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Background: The clinical outcomes of patients with pediatric cancer have significantly improved over the past few decades. However, the treatments are often highly intensive and can advertently pose a risk for developing various health conditions, including bone mass loss and fragility fractures. Since patients with bone malignancies, such as osteosarcoma (OS) and Ewing’s sarcoma (ES), require musculoskeletal surgery as well as chemotherapy, OS/ES survivors are potentially at even greater risk of developing these musculoskeletal conditions than those with other types of cancer. However, these issues in OS/ES survivors are often overlooked by clinicians treating childhood cancers. Thus, this scoping review was designed and conducted to better understand the bone health conditions in OS/ES survivors. Design: We conducted a literature search and included the studies that describe bone mineral density in association with bone health in OS/ES survivors for analysis. Data regarding patients’ demographic, diagnosis, bone mineral density, laboratory examinations, and incidence of fractures were extracted and evaluated. Results: We found that almost half of OS/ES survivors have bone mass deficit and that several factors (such as a frailer physique and younger age at diagnosis) are potentially associated with low bone mass in OS/ES survivors. On the other hand, due to a paucity of information currently available, we could not determine whether long-term OS/ES survivors would ultimately regain bone mass or be at a greater risk of fragility fractures. Conclusions: This scoping review reveals a previously unappreciated knowledge gap in our understanding of bone health conditions in OS/ES survivors and raises awareness among clinicians and care providers of this condition that OS/ES patients may encounter after successful treatment.

Purpose: Cancer survivors with a history of gonadotoxic treatment are at risk for future infertility and reproductive concerns, including worry about infertility. The purpose of this study was to describe factors associated with fertility-related worry among emerging adult survivors of childhood cancer. Methods: This chart review included patients aged 18.00–25.99 years and > 1 year from cancer treatment completion with a history of gonadotoxic treatment. Survivors were offered structured fertility-focused discussions at age ≥ 18 years, which assessed worry about future infertility. Data from this discussion (i.e., reported fertility-related worry (yes/no), sociodemographic, and clinical characteristics were abstracted from the medical record. Multivariable logistic regression with backwards elimination was used to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with fertility-related worry. Results: Survivors (N = 249) were a mean age of 19.1 ± 1.2 years at initial fertility discussion; 55.8% were male, 58.2% non-Hispanic White, and 27.3% were at high risk for future treatment-related infertility. Fertility-related worry was reported by 66.3% of survivors. Factors related to worry on multivariable analysis included female sex (OR: 2.64, 95%CI: 1.44–4.96, p =.002), solid tumor diagnosis (OR: 2.31, 95%CI: 1.15–4.71, p =.019), moderate and high risk of infertility (OR: 2.94, 95%CI: 1.23–7.64, p =.02; OR: 3.25, 95%CI: 1.55–7.17, p =.002), and ≥ 2 fertility discussions during survivorship care OR: 2.71, 95%CI: 1.46–5.20, p =.002). Conclusions: Two-thirds of emerging adult cancer survivors expressed worry about future infertility, which has been linked to a variety of adverse quality of life outcomes. Survivors who are worried about infertility may benefit from psychological interventions. [ABSTRACT FROM AUTHOR]

A clearer understanding of the association between a biomarker of long-term stress reactivity and family functioning among pediatric cancer survivors may guide both survivorship research and clinical practice. The current study examined the relationship between a long-term measure of hypothalamic–pituitary–adrenal (HPA) activity (cortisol concentration; CORTHAIR) and parent-reported family functioning (Family Environment Scale; FES) in a cross-sectional sample of survivors (n = 26) and controls (n = 53). Child CORTHAIR was not different in survivors and controls, though treatment severity was significantly related to child survivor CORTHAIR. Child CORTHAIR and parent CORTHAIR were positively correlated. Cancer survivor parents reported greater FES Organization. Child CORTHAIR was inversely associated with FES Independence, while parent CORTHAIR was inversely correlated with FES Organization. Parent CORTHAIR and FES Independence were significant and unique predictors of child CORTHAIR. Our results provide preliminary evidence for a relationship between a stress biomarker, child CORTHAIR, and family functioning among pediatric cancer survivors and controls. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardio-oncology is an increasingly important field of cardiology that focuses on the detection, monitoring, and treatment of cardiovascular disease (CVD) occurring during and after oncological treatments. The survival rate for childhood cancer patients has dramatically increased thanks to new treatment protocols and cardiovascular (CV) sequelae represent the third most frequent cause of mortality in surviving patients. This study aims to provide a complete and updated review of all the main aspects of cardio-oncology in childhood and to highlight the critical issues. Recent Findings: The problem of CV complications in childhood cancer survivors raises the need to make an early diagnosis of cardiotoxicity by the new imaging and laboratory techniques in order to intervene promptly and to implement pharmacological strategies and lifestyle changes to reduce or even to prevent cardiac injury. Furthermore, a stratification of CV risk, also including new predisposing factors such as the presence of some genetic mutations, is of paramount importance before undertaking oncological treatments. Besides, a systematic and personalized planning of long-term follow-up is fundamental to ensure a transition from pediatric to adult hospital and to avoid missed or late diagnosis of cardiomyopathy. Summary: We reviewed the main risk factors for cardiotoxicity in children, both traditional and emerging ones: the mechanisms of toxicity of both old and new antineoplastic therapies, the techniques for detecting cardiac damage, and the current evidence regarding pharmacological cardioprotection. At the end, we focused our attention on the existing guidelines and strategies about the long-term follow-up of childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Cancer is a prominent cause of death worldwide in the pediatric population. Since childhood cancer is not possible to prevent, it is essential to focus on a prompt and correct diagnosis followed by effective, evidence-based therapy with individualized supportive care. Given the enhancement of childhood cancer management over the past decades, survival rate has significantly improved, thus leading to the progression of several late effects, including metabolic derangements. These metabolic imbalances are associated with the underlying disease and the cancer treatments. As a result, the metabolic state may contribute to a high risk of cardiovascular morbidity and premature mortality among childhood cancer survivors. This review aims to summarize the potential pathophysiological mechanisms linked to the risk of diabetes and metabolic syndrome and screening recommendations. Further investigations are needed to clarify the underlying mechanisms of such metabolic abnormalities and to improve long-term cardiometabolic survival among these patients. [ABSTRACT FROM AUTHOR]

Objective: Childhood cancer survivors experience reduced physical activity level, participation as well as health‐related quality of life. This prospective, pre‐/post‐intervention and follow‐up cohort study aims to determine the efficacy of an interdisciplinary rehabilitation on improving physical fitness, fatigue and body composition. Methods: A total of 24 childhood cancer survivors (mean age: 12.15 years ± 3.2; 14 females; 10 males) were recruited 6 months after medical treatment and received a 4‐month interdisciplinary intervention. Cardiorespiratory fitness (PredVO2peak and PredLoadmax), body composition (dry lean weight) and quality of life (general fatigue) were assessed at baseline, post‐intervention and 1‐year follow‐up. Linear mixed models were used to analyse data. Results: Linear mixed modelling revealed a significant main effect of time on predicted maximal load (F = 13.189, df = 36.179, p < 0.001), dry lean weight (F = 64.813, df = 37.019, p < 0.001) but also significant improvement of general fatigue score (−9.039 ± 4.300, 95% CI −17.741 to −0.336, p = 0.042), indicating a decline in general fatigue. Conclusion: With emerging evidence that physical activity is safe and feasible, together with increasing numbers of childhood cancer survivors at risk for long‐term chronic co‐morbidities, this study advocates for better access to interdisciplinary rehabilitation programmes in order to improve their physical condition and their body composition and reduce fatigue. [ABSTRACT FROM AUTHOR]

Objective: In this sub‐study from the 'PACCS' study, we explored the psychosocial experiences of children and adolescents in everyday life post‐cancer treatment and the possible factors that can moderate these experiences. Methods: This is a qualitative explorative study using semi‐structured interviews with 43 childhood cancer survivors between the ages of nine and 18 from Norway and Denmark. We conducted a secondary thematic analysis using Malterud's systematic text condensation. Results: Two main themes were identified: 'The post‐treatment gap between expectations and reality' comprised two subthemes: (1) lack of mastery and feeling different and (2) lack of understanding and acceptance. The second main theme, 'Managing the gap', comprised three subthemes: (1) information and knowledge, (2) adjustments and adaptions and (3) social support and openness. The findings reveal that the psychosocial challenges resulted from the remaining ability gap(s). Measures such as tailored information, school adjustments and social support were potential dynamic factors affecting the gap(s) positively or negatively. Psychosocial challenges post‐treatment are experiences of lack of acceptance and understanding from others. Conclusion: To safeguard a positive transition back to everyday life, health care providers should support the survivors' psychosocial care, including getting back to school and re‐entering social interactions. [ABSTRACT FROM AUTHOR]

Aims: This study explores experiences of childhood cancer survivors and their parents with a combined physical and social activity intervention during treatment, including how the survivors and their parents perceive physical activity post‐treatment. Design: A process evaluation using semi‐structured interviews. Methods: Using a criterion‐sampling strategy, 18 Danish childhood cancer survivors (aged 11–18 years) and their parents were interviewed from September 2019 through May 2020. Data analysis used an inductive thematic approach focused on meaning. Results: Three themes emerged: (1) being physically active during hospitalization; (2) peers as motivators and (3) physical activity post‐treatment. During hospitalization, daily motivation to do physical activity was dependent on the daily well‐being, that is, presence of the side effects from the child's treatment. Healthy classmates provided distraction, reduced loneliness and promoted normality for those hospitalized. For most of the survivors, their healthy peers provided motivation for being physically active during treatment. When surplus energy was lacking, some survivors preferred doing physical activity alone with a professional. Those who were physically active in the hospital sustained being physically active post‐treatment while their parents continued seeking advice about appropriate activity levels. Conclusion: Childhood cancer survivors and their parents benefited from the intervention which also provided guidance to remaining physically active post‐treatment. This was particularly true for the participants with leukaemia. Impact Healthcare professionals should support children with cancer to be physically active during hospitalization. Including social and physical components in their care plan and being aware of individual preferences is pivotal to improving the survivors' level of physical and social well‐being during and post‐treatment. Patient or Public Contribution: The participants were involved in designing the interview guides to ensure that the interview guides were understandable for the participants to provide rich descriptions of their experiences with a physical and social activity intervention during hospitalization. [ABSTRACT FROM AUTHOR]

This case-control study was conducted to determine the antibody titer against the measles virus in childhood cancer survivors' post-chemotherapy treatment to determine the patient's immune status against the measles virus. We enrolled 38 children who were in complete remission and whose treatments had been stopped for at least 3 months and 38 age and sex-matched healthy controls. We analyzed the medical records of the cancer survivors, and each study participant's serum sample was analyzed by the ELISA method to determine the antibody titer against measles. The cancer survivors had significantly lower measles antibody titers than the healthy control participants, and 78.9% of cancer survivors were unprotected (seronegative) compared to 7.9% in healthy controls. After multivariate analysis, there was no statistically significant factor associated with loss of protective humoral immunity against measles. These results underline the need for post-chemotherapy measles antibody testing and revaccination of seronegative survivors. [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular diseases (CVD) are one of the long-term side effects of childhood cancer treatment. Salusin ß is an indicator of atherosclerosis development. The aim of the study was to evaluate serum salusin ß levels in long-term acute lymphoblastic leukaemia survivors (ALLs) and Wilms' tumour survivors (WTs) and compare these levels to established CVD risk factors. Material and methods: Thirty-seven ALLs and eleven WTs underwent physical examination and laboratory tests after an overnight fast at least 5 years after the end of oncological treatment. The laboratory tests included analysis of lipid profiles, serum glucose levels, renal parameters and salusin ß levels. Results: The groups did not vary in age, time from the end of the treatment, number of obese persons, blood pressure, lipid profile, serum creatinine and glucose levels. The ALLs had greater weights and greater waist circumferences. The serum cystatin level was higher and the cystatin-based estimated glomerular filtration rate was lower in the WTs. Salusin ß was higher in the WT group, but the result was not statistically significant. Conclusions: Acute lymphoblastic leukaemia survivors and WTs differ in terms of types of long-term side effects. Acute lymphoblastic leukaemia survivors more often develop obesity and metabolic problems, whereas WTs tend to develop renal disorders. Salusin ß levels are associated with the level of LDL in ALLs and can indicate lipid disorders in patients with higher risk of obesity, suggesting that it could be a predictor of atherosclerosis. Further investigations are necessary to confirm this result. It is necessary to continue follow-up among adults who have been treated for childhood cancers to reveal long-term side effects such as cardiovascular disorders. [ABSTRACT FROM AUTHOR]

Purpose: Caregivers of childhood cancer survivors (CCS) have diverse needs, which should be addressed to provide comprehensive cancer care. We aimed to evaluate the unmet needs of caregivers of CCS. Methods: The subjects were 700 caregivers recruited at three major hospitals in South Korea. We collected study data using self-administered questionnaires and a thorough review of medical records. We assessed the unmet needs of caregivers using the comprehensive needs assessment tool for cancer caregivers and evaluated factors associated with the highest tertile range of unmet needs by multiple logistic regression analysis. Results: The greatest unmet needs of caregivers had to do with healthcare staff, followed by information. Compared with father-caregivers, mother-caregivers had greater unmet needs related to health and psychological problems, family/social support, and religious/spiritual support, with odds ratios (95% confidence interval) of 3.79 (2.52–5.69), 3.17 (2.09–4.81), and 1.69 (1.14–2.50), respectively. Compared with caregivers of the youngest CCS (< 6 years), caregivers of CCS aged 12–18 years and caregivers of the oldest CCS (≥ 19 years) respectively showed 2.62 (1.24–5.52) and 3.18 (1.34–7.55) times greater unmet needs for information. Caregivers of CCS who received haematopoietic stem-cell transplantation had a 2.01-fold (1.14–3.57) greater need for practical support. Conclusion: Caregivers of CCS had substantial unmet needs required for comprehensive care for CCS. Several individual characteristics of caregivers and their children were significantly associated with greater unmet needs of the caregivers. Implications for Cancer Survivors: Personalized support based on the characteristics of both CCS and their caregivers is required to provide comprehensive care for CCS. [ABSTRACT FROM AUTHOR]

Patient-reported outcomes (PROs) are used in clinical work and research to capture the subjective experiences of childhood cancer patients and survivors. PROs encompass content domains relevant and important to this population, including health-related quality-of-life (HRQOL), symptoms, and functional status. To inform future efforts in the application of PRO measures, this review describes the existing generic and cancer-specific PRO measures for pediatric cancer populations and summarizes their characteristics, available language translations, content coverage, and measurement properties into tables for clinicians and researchers to reference before choosing a PRO measure that suits their purpose. We have identified often unreported measurement properties that could provide evidence about the clinical utility of the PRO measures. Routine PRO assessment in pediatric cancer care offers opportunities to facilitate clinical decision-making and improve quality of care for these patients. However, we suggest that before implementing PRO measures into research or clinical care, the psychometric properties and content coverage of the PRO measures must be considered to ensure that PRO measures are appropriately assessing the intended construct in childhood cancer patients. [ABSTRACT FROM AUTHOR]

Cerebrovascular events (CVEs) are serious late adverse events among childhood cancer survivors. We estimated the incidence and risk factors of symptomatic CVEs and described the clinical characteristics among childhood cancer survivors after upper body radiotherapy. The Dutch Childhood Cancer Survivor Study LATER cohort study includes 5-year childhood cancer survivors diagnosed 50 Gy was associated with 6-fold increased risk, compared to upper body radiotherapy not involving the cranium (hazard ratio = 6.3, 95%CI: 3.3-12.1). In a subgroup with available data on lifestyle and comorbidities, hypertension (odds ratio[OR] = 6.2, 95%CI: 1.6-23.8) and obesity (BMI≥30 vs. <30 = 2.95, 95%CI: 1.1-8.0) significantly increased CVE risk. During CVE episode, 17 (16%) had a life-threatening situation, and two (2%) others died. In 28%, a second CVE developed during follow-up. At end of follow-up, 29% were deceased, and 40% of those alive were unable to carry out normal activities/active work. Childhood cancer survivors treated with higher doses of cranial radiotherapy are at highest risk for developing CVEs. CVEs occur at a young age and cause a high morbidity. Studies to investigate risk-reducing secondary preventive interventions are warranted., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Identifying risk factors contributing the most to mortality of childhood cancer survivors is essential to guide harm reduction efforts in childhood cancer treatments, and long-term follow-up of childhood cancer survivors., Methods: We assessed Life Years Lost from childhood cancer treatments and their health-related late effects among the French Childhood Cancer Survivors Study, a cohort of 7670 5-year childhood cancer survivors. Using a landmark strategy, we also assessed time-varying effects of risk factors, and how the multi-morbidity affects life years lost., Results: We found subsequent malignant neoplasm (9.0 years [95 %CI: 4.3-13.7]), severe cardiac disease (8.0 years [95 %CI: 1.2-14.9]), and the use of radiotherapy (6.0 years [95 %CI: 4.7-7.3]) to be the highest contributors to Life Years Lost among childhood cancer survivors. We found no interaction impact on life years lost between health related late effects considered., Conclusions: Those findings suggest that radiotherapy is the root cause of early mortality among childhood cancer survivors. Moreover patients experiencing a subsequent malignant neoplasm or a cardiac disease should be monitored closely after the event, as comorbidity is common and causes premature deaths., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Childhood cancer survivors are at increased risk of developing (long-term) skeletal adverse effects, such as osteonecrosis, impaired bone mineral density, and fractures. This paper provides an overview of the current understanding of bone health in these survivors, examining whether it represents a significant concern. It focusses on the challenges of assessing and managing bone health in childhood cancer survivors, highlighting diagnostic pitfalls, methods for accurately identifying those at high risk, and suggested strategies for the surveillance and management of osteonecrosis and impaired bone mineral density. The need for improved surveillance strategies, particularly for high-risk survivors, alongside potential prevention and management options, including pharmacological and lifestyle interventions, is emphasised. Given the lack of consensus on optimal prevention and treatment strategies, the paper emphasises the need for further research to optimise care and improve long-term outcomes for childhood cancer survivors with bone health impairments.

Background: Childhood cancer survivors (CCS) are at risk for medical and psychosocial late effects of their disease and its treatment and are recommended to receive annual follow-ups. Yet, rates of follow-up adherence are suboptimal and may be influenced by the organization and delivery of their healthcare. This research aimed to examine experts' perceptions of facilitators and barriers to healthcare organization and delivery to CCS., Procedure: Thirty-one clinicians and administrators in a comprehensive cancer center's research consortium were interviewed about system-level factors that may promote or deter annual follow-ups among CCS. Interview transcripts were coded and inductively analyzed using a study-specific scheme., Results: Three main themes were identified: (1) healthcare system influences (59%); (2) social determinants of health (25%); and (3) intra/interpersonal factors (16%). Prominent subthemes included age-related changes in the transition of healthcare responsibility that disrupt ongoing CCS care (28.1%), the breadth and quality of psychosocial support available to navigate CCS to follow-up (13.5%), and transportation challenges (24.6%; especially in low-resource areas). In contrast, community trust facilitated follow-up (17.3%)., Conclusion: The system of healthcare was prominent in receipt of follow-up by CCS, and further influenced by social determinants of health and intra/interpersonal factors. Easing transitions of responsibility (from parents to CCS, and acute care to survivorship teams) may be beneficial, especially when social determinants of health obstacles are present. Psychosocial wrap-around care is essential, along with promoting staff awareness of obstacles that CCS encounter in low-resource communities., (© 2024 Wiley Periodicals LLC.)

Purpose: Splenectomy might be a risk factor for valvular heart disease (VHD) in adult Hodgkin lymphoma survivors. As this risk is still unclear for childhood cancer survivors (CCS), the aim of this study is to evaluate the association between treatments affecting splenic function (splenectomy and radiotherapy involving the spleen) and VHD in CCS., Methods: CCS were enrolled from the DCCSS-LATER cohort, consisting of 6,165 five-year CCS diagnosed between 1963 and 2002. Symptomatic VHD, defined as symptoms combined with a diagnostic test indicating VHD, was assessed from questionnaires and validated using medical records. Differences in the cumulative incidence of VHD between CCS who received treatments affecting splenic function and CCS who did not were assessed using the Gray test. Risk factors were analyzed in a multivariable Cox proportional hazards model., Results: The study population consisted of 5,286 CCS, with a median follow-up of 22 years (5-50 years), of whom 59 (1.1%) had a splenectomy and 489 (9.2%) radiotherapy involving the spleen. VHD was present in 21 CCS (0.4%). The cumulative incidence of VHD at the age of 40 years was significantly higher in CCS who received treatments affecting splenic function (2.7%, 95% confidence interval (CI) 0.4%-4.9%) compared with CCS without (0.4%, 95% CI 0.1%-0.7%) (Gray's test, p = 0.003). Splenectomy was significantly associated with VHD in a multivariable analysis (hazard ratio 8.6, 95% CI 3.1-24.1)., Conclusions and Implications: Splenectomy was associated with VHD. Future research is needed to determine if CCS who had a splenectomy as part of cancer treatment might benefit from screening for VHD., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: The burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown., Objectives: We evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors., Methods: We conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression tested associations with impaired cardiorespiratory fitness (peak Vo 2  < 80% predicted)., Results: Survivors (50.7% female) were 9.0 ± 5.8 years at cancer diagnosis and 35.5 ± 8.9 years at evaluation. Prevalence (survivors vs control subjects) of elevated resting heart rate (17.9% vs 7.0%), decreased heart rate reserve (21.7% vs 9.1%), decreased systolic blood pressure response to exercise (25.3% vs 12.6%), and delayed heart rate recovery (24.3% vs 10.6%) was more than 2-fold higher among survivors ( P  < 0.001 for all). Carboplatin (adjusted OR: 2.50; 95% CI: 1.42-4.40; P  = 0.001), chest-directed radiation therapy (adjusted OR: 2.06; 95% CI: 1.52-2.75; P  < 0.001), and cranial radiation (adjusted OR: 1.49; 95% CI: 1.08-2.05; P  = 0.015) were associated with an increased likelihood of having ≥2 measures of autonomic dysfunction. Survivors with ≥2 measures of autonomic dysfunction were at increased risk for impaired cardiorespiratory fitness (adjusted OR: 2.71; 95% CI: 1.82-4.02; P  < 0.001)., Conclusions: Survivors of childhood cancer manifest a higher prevalence of autonomic dysfunction associated with impaired cardiorespiratory fitness., Competing Interests: Support to St. Jude Children’s Research Hospital was provided by the National Cancer Institute grants U01 CA195547 (Drs Hudson and Ness) and R01 CA157838 (Dr Armstrong), the Cancer Center Support (CORE) grant P30 CA21765 (Dr C. Roberts), and the American Lebanese-Syrian Associated Charities (ALSAC). Dr Groarke has received research support from Amgen, Inc, was previously employed by Amgen, Inc; and is currently an employee of Pfizer. Dr Nohria has received research support from Bristol Myers Squibb; and consulting fees from AstraZeneca, Bantam Pharmaceuticals, Regeneron Pharmaceuticals, and Takeda Oncology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Childhood cancer survivors are at high risk for developing new cancers (such as cervical and anal cancer) caused by persistent infection with the human papillomavirus (HPV). HPV vaccination is effective in preventing the infections that lead to these cancers, but HPV vaccine uptake is low among young cancer survivors. Lack of a healthcare provider recommendation is the most common reason that cancer survivors fail to initiate the HPV vaccine. Strategies that are most successful in increasing HPV vaccine uptake in the general population focus on enhancing healthcare provider skills to effectively recommend the vaccine, and reducing barriers faced by the young people and their parents in receiving the vaccine. This study will evaluate the effectiveness and implementation of an evidence-based healthcare provider-focused intervention (HPV PROTECT) adapted for use in pediatric oncology clinics, to increase HPV vaccine uptake among cancer survivors 9 to 17 years of age.Methods: This study uses a hybrid type 1 effectiveness-implementation approach. We will test the effectiveness of the HPV PROTECT intervention using a stepped-wedge cluster-randomized trial across a multi-state sample of pediatric oncology clinics. We will evaluate implementation (provider perspectives regarding intervention feasibility, acceptability and appropriateness in the pediatric oncology setting, provider fidelity to intervention components and change in provider HPV vaccine-related knowledge and practices [e.g., providing vaccine recommendations, identifying and reducing barriers to vaccination]) using a mixed methods approach.Discussion: This multisite trial will address important gaps in knowledge relevant to the prevention of HPV-related malignancies in young cancer survivors by testing the effectiveness of an evidence-based provider-directed intervention, adapted for the pediatric oncology setting, to increase HPV vaccine initiation in young cancer survivors receiving care in pediatric oncology clinics, and by procuring information regarding intervention delivery to inform future implementation efforts. If proven effective, HPV PROTECT will be readily disseminable for testing in the larger pediatric oncology community to increase HPV vaccine uptake in cancer survivors, facilitating protection against HPV-related morbidities for this vulnerable population.Trial Registration: ClinicalTrials.gov Identifier: NCT04469569, prospectively registered on July 14, 2020. [ABSTRACT FROM AUTHOR]

Simple Summary: Due to previous cancer and its treatments, long-term childhood cancer survivors (CCS) are at risk of developing medical comorbidities, as well as socioeconomic vulnerability. Above all, work placement, financial independence, and job satisfaction can represent burdensome areas for some CCS. Regarding this topic, it is important to consider the variety of country-specific educational and vocational systems. The aim of this study is to provide a description of the occupational status of CCS in the Italian socio-economic scenery and to evaluate the association between late effects and unemployment and late effects and job satisfaction. Our data contribute to the description of the different country scenery of work placement for CCS in Europe and agree with previous literature on the impact of severe late effects on occupation. Future research in this field can be focused on interventions to improve CCS in obtaining jobs suitable for their health. Late effects of cancer and its treatments during childhood or adolescence can impact work placement and increase the risk of unemployment. The aim of this study is to describe the work placement and the perceived job and economic satisfaction of long-term childhood cancer survivors (CCS). Jobs have been categorized according to the International Standard Classification of Occupations version 08 (ISCO-08), and satisfaction has been evaluated through the Satisfaction Profile (SAT-P). Out of 240 CCS (female = 98) included: 53 were students, 46 were unemployed and 141 were employed. Within unemployed survivors, 89.13% were affected by late effects (n = 41). The presence of at least one severe late effect was significantly associated with the probability of unemployment (OR 3.21; 95% CI 1.13–9.12, p < 0.050), and having any late effect was inversely related to the level of satisfaction of the financial situation of unemployed CCS (b −35.47; 95% CI −59.19, −11.74, p = 0.004). Our results showed that being a survivor with severe comorbidities has a significantly negative impact on occupation and worsens the perception of satisfaction of economic situations. Routinary follow-up care of CCS should include the surveillance of socioeconomic development and provide interventions, helping them to reach jobs suitable for their health. [ABSTRACT FROM AUTHOR]

Background: Adult survivors of childhood cancer are at increased risk of cardiac late effects.Methods: Using whole-genome sequencing data from 1870 survivors of European ancestry in the St. Jude Lifetime Cohort (SJLIFE) study, genetic variants were examined for association with ejection fraction (EF) and clinically assessed cancer therapy-induced cardiac dysfunction (CCD). Statistically significant findings were validated in 301 SJLIFE survivors of African ancestry and 4020 survivors of European ancestry from the Childhood Cancer Survivor Study. All statistical tests were 2-sided.Results: A variant near KCNK17 showed genome-wide significant association with EF (rs2815063-A: EF reduction = 1.6%; P = 2.1 × 10-8) in SJLIFE survivors of European ancestry, which replicated in SJLIFE survivors of African ancestry (EF reduction = 1.5%; P = .004). The rs2815063-A also showed a 1.80-fold (P = .008) risk of severe or disabling or life-threatening CCD and replicated in 4020 Childhood Cancer Survivor Study survivors of European ancestry (odds ratio = 1.40; P = .04). Notably, rs2815063-A was specifically associated among survivors exposed to doxorubicin only, with a stronger effect on EF (3.3% EF reduction) and CCD (2.97-fold). Whole blood DNA methylation data in 1651 SJLIFE survivors of European ancestry showed statistically significant correlation of rs2815063-A with dysregulation of KCNK17 enhancers (false discovery rate <5%), which replicated in 263 survivors of African ancestry. Consistently, the rs2815063-A was associated with KCNK17 downregulation based on RNA sequencing of 75 survivors.Conclusions: Leveraging the 2 largest cohorts of childhood cancer survivors in North America and survivor-specific polygenomic functional data, we identified a novel risk locus for CCD, which showed specificity with doxorubicin-induced cardiac dysfunction and highlighted dysregulation of KCNK17 as the likely molecular mechanism underlying this genetic association. [ABSTRACT FROM AUTHOR]

Objective: Scan‐related anxiety ("scanxiety") refers to the fear, stress, and anxiety in anticipation of tests and scans in follow‐up cancer care. This study assessed the feasibility of Ecological Momentary Assessment (EMA) for real‐world, real‐time capture of scanxiety using patients' personal smartphone. Methods: Adolescent and Young Adult survivors of childhood cancer were prompted to complete EMA surveys on a smartphone app three times per day for 11 days (33 surveys total) around their routine surveillance scans. Participants provided structured feedback on the EMA protocol. Results: Thirty out of 46 contacted survivors (65%) enrolled, exceeding the preregistered feasibility cutoff of 55%. The survey completion rate (83%) greatly exceeded the preregistered feasibility cutoff of 65%. Participants generally found the smartphone app easy and enjoyable to use and reported low levels of distress from answering surveys. Participants reported significantly more daily fear of cancer recurrence (FCR) and negative affect in the days before compared to the days after surveillance scans, aligning with the expected trajectory of scanxiety. Participants who reported greater FCR and scanxiety using comprehensive measures at baseline also reported significantly more daily FCR around their surveillance scans, indicating validity of EMA items. Bodily threat monitoring was prospectively and concurrently associated with daily FCR, thus warranting further investigation as a risk factor for scanxiety. Conclusions: Findings indicate the feasibility, acceptability, and validity of EMA as a research tool to capture the dynamics and potential risk factors for scanxiety. [ABSTRACT FROM AUTHOR]

Objective: Anticancer treatment may be associated with damage to the reproductive organs and risk of infertility in children with cancer. The collectivist cultural norms of Asian societies may lead Chinese parents to have unique concerns regarding infertility. This qualitative study explored the perceptions of infertility risk and parenthood among parents of childhood cancer survivors in Hong Kong. Methods: Thirteen parents were recruited via a snowball sampling approach from a nongovernmental organization in Hong Kong, representing nine survivors of childhood cancer (leukemia n = 5, solid tumors n = 4). The in-depth semistructured interviews were audiotaped and transcribed verbatim. A thematic analysis was performed using ATLAS.ti 8. Results: Parents mostly perceived their children's fertility status as a distant concern (n = 11, 85%) but emphasized the need for timely information from clinicians when their children reach young adulthood (n = 8, 62%). They reported receiving inconsistent fertility information from different oncology practitioners (n = 9, 69%). A few parents acknowledged that under the influence of the Chinese culture, their children, especially sons, have an important duty to continue the family lineage. However, even if the cancer treatment were associated with infertility risk, almost all parents (n = 12, 92%) stated that it would still not affect their willingness to let their child undergo treatment because survival and cure were still their highest priority. Conclusion: Our findings suggest the need to proactively provide fertility information to parents both during active treatment and when survivors reach reproductive age. Future studies should evaluate the benefits of developing culturally relevant decision-making aids to address parents' informational needs regarding fertility issues. [ABSTRACT FROM AUTHOR]

Purpose: Numerous acute effects of chemotherapeutics on kidney function are well described. However, data on the long-term effects of chemotherapy in the growing population of childhood central nervous system (CNS) tumor survivors is limited. We aimed to evaluate the kidney function of a cohort of long-term CNS tumor survivors treated with different standard chemotherapeutic regimens. Methods: Patients treated for a CNS tumor were prospectively evaluated up to 12 years after completion of their therapy. Examination of kidney function was performed during routine follow-up visits. Blood pressure and blood and urine parameters were analyzed for kidney function evaluation. Glomerular function was assessed by calculating the estimated glomerular filtration rate (eGFR), tubular functions were analyzed by measuring serum electrolytes, bicarbonate and phosphate reabsorption, and proteinuria was assessed by calculating the protein/creatinine ratio and phosphate reabsorption. Results: None of the 65 patients evaluated suffered from clinically relevant kidney impairment (eGFR < 90 mL/min/L, 73 m2). There was no association between chemotherapy dose and eGFR. Only two patients showed mild signs of tubulopathy and 11 patients were diagnosed with elevated blood pressure. Conclusion: With adequate supportive measures, such as sufficient hydration according to chemotherapy protocol guidelines, as well as avoidance or close monitoring of additional nephrotoxic medication, impaired kidney function is rare in CNS tumor survivors treated with standard chemotherapy. Nonetheless, long-term follow-up is essential for early detection of mild impairment of kidney function. [ABSTRACT FROM AUTHOR]

Purpose: Living with late effects can affect young childhood cancer survivors' (CCSs) self-management (SM) abilities. In this study, we explored different approaches to SM of everyday life by young CCS. Methods: This is a sub-study of a larger study on Physical Activity among Childhood Cancer Survivors (the PACCS study). We conducted individual interviews with 22 CCS aged 9 to 18 years who were at least 1 year off-treatment. An hybrid inductive-decductive thematic analysis was used. Results: Three main themes were identified: (1) managing everyday life with fatigue, (2) building self-management competence, and (3) cancer survivor as part of identity. Late effects, especially fatigue, contributed to a perceived ability gap compared to peers, limiting participation in everyday activities. CCS developed new SM skills to overcome such challenges and pushed themselves physically and mentally to master and balance activities and rest to regain energy. CCS changed activities, adapted their expectations, or legitimized their apparent lack of SM skills to regain a sense of self-efficacy. Managing the impact of cancer on relationships with family and friends also required use of SM strategies. Conclusions: The findings expand our currently limited knowledge of young CCS and SM skills they develop to manage everyday life after treatment completion. These, combined with ongoing support from family and peers, "make it work". Implications for Cancer Survivors: The perspectives of young CCS illustrate their SM skills and support needs beyond transitioning off-treatment. Conceptualizing this within follow-up care may contribute to a feeling of mastery and increased satisfaction among CCS. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the physical, mental, and general health among young adult childhood cancer survivors (CCS). SAMPLE & SETTING: This secondary analysis study used data from the Behavioral Risk Factor Surveillance System. The analytic sample included 697 young adult CCS (537 women; 160 men). METHODS & VARIABLES: Chi-square tests of independence were done to compare the rates across cancer survivorship groups on categorical variables. Logistic regression was performed to determine correlates with physical, mental, and general health. RESULTS: Female CCS had a significantly (p < 0.0001) greater number of “no days” in which they reported good physical, mental, and general health compared to male CCS. Female CCS were more likely to experience 30 days of poor physical health compared to male CCS (odds ratio [OR] = 1.8, p < 0.05) when controlling for education, race, and age. Depressed female CCS had higher odds of being in poor physical, mental, and general health (OR = 2.9, 7.6, and 2.6, respectively). IMPLICATIONS FOR NURSING: Findings support the need for continued screening, following published practice guidelines, among young adult female CCS for emotional distress with the use of well-established distress and psychosocial assessment measures. [ABSTRACT FROM AUTHOR]

Purpose: To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET).Methods: This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin' sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00- < 30.75, normosmia ≥ 30.75- < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0-10.Results: Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data (P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively.Conclusion: Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings. [ABSTRACT FROM AUTHOR]

Purpose: During the COVID-19 pandemic, childhood cancer survivors (CCS) may have felt more at risk of having severe consequences of COVID-19 and therefore may have been more likely to defer their health care use. We aimed to assess the risk perceptions of CCS related to COVID-19 (perceived infection risk, perceived risk of experiencing a severe illness in the event of infection), and their forgoing of health care during the year 2020.Methods: In December 2020, we interviewed through an online self-report questionnaire 580 5-year CCS participating in the French Childhood Cancer Survivor Study (FCCSS) cohort. Combining clinical and patient-reported outcomes, we studied predictors of perceived risks related to COVID-19 and forgoing health care.Results: Overall, 60% of respondents stated that COVID-19 could have severe consequences for their health if infected. Survivors with a cardiovascular disease and those who felt more at risk of being infected were more likely to think that COVID-19 could have severe health consequences for them. Moreover, 30% of respondents seeking care declared they had forgone at least one medical appointment in 2020. Forgoing medical appointments was more common among CCS who reported a deterioration in their financial situation in 2020 and those who felt more at risk of being infected.Conclusions: This study shows that a considerable proportion of survivors had forgone medical appointments because of the pandemic; forgoing care was more frequent among the most socioeconomically disadvantaged survivors.Implications For Cancer Survivors: This study presents data hitherto absent in the literature and suggests the need to develop telehealth to ensure appropriate long-term follow-up of CCS. [ABSTRACT FROM AUTHOR]

Personal and social resources may buffer the adverse effects of childhood cancer and its impact on cognition and quality of life. While childhood cancer survivors show domain-specific cognitive difficulties, little is known about their personal and social resources. We therefore investigated personal and social resources and their association with cognitive and quality-of-life outcomes in childhood cancer survivors. Seventy-eight survivors of childhood cancer of different etiologies (aged 7–16 years; ≥one year since treatment) and fifty-six healthy controls were included. Cognitive outcome was assessed by neuropsychological tests; personal and social resources, as well as health-related quality of life, were assessed by standardized questionnaires. In the social resource domain, peer integration was worse in survivors than in controls (puncorr < 0.04, d = 0.33). Personal resources and all other subscales of social resources did not significantly differ between survivors and controls. In survivors, the global resource score was significantly correlated with processing speed (r = 0.39, pcorr < 0.001) and quality of life (parent: r = 0.44; self-report: r = 0.46; pscorr < 0.001). In controls, no association occurred between resources and cognitive outcome, and the correlation between the global resource score and quality of life did not withstand correction for multiple comparison (parent: r = 0.28; self-report: r = 0.40, psuncorr < 0.001). After an adverse event such as childhood cancer, resources might play a particularly buffering role on cognitive performance and quality of life (when compared to the everyday life of healthy controls). This highlights the importance of interventions that strengthen the resources of children and their families, even years after cancer. Such resource-focused intervention could help to counteract long-term sequelae in cognitive outcomes and health-related quality of life. [ABSTRACT FROM AUTHOR]

Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations.

Abstract Background Sleep disruption is a prevalent symptom reported by survivors of childhood cancer. However, there is no validated instrument for assessing this symptom in this population group. To bridge the literature gap, this study translated and adapted the Pittsburgh Sleep Quality Index (PSQI) for Hong Kong Chinese cancer survivors and examined its psychometric properties and factor structure. Methods A convenience sample of 402 Hong Kong Chinese childhood cancer survivors aged 6–18 years were asked to complete the Chinese version of the PSQI, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Fatigue Scale-Child (FS-C)/Fatigue Scale-Adolescent (FS-A), and Pediatric Quality of Life Inventory (PedsQL). To assess known-group validity, 50 pediatric cancer patients and 50 healthy counterparts were recruited. A sample of 40 children were invited to respond by phone to the PSQI 2 weeks later to assess test–retest reliability. A cutoff score for the translated PSQI used with the survivors was determined using receiver operating characteristic analysis. Results The Chinese version of the PSQI had a Cronbach alpha of 0.71, with an intraclass correlation coefficient of 0.90. Childhood cancer survivors showed significantly lower mean PSQI scores than children with cancer, and significantly higher mean scores than healthy counterparts. This reflected that childhood cancer survivors had a better sleep quality than children with cancer, but a poorer sleep quality than healthy counterparts. We observed positive correlations between PSQI and CES-DC scores and between PSQI and FS-A/FS-C scores, but a negative correlation between PSQI and PedsQL scores. The results supported that the Chinese version of the PSQI showed convergent validity. Confirmatory factor analysis showed that the translated PSQI data best fit a three-factor model. The best cutoff score to detect insomnia was 5, with a sensitivity of 0.81 and specificity of 0.70. Conclusion The Chinese version of the PSQI is a reliable and valid instrument to assess subjective sleep quality among Hong Kong Chinese childhood cancer survivors. The validated PSQI could be used in clinical settings to provide early assessments for sleep disruption. Appropriate interventions can therefore be provided to minimize its associated long-term healthcare cost. Trial registration This study was registered in ClinicalTrials.gov with the reference number NCT03858218.

BackgroundEwing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown.MethodsThis study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03).ResultsAmong 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively.ConclusionsWith extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551-60. © 2017 American Cancer Society.

Summary: Background: Population-level estimates of hospitalisation risk in children are currently limited. The study aims to characterise morbidity patterns in all children, focusing on childhood cancer survivors versus children without cancer. Methods: Employing hospital records of children aged

Aim: The aim of the study was to investigate how young adult survivors of childhood cancer used an online discussion forum as part of a web-based psycho-educational intervention. Specifically, we aimed to characterize users of the discussion forum, investigate how they used the discussion forum (type of usage) and content of the posted messages. Methods: This study is a part of a randomized controlled trial, Fex-Can Childhood RCT. Participants with self-reported sexual dysfunction or fertility-related distress were drawn from a population-based national cohort. Sociodemographic and clinical characteristics of the intervention group (n = 322) and data on usage of the discussion forum were analysed with descriptive statistics and compared between subgroups. Messages posted in the online discussion forum were analysed with qualitative thematic analysis. Results: Approximately half (48 %) of participants in the intervention group accessed the discussion forum and most of them (76 %) without writing own posts. Users of the discussion forum did not statistically differ in sociodemographic or clinical characteristics from the rest of the intervention group. The 97 written posts, written by 38 individuals, were mainly descriptions of own experiences and thoughts and concerned three themes: A changed body, Concerns around family building and Longing for support. Peer-support and interaction between participants were seen in some forum threads and the ‘like’-function was frequently used, demonstrating engagement and activity. Participants expressed that they felt affinity with and appreciated sharing own experiences and to recognize themselves in others' stories. Conclusions: A discussion forum as part of a web-based intervention appears to be a valuable component by giving participants an opportunity to share intimate experiences and concerns related to surviving cancer. Trial registration: ISRCTN Registry, trial number: 33081791 (registered on November 27, 2019).

ObjectivesWe aimed to compare cardiovascular disease (CVD) risk factors in childhood cancer survivors (CCS) with age- and sex-stratified reference material and examine the association between physical activity (PA) intensities and CVD risk factors in CCS.Materials and methodsWithin the cross-sectional, multicenter Physical Activity in Childhood Cancer Survivors (PACCS) study, we collected data on CVD risk factors [VO2–peak (mL⋅kg–1⋅min–1), body mass index (BMI, kg/m2), systolic blood pressure (SBP, mmHg), and total-cholesterol/HDL-cholesterol (Total/HDL)] among CCS aged 9–18 years. CVD risk factors were compared to references with immediate t-tests. We transformed CVD risk factors into z-scores based on international references and generated an individual CVD risk score: [inverse ZVO2–peak + ZBMI + ZSBP + ZTotal/HDL)/4]. Multivariable mixed linear regression models were used to analyze the associations between device-measured PA intensities and CVD risk factors.ResultsWe included 157 CCS aged on average 13.4 years at inclusion and 8.2 years from diagnosis. Male CCS had lower VO2–peak compared to references (45.4 vs. 49.4 mL⋅kg–1⋅min–1, P = 0.001), higher diastolic BP (67 vs. 63 mmHg, P < 0.001), lower HDL (1.35 vs. 1.44 mmol/L, P = 0.012), as well as a tendency to higher CVD risk score (z-score=0.14 vs. 0.00, P = .075). Female CCS’ CVD risk factors were comparable to references. Vigorous-intensity PA (VPA) was associated with CVD risk factors. A 10-min increase in VPA was associated with higher VO2–peak (β = 4.9, 95% CI, 2.1–7.7), lower Total/HDL (β = −0.3, 95% CI, −0.6 to −0.1) and a lower CVD risk score (β = −0.4, 95% CI, −0.6 to −0.2).ConclusionMale adolescent CCS had less favorable values of CVD risk factors compared to references. VPA in adolescent CCS is associated with clinically meaningful favorable values of CVD risk factors.

Background Plasma biomarkers may aid in the detection of anthracycline‐related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long‐term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction

Abstract Background A debilitating late effect for childhood cancer survivors (CCS) is cancer-related fatigue (CRF). Little is known about the prevalence and risk factors of fatigue in this population. Here we describe the methodology of the Dutch Childhood Cancer Survivor Late Effect Study on fatigue (DCCSS LATER fatigue study). The aim of the DCCSS LATER fatigue study is to examine the prevalence of and factors associated with CRF, proposing a model which discerns predisposing, triggering, maintaining and moderating factors. Triggering factors are related to the cancer diagnosis and treatment during childhood and are thought to trigger fatigue symptoms. Maintaining factors are daily life- and psychosocial factors which may perpetuate fatigue once triggered. Moderating factors might influence the way fatigue symptoms express in individuals. Predisposing factors already existed before the diagnosis, such as genetic factors, and are thought to increase the vulnerability to develop fatigue. Methodology of the participant inclusion, data collection and planned analyses of the DCCSS LATER fatigue study are presented. Results Data of 1955 CCS and 455 siblings was collected. Analysis of the data is planned and we aim to start reporting the first results in 2022. Conclusion The DCCSS LATER fatigue study will provide information on the epidemiology of CRF and investigate the role of a broad range of associated factors in CCS. Insight in associated factors for fatigue in survivors experiencing severe and persistent fatigue may help identify individuals at risk for developing CRF and may aid in the development of interventions.

Background: The survivors of childhood cancer suffer from a number of long-term side effects. These include atherosclerosis and cardiovascular diseases (CVDs) that develop earlier in adulthood than in the rest of the population. The aim of this study was to identify prognostic factors of developing atherosclerosis before the development of symptomatic CVD. Methods: A total of 141 children that were 7–18 years old were examined; there were 116 survivors of childhood malignancies (hematopoietic and lymphoproliferative malignancies—52; neuroblastoma—22; Wilms tumor—24; other solid tumors—18) and 25 healthy controls. Anthropometric measurements, blood pressure measurements, ultrasonography of the abdomen, echocardiography, and laboratory tests were performed. Results: There were no significant differences in gender distribution, time from the end of the treatment, weight, BMI, prevalence of central obesity, blood pressure and resistive index of the renal arteries, lipid profile, or glucose and fibrinogen levels. Patients with solid tumors had a significantly lower height and worse renal function. Patients with hematological malignancies significantly presented the lowest shortening fraction of the left ventricle. The salusin β levels were significantly higher in the control group than among the patients. Conclusions: The type and severity of side effects are closely related to the type of neoplasm and the treatment that has been undergone. Careful observation and regular follow-up are necessary.

Background: Cardiovascular (CV) diseases are a cause of increased long-term morbidity and mortality in childhood cancer survivors (CCSs) treated with anthracyclines. These drugs may affect not only the heart, but also the vascular system. Left ventricular-arterial coupling (LVAC) represents a reliable parameter of altered ventricular and vascular performance, with validated prognostic value and never investigated in this setting. Aim of this study was to assess, in CCSs and matched controls, LVAC changes, performed with different echocardiographic modalities, and their relationship with endothelial function. Methods: Twenty survivors treated with anthracyclines for childhood malignancies and a matched control group of 20 healthy subjects were enrolled. Arterial elastance (Ea), end-systolic elastance (Ees), Ea/Ees ratio, as well as three-dimensional (3D) LVAC (assessed by measurement of End Systolic Volume [ESV]/Stroke Volume [SV] ratio) were performed at rest. Endothelial function was evaluated by measurement of flow-mediated dilatation (FMD) of the brachial artery. Results: 3D SV and 3D ESV/SV ratio resulted respectively significantly lower and higher in CCSs than in controls, while Ea, Ees and Ea/Ees ratio were not different among groups. A positive correlation between 3D ESV/SV ratio and cumulative anthracycline doses, as well as with time after drug exposure were also found. Mean FMD was similar in CCSs and controls (8.45 ± 1.79 versus 9.41 ± 3.41, p = 0.34). Conclusions: In conclusion, conventional LVAC parameters were not shown to be significantly different between CCSs and controls; however, 3D SV and LVAC were significantly impaired in our population. In these patients, endothelial function was comparable to controls. Larger validation studies are therefore needed.

Objectives: This study provided information about sleep disruption, particularly its prevalence and severity among Hong Kong Chinese childhood cancer survivors. Additionally, we identified the factors influencing sleep disruption and explored how fatigue, depressive symptoms and physical activity (PA) affect sleep disruption. Methods: Four hundred two survivors 6–18 years old and 50 age‐ and gender‐matched healthy counterparts were assessed for depressive symptoms, fatigue, PA and subjective sleep quality. Demographic and clinical information were collected. Multiple logistic regression analyses were conducted to identify any factors contributing to poor sleep. Results: Mean scores of depressive symptoms, fatigue for children and that for adolescents, and PA in survivors were 16.1 (SD = 11.1), 24.6 (SD = 10.3), 27.7 (SD = 7.8), and 3.08 (SD = 2.9), respectively. 44.8% of the survivors were poor sleepers, which was more that in healthy counterparts. The three most common sleep problem were prolonged sleep latency (31.9%), daytime dysfunction (23.4%), and sleep disturbance (22.9%). The time since last treatment (children: AOR = 0.54, 95% CI = 0.30–0.96, p = 0.04; adolescents: AOR = 0.80, 95% CI = 0.70–0.92, p < 0.01) and PA levels (children: AOR = 0.46, 95% CI = 0.260–0.82, p = 0.01; adolescents: AOR = 0.70, 95% CI = 0.49–0.98, p = 0.04) were negatively associated with sleep disruption, while depressive symptoms (children: AOR = 1.31, 95% CI = 1.04–1.64, p = 0.02; adolescents: AOR = 1.07, 95% CI = 1.01–1.13, p = 0.03), fatigue (children: AOR = 1.15, 95% CI = 1.00–1.31, p = 0.04; adolescents: AOR = 1.08, 95% CI = 1.02–1.15, p = 0.01), number of treatment received (children: AOR = 16.56, 95% CI = 1.27–216.82, p = 0.03; adolescents: AOR = 7.30, 95% CI = 2.36–22.56, p < 0.01), and co‐sleeping (children: AOR = 29.19, 95% CI = 1.65–511.57, p = 0.02; adolescents: AOR = 4.63, 95% CI = 1.22–17.61, p = 0.02) were positively associated with sleep disruption. Conclusion: Physical activity made the largest contribution to reduce sleep disruption. It is crucial to advocate for the adoption and maintenance of PA in survivorship. [ABSTRACT FROM AUTHOR]

Background: Compared with the general population, childhood cancer survivors (CCS) could be at greater risk of psychological distress following the emergence of the COVID-19 pandemic. Purpose: This cross-sectional study assessed the psychological consequences of COVID-19 on the mental health of CCS. Design and participants: In December 2020, we interviewed through an online self-report questionnaire, 580 5-year CCS participating in the French Childhood Cancer Survivor Study (FCCSS) cohort. Methods: We first compared the mental health score of CCS with that observed in the French general population of the same age and gender. Subsequently, we studied predictors of the mental health score of CCS. Results: External comparisons revealed that the mental health score of CCS was similar to that of the general population. Among CCS, almost 42% stated that their psychological state had been worse during the lockdown. Predictors of poorer mental health included, among others, female gender, reporting a change in the occupational situation, having a relative who had been hospitalized or had died following COVID-19, and a greater perceived infection risk. Interpretation and Implications: Given the pre-existing vulnerability of some CCS to mental distress, the additional psychological consequences of COVID-19 in vulnerable survivors should receive attention from health care providers. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advances in cancer treatment have led to improved survival, with an exponential increase in sequelae among survivors. Around 50% of survivors will experience at least one hormonal disorder, with radiotherapy, hematopoietic stem cell transplantation, and alkylating chemotherapy being the most frequently related. Therefore, lifelong monitoring of childhood cancer survivors at risk is paramount. With this review, we describe in detail the most prevalent endocrine sequelae, considering new approaches such as proton beam therapy and immune-related endocrinopathies with the advent of precision oncology treatment. We hope to encourage oncologists and endocrinologists to develop early detection guidelines that minimize sequelae and have a positive impact on their quality of life. Childhood cancer management has improved considerably over the years, leading to a significant improvement in survival of up to 80%. However, childhood cancer survivors are at the highest risk of developing sequelae resulting from treatment, with endocrine complications being frequently observed among survivors. Multiple predisposing factors for endocrine sequelae have been identified, including age at diagnosis, treatment received, radiation, tumor type, and genetic polymorphisms, which could explain the individual predisposition to develop drug toxicity. Novel agents targeting tumor growth and immune checkpoint inhibitors have recently become the cornerstone for the treatment of different cancers, triggering a myriad of immune-related endocrinopathies. Endocrine sequelae of cancer therapy will have an impact on not only childhood but also on the survival and quality of life of these highly complex patients. Therefore, lifelong monitoring of childhood cancer survivors at risk of endocrine diseases is paramount. Encouraging oncologists and endocrinologists to develop new follow-up and early detection guidelines that minimize sequelae among these patients has become a priority, promoting integration between pediatric and adult units since many sequelae may manifest only after years to decades of follow-up. [ABSTRACT FROM AUTHOR]

Purpose: Metabolic syndrome (MetSyn) is an important late effect of childhood cancer. The combination of rising obesity and high prevalence of under-nutrition at diagnosis makes this a unique population to study in LMIC (lower middle-income countries).Methods: Children ≤ 18 years of age at cancer diagnosis, in a single center in a LMIC, who were disease free and had completed treatment at least 2 years prior to study were included. MetSyn was defined using International Federation for Diabetes criteria for Asian Indians. Logistic regression analyses were carried out to evaluate the influence of various risk factors, including delta BMI (increase in body mass index from diagnosis to evaluation), on MetSyn.Results: A high prevalence of MetSyn (12.2%), central obesity (33%), and dyslipidemia (61.8%) were found in a cohort of 500 Asian Indian childhood cancer survivors (CCS) at a median follow-up age of 17 years. Multivariable analysis revealed older age at diagnosis ≥ 10 years, OR 2.9 (1.6-5); longer survival duration ≥ 10 years, OR 2.2 (1.3-3.8); high BMI at diagnosis, OR 3.2 (1.5-6.9); and large delta BMI ≥ 50, OR 3.15(1.7-5.9) to be independent predictors of MetSyn. Patients who were underweight or normal at diagnosis with large delta BMI ≥ 50 had very high odds (OR, 12.5, 1.7-92) of developing MetSyn compared to those with lower delta BMI.Conclusions and Implications For Cancer Survivors: A high prevalence of MetSyn was observed in CCS with early age at onset. Timely screening and early intervention are proven to be beneficial and delta BMI could be a useful screening tool for LMIC. [ABSTRACT FROM AUTHOR]