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Care for consequences in children treated for leukemia or brain tumor
Aukema, E.J.
Publication date
2013
Document Version
Final published version
Link to publication
Citation for published version (APA):
Aukema, E. J. (2013). Care for consequences in children treated for leukemia or brain tumor.
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CARE FOR CONSEQUENCES
IN CHILDREN TREATED FOR
LEUKEMIA OR BRAIN TUMOR
UITNODIGING
voor het bijwonen van de
openbare verdediging van
het proefschrift
Door
Op woensdag 17 april om 11.00 uur in de Lutherse kerk, Aula van de
Universiteit van Amsterdam, Singel 411 te Amsterdam. U bent ook van harte welkom voor
de receptie (met lunch) na afloop van de promotie in de Singelkerk,
Singel 452 te Amsterdam. Graag rsvp via http://goo.gl/Km1HV Eline Aukema Veembroederhof 262 1019 HC Amsterdam e.aukema@slaz.nl 0628415377 PARANIMFEN
Marie-Anne van Roijen Liesbeth van der Sluijs Veer
Lonneke van der Mark:
Tlvdmark@gmail.com 0616968642 C M Y CM MY CY CMY K Final kaft.pdf 1 3/4/13 9:10 AM
Care for consequences
in children treated for leukemia or brain tumor
© Eline J. Aukema
ISBN: 978-90-820062-1-6
The study presented in this thesis was fi nancially supported by:
KIKA, Johanna Kinderfonds, Gratama foundation, Research school of
Neuroscience and SKK.
The printing of this thesis was fi nancially supported by:
Academic Medical Center (AMC), Psychosocial department Emma
Children’s Hospital, GlaxoSmithKline, Kennedy van der Laan (www.
rechtindezorg.nl) and Tom Voûte Fonds.
Design by:
Care for consequences
in children treated for leukemia or brain tumor
ACADEMISCH PROEFSCHRIFT
ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof.dr. D.C. van den Boom ten overstaan van een door het college voor promoties ingestelde commissie,
in het openbaar te verdedigen in de Aula der Universiteit op woensdag 17 april 2013, te 11:00 uur
door
Eline Johanna Aukema geboren te Nijmegen
Promotiecommissie
Promotores:
prof. dr. M.A. Grootenhuis
prof. dr. B.F. Last
Co-promotores:
dr. A.Y.N. Schouten-van Meeteren
prof. dr. H.N. Caron
Overige leden:
prof. dr. H.S.A. Heymans
prof. dr. F. Nollet
prof. dr. G.J.L Kaspers
dr. S. B. Schagen
dr. J. Huisman
dr. K.J. Oostrom
Faculteit der geneeskunde
Table of content
Chapter 1
General introduction
Chapter 2
Explorative study on the aftercare of pediatric brain tumor survivors: A parents’ perspective.
-
Supportive Care in Cancer, 2011,19 (10): 1637-1646Chapter 3
Childhood brain tumor survivors at risk for impaired Health Related Quality of Life
- Provisionally accepted in Journal of Pediatric Hematology / Oncology
Chapter 4
White matter fractional anisotropy correlates with speed of processing and motor speed in young childhood cancer survivors
- International Journal of Radiation Oncology, Biology, Physics, 2009, 74 (3); 837-843
Chapter 5
Exploring the feasibility of Neurofeedback training as a cognitive intervention for childhood brain tumor survivors: a pilot study
- Submitted as a brief report
Chapter 6
The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia; an open-label study.
- BMC Pediatr, 2008, 8; 25-32
Chapter 7
General discussion
Summary of the thesis (English)
Summary of the thesis (Dutch)
Portfolio
Word of thanks (Dutch)
Curriculum Vitae
8 26 46 64 80 96 114 138 144 151 154 158GENERAL iNtRoduCtioN
ChAPtER 1
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Introduction
This thesis focuses on survivors of a childhood brain tumor or childhood leukemia. The overall survival rate of children who are treated for cancer, including a brain tumor [1] or leukemia [2], has increased substantially as a result of ever-improving treatment strategies. The survival rates for brain tumor subtypes vary considerably. The 5-year survival rate for medulloblastoma has increased to 80-85%; however, little progress has been made in treating high-grade glioma or infants with malignant tumors (the survival rate is 30%) [1]. At present the overall 5-year survival rate for children diagnosed with acute lymphoblastic leukemia (ALL) is 80-90% [2]. As a consequence of the tumor and their multimodal treatment, childhood brain tumor survivors (CBTS) and ALL survivors are at considerable risk for a variety of physical, neurocognitive and/or psychosocial long-term consequences, which materialize especially after cranial radiation therapy (CRT) [3]. These long-term consequences consist of late effects resulting from cancer and its treatment, have a negative impact on daily life and emphasize the need for aftercare. This thesis includes exploratory studies of the scope of long-term consequences for CBTS and ALL survivors, years after treatment. This introductory section describes the medical aspects of brain tumors and ALL, the diversity of late effects and the need for follow-up care and aftercare. The scope of this thesis is outlined in the last paragraph of this introduction.
Medical aspects of brain tumors and ALL
Diagnosis and treatment
In the Netherlands, approximately 600 children are diagnosed with cancer each year, of whom approximately 110 are diagnosed with a brain tumor and 140 are diagnosed with ALL [4].
Brain tumors
Childhood brain tumors are very diverse and can roughly be categorized into low-grade tumors (e.g., low-grade glioma, craniopharyngeoma), and high-grade tumors (e.g., medulloblastoma, ependymoma, high-grade glioma) which behave more aggressively. About 30% of the brain tumors are low-grade tumors [5]. Over the past few decades improved neurosurgical techniques, improvements in chemotherapy schedules and radiation therapy and better diagnostic techniques have all attributed to increased survival rates [1]. Brain tumor treatment most often consists of either neurosurgery only, neurosurgery followed by adjuvant CRT and/ or various chemotherapeutic agents or chemotherapy only. Low-grade brain tumors are more often treated with surgery only, while high-grade brain tumors are mostly treated with adjuvant therapy. In the case of some low-grade tumors a wait-and-see strategy is followed subject to strict imaging control. Children with cancer are treated
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according to well-defined treatment protocols, partly developed as clinical trials in international cooperation and research. The variation in treatment of childhood brain tumors depends on the tumor histology, the location, the stage of the disease and a patient’s age [1].
ALL
Before 1990 children with ALL were treated with CRT in addition to systemic chemotherapy to prevent recurrence of the disease in or from the central nervous system (CNS). Prophylactic intrathecal chemotherapy and high-dose methotrexate (MTX) have replaced CRT in the Netherlands since 1990 since it became evident that CRT was associated with neurocognitive late effects [6, 7]. The knowledge deriving from this irradiated patient group is still important with respect to children with a brain tumor.
Different stages during cancer treatment
The cancer treatment comprises different stages: The diagnosis and acute stage, treatment, early after treatment and survivorship, and each stage has its own characteristics and related emotions [8].
Diagnosis, acute stage and during treatment
The diagnostic stage and start of treatment are very stressful and the medical procedures cause children and their parents pain and distress. When a child is diagnosed with cancer, its family faces a multitude of stressors, including the most feared stressor: potential death of the child. The child, its family and its social environment need to find a way to deal with this new situation. While neurosurgery causes acute severe stress, radiotherapy and chemotherapy do not only affect cancer cells but also normal cells, which can result in temporary side effects during treatment and/or remaining term effects after treatment [9, 10]. These long-term effects are addressed in paragraph 3. Temporary side effects such as sickness (nausea, vomiting) and hair loss can occur within days or months after the start of treatment. The low blood counts and reduced immunity resulting from therapy can cause additional health problems with sometimes life threatening situations.
During treatment most children and parents adjust well to the situation, despite the enormous daily impact of the disease. Psychosocial care is provided to increase the ability to cope with the disease and its treatment. The treatment of a childhood malignancy can take years, and can result in exhaustion in all family members.
Early after treatment and survivorship
At the end of a successful treatment, patients need to make a transition back to ‘normal’ life. At this stage, families often start to realize the emotional and physically exhausting impact of the treatment. Feelings of grief over all loss and the fear of
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relapse are frequently evoked emotions [11]. Regular medical aftercare is needed in order to provide specific aftercare for treatment effects and also to be able to identify disease recurrence at an early stage. Psychosocial aftercare care is also needed to identify difficulties with emotional functioning and to refer patients to specialized care if needed. In the case of learning difficulties referral to neuropsychological aftercare services is necessary. Five years after diagnosis, cancer patients are considered “survivors”. While only a small risk of recurrence remains, the long-term consequences of the tumor and its treatment require ongoing attention, which is the specific focus of this thesis.
Long-term consequences of brain tumors and ALL and their
treatment
Unfortunately, the increase in childhood cancer survival rates has come at a “cost”. As a consequence of the tumor and its treatment, CBTS run a considerable risk for a variety of late effects. ALL survivors treated with CRT also run the risk for late effects. Contemporary professional literature outlines difficulties in physical functioning [3, 12], neurocognitive functioning [6, 7, 13-15] and psychosocial functioning [16-20]. These late effects can have severe negative effects on survivors’ functioning in daily life [21].
The impact of treatment
How medical parameters affect these late effects is as yet unclear. CRT, applied to both patients with a brain tumor or ALL, is associated with an increased risk of endocrine, neurological, psychosocial and neurocognitive late effects, as well as fatigue and secondary malignancies [3, 22]. Meanwhile, it has become clear that survivors of a low-grade brain tumor, often treated with surgery only, also suffer from considerable long-term consequences of their tumor and their treatment [23-25]. Not only ALL survivors treated with CRT but also ALL survivors treated with prophylactic chemotherapy seem to be at risk for long-term consequences, especially more subtle neurocognitive late effects [7, 26-28].
Physical late effects
Of the long-term survivors of childhood cancer, 62-75% have chronic health problems and 25% of them suffer considerably from these conditions [3, 12]. Loss of energy and cancer-related fatigue have a negative impact on daily life [29]. Survivors are at high risk of suffering from long-term neurological (e.g. epilepsy, neuropathy, motor and coordination dysfunction and posterior fossa syndrome) and neurosensory impairments (vision, hearing and pain), which hamper the ability to function in normal everyday life [30].
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because the radiation field often includes the hypothalamic/pituitary region which results in endocrinopathies [26]. Pituitary hormone deficiencies, such as growth hormone deficiency (GHD) resulting in growth failure (in about 80% of the CBTS) and hypothyroidism (in 20-30% of the CBTS after CRT and in 60-80% of the CBTS after CRT and chemotherapy) are frequently seen, and require hormone substitution [26]. Other endocrinological consequences include gonadotropin deficiency, precocious puberty, diabetes insipidus, and obesity. After a suprasellar tumor, patients can also suffer from the hypothalamic obesity syndrome [30]. Furthermore, many survivors live with permanent changes in physical appearance and body image. Scars, hair loss, short stature and sometimes notable changes to the skull bone structure are frequently seen after CRT [30]. Finally patients are at risk for a secondary malignancy following treatment, especially after CRT [31].
Neurocognitive late effects and White matter damage
Neurocognitive late effects
CBTS, especially those treated with CRT, and ALL survivors treated with CRT are at elevated risk for neurocognitive late effects [26]. A decline in intellectual acuity has been documented frequently and can be explained by a slow acquisition rate of knowledge rather than a regression in acquired skills [14, 32, 33]. This results in an increasing gap between survivors and peers. Underlying basic cognitive skills, such as the speed of information processing, attention and working memory are important for the normal acquisition of new skills and knowledge [13, 34]. The basic cognitive skills of the majority of CBTS appear to be damaged, which results in learning disabilities, such as learning disadvantages in spelling, reading and mathematics [6, 7, 32, 35, 36] for which special education services are frequently needed [37]. Neurocognitive late effects also seem to have a negative impact on the emotional and social development of survivors, such as the development of self-esteem (e.g., about learning results), feeling different from peers, and being less socially competent than peers [38].
Several documented risk factors increase neurocognitive late effects, for instance commencing treatment at a younger age, being female, and treatment with CRT [6, 39].
In the past decade several studies have revealed that survivors of low-grade brain tumors who are treated with surgery only can also suffer considerably from late effects and run an elevated risk for poor neurocognitive and adaptive outcomes. Difficulties with information processing speed, visual spatial skills, sustained attention, memory and executive function have been documented in these survivors [23, 40].
In ALL survivors treated with prophylactic chemotherapy, subtle neurocognitive late effects such as subtle problem with attention, complex fine motor skills and non-verbal memory have also been documented [6, 7, 27, 41-43].
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White matter damage
The neurocognitive late effects described above seem to be related to white matter damage caused by CRT, chemotherapeutic agents, and other factors such as CSF obstruction, and hydrocephalus [44-46]. White matter is important for the speed of information processing because it facilitates the rate of transmission of electrical signals along axons [47]. Damage to white matter has been linked to neurocognitive late effects, especially after CRT [7]. White matter damage may be caused by either a failure of ‘normal’ maturation and myelination of the brain at an age-appropriate rate, or by damage to already existing white matter tracts. White matter damage has also been documented in ALL survivors [27, 48]. By using magnetic resonance imaging (MRI) techniques, including diffusion tensor imaging (DTI) to visualize white matter, the understanding of white matter damage and the pathophysiology of neurocognitive late effects is improving.
Psychological and social late effects
Many long-term survivors function relatively well, although symptoms of overall distress and impaired quality of life about physical functioning have been found [49, 50]. In general, no psychopathology as referred to in the Diagnostic Statistical Manual (DSM), such as depression or anxiety disorders, was found in the CBTS documented in various reviews [18, 51, 52, 53]. Despite exposure to major challenges and medical traumas, this positive and relatively adequate functioning of survivors could be indicative of their resilience and strength to cope with cancer [54, 55]. In CBTS, limited opportunities in achieving the normal milestones of young adulthood, including graduating from college, being financially independent and getting married, have been documented [19, 20, 56]. In order to study survivors’ own perceptions of their physical, psychological and social functioning and late effects, health-related quality of life (HRQOL) is measured using patient-reported outcomes. Contradictory results are found among CBTS, varying from low [24, 57-61], to good or equal HRQOL with only lower physical HRQOL, compared with peers [62-64].
What is needed for survivors at risk for long-term consequences?
In general, participation at school and normal peer contact are important for normal childhood and adolescent development. The existence of different late effects can, however, have a negative impact on children’s development and require specialized aftercare.13
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Specialized aftercareTo be able to detect late effects (physical, neurocognitive and psychosocial) early and to refer patients to specialized aftercare, regular follow-up care is necessary. Improvement in survival rates results in a growing group of CBTS and an increased demand for structured aftercare in which respect multidisciplinary follow-up programs are desirable [17, 39, 65, 66]. For each domain of late effects, several aftercare options are available, for instance physiotherapy or medication for physical problems, educational support for learning disabilities and psychological counseling for psychosocial problems.
The need for aftercare for CBTS treated with adjuvant therapy (CRT and chemotherapy) seems obvious. However, children treated with surgery only (most often for low-grade tumors) are assumed to run a minimal risk for late effects [40]. As such, they often do not participate in routine and comprehensive follow-up programs. It is unknown whether professional care providers identify their need for aftercare on time and whether existing options for aftercare are initiated on time.
Interventions for neurocognitive late effects
In recent years, the object of several studies has shifted from documenting neurocognitive late effects to describing potential interventions to remediate these effects [6, 7, 14, 32, 46]. Because of the severity and the impact of cognitive late effects on learning abilities, there is a high need for effective interventions.
To date, only a few intervention programs have been developed to remediate cognitive functioning, such as Butler and Mulhern’s Attention Process Training and the Attention and Memory Training of Hooft et al. [67, 68]. Although some improvement in parent-rated attention and academic skills [67], and in attention and memory tests results [68] have been observed, intensity and compliance have been reported to be a concern, and sustainability of the effects remains to be studied. The high need for interventions and comparable neurocognitive problems makes researchers focus on cognitive interventions in other pediatric populations with neurocognitive problems, for instance children with Attention Deficit Hyperactivity Disorder (ADHD) or traumatic brain injury (TBI) as well. In studying interventions for neurocognitive late effects several options can be considered, such as neurocognitive rehabilitation [6, 7, 35] and pharmacological interventions [69, 70, 71]. Neurocognitive rehabilitation in the form of neurofeedback is of increasing interest in children with ADHD [72, 73]. Neurofeedback training (NFT) is based on operant conditioning in which self-regulation of brain activity is taught [73]. Although CBTS differ from children with ADHD, CBTS seem to have comparable inattention symptoms and pharmacological intervention improves attention functioning in CBTS [74, 75]. As such, the effectiveness of NFT could be hypothesized in CBTS as well.
A pharmacological approach may be the use of growth hormone (GH) treatment, often used in patients with growth hormone deficiency (GHD) in order to improve
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growth. Patients with GHD can experience several cognitive problems [76 -78]. Some studies suggest that GH replacement therapy can have beneficial effects for the cognitive functioning of GHD adults [79-81]. The presence of many binding sites of GH and insulin-like growth factor I (IGF-I), a serum marker for GH status, in the hippocampus could explain this beneficial effect. The hippocampus is a brain structure that is important for learning and memory functions. Since many patients treated with CRT have pituitary hormone deficiencies, such as GHD, GH treatment could benefit not only growth but also neurocognitive late effects in cancer survivors [26].
Background and aims
BackgroundSurviving childhood cancer, especially a brain tumor, often comes with a high risk for a variety of moderate to severe physical, neurocognitive and psychosocial late effects. Based on professional literature and clinical experience, CBTS who were treated with adjuvant therapy seem to be at greatest risk. However, survivors treated with surgery only also seem to experience several late effects, although these late effects tend to be more subtle compared with other survivors. Aftercare facilities for these patients are often not as comprehensive as the aftercare provided to patients treated with adjuvant therapy [25].
Aims
This thesis addresses the long-term consequences for CBTS from different points of view. The subsequent chapters describe the perceived late effects and need for aftercare from parents’ and children’s points of view and finally white matter damage as a pathophysiological substitute for neurocognitive decline. Lastly, we examine two interventions in survivors aimed at reducing neurocognitive late effects.
Participants
Participants in the studies described in Chapters 2-5 were recruited from a patient cohort of survivors who were treated between 1991 and 2006 at the Emma Children’s Hospital AMC. Of the 160 children found in our database, 57 met the inclusion criteria of the different studies described in this thesis. The other 103 were not eligible (e.g., deceased, were lost to follow-up care or had a secondary malignancy other than a brain tumor).
Inclusion criteria were (1) treated for a brain tumor diagnosed between 0 and 18 years of age (2) current age of the survivor is between 4-20 years of age, (3) complete remission or stable residual tumor, (4) at least one year after the end of treatment, and (5) able to complete a questionnaire in Dutch. Children and parents in this group of CBTS were asked to participate in different studies depending on the aim and the
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age range of the separate studies.
The young adult survivors of childhood leukemia referred to in Chapter 6 were selected from a group of 56 patients treated between 1972 and 1990 at the Oncology Departments of the VU University Medical Center and the Academic Medical Center in Amsterdam. Participants had to have reduced bone mineral density and/ or low IGF-I scores to be included in this study.
Outline of this thesis
Chapter 2: Late effects of CBTS are described from a parent’s perspective and the
need for aftercare for these late effects is studied. This chapter describes the aftercare process in terms of timing of the care, type of referrer and needs for improvement. The need for aftercare for survivors who were treated with surgery only versus survivors who were treated with surgery plus adjuvant therapy is compared.
Chapter 3: The HRQOL of CBTS is described in mean scores and percentages at
risk. Differences in HRQOL between survivors who were treated with surgery only and survivors who were treated with surgery plus adjuvant therapy are examined.
Chapter 4: White matter damage is studied by measuring the white matter fractional
anisotropy (WMFA) of CBTS using the Diffusion Tensor Imaging technique on a 3.0-T MRI, in comparison with a control group of ALL patients treated with MTX for CNS prophylaxis and healthy subjects. The relationship between WMFA and information processing speed and motor speed is examined.
Table 1: Overview of the CBTS and ALL participants in the different studies
EoT: End of treatment; HRQOL: Health related Quality of life; WMFA: White matter fractional anisotropy;
NFT: Neurofeedback training; GH: growth hormone; CBTS: Childhood brain tumor survivors; ALL: acute lymphoblastic leukemia; yrs: years
* n=34 from chapter 2; ** n=5 from chapter 2, n=3 from chapter 5, n=1 new; ***n=9 from chapter 2, n=3 from chapter 4
Chapter N Criteria: age at study Criteria: time since EoT 2: Aftercare 42 CBTS 4-20 yrs 1 yrs
3: HRQOL 34 CBTS * 8-18 yrs 1 yrs
4: WMFA 6 CBTS ** 11 ALL
8-16 yrs 2 yrs
5: NFT 9 CBTS *** 8-20 yrs 2 yrs
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Chapter 5: The feasibility of neurofeedback training (NFT) as a potential intervention
for neurocognitive late effects is examined in a pilot study of nine CBTS. Pre- and post NFT assessment consist of neurocognitive tests and psychosocial questionnaires. Parents and participants are interviewed to evaluate their experience with NFT and perceived changes in daily life.
Chapter 6: In this chapter the effects of two years of growth hormone (GH) replacement
therapy as an intervention for reduced bone mineral density and/or low IGF-I scores is studied for its neurocognitive effects in a group of young adult ALL survivors most treated with CRT as CNS prophylaxis.
Finally, a general discussion reflects on the main findings of the studies and future perspectives and the implications for the Dutch pediatric neuro-oncology practice are addressed.
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ChAPtER 2
Explorative study on the
aftercare of pediatric brain
tumor survivors: A parents’
perspective
E.J. Aukema M.Sc. B.F. Last Ph.d. A.Y.N. Schouten-van Meeteren M.d., Ph.d. M.A. Grootenhuis Ph.d.
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Abstract
Purpose: Whilst the need for aftercare for long-term sequelae of brain tumor survivors
is well known and evident, information from a parent’s perspective is lacking on whether the need for aftercare is detected in time, and whether the aftercare is timely initiated and meets the needs for aftercare.
Methods: A survey regarding aftercare in five domains of long-term sequelae
(neurocognitive, physical, emotional, social and parenting problems) was sent to 57 parents of survivors treated for a brain tumor in our center.
Results: Forty-two (74%) parents participated in this study. With a mean period of 8.1
years (SD=3.9) since start of treatment, the majority of the survivors (mean age=14.7 years, SD=3.8) needed aftercare in several domains of functioning. This need was highest and most met for physical sequelae (N=34), and lowest but still substantial and least met for parental difficulties (N=11). Parents of survivors with surgery only as treatment reported a similar need for aftercare as those of survivors with adjuvant therapy. Most of the survivors received aftercare; however, substantial delay of aftercare and self-referral for aftercare were frequently reported. Furthermore, parents showed a lack of knowledge about and use of aftercare services.
Conclusions: Increased awareness for the need for psychosocial aftercare is required.
Coaching, psycho-educative programs about coping with the long-term sequelae and information about available specialized aftercare services are required to meet the needs of brain tumor survivors and their parents more adequately.
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Introduction
The overall survival rate of children with a brain tumor has increased substantially due to multimodal treatment strategies [1]. As a consequence of the tumor and its multimodal treatment, survivors of childhood brain tumors are at considerable risk for a variety of long-term sequelae.The current literature comprehensively outlines the multiple neurocognitive difficulties [2-4], problems in physical functioning [5, 6] and, psychosocial difficulties [7-11] experienced by survivors of childhood brain tumors and the impact on family functioning [12, 14]. There is growing evidence that not only survivors treated with cranio(spinal) radiotherapy, but also survivors of low grade brain tumors treated with surgery only, experience several long-term sequelae [15,16].
The group of brain tumor survivors is growing and results in an increased demand for structured aftercare for which multidisciplinary long-term follow-up programs (e.g. [10,17-20]) are desirable. For example, Wallace et al. [20] proposed a three-level follow-up model to organize the intensity and frequency of the follow-up care. Recently, Bowers et al. [21] evaluated the use of these long-term follow-up programs in different centers from the Children’s Oncology Group (COG) group members and found considerable variations in follow-up care in different centers despite these guidelines. They reported multiple barriers in the delivery of follow-up care, barriers in finance and insurance, but also more intrapersonal barriers knowing patients’ uncertainty about the need to follow-up care and the desire not to be followed in a pediatric aftercare program.
Variation in brain tumors and treatment modalities may influence the amount, interval and length of the follow-up care based on health risks. More knowledge about the necessary follow-up care for children who had surgery only as treatment for their brain tumor compared to those treated with adjuvant therapy is needed. The follow-up care can vary in the degree of care provided. This could be caused by either insufficient awareness of long-term sequelae or due to restrictions in multidisciplinary care for instance a separate neurosurgery department. Research so far indicates that timely intervention and preventive programs improve different aspects of quality of life of survivors of childhood cancer. Recently, several evidence-based interventions became available, including cognitive remediation [22-24] and emotional and social programs [25-27]. By remediating cognitive functions and offering early interventions at school (e.g. extra tutoring, audio books, use of a laptop) new learning facilities are provided, improving future perspective and psychosocial functioning of these survivors.
Although the need for aftercare for sequelae of some survivors are obvious, especially for children treated with adjuvant therapy, information is lacking on whether this need is detected in time by professionals and whether existing aftercare is timely initiated. Furthermore because of the long lasting existence of the sequelae and
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the risk for these survivors to grow further into their deficits [16], it is essential that parents and survivors are well informed about the possible sequelae. Thereby they should have knowledge about available aftercare services. Little is known about the parents’ perspective on the follow-up aftercare; such as whether their own needs for aftercare for their child are met, whether parents have enough knowledge of and make use of aftercare services available or whether parents experience certain barriers in the care trajectory after the treatment.
With a survey we retrieved information from parents of a diverse group of brain tumor survivors in order to gain insight in the needs for aftercare, the course of aftercare and needed improvements regarding the provided aftercare. The aims of this explorative study were to: (1) describe the need for aftercare for longterm sequelae perceived by parents and to explore the aftercare, (2) analyze differences in the need for aftercare in children treated with or without adjuvant therapy and (3) evaluate parents’ knowledge about and use of aftercare services available in the Netherlands.
Methods
Procedure
Parents of all children who had completed treatment for a brain tumor between 1990 and 2006 at the Emma Children’s Hospital Academic Medical Center, Amsterdam, The Netherlands (N=57), were invited to participate in the study. Children with neurofibromatosis were excluded because of their specific cluster of impairments. The inclusion criteria were: (1) treated for a brain tumor of any histology diagnosed between the ages of 0 and 18, (2) current age of the survivor between 4 and 20 years, (3) complete remission or stable residual tumor, (4) at least 1 year after the end of treatment, and (5) able to complete a questionnaire in Dutch.
Parents of survivors who met the inclusion criteria in May 2007 were invited to this study, which was approved by the local medical ethics committee. Parents were firstly contacted by phone and then received an introductory letter explaining the aim of the study and asking for their participation. The letter was accompanied by questionnaires including a survey about the aftercare, as reported in this article, an informed consent form, and a stamped return envelope. Each family received one packet of questionnaires by mail to be completed at home. Non-responders were contacted by phone and a reminder letter was sent to increase response.
Measures
The survey with eight questions per domain of child functioning and parenting includes both pre-coded as open questions about the need for aftercare, the type of provided aftercare, timing and referral, needs for improvements and knowledge about and use of aftercare services. The choices of the specific domains of child functioning and parenting were based on the known long-term sequelae of childhood cancer
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survivors [2-16] and aftercare services available in the Netherlands. The questions were formulated by several experienced oncologists and psycho-oncologists of our hospital.
Answering options with service examples were given as well as space to write down other options. Afterwards, answers were categorized in the categories described below.
First, the prevalence and type of long-term sequelae in five different domains and the need for aftercare were evaluated among the parents. The domains covered different types of long-term sequelae, classified as follows: (1) neurocognitive problems (regarding attention, memory, processing speed, executive function, visual perceptual motor skills, and fine motor skills); (2) physical problems (regarding energy level [e.g., headache, fatigue], hormone function [e.g., early puberty, growth retardation], motor function [e.g., fine and gross dexterity, balance, strength], epilepsy, visual and auditory function); (3) emotional problems (including internalizing [fearfulness, worrying, difficulties in expressing emotions], externalizing [frustration, anger] illness experience [difficulties with the disease, feeling different], and self-esteem); (4) social problems (regarding social isolation [e.g., contact making, maintain relationships], adult-centered, being bullied, and quarreling with peers); and (5) parenting problems (including autonomy encouragement, differences in parenting style, overprotection and overindulgent behavior).
Based on these answers, a mean score of need for care in the different domains (0-5) was calculated per participant.
Second, the type of aftercare as provided was asked, categorized in specific answer options and examples of aftercare services available in the Netherlands for each domain. These were, for neurocognitive problems: educational support at a regular school, special needs school, neurocognitive test administration and/or remediation; for physical problems: physiotherapy and/or occupational therapy, medication, specific diet, motor support equipment (e.g., motor aids, adjusted sport participation), visual support (e.g., eyeglasses or training to cope with visual deficits), auditory support, and special education needs based on motor dysfunction; for emotional problems: therapy from a psychologist, other forms of supportive care (e.g., homeopathy, creative therapy), parental support and contact with fellow-patients; for social problems: therapy from a psychologist, social skills training, parental support and contact with fellow-patients; and for parenting problems: therapy from a psychologist or another professional giving parenting support and contact with fellow parents. We evaluated the aftercare in terms of the referrer and need for improvements regarding (1) timely response to the need for aftercare, (2) psycho-education and support in finding aftercare services, (3) proactive approach from school and (4) proactive screening of needs for aftercare. To explore who referred participants to the aftercare, we created the following categories: hospital staff (doctors, psychologists or other caregivers from the hospital), school staff (teachers or other staff members of the school), and parents
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themselves (whether or not in cooperation with the general practitioner).
Finally, the knowledge of the existence and use of different aftercare institutions and websites in The Netherlands were asked. The knowledge was categorized in websites with psycho-education about acquired brain injury and brain tumors, institutions for aftercare services (rehabilitation centers, hospitals), parents’ association for children with cancer and family camps, and school services (websites with school aids, information and school liaisons).
Individual patient data regarding gender, date of birth and medical data regarding date of primary diagnosis, histological type of tumor, location of tumor, type of treatment, secondary operations (including progression and relapse) and duration of adjuvant treatment were gathered from the medical files.
Statistical analyses
The participants and non-participants were compared with respect to demographic and medical variables using Independent Samples t-tests and the chi square (
χ
2) tests (p<0.05). Frequency analyses were conducted to assess the prevalence and kind of parent-reported longterm sequelae, the need for aftercare and the amount of domains for which aftercare was needed (0-5) was calculated. Then, associations between need for aftercare and treatment (‘surgery only’ and ‘surgery and adjuvant therapy’) were examined withχ
2 tests at p<0.05 and with Mann–Whitney U-tests, differences in the amount of need for care in different domains (0-5) between these two groups were examined at p<0.05. Also, frequency analyses were used to evaluate the provided aftercare and the familiarity with websites and institutions. The Statistical Package for Social Sciences (SPSS) version 16 was used for all analyses.Results
ParticipantsForty-two (74%) of the 57 parents participated in the study and returned their completed survey. Characteristics of the participants and non-participants are presented in Table 1. Half of the participants were treated with surgery plus adjuvant therapy. Non-participants did not differ from participants in demographic and medical variables. The reasons given for not participating were lack of interest or no time to fill in the questionnaires.
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Needs for and exploration of the aftercare in different domains of long-term sequelae
The need for aftercare and received aftercare and needs for improvements with the aftercare trajectory are presented in Tables 2 and 3.
Overall, most parents reported need for aftercare in several domains: 17% reported problems in two domains, 29% reported problems in three domains, 19% reported problems in four domains and 14% reported problems in all domains. Overall, the mean amount of domains for which aftercare was needed according to the parents was 2.8 (median=3, SD=1.4).
Table 1: Characteristics of the (non-)participants (N = 57)
Participants (n = 42) Non-participants (n = 15) M SD Range n M SD Range n
Age at study (yrs) 14.7 3.8 5.7 – 19.8 42 14.9 4.1 7.7 - 19.8 15 Age at start treatment (yrs) 6.5 3.3 1.9 - 16.5 42 8.1 4.4 2.2 - 16.8 15 Time since start treatment (yrs) 8.1 3.9 1.6 - 15.7 42 6.6 3.6 1.7 - 14.4 15 Duration of adjuvant treatment (yrs) 1.3 1.7 0.2 – 8.0 22 1.4 1.1 0.4 – 2.8 4
n % n % 19 45 10 67 Gender Male Female 23 55 5 33 26 62 10 67 Tumor location Infratentorial Supratentorial Tumor Type High grade Low grade 16 19 23 38 45 55 5 3 12 33 20 80 20 48 11 73 22 52 4 27 Treatment Surgery only
Surgery plus adjuvant therapy Other
More specific - -
- - Surgery only 20 48 11 73 Surgery and radiation therapy 1 2 - - Surgery and chemotherapy 5 12 - - Surgery, radiation therapy and
chemotherapy 16 38 4 27 More than one operation
(including progression, relapses)
8 19 3 20 Age at diagnosis ≤3 years >3 years 5 37 12 88 1 14 7 93 Respondent Father Mother Both 6 32 4 14 76 10 - -
32 or after car e per domain (N= 42) 28 ( 93) 31 ( 91) 19 ( 86) 16 ( 76) 8 ( 72) indi ca te d 2 ( 7) 3 ( 9) 3 ( 14) 5 ( 24) 3 ( 27) te rc ar e* N eu ro co gn iti ve te st assessm en t a nd /o r re m ed ia tio n 17 ( 61) Phys iot he ra pi st / O ccu pat io nal the ra pi st 25 ( 81) Ps yc hol og is t 15 ( 79) Ps yc hol og is t 11 ( 69) Pa re nt al s uppor t 7 ( 88) Sp eci al ed ucat io nal serv ic es: 23 ( 82) M ed ic atio n 15 ( 48) Fe llo w p atie nt co nt act 6 ( 32) So cia l s kil ls tr ai ni ng 7 ( 44) Fe llow pa re nt co nt act 1 ( 13) - educ at io na l s uppo rt at a r egu lar s ch oo l - tr ans iti on t o s pe ci al ed ucat ion s ch ool 17 ( 61) 13 ( 46) M ot or s uppor t equi pm ent 12 ( 39) O th er e m otio na l suppor tive c ar e 6 ( 32) Fe llow pa tie nt co nt act 2 ( 12) V is ua l s uppor t 12 ( 39) Pa re nt al s uppor t 2 ( 11) Par en tal s uppo rt 1 ( 6) Sp ec ific d ie t 4 ( 13) Spe ci al m ot or ne ed s s ch ool 3 ( 10) A udi to ry s uppo rt 3 ( 10) w er e p os sib le in o ne p atie nt N eu rocogn it ive n ( % ) P h ysi cal n ( % ) Em ot io na l n (% ) So ci al n ( % ) P aren ti n g n ( % ) 3 1 ( 74 ) 3 8 ( 90 ) 2 7 ( 64 ) 2 4 ( 57 ) 1 6 ( 38 ) s * A tt en tio n 15 ( 48) M oto r fu nc tio n 28 ( 74) In te rn al iz in g 16 ( 59) So cia l is ol atio n 21 ( 88) A ut on om y en cou rage m en t 11 ( 69) Pr oce ss in g s pe ed 14 ( 45) E ne rgy l eve l 19 ( 50) Il ln es s ex per ien ce 12 ( 44) B ei ng b ul lie d 9 ( 38) O ver pr ot ect iv e 9 ( 56) Fin e m oto r s kil ls 13 ( 42) H or m one func tion 14 ( 37) Se lf-es te em 9 ( 33) A du lt ce nt er ed 7 ( 29) O ver in du lgen t 6 ( 38) M em ory 11 ( 36) V is ua l pr obl em 12 ( 32) E xt er na liz ing 8 ( 30) Q uar rel w ith p eer s 6 ( 25) Par en tal di ffe re nce 4 ( 25) E xe cu tive fu nct ion s 8 ( 26) E pil ep sy 6 ( 16) V is uope rc ept ua l m ot or s ki lls 7 ( 23) H ear in g l os s 6 ( 16) tercare 30 ( 97) 34 ( 89) 22 ( 81) 21 ( 88) 11 ( 69) 1 ( 3) 4 ( 11) 5 ( 19) 3 ( 13) 5 ( 31)
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Table 3: Evaluation of the received aftercare in different domains
Neurocognitive n (%) Physical n (%) Emotional n (%) Social n (%) Parenting n (%) Need for aftercare
Yes 30 (97) 34 (89) 22 (81) 22 (88) 11 (69)
Received aftercare
Yes 28 (93) 31 (91) 19 (86) 17 (77) 8 (73) No but was indicated 2 (7) 3 (9) 3 (14) 5 (23) 3 (27)
Referrer *
Hospital staff 10 (36) 29 (85) 8 (42) 2 (17) 1 (13) Schoolteacher or staff 9 (32) 5 (15) 3 (16) 6 (35) 1 (13) Parents themselves 10 (36) 4 (12) 8 (42) 9 (53) 4 (50) Not specified 2 (7) 2 (6) 4 (21) 2 (12) 2 (25)
Need for improvements *
More specific 17 (57) 11 (31) 11 (50) 12 (57) 7 (64) Timely response to need for care 13 (43) 9 (27) 7 (32) 8 (36) 5 (45) Psycho-education about possible long-term
sequelae and available aftercare services and support in finding aftercare service
11 (37) 6 (18) 9 (41) 5 (23) 5 (45 Proactive approach from school 6 (20) 2 (6) 1 (5) 1 (5) / Proactive screening of needs for aftercare 7 (23) 3 (9) 4 (18) 6 (27) 3 (27) * more options were possible in one patient
Neurocognitive domain
Two third of the parents (N=31; 74%) reported neurocognitive problems, most often consisting of problems with attention, processing speed and fine motor skills. Thirty of these survivors (97%) needed aftercare; 28 survivors received specialized aftercare, two survivors did not receive the care they needed. Aftercare was comprised of use of special educational services knowing remedial teaching at a regular school or transition to a school for special education and neuropsychological testing with or without remediation.
Parents reported that the hospital staff, school and parents themselves equally acted as referral sources for specific aftercare. Half of the parents expressed their needs for improvements regarding a sooner response to the need for aftercare and more support and psycho-education in general. In particular, they reported that school should point out problems more actively.
Physical domain
Survivors with physical problems (N=38, 90%) covered motor dysfunctions, such as fine and gross dexterity and balance, being tired and having headaches, as well as early puberty and delayed growth. Most of these survivors (N=34, 89%) needed professional aftercare; 31 survivors received specialized aftercare; three did not receive aftercare though it was needed.
Most survivors received aftercare from a physiotherapist and/or occupational therapist, and received medication (anti-epileptic drugs and/or hormones) and motor or visual support equipment.
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In most cases, the hospital staff referred participants to the particular specialist or therapist. A third of the parents had suggestions for improvements regarding the timing and the need for more support and information about getting the needed aftercare.
Emotional domain
Twenty-seven parents (64%) reported emotional problems in their child, especially internalizing symptoms regarding illness experiences and selfesteem. The majority of these survivors needed aftercare (N=22, 81%); 19 survivors received aftercare; three did not receive the care that was needed. The aftercare given included treatment by a psychologist, other emotional supportive care and fellow patient contact.
The hospital staff and parents initiated this type of aftercare. Needs for improvement were expressed by half of the parents. More specifically, parents asked for more support and psycho-education on the possible emotional long-term sequelae, asked for information on aftercare available and asked for a more timely response on emotional problems.
Social domain
Social problems were reported in 24 survivors (57%) and involved social isolation, being bullied and adult-centered behavior. The majority of these survivors (N=21, 88%) needed aftercare; 16 received specialized aftercare, and five did not receive aftercare although the need existed according to the parents.
Aftercare was primarily comprised of treatment by a psychologist or a social skills training. In almost half of the patients the care was initiated by the parents themselves, followed by school and the hospital staff. Parents expressed their need for improvements regarding a proactive screening for social problems in general and thereby a sooner referral for specific aftercare. Parents also wanted to receive more information about possible difficulties that could arise in the child’s social behavior.
Parenting domain
A third of the parents (N=16, 38%) reported problems with encouraging autonomy in their child and being overprotective and overindulgent to the child. Eleven (69%) needed extra care, of which eight received aftercare and three did not get the needed aftercare. Mostly, aftercare was comprised of professional parental support as was initiated by parents themselves.
More than half of the parents reported that improvements were needed, in particular more information about possible parenting difficulties and better screening and, if necessary, referral for these difficulties.
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Associations and differences between need for aftercare and type of treatment
No significant associations were found between the need for aftercare in the different domains and treatment modalities.
The groups also did not differ in the mean amount of domains for which aftercare was needed (mean amount of domains in ‘surgery only’ group=2.7 and in ‘surgery plus adjuvant therapy’ group=3.0 domains; U=189, p=0.4).
Knowledge about and use of relevant institutions and websites
The familiarity and use of relevant institutions and websites for support and interventions in case of long-term sequelae are reported in Table 4.
Parents were most familiar with the aftercare services in the hospital (81%), the parents’ association of children with cancer and camps for survivors (69%) and websites with psycho-education about required brain injury and brain tumors (64%). They were least familiar with educational services and special educational aids (31%). Despite the knowledge of relevant institutions and websites, only 45% of parents actually made use of institutional aftercare, followed by the parents’ association of children with cancer and camps for survivors (38%), use of websites (19%), and finally school services (10%).
Discussion
Despite the fact that childhood brain tumor survivors are at considerable risk for long term sequelae for which aftercare is needed, little is known about the recognition of this need for aftercare and whether the aftercare meets the needs of the parents of this group of survivors.
Our explorative study from a parents’ perspective highlights a considerable need for aftercare, not only for physical and neurocognitive problems, but also a substantial need for social, emotional and parenting aftercare. These findings are comparable with the outcome of former studies [2-6]. This need for aftercare has been expressed by the parents regardless of whether survivors had received adjuvant therapy, which
Table 4: Knowledge about and use of relevant institutions and websites
Familiar with n % Make use of n % Websites with psycho-education about
acquired brain injury and brain tumors 27 64 8 19 Institutions for aftercare services
(rehabilitation centers, hospitals) 34 81 19 45 Parents’ association for children with
cancer and family camps 29 69 16 38 School services (websites with school aids,
information and school liaisons) 13 31 4 10
