Sleep interventions in pediatric oncology: A systematic review of the evidence.

Sleep concerns are common during pediatric cancer treatment and can last into survivorship. The current systematic review sought to identify intervention studies that addressed sleep as a primary or secondary outcome during pediatric cancer treatment up to 5 years after completing treatment. Quality assessment was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The review identified 16 studies with a total of 943 participants that tested a wide range of interventions including psycho-educational, stress management techniques, medications, and physical activity. Most studies included tested interventions in small samples. None of the included studies had a high risk of bias for all domains, but all included studies had a high risk of bias for at least two risk domains. Several feasible pilot studies were identified that warrant further research to test efficacy. Implications for future research and clinical practice to manage sleep concerns are discussed.

The development of fatigue after treatment for pediatric brain tumors does not differ between tumor locations.

BACKGROUND: Children and adolescents treated for a brain tumor suffer from more fatigue than survivors of other types of childhood cancer. As tumor location might be predictive of fatigue, our aim was to investigate the longitudinal development of fatigue in children with brain tumors and risk factors for fatigue separately for different tumor locations. METHODS: Fatigue was assessed 1235 times for 425 participants. Self-report versions of PedsQL Multidimensional Fatigue Scale were used to repeatedly assess fatigue from the end of treatment up to 8 years later. Mixed models were used to analyze fatigue over time and determinants separately for infratentorial (N = 205), supratentorial hemispheric (N = 91), and supratentorial midline tumors (N = 129). RESULTS: Cognitive fatigue worsened with time, while sleep-rest and general fatigue first decreased and then increased. There was no difference in fatigue between the tumor locations, but the risk factors differed when stratified by location. Radiotherapy was associated with more fatigue for infratentorial tumors, and centralization of care was associated with less fatigue for the supratentorial midline tumors. For supratentorial hemispheric tumors, female sex was associated with more fatigue. Higher parental education was associated with less fatigue regardless of tumor location. CONCLUSIONS: The development of fatigue seems to be more related to sociodemographic and treatment variables than to tumor location. Healthcare providers need to be aware that fatigue may develop in the years following end of treatment, and that patients with a low/middle educational family background might be more vulnerable and in need of targeted support.

The course of health-related quality of life after the diagnosis of childhood cancer: a national cohort study.

BACKGROUND: Comprehensive insight in the longitudinal development of health-related quality of life (HRQOL) after childhood cancer diagnosis could improve quality of care. Thus, we aimed to study the course and biopsychosocial determinants of HRQOL in a unique national cohort of children with cancer. METHODS: HRQOL of 2154 children with cancer was longitudinally reported (median: 3 reports) between diagnosis and 5 years after, using the pediatric quality of life inventory generic core scales (PedsQL). HRQOL was modelled over time since diagnosis using mixed model analysis for children 2-7 years (caregiver-reports) and ≥ 8 years (self-reports). Differences in the course between hematological, solid and central nervous system malignancies were studied. Additional associations of demographics, disease characteristics (age at diagnosis, relapse, diagnosis after the national centralization of childhood cancer care and treatment components) and caregiver distress (Distress thermometer) were studied. RESULTS: Overall, HRQOL improved with time since diagnosis, mostly in the first years. The course of HRQOL differed between diagnostic groups. In children aged 2-7 years, children with a solid tumor had most favorable HRQOL. In children aged ≥ 8 years, those with a hematological malignancy had lower HRQOL around diagnosis, but stronger improvement over time than the other diagnostic groups. In both age-groups, the course of HRQOL of children with a CNS tumor showed little or no improvement. Small to moderate associations (ß: 0.18 to 0.67, p < 0.05) with disease characteristics were found. Centralized care related to better HRQOL (ß: 0.25 to 0.44, p < 0.05). Caregiver distress was most consistently associated with worse HRQOL (ß: - 0.13 to - 0.48, p < 0.01). CONCLUSIONS: The HRQOL course presented can aid in identifying children who have not fully recovered their HRQOL following cancer diagnosis, enabling early recognition of the issue. Future research should focus on ways to support children, especially those with a CNS tumor, for example by decreasing distress in their caregivers.

Longitudinal development of fatigue after treatment for childhood cancer: a national cohort study.

BACKGROUND: Fatigue is a distressing and prevalent long-term sequela of treatment for childhood cancer, and there is a need for longitudinal studies to investigate the development of fatigue over time. The objective of this study was to calculate growth-curves for the longitudinal development of fatigue after treatment for childhood cancer, and to investigate the effects of biopsychosocial predictors. MATERIALS AND METHODS: Participants were recruited from a patient monitoring program and data extracted from medical records. Parent-proxy and self-report versions of PedsQLTM Multidimensional Fatigue Scale were used to repeatedly assess fatigue up to 5 years after the end of treatment for childhood cancer. Fatigue was assessed 2440 times for 761 participants (median:3) with proxy-reports (age 2-8 years) and 2657 times for 990 participants with self-reports (above 8 years) (median:2). Mixed models were used to establish growth-curves and to analyze the effect of predictors separately for participants with solid tumors (ST), hemato-oncological malignancies and central nervous system-tumors (CNS). RESULTS: CNS-tumors were associated with more cognitive fatigue than ST at the end of treatment, for both proxy-reports (-11.30, p<.001) and self-reports (-6.78, p=.002), and for proxy-reports of general fatigue (-6.78, p=.002). The only significant difference in change over time was for self-reports of sleep-rest fatigue. The raw scores for the CNS-group decreased with -0.87 per year (95% CI -1.64; -0.81, p=.031) compared to the ST-group. Parental distress was overall the variable most associated with increased fatigue, while immunotherapy was the most frequent medical predictor. National centralization of childhood cancer care decreased fatigue for the CNS-group, but not for other diagnoses. DISCUSSION: Children and adolescents treated for CNS-tumors reported more fatigue than other participants after the end of treatment, and this difference remained over time. Results from this study may help to facilitate the early recognition of children with insufficient recovery of fatigue symptoms.

Fatigue trajectories during pediatric ALL therapy are associated with fatigue after treatment: a national longitudinal cohort study.

OBJECTIVE: Fatigue is one of the most prevalent and distressing symptoms reported by survivors of childhood cancer. There is currently a lack of longitudinal studies on cancer-related fatigue, and especially on the relationship between the course of fatigue during treatment and fatigue at follow-up. The purpose of the current study was therefore to investigate if the course of fatigue during treatment, treatment intensity, serious adverse events, sex, or age at diagnosis are associated with cancer-related fatigue after treatment. METHODS: Participants were 92 children and adolescents diagnosed with acute lymphoblastic leukemia (mean age at diagnosis was 6.26 years). Fatigue was measured with PedsQL multidimensional fatigue scale proxy reports 5 months after diagnosis, 12 months after diagnosis, 24 months after diagnosis, and at follow-up 12 months after end of treatment. The effect of patient and treatment characteristics on fatigue reported at follow-up was tested through logistic regression analyses. RESULTS: The course of fatigue during treatment significantly predicted fatigue reported at follow-up for general fatigue (p = .038, OR = 9.20), sleep/rest fatigue (p = .011, OR = 15.48), and cognitive fatigue (p < .001, OR = 10.78). None of the other variables were associated with fatigue at follow-up for any of the subscales. CONCLUSIONS: The findings demonstrate that fatigue reported during treatment can predict fatigue at follow-up. These results stress the need for longitudinal assessments. Healthcare professionals need to be aware that pediatric patients who are fatigued during treatment need to receive additional attention and timely interventions since cancer-related fatigue will not resolve by itself in the first year after end of treatment.

Cognitive Fatigue and Processing Speed in Children Treated for Brain Tumours.

OBJECTIVE: The relationship between fatigue and cognition has not been fully elucidated in children and adolescent survivors of brain tumours. The aim of the present study was to investigate the potential relationship between fatigue and cognitive impairments in these survivors, as this group is at risk for both types of deficits. METHODS: Survivors of paediatric brain tumours (n = 45) underwent a neuropsychological testing on average 4 years after diagnosis. Mean age at follow-up was 13.41 years. Cognition was assessed with neuropsychological tests, and fatigue with the Pediatric Quality of Life (PedsQL™) Multidimensional Fatigue Scale. Regression analysis, adjusted for cranial radiotherapy and age at diagnosis, was used to investigate the associations between cognitive variables and fatigue subscales. Cognitive variables associated with fatigue were subsequently exploratively assessed. RESULTS: Significant associations were found for cognitive fatigue and measures of cognitive processing speed; Coding: p = .003, r = .583, 95% CI [9.61; 22.83] and Symbol Search: p = .001, r = .585, 95% CI [10.54; 24.87]. Slower processing speed was associated with poorer results for cognitive fatigue. Survivors with the largest decrease in processing speed from baseline to follow-up also experienced the most cognitive fatigue. Survivors expressed more cognitive fatigue compared to other types of fatigue. CONCLUSIONS: The association between cognitive fatigue and cognitive processing speed in children and adolescents treated for brain tumours is in concordance with the results previously reported in adults. Some survivors experience fatigue without impairment in processing speed, indicating the need for comprehensive assessments. Moreover, the study supports that fatigue is a multidimensional concept which should be measured accordingly.

Sleep problems during and after paediatric brain tumours.

Brain tumours are among the most common cancer diagnoses in paediatrics. Children with brain tumours are at risk of developing sleep problems because of direct and indirect effects of the tumour and its treatment, in addition to psychosocial and environmental factors. Sleep has an important role in physical and psychological wellbeing, and sleep problems are associated with many adverse outcomes. In this Review, we describe the state of the evidence regarding sleep in people with paediatric brain tumours, prevalence and types of sleep problems, risk factors, and effectiveness of interventions. Evidence shows that sleep problems, particularly excessive daytime sleepiness, are common in people with paediatric brain tumours, with high BMI emerging as a consistent predictor of sleep disruption. Further intervention studies are needed, and clinical evaluation of sleep is warranted for people with paediatric brain tumours.

Cognitive fatigue in relation to depressive symptoms after treatment for childhood cancer.

BACKGROUND: Cognitive fatigue after childhood cancer is frequently overlooked despite guidelines recommending follow-up, and might be mistaken for depression due to overlapping symptoms. Our objectives were: 1) to examine ratings of fatigue in survivors of paediatric brain tumours (BT) and acute lymphoblastic leukaemia (ALL) compared to healthy controls, 2) to examine the relationship between symptoms of depression and cognitive fatigue, and 3) to evaluate parent-child concordance in ratings of cognitive fatigue. METHODS: Survivors of BT (n = 30), survivors of ALL (n = 30), and healthy controls (n = 60) aged 8-18 years completed the Pediatric Quality of Life Multidimensional Fatigue Scale and the Beck Youth Inventories. Associations between cognitive fatigue, diagnosis and depression were assessed with general linear modelling. Group differences were analysed using the Kruskal-Wallis test. Parent-child concordance was investigated with internal consistency reliability. RESULTS: Cognitive fatigue was prevalent in 70% of survivors of BT survivors and in 30% of survivors of ALL. Diagnosis was the main predictor of cognitive fatigue (p < .001, ηp2 = 0.178), followed by depression (p = .010, ηp2 = 0.080). Survivors of BT reported significantly more fatigue than healthy controls on all fatigue subscales. While they also expressed more symptoms of depression, we found no evidence for an interaction effect. Parent-child concordance was moderate to good among survivors, but poor for controls. CONCLUSIONS: Survivors of BT and ALL suffer from cognitive fatigue, with survivors of BT expressing more problems. Cognitive fatigue and depression should be assessed in survivors of childhood cancer using both self-rated and proxy-rated measures, and appropriate interventions offered.

Pretreatment Cognition in Patients Diagnosed With Pediatric Brain Tumors.

BACKGROUND: There is a large body of literature identifying risk factors for the long-term cognitive alterations found in survivors of pediatric brain tumors. Less is known about baseline cognitive functioning in this population, but studies suggest that cognitive dysfunctions are often present at the time of diagnosis. This study aimed to identify potential risk factors for lower cognitive function at the time of pediatric brain tumor diagnosis. METHODS: Participants were children and adolescents (n = 101) diagnosed with a pediatric brain tumor between 2006 and 2015, who underwent a pretreatment neuropsychologic assessment. Multivariate regression models were used to estimate the association between gender, age at diagnosis, tumor size and location, increased intracranial pressure, epilepsy, and six different indicators of cognitive functioning. RESULTS: Overall, cognitive performance was relatively intact, with results close to norm means, but impairments were found in memory and cognitive processing speed. Male gender, older age, epilepsy, increased intracranial pressure, and larger tumors were all associated with lower cognitive function at the time of brain tumor diagnosis; whereas tumor location was not. CONCLUSIONS: Pretreatment neuropsychologic assessments, with some adjustments, can be carried out with children and adolescents with brain tumors. Our study adds to a small but growing body of literature documenting cognitive impairments at the time of diagnosis; these impairments may partly explain the longer-term deficits that commonly occur in pediatric brain tumor survivors. Consistent with previous research, pretreatment impairments were more common among boys, older children, and those with increased intracranial pressure, epilepsy, and larger tumors. The relationship between baseline and longer-term cognitive deficits requires further examination.