K. Ribi1 C. Relly1 M. A. Landolt2 F. D. Alber3 E. Boltshauser3 M. A. Grotzer1
Outcome of Medulloblastoma in Children: Long-Term Complications and Quality of Life
Abbreviations
To study the outcomes in long-term survivors of paediatric medulloblastoma (MB), we followed 51 consecutive children who were treated between 1980 and 2000 in a single institution. In 18 of 26 survivors (mean follow-up time 12.2 years), tumour control, neurological, endocrine, and neurocognitive complications and their impact on behavioural and psychological adjustment, and health-related quality of life (QoL) were comprehensively assessed using qualitative and quantitative measures. Endocrine deficits occurred in 61 %, neurological complications in 72 %, and significant school problems in 72 %. All patients had significant deficits in neurocognitive functioning: attention and processing speed was impaired in 79 %, learning and memory in 88 %, language in 56 %, visual perception in 50 %, and executive functions in 64 %. In comparison with healthy controls, social functioning was rated by the patients as the QoL dimension most affected. Parents’ ratings were considerably lower than those of the patients. No MB survivor > 18 years of age (n = 12) had a boy- or girlfriend. Because of their treatment, including craniospinal radiotherapy, MB long-time survivors are not only at great risk for neurological, endocrine, and neurocognitive complications, but also of social isolation thereby decreasing self-rated QoL substantially.
CBCL CNS HRQoL MB PedsQL QoL YSR
Key words Brain tumour · medulloblastoma · primitive neuroectodermal brain tumour · psychological adjustment · quality of life · longterm complication
child behaviour checklist central nervous system health-related quality of life medulloblastoma paediatric quality of life inventory quality of life youth self report
Original Article
Abstract
Introduction Medulloblastoma (MB) is the most common malignant brain tumour in children and constitutes around 20 % of all paediatric brain tumours [17]. Because of the high risk of leptomeningeal dissemination, standard postoperative treatment for MB includes not only local radiotherapy, but also craniospinal radiotherapy and chemotherapy [21, 36]. Such treatment causes longterm morbidity, including endocrine and growth disturbances, as well as neurocognitive dysfunction, which is particularly severe in young children [6, 8, 29, 31, 34, 40, 41]. What is not yet sufficiently documented is the impact that such late effects have on the social and psychological adjustment and the quality of life (QoL) of the survivors. Limitations in the current literature include inadequate assessment techniques, lack of appropriate comparison groups, and small sample sizes [13]. Interest in the measurement of QoL has expanded considerably over the past 10 years, with an increasing appreciation of the im-
Affiliation Division of Oncology, University Children’s Hospital of Zurich, Zurich, Switzerland 2 Division of Psychosomatics and Psychiatry, University Children’s Hospital of Zurich, Zurich, Switzerland 3 Division of Neurology, University Children’s Hospital of Zurich, Zurich, Switzerland 1
Correspondence PD Dr. med. Michael Grotzer · University Children’s Hospital · Steinwiesstrasse 75 · 8032 Zurich · Switzerland · E-mail:
[email protected] Received: June 26, 2005 · Accepted after Revision: September 7, 2005 Bibliography Neuropediatrics © Georg Thieme Verlag KG Stuttgart · New York · DOI 10.1055/s-2005-872880 · Published online November 24, 2005 · ISSN 0174-304X
357
portance of the patient’s perspective [22]. According to the World Health Organisation, health-related quality of life (HRQoL) is to be regarded as a multi-dimensional concept that includes physical, social, cognitive and emotional functioning [54]. The subjective perception and appraisal of functioning is as important as objective health, because individuals with the same objective health status may report very different quality of life [38]. For assessing HRQoL in paediatric populations, there is wide agreement that instruments should be multidimensional, sensitive to cognitive development, easy to complete, and encompass the broadest age range possible. Furthermore, they should meet the required psychometric parameters of sensitivity, reliability, and validity [4,11, 51].
Original Article
To study the outcome of MB in children, we studied 51 consecutive patients at a single hospital treated between January 1980 and December 2000. In survivors, a comprehensive assessment of tumour control, neurological, endocrine and neurocognitive complications and their impact on behavioural and psychological adjustment and HRQoL, was performed using qualitative and quantitative measures (conventional medical follow-up, neuropsychological testing, semi-structured interview, and various questionnaires).
Patients and Methods
358
Patients and therapy Between January 1980 and December 2000, 51 patients with MB were diagnosed at the University Children’s Hospital of Zurich, Switzerland. All diagnoses were confirmed by histological assessment of a tumour specimen obtained at surgery. Clinical information on the 51 patients included date of birth, date of diagnosis, therapy received, and follow-up. The mean age at diagnosis for all patients was 6.7 years (range: 0.1 to 17.0 years). As of February 2004, 26 of the 51 patients were alive. Seven patients could not be contacted because they moved to another country, and one patient was excluded because he was too young to be interviewed (less than 6 years). Of the remaining 18 study patients, all agreed to be assessed by quantitative measures and 16 agreed to be interviewed. Twelve patients were female, and 6 were male. The mean age at diagnosis of the study patients was 6.8 years (range: 1.1 to 14.7 years), and the mean age at assessment was 18.9 years (range: 8.5 to 31.9 years). Mean follow-up time for the 18 study patients was 12.2 years (range: 3.0 to 24.0 years). Postoperative therapy included radiotherapy and/or chemotherapy. Twelve patients received combined radiotherapy and chemotherapy, two patients < 3 years of age at diagnosis had chemotherapy alone and four had radiotherapy alone. Radiotherapy included 23.4 – 36.0 Gy craniospinal irradiation and 48.0 – 55.0 Gy total tumour bed irradiation. Approval to perform the study and to link study data to clinical data was obtained from the Institutional Review Board. Semi-structured interview After obtaining informed consent from parents and patients, an appointment was arranged while patients were attending a routine outpatient visit. If no such visit was planned, the interview took place at the patient’s home. The data gathered in the interview were intended to give a descriptive picture of the particiRibi K et al. Outcome of Medulloblastoma … Neuropediatrics
pant’s past and present life situation. Therefore, the interview included questions about the time of diagnosis and treatment, current medication, physical functioning and satisfaction with physical appearance, neurocognitive functioning, emotional functioning, school or job performance, interpersonal relationships including family and intimate relationships, social activities, personal interests, and wishes about the future (Appendix 1). The questions were phrased in an easy and comprehensible way and almost every question had a yes/no answer. Neuropsychological assessment/instruments Neuropsychological examination was conducted by an experienced child neuropsychologist (F. D.). The neurocognitive functions were assessed in six central domains: intelligence, attention and processing speed (including alertness, and selective, divided and sustained visual attention), learning and memory/ memory span (verbal and visual), visual perception and visuospatial constructional ability, language, and executive functions. All the tests used to assess these six central domains are summarised in Table 1. Youth self report (YSR) To assess behavioural and emotional problems, a German version of the YSR derived from the Child Behaviour Checklist (CBCL) was used [2, 44]. It is a self-administered form designed for use with children and adolescents aged 11 to 18 years. The questionnaire consists of 120 items addressing a variety of behavioural and emotional symptoms. It yields scores for 8 narrow-band clinical sub-scales (withdrawal, somatic complaints, anxiety and depression, social problems, thought problems, attention problems, aggressive behaviour, and delinquent behaviour), 2 broadband scales (internalising and externalising behaviour problems) and an overall Total Behaviour Problems Score. Subjects rated the occurrence of each symptom within the past 6 months and selected their response from 0 (not true) to 2 (very true or often true). The choice of cut-off points to denote clinically significant symptomatology in the various YSR scales is based on the recommendations of Achenbach [1, 2]. Assuming that the YSR is also valid for young adults aged 18 – 30 years, the YSR was used in the present study for 16 patients between 11 and 30 years. The scores of the study population were compared with norm scores provided from a sample of 1093 healthy Swiss children and adolescents [44]. Child behaviour check list (CBCL) To assess patients’ behavioural and emotional problems from a parental point of view, a German version of the CBCL was used [1, 43]. The CBCL is a parent-proxy report scale developed for children and adolescents aged 4 to 18. In order to compare parent-reports with self-reports, the CBCL items correspond with the YSR items. Also, narrow- and broad-band scales are the same as in the YSR, as are the cut-off points. In the present study, the CBCL was used for the parents of the 16 patients assessed by the YSR. The scores of the study population were compared with norm scores provided from a community sample of 1093 Swiss children and adolescents [45]. Paediatric quality of life inventory (PedsQL™) To measure HRQoL, a German version of the PedsQL was used [12, 52]. The PedsQL is a modular instrument for measuring HRQoL in children and adolescents aged 2 to 18 years. The 23-
Table 1 Domains tested, tests used in different age groups, normal values, and literature references Domains tested and tests used
Age range (years)
Definition of significant impairment
References
Standard score < 85
[24]
IQ < 85
[47]
IQ < 85
[46]
Intelligence – K-ABC – WISC-III, German adaptation (HAWIK-III) – WAIS-R, German adaptation (HAWIE-R)
2.5 – 10 10 – 17 > 17
Attention + processing speed >6
P < 16 or < (Mean – 1SD)
[26, 55]
– WISC-III freedom from distractibility
10 – 17
Index < 85
[47]
– WISC-III processing speed
10 – 17
Index < 85
[47]
– Verbal learning + memory test (VLMT)
>7
< (Mean – 1SD)
[39]
– Rey Visual Design Learning Test (RVDLT)
>9
< (Mean – 1SD)
[42]
– Mottier Test
>9
< (Mean – 1SD)
[15]
– Corsi Block Tapping Test
>9
Raw score < 5
[37]
Learning + memory span
– K-ABC spatial memory
5 – 10
Scaled score < 7
[24]
– K-ABC hand movements
2.5 – 10
Scaled score < 7
[24]
– K-ABC number recall
2.5 – 10
Scaled score < 7
[24]
– K-ABC word order
4 – 10
Scaled score < 7
[24]
– WISC-III/WAIS-R coding/digit symbol
> 10
Scaled score < 7
[46, 47]
– WISC-III/WAIS-R digits forward
> 10
Scaled score < 7
[46, 47]
Original Article
– Tests for attention performance (TAP)
Visual perception + visuospatial constructional ability – Hooper Visual Organization Test (VOT)
< (Mean – 1SD)
[19]
– Developmental Test of Visual Perception-2 (DTVP-2)
>7 4 – 10
Composite quotient < 80
[18]
– K-ABC Gestalt closure
2.5 – 10
Scaled score < 7
[24]
– K-ABC triangles
4 – 10
Scaled score < 7
[24]
– K-ABC photo series
6 – 10
Scaled score < 7
[24]
– WISC-III/WAIS-R picture completion
> 10
Scaled score < 7
[46, 47]
– WISC-III/WAIS-R picture arrangement
> 10
Scaled score < 7
[46, 47]
– WISC-III/WAIS-R block design
> 10
Scaled score < 7
[46, 47]
– WISC-III/WAIS-R object assembly
> 10
Scaled score < 7
[46, 47]
Index < 85
[47]
– WISC-III perceptual organisation
10 – 17
Language – K-ABC expressive vocabulary
2.5 – 5
Standard score < 85
[24]
– K-ABC riddles
3 – 10
Standard score < 85
[24]
– K-ABC reading/understanding
Standard score < 85
[24]
– WISC-III/WAIS-R vocabulary
> 10
Scaled score < 7
[46, 47]
– WISC-III/WAIS-R similarities
> 10
Scaled score < 7
[46, 47]
– WISC-III/WAIS-R comprehension
> 10
Scaled score < 7
[46, 47]
10 – 17
Index < 85
[46, 47]
– Verbal fluency (s-words)
>9
< (Mean – 1SD)
[35]
– Verbal fluency (animals)
>9
< (Mean – 1SD)
[35]
– Design fluency (5-point Test)
>9
< (Mean – 1SD)
[35]
– Stroop Test
>9
< (Mean – 1SD)
[53]
– WISC-III verbal comprehension
7 – 10
Executive Functions
– K-ABC matrix analogies – WISC-III/WAIS-R digits backward
5 – 10 > 10
item PedsQL 4.0 Generic Core Scales are multidimensional selfreport and parent proxy-report scales developed as the generic core measures to be integrated with the PedsQL Disease-Specific
Scaled score < 7
[24]
Scaled score < 7
[46, 47]
Modules. The PedsQL 4.0 Generic Core Scales encompass 8 items addressing physical functioning and 5 items each addressing emotional functioning, social functioning, and school functioning. Ribi K et al. Outcome of Medulloblastoma … Neuropediatrics
359
Table 2 Disabilities of 18 childhood MB survivors Characteristics
Affected patients (Percentage)
Endocrine functioning – thyroid dysfunction
8/18
(44%)
– growth hormone deficiency
7/18
(39%)
– gonadal dysfunction
6/18
(33%)
– height < 3rd percentile
8/18
(44%)
– Body Mass Index > 97th percentile
3/18
(17%)
– alopecia
8/18
(44%)
– strabismus
2/18
(11%)
– hemiparesis
2/18
(11%)
– tetraparesis
1/18
(6%)
– facial nerve palsy
4/18
(22%)
– hearing impairment
3/18
(17%)
– visual impairment
2/18
(11%)
– ataxia
9/18
(50%)
– seizures
1/18
(6%)
Physical functioning
Original Article
Neurological functioning
Neurocognitive and school functioning – intelligence deficits
Fig. 1 a and b The Kaplan-Meier curves show the probability of progression-free survival (a) and overall survival (b) for MB in 51 children.
7/18
(39%)
– attention and processing speed deficits
11/16
(79%)
– learning and memory deficits
14/18
(88%)
– language deficits
10/18
(56%)
9/18
(50%)
– executive functions deficits
9/16
(64%)
– significant school problems
13/18
(72%)
7/12
(75%)
6/16
(37%)
7/16
(44%)
12/12
(100%)
– visual perception deficits
360
The scores of the study population were compared with the published scores of 401 healthy controls [50]. The 27-item PedsQL 3.0 Cancer Module encompasses 8 scales: pain and hurt, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication. In the present study, the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cancer Module were used for all patients. For all but one patient, the parents completed a questionnaire for both the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Cancer Module. On a 5-point response scale subjects were asked how much each item had been a problem during the past month: 0 = never a problem, 1 = almost never a problem, 2 = sometimes a problem, 3 = often a problem, and 4 = almost always a problem. Through reverse scoring and linear transformation of items (0 = 100, 1 = 75, 2 = 50, 3 = 25, 4 = 0) a scale was obtained, in which higher scores indicate better HRQoL. Scale scores were computed as the sum of items divided by the number of items answered. Statistical analyses Patient-rated PedsQL scores were compared with the scores from healthy controls by one sample t-tests. All other statistical analyses were performed by non-parametric tests due to the small sample size. Self- and parent-rated PedsQL scores were compared by Mann-Whitney U-tests. Spearman correlation coefficients were calculated to explore the relation between self-rated and parent-rated PedsQL scores and clinical factors. P values < 0.05 were considered as significant.
Ribi K et al. Outcome of Medulloblastoma … Neuropediatrics
– impaired choice of occupation (only > 16 years of age) Social functioning – difficulties in making friends – rejection by peers – no intimate relationship (only > 18 years of age)
Results Tumour control The mean follow-up time of all 51 patients following primary surgery was 6.6 years (range: 0.1 to 24.0 years). The 10-year overall survival was 53 % and the 10-year progression-free survival was 40 % as determined by the Kaplan-Meier method [26]; (Fig. 1). The mean follow-up time of the 18 survivors participating in this study was 12.2 years (range: 3.0 – 24.0 years). Table 2 lists the patients’ disabilities and their neurocognitive and social functioning. Endocrine complications Following primary surgery, chemo- and/or radiotherapy, 11 (61 %) of 18 children required hormonal replacement therapy. Of these, 8 (44 %) required long-term supplementation of thyroid hormone. Growth hormone was administered to 7 (39 %) pa-
Table 3 Comparison of PedsQL scores with intelligence testing and selected clinical factors PedsQLa (self-rated)
PedsQLa (parentrated)
Intelligence
Alopecia
1
not able
44.6
reducedb
yes
2
not able
79.0
reduced
3
54.3
35.9
4
55.7
52.2
5
59.8
75.0
Pat.
Short stature
Age at diagnosis (years)
Gender
Chemotherapy
RT cs (Gy)
RT local (Gy)
Time of follow-up (years)
yes
2.5
female
yes
30.0
44.0
16.2
yes
5.1
female
yes
31.0
55.0
14.6
yes
15.0
female
yes
35.0
51.0
9.4
yes
11.0
male
yes
23.4
54.0
3.9
6.2
female
yes
30.0
54.0
16.1 10.0
62.0
62.5
reduced
yes
13.0
female
no
35.2
53.0
72.2
69.6
reduced
yes
5.8
female
yes
34.5
54.0
5.6
8
75
56.5
reduced
yes
7.9
female
yes
34.5
54.0
24.0 15.2
yes
9
80.4
40.2
4.1
female
yes
30.0
55.0
10
80.7
68.5
2.2
female
yes
0
0
11.8
11
82.6
84.9
reduced
yes
6.2
female
no
30.0
54.0
13.5
12
87.0
91.3
reduced
yes
2.0
male
no
30.0
48.0
18.0
13
90.2
49.0
9.9
male
yes
35.2
55.0
4.1
14
91.3
71.4
15
92.4
77.2
16
97.8
–
17
98.9
87.0
18
100
yes
yes
6.5
male
yes
35.2
55.0
3.9
yes
6.8
male
yes
36.0
56.0
14.2
yes
8.0
male
no
34.0
51.6
10.0
yes
8.9
male
yes
34.0
54.0
22.1
1.1
female
yes
0
0
7.4
91.3
Original Article
6 7
Patients are graded according to the self-rated PedsQL scores. a PedsQL, Paediatric Quality of Life Inventory. b Reduced intelligence is defined as IQ < 85. RT = radiotherapy; cs = craniospinal. No significant correlations were found between self-rated PedsQL scores and clinical factors
tients and sex hormones to 6 (33 %) patients. Deficiency of ACTH and diabetes insipidus were not seen in the patients of this study. Physical functioning At the time of follow-up, 8 (44 %) patients had short stature (< 3rd percentile). Three (17 %) patients had obesity (body mass index > 97th percentile). Eight (44 %) patients had significant, mainly occipital, alopecia. Mainly because of their alopecia, 8 (50 %) of 16 patients interviewed were dissatisfied with their physical appearance. In one patient, tissue expansion for occipital hairline restoration is planned. Neurological complications Thirteen (72 %) of 18 patients had significant perioperative neurological complications that persisted during long-term followup (Table 2). These complications included facial nerve palsy (n = 4), strabismus (n = 2), hearing impairment (n = 3), visual impairment (n = 2), hemi-and tetraparesis (n = 3), and truncal ataxia (n = 9). One patient developed seizures. Three patients had corrective surgery for strabismus, and one patient had plastic surgery for her facial nerve palsy. Of the 4 patients with hearing impairment, one needs hearing aids. Neuropsychological functioning All patients had significant deficits in neurocognitive functioning: attention and processing speed were impaired in 11 (79 %) of 14 patients tested, learning and memory impairments were present in 14 (88 %) of 16 patients, language impairments in 10 (56 %) of 18 patients, visual perception impairments in 9 (50 %)
of 18 patients, and executive function impairments in 9 (64 %) of 14 patients. Significant impairments in the overall level of intellectual functioning (IQ < 85) were seen in 7 (39 %) of 18 patients. All but one of these 7 patients received cranial radiotherapy under the age of 8 years (Table 3). In the two patients who did not receive radiotherapy, language impairments were present in both, but the overall level of intellectual functioning was normal. School performance and occupation Thirteen (72 %) patients experienced significant problems in school. Seven of them were in a special school. The remaining six attended a regular school, but needed remedial teaching. Seven patients complained about their ability to concentrate and 8 mentioned difficulties with comprehension and speed of working. Of the 12 patients of employable age, five had to follow a professional training in a specialised institution, one patient was unemployed at the time of survey. Nine (75 %) of 12 patients were not able to take up their preferred job because they were unable to obtain the required qualifications. Behavioural and emotional problems The number of patients with clinically significant scores regarding behavioural and emotional adjustment problems are shown in Fig. 2. Two of 16 patients assessed were excluded because of their limited cognitive capacity to answer all YSR items. Two other patients were excluded because parental ratings were not available. Two of the remaining 12 patients showed clinically elevated scores on the YSR total behaviour problems scale and 3 on the internalising behaviour problems scale. On the externalisRibi K et al. Outcome of Medulloblastoma … Neuropediatrics
361
Original Article
Fig. 2 Behavioural and psychological adjustment as rated by the MB patients (n = 12; Youth Self Report) and their parents (n = 12; Child Behaviour Checklist). The numbers of patients with clinically significant scores are shown.
ing behaviour problems scale, all of the respondents were in the clinically normal range, but two attained scores in the transition range, defined as transition from clinically normal to clinically significant. On the narrow band scales regarding attention problems, the score of one survivor was clinically significant. Compared to self-rated YSR, the scores of parent-rated CBCL were more often clinically significant. According to the parents, 7 of 12 patients showed clinically significant internalising behaviour problems. In contrast to the self-rated YSR subscales, on each of the parent-rated CBCL sub-scales, except aggressive behaviour, 1 to 4 patients had clinically significant scores.
Fig. 3 Health-related quality of life (HRQoL) in 16 MB survivors as rated by themselves and by their parents using the PedsQL 4.0 Generic Core. Compared to healthy controls, MB survivors rated their HRQoL lower in social functioning. Parent ratings were lower in all dimensions with most disconcordance in psychosocial, emotional, and school functioning. Horizontal lines are median values; solid box shows 25th to 75th percentiles; whisker bars represent lowest and highest values; outlying values are shown as crosses. For self-report controls, horizontal lines are means, there are no boxes or whisker plots because data were not available.
for perceived physical appearance, 88.1 for treatment anxiety, and 98.3 for pain. Concordance between patient and parents ratings was variable with lower parent ratings in all domains except the dimension nausea.
Discussion 362
Social problems Although a majority of the patients indicated they had a friend, these friendships mainly turned out to be not very strong and four survivors did not have any friends at all. Six (37 %) of 16 patients interviewed reported difficulties in making friends, and 7 (44 %) of 16 patients experienced rejection by peers. No MB survivor > 18 years of age (n = 12) had a boy- or girlfriend. Health-related quality of life Two of 18 patients assessed were excluded because of their limited cognitive capacity to answer all PedsQL items. In comparison with healthy controls, the MB survivors rated their HRQoL lower in social functioning (patient mean: 77.2; control mean: 87.4; p = 0.046, Fig. 3). Notably, patients rated their social functioning lower than their school functioning. Concordance between patient and parent ratings was variable, with lower parent ratings in all domains. In comparison to patient’s self-perception, parents rated psychosocial health, school, and emotional functioning as most impaired. Significant differences between patient ratings and parent ratings were seen in psychosocial functioning (p = 0.029), school functioning (p = 0.041), and emotional functioning (p = 0.046). Considering the results of the PedsQL 3.0 Cancer Module, the most severely impaired dimensions according to patients reports were nausea (mean 70.0) and cognitive problems (mean 75.0). The mean values of the other dimensions were, 78.5 for worry, 80.3 for procedural anxiety, 81.2 for difficult communication, 85.9 Ribi K et al. Outcome of Medulloblastoma … Neuropediatrics
With improved survival rates in MB survivors, awareness of significant tumour and/or therapy-related long-term complications has increased, including endocrine and growth disturbances, as well as neurocognitive dysfunction. Studies investigating longterm treatment effects in MB survivors focused on associations between clinical factors (including age at diagnosis, tumour location, treatment intensity, and time since treatment) and neurocognitive function [6 – 9, 20, 29, 32, 34, 40, 41]. The younger the child is at the time of whole-brain radiotherapy, the greater is the likelihood and severity of neurocognitive deficits that detrimentally effect school problems. However, information about the impact of these complications on social and psychological adjustment and quality of life of the long-term survivors is scant [5, 25]. The present study comprehensively assessed neurological, endocrine and neurocognitive complications and their impact on behavioural and psychological adjustment and HRQoL. The present study confirms previous findings concerning neurocognitive complications in MB patients treated with whole-brain irradiation: all patients had significant impairments in at least one neurocognitive function tested (attention and processing speed [79 %], learning and memory [88 %], language [56 %], visual perception [50 %], and executive functions [64 %]). In 7 (39 %) patients, overall intelligence was significantly impaired. This resulted in major school problems in more than two-thirds of the patients and most of the patients of employable age were not
able to take up their favoured job because they were unable to obtain the required qualifications.
Social functioning was rated by the patients as the QoL dimension most affected in comparison to healthy controls. Although almost all of the participants indicated that they had a friend, these friendships mainly turned out to be not very strong and four survivors did not have any friends at all. In addition, no study participant old enough to form an intimate relationship had a boy- or girlfriend. These findings agree with studies investigating peer-relations in brain tumour survivors. Levels of social isolation were found to be significantly higher in survivors of brain tumours as compared with classmates, regardless of whether teacher, parent or survivors acted as informants [49]. In addition, evidence exists that survivors of central nervous system tumours are less popular with other school-aged children [30]. This may be related to dissatisfaction with physical appearance (little hair, facial nerve palsy, short stature). One report about body image and social adjustment in adolescent cancer survivors demonstrated that higher ratings by subjects regarding how cancer affected their appearance correlated with more feelings of loneliness and more social anxiety [33]. Similarly, disfigurement was one factor influencing the social competence and the behavioural adjustment of children with brain tumours [28]. In line with other findings [48], the parents in this study consistently judged the HRQoL as more impaired than the patients themselves. Differences between self and parent report may result from different perspectives of the same situation. For example, in rating school functioning, parents may emphasise the future prospects for their children, whereas patients themselves focus more on the present situation, without considering the consequences of their actual school performance for their future life. Another explanation may be the restricted capability of MB survivors to see their impairments in a realistic way. An optimistic bias of the own quality of life might fulfil a protective function in maintaining self-esteem. In an effort to identify factors associated with unfavourable HRQoL, we compared self-rated and parent-rated PedsQL scores with clinical factors (including gender, age at diagnosis, and therapy received), intelligence, and factors of physical appearance
One strategy to reduce treatment-related long-term effects in patients at the greatest risk for severe radiation-induced brain injury is to delay or even avoid radiotherapy through the use of prolonged chemotherapy [3,10]. In older MB patients, one strategy to reduce treatment-related long-term effects is to reduce craniospinal radiation doses in standard risk patients [14]. Moreover, over the last decade, important biological prognostic markers for MB have been identified (reviewed in: [16]). Following validation in ongoing prospective studies, biological prognostic factors, in addition to clinical factors, will define risk groups and help direct therapy decisions for children with MB. In MB with favourable biological factors and no evidence of leptomeningeal tumour dissemination, therapy with reduced craniospinal radiation might retain the efficacy but reduce the toxicity and therefore improve the quality of life for the survivors. We are well aware that our study has limitations: the sample size is limited, and the age range of patients is broad. Despite these limitations, we hope that our results may be helpful in the management of patients with MB. This study points to the necessity of careful follow-up for these patients to provide them with the help needed to achieve their best possible integration into professional and social life. Future large prospective studies on HRQoL in MB survivors need to include both self- and proxyrated measurements, since self-rated measurements alone may underestimate treatment-related impairments.
Acknowledgements Supported by the Schweizer Forschungsstiftung Kind & Krebs. We are grateful to Dr. M. Weissert, Dr. H. Spescha, and U. Heiniger for sharing follow-up data.
Appendix 1: Semi-Structured Interview Questions Time before the diagnosis – Do you remember? What do you remember first of all? Moment of the diagnosis – Can you remember the time of the diagnosis? – Did you understand what it was about? How did you feel? – How much do you know about your disease? Did you take a particular interest in it? – How did you feel during the treatment? What was particularly bad, what less bad? – Is there anything concerning your disease which was difficult for you and which you now consider to be less difficult? – What helped you during difficult times in the treatment? Could you help yourself or did others help you? How?
Ribi K et al. Outcome of Medulloblastoma … Neuropediatrics
Original Article
Behavioural and emotional adjustment problems have been reported in 20 – 51 % of brain tumour patients according to proxyrated CBCL [23, 27, 28]. In the present study, behavioural or emotional disturbances occurred in 17 % of the patients according to the self-rated YSR. Concordance between patient and parent ratings was variable, with less favourable parent ratings in all domains. According to the parent-rated CBCL, 42 % of the patients showed clinically significant emotional and behavioural problems. Internalising behaviour problems were the most important disturbances, with 58 % of the patients having significant problems of this kind. These problems contributed to the social problems of many MB survivors. Another important factor contributing to the social problems was dissatisfaction with their physical appearance. Alopecia, short stature, and facial nerve palsy were judged by the MB survivors to be significant problems.
(short stature, alopecia) (Table 3). No significant correlations were found for the factors tested. Although young patients who received radiotherapy tended to have more severe neurocognitive deficits, this did not necessarily result in lower self- or parent-rated quality of life, indicating important differences in coping strategies.
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Present medication – Do you take any medicine now? Which one? Are there medicines which you have taken in the past and which you don’t take any more? – Are you disturbed by having to take these medicines every day? – Do you have, or have you had, any side effects due to the therapy? Physical appearance – Are you satisfied with your appearance? What disturbs you most about your appearance? If you could, would you change anything about your appearance? If yes, what?
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General body fitness/Neurocognitive functions – Do you feel your physical ability has been affected by your illness? How much? – Do you take part in any sport? Which one? Is there any sport you like but which you can’t take part in? – Can you concentrate well at school, at work? Do you believe your ability to concentrate has been impaired by your illness? What about your speed in solving tasks or in understanding new things? – Do you often have gaps in your memory? Emotions – What positive feelings do you have towards your illness? What negative feelings about your illness? – Are you afraid of getting ill again?
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School – Which school do you or did you attend? – How do you get on at school? Do you have any difficulties? If so, are they due to your illness? Do you like going to school? If yes, why? – How often do you not attend school? – Do you feel comfortable in your class? – Did anything change in your relationship to your schoolmates after your illness? If yes, what? – Have people in your school/at work been informed about your illness? Did you tell them about it? Job – Which job did you train for or would you like to train for? Is this the job of your dreams? – Have you started an apprenticeship? Did you finish it? If not, why? – Did you attend the grammar school/the university? – What work do you do now? Are you happy with it? If not, why? – Did you have any other job before? Why did you change your job? Hobbies – Do you have any hobbies? What are they? – Do you pursue your hobbies alone or with friends? – Are you a member of any club? – Do you play music? – Have you got a particularly strong interest in anything? – Do you have a pet? Ribi K et al. Outcome of Medulloblastoma … Neuropediatrics
Social situation – Do you live with your parents or alone? With boy-/girlfriends? – Do you live in a special home (hostel)? – How is your relationship with your parents/brothers and sisters? Do you often get angry with them? Would you prefer to live away from home? – Do you have a girl-/boy-friend, or have you ever had one? – If you have no relationship: do you miss it? Can you imagine your future without a partner? – Do you have a good boy-/girlfriend? Are you in touch with him/her? How often? – How do you relate to your teachers/schoolmates/colleagues? – How do you relate to the doctor treating you? Who is he/she? Does he/she support you? Does he/she give enough time to you? Does he/she explain to you what he/she is going to do? – Are you independent in your daily life? Do you need help with particular things? – What is your source of income (wages/parents/state)? Do you receive a revenue? If yes, would you prefer any other source of income? Future – How do you see your future? – What would you most like to happen? Additional comments – …
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