the most common solid tumours
that occur in children. Medulloblastoma is the most common CNS tumour in children.
Signs and symptoms of CNS tumours are generally caused by increased intracranial
pressure and include headaches, vomiting, drowsiness, irritability, fits and diplopia.
Other symptoms may include weakness or unsteadiness on walking. Treatment varies
depending on the underlying tumour, but surgery, radiotherapy or chemotherapy may
be used alone, or in combination. Five-year survival rate for medulloblastoma is about
80% for children with standard risk disease and between 40 and 60% in those with
high-risk disease (i.e. with disseminated disease or have undergone a subtotal resection)
(Packer et al., 1994; Crawford et al., 2007).
r Neuroblastoma: This is most common before the age of 5 years and accounts for 8% of
all childhood cancers. It arises from the neural crest tissue in the adrenal medulla and
elsewhere in the sympathetic nervous system; therefore, it most frequently occurs in
one of the adrenal glands but can also occur alongside the spinal cord in the neck, chest,
abdomen or pelvis. Most children present with an abdominal mass, loss of appetite,
lethargy and bone pain. At presentation the tumour mass can often be large and complex.
Treatment and survival depend on the stage of the disease. Recently, there have been
further clarified risk groups, leading to very low, low, intermediate and high-risk group
patients, with treatment for some of the low risk and very low-risk group patients being
observed only as the disease can show spontaneous regression in very young infants.
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Those with high-risk disease treatment involve chemotherapy, surgery, radiotherapy
and in some cases high-dose chemotherapy and autologous stem cell transplant. The
use of 13-cis-retinoic acid is being used as a differentiating agent to reduce the risk of
relapse in high-risk patients. Five-year survival rate is currently around 64% (CCLG,
2008).
Wilms? tumour: It is most commonly seen in children under the age of 5 years, with
the majority presenting with a large abdominal mass. Other symptoms may include
poor weight gain and loss of appetite, blood in the urine and high blood pressure. It is
a congenital malignant kidney tumour, which can be bilateral. Treatment depends on
histology and the stage of the tumour but usually involves surgery, chemotherapy and
occasionally radiotherapy. Prognosis for Wilms? tumour is good with 5-year survival
rates around 90% (CCLG, 2008).
Rhabdomyosarcoma: It is the most common type of soft tissue sarcoma in children,
which develops from muscle or fibrous tissue. It can develop at any age but is more
common in children under 10 years. There are two main subgroups: embryonal (80%)
and alveolar (20%). Rhabdomyosarcoma occurs at a wide variety of primary sites
but is most common around head and neck sites. Other sites include genitourinary and
occasionally limb, chest or abdominal wall. Treatment depends on tumour size, position
and whether metastatic disease is present but involves chemotherapy, surgical resection
and sometimes radiotherapy. Five-year survival rate is around 65% (CCLG, 2008).
Ewing?s sarcoma and peripheral primitive neuroectodermal tumour (pPNET): Ewing?s
sarcoma is a type of bone tumour. Any bone can be affected but is more common
in the pelvis, femur or shinbone. It can occur in the teenage years but is also seen
in younger children. Persistent localised bone pain is a characteristic symptom that
usually precedes the detection of a mass. Treatment involves chemotherapy followed
by surgery, usually limb sparing, but sometimes amputation is unavoidable followed by
further chemotherapy and in some cases radiotherapy especially if surgical resection is
impossible or incomplete. Poor responders may receive high-dose chemotherapy and
autologous stem cell transplant. Five-year survival rates are around 65% (CCLG, 2008).
Treatment lasts about a year. pPNET is a soft tissue sarcoma of neuroepithelial origin,
which can be thought of as being similar to an Ewing?s sarcoma.
Osteosarcoma: This is a high-grade bone tumour, which is more commonly seen in
older children and teenagers and is more common in boys. It often occurs at the end
of bones where new bone tissue is forming and is most common in the arms or legs,
particularly around the knee. Pain and swelling around the affected bone are the most
common symptoms. Treatment depends on factors including size, position and stage of
the tumour but involves chemotherapy initially to shrink the tumour prior to surgery.
Surgery may be amputation or limb sparing surgery. Further chemotherapy is then
given and treatment lasts for about a year. Five-year survival rates are around 50?60%
(CCLG, 2008).
Retinoblastoma: This is the commonest malignant eye tumour in children, accounting
for around 3% of childhood cancers, with most occurring under the age of 5 years.
All bilateral tumours are thought to be hereditary, as are 20% of unilateral cases.
Children of affected families are screened from birth. Treatment options include local
treatment with cryotherapy, laser therapy, external beam therapy, chemotherapy, plaque
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brachytherapy and in some cases enucleation is necessary. Five-year survival rates are
over 90% (CCLG, 2008).
r Germ cell tumours: These are rare and may be malignant or benign. They arise from
the primitive germ cells, which migrate in the embryo from yolk sac endoderm to
form gonads, and therefore most tumours affect the ovaries or testes. If the tumour is
malignant and completely removed by surgery, chemotherapy may not be needed. If the
tumour cannot be easily removed by surgery or has spread then chemotherapy is given.
They are very chemotherapy-sensitive tumours, and survival is over 90% (CCLG, 2008).
Aetiology of malnutrition in children with cancer
The incidence of malnutrition in paediatric oncology at diagnosis is variable partly due to
the variation in studies conducted on different types of paediatric malignancies and variation in nutritional assessment parameters used (Sala et al., 2004). However, it is estimated
that the incidence of malnutrition ranges from 6 to 50% depending on the type, stage
and location of the disease (Van Eys, 1979; Donaldson et al., 1981; Carter et al., 1983).
It is estimated that malnutrition is present in less than 10% of children with standard
risk acute lymphoblastic leukaemia, but the prevalence increases to 50% in children with
advanced solid tumours such as neuroblastoma, Wilms? tumours and sarcomas (Carter
et al., 1983; Reilly et al., 1999). Malnutrition is more severe with aggressive tumours
in the later stages of malignancy, occurring in up to 37.5% of newly diagnosed patients
with metastatic disease (Smith et al., 1991). The risk of nutritional morbidity is greater
in patients with a greater tumour burden and higher treatment intensity. The initial nutritional problems resulting from the tumour are soon compounded by iatrogenic nutritional
abnormalities, the consequence of the treatment and its complications. Metabolic and
psychological factors also have a role (Mauer et al., 1990).
Metabolic factors
Cancer cachexia is complex and multifactorial, marked by early satiety, weight loss,
organ dysfunction and tissue wasting. Changes in the metabolism of fat, carbohydrate
and protein have been demonstrated in the cancer-bearing host (Rossi-Fanelli et al., 1991;
Picton, 1998). In children with cancers, the result is a cascade of metabolic events, which
are typically characteristic of the acute metabolic response. In addition to glycogenolysis
and lipolysis, this response includes a marked increase in energy expenditure, proteolysis
and gluconeogenesis. This response results in an accelerated depletion of endogenous
energy and substrate stores in the face of decreased exogenous fuel substrate provision
(Andrassy & Chwals, 1998).
Cachexia is more common in children with solid tumours at diagnosis (33%) and during treatment (57%) compared with children with leukaemia (12 and 38%, respectively)
(Picton et al., 1995). Solid tumour patients who developed cachexia during treatment were
found to have a significantly raised sleeping energy expenditure at diagnosis, whereas children with leukaemia at risk of developing cachexia had no changes in energy expenditure
at diagnosis (Picton et al., 1995). A small study of children with ALL found no significant
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difference in resting energy expenditure at diagnosis and also throughout set points in
therapy when compared to controls (Delbecque-Boussard et al., 1997). Severe weight
loss in children with leukaemia appears to be associated with more intensive treatment
regimens such as those for AML (Picton, 1998) and more recently children treated on
regimen C.
As treatment regimens increase in intensity and more treatments become available for
children with relapsed disease, the greater the number of children at risk of the metabolic
demands of their disease and treatment.
Complications of the disease and treatment
As a consequence of aggressive treatment modalities used in treating children with cancer,
most of the malnutrition seen occurs as a result of treatment. Anorexia, mucositis, vomiting, diarrhoea and alterations in taste are important contributory factors to weight loss
in children undergoing treatment for cancer (Barr, 2002). Nutrition status can deteriorate
rapidly, particularly during the initial intensive phases of treatment if nutrition support is
not provided (Coates et al., 1986; Ward et al., 2009a). Table 16.1 shows the side effects
relating to drugs commonly used in treatment of paediatric malignancies.
Psychological factors
Learned food aversions associated with links between foods consumed close to chemotherapy administration and nausea and vomiting have been demonstrated in children with
cancer along with the phenomenon of anticipatory vomiting (Bernstein, 1994). Food is
one area of treatment that both the child and parent can try to control, resulting in increased
Table 16.1 Side effects relating to drugs used in treatment of paediatric oncology
Side effect
Causative drug
Infection
Both chemotherapy and radiotherapy are known
immune depressants
Diarrhoea
Actinomycin, doxorubicin, methotrexate, cytosine
Nausea and vomiting
Actinomycin, carboplatin, cisplatin,
cyclophosphamide, doxorubicin, ifosfamide, cytosine,
etoposide, methotrexate, procarbazine, thioguanine
Stomatitis/mucositis
Actinomycin, adriamycin, daunorubicin, doxorubicin,
epirubicin, bleomycin, melphalan, methotrexate
Renal damage and nutrient loss
Cisplatin, cyclophosphamide, ifosfamide
Constipation
Vincristine
Weight gain and raised blood
glucose levels
Dexamethasone, prednisolone
Hypoalbuminaemia
L-Asparaginase
Pancreatitis
L-Asparaginase
Weight loss
?-Interferon
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tension and anxiety about food, which can lead to negative feeding behaviour and eating
becoming an unpleasant experience for both the child and their family.
Identification of nutritional risk
Assessment of nutritional status in children with cancer is a vital component of supportive care and essential for monitoring the need for nutritional intervention. Nutritional
status indices may also be a useful tool as prognostic markers of response to therapy
or toxicity (Atkinson, 2008a). Criteria used to determine malnutrition in children with
cancer differ, and despite various anthropometric measurements reflecting changes in
body composition, some of these require cautious interpretation. Accurate height and
weight measurements and the subsequent transformation to anthropometric indices are
the mainstay of nutritional assessment in children with cancer (Brennan, 2003). However, the reliability of weight-related indices is reduced in children with solid tumours,
particularly those with large abdominal tumours, for example, neuroblastoma, hepatoblastoma, Wilms? tumour, and therefore a measurement independent of tumour mass such
as mid-upper arm circumference or triceps skinfold thickness should be undertaken.
It is well documented that the determination of the nutritional risk of the child with
cancer is associated with the diagnosis of certain tumours and stages of the disease either
as a result of the underlying disease or as a result of the anticipated toxicity from the
current treatment protocol (Table 16.2) (Han-Markey, 2000; Ward, 2007). Recently, a
new child-specific, nurse-administered nutrition screening tool has been developed and
validated (STAMP ? screening tool for the assessment of malnutrition in paediatrics),
which can be used to identify the child with cancer at risk of malnutrition (McCarthy
& Dixon, 2008). However, due to the scoring system used, the vast majority of children
on active treatment will score as being high risk. A recent study highlighted that no
Table 16.2 Types of paediatric cancers associated with high or low nutritional risk
High nutritional risk
Low nutritional risk
Advanced disease during initial intense treatment
High-risk neuroblastoma
Stage III and Stage IV Wilms? tumour
High-risk rhabdomyosarcoma
Ewing?s sarcoma/pPNET
Osteosarcoma
Medulloblastoma/CNS PNET
B-cell NHL
AML
Some ALL
Infants and teenagers
Regimen B and C patients
Relapsed ALL
Bone marrow transplant patients
Allogeneic
Autologous
ALL regimen A
Non-metastatic solid tumours
Retinoblastoma
Hodgkin?s disease
Germ cell tumours
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simple nutritional measures were found to accurately identify poor nutritional status in
children treated for paediatric malignancy (Murphy et al., 2009). The following criteria
can be useful to identify children with cancer who are likely to require nutritional support
(Andrassy & Chwals, 1998):
r Total weight loss of more than 5% relative to pre-illness weight
r Weight for height less than 90%
r Serum albumin less than 32 mmol/L (in absence of recent acute metabolic stress within
the last 14 days and excluding children who have recently received l-asparaginase)
r A decrease in current percentiles for weight (or height) of two major centiles
r Adipose energy reserves as determined by triceps skinfold thickness less than fifth
percentile for age and sex
r Voluntary food intake less than 70% of estimated requirements for 5 days for wellnourished patients
r Anticipated gut dysfunction resulting from treatment for more than 5 days for wellnourished patients
r High nutritional risk patients based on tumour type and treatment regimens
r Bone marrow transplantation as a treatment for any cancer
The consequences of malnutrition are multiple and include a possible influence on
outcome, with children who are underweight at diagnosis having a poorer outcome compared to those who are adequately nourished at diagnosis (Donaldson et al., 1981; Lange
et al., 2005). Malnutrition contributes to a reduced tolerance to therapy and may also
affect the sensitivity to chemotherapy agents (Andrassy & Chwals, 1998]; Sala et al.,
2004; Ladas et al., 2005). Malnutrition may contribute to problems of drug toxicity due
to altered pharmakinetics secondary to changes in body composition and relationship between body surface area and lean body mass (Ladas et al., 2005; Tabori et al., 2005). The
relationship between malnutrition and increased risk of infection is well documented in
the child with cancer (Smith et al., 1991; Sala et al., 2004). Given the potential impact the
nutritional status and intervention can have in children undergoing treatment for cancer
nutritional assessment and early identification for nutritional support is a crucial role of
the multidisciplinary team caring for these children.
Nutritional support
Children undergoing treatment for cancer are at risk of depleted nutrient stores due to a
decreased intake or increased losses due to vomiting, diarrhoea or renal losses.
The aims of nutritional intervention are to reverse any malnutrition at diagnosis, prevent
any future malnutrition associated with treatment and to promote normal growth and
development throughout treatment. Nutritional support will improve immune competence,
tolerance to treatment and quality of life (van Eys, 1998). Successful nutritional support
requires a multidisciplinary approach to provide safe, appropriate and effective nutritional
support.
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Table 16.3 DRV for fluid, protein and energy for children
Energy (EAR)
Protein (RNI)
Weighta
(kg)
Fluid
(mL/kg)
(kcal/kg per
day)
Males
0?3 months
4?6 months
7?9 months
10?12 months
1?3 years
4?6 years
7?10 years
11?14 years
15?18 years
5.9
7.7
8.9
9.8
12.6
17.8
28.3
43.1
64.5
150
150
120
120
90
80
60
50
40
115?100
95
95
95
95
90
?
?
?
545
690
825
920
1230
1715
1970
2220
2755
2.1
1.6
1.5
1.5
1.1
1.1
?
?
?
12.5
12.7
13.7
14.9
14.5
19.7
28.3
42.1
55.2
Females
0?3 months
4?6 months
7?9 months
10?12 months
1?3 years
4?6 years
7?10 years
11?14 years
15?18 years
5.9
7.7
8.9
9.8
12.6
17.8
28.3
43.8
55.5
150
150
120
120
90
80
60
50
40
115?100
95
95
95
95
90
?
?
?
515
645
765
865
1165
1545
1740
1845
2110
2.1
1.6
1.5
1.5
1.1
1.1
?
?
?
12.5
12.7
13.7
14.9
14.5
19.7
28.3
42.1
45.4
Age
(kcal/day) (g/kg per day) (g/day)
Department of Health (1991).
EAR, estimated average requirements.
a
Standard weights for age ranges.
Nutritional requirements in children with cancer
Table 16.3 gives the dietary reference values (DRVs) for fluid, protein and energy for different age groups of children from the Department of Health Report on Dietary Reference
Values (Department of Health, 1991). The DRVs are for healthy populations of infants fed
artificial formulas and for older children consuming food. These recommendations are for
groups, not for individuals; however, they can be used as a basis for estimating suitable
intakes for the individual, using the reference nutrient intake (RNI) (Shaw & Lawson,
2007). This level should satisfy the requirements of 97.5% of the healthy population group
and is a useful starting basis for the non-catabolic, low nutritional risk child with cancer.
An estimation of the protein and energy requirements for sick children is given in Table
16.4 and can be useful when determining the protein and calorie requirements for the
catabolic child with cancer. However, when estimating requirements for the individual
child with cancer, it is important to calculate energy and nutrient intakes based on actual
body weight and not expected body weight as the latter will lead to an intake that is
inappropriately high for child who has an abnormally low body weight (Shaw & Lawson,
2007). Consideration of requirements and method of nutritional support must be tailor
made to each individual child, taking into account their age, weight and clinical condition.
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Table 16.4 An estimated guide to oral requirements in sick children
Energy
Protein
Infants (0?1 year) (based on actual
weight, not expected weight)
Children (1?15 years)
High: 130?150 kcal/kg per day
High: 3.0?4.5 g/kg per day
High: 120% EAR for age
High: 2 g/kg per day, actual body weight
Shaw and Lawson (2007).
Oral feeding
The initial step in providing nutritional support begins with giving the child and family
advice on the impact of cancer and its treatment on nutritional status along with specific
advice on eating problems related to the side effects of treatment (Henry, 2010). Advice
with regard to the use of high-energy foods and small frequent meals and snacks should
be given routinely.
Oral feeding is the best method of support in patients with a low nutritional risk, unless
complicated by relapse, sepsis or major abdominal procedures, if they are able to consume
enough nutrients. However, some will require dietary supplements, which should be age
appropriate, and advice on their usage and how to modify them in order to improve their
palatability should be given. Many children often have good intentions to comply with
taking dietary supplements, but this is often hindered by taste abnormalities associated
with treatment, limiting their usefulness in this patient group.
Ideally, there should be flexibility with regard to menu choice, mealtimes and parental
involvement, and studies have shown that a more flexible meal service can lead to a
significant increase in the children?s food, protein and energy intakes (Williams et al.,
2004; Houlston et al., 2009). Some treatment centres have moved towards meals being
prepared at the ward level, and there is currently a national campaign in the UK by one
of the leading childhood cancer support charities, CLIC Sargent, to encourage all centres
to provide a more flexible meal service. Recommendations to consider include involving
the children in food choices, appreciating individuality, taking orders close to mealtimes,
enable snacking, provide meals on demand, make menus age appropriate, consider choice
of eating environment, portion sizes and meal presentation. The aim is to provide the right
food at the right time by taking a flexible approach, tailored to the individual needs of
the child, and subsequently reduce the reliance on dietary supplements (CLIC Sargent,
2008).
Enteral nutrition
Children deemed to be a higher nutritional risk due to their disease and/or treatment should
be identified early in treatment and enteral nutrition instigated. Early enteral intervention
can prevent nutritional decline during treatment (Ward et al., 2009a). Enteral nutrition
has been successful in reversing malnutrition and maintaining adequate nutritional status.
Studies report that nasogastric feeding during intensive treatment results in improved
nutritional status with minimal complications, improves energy intake and well-being
(den Broeder et al., 1998; Pietsch et al., 1999; Deswarte-Wallace et al., 2001). Even
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in children undergoing bone marrow transplant where the nutritional management is
complex, enteral feeding is feasible and not associated with excessive gastrointestinal
disturbances, leading to a better response and fewer complications (Papadopoulou et al.,
1998; Langdana et al., 2001; Hastings et al., 2006).
Enteral nutrition is also practical and has numerous advantages over parenteral nutrition,
including a low risk of infection and other catheter-related complications, and can be more
easily adapted to fit in with the child?s normal daily routine involving both the parent and
child. It is well documented that enteral feeding also preserves the integrity of the intestinal
mucosa, reduces the risk of bacterial translocation and is more economical (Pietsch et al.,
1999; Han-Markey, 2000; Deswarte-Wallace et al., 2001). Enteral feeding also has the
advantage of offering an alternative route for administration of medication, additional
fluids and can help to reduce both parental and child anxiety related to achieving an
adequate nutritional intake via the oral route.
Whilst nasogastric feeding is effective, when there is a need for long-term nutritional
support the child may find it psychologically unacceptable especially if going to school
and participating in normal activities. Other problems such as vomiting, thrombocytopenia, mucositis, dysphagia also result in a reduced acceptance to nasogastric feeding. In
some cases the presence of the tube can hinder oral food intake. Previously, the use of
gastrostomy feeding in children with cancer was limited due to the perceived risk of
infectious complications in immunosuppressed patients and tube-related complications.
However, studies have demonstrated gastrostomy feeding to be a safe and effective method
of nutritional support in terms of cost and nutritional status and only associated with minor complications such as inflammation, minor site infections and overgranulation that
required topical or systemic antibiotics (Mathew et al., 1996; Barron et al., 2000; Skolin
et al., 2002). Table 16.5 gives indications for gastrostomy tube placement in children with
cancer.
Nasojejunal or jejunostomy feeding should be considered in children with prolonged
vomiting or gastric dysmotility associated with treatment in whom antiemetics and prokinetics have had a limited effect.
The choice of enteral feed will depend on the child?s age, gastrointestinal function and
to some degree their treatment protocol. Generally, an age-appropriate standard nutritionally complete enteral feed will be tolerated in children with a normal gastrointestinal
function. Children at risk of constipation due to vincristine should routinely receive a
Table 16.5 Suggested criteria for gastrostomy tube placement
Indications for gastrostomy placement:
? Patients treated on intensive protocols with high emetogenicity or risk of mucositis
? Patients requiring long-term nutritional support ?3 months
? Patients unwilling to accept or tolerate a nasogastric tube
? Adolescent patients should routinely be offered the choice of a gastrostomy
Contraindications for gastrostomy placement:
? Poor anaesthetic risk
? Short-term feeding <3 months
? Abdominal disease present (assessed on an individual basis)
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Table 16.6 Examples of paediatric enteral feeds for children more than 1 year of age (8 kg)
Feed ? whole protein
Recommended age
(weight)
Feed ? hydrolysate and
amino acid
Whole protein (1 kcal/mL)
Clinutren Junior powder (Nestlea )
1?6 years (8?20 kg)
Hydrolysate feeds
Nutrini Peptisorb (Nutriciac )
? ready to feed (1 kcal/mL)
Frebini Original (Freseniusb )
1?10 years (8?30 kg)
Peptamen Junior liquid
(Nestlea ) ? ready to feed
(1 kcal/mL)
Nutrini (Nutriciac )
1?6 years (8?20 kg)
Peptamen Junior powder
(Nestlea ) ? powdered
version
Paedisure (Abbottd )
1?10 years (8?30 kg)
Pepdite 1+ (SHSe ) ?
powdered
Tentrini (Nutriciac )
7?12 years (21?45 kg)
MCT Pepdite 1+ (SHSe ) ?
powdered
Frebini Original Fibre (Freseniusb )
Nutrini Multifibre (Nutriciac )
Paediasure Fibre (Abbottc )
1?10 years (8?30 kg)
1?6 years (8?20 kg)
1?10 years (8?30 kg)
Tentrini Multifibre (Nutriciac )
7?12 years (21?45 kg)
Whole protein (1.5 kcal/mL)
Frebini Energy (Freseniusb )
Nutrini Energy (Nutriciac )
Paedisure Plus (Abbottd )
Tentrini Energy (Nutriciac )
Frebini Energy Fibre (Freseniusb )
Nutrini Energy Multifibre (Nutriciac )
Paedisure Plus Fibre (Abbottd )
Tentrini Energy Multifibre (Nutriciac )
Amino acid feeds
Neocate Advance (SHSe ) ?
powdered (ages 1?10 years)
Elemental 028 (SHSe ) ?
powdered (age >5 years)
Elemental 028 extra (SHSe )
? powdered (age >5 years)
Emsogen (SHSe ) ?
powdered (age >5 years)
1?10 years (8?30 kg)
1?6 years (8?20 kg)
1?10 years (8?30 kg)
7?12 years (21?45 kg)
1?10 years (8?30 kg)
1?6 years (8?20 kg)
1?10 years (8?30 kg)
7?12 years (21?45 kg)
a
Nestle Clinical Nutrition.
Fresenius Kabi Limited.
c
Nutricia Limited.
d
Abbott Laboratories Limited.
e
Scientific Hospital Supplies, International Limited.
b
fibre-containing feed. However, following chemotherapy a protein hydrolysate or amino
acid-based feed may be more appropriate if malabsorption occurs and should be considered in children with lower gut mucositis, radiation enteritis and with graft-versus-host
disease (GvHD) involving the gut following bone marrow transplant. They can be useful
whilst initially weaning from parenteral nutrition to enteral feeding. Table 16.6 gives
examples of paediatric feeds. Children with cancer may develop temporary lactose intolerance due to their chemotherapy, rotovirus infection or in particular in GvHD and
therefore require a lactose-free feed.
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The volume and delivery of the feed regimen should be determined according to the
child?s normal daily routine and can be provided as a continuous infusion, intermittent
bolus feeds or a combination of both. Continuous feed regimens are generally better
tolerated than intermittent bolus feeding due to the gastrointestinal side effects of treatment
such as nausea and vomiting. Nocturnal continuous feeding with daytime oral feeding
or bolus feeding tends be the pattern of choice and works well to achieve the nutritional
needs with minimal disruption to lifestyle. However, during periods of intensive treatment
or admissions for febrile neutropenia, it may be necessary to feed continuously 20?24
hours in order to achieve tolerability and maximum nutrient intake.
Additional electrolyte supplementation, potassium, phosphate, magnesium or calcium
may be needed depending on the child?s chemotherapy regimen. If the child has an enteral
tube in situ, this can help with their administration and subsequently improve compliance.
They can either be administered directly via the tube or added to the feed, with the
exception of calcium and phosphate due to the risk of precipitation.
Frequent continued support and monitoring is essential as feed tolerance and oral intake
can vary throughout treatment due to side effects, and adjustment to feed type, volume and
delivery is necessary to provide effective enteral feeding support. The majority of children
receiving enteral feeding will require it throughout their intensive treatment protocol, but
once treatment is completed or they go onto maintenance treatment, appetite usually
improves and a conscious effort should be made to wean off enteral feeding.
Parenteral nutrition
Parenteral nutrition (PN) previously was widely used and often the method of choice in
children with cancer as they already had central venous access and had been successful
in preventing and correcting malnutrition (Papadopoulou et al., 1998). However, with the
recognition of the advantages of using the enteral route in terms of cost-effectiveness
and maintenance of gut integrity along with a wider range of paediatric enteral feeds,
PN should be reserved for when the gastrointestinal tract is not functioning or cannot be
accessed or for patients whose enteral feed regimen cannot provide adequate nutrients. PN
is commonly indicated for children with severe mucositis and enteritis. Other indications
include typhlitis, neutropenic enterocolitis, ileus, chylous ascites post-surgery or severe
GvHD disease involving the gut following bone marrow transplantation.
Careful consideration should be given before commencement of PN and is of limited
nutritional benefit if required for less than 1 week. The child?s clinical condition may also
limit the effectiveness of PN due to medical problems, which may restrict fluid intake, with
medication and blood products taking precedence over nutrition. The majority of children
with cancer will have central venous access, and therefore more concentrated solutions
can be prescribed in order to maximum protein and calorie intake, although children
with single lumen lines in situ may require the PN to be interrupted for medication
or blood products, therefore potentially restricting the amount of parenteral nutrition
given.
Metabolic complications of PN are well documented (Koletzko et al., 2005) and are
not significantly different between children with malignancies and other children requiring nutritional support. However, it is important that electrolyte levels are monitored
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closely, in particular children with severe diarrhoeal losses or those receiving chemotherapy drugs that impair renal function. Drugs such as cisplatin and ifosfamide can cause
renal tubular damage associated with excess losses of magnesium, potassium, phosphate and calcium. Frequently children with large diarrhoeal losses and/or renal tubular
dysfunction require electrolyte additions above those normally recommended to PN as
outlined in the European Society of Paediatric Gastroenterology, Hepatology and Nutrition guideline (Koletzko et al., 2005). The use of the antifungal amphotericin can result in
hypokalaemia, resulting in a higher potassium requirement to PN; however, care should
be taken if the potassium-sparing diuretics amiloride or spironolactone are subsequently
used to counteract this effect. Routine monitoring of plasma glucose and lipid levels is
essential. In children with GvHD involving the gut who are receiving steroids as part
of their management, hyperglycaemia and hyperlipidaemia can occur with PN, and it
may be necessary to use intravenous insulin infusions to manage hyperglycaemia when
a reduction in glucose is inappropriate due to compromising nutritional intake. Children
who develop veno-occlusive disease of the liver following allogeneic or autologous bone
marrow transplant often require to be fluid restricted, and therefore concentrated solutions
should be considered to maximise nutrition, with sodium additions kept to a minimum to
prevent/treat any ascites.
Lipid is an integral part of PN in order to provide high energy needs without carbohydrate overload, and its high-energy density is of particular value in fluid-restricted patients.
It provides essential fatty acids, and hence in severe cases of marked hyperlipidaemia, it
is highly preferable to reduce the amount of lipid provided rather than stop it completely.
However, essential fatty deficiency is preventable with as little as 0.1 g/kg body weight
per day of linoleic acid (Koletzko et al., 2005), although a suboptimal energy intake will
result.
Parenteral iron should not be routinely supplemented in children with cancer as the
majority receive frequent blood transfusions and hence the potential risk for iron overload.
Trace element levels should routinely be monitored if PN is required for longer than 2
weeks and then monthly thereafter, as children with cancer receiving PN frequently require
extra additions of zinc and selenium to PN.
The PN prescription should be based on standard nutrient requirements and adjusted
depending on the individual child?s clinical condition in conjunction with the multidisciplinary team to provide the correct amount of fluid and nutrients for that individual
child.
Nutritional support in the infant with cancer
Providing adequate nutrition for the infant with cancer to maintain adequate growth during
the first year of life can be particularly challenging with obstacles such as vomiting, diarrhoea and mucositis. The majority of infants will require supplementary enteral feeding
to achieve an adequate intake. A well infant will tolerate 4-hourly feeds six times daily
once a body weight of 3.5 kg is reached and by the age of 3?6 weeks may sleep longer and
drop a night-time feed (Shaw & Lawson, 2007). A sick child may require smaller, more
frequent feeds, especially if vomiting occurs and depending on their clinical condition
may have increased or decreased fluid requirements.
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If enteral feeding is indicated, some infants may achieve an adequate intake by using
their normal standard infant formula in particular if a sore mouth was the initial cause of
a reduced oral intake. Mothers who are breastfeeding should be encouraged to continue
with this, and expressed breast milk (EBM) can be given via the tube. Although EBM may
have a lower energy density, especially if the fore milk is used which is lower in fat, the
physiological and psychological benefits in terms of the presence of immunoglobulins,
antimicrobial factors and the mother being able to contribute to the care of her sick infant
are important benefits (Johnson, 2007). If weight gain is inadequate with breast milk
alone, it can be supplemented with additional breast milk fortifiers or standard infant
formula.
Infants who have higher increased nutrient requirements or those who require a fluid restriction will benefit from a nutrient-dense formula such as SMA High Energy or Infatrini.
Another option would be to consider concentrating a normal infant formula to provide a
more nutrient-dense formula. Standard infant formulas in the United Kingdom are made
up to a dilution of 13%, but by making to a 15% concentration, a more nutrient-dense
formula will be achieved, which retains the appropriate protein?energy ratio (7.5?12%);
however, it is important to recognise that this is only used as a therapeutic procedure
and is not usual practice (Shaw & Lawson, 2007). In some situations, particularly in the
severely fluid-restricted infant, it may be necessary to add extra energy and/or protein
supplements to the infant formula.
Infants with impaired gut function, such as diarrhoea or mucositis, frequently do not
tolerate a standard whole protein, cow?s milk-based formula, and the use of a hydrolysed
protein or amino acid formula should be considered (Table 16.7).
It is important to try to maintain some oral intake for feeding skills to develop. Often,
the method of choice for tube feeding is by top-up bolus feeding, thus maintaining a
normal infant feeding pattern and preserving some oral intake. This is unfortunately not
always possible due to poor tolerance of top-up feeds. If vomiting occurs with large feed
Table 16.7 Examples of extensively hydrolysed infant formulas
Feed
Casein based
Pregestimil (Mead Johnsona )
Whey based
Pepti-Junior (Cow & Gateb )
Aptimil Pepti (Milupac )
Pork collagen and soya
Prejomin (Milupac )
Pepdite (SHSd )
MCT Peptide (SHSd )
Amino acid-based formulas
Neocate (SHSd )
Nutramigen AA (Mead Johnsona )
a
Per 100 mL
energy (kcal)
Protein
(g)
Osmolality
(mOsm/kg H2 O)
68
1.9
330
?
67
66
1.8
1.6
200
240
Trace
40% (of CHO)
75
71
68
2.0
2.1
2.0
193
237
290
?
?
?
71
68
2.0
1.9
360
348
?
?
Mead Johnson Nutrition.
Cow & Gate.
c
Milupa Ltd.
d
Scientific Hospital Supplies, International Limited.
b
Lactose
present
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volumes then smaller, more frequent feeds may be more appropriate, and the use of a
feed thickener should be considered such as Thixo D or Thick & Easy or a period of
continuous feeding with small oral/bolus feeds.
Infants treated for ALL or AML can be more challenging due to the length of treatment,
problems with gut toxicity and stomatitis. Weaning should be started around 17 weeks in
order to achieve a higher energy intake and to establish some oral feeding skills in between
periods of severe oral mucositis, otherwise feeding development becomes delayed, making
it harder for the infant to develop normal feeding skills (Ward et al., 2002).
Complementary and alternative diets
There is an increasing awareness amongst parents and families with regard to the role
of alternative or complementary nutritional therapies, and many are highly motivated to
seek information on food choices, dietary supplements and complementary nutritional
therapies in a bid to improve quality of life and increase chances of survival (Schmidt &
Ernst, 2004). The majority of such diets are made up of components, which claim to have
three major functions: detoxification, strengthening of the immune system and specific
therapies to attack the cancer cell (Weitzman, 2008).
The majority of the diets generally advocate a strict vegetarian or vegan regimen and
restrict animal products, salt and refined carbohydrates and only allow small quantities
of fat. Many are high-fibre, high-fruit/fruit juice and vegetable diets and may involve
additional detoxification in the form of fasting for several days or weeks as well as the use
of laxatives and enemas. Some involve the addition of different supplements to the basic
diet, which can be in potentially toxic doses. Diets involving frequent regular fruit juice
can result in early satiety and diarrhoea (Kogut, 2001), which will be more pronounced
in children leading to weight loss. Malnutrition can therefore occur due to the high-fibre
content of the diet, the low-calorie density and low-protein content, which in turn can
result in a reduced immune function, increased toxicity from conventional treatment and
therefore a poorer response (Weitzman, 2008).
High doses of vitamins and minerals may be harmful to children as well as the risk
of interaction with conventional treatment. With a current 80% cure rate of childhood
cancer by conventional treatments, it is imperative to ensure nothing is given which has
a negative interaction with treatment (Weitzman, 2008). It is essential that any parent
contemplating the use of an alternative diet should seek the appropriate advice from their
child?s physician or dietitian and those treating the child inquire non-judgementally about
their use.
Vitamin supplementation
Parents frequently ask if it is necessary for their child to take vitamin supplements,
especially the antioxidant vitamins A, C, E and ?-carotene, whilst being treated for cancer.
The mode of action of certain chemotherapy agents involves the generation of free radical
oxidants to cause cellular damage and necrosis/apoptosis of malignant cells, such as
alkylating agents, antitumour antibiotics and platinum compounds. The formation of free
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radicals leading to oxidative stress is one of the main pathogenic mechanisms for toxicity,
with toxicity being a dose-limiting factor for treatment.
Currently, there have been very few studies looking at changes in antioxidant status
and oxidative stress in children undergoing treatment for cancer, and studies generally
tend to only involve small patient numbers. However, one larger study of children undergoing treatment for ALL showed that a higher intake of vitamin C, ?-carotene and total
carotenoids was associated with a lower incidence of chemotherapy-related toxicity and
higher vitamin E intake at 3 months was associated with a lower incidence of infection
(Kennedy et al., 2004). A significant percentage of the children had inadequate intakes
and low plasma concentrations of antioxidants. As the children had an adequate energy
intake, which is often the case in children treated for ALL, the author suggested nutritional
counselling aimed at increasing fruit and vegetable intake in order to increase antioxidant intake and that more information is needed before antioxidant supplementation is
recommended. It is clear that further studies are required, and until then currently in the
United Kingdom the following is advised for children with cancer: supplementation of
vitamins and minerals above the RNI is not recommended because of potential toxicity
and interactions with the efficacy of conventional treatment. Children receiving enteral
feeds or nutritionally complete oral sip feeds should not need additional supplements.
Children not receiving nutritional support but who have a limited fruit and vegetable intake may benefit from a general multivitamin supplement but should be given extra advice
on how to incorporate more fruit and vegetables into their diet. As children undergoing
treatment for cancer frequently require blood transfusions, it is advisable that they take a
supplement which does not contain any iron or a small amount of iron (maximum of 15%
recommended daily allowance).
Glutamine
Many chemotherapy drugs, in particular anthracyclines, actinomycin and high-dose
methotrexate, result in both structural and functional injuries to the gastrointestinal tract,
resulting in mucositis severe enough to prevent an adequate oral intake. It is well documented that glutamine is a major fuel and important nitrogen source for enterocytes and
plays a key role in maintaining mucosal cell integrity and gut barrier function (van Acker
et al., 1999). Whilst there have been several studies looking at the role of both enteral and
parenteral glutamine in adult oncology patients, there are very few published studies looking at glutamine in paediatric oncology patients. An oral dose of up to 0.65 g/kg has been
shown to be safe and acceptable to use in paediatric oncology patients (Ward et al., 2003).
A significant reduction in the severity and duration of stomatitis using a smaller dose of
oral glutamine in children has been demonstrated (Anderson et al., 1998). Although no
significant difference in oral mucositis was observed, significant reductions in number of
children requiring PN and duration of PN have been demonstrated in other oral studies
(Aquino et al., 2005; Ward et al., 2009b), perhaps reflecting the role of glutamine in
improving lower gut mucositis. Currently, there are no studies looking at the role of parenteral glutamine in paediatric oncology patients partly due to stability problems adding
glutamine to small volumes of PN in paediatric patients. Although now available as a
dipeptide of glutamine and alanine (Dipeptiven, Fresenuis Kabi), its safety and efficacy in
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children have not yet been determined. Oral glutamine has been shown to be safe to use in
paediatric oncology patients, but further studies are still required to determine its effect in
particular regarding use in children undergoing high-dose chemotherapy and bone marrow
transplantation.
Other agents currently being investigated to prevent or alleviate symptoms of oral
mucositis in paediatric oncology patients include Gel-Clair (Cambridge Laboratories).
Steroid-induced diabetes
Children treated for ALL regularly receive the corticosteroid dexamethasone as part of
their treatment. Dexamethasone has potent lymphocytotoxic activity causing lymphoblast
lysis. However, its side effects include an increased appetite and raised blood glucose levels. Hyperglycaemia is usually only transient whilst the child is receiving dexamethasone;
however, in some cases it may be permanent. Children who appear more susceptible
to hyperglycaemia include those with a family history of diabetes, those overweight at
diagnosis and older children/adolescents.
Treatment involves the use of sliding scale intravenous insulin until blood sugar levels
are controlled. Subsequently, alteration in diet may be all that is necessary to control
blood sugar levels; however, the use of a twice daily injection of pre-mixed analogue and
isophane insulin may be advised or the use of a basal bolus regimen. Using basal and
rapid acting analogue insulins allows greater flexibility with regard to mealtimes as there
is no need to adhere to rigid meal and snack times as a bolus of insulin is injected prior to
food. Children treated for ALL can have variable appetites and food intakes, and hence a
basal bolus regimen allows for this variation.
Dietary advice should be simple, and the avoidance of rapidly absorbed carbohydrate
should be given along with advice on suitable alternatives and snack suggestions. High-fat
foods should not routinely be restricted especially in children who have poor appetites
and would be unable to achieve an adequate energy intake if fatty foods were restricted.
Similarly, high-fibre foods may not be appropriate due to being less energy dense, and
they may compromise the child?s energy intake. However, children who are eating well
and have a good appetite would benefit from an increased fibre intake as constipation is a
common side effect of vincristine, which is used in the treatment of ALL.
Late effects
The development of curative therapy for the majority of paediatric cancers has resulted
in a growing population of childhood cancer survivors who are at an increased risk of
various health problems (Wasilewski-Masker et al., 2008).
Bone morbidity in children with cancer both during and after completion of treatment is increasingly recognised as both a short-term and long-term problem (Rogers,
2008). This is especially the case in children who receive large cumulative doses of
glucocorticosteroids and methotrexate for treatment, such as ALL. Peak bone mass is
attained by late adolescence or early adulthood, with approximately 40% of total bone
mass accumulated in adolescence. Any interruptions to the normal process of bone mass
accretion during childhood and adolescence may impact on skeletal fragility in adulthood
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(Atkinson, 2008b). Hence, children and adolescents treated for cancer potentially miss the
opportunity for skeletal maturation. Other risk factors include reduced physical activity,
nutritional disorders of calcium and vitamin D deficiency and genetic factors (van der
Sluis & van der Heuvel-Eibrink, 2008). Other patients at risk include those treated for
Ewing?s sarcoma and osteosarcoma who have received methotrexate and ifosfamide (Sala
& Barr, 2007; Wasilewski-Masker et al., 2008).
Correction of bone mineral loss may be possible by correction of dietary deficiencies
including those of calcium and vitamin D; however, in some cases it is judged to use bisphosphonates such as pamidronate or alendronate. Calcium and vitamin D dietary advice
should be given along with supplementation such as Calcichew D3 Forte (Shire), Cacit
D3 (Proctor & Gamble Pharmaceuticals) and Adcal-D (Strakan). Advice on improving
diet and physical activity should also be recognised as a strategy for amelioration and
prevention (Sala & Barr, 2007).
Another well-reported effect in childhood cancer survivors is the recognition of the
prevalence of obesity particularly in children treated for ALL and brain tumours (Ladas
et al., 2005). The majority of studies have looked at ALL survivors and have revealed as
well as obesity a high prevalence of endocrine and metabolic disorders such as growth
hormone deficiency, hypothyroidism, insulin resistance and hyperlipidaemia (Gurney
et al., 2005; Steffens et al., 2008) with it being most detrimental in those patients treated
with bone marrow transplant/total body irradiation (Steffens et al., 2008).
The mechanism for the onset of obesity following treatment for ALL may be partly
due to a sustained imbalance between energy expenditure and energy intake. Lack of
physical activity, high calorie intake and metabolic changes following prolonged courses
of chemotherapy may all play a part in altering body composition in ALL survivors
(Warner, 2008). Reduced physical activity has been documented in ALL survivors and
could be due to a subtle psychological effect of cranial irradiation affecting motivational
drive or as a result of anthracycline-induced cardiomyopathy (Reilly et al., 1999; Warner,
2008). Very few children with ALL nowadays receive cranial radiation; therefore, one of
the major causes of obesity identified is lack of physical activity. It is clear that thought
should be given to routinely giving ?healthy eating? advice to children treated for ALL
and perhaps this should be at the start of or during long-term maintenance therapy.
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Houlston, A., Buttery, E. and Powell, B. (2009) Cook to order: meeting the nutritional needs of
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Yaris, N., Akyuz, C., Coskun, T., et al. (2002) Nutritional status of children with cancer and its
effect on survival. Turkish Journal of Pediatrics 44(1), 35?39.
r Brain tumours: Brain and spinal CNS tumours are the most common solid tumours
that occur in children. Medulloblastoma is the most common CNS tumour in children.
Signs and symptoms of CNS tumours are generally caused by increased intracranial
pressure and include headaches, vomiting, drowsiness, irritability, fits and diplopia.
Other symptoms may include weakness or unsteadiness on walking. Treatment varies
depending on the underlying tumour, but surgery, radiotherapy or chemotherapy may
be used alone, or in combination. Five-year survival rate for medulloblastoma is about
80% for children with standard risk disease and between 40 and 60% in those with
high-risk disease (i.e. with disseminated disease or have undergone a subtotal resection)
(Packer et al., 1994; Crawford et al., 2007).
r Neuroblastoma: This is most common before the age of 5 years and accounts for 8% of
all childhood cancers. It arises from the neural crest tissue in the adrenal medulla and
elsewhere in the sympathetic nervous system; therefore, it most frequently occurs in
one of the adrenal glands but can also occur alongside the spinal cord in the neck, chest,
abdomen or pelvis. Most children present with an abdominal mass, loss of appetite,
lethargy and bone pain. At presentation the tumour mass can often be large and complex.
Treatment and survival depend on the stage of the disease. Recently, there have been
further clarified risk groups, leading to very low, low, intermediate and high-risk group
patients, with treatment for some of the low risk and very low-risk group patients being
observed only as the disease can show spontaneous regression in very young infants.
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Those with high-risk disease treatment involve chemotherapy, surgery, radiotherapy
and in some cases high-dose chemotherapy and autologous stem cell transplant. The
use of 13-cis-retinoic acid is being used as a differentiating agent to reduce the risk of
relapse in high-risk patients. Five-year survival rate is currently around 64% (CCLG,
2008).
Wilms? tumour: It is most commonly seen in children under the age of 5 years, with
the majority presenting with a large abdominal mass. Other symptoms may include
poor weight gain and loss of appetite, blood in the urine and high blood pressure. It is
a congenital malignant kidney tumour, which can be bilateral. Treatment depends on
histology and the stage of the tumour but usually involves surgery, chemotherapy and
occasionally radiotherapy. Prognosis for Wilms? tumour is good with 5-year survival
rates around 90% (CCLG, 2008).
Rhabdomyosarcoma: It is the most common type of soft tissue sarcoma in children,
which develops from muscle or fibrous tissue. It can develop at any age but is more
common in children under 10 years. There are two main subgroups: embryonal (80%)
and alveolar (20%). Rhabdomyosarcoma occurs at a wide variety of primary sites
but is most common around head and neck sites. Other sites include genitourinary and
occasionally limb, chest or abdominal wall. Treatment depends on tumour size, position
and whether metastatic disease is present but involves chemotherapy, surgical resection
and sometimes radiotherapy. Five-year survival rate is around 65% (CCLG, 2008).
Ewing?s sarcoma and peripheral primitive neuroectodermal tumour (pPNET): Ewing?s
sarcoma is a type of bone tumour. Any bone can be affected but is more common
in the pelvis, femur or shinbone. It can occur in the teenage years but is also seen
in younger children. Persistent localised bone pain is a characteristic symptom that
usually precedes the detection of a mass. Treatment involves chemotherapy followed
by surgery, usually limb sparing, but sometimes amputation is unavoidable followed by
further chemotherapy and in some cases radiotherapy especially if surgical resection is
impossible or incomplete. Poor responders may receive high-dose chemotherapy and
autologous stem cell transplant. Five-year survival rates are around 65% (CCLG, 2008).
Treatment lasts about a year. pPNET is a soft tissue sarcoma of neuroepithelial origin,
which can be thought of as being similar to an Ewing?s sarcoma.
Osteosarcoma: This is a high-grade bone tumour, which is more commonly seen in
older children and teenagers and is more common in boys. It often occurs at the end
of bones where new bone tissue is forming and is most common in the arms or legs,
particularly around the knee. Pain and swelling around the affected bone are the most
common symptoms. Treatment depends on factors including size, position and stage of
the tumour but involves chemotherapy initially to shrink the tumour prior to surgery.
Surgery may be amputation or limb sparing surgery. Further chemotherapy is then
given and treatment lasts for about a year. Five-year survival rates are around 50?60%
(CCLG, 2008).
Retinoblastoma: This is the commonest malignant eye tumour in children, accounting
for around 3% of childhood cancers, with most occurring under the age of 5 years.
All bilateral tumours are thought to be hereditary, as are 20% of unilateral cases.
Children of affected families are screened from birth. Treatment options include local
treatment with cryotherapy, laser therapy, external beam therapy, chemotherapy, plaque
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brachytherapy and in some cases enucleation is necessary. Five-year survival rates are
over 90% (CCLG, 2008).
r Germ cell tumours: These are rare and may be malignant or benign. They arise from
the primitive germ cells, which migrate in the embryo from yolk sac endoderm to
form gonads, and therefore most tumours affect the ovaries or testes. If the tumour is
malignant and completely removed by surgery, chemotherapy may not be needed. If the
tumour cannot be easily removed by surgery or has spread then chemotherapy is given.
They are very chemotherapy-sensitive tumours, and survival is over 90% (CCLG, 2008).
Aetiology of malnutrition in children with cancer
The incidence of malnutrition in paediatric oncology at diagnosis is variable partly due to
the variation in studies conducted on different types of paediatric malignancies and variation in nutritional assessment parameters used (Sala et al., 2004). However, it is estimated
that the incidence of malnutrition ranges from 6 to 50% depending on the type, stage
and location of the disease (Van Eys, 1979; Donaldson et al., 1981; Carter et al., 1983).
It is estimated that malnutrition is present in less than 10% of children with standard
risk acute lymphoblastic leukaemia, but the prevalence increases to 50% in children with
advanced solid tumours such as neuroblastoma, Wilms? tumours and sarcomas (Carter
et al., 1983; Reilly et al., 1999). Malnutrition is more severe with aggressive tumours
in the later stages of malignancy, occurring in up to 37.5% of newly diagnosed patients
with metastatic disease (Smith et al., 1991). The risk of nutritional morbidity is greater
in patients with a greater tumour burden and higher treatment intensity. The initial nutritional problems resulting from the tumour are soon compounded by iatrogenic nutritional
abnormalities, the consequence of the treatment and its complications. Metabolic and
psychological factors also have a role (Mauer et al., 1990).
Metabolic factors
Cancer cachexia is complex and multifactorial, marked by early satiety, weight loss,
organ dysfunction and tissue wasting. Changes in the metabolism of fat, carbohydrate
and protein have been demonstrated in the cancer-bearing host (Rossi-Fanelli et al., 1991;
Picton, 1998). In children with cancers, the result is a cascade of metabolic events, which
are typically characteristic of the acute metabolic response. In addition to glycogenolysis
and lipolysis, this response includes a marked increase in energy expenditure, proteolysis
and gluconeogenesis. This response results in an accelerated depletion of endogenous
energy and substrate stores in the face of decreased exogenous fuel substrate provision
(Andrassy & Chwals, 1998).
Cachexia is more common in children with solid tumours at diagnosis (33%) and during treatment (57%) compared with children with leukaemia (12 and 38%, respectively)
(Picton et al., 1995). Solid tumour patients who developed cachexia during treatment were
found to have a significantly raised sleeping energy expenditure at diagnosis, whereas children with leukaemia at risk of developing cachexia had no changes in energy expenditure
at diagnosis (Picton et al., 1995). A small study of children with ALL found no significant
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difference in resting energy expenditure at diagnosis and also throughout set points in
therapy when compared to controls (Delbecque-Boussard et al., 1997). Severe weight
loss in children with leukaemia appears to be associated with more intensive treatment
regimens such as those for AML (Picton, 1998) and more recently children treated on
regimen C.
As treatment regimens increase in intensity and more treatments become available for
children with relapsed disease, the greater the number of children at risk of the metabolic
demands of their disease and treatment.
Complications of the disease and treatment
As a consequence of aggressive treatment modalities used in treating children with cancer,
most of the malnutrition seen occurs as a result of treatment. Anorexia, mucositis, vomiting, diarrhoea and alterations in taste are important contributory factors to weight loss
in children undergoing treatment for cancer (Barr, 2002). Nutrition status can deteriorate
rapidly, particularly during the initial intensive phases of treatment if nutrition support is
not provided (Coates et al., 1986; Ward et al., 2009a). Table 16.1 shows the side effects
relating to drugs commonly used in treatment of paediatric malignancies.
Psychological factors
Learned food aversions associated with links between foods consumed close to chemotherapy administration and nausea and vomiting have been demonstrated in children with
cancer along with the phenomenon of anticipatory vomiting (Bernstein, 1994). Food is
one area of treatment that both the child and parent can try to control, resulting in increased
Table 16.1 Side effects relating to drugs used in treatment of paediatric oncology
Side effect
Causative drug
Infection
Both chemotherapy and radiotherapy are known
immune depressants
Diarrhoea
Actinomycin, doxorubicin, methotrexate, cytosine
Nausea and vomiting
Actinomycin, carboplatin, cisplatin,
cyclophosphamide, doxorubicin, ifosfamide, cytosine,
etoposide, methotrexate, procarbazine, thioguanine
Stomatitis/mucositis
Actinomycin, adriamycin, daunorubicin, doxorubicin,
epirubicin, bleomycin, melphalan, methotrexate
Renal damage and nutrient loss
Cisplatin, cyclophosphamide, ifosfamide
Constipation
Vincristine
Weight gain and raised blood
glucose levels
Dexamethasone, prednisolone
Hypoalbuminaemia
L-Asparaginase
Pancreatitis
L-Asparaginase
Weight loss
?-Interferon
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tension and anxiety about food, which can lead to negative feeding behaviour and eating
becoming an unpleasant experience for both the child and their family.
Identification of nutritional risk
Assessment of nutritional status in children with cancer is a vital component of supportive care and essential for monitoring the need for nutritional intervention. Nutritional
status indices may also be a useful tool as prognostic markers of response to therapy
or toxicity (Atkinson, 2008a). Criteria used to determine malnutrition in children with
cancer differ, and despite various anthropometric measurements reflecting changes in
body composition, some of these require cautious interpretation. Accurate height and
weight measurements and the subsequent transformation to anthropometric indices are
the mainstay of nutritional assessment in children with cancer (Brennan, 2003). However, the reliability of weight-related indices is reduced in children with solid tumours,
particularly those with large abdominal tumours, for example, neuroblastoma, hepatoblastoma, Wilms? tumour, and therefore a measurement independent of tumour mass such
as mid-upper arm circumference or triceps skinfold thickness should be undertaken.
It is well documented that the determination of the nutritional risk of the child with
cancer is associated with the diagnosis of certain tumours and stages of the disease either
as a result of the underlying disease or as a result of the anticipated toxicity from the
current treatment protocol (Table 16.2) (Han-Markey, 2000; Ward, 2007). Recently, a
new child-specific, nurse-administered nutrition screening tool has been developed and
validated (STAMP ? screening tool for the assessment of malnutrition in paediatrics),
which can be used to identify the child with cancer at risk of malnutrition (McCarthy
& Dixon, 2008). However, due to the scoring system used, the vast majority of children
on active treatment will score as being high risk. A recent study highlighted that no
Table 16.2 Types of paediatric cancers associated with high or low nutritional risk
High nutritional risk
Low nutritional risk
Advanced disease during initial intense treatment
High-risk neuroblastoma
Stage III and Stage IV Wilms? tumour
High-risk rhabdomyosarcoma
Ewing?s sarcoma/pPNET
Osteosarcoma
Medulloblastoma/CNS PNET
B-cell NHL
AML
Some ALL
Infants and teenagers
Regimen B and C patients
Relapsed ALL
Bone marrow transplant patients
Allogeneic
Autologous
ALL regimen A
Non-metastatic solid tumours
Retinoblastoma
Hodgkin?s disease
Germ cell tumours
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simple nutritional measures were found to accurately identify poor nutritional status in
children treated for paediatric malignancy (Murphy et al., 2009). The following criteria
can be useful to identify children with cancer who are likely to require nutritional support
(Andrassy & Chwals, 1998):
r Total weight loss of more than 5% relative to pre-illness weight
r Weight for height less than 90%
r Serum albumin less than 32 mmol/L (in absence of recent acute metabolic stress within
the last 14 days and excluding children who have recently received l-asparaginase)
r A decrease in current percentiles for weight (or height) of two major centiles
r Adipose energy reserves as determined by triceps skinfold thickness less than fifth
percentile for age and sex
r Voluntary food intake less than 70% of estimated requirements for 5 days for wellnourished patients
r Anticipated gut dysfunction resulting from treatment for more than 5 days for wellnourished patients
r High nutritional risk patients based on tumour type and treatment regimens
r Bone marrow transplantation as a treatment for any cancer
The consequences of malnutrition are multiple and include a possible influence on
outcome, with children who are underweight at diagnosis having a poorer outcome compared to those who are adequately nourished at diagnosis (Donaldson et al., 1981; Lange
et al., 2005). Malnutrition contributes to a reduced tolerance to therapy and may also
affect the sensitivity to chemotherapy agents (Andrassy & Chwals, 1998]; Sala et al.,
2004; Ladas et al., 2005). Malnutrition may contribute to problems of drug toxicity due
to altered pharmakinetics secondary to changes in body composition and relationship between body surface area and lean body mass (Ladas et al., 2005; Tabori et al., 2005). The
relationship between malnutrition and increased risk of infection is well documented in
the child with cancer (Smith et al., 1991; Sala et al., 2004). Given the potential impact the
nutritional status and intervention can have in children undergoing treatment for cancer
nutritional assessment and early identification for nutritional support is a crucial role of
the multidisciplinary team caring for these children.
Nutritional support
Children undergoing treatment for cancer are at risk of depleted nutrient stores due to a
decreased intake or increased losses due to vomiting, diarrhoea or renal losses.
The aims of nutritional intervention are to reverse any malnutrition at diagnosis, prevent
any future malnutrition associated with treatment and to promote normal growth and
development throughout treatment. Nutritional support will improve immune competence,
tolerance to treatment and quality of life (van Eys, 1998). Successful nutritional support
requires a multidisciplinary approach to provide safe, appropriate and effective nutritional
support.
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Table 16.3 DRV for fluid, protein and energy for children
Energy (EAR)
Protein (RNI)
Weighta
(kg)
Fluid
(mL/kg)
(kcal/kg per
day)
Males
0?3 months
4?6 months
7?9 months
10?12 months
1?3 years
4?6 years
7?10 years
11?14 years
15?18 years
5.9
7.7
8.9
9.8
12.6
17.8
28.3
43.1
64.5
150
150
120
120
90
80
60
50
40
115?100
95
95
95
95
90
?
?
?
545
690
825
920
1230
1715
1970
2220
2755
2.1
1.6
1.5
1.5
1.1
1.1
?
?
?
12.5
12.7
13.7
14.9
14.5
19.7
28.3
42.1
55.2
Females
0?3 months
4?6 months
7?9 months
10?12 months
1?3 years
4?6 years
7?10 years
11?14 years
15?18 years
5.9
7.7
8.9
9.8
12.6
17.8
28.3
43.8
55.5
150
150
120
120
90
80
60
50
40
115?100
95
95
95
95
90
?
?
?
515
645
765
865
1165
1545
1740
1845
2110
2.1
1.6
1.5
1.5
1.1
1.1
?
?
?
12.5
12.7
13.7
14.9
14.5
19.7
28.3
42.1
45.4
Age
(kcal/day) (g/kg per day) (g/day)
Department of Health (1991).
EAR, estimated average requirements.
a
Standard weights for age ranges.
Nutritional requirements in children with cancer
Table 16.3 gives the dietary reference values (DRVs) for fluid, protein and energy for different age groups of children from the Department of Health Report on Dietary Reference
Values (Department of Health, 1991). The DRVs are for healthy populations of infants fed
artificial formulas and for older children consuming food. These recommendations are for
groups, not for individuals; however, they can be used as a basis for estimating suitable
intakes for the individual, using the reference nutrient intake (RNI) (Shaw & Lawson,
2007). This level should satisfy the requirements of 97.5% of the healthy population group
and is a useful starting basis for the non-catabolic, low nutritional risk child with cancer.
An estimation of the protein and energy requirements for sick children is given in Table
16.4 and can be useful when determining the protein and calorie requirements for the
catabolic child with cancer. However, when estimating requirements for the individual
child with cancer, it is important to calculate energy and nutrient intakes based on actual
body weight and not expected body weight as the latter will lead to an intake that is
inappropriately high for child who has an abnormally low body weight (Shaw & Lawson,
2007). Consideration of requirements and method of nutritional support must be tailor
made to each individual child, taking into account their age, weight and clinical condition.
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Table 16.4 An estimated guide to oral requirements in sick children
Energy
Protein
Infants (0?1 year) (based on actual
weight, not expected weight)
Children (1?15 years)
High: 130?150 kcal/kg per day
High: 3.0?4.5 g/kg per day
High: 120% EAR for age
High: 2 g/kg per day, actual body weight
Shaw and Lawson (2007).
Oral feeding
The initial step in providing nutritional support begins with giving the child and family
advice on the impact of cancer and its treatment on nutritional status along with specific
advice on eating problems related to the side effects of treatment (Henry, 2010). Advice
with regard to the use of high-energy foods and small frequent meals and snacks should
be given routinely.
Oral feeding is the best method of support in patients with a low nutritional risk, unless
complicated by relapse, sepsis or major abdominal procedures, if they are able to consume
enough nutrients. However, some will require dietary supplements, which should be age
appropriate, and advice on their usage and how to modify them in order to improve their
palatability should be given. Many children often have good intentions to comply with
taking dietary supplements, but this is often hindered by taste abnormalities associated
with treatment, limiting their usefulness in this patient group.
Ideally, there should be flexibility with regard to menu choice, mealtimes and parental
involvement, and studies have shown that a more flexible meal service can lead to a
significant increase in the children?s food, protein and energy intakes (Williams et al.,
2004; Houlston et al., 2009). Some treatment centres have moved towards meals being
prepared at the ward level, and there is currently a national campaign in the UK by one
of the leading childhood cancer support charities, CLIC Sargent, to encourage all centres
to provide a more flexible meal service. Recommendations to consider include involving
the children in food choices, appreciating individuality, taking orders close to mealtimes,
enable snacking, provide meals on demand, make menus age appropriate, consider choice
of eating environment, portion sizes and meal presentation. The aim is to provide the right
food at the right time by taking a flexible approach, tailored to the individual needs of
the child, and subsequently reduce the reliance on dietary supplements (CLIC Sargent,
2008).
Enteral nutrition
Children deemed to be a higher nutritional risk due to their disease and/or treatment should
be identified early in treatment and enteral nutrition instigated. Early enteral intervention
can prevent nutritional decline during treatment (Ward et al., 2009a). Enteral nutrition
has been successful in reversing malnutrition and maintaining adequate nutritional status.
Studies report that nasogastric feeding during intensive treatment results in improved
nutritional status with minimal complications, improves energy intake and well-being
(den Broeder et al., 1998; Pietsch et al., 1999; Deswarte-Wallace et al., 2001). Even
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in children undergoing bone marrow transplant where the nutritional management is
complex, enteral feeding is feasible and not associated with excessive gastrointestinal
disturbances, leading to a better response and fewer complications (Papadopoulou et al.,
1998; Langdana et al., 2001; Hastings et al., 2006).
Enteral nutrition is also practical and has numerous advantages over parenteral nutrition,
including a low risk of infection and other catheter-related complications, and can be more
easily adapted to fit in with the child?s normal daily routine involving both the parent and
child. It is well documented that enteral feeding also preserves the integrity of the intestinal
mucosa, reduces the risk of bacterial translocation and is more economical (Pietsch et al.,
1999; Han-Markey, 2000; Deswarte-Wallace et al., 2001). Enteral feeding also has the
advantage of offering an alternative route for administration of medication, additional
fluids and can help to reduce both parental and child anxiety related to achieving an
adequate nutritional intake via the oral route.
Whilst nasogastric feeding is effective, when there is a need for long-term nutritional
support the child may find it psychologically unacceptable especially if going to school
and participating in normal activities. Other problems such as vomiting, thrombocytopenia, mucositis, dysphagia also result in a reduced acceptance to nasogastric feeding. In
some cases the presence of the tube can hinder oral food intake. Previously, the use of
gastrostomy feeding in children with cancer was limited due to the perceived risk of
infectious complications in immunosuppressed patients and tube-related complications.
However, studies have demonstrated gastrostomy feeding to be a safe and effective method
of nutritional support in terms of cost and nutritional status and only associated with minor complications such as inflammation, minor site infections and overgranulation that
required topical or systemic antibiotics (Mathew et al., 1996; Barron et al., 2000; Skolin
et al., 2002). Table 16.5 gives indications for gastrostomy tube placement in children with
cancer.
Nasojejunal or jejunostomy feeding should be considered in children with prolonged
vomiting or gastric dysmotility associated with treatment in whom antiemetics and prokinetics have had a limited effect.
The choice of enteral feed will depend on the child?s age, gastrointestinal function and
to some degree their treatment protocol. Generally, an age-appropriate standard nutritionally complete enteral feed will be tolerated in children with a normal gastrointestinal
function. Children at risk of constipation due to vincristine should routinely receive a
Table 16.5 Suggested criteria for gastrostomy tube placement
Indications for gastrostomy placement:
? Patients treated on intensive protocols with high emetogenicity or risk of mucositis
? Patients requiring long-term nutritional support ?3 months
? Patients unwilling to accept or tolerate a nasogastric tube
? Adolescent patients should routinely be offered the choice of a gastrostomy
Contraindications for gastrostomy placement:
? Poor anaesthetic risk
? Short-term feeding <3 months
? Abdominal disease present (assessed on an individual basis)
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Table 16.6 Examples of paediatric enteral feeds for children more than 1 year of age (8 kg)
Feed ? whole protein
Recommended age
(weight)
Feed ? hydrolysate and
amino acid
Whole protein (1 kcal/mL)
Clinutren Junior powder (Nestlea )
1?6 years (8?20 kg)
Hydrolysate feeds
Nutrini Peptisorb (Nutriciac )
? ready to feed (1 kcal/mL)
Frebini Original (Freseniusb )
1?10 years (8?30 kg)
Peptamen Junior liquid
(Nestlea ) ? ready to feed
(1 kcal/mL)
Nutrini (Nutriciac )
1?6 years (8?20 kg)
Peptamen Junior powder
(Nestlea ) ? powdered
version
Paedisure (Abbottd )
1?10 years (8?30 kg)
Pepdite 1+ (SHSe ) ?
powdered
Tentrini (Nutriciac )
7?12 years (21?45 kg)
MCT Pepdite 1+ (SHSe ) ?
powdered
Frebini Original Fibre (Freseniusb )
Nutrini Multifibre (Nutriciac )
Paediasure Fibre (Abbottc )
1?10 years (8?30 kg)
1?6 years (8?20 kg)
1?10 years (8?30 kg)
Tentrini Multifibre (Nutriciac )
7?12 years (21?45 kg)
Whole protein (1.5 kcal/mL)
Frebini Energy (Freseniusb )
Nutrini Energy (Nutriciac )
Paedisure Plus (Abbottd )
Tentrini Energy (Nutriciac )
Frebini Energy Fibre (Freseniusb )
Nutrini Energy Multifibre (Nutriciac )
Paedisure Plus Fibre (Abbottd )
Tentrini Energy Multifibre (Nutriciac )
Amino acid feeds
Neocate Advance (SHSe ) ?
powdered (ages 1?10 years)
Elemental 028 (SHSe ) ?
powdered (age >5 years)
Elemental 028 extra (SHSe )
? powdered (age >5 years)
Emsogen (SHSe ) ?
powdered (age >5 years)
1?10 years (8?30 kg)
1?6 years (8?20 kg)
1?10 years (8?30 kg)
7?12 years (21?45 kg)
1?10 years (8?30 kg)
1?6 years (8?20 kg)
1?10 years (8?30 kg)
7?12 years (21?45 kg)
a
Nestle Clinical Nutrition.
Fresenius Kabi Limited.
c
Nutricia Limited.
d
Abbott Laboratories Limited.
e
Scientific Hospital Supplies, International Limited.
b
fibre-containing feed. However, following chemotherapy a protein hydrolysate or amino
acid-based feed may be more appropriate if malabsorption occurs and should be considered in children with lower gut mucositis, radiation enteritis and with graft-versus-host
disease (GvHD) involving the gut following bone marrow transplant. They can be useful
whilst initially weaning from parenteral nutrition to enteral feeding. Table 16.6 gives
examples of paediatric feeds. Children with cancer may develop temporary lactose intolerance due to their chemotherapy, rotovirus infection or in particular in GvHD and
therefore require a lactose-free feed.
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The volume and delivery of the feed regimen should be determined according to the
child?s normal daily routine and can be provided as a continuous infusion, intermittent
bolus feeds or a combination of both. Continuous feed regimens are generally better
tolerated than intermittent bolus feeding due to the gastrointestinal side effects of treatment
such as nausea and vomiting. Nocturnal continuous feeding with daytime oral feeding
or bolus feeding tends be the pattern of choice and works well to achieve the nutritional
needs with minimal disruption to lifestyle. However, during periods of intensive treatment
or admissions for febrile neutropenia, it may be necessary to feed continuously 20?24
hours in order to achieve tolerability and maximum nutrient intake.
Additional electrolyte supplementation, potassium, phosphate, magnesium or calcium
may be needed depending on the child?s chemotherapy regimen. If the child has an enteral
tube in situ, this can help with their administration and subsequently improve compliance.
They can either be administered directly via the tube or added to the feed, with the
exception of calcium and phosphate due to the risk of precipitation.
Frequent continued support and monitoring is essential as feed tolerance and oral intake
can vary throughout treatment due to side effects, and adjustment to feed type, volume and
delivery is necessary to provide effective enteral feeding support. The majority of children
receiving enteral feeding will require it throughout their intensive treatment protocol, but
once treatment is completed or they go onto maintenance treatment, appetite usually
improves and a conscious effort should be made to wean off enteral feeding.
Parenteral nutrition
Parenteral nutrition (PN) previously was widely used and often the method of choice in
children with cancer as they already had central venous access and had been successful
in preventing and correcting malnutrition (Papadopoulou et al., 1998). However, with the
recognition of the advantages of using the enteral route in terms of cost-effectiveness
and maintenance of gut integrity along with a wider range of paediatric enteral feeds,
PN should be reserved for when the gastrointestinal tract is not functioning or cannot be
accessed or for patients whose enteral feed regimen cannot provide adequate nutrients. PN
is commonly indicated for children with severe mucositis and enteritis. Other indications
include typhlitis, neutropenic enterocolitis, ileus, chylous ascites post-surgery or severe
GvHD disease involving the gut following bone marrow transplantation.
Careful consideration should be given before commencement of PN and is of limited
nutritional benefit if required for less than 1 week. The child?s clinical condition may also
limit the effectiveness of PN due to medical problems, which may restrict fluid intake, with
medication and blood products taking precedence over nutrition. The majority of children
with cancer will have central venous access, and therefore more concentrated solutions
can be prescribed in order to maximum protein and calorie intake, although children
with single lumen lines in situ may require the PN to be interrupted for medication
or blood products, therefore potentially restricting the amount of parenteral nutrition
given.
Metabolic complications of PN are well documented (Koletzko et al., 2005) and are
not significantly different between children with malignancies and other children requiring nutritional support. However, it is important that electrolyte levels are monitored
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closely, in particular children with severe diarrhoeal losses or those receiving chemotherapy drugs that impair renal function. Drugs such as cisplatin and ifosfamide can cause
renal tubular damage associated with excess losses of magnesium, potassium, phosphate and calcium. Frequently children with large diarrhoeal losses and/or renal tubular
dysfunction require electrolyte additions above those normally recommended to PN as
outlined in the European Society of Paediatric Gastroenterology, Hepatology and Nutrition guideline (Koletzko et al., 2005). The use of the antifungal amphotericin can result in
hypokalaemia, resulting in a higher potassium requirement to PN; however, care should
be taken if the potassium-sparing diuretics amiloride or spironolactone are subsequently
used to counteract this effect. Routine monitoring of plasma glucose and lipid levels is
essential. In children with GvHD involving the gut who are receiving steroids as part
of their management, hyperglycaemia and hyperlipidaemia can occur with PN, and it
may be necessary to use intravenous insulin infusions to manage hyperglycaemia when
a reduction in glucose is inappropriate due to compromising nutritional intake. Children
who develop veno-occlusive disease of the liver following allogeneic or autologous bone
marrow transplant often require to be fluid restricted, and therefore concentrated solutions
should be considered to maximise nutrition, with sodium additions kept to a minimum to
prevent/treat any ascites.
Lipid is an integral part of PN in order to provide high energy needs without carbohydrate overload, and its high-energy density is of particular value in fluid-restricted patients.
It provides essential fatty acids, and hence in severe cases of marked hyperlipidaemia, it
is highly preferable to reduce the amount of lipid provided rather than stop it completely.
However, essential fatty deficiency is preventable with as little as 0.1 g/kg body weight
per day of linoleic acid (Koletzko et al., 2005), although a suboptimal energy intake will
result.
Parenteral iron should not be routinely supplemented in children with cancer as the
majority receive frequent blood transfusions and hence the potential risk for iron overload.
Trace element levels should routinely be monitored if PN is required for longer than 2
weeks and then monthly thereafter, as children with cancer receiving PN frequently require
extra additions of zinc and selenium to PN.
The PN prescription should be based on standard nutrient requirements and adjusted
depending on the individual child?s clinical condition in conjunction with the multidisciplinary team to provide the correct amount of fluid and nutrients for that individual
child.
Nutritional support in the infant with cancer
Providing adequate nutrition for the infant with cancer to maintain adequate growth during
the first year of life can be particularly challenging with obstacles such as vomiting, diarrhoea and mucositis. The majority of infants will require supplementary enteral feeding
to achieve an adequate intake. A well infant will tolerate 4-hourly feeds six times daily
once a body weight of 3.5 kg is reached and by the age of 3?6 weeks may sleep longer and
drop a night-time feed (Shaw & Lawson, 2007). A sick child may require smaller, more
frequent feeds, especially if vomiting occurs and depending on their clinical condition
may have increased or decreased fluid requirements.
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If enteral feeding is indicated, some infants may achieve an adequate intake by using
their normal standard infant formula in particular if a sore mouth was the initial cause of
a reduced oral intake. Mothers who are breastfeeding should be encouraged to continue
with this, and expressed breast milk (EBM) can be given via the tube. Although EBM may
have a lower energy density, especially if the fore milk is used which is lower in fat, the
physiological and psychological benefits in terms of the presence of immunoglobulins,
antimicrobial factors and the mother being able to contribute to the care of her sick infant
are important benefits (Johnson, 2007). If weight gain is inadequate with breast milk
alone, it can be supplemented with additional breast milk fortifiers or standard infant
formula.
Infants who have higher increased nutrient requirements or those who require a fluid restriction will benefit from a nutrient-dense formula such as SMA High Energy or Infatrini.
Another option would be to consider concentrating a normal infant formula to provide a
more nutrient-dense formula. Standard infant formulas in the United Kingdom are made
up to a dilution of 13%, but by making to a 15% concentration, a more nutrient-dense
formula will be achieved, which retains the appropriate protein?energy ratio (7.5?12%);
however, it is important to recognise that this is only used as a therapeutic procedure
and is not usual practice (Shaw & Lawson, 2007). In some situations, particularly in the
severely fluid-restricted infant, it may be necessary to add extra energy and/or protein
supplements to the infant formula.
Infants with impaired gut function, such as diarrhoea or mucositis, frequently do not
tolerate a standard whole protein, cow?s milk-based formula, and the use of a hydrolysed
protein or amino acid formula should be considered (Table 16.7).
It is important to try to maintain some oral intake for feeding skills to develop. Often,
the method of choice for tube feeding is by top-up bolus feeding, thus maintaining a
normal infant feeding pattern and preserving some oral intake. This is unfortunately not
always possible due to poor tolerance of top-up feeds. If vomiting occurs with large feed
Table 16.7 Examples of extensively hydrolysed infant formulas
Feed
Casein based
Pregestimil (Mead Johnsona )
Whey based
Pepti-Junior (Cow & Gateb )
Aptimil Pepti (Milupac )
Pork collagen and soya
Prejomin (Milupac )
Pepdite (SHSd )
MCT Peptide (SHSd )
Amino acid-based formulas
Neocate (SHSd )
Nutramigen AA (Mead Johnsona )
a
Per 100 mL
energy (kcal)
Protein
(g)
Osmolality
(mOsm/kg H2 O)
68
1.9
330
?
67
66
1.8
1.6
200
240
Trace
40% (of CHO)
75
71
68
2.0
2.1
2.0
193
237
290
?
?
?
71
68
2.0
1.9
360
348
?
?
Mead Johnson Nutrition.
Cow & Gate.
c
Milupa Ltd.
d
Scientific Hospital Supplies, International Limited.
b
Lactose
present
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volumes then smaller, more frequent feeds may be more appropriate, and the use of a
feed thickener should be considered such as Thixo D or Thick & Easy or a period of
continuous feeding with small oral/bolus feeds.
Infants treated for ALL or AML can be more challenging due to the length of treatment,
problems with gut toxicity and stomatitis. Weaning should be started around 17 weeks in
order to achieve a higher energy intake and to establish some oral feeding skills in between
periods of severe oral mucositis, otherwise feeding development becomes delayed, making
it harder for the infant to develop normal feeding skills (Ward et al., 2002).
Complementary and alternative diets
There is an increasing awareness amongst parents and families with regard to the role
of alternative or complementary nutritional therapies, and many are highly motivated to
seek information on food choices, dietary supplements and complementary nutritional
therapies in a bid to improve quality of life and increase chances of survival (Schmidt &
Ernst, 2004). The majority of such diets are made up of components, which claim to have
three major functions: detoxification, strengthening of the immune system and specific
therapies to attack the cancer cell (Weitzman, 2008).
The majority of the diets generally advocate a strict vegetarian or vegan regimen and
restrict animal products, salt and refined carbohydrates and only allow small quantities
of fat. Many are high-fibre, high-fruit/fruit juice and vegetable diets and may involve
additional detoxification in the form of fasting for several days or weeks as well as the use
of laxatives and enemas. Some involve the addition of different supplements to the basic
diet, which can be in potentially toxic doses. Diets involving frequent regular fruit juice
can result in early satiety and diarrhoea (Kogut, 2001), which will be more pronounced
in children leading to weight loss. Malnutrition can therefore occur due to the high-fibre
content of the diet, the low-calorie density and low-protein content, which in turn can
result in a reduced immune function, increased toxicity from conventional treatment and
therefore a poorer response (Weitzman, 2008).
High doses of vitamins and minerals may be harmful to children as well as the risk
of interaction with conventional treatment. With a current 80% cure rate of childhood
cancer by conventional treatments, it is imperative to ensure nothing is given which has
a negative interaction with treatment (Weitzman, 2008). It is essential that any parent
contemplating the use of an alternative diet should seek the appropriate advice from their
child?s physician or dietitian and those treating the child inquire non-judgementally about
their use.
Vitamin supplementation
Parents frequently ask if it is necessary for their child to take vitamin supplements,
especially the antioxidant vitamins A, C, E and ?-carotene, whilst being treated for cancer.
The mode of action of certain chemotherapy agents involves the generation of free radical
oxidants to cause cellular damage and necrosis/apoptosis of malignant cells, such as
alkylating agents, antitumour antibiotics and platinum compounds. The formation of free
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radicals leading to oxidative stress is one of the main pathogenic mechanisms for toxicity,
with toxicity being a dose-limiting factor for treatment.
Currently, there have been very few studies looking at changes in antioxidant status
and oxidative stress in children undergoing treatment for cancer, and studies generally
tend to only involve small patient numbers. However, one larger study of children undergoing treatment for ALL showed that a higher intake of vitamin C, ?-carotene and total
carotenoids was associated with a lower incidence of chemotherapy-related toxicity and
higher vitamin E intake at 3 months was associated with a lower incidence of infection
(Kennedy et al., 2004). A significant percentage of the children had inadequate intakes
and low plasma concentrations of antioxidants. As the children had an adequate energy
intake, which is often the case in children treated for ALL, the author suggested nutritional
counselling aimed at increasing fruit and vegetable intake in order to increase antioxidant intake and that more information is needed before antioxidant supplementation is
recommended. It is clear that further studies are required, and until then currently in the
United Kingdom the following is advised for children with cancer: supplementation of
vitamins and minerals above the RNI is not recommended because of potential toxicity
and interactions with the efficacy of conventional treatment. Children receiving enteral
feeds or nutritionally complete oral sip feeds should not need additional supplements.
Children not receiving nutritional support but who have a limited fruit and vegetable intake may benefit from a general multivitamin supplement but should be given extra advice
on how to incorporate more fruit and vegetables into their diet. As children undergoing
treatment for cancer frequently require blood transfusions, it is advisable that they take a
supplement which does not contain any iron or a small amount of iron (maximum of 15%
recommended daily allowance).
Glutamine
Many chemotherapy drugs, in particular anthracyclines, actinomycin and high-dose
methotrexate, result in both structural and functional injuries to the gastrointestinal tract,
resulting in mucositis severe enough to prevent an adequate oral intake. It is well documented that glutamine is a major fuel and important nitrogen source for enterocytes and
plays a key role in maintaining mucosal cell integrity and gut barrier function (van Acker
et al., 1999). Whilst there have been several studies looking at the role of both enteral and
parenteral glutamine in adult oncology patients, there are very few published studies looking at glutamine in paediatric oncology patients. An oral dose of up to 0.65 g/kg has been
shown to be safe and acceptable to use in paediatric oncology patients (Ward et al., 2003).
A significant reduction in the severity and duration of stomatitis using a smaller dose of
oral glutamine in children has been demonstrated (Anderson et al., 1998). Although no
significant difference in oral mucositis was observed, significant reductions in number of
children requiring PN and duration of PN have been demonstrated in other oral studies
(Aquino et al., 2005; Ward et al., 2009b), perhaps reflecting the role of glutamine in
improving lower gut mucositis. Currently, there are no studies looking at the role of parenteral glutamine in paediatric oncology patients partly due to stability problems adding
glutamine to small volumes of PN in paediatric patients. Although now available as a
dipeptide of glutamine and alanine (Dipeptiven, Fresenuis Kabi), its safety and efficacy in
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children have not yet been determined. Oral glutamine has been shown to be safe to use in
paediatric oncology patients, but further studies are still required to determine its effect in
particular regarding use in children undergoing high-dose chemotherapy and bone marrow
transplantation.
Other agents currently being investigated to prevent or alleviate symptoms of oral
mucositis in paediatric oncology patients include Gel-Clair (Cambridge Laboratories).
Steroid-induced diabetes
Children treated for ALL regularly receive the corticosteroid dexamethasone as part of
their treatment. Dexamethasone has potent lymphocytotoxic activity causing lymphoblast
lysis. However, its side effects include an increased appetite and raised blood glucose levels. Hyperglycaemia is usually only transient whilst the child is receiving dexamethasone;
however, in some cases it may be permanent. Children who appear more susceptible
to hyperglycaemia include those with a family history of diabetes, those overweight at
diagnosis and older children/adolescents.
Treatment involves the use of sliding scale intravenous insulin until blood sugar levels
are controlled. Subsequently, alteration in diet may be all that is necessary to control
blood sugar levels; however, the use of a twice daily injection of pre-mixed analogue and
isophane insulin may be advised or the use of a basal bolus regimen. Using basal and
rapid acting analogue insulins allows greater flexibility with regard to mealtimes as there
is no need to adhere to rigid meal and snack times as a bolus of insulin is injected prior to
food. Children treated for ALL can have variable appetites and food intakes, and hence a
basal bolus regimen allows for this variation.
Dietary advice should be simple, and the avoidance of rapidly absorbed carbohydrate
should be given along with advice on suitable alternatives and snack suggestions. High-fat
foods should not routinely be restricted especially in children who have poor appetites
and would be unable to achieve an adequate energy intake if fatty foods were restricted.
Similarly, high-fibre foods may not be appropriate due to being less energy dense, and
they may compromise the child?s energy intake. However, children who are eating well
and have a good appetite would benefit from an increased fibre intake as constipation is a
common side effect of vincristine, which is used in the treatment of ALL.
Late effects
The development of curative therapy for the majority of paediatric cancers has resulted
in a growing population of childhood cancer survivors who are at an increased risk of
various health problems (Wasilewski-Masker et al., 2008).
Bone morbidity in children with cancer both during and after completion of treatment is increasingly recognised as both a short-term and long-term problem (Rogers,
2008). This is especially the case in children who receive large cumulative doses of
glucocorticosteroids and methotrexate for treatment, such as ALL. Peak bone mass is
attained by late adolescence or early adulthood, with approximately 40% of total bone
mass accumulated in adolescence. Any interruptions to the normal process of bone mass
accretion during childhood and adolescence may impact on skeletal fragility in adulthood
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(Atkinson, 2008b). Hence, children and adolescents treated for cancer potentially miss the
opportunity for skeletal maturation. Other risk factors include reduced physical activity,
nutritional disorders of calcium and vitamin D deficiency and genetic factors (van der
Sluis & van der Heuvel-Eibrink, 2008). Other patients at risk include those treated for
Ewing?s sarcoma and osteosarcoma who have received methotrexate and ifosfamide (Sala
& Barr, 2007; Wasilewski-Masker et al., 2008).
Correction of bone mineral loss may be possible by correction of dietary deficiencies
including those of calcium and vitamin D; however, in some cases it is judged to use bisphosphonates such as pamidronate or alendronate. Calcium and vitamin D dietary advice
should be given along with supplementation such as Calcichew D3 Forte (Shire), Cacit
D3 (Proctor & Gamble Pharmaceuticals) and Adcal-D (Strakan). Advice on improving
diet and physical activity should also be recognised as a strategy for amelioration and
prevention (Sala & Barr, 2007).
Another well-reported effect in childhood cancer survivors is the recognition of the
prevalence of obesity particularly in children treated for ALL and brain tumours (Ladas
et al., 2005). The majority of studies have looked at ALL survivors and have revealed as
well as obesity a high prevalence of endocrine and metabolic disorders such as growth
hormone deficiency, hypothyroidism, insulin resistance and hyperlipidaemia (Gurney
et al., 2005; Steffens et al., 2008) with it being most detrimental in those patients treated
with bone marrow transplant/total body irradiation (Steffens et al., 2008).
The mechanism for the onset of obesity following treatment for ALL may be partly
due to a sustained imbalance between energy expenditure and energy intake. Lack of
physical activity, high calorie intake and metabolic changes following prolonged courses
of chemotherapy may all play a part in altering body composition in ALL survivors
(Warner, 2008). Reduced physical activity has been documented in ALL survivors and
could be due to a subtle psychological effect of cranial irradiation affecting motivational
drive or as a result of anthracycline-induced cardiomyopathy (Reilly et al., 1999; Warner,
2008). Very few children with ALL nowadays receive cranial radiation; therefore, one of
the major causes of obesity identified is lack of physical activity. It is clear that thought
should be given to routinely giving ?healthy eating? advice to children treated for ALL
and perhaps this should be at the start of or during long-term maintenance therapy.
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