BackgroundDexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy with negative consequences for muscle mass, muscle strength, and... Show moreBackgroundDexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy with negative consequences for muscle mass, muscle strength, and functional abilities. The aim of this study was to establish the effect of a dexamethasone course on sarcopenia and physical frailty in children with ALL, and to explore prognostic factors.MethodsPatients with ALL aged 3-18 years were included during maintenance therapy. Patients had a sarcopenia/frailty assessment on the first day of (T1) and on the day after (T2) a 5-day dexamethasone course. Sarcopenia was defined as low muscle strength in combination with low muscle mass. Prefrailty and frailty were defined as having two or >= three of the following components, respectively: low muscle mass, low muscle strength, fatigue, slow walking speed, and low physical activity. Chi-squared and paired t-tests were used to assess differences between T1 and T2. Logistic regression models were estimated to explore patient- and therapy-related prognostic factors for frailty on T2.ResultsWe included 105 patients, 61% were boys. Median age was 5.3 years (range: 3-18.8). At T1, sarcopenia, prefrailty, and frailty were observed in respectively 2.8%, 23.5%, and 4.2% of patients. At T2, the amount of patients with frailty had increased to 17.7% (p = 0.002), whereas the number of patients with sarcopenia and prefrailty remained similar. Higher ASMM (odds ratio [OR]: 0.49, 95% CI: 0.28-0.83), stronger handgrip strength (OR: 0.41, 95% CI: 0.22-0.77) and more physical activity minutes per day (OR: 0.98, 95% CI: 0.96-0.99) decreased the risk of frailty at T2. Slower walking performance (OR: 2, 95% CI: 1.2-3.39) increased the risk. Fatigue levels at T1 were not associated with frailty at T2.ConclusionPhysical frailty increased strikingly after a 5-days dexamethasone course in children with ALL. Children with poor physical state at start of the dexamethasone course were more likely to be frail after the course.Dexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy. After a 5-day dexamethasone course. Physical frailty increased with 13.5% in pediatric ALL patients. A poorer physical state at start of a dexamethasone course (lower muscle mass, muscle strength, or slower movement ability) was prognostic for developing frailty after a dexamethasone course.image Show less
Penson, A.; Walraven, I.; Bronkhorst, E.; Grootenhuis, M.A.; Maurice-Stam, H.; Beijer, I. de; ... ; utch LATER Study Grp 2023
Background: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). Patients and methods: Participants were included from the... Show moreBackground: The purpose of this study was to determine factors associated with chronic fatigue (CF) in childhood cancer survivors (CCS). Patients and methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS (>= 5 years after diagnosis) and siblings as controls. Fatigue severity was assessed with the 'fatigue severity subscale' of the Checklist Individual Strength ('CIS-fatigue'). CF was defined as scoring >35 on the 'CIS-fatigue' and having fatigue symptoms for >6 months. Twenty-four parameters were assessed, categorized into assumed fatigue triggering, maintaining and moderating factors. Multivariable logistic regression analyses were carried out to investigate the association of these factors with CF. Results: A total of 1927 CCS participated in the study (40.7% of invited cohort), of whom 23.6% reported CF (compared with 15.6% in sibling controls, P < 0.001). The following factors were associated with CF: obesity [versus healthy weight, odds ratio (OR) 1.93; 95% confidence interval (CI) 1.30-2.87], moderate physical inactivity (versus physical active, OR 2.36; 95% CI 1.67-3.34), poor sleep (yes versus no, OR 2.03; 95% CI 1.54-2.68), (sub)clinical anxiety (yes versus no, OR 1.55; 95% CI 1.10-2.19), (sub)clinical depression (yes versus no, OR 2.07; 95% CI 1.20-3.59), pain (continuous, OR 1.49; 95% CI 1.33-1.66), self-esteem (continuous, OR 0.95; 95% CI 0.92-0.98), helplessness (continuous, OR 1.13; 95% CI 1.08-1.19), social functioning (continuous, OR 0.98; 95% CI 0.97-0.99) and female sex (versus male sex, OR Conclusion: CF is a prevalent symptom in CCS that is associated with several assumed maintaining factors, with lifestyle and psychosocial factors being the most prominent. These are modifiable factors and may therefore be beneficial to prevent or reduce CF in CCS. Show less
Hulst, A.M. van; Verwaaijen, E.J.; Berg, S.A.A. van den; Litsenburg, R.R.L. van; Grootenhuis, M.A.; Fiocco, M.; ... ; Akker, E.L.T. van den 2023
Background & aims: Children with acute lymphoblastic leukemia (ALL) receive high doses dexamethasone during treatment, which induce acute side effects. The aims of the current study were to... Show moreBackground & aims: Children with acute lymphoblastic leukemia (ALL) receive high doses dexamethasone during treatment, which induce acute side effects. The aims of the current study were to determine the influence of a five-day dexamethasone course on changes in leptin, fat mass, BMI, hunger, sleep and fatigue and to explore associations between these changes.Methods: Pediatric ALL patients were included during maintenance treatment. Data was collected before (T1) and after (T2) a five-day dexamethasone course (6 mg/m(2)/day). BMI, fat mass (bioelectrical impedance analysis) and leptin were assessed on both timepoints, as well as parent-reported questionnaires regarding hunger, fatigue and sleep problems. Changes between T1 and T2 were assessed using paired tests. Correlation coefficients were calculated to assess associations between these changes (Delta scores: T2-T1). Univariable regression models were estimated to study associations between covariates and elevated leptin.Results: We included 105 children with median age 5.4 years (range 3.0-18.8). Leptin and fat mass, as well as hunger scores, fatigue and sleep deteriorated after five days of dexamethasone (p < 0.001), in contrast to BMI (p = 0.12). No correlations between delta leptin and delta fat mass, BMI, hunger, fatigue or sleep were found. Elevated leptin on T1 was associated with older age (odds ratio (OR) 1.51, 95%-confidence interval (95%-CI) 1.28-1.77), higher fat mass (OR 1.19, 95%-CI 1.07-1.33) and earlier maintenance week (OR 0.96, 95%-CI 0.92-0.99).Conclusions: Five days of high dose dexamethasone treatment lead to direct and significant changes in leptin, hunger scores and fat mass. Since children with ALL are at increased risk for metabolic adverse events, understanding underlying mechanisms is important, and a dexamethasone-induced state of acute leptin resistance might play a role. Show less
Joosten, M.M.H.; Gorp, M. van; Dijk, J. van; Kremer, L.C.M.; Dulmen-den Broeder, E. van; Tissing, W.J.E.; ... ; Dutch LATER Study Grp 2023
ObjectiveTo describe psychosocial outcomes among adult siblings of very long-term childhood cancer survivors (CCS), to compare these outcomes to reference populations and to identify factors... Show moreObjectiveTo describe psychosocial outcomes among adult siblings of very long-term childhood cancer survivors (CCS), to compare these outcomes to reference populations and to identify factors associated with siblings' psychosocial outcomes. MethodsSiblings of survivors (diagnosed <18 years old, between 1963 and 2001, >5 years since diagnosis) of the Dutch Childhood Cancer Survivor Study DCCSS-LATER cohort were invited to complete questionnaires on HRQoL (TNO-AZL Questionnaire for Adult's HRQoL), anxiety/depression (Hospital Anxiety and Depression Scale), post-traumatic stress (Self-Rating Scale for Post-traumatic Stress Disorder), self-esteem (Rosenberg Self-Esteem Scale) and benefit and burden (Benefit and Burden Scale for Children). Outcomes were compared to a reference group if available, using Mann-Whitney U and chi-Square tests. Associations of siblings' sociodemographic and CCS' cancer-related characteristics with the outcomes were assessed with mixed model analysis. ResultsFive hundred five siblings (response rate 34%, 64% female, mean age 37.5, mean time since diagnosis 29.5) of 412 CCS participated. Siblings had comparable HRQoL, anxiety and self-esteem to references with no or small differences (r = 0.08-0.15, p < 0.05) and less depression. Proportions of symptomatic PTSD were very small (0.4%-0.6%). Effect sizes of associations of siblings' sociodemographic and CCS cancer-related characteristics were mostly small to medium (& beta; = 0.19-0.67, p < 0.05) and no clear trend was found in the studied associated factors for worse outcomes. ConclusionsOn the very long-term, siblings do not have impaired psychosocial functioning compared to references. Cancer-related factors seem not to impact siblings' psychosocial functioning. Early support and education remain essential to prevent long-term consequences. Show less
Maas, A.; Maurice-Stam, H.; Aa-van Delden, A.M. van der; Dalen, E.C. van; Dulmen-den Broeder, E. van; Tissing, W.J.E.; ... ; Dutch LATER Study Group 2023
Purpose: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS,... Show morePurpose: Numerous studies investigated generic psychosocial outcomes in survivors of childhood cancer (CCS). The present study aimed to describe survivor-specific psychosocial consequences in CCS, and to identify socio-demographic and medical associated factors. Methods: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age >= 18 years, diagnosed < 18 years, >= 5 years since diagnosis) completed the Benefit & Burden Scale (BBSC) and the Impact of Cancer-Childhood Cancer (IOC-CS). Items were scored on a 5-point Likert scale (range 1-5). We examined outcomes with descriptive statistics, and socio-demographic and medical associated factors with regression analyses, corrected for multiple testing (p < 0.004). Results: CCS, N = 1713, age mean (M) 36 years, 49% female, >= 15 years since diagnosis, participated. On average, CCS reported 'somewhat' Benefit (M = 2.9), and 'not at all' to 'a little' Burden (M = 1.5) of childhood cancer. Average scores on IOC-CS' positive impact scales ranged from 2.5 (Personal Growth) to 4.1 (Socializing), and on the negative impact scales from 1.4 (Financial Problems) to 2.4 (Thinking/Memory). Apart from cognitive problems, CCS reported challenges as worries about relationship status, fertility, and how cancer had affected siblings. Female sex was associated with more Personal Growth, and more negative impact. CCS more highly educated, partnered, and employed had higher positive and lower negative impact. CCS older at diagnosis reported more positive impact. CNS tumor survivors and those who had head/cranium radiotherapy had higher negative impact. CNS tumor survivors reported less positive impact. Conclusion and implications: The majority of CCS reported positive impact of cancer while most CCS reported little negative impact. While this may indicate resiliency in most CCS, health care providers should be aware that they can also experience survivor-specific challenges that warrant monitoring/screening, information provision and psychosocial support. Show less
Hulst, A.M. van; Akker, E.L.T. van den; Verwaaijen, E.J.; Fiocco, M.; Rensen, N.; Litsenburg, R.R.L. van; ... ; Heuvel-eibrink, M.M. van den 2023
Background: Dexamethasone is a cornerstone of paediatric acute lymphoblastic leukaemia (ALL) treatment, although it can induce serious side-effects. Our previous study suggests that children who... Show moreBackground: Dexamethasone is a cornerstone of paediatric acute lymphoblastic leukaemia (ALL) treatment, although it can induce serious side-effects. Our previous study suggests that children who suffer most from neurobehavioural side-effects might benefit from physiological hydrocortisone in addition to dexamethasone treatment. This study aimed to validate this finding.Methods: Our phase three, double-blind, randomised controlled trial with cross-over design included ALL patients (3-18 years) during medium-risk maintenance therapy in a national tertiary hospital between 17th May 2018 and 5th August 2020. A baseline measurement before and after a 5-day dexamethasone course was performed, whereafter 52 patients with clinically relevant neurobehavioural problems were randomised to receive an intervention during four subsequent dexamethasone courses. The intervention consisted of two courses hydrocortisone (physiological dose 10 mg/m2/d in circadian rhythm), followed by two courses placebo, or vice versa. Neurobehavioural problems were assessed before and after each course using the parent-reported Strengths and Difficulties Questionnaire (SDQ) as primary end-point. Secondary end-points were sleep problems, health-related quality of life (HRQoL), hunger feeling, and parental stress, measured with questionnaires and actigraphy. A generalised mixed model was estimated to study the intervention effect.Results: The median age was 5.5 years (range 3.0-18.8) and 61.5% were boys. The SDQ filled in by 51 primary caregivers showed no difference between hydrocortisone and placebo in reducing dexamethasone-induced neurobehavioral problems (estimated effect-2.05 (95% confidence interval (CI)-6.00-1.90). Also, no benefit from hydrocortisone compared to pla-cebo was found for reducing sleep problems, hunger, parental stress or improving HRQoL.Conclusions: Hydrocortisone, when compared to placebo, had no additional effect in redu-cing clinically relevant dexamethasone-induced neurobehavioural problems. Therefore, hy-drocortisone is not advised as standard of care for children with ALL who experience dexamethasone-induced neurobehavioural problems. Trial registration: NetherlandsTrial Register NTR6695/NL6507 (https://trialsearch.who.int/) and EudraCT 2017-002738-22 (https://eudract.ema.europa.eu/).(c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/). Show less
Atteveld, J.E.; Winter, D.T.C. de; Pluimakers, V.G.; Fiocco, M.; Nievelstein, R.A.J.; Hobbelink, M.G.G.; ... ; Dutch LATER study grp 2023
Background: Childhood cancer survivors appear to be at increased risk of frailty and sarcopenia, but evidence on the occurrence of and high-risk groups for these aging phenotypes is scarce,... Show moreBackground: Childhood cancer survivors appear to be at increased risk of frailty and sarcopenia, but evidence on the occurrence of and high-risk groups for these aging phenotypes is scarce, especially in European survivors. The aim of this cross-sectional study was to assess the prevalence of and explore risk factors for pre-frailty, frailty, and sarcopenia in a national cohort of Dutch childhood cancer survivors diagnosed between 1963 and 2001.Methods: Eligible individuals (alive at the time of study, living in the Netherlands, age 18-45 years, and had not previously declined to participate in a late-effects study) from the Dutch Childhood Cancer Survivor Study (DCCSS-LATER) cohort were invited to take part in this cross-sectional study. We defined pre-frailty and frailty according to modified Fried criteria, and sarcopenia according to the European Working Group on Sarcopenia in Older People 2 definition. Associations between these conditions and demographic and treatment-related as well as endocrine and lifestyle-related factors were estimated with two separate multivariable logistic regression models in survivors with any frailty measurement or complete sarcopenia measurements. Findings: 3996 adult survivors of the DCCSS-LATER cohort were invited to participate in this cross-sectional study. 1993 non-participants were excluded due to lack of response or a decline to participate and 2003 (50.1%) childhood cancer survivors aged 18-45 years were included. 1114 (55.6%) participants had complete frailty measurements and 1472 (73.5%) participants had complete sarcopenia measurements. Mean age at participation was 33.1 years (SD 7.2). 1037 (51.8%) participants were male, 966 (48.2%) were female, and none were transgender. In survivors with complete frailty measurements or complete sarcopenia measurements, the percentage of pre-frailty was 20.3% (95% CI 18.0-22.7), frailty was 7.4% (6.0-9.0), and sarcopenia was 4.4% (3.5-5.6). In the models for pre-frailty, underweight (odds ratio [OR] 3.38 [95% CI 1.92-5.95]) and obesity (OR 1.67 [1.14-2.43]), cranial irradiation (OR 2.07 [1.47-2.93]), total body irradiation (OR 3.17 [1.77-5.70]), cisplatin dose of at least 600 mg/m2 (OR 3.75 [1.82-7.74]), growth hormone deficiency (OR 2.25 [1.23-4.09]), hyperthyroidism (OR 3.72 [1.63-8.47]), bone mineral density (Z score <=-1 and >-2, OR 1.80 [95% CI 1.31-2.47]; Z score <=-2, OR 3.37 [2.20-5.15]), and folic acid deficiency (OR 1.87 [1.31-2.68]) were considered significant. For frailty, associated factors included age at diagnosis between 10-18 years (OR 1.94 [95% CI 1.19-3.16]), underweight (OR 3.09 [1.42-6.69]), cranial irradiation (OR 2.65 [1.59-4.34]), total body irradiation (OR 3.28 [1.48-7.28]), cisplatin dose of at least 600 mg/m2 (OR 3.93 [1.45-10.67]), higher carboplatin doses (per g/m2; OR 1.15 [1.02-1.31]), cyclophosphamide equivalent dose of at least 20 g/m2 (OR 3.90 [1.65-9.24]), hyperthyroidism (OR 2.87 [1.06-7.76]), bone mineral density Z score <=-2 (OR 2.85 [1.54-5.29]), and folic acid deficiency (OR 2.04 [1.20-3.46]). Male sex (OR 4.56 [95%CI 2.26-9.17]), lower BMI (continuous, OR 0.52 [0.45-0.60]), cranial irradiation (OR 3.87 [1.80-8.31]), total body irradiation (OR 4.52 [1.67-12.20]), hypogonadism (OR 3.96 [1.40-11.18]), growth hormone deficiency (OR 4.66 [1.44-15.15]), and vitamin B12 deficiency (OR 6.26 [2.17-1.81]) were significantly associated with sarcopenia. Interpretation: Our findings show that frailty and sarcopenia occur already at a mean age of 33 years in childhood cancer survivors. Early recognition and interventions for endocrine disorders and dietary deficiencies could be important in minimising the risk of pre-frailty, frailty, and sarcopenia in this population. Copyright (C) 2023 The Author(s). Published by Elsevier Ltd. Show less
Background: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely... Show moreBackground: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side-effects of two dimensional planned radiotherapy. Aims: The Dutch pediatric 3D-planned radiotherapy (3D-RT) study aims to gain insight in the long-term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data-collection methods, and baseline cohort characteristics. Methods and Results: The 3D-RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000-2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]-scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry-linkage. With a median follow-up of 10.9 (interquartile range [IQR]: 7.9-14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region. Conclusion: The 3D-RT study will provide knowledge on the risk of adverse late health outcomes and radiation-associated dose-effect relationships. This information is valuable to guide follow-up care of childhood cancer survivors and to refine future treatment protocols. Show less
Hulst, A.M. van; Akker, E.L.T. van den; Verwaaijen, E.J.; Fiocco, M.; Rensen, N.; Litsenburg, R.R.L. van; ... ; Heuvel‐Eibrink, M.M. van den 2023
Background: Childhood cancer survivors are at risk for developing long term adverse health outcomes. To identify the risk of and risk factors for specific health outcomes, well-established cohorts... Show moreBackground: Childhood cancer survivors are at risk for developing long term adverse health outcomes. To identify the risk of and risk factors for specific health outcomes, well-established cohorts are needed with detailed information on childhood cancer diagnosis, treatment, and health outcomes. We describe the design, methodology, characteristics, and data availability of the Dutch Childhood Cancer Survivor Study LATER cohort (1963- 2001) part 1; questionnaire and linkage studies. Methods: The LATER cohort includes 5 year childhood cancer survivors, diagnosed in the period 1963- 2001, and before the age of 18 in any of the seven former pediatric oncology centers in the Netherlands. Information on health outcomes from survivors and invited siblings of survivors was collected by questionnaires and linkages to medical registries. Results: In total, 6165 survivors were included in the LATER cohort. Extensive data on diagnosis and treatment have been collected. Information on a variety of health outcomes has been ascertained by the LATER questionnaire study and linkages with several registries for subsequent tumors, health care use, and hospitalizations. Conclusion: Research with data of the LATER cohort will provide new insights into risks of and risk factors for long term health outcomes. This can enhance risk stratification for childhood cancer survivors and inform surveillance guidelines and development of interventions to prevent (the impact of) long term adverse health outcomes. The data collected will be a solid baseline foundation for future follow-up studies. Show less
Gorp, M. van; Joosten, M.M.H.; Maas, A.; Drenth, B.L.; Aa-van Delden, A. van der; Kremer, L.C.M.; ... ; Dutch LATER Study Grp 2022
ObjectiveTo describe health-related quality of life (HRQoL), post-traumatic stress and post-traumatic growth of parents of long-term survivors of childhood cancer (CCS) and study associated factors... Show moreObjectiveTo describe health-related quality of life (HRQoL), post-traumatic stress and post-traumatic growth of parents of long-term survivors of childhood cancer (CCS) and study associated factors. MethodsParents of survivors of the Dutch Childhood Cancer Survivor Study LATER cohort below 30 years and diagnosed 1986-2001 were invited to complete the TNO-AZL Questionnaire for Adult's HRQoL (e.g., sleep and aggressive emotions), Self-Rating Scale for Post-traumatic Stress Disorder, Post-traumatic Growth Inventory, and Illness Cognition Questionnaire. HRQoL domain scores were compared to references using Mann-Whitney U tests. Correlations between post-traumatic stress, growth and HRQoL were evaluated. Medical characteristics of their child and illness cognitions were studied as associated factors of HRQOL, post-traumatic stress and growth. p Parents (n = 661 of n = 448 survivors, 56% female, mean time since child's diagnosis: 21.3 [SD: 3.3] years) reported better HRQoL in social functioning and aggressive emotions than references (r = .08-0.17). Mothers additionally reported better HRQoL in pain, daily activities, sexuality, vitality, positive and depressive emotions (r = .07-0.14). Post-traumatic stress was symptomatic in 3%, and associated with worse HRQoL (r = -0.27-0.48). Post-traumatic growth was positively associated to post-traumatic stress and better HRQoL (r = 0.09-0.12). Cancer recurrence was associated to better HRQoL (beta = 0.37-0.46). Acceptance illness cognitions were associated to better (beta = 0.12-0.25), and helplessness to worse outcomes (beta = 0.14-0.38). ConclusionsHRQoL of parents of young adult survivors of CCS is comparable to references or slightly better. Only a small proportion reports symptomatic post-traumatic stress. Improving acceptance and reducing feelings of helplessness may provide treatment targets for parents with psychosocial problems. Show less
Atteveld, J.E. van; Winter, D.T.C. de; Pluimakers, V.G.; Fiocco, M.; Nievelstein, R.A.J.; Hobbelink, M.G.G.; ... ; Heuvel-Eibrink, M.M. van den 2022
Objectives: Children with cancer often experience sleep problems, which are associated with many negative physical and psychological health outcomes, as well as with a lower quality of life.... Show moreObjectives: Children with cancer often experience sleep problems, which are associated with many negative physical and psychological health outcomes, as well as with a lower quality of life. Therefore, interventions are strongly required to improve sleep in this population. We evaluated interactive education with respect to sleep hygiene with a social robot at a pediatric oncology outpatient clinic regarding the feasibility, experiences, and preliminary effectiveness. Methods: Researchers approached children (8 to 12 years old) who were receiving anticancer treatment and who were visiting the outpatient clinic with their parents during the two-week study period. The researchers completed observation forms regarding feasibility, and parents completed the Children's Sleep Hygiene Scale before and two weeks after the educational regimen. The experiences of children and parents were evaluated in semi-structured interviews. We analyzed open answers by labeling each answer with a topic reflecting the content and collapsed these topics into categories. We used descriptive statistics to describe the feasibility and experiences, and a dependent-samples t-test to evaluate the preliminary effectiveness. Results: Twenty-eight families participated (58% response rate) and all interactions with the robot were completed. The children and parents reported that they learned something new (75% and 50%, respectively), that they wanted to learn from the robot more often (83% and 75%, respectively), and that they applied the sleeping tips from the robot afterwards at home (54%). Regarding the preliminary effectiveness, children showed a statistically significant improvement in their sleep hygiene (p = 0.047, d = 0.39). Conclusions: Providing an educational regimen on sleep hygiene in a novel, interactive way by using a social robot at the outpatient clinic seemed feasible, and the children and parents mostly exhibited positive reactions. We found preliminary evidence that the sleep hygiene of children with cancer improved. Show less
Penson, A.; Walraven, I.; Bronkhorst, E.; Maurice-Stam, H.; Grootenhuis, M.A.; Heiden-van der Loo, M. van der; ... ; Loonen, J. 2022
Simple Summary Survivors of childhood cancer have an increased risk to experience symptoms of severe and persistent fatigue. We studied how fatigue might affect the health-related quality of life... Show moreSimple Summary Survivors of childhood cancer have an increased risk to experience symptoms of severe and persistent fatigue. We studied how fatigue might affect the health-related quality of life of these survivors. Questionnaire items asking about a broad range of daily life aspects were compared between fatigued survivors, survivors without fatigue and the general Dutch population. A total of eleven aspects were studied which were all negatively affected by fatigue, with the largest impact seen for Vitality (how much energy does a person have), General Health (perception of current and future health) and Role Limitations (work-related activities). Results show the negative impact fatigue can have on the daily lives of survivors and why it is important to treat fatigue adequately. Background: Early detection and management of late effects of treatment and their impact on health-related quality of life (HRQOL) has become a key goal of childhood cancer survivorship care. One of the most prevalent late effects is chronic fatigue (CF). The current study aimed to investigate the association between CF and HRQOL in a nationwide cohort of CCS. Methods: Participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort, a nationwide cohort of CCS. Participants completed the Checklist Individual Strength (CIS) to indicate CF (CIS fatigue severity subscale >= 35 and duration of symptoms >= 6 months) and the Short Form-36 (SF-36) and TNO (Netherlands Organization for Applied Scientific Research) and AZL (Leiden University Medical Centre) Adult's Health-Related Quality of Life questionnaire (TAAQOL) as measures for HRQOL. Differences in mean HRQOL domain scores between CF and non-CF participants were investigated using independent samples t-tests and ANCOVA to adjust for age and sex. The association between CF and impaired HRQOL (scoring >= 2 SD below the population norm) was investigated using logistic regression analyses, adjusting for confounders. Results: A total of 1695 participants were included in the study. Mean HRQOL domain scores were significantly lower in participants with CF. In addition, CF was associated with impaired HRQOL on all of the domains (except physical functioning) with adjusted odds ratios ranging from 2.1 (95% CI 1.3-3.4; sexuality domain) to 30.4 (95% CI 16.4-56.2; vitality domain). Conclusions: CF is associated with impaired HRQOL, urging for the screening and regular monitoring of fatigue, and developing possible preventative programs and interventions. Show less
Maurice-Stam, H.; Erp, L.M.E. van; Maas, A.; Oers, H.A. van; Kremer, L.C.M.; Dulmen-den Broeder, E. van; ... ; Dutch LATER Study Grp 2022
Purpose The study aimed to compare the psychosocial development of young adult survivors of childhood cancer (YACCS) with a norm group of young adults from the general population. Methods From 2017... Show morePurpose The study aimed to compare the psychosocial development of young adult survivors of childhood cancer (YACCS) with a norm group of young adults from the general population. Methods From 2017 to 2020, 558 YACCS (18-30 years, 51% female, 10.9% CNS cancer) who participated in the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort (diagnosed 1963-2001) part 2 completed the Course of Life Questionnaire (CoLQ), assessing the achievement of milestones. Items were grouped into the scales autonomy, psychosexual, and social development. Differences between YACCS and norm group were examined with ANOVA and Cohen's d (CoLQ scales) and with logistic regression analysis and odds ratio (OR) (CoLQ items), for the total group and YACCS of CNS cancer. Results The total group of YACCS did not report a less favorable psychosocial development than the norm group. YACCS of CNS cancer scored lower than the norm group (p < 0.001) on the scales autonomy (d = - 0.36) and psychosexual (d = - 0.46). Additionally, on half of the items of autonomy (0.25 <= OR <= 0.34), psychosexual (0.30 <= OR <= 0.48), and social (0.23 <= OR <= 0.47) development, YACCS of CNS cancer were less likely (p < 0.01) than the norm group to have achieved the milestones. Conclusion Overall, psychosocial development of YACCS was as favorable as the norm, but YACCS of CNS cancer were at risk of an unfavorable psychosocial development in all domains. Monitoring psychosocial development should be included in the standards of psychosocial care, especially for CNS cancer patients and survivors, to be able to trace delay. Personalized interventions should be offered to improve the psychosocial development in an early stage. Show less
Heesterbeek, M.R.; Luijten, M.A.J.; Gouw, S.C.; Limperg, P.F.; Fijnvandraat, K.; Coppens, M.; ... ; Haverman, L. 2022
Background Fatigue is often reported by patients with childhood cancer both during and after cancer treatment. Several instruments to measure fatigue exist, although none are specifically validated... Show moreBackground Fatigue is often reported by patients with childhood cancer both during and after cancer treatment. Several instruments to measure fatigue exist, although none are specifically validated for use in childhood cancer survivors (CCS). The aim of the current study was to present norm values and psychometric properties of the Checklist Individual Strength (CIS) and Short Fatigue Questionnaire (SFQ) in a nationwide cohort of CCS. Methods In total, 2073 participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort. Normative data, construct validity, structural validity, and internal consistency were calculated for the CIS and SFQ. In addition, reliability and a cutoff score to indicate severe fatigue were determined for the SFQ. Results Correlations between CIS/SFQ and vitality measures asking about fatigue were high (>0.8). Correlations between CIS/SFQ and measures of different constructs (sleep, depressive emotions, and role functioning emotional) were moderate (0.4-0.6). Confirmatory factor analysis resulted in a four-factor solution for the CIS and a one-factor solution for the SFQ with Cronbach's alpha for each (sub)scale showing good to excellent values (>0.8). Test-retest reliability of the SFQ was adequate (Pearson's correlation = 0.88; ICC = 0.946; weighted Cohen's kappa item scores ranged 0.31-0.50) and a cut-off score of 18 showed good sensitivity and specificity scores (92.6% and 91.3%, respectively). Conclusion The current study shows that the SFQ is a good instrument to screen for severe fatigue in CCS. The CIS can be used as a tool to assess the multiple fatigue dimensions in CCS. Show less
Hulst, A.M. van; Verwaaijen, E.J.; Fiocco, M.; Pluijm, S.M.F.; Grootenhuis, M.A.; Pieters, R.; ... ; Heuvel-Eibrink, M.M. van den 2021
Background: Dexamethasone, a highly effective drug in treating pediatric acute lymphoblastic leukemia (ALL), can induce serious neurobehavioral side effects. These side effects are experienced by... Show moreBackground: Dexamethasone, a highly effective drug in treating pediatric acute lymphoblastic leukemia (ALL), can induce serious neurobehavioral side effects. These side effects are experienced by patients and parents as detrimental with respect to health related quality of life (HRQoL). Based on previous studies, it has been suggested that neurobehavioral side effects are associated to cortisol depletion of the mineralocorticoid receptor in the brain. Our previously reported randomized controlled trial, the Dexadagen study (NTR3280), suggests that physiological hydrocortisone addition during dexamethasone treatment may overcome clinically relevant neurobehavioral problems in patients who experience these problems during dexamethasone treatment. With our current study, we aim to replicate these results in a targeted larger sample before further implementing this intervention into standard of care.Methods: In a national center setting, pediatric ALL patients between 3 and 18 years are enrolled in an Identification study, which identifies patients with clinically relevant dexamethasone-induced neurobehavioral side effects using the Strengths and Difficulties Questionnaire (SDQ). Contributing factors, such as genetic susceptibility, dexamethasone pharmacokinetics as well as psychosocial and family factors are studied to determine their influence in the inter-patient variability for developing dexamethasone-induced neurobehavioral side effects.Patients with clinically relevant problems (i.e. a rise of >= 5 points on the SDQ Total Difficulties Score after 5 days of dexamethasone) are subsequently included in a randomized double-blind placebo-controlled trial with a cross-over design. They receive two courses placebo followed by two courses hydrocortisone during dexamethasone treatment, or vice versa, each time at least 16 days without study medication in between. The primary endpoint is change in SDQ score. The secondary endpoints are sleep (measured with actigraphy and the Sleep Disturbance Scale for Children) and HRQoL (Pediatric Quality of Life Questionnaire).Discussion: The results of our current study may contribute to the management of future ALL patients who experience dexamethasone-induced neuropsychological problems as it may improve HRQoL for patients who suffer most from dexamethasone-induced neurobehavioral side effects. Furthermore, by investigating multiple risk factors that could be related to inter-patient variability in developing these side effects, we might be able to identify and treat patients who are at risk earlier during treatment. Show less
Hulst, A.M. van; Verwaaijen, E.J.; Fiocco, M.F.; Pluijm, S.M.F.; Grootenhuis, M.A.; Pieters, R.; ... ; Heuvel-Eibrink, M.M. van den 2021
Background: Dexamethasone, a highly effective drug in treating pediatric acute lymphoblastic leukemia (ALL), can induce serious neurobehavioral side effects. These side effects are experienced by... Show moreBackground: Dexamethasone, a highly effective drug in treating pediatric acute lymphoblastic leukemia (ALL), can induce serious neurobehavioral side effects. These side effects are experienced by patients and parents as detrimental with respect to health related quality of life (HRQoL). Based on previous studies, it has been suggested that neurobehavioral side effects are associated to cortisol depletion of the mineralocorticoid receptor in the brain. Our previously reported randomized controlled trial, the Dexadagen study (NTR3280), suggests that physiological hydrocortisone addition during dexamethasone treatment may overcome clinically relevant neurobehavioral problems in patients who experience these problems during dexamethasone treatment. With our current study, we aim to replicate these results in a targeted larger sample before further implementing this intervention into standard of care.Methods: In a national center setting, pediatric ALL patients between 3 and 18 years are enrolled in an Identification study, which identifies patients with clinically relevant dexamethasone-induced neurobehavioral side effects using the Strengths and Difficulties Questionnaire (SDQ). Contributing factors, such as genetic susceptibility, dexamethasone pharmacokinetics as well as psychosocial and family factors are studied to determine their influence in the inter-patient variability for developing dexamethasone-induced neurobehavioral side effects.Patients with clinically relevant problems (i.e. a rise of >= 5 points on the SDQ Total Difficulties Score after 5 days of dexamethasone) are subsequently included in a randomized double-blind placebo-controlled trial with a cross-over design. They receive two courses placebo followed by two courses hydrocortisone during dexamethasone treatment, or vice versa, each time at least 16 days without study medication in between. The primary endpoint is change in SDQ score. The secondary endpoints are sleep (measured with actigraphy and the Sleep Disturbance Scale for Children) and HRQoL (Pediatric Quality of Life Questionnaire).Discussion: The results of our current study may contribute to the management of future ALL patients who experience dexamethasone-induced neuropsychological problems as it may improve HRQoL for patients who suffer most from dexamethasone-induced neurobehavioral side effects. Furthermore, by investigating multiple risk factors that could be related to inter-patient variability in developing these side effects, we might be able to identify and treat patients who are at risk earlier during treatment. Show less
Aim: To investigate the health-related quality of life (HRQOL) of Dutch adult childhood cancer survivors (CCS) and to identify risk factors of impaired HRQOL.Methods: Adult CCS (age >18,... Show moreAim: To investigate the health-related quality of life (HRQOL) of Dutch adult childhood cancer survivors (CCS) and to identify risk factors of impaired HRQOL.Methods: Adult CCS (age >18, diagnosed <18, >= 5 years since diagnosis) from the Dutch LATER registry completed the Medical Outcome Study Short Form 36 (SF-36) to measure HRQOL and provided sociodemographic characteristics. Age-adjusted mean SF-36 scale scores of CCS were compared to the Dutch general population for men and women separately using t-tests, with effect size d. Multivariate logistic regression models were built to identify sociodemographic and cancer-related risk factors for impaired physical and mental HRQOL.Results: Both male and female CCS (N = 2301, mean age = 35.4 years, 49.6% female) reported significantly (p <= .005) worse HRQOL than the general population on almost all scales of the SF-36 (-.11 <= d <= -.56). Largest differences were found on vitality and general health perceptions. Significant risk factors (p <= .05) for impaired physical HRQOL were female sex, older age at diagnosis, not having a partner, low educational attainment, disease recurrence and exposure to radiotherapy, specifically to lower extremity radiation. Odds ratios (ORs) ranged from 1.6 to 3.7. Significant risk factors for impaired mental HRQOL were age 26-35 years, male sex, not having a partner and low educational attainment. ORs ranged from 1.3 to 2.0.Conclusion: Adult CCS had worse HRQOL than the general population. CCS most at risk were those with low educational attainment and without a partner. Adult CCS could benefit from routine surveillance of their HRQOL. Special attention for CCS' vitality and health perceptions and beliefs is warranted. (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
