Outcome of craniopharyngioma in children: long‐term complications and quality of life

Outcome of craniopharyngioma in children: long-term complications and quality of life Andrea Poretti MB BS, Division of Neurology; Michael A Grotzer MD; Karin Ribi MPsych, Division of Oncology; Eugen Schönle MD, Division of Endocrinology; Eugen Boltshauser* MD, Division of Neurology, University Children’s Hospital of Zurich, Switzerland. *Correspondence to last author at Division of Neurology, University Children’s Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland. E-mail: eugen.boltshauser@kispi.unizh.ch Childhood craniopharyngiomas are histologically benign tumours arising from remnants of Rathke’s pouch in the hypothalamic–pituitary region. The two common treatment approaches are primary total resection or limited resection followed by radiotherapy. To study the outcome after a primary surgical approach, we followed 25 consecutive patients (10 females, 15 males) under 16 years of age who were treated in a single institution with a management policy of radical tumour excision (mean age at diagnosis 9 years 2 months, SD 4 years 3 months; range 2 years 9 months to 15 years 11 months). Mean follow-up after primary surgery was 11 years 3 months (SD 7 years 7 months). Tumour control, and neurological, endocrine, and hypothalamic complications and their impact on healthrelated quality of life were assessed (medical follow-up, semistructured interview, and questionnaires). Results of tumour control were generally good, however, local failure was observed in 6 of 25 patients, and severe late-treatment complications decreased quality of life for many long-time survivors. Endocrine deficiency occurred in 24/25, visual complications in 16/24, neurological complications in 8/24, obesity in 14/23, increased daytime sleepiness in 6/21, and significant school problems in 10/20. Patients with craniopharyngioma rated their health-related quality of life as considerably lower than healthy controls; the domains of social and emotional functioning were particularly affected. Parents’ ratings were considerably lower than those of the patients. Poor functional outcome was associated with large tumours infiltrating or displacing the hypothalamus, the occurrence of hydrocephalus, and young age at diagnosis, but also with multiple operations due to tumour recurrence. Alternative treatment strategies should be considered, especially in very young patients with large tumours. See end of paper for list of abbreviations. 220 Developmental Medicine & Child Neurology 2004, 46: 220–229 Craniopharyngioma is a slow-growing benign tumour of epithelial origin that arises in the sellar and/or suprasellar region and develops from remnants of Rathke’s pouch (Brada and Thomas 1993, Hayward 1999, Moore and Couldwell 2000). Craniopharyngiomas account for 1.2 to 4.6% of all intracranial tumours, corresponding to 0.5 to 2.5 new cases per million population per year. They are the most common non-neuroepithelial intracerebral neoplasms in children, accounting for 5 to 10% of intracranial tumours in this age group (Bunin et al. 1998). The 10-year survival rate reported in children with craniopharyngioma is in the region of 90%, with no significant difference between patients undergoing radical surgery and those receiving radiotherapy after incomplete resection (Hetelekidis et al. 1993). This is clearly an improvement over the situation two decades ago. With improved survival rates, however, has come an increased awareness of significant tumour and/or therapy-related long-term complications. Despite their benign nature, craniopharyngiomas can cause severe and permanent damage to visual (Pierre-Kahn et al. 1994, Abrams and Repka 1997), hypothalamic (De Vile et al. 1996a, Muller et al. 2001), endocrine (Paja et al. 1995, De Vile et al. 1996b, Tiulpakov et al. 1998), and neurocognitive functions (Cavazzuti et al. 1983, Anderson et al. 1997, Villani et al. 1997, Fisher et al. 1998, Riva et al. 1998) and can threaten life. What is not yet sufficiently documented is the impact that such late effects have on the quality of life (QoL) of the survivors. Interest in the measurement of QoL has expanded considerably over the past 10 years, with an increasing understanding of the importance of patients’ perspectives (Jenney 1998). According to the World Health Organization (WHO 1948), health-related quality of life (HRQoL) is seen as a multidimensional concept including physical, social, cognitive, and emotional functioning. The subjective perception and appraisal of functioning are as important as objective health, because individuals with the same objective health status can report very different QoL (Schipper et al. 1996). For assessing HRQoL in paediatric populations there is wide agreement that instruments should be multidimensional, sensitive to cognitive development and easy to complete, and should encompass the broadest age range possible. Furthermore, they should meet the required psychometric parameters of sensitivity, reliability, and validity (Bradlyn et al. 1996, Eiser and Morse 2001, Varni et al. 2001). To study the outcome of craniopharyngioma in children treated with a primary surgical approach, we followed 25 consecutive patients at a single hospital treated between 1980 and 2002. A comprehensive assessment of tumour control, and of neurological, endocrine, and hypothalamic complications and their impact on HRQoL, was performed with qualitative and quantitative measures. Method PATIENTS Between 1980 and 2002, 25 patients under the age of 16 years with craniopharyngioma underwent surgery at the Department of Neurosurgery of the University Hospital of Zurich, Switzerland. All diagnoses were confirmed by histological assessment of a tumour specimen. Total resection was defined as complete tumour removal as reported by the operating neurosurgeon and confirmed by postoperative neuroimaging (magnetic resonance imaging or computerized tomography). As of March 2003, 22 of the 25 patients were alive. One patient died as a result of an intracerebral bleed at postoperative day four, one patient died of hypovolaemic shock after abrupt stopping of the vasopressin medication 2 months after surgery, and one patient died as a result of drug abuse 17 years and 5 months after surgery. One patient had moved to another country and could not be contacted. The remaining 21 patients agreed to be interviewed and to be assessed by quantitative measures. Nine patients were female; 12 were male. Tumour location was suprasellar in 10 patients and supra-/intrasellar in 11 patients. The hypothalamus was infiltrated or displaced by the tumour in 17 of 21 patients (as judged by AP, MAG and EB). Ten of 21 patients had hydrocephalus at diagnosis. Mean age at diagnosis was 9 years (standard deviation [SD] 4 years 6 months; range 2 years 10 months to 15 years 11 months), and the mean age at the time of this study was 20 years 7 months (SD 7 years 4 months; range 4 years 6 months to 32 years 5 months). MEASURES Semi-structured interview After receiving the written informed consent of parents and patients, an appointment was arranged to coincide with a routine outpatient visit. If no such visit was planned, the interview took place at the patient’s home. Together with the information obtained from medical notes, the data gathered in the interview sought to give a picture of the participants’ past and present life situation. The interview, therefore, included questions about the time of diagnosis and treatment, current medication, physical and visual functioning, height and weight, satisfaction with physical appearance, emotional functioning, interpersonal relationships including school performance, personal interests, social activities, thoughts, family relations, intimate relationships, and wishes about the future (Appendix I). The questions were phrased in an easily comprehensible way and almost every question had a yes/no answer. One author (AP) performed all interviews and interpreted all data. A visual acuity of 0.7 or less in at least one eye was defined as decreased. A Body Mass Index (BMI) more than the 97th age-adjusted centile was defined as obesity. A body height of less than the 3rd age-adjusted centile was defined as short stature. Epworth Sleepiness Scale (ESS) To assess the subjective level of daytime sleepiness, a German version of the ESS was used (Johns 1991, Bloch et al. 1999). The ESS contains eight situations related to usual daily activities and the patient is asked to rate how likely he or she would be to doze off or fall asleep. Patients older than 13 years of age can self-rate, children younger than 13 years are rated by the parents. In the present study we used the ESS for all patients. The scores of the study population were compared with the scores of 159 healthy Swiss controls (Bloch et al. 1999). Youth Self Report (YSR) To assess behavioural and emotional problems, a German version of the YSR derived from the Child Behavior Checklist (CBCL) was used (Achenbach 1991a, Steinhausen et al. 1999). The YSR includes self-report scales developed for children and adolescents aged 11 to 18 years. The questionnaire consists of 120 items addressing behavioural and emotional symptoms. It yields scores for eight narrow-band clinical sub-scales (withdrawn, somatic complaints, anxiety and depression, social problems, thought problems, attention problems, aggressive behaviour, and delinquent behaviour), two broadband scales (internalizing and externalizing behaviour problems), and an overall total behaviour problems score. Participants rate the occurrence of each symptom within the past 6 months. The choice of cut-off points to denote clinical significance was based on the recommendations of Achenbach (1991a). Assuming that the instrument is also valid for young adults aged 18 to 22 years, the YSR was used in the present study for 12 patients aged between 11 and 22 years. The scores of the study population were compared with the previously reported scores of 1093 healthy Swiss control participants (Steinhausen and Winkler Metzke 1998). Child Behavior Checklist (CBCL) To assess behavioural and emotional problems from a parental point of view, a German version of the CBCL was used (Achenbach 1991b, Steinhausen et al. 1996). The CBCL are parent proxy-report scales developed for children and adolescents aged 4 to 18 years. To compare parent reports with self reports, the CBCL items were compared with the YSR items. The cut-off points were the same as in the YSR. In the present study the CBCL was used for the parents of the 12 patients assessed by the YSR. Fertigkeitenskala Munster–Heidelberg Abilities Scale (FMH) To assess the ability to perform daily life actions, the German ‘Fertigkeitenskala Münster–Heidelberg’ Scale (FMH) was used (Wolff et al. 1996). The FMH is a standardized tool for measuring motor and verbal functioning. A point score leads to an agerelated centile ranking similar to typical centiles in paediatrics. Consisting of 56 items like ‘can walk without aids’ or ‘earns money’, the FMH items are self-report scales (yes or no) developed for children, adolescents, and adults with brain tumours. Dimensions covered include locomotion, eating/drinking, personal hygiene, general independence, understanding and writing/reading/ calculating. In the present study the FMH was used for all patients. The scores of the study patients were expressed as age-dependent centile values based on the published scores of 971 healthy controls (Wolff et al. 1996). Pediatric Quality of Life Inventory (PedsQL) To measure HRQoL, a German version of the Pediatric Quality of Life Inventory (PedsQL) was used (Varni et al. 1999, FelderPuig et al. 2004). The PedsQL is a modular instrument for measuring HRQoL in children and adolescents aged 2 to 18 years. The 23-item PedsQL 4.0 Generic Core Scales are multidimensional self-report and parent proxy-report scales, developed as the generic core measure to be integrated with the PedsQL Disease-Specific Modules. The PedsQL 4.0 Generic Core Scales consist of eight items addressing physical functioning and five items each addressing emotional functioning, social functioning, and school functioning. In the present study PedsQL 4.0 was used for all patients. The scores of the study population were compared with the published scores of 401 healthy controls (Varni et al. 2002). The 27-item PedsQL 3.0 Cancer Module comprises eight scales: pain and hurt, nausea, procedural anxiety, treatment anxiety, worry, cognitive problems, perceived physical appearance, and communication. In the present study the PedsQL 3.0 Cancer Module was used for all patients. For all except one patient the parents completed a questionnaire for both the PedsQL 4.0 Generic Cores Scales Outcome of Craniopharyngioma in Children Andrea Poretti et al. 221 and the PedsQL 3.0 Cancer Module. Approval to perform the study and to link study data to clinical data was obtained from the Institutional Review Board. Parents and patients gave informed consent. Results LOCAL TUMOUR CONTROL AND RELAPSE - FREE INTERVAL Resection was assessed as ‘macroscopically total’ at first surgery in 23 of 25 patients. Two patients had a subtotal resection. The surgical approach was pterional in 18 patients, combined (pterional and transcallosal) in six patients, and transsphenoidal in one patient. Mean follow-up time of all patients after primary surgery was 11 years 3 months (SD 7 years 7 months; range 4 days to 22 years 7 months). The 10-year overall survival was 92% and the 10-year progression-free survival was 68% as determined by the Kaplan–Meier method (Kaplan and Meier 1958; Fig. 1). Local failure (defined as a recurrence after complete resection or tumour progression of residual tumour) was observed in six of 25 patients after a mean interval of 3 years 1 month (SD 1 year 10 months; range 10 months to 5 years 8 months). Both patients with subtotal resection had tumour progression. Five of six patients with tumour recurrence were treated with further surgery aimed at total removal. Three patients had additional local radiotherapy (two by external beam radiation, one by gamma knife radiosurgery). Five of the six patients with tumour recurrence had two recurrences; one patient had three recurrences. a PFS probability 1.0 0.8 0.6 Together with the information obtained from the medical notes, the data gathered in the interview sought to give a description of the patients’ disabilities and their past and present life situation. Table I summarizes this information, including its impact on QoL as rated by the patients. For patients who could not be interviewed because of death (n=3) or relocation (n=1), information was retrieved as far as possible from medical notes. ENDOCRINE COMPLICATIONS After primary surgery, 24 of 25 children required hormonal replacement therapy. Diabetes insipidus requiring vasopressin supplementation was identified in the immediate postoperative period in all patients, but was transient in two patients. Twenty-one patients required long-term thyroid hormone replacement. Adrenal hormone supplementation was administered at some point to 19 patients. Sex hormones were administered or are expected to be administered to 21 patients. Growth hormone was administered or is expected to be administered to 20 patients. At the time of this report, three patients had short stature. Six of 20 patients affected felt that their endocrine deficits reduced their QoL. NEUROLOGICAL AND VISUAL COMPLICATIONS Nine of 25 patients had severe perioperative neurological complications that persisted during long-term follow-up. These complications included total blindness (n=2), unilateral loss of vision (n=4), strabismus (n=3), facial nerve palsy (n=3), and hemiparesis (n=2). Moderate perioperative neurological complications that persisted included decreased visual acuity (n=3) and visual field constriction (n=14). Four patients developed seizures. Hemiparesis, facial nerve palsy, and strabismus were reported to reduce QoL in all patients affected. HYPOTHALAMIC OBESITY 0.4 0.2 0.0 0 5 10 15 20 25 Years since diagnosis b Three patients had a history of significant weight gain before the diagnosis of craniopharyngioma. All three patients showed a further increase in BMI after surgery. Postoperatively, an additional 11 patients experienced appetite disorders and hypothalamic obesity. Mainly because of their obesity, 15 of 20 patients interviewed were dissatisfied with their physical appearance, leading to a decrease in QoL for most of them (13 of 15 patients). DAYTIME SLEEPINESS 1.0 Survival probability ASSESSMENT OF DISABILITIES AND THEIR IMPACT ON Q OL The mean ESS score of the 21 patients with craniopharyngioma assessed was 8.1 (SD 5.1; range 2 to 20). This is higher than the ESS score of healthy controls (mean 5.7; SD 3; range 5.2 to 6.2), although the difference was statistically not significant. However, 6 of 21 patients with craniopharyngioma had an ESS score of more than 10, which is considered to be significant excessive daytime sleepiness. Five of these six patients had obesity. 0.8 0.6 0.4 0.2 0.0 0 5 10 15 20 25 Years since diagnosis Figure 1: Kaplan–Meier curves show probability of (a) progression-free survival (PFS) and (b) overall survival for 25 children with craniopharyngioma. 222 Developmental Medicine & Child Neurology 2004, 46: 220–229 SCHOOL PERFORMANCE AND OCCUPATION Of the 20 interviewed patients who were older than 7 years, 10 experienced significant problems in school. One patient was placed in a lower grade than his age peers, seven needed remedial teaching, and two left school because of the medical condition. Of the 15 patients interviewed who were old enough to be employed, nine felt that the choice of occupation was negatively influenced by their medical condition. Seven patients were not able to take up their favoured job, and two had to change their occupation because they were unable to obtain the required qualifications. BEHAVIOURAL AND EMOTIONAL PROBLEMS The numbers of patients with clinically significant scores of behavioural and psychological adjustment are shown in Figure 2. Five of 12 patients assessed had clinically elevated scores on the YSR total behaviour problems scale, six on the internalizing behaviour problems scale, and two on the externalizing behaviour problems scale. Social problems were rated as the dimension most often affected. In comparison with the YSR, the scores of the parent-rated CBCL were more often clinically significant. Again, social problems were rated as the dimension most often affected (7 of 12 patients). The parents and the patients themselves reported problems in relating to their peers (n=11), rejection by other children (n=7), and relations with the opposite sex (n=5). DAILY LIFE ACTIVITIES Nine of 21 patients assessed had FMH scores below the 25th centile, indicating decreased age-appropriate ability to perform daily life actions. Low FMH centiles were associated with large tumours infiltrating or displacing the hypothalamus, hydrocephalus, and young age at diagnosis, but also with a history of multiple operations because of tumour recurrence and a BMI of more than the 97th centile (Table II). HEALTH - RELATED Q OL In comparison with healthy controls, the patients with craniopharyngioma rated their HRQoL to be lower (Fig. 3). The domains with greatest differences between patient and healthy control values included social functioning (patient median 70; control mean 87.4) and emotional functioning (patient median 70; control mean 80.9). Notably, patients with craniopharyngioma rated their psychosocial health to be lower than their physical health (patient median 68.3; control mean 84.4). Concordance between patient and parent ratings was variable, with lower parent ratings in all domains except emotional functioning. The greatest differences between patient ratings and parent ratings were seen in social and school functioning. Considering the results of the PedsQL 3.0 Cancer Module, Table I: Postoperative conditions of 25 childhood patients with craniopharyngioma and impact on quality of life Characteristics Endocrine functioning Endocrine deficits Physical functioning Height <3rd centile Body Mass Index >97th centile Not satisfied with physical appearance (only >7 years of age) Impaired fitness Visual functioning Impaired visual acuity Constricted visual field Neurological functioning Strabismus Hemiparesis Facial nerve palsy Seizures Frequent headache Emotional functioning Mood swings Sleep Sleep disturbance Neurocognitive and school functioning Concentration difficulties Learning difficulties Memory difficulties Remedial teaching Impaired choice of occupation (only >16 years of age) Social functioning Difficulties in making friends Rejection by other children No partnership experience (only >18 years of age) No sexual experience (only >18 years of age) No family (only >20 years of age) No children (only >20 years of age) Independence Impaired independence Affected patients Limiting quality of life 24/25 6/20 3/23 14/23 15/20 19/21 1/3 11/13 13/15 15/19 9/24 14/24 4/6 7/12 3/24 2/24 3/24 4/24 12/24 2/2 2/2 2/2 1/4 3/12 3/21 1/3 11/21 7/11 7/21 8/21 12/21 10/20 9/15 5/7 5/8 6/12 3/10 5/9 11/21 7/21 5/14 7/14 9/11 11/11 9/11 7/7 2/5 5/7 1/9 3/11 11/21 1/11 Outcome of Craniopharyngioma in Children Andrea Poretti et al. 223 the most severely impaired dimensions according to patient reports were perceived physical appearance (median 45.8) and worry (median 70.8). The median values of the other dimensions were 80 for cognitive problems, 83.3 for procedural anxiety, 83.3 for treatment anxiety, 87.5 for pain and hurt, 87.5 for difficult communication, and 90 for nausea. Concordance between parent and survivor ratings of HRQoL varied; parent ratings were lower in cognitive problems, procedural anxiety, communication, and pain and hurt. Nr. of patients with clinically significant scores Discussion Craniopharyngiomas are histologically benign tumours, and the goal of their management should be long-term progression-free survival with minimal morbidity and minimally impaired QoL. There is considerable debate as to whether primary radical surgery or conservative surgery followed by radiation therapy offers the child the best hope of cure with the lowest risk of long-term sequelae (Sanford 1994). In the present study we have reported our institution’s experience with craniopharyngioma in children treated with a primary radical surgery approach in an effort to assess comprehensively the neurological, cognitive, and endocrine effects of surgery and their impact on QoL. Disease control was highly successful in our series. No patient died of tumour progression. Local failure was observed only in six of 25 patients. The 10-year progression-free survival rate as shown in this report and other published series ranged from 40 to 90% after total surgery and from 0 to 40% after subtotal tumour resection (Colangelo et al. 1990, Yasargil et al. 1990, Hoffman et al. 1992, De Vile et al. 1996c, Khafaga et al. 1998, Fahlbusch et al. 1999, Merchant et al. 2002, Van Effenterre and Boch 2002, Kalapurakal et al. 2003). A review of the literature up to 1993 reported a 12% average mortality rate (Brada and Thomas 1993). In our series, only 1 of 25 patients died as a result of surgery. Although largely effective in controlling tumour growth, radical surgery resulted in a high probability of endocrine, neurological, and hypothalamic complications, decreasing the QoL of most of our long-term survivors. Endocrine deficiency requiring lifelong hormone replacement occurred in 24 of 25 of the patients. This is similar to the rate of 70 to 100% reported in other series with radical surgery (Yasargil et al. 1990, Hoffman et al. 1992, Paja et al. 1995, De Vile et al. 1996b, Tiulpakov et al. 1998, Fahlbusch et al. 1999, Kalapurakal et al. 2003). Visual complications, including decreased visual acuity (9/24) and constriction of the visual field (14/24) also occurred at rates comparable to those of published series after radical surgery (Yasargil et al. 1990, Hoffman et al. 1992, Pierre-Kahn et al. 1994, Abrams and Repka 1997). Other neurological complications in our series included hemiparesis in two of 24 patients, and facial nerve palsy in three of 24 patients; this is more than in other series (Colangelo et al. 1990, De Vile et al. 1996c, Zuccaro et al. 1996, Abrams and Repka 1997). However, these complications were infrequent and the numbers are too small for firm conclusions to be drawn. Morbidity due to hypothalamic damage can result in obesity, defective short-term memory, limited concentration span, defective thirst sensation, and sleep disturbances (Hayward 1999). In the present study three patients had obesity preoperatively 8 7 6 Patients (n=12) Parents (n=12) 5 4 3 2 1 An xio us /d ep re ss ed So cia lp ro bl em Th s ou gh tp ro bl em At s te nt io n pr ob De le m lin s qu en tb eh av Ag io ur gr es siv e be ha vio ur co m pl ai nt s So m at ic W ith dr aw n be ha vio ur be ha vio ur Ex te rn al izi ng In te rn al izi ng To ta ls co re 0 Youth Self Report/Child Behavior Checklist Figure 2: Behavioural and psychological adjustment as rated by patients with craniopharyngioma (n=12; Youth Self Report) and their parents (n=12; Child Behavior Checklist). Numbers of patients with clinically significant scores are shown. 224 Developmental Medicine & Child Neurology 2004, 46: 220–229 and 11 of 23 patients developed obesity postoperatively, resulting in an obesity rate of 14 of 23 for the entire group. Morbid obesity after radical surgery has been reported in 30 to 50% of children secondarily to hypothalamic injury (Hoffman et al. 1992, De Vile et al. 1996a, Muller et al. 2001). Neurocognitive dysfunction, including difficulties with concentration, learning, and memory are well-known complications associated with radical surgery (Hoffman et al. 1992, De Vile et al. 1996c, Anderson et al. 1997, Villani et al. 1997, Kalapurakal et al. 2003). In the present study 10 of 20 of the patients experienced significant problems in school. This is within the range of 25 to 80% reported by other series (Galatzer et al. 1981, Hoffman et al. 1992, Anderson et al. 1997, Riva et al. 1998, Van Effenterre and Boch 2002). The series of Riva et al. (1998) is exceptional in this context due to the absence of cognitive deficits and only minor attention deficits. However, the authors noted that only 17% of their patients achieved a good academic performance. Emotional and behavioural disturbances occurred in 5 of 12 of the patients assessed by YSR. Difficulties in interpersonal relationships have been reported in 9 to 50% of patients who had radical surgery (Galatzer et al. 1981, Anderson et al. 1997, Van Effenterre and Boch 2002). Other reports demonstrated anxiety in 42% (Riva et al. 1998). Confirmation of the significance of these problems comes from the parents’ ratings, which were even lower in this dimension. In an effort to identify factors predicting an unfavourable functional outcome, we compared the FMH scores with clinical factors and found that poor functional outcome was associated with large tumours infiltrating or displacing the hypothalamus, a history of hydrocephalus, and young age at diagnosis. This confirms the findings of De Vile et al. (1996c) and Hayward (1999). What has not been studied well so far is the impact of these complications on the QoL as rated by the patients themselves. To our knowledge, only one report of paediatric craniopharyngioma survivors includes their subjective perception of QoL (Villani et al. 1997). Analyzing 27 patients with a self-designed functional evaluation scale, these authors did not find any patients with subjective poor outcome. This is in contrast to the present study in which we used well-established HRQoL measures. In comparison with healthy controls, QoL was impaired in 15 of 21 craniopharyngioma survivors. In all QoL dimensions assessed, the parent ratings were low. This confirms the findings of Galatzer et al. (1981) and Anderson et al. (1997), who assessed QoL by parent ratings only. In comparison with healthy controls, social functioning was rated by the patients as the QoL dimension most affected. There could be multiple reasons for this, including dissatisfaction with physical appearance (obesity, facial nerve palsy, short stature), neurocognitive dysfunctions (weak school performance), or emotional problems due to hypothalamic damage. The parents consistently judged the HRQoL as more impaired than did the children themselves in all domains except emotional functioning. Levi and Drotar (1999) reported that this difference is based on different perspectives: parent reports are based on observation of and communication with the child, whereas child reports are based on subjective personal experience and on symptoms of which parents have only indirect accounts (Levi and Drotar 1999). Table II: Comparison of Fertigkeitenskala Munster–Heidelberg Scale (FMH) with Pediatric Quality of Life Inventory (PedsQL) scores and clinical factors Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 FMH (centile) PedsQL Sex Age at diagnosis (y:m) Hypothalamus damage Hydrocephalus at diagnosis Tumour recurrence BMI at follow-up (centile) 10–25 10–25 10–25 10–25 10–25 10–25 10–25 10–25 10–25 25–50 25–50 25–50 25–50 50–75 50–75 50–75 95+ 95+ 95+ 95+ 95+ 46.7 64.1 71.7 71.7 72.8 73.9 80.4 81.3 84.8 63.0 65.9 70.7 88.0 59.8 68.5 90.2 68.5 77.2 90.2 94.6 96.7 Female Male Female Male Male Male Male Female Male Male Female Male Female Male Female Male Female Female Male Male Male 13:6 5:1 2:11a 5:0a 3:7a 10:11 4:11a 3:5a 13:2 15:1 15:11 7:0 4:11a 15:0 9:1 13:0 7:5 6:4 9:1 7:11 15:9 Yesa Yesa Yesa Yesa Yesa Yesa Yesa Yesa Yesa Yesa Yesa Yesa No Yesa No No No Yesa Yesa Yesa Yesa Yesa Yesa No No Yesa Yesa Yesa Yesa Yesa Yesa No No Yesa No No No No No Yesa No No Yesa No Yesa No Yesa No No No No No No Yesa No Yesa No No No No No No No 97+a 97+a 97+a 97+a 97+a 90–97 75–90 90–97 90–97 97+a 97+a 97+a 90–97 97+a 50–75 75–90 97+a 97+a 75–90 97+a 97+a Patients were graded according to FMH centile. Hypothalamus damage was determined as infiltration or displacement of hypothalamus from tumour. aPossible clinical risk factors. BMI, Body Mass Index. Outcome of Craniopharyngioma in Children Andrea Poretti et al. 225 HRQoL and FMH scores did not correlate well in the present study. We had patients with unfavourable functional outcome (low FMH score) who rated their QoL as good, and patients with favourable functional outcome who rated their QoL as low. Lannering et al. (1990) found similar results in an unselected series of long-term survivors of paediatric brain tumour. Clearly, HRQoL is not only a measurement of outcome but also includes a subjective judgement of the relative acceptability of any health state (Kennedy and Leyland 1999). Controversy about the optimum management of craniopharyngioma has been continual over about 20 years (Shapiro et al. 1979, Cabezudo et al. 1981). In our opinion, radical surgery can be only recommended when comorbidity is limited. Especially in very young children with large tumours infiltrating the hypothalamus, alternative treatment strategies to radical surgery with potentially smaller risks for late-treatment complications should be considered (Hayward 1999, Eisenstat 2001, Merchant et al. 2002). For cystic craniopharyngioma, intracystic chemotherapy with bleomycin (Hader et al. 2000, Mottolese et al. 2001) or intracavitary irradiation with stereotactically applied radioactive sources was suggested to induce a slow shrinkage of the cyst, facilitating the surgical removal of tumour remnants (Voges et al. 1997, Schefter et al. 2002). Newer radiation techniques including fractionated stereotactic radiotherapy and intensity-modulated radiation therapy have been developed and used in craniopharyngiomas. Fractionated stereotactic radiotherapy after subtotal surgery offers an optimal sparing of normal tissue surrounding the tumour (Schulz-Ertner et al. 2002, Selch et al. 2002). In comparison with radiosurgery, fractionated stereotactic radiotherapy fully exploits the advantages of fractionation, with a consequent lower incidence and severity of radiation-induced side effects. Intensity-modulated radiation therapy also has the ability to spare normal tissue surrounding the craniopharyngioma. This is achieved by varying the intensity of the beam across each field with the use of a moving collimator (Paulino and Skwarchuk 2002, Swift 2002). In summary, this study confirms that radical surgery results in a high probability of tumour control. However, such surgery often leads to significant damage to visual, hypothalamic, endocrine, and neurocognitive functions. The impact of this damage on the patients’ abilities and QoL is considerable. The most impaired dimension of the HRQoL is social functioning. The reports of children and parents are similar in the evaluation of the different dimensions. Parents generally judge the QoL of their children as more impaired than do the children PedsQL 4.0 Generic Core scales 100 50 x x x x 0 Total score Physical health Healthy controls (mean) Patients (n=21) Parents (n=21) Psychosocial health Emotional functioning Social functioning School functioning Health-related quality of life items Figure 3: Health-related quality of life (HRQoL) in 21 patients with craniopharyngioma as rated by themselves and their parents with PedsQL 4.0 Generic Core. In comparison with healthy controls, patients with craniopharyngioma rated their HRQoL lower in all dimensions, with social functioning as the dimension with greatest difference. Parent ratings were even lower, with most differences between adults and children shown in school and social functioning. Horizontal lines are median values; solid boxes show 25th to 75th centiles; whisker bars are 10th and 90th centiles; outliers are shown as crosses. For self-reports of controls, horizontal lines are means, and there are no boxes or whisker plots because data were not available. 226 Developmental Medicine & Child Neurology 2004, 46: 220–229 themselves. Predictors for poor outcome are young age, hypothalamus damage and hydrocephalus at diagnosis, and tumour recurrence. With these children an alternative approach with potentially smaller risks for late-treatment complications should be considered. Future studies of outcome in childhood craniopharyngiomas should include not only assessment of tumour control and of neurological, endocrine, and hypothalamic complications, but also the impact on HRQoL with the use of qualitative and quantitative measures. We suggest that the management of patients with craniopharyngioma should be limited to few specialized centres because it is likely that the results will be more favourable. DOI: 10.1017/S0012162204000374 Accepted for publication 31st October 2003. 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Childs Nerv Syst 12: 385–390. 228 Developmental Medicine & Child Neurology 2004, 46: 220–229 List of abbreviations CBCL ESS FMH HRQoL PedsQL QoL YSR Child Behavior Checklist Epworth Sleepiness Scale Fertigkeitenskala Münster–Heidelberg Scale of daily living Health-related quality of life Pediatric Quality of Life Inventory Quality of life Youth Self Report Appendix I: Semi-structured interview questions Time before diagnosis What do you remember first of all? Did you have difficulties that have particularly distressed you? Moment of diagnosis Can you remember the moment when the diagnosis was made? Did you understand what the diagnosis meant? How did you experience it? How much do you know about your disease? Did you take a particular interest in it? How did you experience the treatment? What was particularly unpleasant, what was not so bad? Is there anything concerning your disease which was difficult for you and which you consider today to be less difficult? What helped you during difficult times in the treatment? Could you help yourself or did others help you? How was help given? Present medication Do you take any medicine now? What type? Are there medicines which you have taken in the past and which you don’t take any more? Are you distressed by having to take these medicines every day? Have or have you had any side effects due to the therapy? Who checks the hormonal situation regularly? Eyes Can you see clearly? With both eyes? Do you wear glasses? Do you see clearly with your glasses or do you still have difficulties? Are you hindered in your every-day life by reduced vision? Can you ride a bike or a motorbike or drive a car? If not, why? Can you recognize people? Can you see clearly in all directions or do you have any black fields? Do you have your eyes tested regularly? Height/weight/physical appearance What is your height/weight now? Are you satisfied with your appearance? What disturbs you most about your appearance? If you could, would you change anything about your appearance? If so, what? Are you dissatisfied with your weight in your daily life? When did you start puberty? How did you experience it, particularly comparing yourself with your friends? Did it cause you any problems? Thirst/Appetite Are you normally very thirsty? Do you have to drink a lot? Do you have to get up at night to urinate? Are hungry very often? If yes, can you control your appetite? continued... Complaints/sleep-wake cycle Have you any pain connected with your illness? Do you often have headache? If yes, when in particular? Where is the pain located? Does it distress you? Do you need any pain relief medication? Do you often feel ill? Do you often vomit, especially in the morning? Are you sensitive to the cold/the heat? Do you sleep a lot? Are you often tired? Does this disturb you during the day? Can you sleep all through the night? Do you have difficulties falling asleep? What work do you do now? Are you happy with it? If not, why? Did you have any other job before this one? If so, why did you change your job? General body fitness/neurocognitive functions Do you feel your physical ability has been affected by your illness? If so, how much? Do you practise any sport? What type? Is there any sport you like that you’re unable to participate in? Can you concentrate well at school, at work? Do you believe your ability to concentrate has been impaired by your illness? Has your speed in solving tasks or in understanding new things been affected by your illness? Do you often have gaps in your memory? Do you often get angry with people? Social situation Do you live with your parents or alone? With boy-/girlfriends? Do you live in a residential 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-/boyfriend, or have you ever had one? Are you married? How do you experience your relationship? Do you have any children? Would you like to have children? If you are not in a relationship do you wish you were in one? Can you imagine your future without a partner? Can I ask you an intimate question? If yes: – If you are in a relationship: is sexuality important for you in the relationship? Does it correspond to your desire? If not, what would you prefer? – If you are not in a relationship: is sexuality important for you? Do you have a good boy-/girlfriend? Do you keep in regular contact with him/her? How often? How do you relate to your teachers/schoolmates/colleagues? How do you relate to your doctor? Who is s/he? Does s/he support you? Does s/he give enough time to you? Does s/he explain to you what s/he 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 government financial support? If yes, would you prefer any other source of income? Emotions Do you have any positive feelings towards your illness? If so, what are they? Do you have any negative feeling towards your illness? If so, what are they? Are you afraid of getting ill again? School Which school do you or did you attend? Do you have any difficulties at school? 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 relation to your schoolmates after your illness? If yes, what? Have people in your school 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 secondary school and/or university? 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? Future How do you see your future? What would you like the most? Additional comments Is there anything else you would like to add? Outcome of Craniopharyngioma in Children Andrea Poretti et al. 229