Nutrition & Dietetics 2006; 63: 227239 DOI: 10.1111/j.1747-0080.2006.00107.

x
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
227
E.B. Ikeda, MMedScNut, MScNutDiet
C.E. Collins, PhD, AdvAPD, Senior Lecturer
F. Alvaro, MB BS, FRACP, Paediatric Haematologist/Oncologist
G. Marshall, MB BS, FRACP, MD, Director
M.L. Garg, PhD, APD, Director
Correspondence: C. Collins, Mail Box 38 Hunter Building, School of
Health Sciences, Faculty of Health, University of Newcastle, NSW 2308,
Australia. Email: clare.collins@newcastle.edu.au
Blackwell Publishing AsiaMelbourne, AustraliaNDINutrition & Dietetics1446-6368 2006 The Authors; Journal compilation 2006 Dietitians Association of Australiaxxx 2006634227239MiscellaneousWellbeing and side effects in children undergoing chemotherapyE.B. Ikeda
et al.
INSIGHT
Wellbeing and nutrition-related side effects in children
undergoing chemotherapy
E. Beatrix IKEDA,
1
Clare E. COLLINS,
1
Frank ALVARO,
2
Glenn MARSHALL
3,4
and Manohar L. GARG
5
1
Nutrition and Dietetics, School of Health Sciences and
5
School of Biomedical Sciences, University of Newcastle,
Callaghan,
2
Department of Paediatric Oncology/Haematology, John Hunter Childrens Hospital, Newcastle,
3
Centre
for Childrens Cancer and Blood Disorders, School of Womens and Childrens Health, University of New South Wales,
and
4
Sydney Childrens Hospital, Sydney, New South Wales, Australia
Abstract
Objective: To describe wellbeing and nutrition-related side effects in a group of paediatric oncol-
ogy patients undergoing chemotherapy, and to examine associations with nutritional status, disease
and treatment-related factors.
Methods: Cross-sectional survey of patients attending the Sydney (n = 41) or John Hunter Chil-
drens Hospitals (n = 13). Wellbeing was assessed using the Multi-attribute Health Status Classica-
tion Scheme (MHSCS) and the Play Performance Scale (PPS). Disease and treatment details were
obtained through patient and parent interviews and audit of medical records. Nutritional status was
assessed using anthropometric and biochemical measurements.
Results: Twenty-four per cent and 33% scored maximum points on the MHSCS and PPS, respec-
tively. Advanced stage of solid tumour or lymphoma was associated with worse MHSCS scores,
P = 0.008. Longer time on treatment correlated negatively with PPS scores (r = 0.35; P = 0.030). The
most frequent side effects were nausea, decreased appetite, vomiting and changes in taste. While
67% experienced ve or more side effects concurrently, the number increased with length of time on
treatment (r = 0.38; P = 0.006). Of the 23 patients experiencing ve or more side effects, only two
had been seen by a dietitian in the previous two months.
Conclusion: Nutrition-related side effects are common in children undergoing chemotherapy, with
the number of side effects not decreasing over time. While wellbeing scores were generally satis-
factory, those with advanced stage of solid tumour or lymphoma, or with longer time on treatment,
reported lower scores. We recommend that all paediatric oncology patients are referred for dietetic
review, even those in the later stages of treatment, in order to optimise nutritional status and
wellbeing.
Key words: chemotherapy, paediatric oncology, quality of life, side effects, wellbeing.
INTRODUCTION
Because of advances in cancer treatment, survival rates
in paediatric patients have improved dramatically over
the past 30 years,
1
with ve-year survival rates increas-
ing from 45% in the 1970s to 70% in the 1990s.
2
How-
ever, although cancer treatments are increasingly
effective, they are also intrusive and burdensome for
children and adolescents, impacting not only on their
nutritional health, but also on their wellbeing, or quality
of life (QOL).
3
Invasive procedures, including lumbar
puncture and bone marrow aspiration, treatment side
effects and frequent clinic visits and hospitalisations, all
impact adversely on physical, psychological and social
wellbeing.
4,5
The importance of measuring the wellbeing
E.B. Ikeda et al.
228
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
or QOL in patients undergoing cancer treatment has
been acknowledged, as information about it could con-
tribute to improvements in management.
6
For example,
knowledge about a patients QOL might inuence deci-
sion-making regarding choices between alternative
treatments, or initiating appropriate intervention if QOL
is deteriorating.
6
Quality of life or wellbeing has, until recently, been
underexplored in children with cancer.
7
In the present
study, we have opted to use the term wellbeing rather
than QOL.
In order to improve wellbeing, treatment tolerance,
growth and clinical outcomes, nutritional support has
been recognised as an important part of the oncology
care in children undergoing treatment for cancer.
810
Thorough nutritional assessment and monitoring of
nutritional status, as well as implementation of nutri-
tional support strategies, are important in order to pre-
vent or treat nutritional deciencies, to promote normal
growth and development, and to improve wellbeing,
immune competence and possibly survival.
8,9,1117
The aim of the present study was: (i) to describe well-
being and nutrition-related treatment side effects in a
cross-sectional group of paediatric oncology patients;
and (ii) to examine any associations with nutritional
status and disease and treatment-related factors (stage of
cancer, treatment intensity, length of time on treatment
and nutritional support).
METHODS
All data collected focused on the two months prior to
recruitment.
Sample and recruitment
Eligibility criteria for recruitment in the present study
included paediatric oncology patients aged 118 years,
attending either the Sydney Childrens Hospital, Rand-
wick (SCH) or the John Hunter Childrens Hospital
( JHCH), Newcastle, for chemotherapy. Patients who had
completed their treatment within six months prior were
also eligible, as it was assumed that their nutritional sta-
tus and wellbeing would still be affected by the disease
and the treatment, and they might still experience some
of the side effects associated with their treatment.
Exclusion criteria included termination of treatment
more than six months prior to recruitment, and age <1
or >18 years. It was assumed that there would be few
diagnoses in infants under 1 year of age, and informa-
tion about dietary intake and blood samples for assess-
ment of nutritional status would be difcult to obtain
in this age group. Further exclusions were subse-
quently set, as the physical and emotional state of the
patients and their parents was considered at recruit-
ment. The oncology nurses alerted the researchers
about patients in difcult family situations or vulnera-
ble psychological states, and advised not to attempt
recruiting these patients. Therefore, it was decided only
to approach potential participants for whom an invita-
tion to participate in the present study was considered
appropriate.
The patients and their parents were approached in the
outpatient clinics and paediatric wards. Detailed infor-
mation about the study was given both verbally and in
writing, and the patients and parents were made aware
that participation in the study was voluntary and with-
drawal was possible at any stage, without affecting the
childs medical care. The patients and their parents were
also asked for permission to access the patients medical
records.
During the recruitment period OctoberDecember
2000, 60 patients and their parents were invited to par-
ticipate. Written consent was obtained from 54 patients/
parents (n = 41 from SCH and n = 13 from JHCH). The
six patients and their parents who refused to participate,
all stated the large amount of stress and emotional bur-
den present in their lives as the reason for their refusal.
Measuring wellbeing
The Multi-attribute Health Status Classication Scheme
(MHSCS) and the Play Performance Scale (PPS) are
among the most frequently used instruments to assess
QOL and wellbeing in paediatric oncology patients. The
MHSCS has been devised to provide a comprehensive
description of the health status of survivors of childhood
cancer.
18
The tool is intended to assess physical and
mental wellbeing through evaluating the level of func-
tion for seven attributes: sensation, mobility, emotion,
cognition, self-care, pain and fertility. For each attribute,
three to ve levels of functioning are dened, ranging
from poor to optimum functioning.
18
The best possible
score is 6 (where 1 is scored for each attribute), and the
worst possible score is 27 (if a 4 or 5 is scored for each
attribute).
The PPS, based on the Karnofsky Scale of Perfor-
mance Status used to measure functional status in
adults, was designed to assess general wellbeing and
physical performance status in children through rating
usual play activity.
1921
It includes a spectrum of age-
appropriate play described with varying participation in
active and quiet activities, ranging from unresponsive
to fully active, normal functioning.
20
The maximum
score is 100 (fully active, normal) and the worst pos-
sible score is 0 (unresponsive).
Wellbeing and side effects in children undergoing chemotherapy
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
229
The MHSCS was completed by 45 patients/parents,
whereas the PPS was completed by 43. The remaining
participants did not return the questionnaires, or
returned incomplete questionnaires, and were therefore
excluded.
Side effects
The patients and their parents were interviewed about
nutrition-related treatment side effects experienced in
the last two months prior to recruitment.
Measuring nutritional status
Anthropometric measurements were performed accord-
ing to standard methodology.
2225
Height/length and
weight were measured with the usual equipment avail-
able in each outpatient clinic or wards, and recorded to
the nearest 10 g (g) and millimetre (mm), respectively.
Mid-upper arm circumference (MUAC) and triceps
skinfold thickness (TST) were measured according to
anthropometric recommendations
23
using a disposable
paper tape measure and Harpenden skinfold calliper
(Baty International, West Sussex, UK). All the anthro-
pometric measurements were taken by a single
observer (EBI) and the average of three measures was
used.
Weight-for-height (WFH), and age and gender-
specic percentiles and z-scores for all the above-
mentioned measures were calculated using the
nutritional anthropometry program NutStat in EpiInfo
2000 version 1.0.5 software (Centre for Disease Control
and Prevention, Atlanta, GA, USA).
Arm muscle area (AMA), an indicator of muscle pro-
tein reserves, and arm fat area (AFA), an indicator of cal-
orie reserves in the form of fat, were calculated from
MUAC and TST, respectively, using the following
formulae:
24
Upper arm area (UAA) (mm
2
) = /4 (M/)2
AMA (mm
2
) = [(M T)2]/4
AFA (mm
2
) = UAA AMA
where M = MUAC (mm) and T = TST (mm).
A one-off blood sample was drawn from each patient
as part of their routine blood testing or just before the
administration of chemotherapy. Serum albumin was
determined using a Cobas/Integra Albumin cassette,
applying the modied bromcresol green binding assay,
25
and serum pre-albumin was determined quantitatively
by rate nephelometry using an IMMAGE Immuno-
chemistry Systems PAB Test (Beckman Coulter Inc.,
Fullerton, CA, USA).
Disease and treatment details
Through interviews with the patients and their parents,
and audit of the medical records, details were obtained
about the disease and the treatment, including dietetic
referrals and nutritional interventions.
Statistics
Statistical analyses were performed using Minitab v.12
for Windows (Minitab Inc., State College, PA, USA). Dif-
ferences between groups were compared using the Stu-
dents two-sample t-test or one-way analysis of variance
(ANOVA), the KruskalWallis test (non-parametric vari-
ables) or the chi-squared test (categorical variables).
Spearmans rank correlation was used to examine the
strength of linear relationships between continuous
variables (wellbeing scores, number of side effects and
length of time on treatment). Regression models were
developed using a best ts model. We tested which
groups of variables appeared to explain the most varia-
tion in the test variable; then removed variables in a
stepwise manner to determine the strongest model.
Differences were considered signicant at P < 0.05.
For consistency, median values and the 25th and 75th
percentiles are reported for all data.
Ethics
The Ethics Committees of the University of Newcastle,
the Hunter Area Health Service and the South Eastern
Sydney Area Health Service approved the study
protocol.
RESULTS
Demographics
The median (P
25
, P
75
) age was six (4, 11) years for boys
(n = 33) and 11 (5.5, 14) years for girls. Five patients
were within six months of completion of treatment,
whereas 49 (91%) were on active treatment at the time
of recruitment. Median (P
25
, P
75
) length of time on treat-
ment was seven (4, 13) months. Two patients with solid
tumour had also received radiotherapy in the two
months prior to recruitment.
Forty patients (74%) had leukaemia or lymphoma,
and 14 (26%) had various solid tumours. The most rep-
resented disease was acute lymphoblastic leukaemia
(ALL) (n = 30). Data describing the different diagnoses
and stages of cancer represented, types of chemotherapy
protocols, stage of chemotherapy at recruitment and
types of medications taken are presented in a separate
article.
26
The oncology teams assessed stage of cancer
E.B. Ikeda et al.
230
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
and intensity of treatment. Solid tumours and lympho-
mas were classied as either stage 1 or 2 (localised)
(n = 7) or stage 3 or 4 (widespread disease) (n = 10),
with seven unable to be classied. ALL was classied as
Standard risk (n = 17) or High risk (n = 13). The
intensity of the treatment received by each patient was
classied as Low (n = 20), Medium (n = 18) or High
intensity (n = 9), based on the type, frequency and
dosage of the chemotherapeutic medications in the
treatment protocol.
A signicantly larger proportion of patients with solid
tumours were receiving high intensity treatment
compared with ALL or lymphoma (64% vs 6%;
P < 0.001).
The anthropometric and biochemical results are pre-
sented in detail separately.
27
Figure 1 illustrates the distribution of the QOL scores.
Of the 45 patients (83.3%) who completed the MHSCS,
38 (84.4%) scored 9 or lower (better). Of these, 11
(24.4%) patients scored 6, the best possible score. Seven
(15.6%) patients scored 10 or higher (worse). The worst
score obtained was 14 (n = 1). Median (P
25
, P
75
) score
was 8 (6.5, 9).
Of the 43 patients (79.6%) who completed the PPS,
36 (83.7%) scored 80 or better. Of these, 14 (32.6%)
patients scored 100, the maximum score. Seven (16.3%)
patients scored 70 or worse, the poorest score obtained
being 30 (n = 1). Median (P
25
, P
75
) score was 80 (80,
100).
MHSCS and PPS scores were compared between
patients with (i) solid tumour versus those with leu-
kaemia or lymphoma; (ii) different stages of cancer; and
(iii) different treatment intensities. The results are
shown in Table 1. A signicant difference was only
found in the case of MHSCS scores, where patients with
stage 3 or 4 solid tumour or lymphoma scored signi-
cantly higher (i.e. worse) compared with those with
stage 1 or 2.
MHSCS and PPS scores were compared between
patients with WFH percentiles at the 25th or below
(n = 8), and patients with WFH percentiles at the 75th
or above (n = 17). No signicant differences in either of
the scores were found between the two groups (median
(P
25
, P
75
) MHSCS total score 7 (6, 8.8) vs 8 (7, 9);
P = 0.606, and PPS score 90 (62.5, 100) vs 80 (80,
100); P = 0.860). This was repeated for other anthropo-
metric variables, but no signicant differences in either
MHSCS or PPS scores were found between the groups
(P > 0.05; data not shown).
Length of time on treatment correlated positively with
MHSCS total score (r
s
= 0.376; P = 0.015) and nega-
tively with PPS score (r
s
= 0.348; P = 0.030).
Figure 1 Distribution of scores obtained on the Multi-attribute Health Status Classication Scheme (MHSCS)* (n = 35) and
the Play Performance Scale (PPS)** (n = 43) in a sample of paediatric oncology patients.
(a)
5 6 7 8 9 10 11 12 13 14 15
0
5
10
Multi-attribute Health Status Classification
Scheme total score
N
o
.

p
a
t
i
e
n
t
s
*In the MHSCS, the optimum score is 6,
representing optimal wellbeing and
best possible functioning in all attributes
measured (sensation, mobility, emotion,
cognition, self-care and pain).
The poorest obtainable score is 27.
(b)
100 50 0
0
5
10
15
Play Performance Scale score
N
o
.

p
a
t
i
e
n
t
s
**In the PPS, the optimum score is 100
(fully active, normal), representing
optimal wellbeing and physical
performance.
The poorest obtainable score is 0,
representing poor wellbeing and
physical performance(unresponsive).
Wellbeing and side effects in children undergoing chemotherapy
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
231
Even though there was no signicant difference in
PPS scores when patients with different stages of cancer
were compared, a regression model containing the vari-
ables stage of cancer (for patients with solid tumour or
lymphoma) and serum albumin explained a signicant
amount of the variation in PPS score (R
2
adjusted = 85.6%; P = 0.005).
The regression Equation 1 is:
PPS score = 91.8 2.36 Stage of solid tumour/
lymphoma + 5.22 Albumin (g/L)
This indicates that an increase in stage of cancer by one
unit (e.g. from stage 1 to stage 2) is associated with a
decrease in PPS score of approximately 2.4 points. Every
g/L increase in albumin is associated with an increase in
PPS score of 5.2 points.
Side effects
Within the two months prior to recruitment, 50 patients
(92.6%) reported having experienced nutrition-related
side effects from their treatment (Figure 2). Of these, 23
(66.7%) experienced ve or more side effects, and
14.8% experienced nine or more side effects
concurrently.
No signicant association was found between the
number of side effects and type of cancer (solid tumour
or leukaemia/lymphoma), stage of cancer or treatment
intensity (P > 0.05; data not shown) when the patients
were divided into two groups: those who experienced
ve or less and those who experienced more than ve
side effects. However, a signicant positive correlation
was found between the number of side effects experi-
enced and length of time on treatment (r
s
= 0.38,
P = 0.006).
Referrals for dietetic and
nutritional support
In the previous two months, 17 patients (31.5%) had
been seen by a dietitian and 15 (27.8%) had received
nutritional support in hospital. A signicantly larger
proportion of patients with solid tumours had been seen
by a dietitian and had received nutritional support
(P = 0.001 and P = 0.004, respectively) (Table 2). A sig-
nicantly larger proportion of patients receiving high
intensity treatment had also received nutritional support
compared with those on low or medium intensity treat-
ment (P = 0.033) (Table 2).
Of the 23 patients who had experienced ve or more
side effects, only three had been seen by a dietitian.
Nutritional status and side effects
No signicant differences in any of the anthropometric
variables, serum albumin or pre-albumin, were detected
Table 1 Comparison of wellbeing scores (Multi-attribute Health Status Classication Scheme, MHSCS and Play Performance
Scale, PPS) between patients with (i) solid tumour versus leukaemia or lymphoma; (ii) different stage of cancer; and (iii) dif-
ferent treatment intensities
Median (P
25
, P
75
)
(a)
MHSCS score PPS score
Cancer type
Leukaemia/Lymphoma (n = 36) 8 (6, 9) 80 (80, 100)
Solid tumours (n = 9) 7 (7, 10) 85 (80, 100)
P = 0.554 P = 0.806
Cancer stage
Solid tumour/lymphoma stage 1 or 2 (n = 6) 7 (6, 7) 95 (82.5, 100)
Solid tumour/lymphoma stage 3 or 4 (n = 5) 8.5 (7.8, 12.5) 80 (50, 90)
P = 0.008 P > 0.050
ALL standard risk (n = 16) 8 (6, 8.8) 80 (80, 100)
ALL high risk (n = 10) 9 (8, 9) 85 (60, 100)
P = 0.085 P = 0.558
Treatment intensity
Low (n = 17) 7 (6, 8.3) 90 (80, 100)
Medium (n = 15) 8.5 (7, 9) 80 (60, 90)
High (n = 5) 8 (7, 10.5) 80 (80, 100)
P = 0.166 P = 0.286
(a)
Median (25th and 75th percentiles).
ALL = acute lymphoblastic leukaemia.
E.B. Ikeda et al.
232
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
when patients experiencing ve or less side effects were
compared with those experiencing more than ve side
effects (P > 0.05; data not shown). Some side effects
were found be associated with certain measures of nutri-
tional status. As shown in Figure 3, pre-albumin levels
were signicantly lower in patients who experienced
oral mucositis (n = 23) (P = 0.013) or dysphagia (n = 9)
(P = 0.034) compared with those who did not. Serum
pre-albumin was signicantly higher in patients experi-
encing changes in taste sensation (n = 29) (P = 0.039)
Figure 2 The most common nutrition-related treatment side effects experienced in the previous two months in 54 paediatric
oncology patients.
0
10
20
30
40
50
60
70
80
90
N
a
u
s
e
a
D
e
c
r
e
a
s
e
d
a
p
p
e
t
i
t
e
V
o
m
i
t
i
n
g
H
y
p
o
g
e
u
s
i
a
/
t
a
s
t
e
c
h
a
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s
O
r
a
l

m
u
c
o
s
i
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i
s
D
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o
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i
a
/
s
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e
s
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i
a
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a
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e
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o
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f
l
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f
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s
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i
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f
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Side effects
%

p
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Table 2 Comparison by cancer type and treatment intensity of the proportion of paediatric oncology patients who had been
seen by a dietitian or received nutritional support in the previous two months (n = 54)
Seen by a dietitian*
Cancer type (n = 45) Yes (n = 17) (%) No (n = 28) (%)
Leukaemia/lymphoma (n = 34) (75.6%) 23.5 76.5
Solid tumours (n = 11) (24.4%) 81.2 18.2
Nutritional support**
Cancer type (n = 54) Yes (n = 15) (%) No (n = 39) (%)
Leukaemia/lymphoma (n = 40) (74.1%) 17.5 82.5
Solid tumours (n = 14) (25.9%) 57.1 42.9
Seen by a dietitian***
Treatment intensity (n = 39) Yes (n = 13) (%) No (n = 26) (%)
Low (n = 16) (41%) 18.7 81.3
Medium (n = 17) (43.6%) 35.3 64.7
High (n = 6) (15.4%) 66.7 33.3
Nutritional support****
Treatment intensity (n = 47) Yes (n = 12) (%) No (n = 35) (%)
Low (n = 20) (42.6%) 10.0 90.0
Medium (n = 18) (38.2%) 27.8 72.2
High (n = 9) (19.2%) 55.6 44.4
*Chi-squared test, P = 0.001; **Chi-squared test, P = 0.004; ***Chi-squared test, P = 0.102; ****Chi-squared test, P = 0.033.
Wellbeing and side effects in children undergoing chemotherapy
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
233
and albumin was signicantly higher in patients expe-
riencing nausea (n = 37) (P = 0.010) compared with
patients not experiencing these side effects (Figure 3).
Nutritional status and referrals for
dietetic and nutritional support
Table 3 compares anthropometric data between patients
who had been seen by a dietitian in the last two months
and those who had not. As shown, the majority of the
variables were signicantly lower in the patients who
had been seen by a dietitian.
No signicant differences in the biochemical variables
were found between patients who in the last two
months had been seen, and those who had not been
seen by a dietitian. Patients who had received nutri-
tional support in the last two months had a strong trend
towards lower levels of serum albumin compared with
patients who had not received nutritional support
(P = 0.056) (Figure 4).
Figure 3 Comparison of serum albumin and pre-albumin between patients who had experienced some selected treatment
side effects and those who had not, in 54 paediatric oncology patients. * = outlier positions.
(a) (b)
0.0
0.1
0.2
0.3
0.4
0.5
Oral mucositis
S
e
r
u
m

p
r
e
-
a
l
b
u
m
i
n

(
g
/
L
)
P = 0.013;
KruskalWallis test
No (n = 22) Yes (n = 23)
No (n = 36) Yes (n = 9)
0.0
0.1
0.2
0.3
0.4
0.5
Dysphagia/difficulty chewing
S
e
r
u
m

p
r
e
-
a
l
b
u
m
i
n

(
g
/
L
)
P = 0.034;
KruskalWallis test
(c) (d)
Yes (n = 29) No (n = 16)
0.5
0.4
0.3
0.2
0.1
0.0
Taste changes
S
e
r
u
m

p
r
e
-
a
l
b
u
m
i
n

(
g
/
L
)
KruskalWallis test
P = 0.039;
Yes (n = 37)
No (n = 8)
44
34
24
Nausea
S
e
r
u
m

a
l
b
u
m
i
n

(
g
/
L
)
KruskalWallis test
P = 0.010;
E.B. Ikeda et al.
234
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
Using regression analysis, having received nutritional
support in the last two months explained a signicant
amount of the variability in WFH percentile
(R
2
adjusted = 13.5%; P = 0.005). The regression
Equation 2 is:
WFH percentile = 65.1 25.8 Nutritional support
This indicates that being in the group receiving nutri-
tional support was associated with a WFH percentile
approximately 26 percentile points lower compared
with those who did not receive nutritional support.
DISCUSSION
One of the most important factors that inuences well-
being in oncology patients is believed to be the side
effects experienced while undergoing treatment. Com-
bination chemotherapy, used today in the treatment of
many childhood neoplasms,
28,29
involves a variety of
agents that affect host cells in individual ways, therefore
creating numerous side effects that can often result in
decreased appetite, anorexia, weight loss and eventually
malnutrition.
3034
The most common side effects experienced by paedi-
atric oncology patients are:
1 Nausea and vomiting;
3538
often accompanied by
dehydration, loss of protein and electrolyte-rich
gastrointestinal contents,
39
anorexia, weakness and
weight loss;
38
2 Mucositis;
40
due to altered integrity of the mucosal
epithelial cells of the gastrointestinal tract, leading to,
a generalised inammatory response.
39,41
It is often
associated with pain and difculties in chewing and
swallowing;
38
3 Xerostomia;due to altered composition and
amount of saliva;
40,42
4 Taste and smell abnormalities;often leading to
reduced appetite, anorexia
30,31,39
and learned food
aversions, which stimulate further nausea and vom-
iting;
30,34,39,41
5 Diarrhoea,
39
fatigue,
43
pain
39
and infections;
8
all of
which exacerbate nutritional problems such as poor
appetite, and increase the risk of weight loss, nutri-
tional deciencies and worse prognosis.
In children, psychological factors such as stress, fear,
anxiety, depression and poor QOL, are believed to con-
tribute to a decrease or loss of appetite with an accom-
panying reduced quality and quantity of food
consumed.
35,44
Table 3 Comparison of anthropometric data between paediatric oncology patients who had been seen by a dietitian or
received nutritional support, and those who had not (n = 54)
Variable Median (P
25
, P
75
)
(a)
P-value
Seen by a dietitian (n = 17) Not seen by a dietitian (n = 28)
z-score for height
(b)
0.04 (0.8, 0.8) (n = 16) 0.3 (0.7, 0.6) (n = 27) 0.980
z-score for weight
(b)
0.1 (1.1, 0.3) (n = 16) 0.2 (0.1, 1.4) (n = 27) 0.029
WFH percentile 32.3 (24.7, 66.8) (n = 14) 81 (52.4, 93.5) (n = 26) 0.006
AMA percentile 25 (10, 50) (n = 15) 75 (37.5, 90) (n = 25) 0.022
AFA percentile 25 (10, 50) (n = 15) 75 (50, 90) (n = 25) 0.001
Nutritional support (n = 15) No nutritional support (n = 39)
z-score for height
(b)
0.5 (0.8, 0.8) (n = 14) 0.3 (0.9, 0.6) (n = 38) 0.220
z-score for weight
(b)
0.1 (1.3, 0.5) (n = 14) 0.1 (0.5, 0.9) (n = 38) 0.430
WFH percentile 26 (17.5, 63.5) (n = 13) 64.1 (47.7, 90.3) (n = 36) 0.011
AMA percentile 25 (10, 50) (n = 11) 50 (25, 75) (n = 35) 0.020
AFA percentile 25 (10, 50) (n = 11) 50 (50, 90) (n = 35) 0.024
(a)
Median (25th and 75th percentiles).
(b)
Normally distributed data.
AFA = arm fat area; AMA = arm muscle area; WFH = weight-for-height.
Figure 4 Comparison of serum albumin between paediatric
oncology patients who had received nutritional support and
those who had not (n = 45).
No (n = 33) Yes (n = 12)
24
34
44
Nutritional support in the last two months
S
e
r
u
m

a
l
b
u
m
i
n

(
g
/
L
)
P = 0.056;
KruskalWallis test
Wellbeing and side effects in children undergoing chemotherapy
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
235
Many side effects are temporary and reversible; how-
ever, their nutritional consequences may persist for long
periods leading to a negative impact on health and well-
being and may lead to longer hospitalisation, decreased
response to the treatment and reduced clinical
outcome.
8,11,12,39,42,4547
Our results indicate that for this group of paediatric
oncology patients, attending two major paediatric
teaching hospitals in New South Wales, wellbeing (or
QOL) is satisfactory. These results support some of the
literature suggesting that QOL, in the majority of pae-
diatric oncology patients, is not impaired. Noll et al.
investigated whether intensive chemotherapy has dete-
riorating effects on social, behavioural and emotional
QOL in 76 children aged 815 years with various types
of cancer, except brain tumours, undergoing chemo-
therapy.
48
Social functioning (peer relationships), emo-
tional wellbeing and behavioural functioning were
evaluated using several different assessment tools, and
the results of children with cancer were compared with
76 healthy children (classroom peers of the patients).
Results showed that apart from lower satisfaction with
athletic competence in children with cancer, measures
of depression, loneliness, anxiety or self-concept did
not differ between the children with cancer and the
controls.
From our results, it appears that children with solid
tumours do not have poorer wellbeing than those with
leukaemia or lymphoma, as the median scores obtained
in the two groups were not signicantly different. It does
appear, however, that stage of cancer is an important
determinant of wellbeing in children with solid tumour
or lymphoma, as the median MHSCS total score
obtained in those with cancer stage 1 or 2 was signi-
cantly better compared with those with stage 3 or 4.
Along with serum albumin, stage of solid tumour or
lymphoma contributed to signicantly explain the
majority of the variability in PPS scores (Eqn 1).
This is the rst report of poorer QOL in children with
advanced, compared with those with less advanced
cancer.
Our results suggest that intensity of treatment and
referrals for dietetic or nutritional support are not asso-
ciated with impairments in wellbeing. This is despite the
nding that serum albumin levels contributed to the
variability of PPS scores. Number or type of nutrition-
related treatment side effects experienced were also not
associated with impairments in wellbeing. However,
children and adolescents with cancer consider treatment
side effects, such as nausea and alopecia, the most dif-
cult aspects of the treatment.
4
This suggests that sup-
portive therapies given, including medications and
nutritional support, are effective in ameliorating side
effects that impact on QOL, even in the presence of sub-
optimal clinical indicators.
Length of time on cancer treatment does, however,
seem to impact on wellbeing. A signicant positive cor-
relation between length of time on treatment and
MHSCS total score and a signicant negative correlation
between length of time on treatment and PPS score sug-
gest that wellbeing is poorer with longer time on treat-
ment. This association has not been reported previously,
although it has been suggested that QOL after cessation
of cancer treatment may be even more impaired than
during the treatment period.
49
In a study of QOL in 51 children and adolescents on
treatment for cancer (n = 16) and off treatment (n = 35),
von Essen et al. found that although the QOL of cancer
patients receiving treatment did not differ from healthy
children (data for healthy children were previously
obtained by other researchers), levels of depression and
anxiety were higher, and levels of psychological wellbe-
ing and physical self-esteem were lower, in patients who
had nished their treatment compared with healthy
children.
49
Meeske et al. investigated the health-related QOL of
paediatric oncology patients using responses obtained
from parents to the Paediatric Oncology Quality of Life
Inventory (PedsQL) 4.0 Generic Core scales, the
PedsQL 3.0 Acute Cancer Module and the PedsQL
Multidimensional Fatigue Scales.
50
The participants of
the study were the parents of children aged between two
and 18 years, diagnosed with either a brain tumour (BT;
n = 86) or ALL (n = 170). In general, patients with BT
experienced more health-related QOL problems than
patients with ALL. The majority of BT survivors had sig-
nicant physical, psychosocial and fatigue problems.
Long-term ALL survivors tended to return to normal
functioning; however, a small group continued to strug-
gle with psychosocial problems.
Similarly, Eiser et al. investigated QOL of 68 children
who had been diagnosed with ALL (n = 45) or central
nervous system tumours (n = 27).
51
All the children
were over the age of eight years, well and in remission
and had been diagnosed for more than four years, at the
time of the study. QOL was measured using the PedsQL
4.0 questionnaires and was completed by each child and
their mothers. Survivors of central nervous system
tumours reported poorer physical and psychosocial
health than ALL patients. The ALL patients QOL scores
indicated that psychosocial health was poorer in com-
parison with their physical health. This challenges the
common assumption that the end of treatment brings
relief and a return to normal life.
1,49
The tools used to assess wellbeing in the present
study are not perfect. It is not known how accurately the
E.B. Ikeda et al.
236
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
parents and the children may have reported the wellbe-
ing, and therefore, how representative their answers are
of the childrens actual experience.
When Lansky et al. tested the PPS, they found that
parents competently and reliably rated the childrens
play performance, and that they were able to discrimi-
nate adequately between differences in levels of func-
tioning.
20
The PPS has been found to be a valid tool
providing quantiable, reproducible and meaningful
data.
20
However, the PPS apparently is not sensitive
enough to differences in status for those patients func-
tioning in the healthy range.
52
Another disadvantage of
the PPS is that it does not include a time factor, thus
unless asked separately, it is not known how long the
patient has been in a certain health state or when
changes happened. The validity of the MHSCS has not
yet been assessed.
The present study, being a cross-sectional assessment
of wellbeing, is unable to detect changes in wellbeing
over time. In addition, the cross-sectional study design
and small numbers of oncology patients means that the
time into the treatment at which patients participated
in the present study could not be standardised. There-
fore, data were collected from newly diagnosed patients
as well as from patients who were almost nished with
their treatment. The stage of treatment a patient was at,
and thus the intensity of the treatment, may have
inuenced the patients responses. Furthermore, there
were no controls in the present study, and the results
were therefore not compared with subjective responses
of healthy children and adolescents. In addition, the
large number of analyses undertaken increase the risk
of nding statistically signicant ndings by chance
alone and hence all results should be interpreted with
caution.
As expected, based on the literature to date, nutrition-
related side effects of chemotherapy appear to be very
common in this cross-sectional group of paediatric
oncology patients. The vast majority of the patients
(92.6%) had experienced nutrition-related side effects
in the last two months prior to recruitment, and most of
these patients (66.7%) experienced ve or more side
effects concurrently. The most commonly reported side
effects were nausea, decreased appetite, vomiting,
changes in taste and smell sensation and oral mucositis
(Figure 2). This is consistent with previous reports.
3540
The relationship between side effects and nutritional
status is unclear. When looking at the number of side
effects experienced, there were no anthropometric or
biochemical differences between patients experiencing
ve or less, and those experiencing more than ve side
effects. When looking at type of side effects, in most
cases, no anthropometric differences were found
between patients who had and those who had not expe-
rienced the respective side effects. Serum pre-albumin
was, however, lower in patients experiencing oral
mucositis (P = 0.013) or dysphagia (P = 0.034) com-
pared with patients not experiencing these problems
(Figure 3). Interestingly, pre-albumin was higher in
patients experiencing taste changes (P = 0.039), and
albumin was higher in patients experiencing nausea
(P = 0.010), compared with patients not experiencing
these side effects (Figure 3). It may be that the patients
were able to maintain their food intake despite having
taste changes or nausea, whereas food intake, and there-
fore nutritional status, declined when experiencing
mucositis or dysphagia. The fact that almost everybody
(50 of 54) had been experiencing side effects may have
reduced the power to detect differences between the
groups.
Although serum albumin is the most commonly used
biochemical indicator of nutritional status,
53
because of
its long half-life levels can remain within the normal
range for weeks even after the onset of protein deple-
tion. Therefore, it might not be sufciently sensitive to
detect mild forms of malnutrition or acute changes in
nutritional status.
5456
Pre-albumin, with its shorter half-
life, is thought to be a better and more sensitive indica-
tor of nutritional status than albumin.
46
Type or stage of cancer, or intensity of treatment, were
not found to be related to the number of side effects
experienced. It could be that type and stage of cancer,
and treatment intensity inuence the severity rather
than the number of problems experienced. However, as
the present study did not measure or grade the severity
of the problems and side effects experienced, it is dif-
cult to say whether this is the case. This could be exam-
ined more closely in a prospective study.
A signicant positive correlation between the number
of side effects experienced and length of time on treat-
ment (r
s
= 0.379, P = 0.006) indicated that longer time
on treatment was associated with an increase in the
number of side effects experienced. This is in contrast to
the expectation that side effects decrease with time.
When looking at the individual side effects, those who
had experienced increased appetite and/or taste changes
had been on treatment for a longer length of time. Leu-
kaemia and lymphoma patients had been on treatment
longer than solid tumour patients, and the majority
were on continuation therapy, which is the last stage in
the treatment protocol involving less intensive chemo-
therapy than previous stages. Nevertheless, patients still
reported large numbers of problems even at this stage.
This indicates that it is the length of time on treatment
rather than treatment intensity that inuences the num-
ber of side effects experienced.
Wellbeing and side effects in children undergoing chemotherapy
2006 The Authors
Journal compilation 2006 Dietitians Association of Australia
237
In the present study, approximately one-third of the
patients had been referred to a dietitian for a nutritional
review, and approximately the same proportion had
received nutritional support in the previous two
months. Among the patients seen by a dietitian and/or
receiving nutritional support, the majority had a solid
tumour. Therefore, it was not surprising that referrals
for dietetic and nutritional support were more common
among patients on high-intensity treatment (Table 2), as
more of these had a diagnosis of solid tumour. Referrals
for dietetic or nutritional support were not found to be
more common among higher stages of cancer, but this
could be due to the low number of subjects in these
groups.
Results indicate that referrals for dietetic and nutri-
tional support were generally received for patients who
had worse nutritional status (Table 3). This is further
conrmed by the nding that having received nutri-
tional support signicantly explained the variability in
several anthropometric variables. Receiving nutritional
support was associated with a signicantly lower WFH
percentile (26%) (Eqn 2).
Although it was not surprising to nd that patients
who are at obvious nutritional risk are the ones who are
being referred to a dietitian and/or receive nutritional
support, it was surprising to nd that only two of 23
patients who experienced more than ve side effects in
the last two months had been seen by a dietitian. This
suggests that many patients at risk of developing nutri-
tional problems as a result of multiple side effects of the
treatment are not being monitored regularly.
The importance of providing supportive interven-
tions to manage nutritional problems early and the iden-
tication of patients who are at risk at an early stage
could be evaluated in a prospective study.
Signicant differences in albumin and pre-albumin
were not found between those referred and those not
referred; however, there was a trend towards lower
levels of serum pre-albumin in patients referred to a
dietitian (P = 0.081), and a strong trend towards lower
levels of serum albumin in patients referred for nutri-
tional support compared with those not referred
(P = 0.056; Figure 4). These results may have been con-
founded by the timing of the study as the nutritional
problems of the patients seen by a dietitian and/or
receiving nutritional support are likely to have begun to
be resolved by the time the blood samples were taken.
Our results support those of Tyc et al., who examined
nutritional and treatment-related characteristics in 173
children with cancer who had been referred for nutri-
tional support and 43 children with similar treatment
protocols who had not been referred for nutritional sup-
port.
57
That study found that nutritional status, mea-
sured by serum albumin, and dietary intake were poorer
in children in the group referred compared with those in
the latter group, and that solid tumour patients were
more nutritionally depleted than patients with other
types of cancer.
CONCLUSION
In summary, the present study indicates that wellbeing
was generally satisfactory in this sample of children with
cancer. However, patients with advanced stage of cancer
or those with longest time on treatment appear to
achieve lower wellbeing scores. Nutrition-related side
effects were commonly experienced in children under-
going chemotherapy, although it is unclear how much
side effects impact on nutritional status or treatment
outcomes. Contrary to what was expected, the number
of side effects experienced do not seem to decrease with
longer time on treatment.
Although referrals for nutritional support were found
to be common in patients with solid tumours and those
with obviously poor nutritional status, many patients at
risk for developing nutritional problems as a result of
multiple treatment side effects are not being monitored
regularly by a dietitian. We therefore recommend that all
paediatric patients with cancer would benet from a
referral for nutritional support, even those in the later
stages of their treatment. This would provide the oppor-
tunity to optimise nutritional status throughout the
treatment in order to further optimise wellbeing,
response to treatment and outcome.
ACKNOWLEDGEMENTS
We thank R Lessem and N Linabury for help with data
collection; the oncology teams at JHCH and SCH for
help with recruitment of subjects and blood collection;
Mr L Clark and HAPS for assistance with biochemical
analyses; Drs S Ryan and J Chamberlain ( JHCH) and B
Richmond (SCH) for assistance with diagnostic data;
and JHCH Cancer Research and Support Fund for fund-
ing. Finally we wish to thank the patients and their fam-
ilies for participating in the study.
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