Pediatr Blood Cancer 2009;53:570–575

Nutritional Problems in Children Treated for Medulloblastoma:Implications for Enteral Nutrition Support

Evelyn Ward, BSc, RD,1* Monica Hopkins, Bnurs, MSc, PG Dip Ed, RSCN, RGN,2 Lesley Arbuckle, BSc, PG Dip, RD,3

Nicola Williams, BSc, MSc, RD,4 Lynette Forsythe, BSc, RD,4

Sylwia Bujkiewicz, PhD,5 Barry Pizer, MB, ChB, PhD, MRCP, FRCPCH,2

Edward Estlin, BSc, PhD, MRCP, FRCPCH,6 and Susan Picton, BM, BS, BmedSci, MRCP, FRCPCH7

INTRODUCTION

Medulloblastoma is the most common malignant primary

central nervous system tumour occurring in childhood [1,2].

Current treatment includes surgery, radiotherapy to the whole

neuraxis with concomitant chemotherapy followed by eight cycles

of the three drug chemotherapy regimen, cisplatin, vincristine and

lomustine [1–4]. Currently survival rates are now around 80% for

children with standard risk, medulloblastoma and between 40% and

60% in those with high risk disease [1–3,5]. However survivors are

at risk of long term sequelae due to the tumour, surgery (cerebellar

mutism) and the adjuvant treatment, particularly whole brain

radiotherapy [1,2,6–11]. During treatment toxicity problems such

as vomiting and constipation, are common [12]. In addition patients

may develop significant nutritional problems and require nutritional

support. Malnutrition is a common complication of cancer and its

treatment, which can have a profound effect on a child’s energy

levels and subsequently quality of life [13]. Malnutrition contributes

to a reduced tolerance to therapy and protein calorie intake may also

affect sensitivity to chemotherapy agents [12,14]. Malnutrition

is also associated with a higher risk of infectious complications [15].

There are very few published studies looking specifically at

nutritional problems in children and adolescents treated for

medulloblastoma receiving multimodal therapy. In 2006 the

Children’s Cancer and Leukaemia Group (CCLG) CNS division

undertook an audit to investigate nutritional problems in children

and adolescents treated for medulloblastoma according to the SIOP

HIT PNET IV protocol [4]. Therefore the aims of this audit were to

identify the nature and severity of nutritional problems associated

with the current treatment of medulloblastoma in children and

adolescents in three CCLG centres as well as to identify current

methods of nutritional support used and their efficacy in terms of

outcome and to identify risk factors for nutritional morbidity during

treatment.

MATERIALS AND METHODS

Subjects

Children and adolescents treated for medulloblastoma in

three paediatric CCLG centres in the UK from January 2001 to

January 2006. All patients had been treated according to the HIT-

SIOP PNET IV protocol. This was a randomised study of two

different fractionation regimens (standard and hyperfractionated)

for craniospinal radiotherapy and adjuvant chemotherapy with

vincristine weekly during radiotherapy followed by up to eight

6-week cycles of the three drug chemotherapy regimen cisplatin,

vincristine and lomustine [4] (Fig. 1).

Data Collection

A multicentre retrospective audit of medical and dietetic notes of

the children and adolescents treated in the three CCLG centres using

a pre-designed clinical research form was undertaken. Data on

Background. The aim of this study was to identify the natureand severity of nutritional problems associated with the currenttreatment of medulloblastoma and to identify any risk factors fornutritional morbidity during treatment. Procedure. A multicentreretrospective audit of medical and dietetic notes of 41 childrentreated for medulloblastoma in three UK paediatric oncology centreswas undertaken. Data on nutritional status, nutritional support,mutism, swallowing and common toxicity criteria (CTC) scoresfor vomiting, constipation and mobility were collected at definedpoints in treatment from diagnosis until 12 months post-treatment.Results. Significant problems including weight loss, vomiting andconstipation were highlighted early on in treatment. The majority ofpatients were well nourished at diagnosis with a mean percentageweight: height of 99.8%, however nutritional status started to decline

early in treatment during radiotherapy, coinciding with 49% ofpatients having grade 1 or above CTC score for vomiting andconstipation. The decline in nutritional status continued, peaking bycourse 2 of chemotherapy with a mean weight loss of 8.2% sincediagnosis. Proactive supplementary feeding early in treatment byone of the three centres demonstrated a superior nutritional outcomewhen compared statistically to the two centres that fed only as aresponse to nutritional decline. Conclusion. The study highlightedsignificant morbidity associated with the current treatment ofmedulloblastoma. Findings suggest the need to consider earlierproactive nutritional intervention to prevent nutritional declineduring treatment. These early nutritional problems may be related totoxicities of radiotherapy and concomitant vincristine. Pediatr BloodCancer 2009;53:570–575. � 2009 Wiley-Liss, Inc.

Key words: child; enteral nutrition; longitudinal study; medulloblastoma; toxicity

� 2009 Wiley-Liss, Inc.DOI 10.1002/pbc.22092Published online 15 June 2009 in Wiley InterScience(www.interscience.wiley.com)

——————1Dietetic Department, St James’s University Hospital, Leeds UK;2Oncology Department, Alder Hey Children’s Foundation, Liverpool,

UK; 3Dietetic Department, Alder Hey Children’s NHS Foundation,

Liverpool, UK; 4Dietetic Department, Royal Manchester Children’s

Hospital, Manchester, UK; 5Children’s Cancer and Leukaemia Group,

University of Leicester, Leicester, UK; 6Oncology Department, Royal

Manchester Children’s Hospital, Manchester, UK; 7Paediatric

Oncology Department, St James’s University Hospital, Leeds, UK

Grant sponsor: Cancer Research UK; Grant sponsor: Samantha

Dickson Brain Tumour Trust.

*Correspondence to: Evelyn Ward, Senior Paediatric Dietitian, Level

04, Gledhow Wing, St James’s University Hospital, Beckett Street,

Leeds LS9 7TF, UK. E-mail: evelyn.ward@leedsth.nhs.uk

Received 22 December 2008; Accepted 8 April 2009

nutritional status, nutritional intervention, mutism and swallowing

were collected. Swallowing problems were deemed to be present in

children with cerebellar mutism or obvious swallowing difficulties

on assessment by a speech and language therapist. Common toxicity

criteria (CTC) [16] scores for vomiting, constipation and mobility

were also collected. Data were taken at defined points namely, at

diagnosis, post-surgery, during radiotherapy, the start of each cycle

of chemotherapy and up to 12 months post-treatment.

Approach to Nutritional Intervention

Approach to nutritional intervention varied between the centres

with two of the centres only instigating enteral feeding support in

response to nutritional decline (centres 1 and 2) whereas the third

centre had a more proactive approach by starting enteral

feeding early in treatment (centre 3) irrespective of nutritional

compromise.

Statistical Analysis

Using Microsoft ExcelTM, data on weight, percentage weight

loss and nutritional intervention was reviewed overall and between

two groups of centres, the two centres that fed in response to

nutritional decline and the centre that fed proactively.

Mean values or proportions at each time point were calculated to

describe the longitudinal data on weight loss, patients on feeds and

toxicities. These were calculated using data on all participants

throughout the whole study period regardless of whether they were

given nutrition or not.

To study the effect of nutrition on weight loss in the two groups of

centres, multilevel modelling techniques were used. A mixed (fixed

and random effects) model was applied to investigate the overall

change in weight loss as an outcome (allowing negative values

corresponding to weight gain) over time. To be able to compare the

effect of feeding approaches between centres, in this part of

statistical analysis only patients who were given nutritional

intervention were included, and those not fed were excluded. One

male age 19 who was given feeding only initially after surgery and

gained considerable weight post-diagnosis (from 56.8 to 80 kg by

course five of chemotherapy—within a period of 41 weeks, possibly

due to problems with mobility and steroid administration) was not

included in the analysis as a highly influential observation. Although

data was recorded over a 26 months period, to avoid the influence of

the cessation of the toxic chemotherapy, the statistical modelling

examining the role of nutrition was confined to the active oncology

treatment period only.

Mean values were calculated with number of nonmissing values

taken in the denominator, and proportions with total number of

patients in the denominator. The overall difference in % weight

loss model used fixed and random effects method as this is robust

to missing values. Statistical analysis was performed using

statistical package Stata (Release 10. StataCorp LP, College

Station, TX).

RESULTS

A total of 41 patients were studied (24 from centres 1 and 2 and

17 from centre 3). A total of 5 out of the 41 patients were randomised

to receive hyperfractionated radiotherapy, 4 from centres 1 and 2

and 1 from centre 3 (Table I). Only one patient did not receive

concurrent vincristine during radiotherapy.

Weight Changes After Initiation of Treatment

Significant problems including weight loss, vomiting, constipa-

tion and mobility problems were highlighted early in treatment. The

majority of the patients were well nourished at diagnosis with a

mean percentage weight/height (percentage expected weight for

Pediatr Blood Cancer DOI 10.1002/pbc

Fig. 1. Outline of SIOP HIT PNET IV protocol.

TABLE I. Characteristics and Treatment Information of the 41 Patients Studied

Parameter All Centres, N¼ 41 Centres 1 and 2, N¼ 24 Centre 3, N¼ 17

Sex Male¼ 25; female¼ 16 Male¼ 17; female¼ 7 Male¼ 8; female¼ 9

Mean age and range 9.3 years (2.2–19.8 years) 10.2 years (3.1–19.8 years) 8.0 years (2.2–11.6 years)

Mean percentage weight/height at diagnosis and range 99.8% (78–146%) 99.2% (78–133%) 100.8% (87–146%)

No. of patients who received standard radiotherapy 36 (88%) 20 (83%) 16 (94%)

No. of patients who received hyperfractionated

radiotherapy 5 (12%) 4 (17%) 1 (6%)

No. of patients who did not receive concurrent

vincristine during radiotherapy 1 1 0

Nutritional Problems in Children With Medulloblastoma 571

height) of 99.8% (range 78–146%). However nutritional status

started to decline early in the treatment schedule during radio-

therapy. The decline in nutritional status continued, peaking by

course 2 of chemotherapy, with a mean weight loss since diagnosis

of 8.23% (range 0–21%). The mean percentage weight/height

had also dropped to 91.3% (range: 70–146%) at this stage in

treatment. Figure 2 demonstrates that the nutritional outcome was

superior in centre 3 as nutritional status started to improve after

course 2 of chemotherapy whereas it continued to decline further in

centres 1 and 2 peaking by course 7 of chemotherapy, with a mean

percentage weight loss of 11.6% compared to 2.4% in centre 3.

Effect of Proactive Feeding Versus ReactiveEnteral Feeding Support

Figure 3 highlights the difference in numbers of patients being

fed between the two groups of centres with 76% of patients in centre

3 receiving enteral nutrition by the start of chemotherapy and 94%

by the 3rd course compared to 41% and 58% respectively of patients

in centres 1 and 2. To quantify the difference in percentage weight

loss between the two groups of centres in terms of different

approaches to feeding, a mixed model with percentage weight loss

as an outcome predicted by the centre group only was used. In

centres 1 and 2, six (25%) patients were not on feeds whereas

in centre 3 only one patient (6%) was not given nutrition. As shown

in Figure 4 the percentage weight loss had a parabolic pattern

with the slopes of parabolas corresponding to the rates of change of

% weight loss in time. Here the scatter plots represent observed data

for individual patients while line plots show predicted outcome from

the mixed model. Solid curve and solid circles are outcomes for

patients from centres 1 and 2 while dashed curve and hollow circles

correspond to patients from centre 3. These rates differed between

the groups of centres and the two parabolas departed quickly in time

giving a significant difference in the percentage weight loss between

the groups. For example at 26 weeks after surgery (marked by a

vertical line in Fig. 4) the average percentage weight loss in centres

1 and 2 was 9.7% (95% CI: 7.0–12.3%, P< 0.001) which

was higher than in centre 3 with the difference of 5.9% (95% CI:

2.1–9.7%, P¼ 0.002).

Associations of Weight Loss With Other Toxicities

Significant toxicity problems, particularly vomiting and con-

stipation were also highlighted. Figure 5 indicates the degree of

constipation and vomiting experienced during therapy. Most

patients (29 out of 41) had both vomiting and constipation but not

always at the same time. Two patients had constipation alone and

10 had vomiting only. The effect of toxicity on weight loss was not

found statistically significant. This was evaluated by applying a

mixed model which, as previously, took percentage weight loss as an

outcome measure predicted in addition to the group of centre by

constipation and vomiting as binary variables (0 if CTC score was

Pediatr Blood Cancer DOI 10.1002/pbc

Fig. 2. Mean percentage weight loss from diagnosis through

defined points in treatment until 12 months post-treatment for centres

1 and 2 compared to centre 3.

Fig. 3. Percentage of patients on supplemental enteral feeds in centres

1 and 2 compared to centre 3.

Fig. 4. The curves represent the predicted percentage weight loss

obtained from the mixed model, for centres 1 and 2 (solid line) and

centre 3 (dashed line). Scatter points mark the observations for

individual patients. For clarity the dots of the scatter plots were shifted

apart for the two groups to avoid overlap. The solid circles correspond to

measurements for patients in centres 1 and 2 and the hollow circles for

patients in centre 3. Vertical solid line marks time at 6 months.

572 Ward et al.

below 2 and 1 if CTC was 2 or above) as well as age group (�10 and

>10 years). None of these results were significant. This lack of

statistical significance in the model described above may be due to

the small number of patients analysed (33 patients included in the

model).

Facilitation of Enteral Feeding

Overall a total of 26 out of the 41 patients had gastrostomies sited

and 17 had nasogastric tubes passed. Nine patients with a

nasogastric tube subsequently had a gastrostomy sited. Fourteen

out of the 17 patients treated in centre 3 had a gastrostomy sited

compared to 12 of the 24 in centres 1 and 2. Thirteen out of the 26

patients with a gastrostomy had at least 1 site infection, 10 were

treated with oral antibiotics and 3 required intravenous antibiotics.

None required the gastrostomy to be removed. There was no

difference between centres with regard to feed type, administration

or percentage of estimated average requirement (EAR) for energy

provided by the feed.

DISCUSSION

Previous studies of medulloblastoma treatment have focussed on

survival and long-term morbidity associated with treatment [2,6–9]

with very few looking specifically at nutritional problems.

In a retrospective study of 56 patients aged 10–20 years who

received adjuvant treatment for medulloblastoma, 41 (73%) had a

weight loss greater than 10% and 27 (48%) required either enteral or

parenteral feeding [12]. In another retrospective study of 103

children treated for medulloblastoma and supra-tentorial (PNET)

over a 10-year period those who received chemotherapy had a

significant loss of weight compared to those who did not receive

chemotherapy (P< 0.001). Forty-six percent of those treated with

chemotherapy lost >5% of their body weight and were more likely

to be referred for dietetic intervention (66.7% vs. 4%) [17]. Both

studies demonstrated weight loss in children and adolescents

receiving multimodal therapy on various treatment protocols.

The current study of acute toxicity identified a pattern of

increased toxicity early on in the treatment journey, that is, during

radiotherapy and the first half of the chemotherapy schedule, which

paralleled a sharp decline in nutritional status. Most patients had

problems with both vomiting and constipation. However, whilst the

toxicities coincide in individual patients this was not always at the

same time and some patients had one of the toxicities occurring

more often than the other. The toxicity early in treatment may be as a

result of administering radiotherapy in combination with vincris-

tine. Very few studies have looked at vincristine related toxicity in

CNS tumour treatment in children. In a randomised study of 48

paediatric medulloblastoma patients, 21 were randomised to receive

radiotherapy only and 27 to receive radiotherapy with

concurrent weekly vincristine followed by 4 cycles of etoposide

and cisplatinum. In the group randomised to radiotherapy

myelosuppression was the only acute toxicity, whereas in the group

who received both chemotherapy and radiotherapy 11% developed

grade 2 peripheral neuropathy [18]. Similarly in a study of 30

children treated for diffuse intrinsic brain stem glioma who received

radiotherapy and concurrent vincristine, 10% had grade 3

constipation and 10% grade 3–4 vomiting [19]. Vincristine is used

in other treatment regimens in paediatric oncology with less

problems of constipation and neurotoxicity. In a study of 242

children with stage 1 Wilms tumour treated with nephrectomy

followed by 10 weekly injections of vincristine 2.4% developed

grade 3 or above neurotoxicity with 8.2% experiencing up to a

maximum of grade 2 constipation [20] and it has been suggested that

craniospinal irradiation may potentiate vincristine toxicity [21].

At presentation of medulloblastoma, vomiting is a common

symptom [2,22] and 63% of the children in the current study had

problems with vomiting at diagnosis and this continued during

therapy. Both vomiting and constipation can have a profound effect

on a child’s appetite and oral intake. This can be heightened by post-

radiation somnolence [23] during the initial chemotherapy courses.

Constipation and vomiting were not significantly associated with

weight loss. This could be the result of a small sample size and

difficulty scoring retrospectively. The incidence of malnutrition at

diagnosis in paediatric cancers ranges from 6% to 50% depending

on the type, stage and location of the disease [14,15,24], occurring in

up to 37.5% of newly diagnosed patients with metastatic disease

[25]. In line with previous data, children presenting with

medulloblastoma were found to be adequately nourished in this

study [17]. By the 2nd course of chemotherapy marked nutritional

decline had occurred. This deterioration in weight during treatment

has been described in earlier studies [12,17]. However, the current

study confirmed a sharp decline in weight early on in treatment.

Problems of malnutrition have previously been well documented in

children treated for cancer and include a reduced tolerance to

therapy and may also affect sensitivity to chemotherapy agents

[13,14,26] Malnutrition may contribute to problems of drug toxicity

due to altered pharmacokinetics secondary to changes in body

composition and relationship between body surface area and lean

body mass [12,14]. The relationship between malnutrition and

increased infection is well documented [26].

As a result of being proactive and instigating feeding earlier in

treatment the nutritional outcome in centre 3 patients was superior.

Patients in centre 3 generally had a prophylactic gastrostomy sited

prior to starting radiotherapy with supplemental feeding instigated

by the end of radiotherapy. In centres 1 and 2 not only was

supplemental feeding started later in treatment but criteria for

gastrostomy placement was not so clearly defined and depended on

the incidence of vomiting, mucositis and patient preference between

Pediatr Blood Cancer DOI 10.1002/pbc

Fig. 5. Percentage of patients recording grade 1 or above of CTC

score for vomiting and constipation.

Nutritional Problems in Children With Medulloblastoma 573

a gastrostomy and nasogastric tube. The statistical model showed

that the percentage weight loss was lower in centre 3 patients who

were on feeds on average for a longer period of time and started the

feeds earlier in treatment suggesting that feeding has a positive

association with the patients’ weight. However, it is difficult to

assess the causality of the effect of nutritional intervention on

weight, as this was not a randomised study and no control group was

used. It is, however, recommended that there is a need to consider

earlier proactive nutritional intervention in view of the significant

difference in predicted weight loss between the two groups of

centres. Whereas gastrostomy feeding has become the main method

of providing nutritional support in some areas of paediatrics until

recently it has not been commonly use in paediatric oncology due to

a perceived risk of infectious and tube related complications in

immunocompromised patients. However, the few published studies

looking at gastrostomy feeding in paediatric oncology patients have

shown it to be a safe and effective method of nutritional support in

terms of cost and improvement of nutritional status and only

associated with minor complications such as site inflammation and

over-granulation [27–29]. The incidence of minor site infections in

the current study were no higher than those reported previously and

therefore confirms the safety and effectiveness of gastrostomy

feeding in this population. As vomiting was a major toxicity of

the treatment protocol the use of gastrostomy feeding alleviates the

need for frequent nasogastric tube placement. This study did not

include any measurement of quality of life and therefore further

studies of the effect of nutritional support are recommended.

CONCLUSION

The current study highlights significant morbidity associated

with current treatment of medulloblastoma. A pattern of increased

toxicity during radiotherapy and during the first half of chemo-

therapy emerged that could be as a result of radiotherapy in

combination with chemotherapy. In view of the significant dif-

ference in predicted weight loss between the two approaches to

feeding the authors recommend earlier proactive enteral nutrition to

prevent nutritional decline during treatment. A prospective further

audit is planned.

ACKNOWLEDGMENT

The study was undertaken on behalf of the CNS Division of

the Children’s Cancer and Leukaemia Group (CCLG). The CCLG

is supported by Cancer Research UK. The CNS division is

additionally supported by a grant from the Samantha Dickson Brain

Tumour Trust.

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