Longitudinal development of cancer-related fatigue and physical activity in childhood cancer patients.

PURPOSE: Cancer-related fatigue is one of the most distressing side effects of childhood cancer treatment. Physical activity can decrease fatigue and has positive effects on other health outcomes. Most research on physical activity pertains to adults, and the few studies that focus on children have limited follow-up time. This study evaluates cancer-related fatigue in children and its association with physical activity over a one-year time period. METHODS: Sixty-eight children with cancer (7-18 years) were recruited during or within the first year after treatment. Physical activity (Actical activity monitor) and cancer-related fatigue (Pediatric Quality-of-Life Questionnaire Multidimensional Fatigue Scale (PedsQL-MFS), self- and parent- reports) were assessed at baseline, 4 months, and 12 months. PedsQL-MFS scores were compared with Dutch norms. Longitudinal association of cancer-related fatigue with physical activity was evaluated (No. NTR 1531). RESULTS: Generally, PedsQL-MFS scores were worse than norms at baseline and 4 months, and recovered by 12 months except for the parent-proxy scores in adolescents. Younger children (≤12 years) self-reported comparable or better scores than norms. Physical activity generally improved over time, but patients mostly remained sedentary. During follow-up, increased physical activity was associated with less cancer-related fatigue. CONCLUSION: Cancer-related fatigue in children improves over time, and increased physical activity is associated with less cancer-related fatigue. Given the sedentary lifestyle of this population, the positive effect of physical activity on cancer-related fatigue, and the many other health benefits of an active lifestyle, it is important to stimulate physical activity in childhood cancer patients and survivors.

Effects of a combined physical and psychosocial training for children with cancer: a randomized controlled trial.

BACKGROUND: Physical fitness and psychosocial function is often reduced in children during or shortly after cancer treatment. This study evaluates the effect of a combined physical exercise and psychosocial intervention on cardiorespiratory fitness, muscle strength, body composition, psychosocial function and health-related quality of life (HrQoL). In addition, intervention mediators, applicability and adherence were examined. METHODS: This multicenter randomized controlled trial included 68 children with cancer [mean age 13.2 (SD: 3.1) years; 54% male] during treatment or within 12-months post-treatment. The 12-week intervention consisted of 24 individual physical exercise sessions supervised by a physiotherapist, and 6 psychosocial training sessions for children and 2 for parents. Physical fitness and psychosocial function were assessed at baseline, directly post-intervention and at 12 months' post-baseline. Generalized estimating equations were used to simultaneously assess intervention effects at short and long-term. Additionally, we evaluated within-group differences over time. Potential physical and psychosocial mediators in the intervention effect on HrQoL were examined using the product-of-coefficient test. Applicability and adherence were assessed by trainer-report. RESULTS: This study was able to compare 26 children who received the study intervention, with 33 children who received usual care. No significant differences in the effects of the intervention were found on physical fitness and psychosocial function at short-term. At 12-months follow-up, significantly larger improvements in lower body muscle strength (ß = 56.5 Newton; 95% CI: 8.5; 104.5) were found in the intervention group when compared to the control group. Within-group changes showed significant improvements over time in HrQoL and bone density in both groups. Intervention effects on HrQoL were not significantly mediated by physical fitness and psychological function. Intervention applicability was satisfactory with an average session attendance of 67% and 22% dropout (mainly due to disease recurrence). CONCLUSIONS: This 12-week physical exercise and psychosocial training intervention for children with cancer was applicable and showed satisfactory adherence. We found no significant between-group differences in effect, except for a significant improvement in lower body muscle strength at long-term in the intervention group compared to the control group. Yet, both the intervention and the control group showed improvements in bone mineral density and HrQoL over time. TRIAL REGISTRATION: The trial was registered at the Dutch Trial Registry ( NTR1531 ). Registered 12 November 2008.

Cardiorespiratory fitness and physical activity in children with cancer.

PURPOSE: This study assessed cardiorespiratory fitness (CRF), physical activity (PA), and sedentary behavior (SB), as well as factors associated with these outcomes in children during or shortly after cancer treatment. METHODS: Cross-sectionally, CRF data, obtained by the cardiopulmonary exercise test, and PA and SB data, obtained by an accelerometer, were assessed in children with cancer (8-18 years old). Linear regression models were used to determine associations between CRF, PA, or SB and patient characteristics. RESULTS: Among 60 children with cancer, mean age 12.6 years, 35 boys, 28 % were during cancer treatment. CRF, reported as the z score of VO2peak, showed that 32 children had a VO2peak z score which was -2 below the predicted value. CRF was significantly associated with PA and SB: each additional activity count per minute resulted in 0.05 ml/kg/min VO2peak increase and each additional minute sedentary reduced VO2peak by 0.06 ml/kg/min. Multiple linear regression models of PA and SB showed that decreased activity was significantly associated with higher age, being fatigued, being during childhood cancer treatment (p < 0.001), or having a higher percentage of fat mass. The multiple linear regression model showed that lower CRF was significantly associated with increased fatigue, being during cancer treatment, having a higher percentage of fat mass, and lower belief of own athletic competence (p < 0.001). CONCLUSION: This study revealed that children during or shortly after cancer treatment have low CRF scores. The most inactive children had a higher fat mass, were fatigued, older, and during childhood cancer treatment. Unexpectedly, treatment-related factors showed no significant association with activity behavior.

Effects of a combined physical and psychosocial intervention program for childhood cancer patients on quality of life and psychosocial functioning: results of the QLIM randomized clinical trial.

OBJECTIVE: Although survival rates in childhood cancer have improved, prevention and reduction of late effects remain important. This study evaluates the effects of a combined physical exercise and psychosocial intervention on health-related quality of life (HrQoL) and psychosocial functioning in childhood cancer patients. METHODS: In this multicenter randomized controlled trial, cancer patients (aged 8-18 years) and their parents filled in questionnaires on HrQoL, depressive symptoms, behavioral problems, and self-esteem. Measurements were conducted at baseline, shortly after the 12-week intervention period and 12 months after baseline. Generalized estimating equations analyses were performed to assess short-term and long-term psychosocial effects. RESULTS: Of the 174 eligible patients, 68 (39.1%) participated. The intervention group consisted of 30 participants at baseline [mean age 13.0 (SD 3.0) years; 53% male], 26 at short-term and 22 at long-term follow-up. The 'care as usual' control group consisted of 38 participants at baseline [mean age 12.6 (SD 3.1) years; 53% male], 33 at short-term and 31 at long-term follow-up. Overall, the intervention did not improve psychosocial functioning and HrQoL. According to parent-proxy reports, the intervention leads to a greater improvement on pain-related HrQoL on both the short (ß = 13.4; 95% CI: 3.0; 23.8) and long term (ß = 13.0; 95% CI: 1.6; 24.4) and to greater improvement on procedural anxiety immediately after the intervention (ß = 12.6; 95% CI: 1.9; 23.3). CONCLUSION: A combined physical and psychosocial training for children with cancer did not have effects on HrQoL or psychosocial functioning, with exception of modest positive effects on parent-reported pain and procedural anxiety Copyright © 2015 John Wiley & Sons, Ltd.

Applicability and evaluation of a psychosocial intervention program for childhood cancer patients.

PURPOSE: The purpose of this study is to explore the applicability of a psychosocial intervention in childhood cancer patients. METHODS: This individualized structured psychosocial program to enhance social-emotional functioning and coping with disease-related effects includes six sessions for children and two sessions for parents. This program was part of a combined intervention with physical exercise. Questionnaires are used to evaluate completion of the psychosocial intervention, coping and satisfaction with the psychosocial intervention by patients and psychologists, and ranking of the individual topics by patients, parents, and psychologists. RESULTS: Of the 30 patients (mean age 13.0 (SD 3.0); 53.3 % male; 30 % still on treatment) who participated in the psychosocial intervention, two dropped out due to medical complications and one due to lack of time; 90 % completed the psychosocial intervention. Overall, patients liked participation in the intervention (4.2 on a 5-point scale; SD 0.8) and were positive about the psychologists (8.1 on a 10-point scale; SD 1.3). Psychologists rated the intervention on several points (e.g., clarity of the manual and content of the intervention), and mean scores ranged from 7.1 (SD 1.1) to 8.6 (SD 0.9) on 10-point scales. Minor adaptations were suggested by patients and psychologists, including customizing according to age and a more patient-tailored approach. CONCLUSION: This psychosocial intervention for childhood cancer patients appears to be applicable. Future studies need to establish whether this intervention combined with a physical exercise intervention actually improves psychosocial functioning of childhood cancer patients. When proven effective, this combined intervention can be offered to childhood cancer patients and may enhance their physical health and quality of life.

Surviving a brain tumor in childhood: impact on family functioning in adolescence.

OBJECTIVE: To investigate family functioning in families with an adolescent survivor of a pediatric brain tumor. We explored whether adolescent, parent, disease and treatment factors, and demographic characteristics predicted family functioning. METHODS: In this cross-sectional study, 45 adolescent survivors of pediatric brain tumors and their parents completed self-report questionnaires on family functioning, and emotional and behavioral problems. Parents completed questionnaires on their own mental health and the burden of treatment. RESULTS: Compared to general population norms, adolescents reported higher levels of cohesion, expressiveness, organization, control, family values and social orientation, and absence of conflict. Parents reported higher levels of social orientation and lower levels of conflict and family values. The only predictor of family functioning was current age of the adolescent; older adolescents reported less family conflict. No relation was found between family functioning and emotional and behavioral problems, disease- or treatment factors, and demographic variables. CONCLUSIONS: In this exploratory study, adolescent survivors of a pediatric brain tumor characterized their families by higher levels of cohesion, expressiveness, organization, control, family values and social orientation, and absence of conflict, which differs from the more normative view held by their parents. A higher adolescent age predicted less family conflict, which may indicate deviant autonomy development in these survivors. Because of limitations of this study, conclusions should be considered provisional; they provide clues for further research in this area.

Factors influencing childhood cancer patients to participate in a combined physical and psychosocial intervention program: Quality of Life in Motion.

BACKGROUND: For a multi-center randomized trial investigating the effects of a 12-week physical and psychosocial intervention program for children with cancer, we invited 174 patients (8-18 years old) on treatment or within 1 year after treatment; about 40% participated. Reasons for non-participation were investigated. METHODS: Eligible patients received written and verbal information about the study. Those declining to participate were asked to complete questionnaires concerning: reasons for non-participation, daily physical activity, health-related quality of life (HrQoL), and behavioral problems. Participants completed the same questionnaires at baseline (excluding 'reasons for non-participation'). RESULTS: Of 174 eligible patients, 106 did not participate; of these, 61 (57.5%) completed the one-time survey. The main reasons for non-participation as reported by the parents were 'too time consuming' and 'participation is too demanding for my child', while children most frequently reported 'too time consuming' and 'already frequently engaged in sports'. No differences between participants and non-participants were found for age, HrQoL, parental-reported behavior problems, sport participation, school type, BMI, and perceived health. A greater distance from home to hospital resulted in reduced participation (ß: -0.02; p = 0.01). Non-participants rated their fitness level higher (p = 0.03). Participating children (11-18 years old) reported more behavioral problems (p = 0.02), in particular internalizing problems (p = 0.06). CONCLUSIONS: Participation of childhood cancer patients in an intensive physical and psychosocial intervention program seems related to the burden of the intervention and the travel distance from home to hospital. In general, non-participants rated their fitness level higher compared with participants. Patients with more (internalizing) behavioral problems seem more likely to participate in the study.

Determinants of quality of life during induction therapy in pediatric acute lymphoblastic leukemia.

PURPOSE: Improvement in survival of pediatric acute lymphoblastic leukemia (ALL) has increased the attention to quality of life (QoL) . QoL is impaired during maintenance treatment, but little is known about QoL during induction therapy. Identification of patients with poor QoL during induction will provide opportunities for early interventions, and may subsequently improve future QoL. This national multi-center study aimed to assess QoL and its determinants during ALL induction treatment. METHODS: Proxy reports of the Child Health Questionnaire (CHQ) and the PedsQL cancer version were collected. Child, treatment, and parental characteristics were analyzed as potential determinants in a multiple regression model. RESULTS: One hundred thirty parents of children participated (response rate 82 %), median child age was 5.7 years and 48 % were female. QoL, as measured with the CHQ, was significantly lower than the norm, the effect sizes were large, and the differences were clinically relevant. Physical QoL was more often affected than psychosocial QoL. Regression models could be constructed for 4/ 10 CHQ scales and 6/ 8 PedsQL cancer scales, accounting for 7 to 36 % of the variance in scores. Impaired QoL was most often associated with older children, girls, and time since diagnosis. Also, father respondents seem to have a lower QoL perception compared to mother respondents although this needs to be confirmed in future research. CONCLUSIONS: Specific counseling for subsets of patients with a higher risk of low QoL during the early phases of therapy is warranted.

Health status utilities in pediatrics: a systematic review of acute lymphoblastic leukemia.

BACKGROUND: Measuring utilities and health-related quality of life (HRQL) in children is challenging due to their cognitive abilities and changing developmental stages. PURPOSE: . To identify methodological issues on utility measurements in children, we performed a systematic review on utilities measured with a single instrument, the Health Utilities Index (HUI), in pediatric acute lymphoblastic leukemia (ALL). The secondary goal was to facilitate future cost-utility analyses without the need for time-consuming assessments. Data Sources. PubMed, Embase, Cochrane Library, CINAHL, and PsycINFO were searched from inception to June 2012. Studies had to report on utility scores in pediatric ALL, either on or after treatment, to be included. RESULTS: . Fifteen studies were included. Most studies had methodological shortcomings, which mainly concerned STUDY DESIGN: and definition and representativeness of the study group. Utility scores were dependent on treatment variables, and there generally was an improvement in HRQL as treatment or survivorship advanced. In general, proxy-respondents were less reliable for subjective phenomena than for observable conditions. HUI2 and HUI3 scores were not interchangeable. Limitations. Studies may have been missed because no validated search method for utility studies exists, due to language bias or the exclusion of non-peer-reviewed papers. CONCLUSIONS: . Most studies in this review were methodologically suboptimal. Future developments should focus on including developmentally appropriate items for the whole pediatric age group. Adding disease-specific domains may enhance the sensitivity and responsiveness of instruments. Efforts should be undertaken to elicit valuation of health states from older children and teenagers as much as possible. For now, it remains difficult to make valid and informed decisions on the financing of interventions until health state valuation in children has become more methodologically robust.

Development and validation of the distress thermometer for parents of a chronically ill child.

OBJECTIVE: To develop and validate a Distress Thermometer for Parents (DT-P) for chronically ill children and to determine a cutoff score for clinical distress. STUDY DESIGN: Parents of a chronically ill child (0-18 years) were recruited via announcements or were actively approached at the outpatient clinics of the Emma Children's Hospital/Academic Medical Center and Vrije Universiteit Medical Center. We modeled the development of the DT-P on the Distress Thermometer used in oncology medical care. The DT-P consists of a thermometer score from 0 (no distress) to 10 (extreme distress) and a problem list (practical, social, emotional, physical, cognitive, and parenting domains). The DT-P was validated with the Hospital Anxiety and Depression Scale (HADS) and the Parenting Stress Index. RESULTS: The mean thermometer score of the 706 participating parents was 3.7 (SD 3.0). The thermometer score and the scores in the practical, emotional, physical, and cognitive problem domains were strongly related to anxiety, depression, and the total score of the HADS (0.55 ≤ r ≤ 0.72). The thermometer score and all problem domain scores were moderately-to-strongly related to the Parenting Stress Index (0.38 ≤ r ≤ 0.63). A cutoff-score of 4 correctly identified 86% of "clinical HADS cases" (sensitivity) and 67% of "nonclinical HADS cases" (specificity). CONCLUSIONS: We developed the DT-P and examined its diagnostic utility in a large sample. The DT-P appeared to be a valid and useful short screening-tool for identifying parental distress.

Health-related quality of life and utility scores in short-term survivors of pediatric acute lymphoblastic leukemia.

PURPOSE: Increase of survival in pediatric acute lymphoblastic leukemia (ALL) has made outcomes such as health-related quality of life (HRQL) and economic burden more important. To make informed decisions on the use of healthcare resources, costs as well as utilities need to be taken into account. Among the preference-based HRQL instruments, the Health Utilities Index (HUI) is the most employed in pediatric cancer. Information on utility scores during ALL treatment and in long-term survivors is available, but utility scores in short-term survivors are lacking. This study assesses utility scores, health state, and HRQL in short-term (6 months to 4 years) ALL survivors. METHODS: Cross-sectional single-center cohort study of short-term ALL survivors using HUI3 proxy assessments. RESULTS: Thirty-three survivors (median 1.5 years off treatment) reported 14 unique health states. The majority of survivors (61 %) enjoyed a perfect health, but 21 % had three affected attributes. Overall, HRQL was nonsignificantly lower compared to the norm, although the difference was large and may be clinically relevant. Cognition was significantly impaired (p = 0.03). CONCLUSION: Although 61 % of short-term survivors of ALL report no impairment, the health status of the other patients lead to a clinically important impaired HRQL compared to norms. Prospective studies assessing utility scores associated with pediatric ALL should be performed, enabling valid and reliable cost-utility analyses for policy makers to make informed decisions.

Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. This cross-sectional study examined sleep and fatigue in relation to depression and quality of life (QoL) after treatment for childhood ALL. PROCEDURE: Sleep, fatigue, depression, and QoL were evaluated by parent proxy and/or child self-reports of the Children's Sleep Habits Questionnaire, the PedsQL™ multidimensional fatigue scale, the Children's Depression Inventory and the Child Health Questionnaire. All total scores were compared to Dutch norm references. RESULTS: Sixty-two children were included, being 36 (interquartile range 22-62) months after finishing treatment. Parents rated the ALL survivors as having more disturbed sleep, more fatigue and poorer physical QoL compared to the Dutch norm. ALL survivors themselves reported less sleep problems, less depressive symptoms, and better psychosocial QoL than the Dutch norm. More sleep disturbances and fatigue correlated with more symptoms of depression and a worse QoL. CONCLUSIONS: Differences in parental and self-reports, including worse parental ratings, might be explained by worried parents and/or the adaptive style of the children. Impaired sleep and fatigue correlated with more depressive symptoms and a worse QoL.

Alpe d'HuZes cancer rehabilitation (A-CaRe) research: four randomized controlled exercise trials and economic evaluations in cancer patients and survivors.

BACKGROUND: Previous studies showed that exercise in cancer patients is feasible and may reduce fatigue and improve physical fitness and quality of life. However, many previous studies had methodological weaknesses related to trial design, sample size, comparison group, outcome measures, short follow-up durations and programme content. PURPOSE: This paper aims to present the rationale and design of the clinical research subprogramme of the Alpe d'HuZes Cancer Rehabilitation (A-CaRe) programme. METHOD: A-CaRe Clinical Research includes four randomized controlled trials in patients: (a) after chemotherapy, (b) during chemotherapy, (c) after stem cell transplantation and (d) during childhood cancer. These trials compare high-intensity resistance and endurance exercise interventions with usual care or a waiting list control group. In two studies, a second intervention arm consisting of low-to-moderate intensity exercise is included. All four A-CaRe trials use similar methods. RESULTS: Outcome measures are carefully chosen based on the International Classification of Functioning Disability and Health model. Measurements will be performed prior to randomization (T0), after completion of the intervention (T1) and at follow-up (T2). The primary outcome measures are cardiorespiratory fitness, muscle strength and fatigue. Secondary outcome measures include health-related quality of life and psychosocial functioning. Furthermore, cost-effectiveness and cost-utility analyses are performed from a societal perspective. CONCLUSION: We hypothesize that exercise is more effective at improving physical fitness and thereby reducing fatigue and more cost-effective compared with usual care or a waiting list control group. If so, the programmes will be implemented in the Dutch clinical practice.

Effects of growth hormone therapy on bone mass, metabolic balance, and well-being in young adult survivors of childhood acute lymphoblastic leukemia.

Growth hormone deficiency (GHD), mostly after cranial radiotherapy (CRT), may lead to several negative effects. Young adult survivors of acute lymphoblastic leukemia (ALL) could benefit from GH therapy in different ways. Twenty ALL survivors (17.1 ± 4.3 y after diagnosis) with low bone mineral densities and/or low insulin-like growth factor-1 were included. Two of the 3 patients who only received chemotherapy had GHD. Of the 20 patients, 17 started with GH therapy and 14 completed the 2-year study period. At several time points, bone mineral density (BMD) was measured. Psychological functioning was assessed. At the start of the study, standard deviation scores of height, insulin-like growth factor-1, lumbar spine, and femoral neck BMD were all below -1. After 2 years of GH therapy, total body BMD and lean mass were significantly higher (P < 0.01 and P < 0.001, respectively), whereas the percentage fat was significantly lower (P < 0.02). Several psychological measures improved significantly after 2 years. In conclusion, GH therapy during 2 years in young adult survivors of childhood ALL did have a number of benefits, such as improvement of total body bone density and body composition. Results also suggest improvement of psychological well being. Furthermore, it also became clear that patients after chemotherapy alone should be tested for GHD.

Impaired sleep affects quality of life in children during maintenance treatment for acute lymphoblastic leukemia: an exploratory study.

BACKGROUND: With the increase of pediatric cancer survival rates, late effects and quality of life (QoL) have received more attention. Disturbed sleep in pediatric cancer is a common clinical observation, but research on this subject is sparse. In general, sleep problems can lead to significant morbidity and are associated with impaired QoL. Information on sleep is essential to develop interventions to improve QoL. METHODS: Children (2-18 years) with acute lymphoblastic leukemia (ALL) were eligible for this multi-center study. The Children's Sleep Habits Questionnaire (CSHQ), Child Health Questionnaire (CHQ) and Pediatric Quality of Life Inventory 3.0™ Acute Cancer Version (PedsQL) were used to assess sleep and QoL halfway through maintenance therapy. Sleep and QoL were measured during and after dexamethasone treatment (on-dex and off-dex). RESULTS: Seventeen children participated (age 6.7 ± 3.3 years, 44% boys). Children with ALL had more sleep problems and a lower QoL compared to the norm. There were no differences on-dex and off-dex. Pain (r = -0.6; p = 0.029) and worry (r = -0.5; p = 0.034) showed a moderate negative association with sleep. Reduced overall QoL was moderately associated with impaired overall sleep (r = -0.6; p = 0.014) and more problems with sleep anxiety (r = -0.8; p = 0.003), sleep onset delay (r = -0.5; p = 0.037), daytime sleepiness (r = -0.5; p = 0.044) and night wakenings (r = -0.6; p = 0.017). CONCLUSION: QoL is impaired in children during cancer treatment. The results of this study suggest that impaired sleep may be a contributing determinant. Consequently, enhanced counseling and treatment of sleep problems might improve QoL. It is important to conduct more extensive studies to confirm these findings and provide more detailed information on the relationship between sleep and QoL, and on factors affecting sleep in pediatric ALL and in children with cancer in general.

Design of the Quality of Life in Motion (QLIM) study: a randomized controlled trial to evaluate the effectiveness and cost-effectiveness of a combined physical exercise and psychosocial training program to improve physical fitness in children with cancer.

BACKGROUND: Childhood cancer and its treatment have considerable impact on a child's physical and mental wellbeing. Especially long-term administration of chemotherapy and/or radiotherapy impairs physical fitness both during and after therapy, when children often present with muscle weakness and/or low cardiorespiratory fitness. Physical exercise can improve these two elements of physical fitness, but the positive effects of physical exercise might be further increased when a child's wellbeing is simultaneously enhanced by psychosocial training. Feeling better may increase the willingness and motivation to engage in sports activities. Therefore, this multi-centre study evaluates the short and long-term changes in physical fitness of a child with a childhood malignancy, using a combined physical exercise and psychosocial intervention program, implemented during or shortly after treatment. Also examined is whether positive effects on physical fitness reduce inactivity-related adverse health problems, improve quality of life, and are cost-effective. METHODS: This multi-centre randomized controlled trial compares a combined physical and psychosocial intervention program for children with cancer, with care as usual (controls). Children with cancer (aged 8-18 years) treated with chemotherapy and/or radiotherapy, and who are no longer than 1 year post-treatment, are eligible for participation. A total of 100 children are being recruited from the paediatric oncology/haematology departments of three Dutch university medical centres. Patients are stratified according to pubertal stage (girls: age ≤10 or >10 years; boys: ≤11 or >11 years), type of malignancy (haematological or solid tumour), and moment of inclusion into the study (during or after treatment), and are randomly assigned to the intervention or control group. DISCUSSION: Childhood cancer patients undergoing long-term cancer therapy may benefit from a combined physical exercise and psychosocial intervention program since it may maintain or enhance their physical fitness and increase their quality of life. However, the feasibility, patient need, and effectiveness of such a program should be established before the program can be implemented as part of standard care. TRIAL REGISTRATION NUMBER: NTR1531 (The Netherlands National Trial Register).

Restrictions in daily life after retinoblastoma from the perspective of the survivors.

BACKGROUND: Little is known about the impact of retinoblastoma (RB) on the health status of survivors in terms of disabilities and worries, both of which may restrict participation in activities of daily life. METHODS: In this population-based cross-sectional study, content analysis was used to extract data on perceived restrictions and worries, from semi-structured interviews held with 156 RB survivors aged 8-35 years. The International Classification of Functioning Disabilities and Health (ICF) was used as a framework. RESULTS: Of all survivors, 55% perceive RB-related restrictions in daily life activities (school, professional career, mobility, self-care, intimate relationships). Young/adolescent survivors (6%) and adult survivors (15%) frequently report anxiety about developing a second primary tumor (SPT). Compared with the general population, RB survivors did not differ in rates of employment or marital status. However, special educational services were more frequently offered, and the level of completed education was lower. CONCLUSION: RB has influenced the lives of most survivors and, even though their prognosis was good, illness-related restrictions are common. Especially fear of developing SPT and of further loss of vision are important life-long problems, and many survivors had special education needs. The ICF might serve as a bridge between families and professionals, because this classification may facilitate early detection of problems.

Effect of dexamethasone on quality of life in children with acute lymphoblastic leukaemia: a prospective observational study.

BACKGROUND: Glucocorticoids are important in the treatment of childhood acute lymphoblastic leukaemia (ALL). However, cyclic administration of high dose glucocorticoids may cause rapid and substantial changes in quality of life (QoL). The maintenance phase of the Dutch ALL-9 protocol consisted of alternating two weeks on and five weeks off dexamethasone (6 mg/m(2)/day). The present study was performed to assess the effect of dexamethasone on QoL during treatment for ALL according to this protocol. METHODS: In a multicentre prospective cohort study, QoL was assessed halfway (T1) and at the end of the two-year treatment (T2). A generic (Child Health Questionnaire) and disease specific (PedsQL cancer version) QoL questionnaire were used to assess QoL in two periods: on and off dexamethasone, respectively. RESULTS: 41 children (56% males) were evaluated, mean age at diagnosis was 5.6 years. The CHQ physical and psychosocial summary scores were significantly lower than population norms. At T1 and T2, overall QoL showed no significant change. However, regarding specific domains (pain, cognitive functioning, emotion/behaviour and physical functioning) QoL decreased over time. QoL was significantly more impaired during periods on dexamethasone. CONCLUSION: Dexamethasone was associated with decreased QoL. At the end of treatment, reported QoL during dexamethasone deteriorated even more on certain scales (pain, cognitive functioning, emotion/behaviour and physical functioning). Knowledge of the specific aspects of QoL is essential to improve counselling and coping in paediatric oncology. Adverse effects of specific drugs on QoL should be taken into account when designing treatment protocols.

The usefulness of growth hormone treatment for psychological status in young adult survivors of childhood leukaemia: an open-label study.

BACKGROUND: To reduce the risk of brain damage children with acute lymphoblastic leukaemia (ALL) are nowadays mainly treated with intrathecal chemotherapy (ITC) instead of central nervous system (CNS) radiation therapy (CRT) to prevent CNS relapse. However, chemotherapy may also lead to cognitive deficits. As growth hormone deficiency (GHD) or impaired growth hormone secretion are frequently found in ALL patients treated with cranial radiation therapy and/or chemotherapy, we hypothesized that GH therapy may reduce cognitive deficits in these patients. METHODS: Twenty young adult survivors of childhood ALL with reduced bone mineral density (<-1 SD) and/or low IGF-I SD-scores (<-1 SD) were included in the study. A final group of 13 patients (9 males and 4 females), mean age 23.7 +/- 2.9 years (range 20 - 29.7) completed a 2-year treatment with GH.IQ and neuropsychological performance were assessed at pre-treatment (T1) and after one (T2) and two (T3) years. ANOVA was performed with assessment at T1, T2 and T3 as repeated measurements factor. Relations between test score changes and changes of IGF-I levels were determined by calculating the Pearson correlation coefficient. RESULTS: Scores on the cognitive tests were in the normal range. Verbal short- and long-term memory performance decreased between T1 and T2, and increased between T2 and T3. Performance at T3 was not significantly different from that at T1. Performance for sustained attention improved from T1 to T2 and from T1 to T3. Visual-spatial memory was improved after one year of GH treatment. A significant positive correlation was found for Delta IGF-I (T2-T1) with difference scores of visual-spatial memory (T2-T1 and T3-T1), indicating that IGF-I increase after one year of GH treatment is associated with increase in cognitive-perceptual performance at month 12 and 24. CONCLUSION: Since the level of intellectual functioning of our patient cohort was in the normal range the present finding that GH treatment has negative effects on verbal memory and positive on attention and visual-spatial memory warrants similar studies in other groups of ALL survivors. Also, a lower dose of GH should be determined inducing as much IGF as needed to improve verbal as well as visual cognitive functions. The present findings indicate that more knowledge is needed before GH treatment may be recommended to enhance cognitive functions in ALL survivors.

Health-related quality of life of child and adolescent retinoblastoma survivors in the Netherlands.

BACKGROUND: To assess health-related quality of life (HRQoL) in children (8-11 years) and adolescents (12-18 years) who survived retinoblastoma (RB), by means of the KIDSCREEN self-report questionnaire and the proxy-report version. METHODS: This population-based cross-sectional study (participation rate 70%) involved 65 RB survivors (8-18 years) and their parents. Child/adolescents' and parents' perception of their youth's HRQoL was assessed using the KIDSCREEN, and the results were compared with Dutch reference data. Relations with gender, age, marital status of the parents, and visual acuity were analyzed. RESULTS: RB survivors reported better HRQoL than did the Dutch reference group on the dimensions "moods and emotions" and "autonomy". Increased ratings of HRQoL in RB survivors were mainly seen in perceptions of the younger children and adolescent girls. RB survivors with normal visual acuity scored higher on "physical well-being" than visually impaired survivors. Age was negatively associated with the dimensions "psychological well-being", "self-perception" (according to the child and parent reports) and "parent relations and home life" (according to the child). "Self-perception" was also negatively associated with visual acuity (according to the child). Only parents of young boys surviving RB reported lower on "autonomy" than the reference group, and parents of low visual acuity and blind RB survivors reported higher on "autonomy" than parents of visually unimpaired survivors. Survivors' perceptions and parents' perceptions correlated poorly on all HRQoL dimensions. CONCLUSION: RB survivors reported a very good HRQoL compared with the Dutch reference group. The perceptions related to HRQoL differ substantially between parents and their children, i.e. parents judge the HRQoL of their child to be relatively poorer. Although the results are reassuring, additional factors of HRQoL that may have more specific relevance, such as psychological factors or coping skills, should be explored.