The cumulative burden of self-reported, clinically relevant outcomes in long-term childhood cancer survivors and implications for survivorship care: A DCCSS LATER study.

BACKGROUND: The aim of this study is to evaluate how cumulative burden of clinically relevant, self-reported outcomes in childhood cancer survivors (CCSs) compares to a sibling control group and to explore how the burden corresponds to levels of care proposed by existing risk stratifications. METHODS: The authors invited 5925 5-year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete a questionnaire on health outcomes. Health outcomes were validated by self-reported medication use or medical record review. Missing data on clinically relevant outcomes in CCSs for whom no questionnaire data were available were imputed with predictive mean matching. We calculated the mean cumulative count (MCC) for clinically relevant outcomes. Furthermore, we calculated 30-year MCC for groups of CCSs based on primary cancer diagnosis and treatment, ranked 30-year MCC, and compared the ranking to levels of care according to existing risk stratifications. RESULTS: At median 18.5 years after 5-year survival, 46% of CCSs had at least one clinically relevant outcome. CCSs experienced 2.8 times more health conditions than siblings (30-year MCC = 0.79; 95% confidence interval [CI], 0.74-0.85 vs. 30-year MCC = 0.29; 95% CI, 0.25-0.34). CCSs' burden of clinically relevant outcomes consisted mainly of endocrine and vascular conditions and varied by primary cancer type. The ranking of the 30-year MCC often did not correspond with levels of care in existing risk stratifications. CONCLUSIONS: CCSs experience a high cumulative burden of clinically relevant outcomes that was not completely reflected by current risk stratifications. Choices for survivorship care should extend beyond primary tumor and treatment parameters, and should consider also including CCSs' current morbidity.

Risk and Protective Factors of Psychosocial Functioning in Survivors of Childhood Cancer: Results of the DCCSS-LATER Study.

OBJECTIVE: This study examines the association between psychosocial risk and protective factors and a wide range of psychosocial outcomes including emotional, social, cognitive, and physical domains in childhood cancer survivors (CCS). 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 questionnaires on psychosocial risk and protective factors (Benefit and Burden Scale, Illness Cognition Questionnaire, Rosenberg Self-Esteem Scale, and Impact of Cancer Scale), and psychosocial outcomes (Hospital Anxiety and Depression Scale, Self-Rating Scale for Post-Traumatic Stress Disorder, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and Short Form-36). Associations were assessed with regression analysis, adjusting for attained age, sex, number of health conditions, and time since diagnosis, while correcting for multiple testing (p < 0.004). RESULTS: A total of 1382 CCS participated, all diagnosed ≥ 15 years ago. The mean age of participating CCS was 36 years, and 51% were female. Perceived benefit and burden, acceptance, and helplessness, self-esteem and social support were associated with the psychosocial outcomes. In the models including all psychosocial factors, most associations with psychosocial outcomes were seen for self-esteem (10×), and perceived burden (9×). Self-esteem (all ß ≤ 0.47) and perceived burden (all ß ≤ 0.38) demonstrated strongest associations of medium/large size. CONCLUSIONS: Perceptions of childhood cancer, illness cognitions, self-esteem, and social support play a role in explaining psychosocial functioning in CCS, outweighing the influence of socio-demographic and medical variables. Addressing negative perceptions and reducing feelings of helplessness, while promoting acceptance, self-esteem, and social support, could provide intervention targets for CCS who encounter psychosocial challenges.

Recording diagnostic conversations for communication research purposes in pediatric leukemia.

Recordings of patient-doctor interactions is a recommended method in communication research. However, concerns are expressed regarding audio-recording of conversations with vulnerable patients. Our study examined experiences of children, parents, and oncologists with recording diagnostic conversations in the pediatric acute leukemia setting. Results show that recording conversations is generally well received by virtually all children and parents. Pediatric oncologists seem to overestimate the expected emotional burden for children and parents, which may lead to gatekeeping by professionals. This in turn may lead to a decrease in patient autonomy and research quality when addressing relevant questions in communication science.

Experiences of families post treatment for childhood brain tumours during medical clinic consultations regarding health-related quality of life, unmet needs and communication barriers: A qualitative exploration.

BACKGROUND: Many studies highlight poor health-related quality of life (HRQoL) in children treated for brain tumours and their parents. However, little is known about the extent to which their informational, healthcare and communication needs regarding HRQoL are met during medical outpatient consultations. AIM: To explore the experiences of families regarding communication with physicians about HRQoL issues during consultations after treatment for childhood brain tumours. METHODS: Interviews were conducted with 18 families of children and adolescents aged 8-17 years after completion of brain tumour treatment. Participants had completed treatment within the last 5 years and were receiving regular outpatient follow-up care. Thematic analysis was undertaken using the Framework Method. RESULTS: Five main themes were identified: (i) unmet emotional and mental health needs; (ii) double protection; (iii) unmet information needs; (iv) communication barriers within consultations; and (v) finding a new normal. CONCLUSION: There was a need to improve communication between clinicians and these families, improve information provision, and overcome barriers to conversing with children within these outpatient consultations. Children and their parents should be supported to voice their current needs and concerns regarding their HRQoL. These findings will inform further development of the UK version of the 'KLIK' patient- and parent-reported outcome (PROM) portal.

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.

Different subtypes of chronic fatigue in childhood cancer survivors: A DCCSS LATER study.

INTRODUCTION: The aim of the current study was to investigate whether subtypes of chronic fatigue (CF) can be identified in childhood cancer survivors (CCS), and if so, to determine the characteristics of participants with a specific subtype. METHODS: Participants were included from the nationwide DCCSS LATER cohort. The Checklist Individual Strength (CIS) was completed to assess fatigue. Participants with CF (scored ≥35 on the fatigue severity subscale and indicated to suffer from fatigue for ≥6 months) were divided into subgroups using two-step cluster analysis based on the CIS concentration, motivation, and physical activity subscales. Differences between groups on demographics, psychosocial, lifestyle, and treatment-related variables were determined using ANOVA and chi-square analyses (univariable) and multinomial regression analysis (multivariable). RESULTS: A total of 1910 participants participated in the current study (n = 450 with CF; n = 1460 without CF). Three CF subgroups were identified: Subgroup 1 (n = 133, 29% of participants) had CF with problems in physical activity; Subgroup 2 (n = 111, 25% of participants) had CF with difficulty concentrating; and Subgroup 3 (n = 206, 46% of participants) had multi-dimensional CF. Compared to Subgroup 1, Subgroup 2 more often reported sleep problems, limitations in social functioning, and less often have more than two comorbidities. Subgroup 3 more often reported depression, sleep problems, a lower self-esteem, and limitations in social functioning and a lower educational level compared to Subgroup 1. CONCLUSION: Different subgroups of CCS with CF can be identified based on fatigue dimensions physical activity, motivation and concentration. Results suggest that different intervention strategies, tailored for each subgroup, might be beneficial.

Monitoring health related quality of life in survivorship care of young adult survivors of childhood cancer using web-based patient-reported outcome measures: survivors' and health care practitioners' perspectives on the KLIK method.

PURPOSE: The KLIK method is a tool to systematically monitor and discuss Health Related Quality of Life (HRQOL) in clinical practice. It has been successfully used in clinical practice in The Netherlands, and has recently been implemented in survivorship care for young adult childhood cancer survivors (CCSs). This study evaluates implementation fidelity and satisfaction of CCSs and healthcare practitioners (HCPs) with the KLIK method in survivorship care. METHODS: CCSs' HRQOL was monitored using the KLIK questionnaire (PedsQL generic 18-30 years). In a mixed-methods design, implementation fidelity was based on registrations, and user satisfaction was assessed with evaluation surveys (CCSs) and semi-structured interviews (CCSs, HCPs). Descriptive statistics and qualitative analysis methods were used. RESULTS: A total of 245 CCSs were eligible for the study. Fidelity was 79.2% (194/245) for registration in the KLIK PROM portal, 89.7% (174/194) for completed KLIK questionnaires, 74.7% (130/174) for its discussion during consultation. Of the eligible CCSs, 17.6% (43/245) completed the study evaluation survey. Five CCSs and HCPs were invited for an interview and participated. CCSs (7.7/10) and HCPs (7.5/10) were satisfied with the KLIK method. Reported facilitators included increased insight into CCSs' functioning, improved preparation before, and communication during consultation, without lengthening consultation duration. Barriers included CCSs not always completing KLIK questionnaires, incomplete content of the KLIK questionnaire, and the need for customization for CCSs with cognitive disabilities. CONCLUSION: The KLIK method is a feasible and valuable tool to systematically monitor and discuss HRQOL in survivorship care. Integration of the KLIK method within the organization is essential, with structural support in reminding CCSs to complete questionnaires.

Truth and dare: patients dare to tell the truth when using PROMs in clinical practice.

PURPOSE: As patient-reported outcome measures (PROMs) are increasingly used in clinical practice for screening, monitoring, and management, the potential for response bias has been raised (e.g., over-reporting problems for attention, under-reporting to avoid treatment changes/discontinuation). We investigated whether patients systematically bias their responses when they know clinicians will review their PROM results. METHODS: We conducted secondary analyses of three experimental studies evaluating PROMs in adult and pediatric care. Prior to PROM completion, intervention group patients were informed that the results would be shown to their clinicians ("feedback" arm), whereas control group patients were told that their clinicians would not see their responses ("no feedback" arm). Independent sample t-tests compared the "feedback" and "no feedback" arms' PROM scores at baseline. Effect sizes and 95% confidence intervals were estimated using Cohen's d statistics with Hedges' g correction, and effect sizes > 0.50 were considered clinically relevant. RESULTS: Across the 29 domains assessed in the three studies, no between-arm differences reached an effect size of ± 0.50. Only 3/29 effect sizes exceeded ± 0.30. The confidence intervals for 14 domains included ± 0.50, with 4 favoring the "no feedback" arm and 10 favoring the "feedback" arm. Two domains reached statistical significance, one favoring the "no feedback" arm and one favoring the "feedback" arm. CONCLUSION: This study does not support the hypothesis that patients systematically bias their PROM responses if they know that clinicians will see their results. These findings support using PROMs in clinical practice as a valid mechanism to promote patient-centered care.

Pain monitoring app leads to less pain in children with cancer at home: Results of a randomized controlled trial.

BACKGROUND: The authors developed a pain monitoring app offering educational information, and real-time health care professional feedback on clinically significant pain (>4 numeric rating scale [NRS]-11) for children with cancer to reduce pain at home. METHODS: This monocenter, nonblinded randomized controlled trial enrolled Dutch children (0-18 years old) receiving cancer treatment (≥3 months after diagnosis, ≥2 months treatment remaining). Children were randomly assigned to use the app or receive usual care (two parallel groups). We assessed whether use of the app yielded less clinically significant pain (aim 1) and whether it affected pain severity, duration, interference, pain management strategies, and parental emotional well-being (aim 2). The app was also evaluated by families (aim 3). RESULTS: A total of 94 children were randomized to use the app (15 drop-outs), and 90 were to receive care as usual (11 drop-outs). The app group (n = 79, mean age: 7.5 [5.1] years, 48% girls, 63% hemato-oncology diagnosis) reported significantly less clinically significant pain compared to usual care (n = 79, mean age: 7.5 [5.4] years, 52% girls, 65% hemato-oncology diagnosis) (odds ratio [OR], 0.38; 95% confidence interval [CI], 0.198-0.734]) (aim 1), as well as significantly lower pain severity (ß = -0.27; 95% CI, -0.407 to -0.142). No differences were found for duration, interference, or management strategies. Parents in the app group reported significantly less distress compared to usual care (ß = -0.84; 95% CI, -1.61 to -0.03]) (aim 2). Families generally evaluated the app positively (aim 3). CONCLUSIONS: Use of the app resulted in less clinically significant pain at home. The exact working mechanisms of the app should be further elucidated.

Psychosocial outcomes in long-term Dutch adult survivors of childhood cancer: The DCCSS-LATER 2 psycho-oncology study.

BACKGROUND: This study compares a comprehensive range of psychosocial outcomes of adult childhood cancer survivors (CCS) to general population-based references and identifies sociodemographic and medical risk factors. METHODS: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (attained age ≥18 years, diagnosed <18 years, ≥5 years since diagnosis) completed the Rosenberg Self-Esteem Scale, Hospital Anxiety and Depression Scale, Distress Thermometer, Self-Rating Scale for Post-Traumatic Stress Disorder, and the Short Form-36 (Health Related Quality of Life). CCS' scores were compared with references using analysis of variances and logistic regression analysis, controlling for age and sex (p < .05). Risk factors for worse psychosocial outcomes were assessed with regression analyses (p < .05). RESULTS: CCS, N = 1797, mean age 35.4 years, 49.0% female, all ≥15 years since diagnosis, participated. Three percent reported posttraumatic stress disorder because of childhood cancer and 36.6% experienced clinical distress. CCS did not differ from references on self-esteem and anxiety but were less depressed (d = -.25), and scored poorer on all health-related quality of life scales, except for bodily pain (.01 ≤ d  ≥  -.36). Female sex, lower educational attainment, not being in a relationship, and being unemployed were negatively associated with almost all psychosocial outcomes. Except for a central nervous system tumor diagnosis, few medical characteristics were associated with psychosocial outcomes. CONCLUSION: CCS appear resilient regarding mental health but have slightly poorer health-related quality of life than references. Sociodemographic characteristics and central nervous system tumors were related to most psychosocial outcomes, but no clear pattern was observed for other medical factors. Future studies should address additional factors in explaining CCS' psychosocial functioning, such as coping, social support, and physical late effects.

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.

Psychosocial functioning of adult siblings of Dutch very long-term survivors of childhood cancer: DCCSS-LATER 2 psycho-oncology study.

OBJECTIVE: To 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. METHODS: Siblings 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. RESULTS: Five 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 (ß = 0.19-0.67, p < 0.05) and no clear trend was found in the studied associated factors for worse outcomes. CONCLUSIONS: On 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.

Psychosexual development, sexual functioning and sexual satisfaction in long-term childhood cancer survivors: DCCSS-LATER 2 sexuality substudy.

OBJECTIVES: Childhood cancer may negatively impact childhood cancer survivors' (CCS) sexuality. However, this is an understudied research area. We aimed to describe the psychosexual development, sexual functioning and sexual satisfaction of CCS, and identify determinants for these outcomes. Secondarily, we compared the outcomes of a subsample of emerging adult CCS to the Dutch general population. METHODS: From the Dutch Childhood Cancer Survivor Study LATER cohort (diagnosed 1963-2001), 1912 CCS (18-71 years, 50.8% male) completed questions on sexuality, psychosocial development, body perception, mental and physical health. Multivariable linear regressions were used to identify determinants. Sexuality of CCS age 18-24 (N = 243) was compared to same-aged references using binomial tests and t-tests. RESULTS: One third of all CCS reported hindered sexuality due to childhood cancer, with insecure body the most often reported reason (44.8%). Older age at study, lower education, surviving central nervous system cancer, poorer mental health and negative body perception were identified as determinants for later sexual debut, worse sexual functioning and/or sexual satisfaction. CCS age 18-24 showed significantly less experience with kissing (p = 0.014), petting under clothes (p = 0.002), oral (p = 0.016) and anal sex (p = 0.032) when compared to references. No significant differences with references were found for sexual functioning and sexual satisfaction, neither among female CCS nor male CCS age 18-24. CONCLUSIONS: Emerging adult CCS reported less experience with psychosexual development, but similar sexual functioning and sexual satisfaction compared to references. We identified determinants for sexuality, which could be integrated in clinical interventions for CCS at risk for reduced sexuality.

Psychosocial functioning of parents of Dutch long-term survivors of childhood cancer.

OBJECTIVE: To 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. METHODS: Parents 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 < 0.05 was considered statistically significant. RESULTS: 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 (ß = 0.37-0.46). Acceptance illness cognitions were associated to better (ß = 0.12-0.25), and helplessness to worse outcomes (ß = 0.14-0.38). CONCLUSIONS: HRQoL 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.

Fatigue mediates the relationship between emotional and cognitive functioning in children post-cancer treatment.

BACKGROUND/OBJECTIVES: Children treated for cancer are at risk to develop cognitive problems. Insight in underlying associations with emotional functioning and fatigue can be used to optimize interventions. We therefore aim to study emotional functioning, fatigue, and cognitive functioning in children postcancer treatment and investigate whether fatigue mediates the relationship between emotional and cognitive functioning. DESIGN/METHODS: Emotional functioning, fatigue, and cognitive functioning were assessed in children post-cancer treatment using subscales of the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales, Multidimensional Fatigue Scale and Cognitive Functioning Scale. A one sample t-test was used to compare outcomes with general population peers and mediation analysis was used to address the effect of fatigue on the relationship between emotional and cognitive functioning. RESULTS: A total of 137 children (mean age: 13.6, SD ± 3.3 years; mean time since end of treatment: 7.1 months, SD ± 5.9) participated. Lower scores on emotional functioning (Cohen's d [D]: 0.4), fatigue (D: 0.8) and cognitive functioning (D: 0.6) were found (p < .001) in children post-cancer treatment than in peers. A medium association was found between emotional and cognitive functioning (standardized regression coefficient [ß]: 0.27, p < .001), which was mediated by fatigue (ß = 0.16). CONCLUSIONS: Outcomes on emotional and cognitive functioning are decreased and fatigue is increased in children postcancer treatment. Fatigue mediates the relationship between emotional and cognitive functioning. Our results show the importance to focus on fatigue amongst stress as a target for intervention to improve cognitive functioning.

Clinical evaluation of late outcomes in Dutch childhood cancer survivors: Methodology of the DCCSS LATER 2 study.

BACKGROUND: Childhood cancer survivors face late health problems; despite advances in research, details on risk remain unclear. We describe the methodological aspects of the Dutch Childhood Cancer Survivor Study (DCCSS) cross-sectional clinical study (LATER 2 study). PROCEDURE: From the multi-center DCCSS LATER cohort of 6165 five-year survivors diagnosed during 1963-2001, we invited 4735 eligible survivors in 2016, as well as siblings and parents of survivors. Gaps in evidence identified during development of surveillance guidelines were translated into clinical research questions for 16 outcome-specific subprojects. The regular care visit to the LATER outpatient clinic forms the backbone of outcome assessment complemented with research-defined measurements (physical examination, clinical tests, questionnaires). Furthermore, blood/saliva samples were taken for deoxyribonucleic acid (DNA) extraction. RESULTS: In total, 2519 (53.2%) survivors participated in the LATER 2 study. When comparing participants with nonparticipants, we observed that males, CNS survivors, and those treated with surgery only were less likely to participate. Of the participating survivors, 49.3% were female. Median time since childhood cancer diagnosis was 26.9 years (range 14.8-54.7 years) and median attained age was 34.4 years (range 15.4-66.6 years). CONCLUSIONS: The high-quality data generated in the LATER 2 study will provide valuable insights into risks of and risk factors for clinical and physical and psychosocial health outcomes and factors for early recognition of those health outcomes in long-term childhood cancer survivors. This will contribute to fill in important gaps in knowledge and improve the quality of life and care for childhood cancer survivors.

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.

A grounded theory study on the dynamics of parental grief during the children's end of life.

AIM: Parents are increasingly confronted with loss during their child's end of life. Healthcare professionals struggle with parental responses to loss. This study aimed to understand parental coping with grief during their child's end of life. METHODS: A grounded theory study was performed, using semi-structured interviews with parents during the child's end of life and recently bereaved parents. Data were collected in four children's university hospitals and paediatric homecare services between October 2020 and December 2021. A multidisciplinary team conducted the analysis. RESULTS: In total, 38 parents of 22 children participated. Parents strived to sustain family life, to be a good parent and to ensure a full life for their child. Meanwhile parents' grief increased because of their hypervigilance towards signs of loss. Parents' coping with grief is characterised by an interplay of downregulating grief and connecting with grief, aimed at creating emotional space to be present and connect with their child. Parents connected with grief when it was forced upon them or when they momentarily allowed themselves to. CONCLUSION: The parents' ability to engage with grief becomes strained during the end of life. Healthcare professionals should support parents in their search for a balance that facilitates creating emotional space.

Online cognitive-behavioral group intervention for young adult survivors of childhood cancer: a pilot study.

BACKGROUND: Young adult childhood cancer survivors (YACCS) are a vulnerable group in need of psychosocial support, but tailored interventions are lacking. AIM: To examine feasibility and satisfaction, and to explore preliminary effectiveness of an online group intervention (Op Koers Online for YACCS) aimed at teaching active coping skills and providing peer-contact, thereby reducing and preventing psychosocial problems in YACCS. The intervention is based on psycho-education, cognitive behavioral therapy, and aspects of acceptance and commitment therapy. METHODS: YACCS completed questionnaires pre- and post-intervention. Feasibility was based on attendance, drop-out, and an evaluation questionnaire was administered to assess satisfaction. Preliminary effectiveness was evaluated with the Mastery Scale, Illness Cognition Questionnaire, Distress Thermometer, Impact of Cancer - Childhood Survivors, and Pediatric Quality of Life Inventory. Preliminary effectiveness was investigated by testing differences on the psychosocial outcomes (coping and psychosocial wellbeing) between T0 and T1 within respondents, using paired samples t tests and Cohen's d. RESULTS: 10 YACCS participated in the intervention and completed all questionnaires. There was no drop-out; 90% of participants attended five out of six sessions. Overall, participants were satisfied with the intervention; 7.6 on a 0-10 scale. Distress (Cohen's d=-.6, p=.030) and feelings of helplessness (Cohen's d=-.8, p=.001) reduced from T0 to T1, while self-efficacy (Cohen's d=.8, p=.013,) improved. Other outcomes displayed small effects, but did not change significantly. CONCLUSIONS: This first, small pilot study showed short-term decrease in distress and feelings of helplessness and improvement of self-efficacy. Op Koers Online was positively evaluated by YACCS and course leaders, filling a gap in psychosocial services for YACCS.

Prevalence and risk factors of cancer-related fatigue in childhood cancer survivors: A DCCSS LATER study.

BACKGROUND: Cancer-related fatigue is a debilitating late effect after treatment for childhood cancer. The prevalence of fatigue in childhood cancer survivors (CCSs) and associated factors for fatigue has varied widely in previous studies. Two important aspects of cancer-related fatigue, its severity and chronicity, are often not assessed. This study investigated the prevalence of, and risk factors for, severe chronic fatigue (CF) in a national cohort of Dutch CCSs. METHODS: In this study, 2810 CCSs (5-year survivors of all childhood malignancies diagnosed between 1963 and 2001 with a current age of 12-65 years) and 1040 sibling controls were included. CF was assessed with the Short Fatigue Questionnaire and was defined as a score ≥ 18 and persistence of fatigue for ≥6 months. Cancer- and treatment-related characteristics, current health problems, and demographic and lifestyle variables were assessed as potential risk factors for CF via multivariable logistic regression analyses. RESULTS: In adult CCSs and sibling controls (≥18 years old), the prevalence of CF was 26.1% and 14.1%, respectively (P < .001). In adolescent CCSs and sibling controls (<18 years old), the prevalence of CF was 10.9% and 3.2%, respectively. Female gender (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.73-2.62), unemployment (OR, 2.18; 95% CI, 1.67-2.85), having 1 or more health problems (OR for 1-2, 1.48; 95% CI, 1.18-1.87; OR for >2, 2.20; 95% CI, 1.50-3.21), and a central nervous system diagnosis (OR, 1.74; 95% CI, 1.17-2.60) were significantly associated with CF in adult CCSs. CONCLUSIONS: This study shows that CCSs, regardless of their cancer diagnosis, report CF more often than sibling controls. This study provides new evidence for the prevalence of fatigue in CCSs.