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Objective: To characterize the prevalence and predictors of concerns regarding future health and cancer risk among siblings of childhood cancer survivors. Methods: This study reports longitudinal data (baseline and follow-up) from 3969 adult siblings (median age = 29 [range 18–56] years) of long-term survivors of childhood cancer (median time since diagnosis 19.6 [9.6–33.8] years). Self-reported future health and cancer risk concerns (concerned vs not concerned) were assessed. Demographics and health data reported by both the siblings and their matched cancer survivors were examined as risk factors for health concerns using multivariable logistic regression. Results: Percentage of siblings reporting future health and cancer risk concerns, respectively, decreased across decade of survivors' diagnosis: 1970s (73.3%; 63.9%), 1980s (67.2%; 62.6%), and 1990s (45.7%; 52.3%). Risk factors associated with future health concerns included sibling chronic health conditions (grade 2 Odds Ratio [OR]=1.57, 95% CI: 1.12–2.20; grades 3–4 OR=1.86, 95% CI: 1.18–2.94; compared to less than grade 2). Risk factors associated with future cancer concerns included sibling chronic health conditions (grade 2 OR=1.43, 95% CI: 1.05–1.94; grades 3–4 OR=1.64, 95% CI: 1.09–2.47; compared to less than grade 2). Conclusions: Sibling concerns regarding future health and cancer have diminished in recent decades. There are subgroups of siblings that are at-risk for future health and cancer risk concerns. Implications for Cancer Survivors: Routine screening of concerns in at-risk siblings of survivors of childhood cancer may benefit the siblings of cancer survivors. These individuals may benefit from early interventions during diagnosis and treatment of their siblings. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors (CCSs) may suffer from a multitude of health impairments, resulting in a compromised quality of life (QoL). This review's objective was to examine CCSs' adherence to supervised exercise training interventions and the impact of these interventions on health outcomes. Methods: The following databases were searched in May 2022: PubMed, Embase, Cochrane Library, and Web of Science. The included studies were limited to randomized controlled trials (RCTs), published in English involving CCSs aged 18 years and below. Results: Nine RCTs (n = 642 participants) were included in the systematic review, and seven of them (n = 551 participants) were included in the meta-analysis. Both the mean retention rate and adherence to the supervised exercise interventions were 87%. Supervised exercise interventions significantly improved muscle strength (standardized mean difference (SMD) = 1.42, p = 0.03), level of daily physical activity (SMD = 1.05, p < 0.001), body mass index (BMI) (mean difference (MD) = 1.06, p = 0.03), and fatigue (SMD = −0.44, p < 0.001), while there was no statistical significance in the quality of life (QoL) (SMD = 0.21, p = 0.20). Conclusions: The adherence of CCSs to supervised exercise interventions is high, and supervised exercise interventions are safe and effective. [ABSTRACT FROM AUTHOR]

Simple Summary: The most common malignancy diagnosed in childhood is acute lymphoblastic leukemia (ALL). With significant advances in ALL treatment and excellent supportive care, overall survival is now up to 90%, depending on the risk group. As a result, the survivor population is growing significantly. At the same time, it is observed that survivors experience many health problems that substantially reduce their quality of life. Emerging evidence suggests that the increased susceptibility to multiple disorders related to accelerated aging in CCS may be attributed to chronic inflammation. Therefore, this study aimed to investigate whether asymptomatic survivors of ALL have a biological phenotype of accelerated cellular senescence early in life. For this purpose, a broad panel of 51 cytokines was tested. We show that survivors after ALL treatment have an inflammatory profile associated with premature cellular aging. Factors that increase the risk of immunological alterations include younger age at diagnosis, high-risk protocols, and radiation therapy. Childhood acute lymphoblastic leukemia (ALL) survivors are at higher risk of developing many late effects later in life. They experience multiple health problems that have significant public health implications, such as frailty, premature onset of lifestyle diseases, and second tumors. There is some evidence that chronic inflammation causes accelerated aging in childhood cancer survivors; however, the available data are very limited. The aim of the study was to evaluate the broad panel of cytokines among asymptomatic ALL survivors after anticancer treatment. The study included 56 subjects with a mean age of 16.11 ± 3.98 years. The commercially available Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay and Bio-Plex TGF-β Assay were used for simultaneous determination of 48 cytokines and 3 isoforms of TGF-β. Among 51 tested cytokines, the levels of 33 were statistically significantly higher in ALL survivors than in the control group (p < 0.05). Increased levels of pro-inflammatory cytokines, including the IL-1 family (IL-1 β, IL-1Ra; p < 0.0001), IL-6 (p < 0.001), IL-17 (p < 0.001), IL-18 (p < 0.05), TNFα (p < 0.01), IFNα2 (p < 0.05), and IFNγ (p < 0.01), were found elevated in the entire study group, compared with the controls. Subjects treated previously according to the high-risk protocol had higher IL-18 levels than low- and intermediate-risk groups (p < 0.05). Elevated levels of IL-1ra, IL-6, IL-12 (p70), IL-17, LIF, M-CSF, CSF, and VEGF were found in ALL survivors treated before the age of 5, compared with subjects treated over 5 years of age (p < 0.05). Moreover, individuals who received radiotherapy presented elevated levels of both IL-18 (p < 0.05) and MIG (p < 0.05). In conclusion, we found that young asymptomatic survivors after ALL treatment demonstrated a biological profile of complex low-grade chronic inflammation. [ABSTRACT FROM AUTHOR]

Purpose: With increasing numbers of childhood cancer survivors (CCS), it is important to identify the impact of cancer and CCS' needs for support services that can mitigate the long-term impact on psychosocial wellbeing, including health-related quality of life (HRQOL). We aimed (1) to describe survivors' wellbeing, impact of cancer, and supportive care needs and (2) to determine how socio-demographic or clinical characteristics and impact of cancer relate to survivors' unmet needs. Method: In this mixed methods study, a quantitative survey was used to assess HRQOL, psychological distress, impact of cancer, and supportive care needs. Qualitative interviews were conducted to explore the meaning of wellbeing, health, and impact of cancer. Results: Overall, 69 CCS participated in the survey of which 28 participated in qualitative interviews (aged ≥ 18 years, diagnosed with cancer ≤ 18 years). Few CCS (13%) reported poor physical HRQOL, but almost half reported poor mental HRQOL (49%) and psychological distress (42%). Health was considered to encompass both: physical and emotional aspects of wellbeing. Cancer positively impacted CCS' ability to care and attitude towards life, whereas relationships and insurance were negatively impacted. Risks for unmet needs increased in CCS with self-reported low health status, late effects, psychological distress, with older age at study or longer time since end of treatment. Conclusion: In our study, many CCS experienced various psychosocial, psychological and informational unmet needs, indicating that survivors' needs are currently not duly addressed. Current efforts to provide supportive psychosocial care in Switzerland should be further operationalized to provide adequate support. [ABSTRACT FROM AUTHOR]

This multi-center cohort-study examined late mortality among 6,165 Dutch five-year childhood cancer survivors diagnosed 1963–2001. Clinical details and cause of death were based on medical records. Mortality was 12-fold that of the general population, with 51.3 additional deaths per 10,000 person-years (21.9 yrs median follow-up). Cumulative mortality 15 yrs post-diagnosis was 6.9%, predominantly from late recurrences; thereafter the absolute contribution of other health outcomes increased. Cumulative all-cause and recurrence-related mortality were highest for Central Nervous System and bone tumor survivors. All-cause, but not subsequent tumor and circulatory disease-related cumulative mortality, was highest for patients diagnosed 1963–1979 vs. later (p-trend <0.001). [ABSTRACT FROM AUTHOR]

Purpose: Late effects in childhood cancer survivors are a major cause of morbidity and mortality. The objective was to establish knowledge about the disease, late effects, self-care practices, application of health knowledge/education, sources of information, and biopsychosocial impact of cancer, and compare the results of Chile and Croatia.Methods: One-hundred-and-seventy-one, 5-year survivors who were treated for leukemia or non-Hodgkin's lymphoma responded to a questionnaire (119 in Chile and 52 in Croatia). The questionnaire was reviewed by BFM-ELTEC.Results: Health knowledge about past diagnosis and general treatment had 96% Chilean and 85% Croatian survivors. Ninety percent of Chilean and 73% of Croatian survivors were unaware of possible late effects, and half did not know which specialist to visit for follow-up. Forty-six percent of Chilean and 35% of Croatian survivors knew about healthy lifestyles, but most did not practice them. The 74% of Chileans and 87% of Croatian survivors recalled having received health education during treatment. About 50% of survivors in both groups were afraid or anguish, but it was also a growth experience for 60% of Chilean and 42% of Croatian survivors. Eighty-seven percent Chilean and 77% Croatian survivors considered themselves physically independent, while 76% and 75% felt psychologically independent, respectively.Conclusion: A significant lack of knowledge about the specific treatment, late effects, and future health in both countries was detected. They did not achieve significant learning with the education received. Psychological sequelae were found that are important to prevent. [ABSTRACT FROM AUTHOR]

Thyroid dysfunction has been observed in childhood cancer survivors (CCSs) who have undergone hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the thyroid function of 54 CCSs who underwent HSCT and were referred to our endocrinology department at Chiba Children's Hospital between January 1, 2008, and December 31, 2019. Three patients developed autoimmune thyroid disease (AITD) after HSCT. Two of these patients had Graves' disease (GD), and the third had autoimmune thyroiditis. The association between HSCT and AITD remains unclear. All three patients had chronic graft versus host disease (GVHD). AITD was reported to be induced by the transmission of abnormal T or B lymphocyte clones from the donor to the recipient. One patient with GD was treated with a high dose of anti-thymocyte globulin (ATG). Some studies have reported that ATG is associated with a risk of severe T cell depletion and GD onset. In conclusion, CCSs who received HSCT rarely developed AITD. We suggest that CCSs treated with ATG and/or experiencing an onset of chronic GVHD should be carefully monitored for thyroid function because it might reveal AITD. [ABSTRACT FROM AUTHOR]

Breast cancer is a well-recognised late adverse effect in female childhood cancer survivors (CCSs), especially after chest radiotherapy; information on subsequent male breast cancer (SMBC) is limited. We summarised the existing evidence on SMBC after childhood cancer in a systematic review and investigated the risk of SMBC among males in a Pan-European cohort. We searched Medline/PubMed for cohort studies and case reports/series that assessed SMBC after childhood cancer (≤21 years). Furthermore, we analysed data on SMBC in the PanCareSurFup cohort, reporting standardised incidence ratios (SIRs), absolute excess risks (AERs), and 5- and 10-year survival rates. The systematic review included 38 of 7080 potentially eligible articles. Cohort-specific SMBC frequencies were 0–0.40% (31 studies). SMBC occurred after a follow-up ranging from 24.0 to 42.0 years. Nine case reports/series described 11 SMBC cases, occurring 11.0–42.5 years after primary childhood cancer. In the PanCareSurFup cohort (16 SMBC/37,738 males; 0.04%), we observed a 22.3-fold increased risk of SMBC relative to the general male population (95% CI 12.7–36.2; absolute excess risk/100,000 person-years: 2.3, 95% CI 1.3–3.7). The five- and ten-year survival rates after SMBC diagnosis were 60.3% (95% CI 35.6%–85.0%) and 43.0% (95% CI 16.1%–69.9%), respectively. Clear evidence of risk factors did not emerge from these comprehensive efforts. Compared to the general population, male CCSs have an elevated risk of developing subsequent breast cancer, although the absolute risk is low. Health care providers should be aware of this rare yet serious late effect; male CCSs with symptoms potentially related to SMBC warrant careful examination. • Male childhood cancer survivors have an elevated risk of developing breast cancer. • The absolute risk of male breast cancer in childhood cancer survivors is low. • Risk factors of subsequent male breast cancer remain unclear. • Survivors and their caregivers should be aware of this rare yet serious disease. • Male survivors with breast cancer-related symptoms warrant careful examination. [ABSTRACT FROM AUTHOR]

Owing to advances in treatment modalities and supportive care, overall survival rates have reached up to 90% among children with acute lymphoblastic leukemia (ALL). However, due to the underlying illness and therapy, they are at a greater risk of developing lifestyle diseases. Hence, special attention is paid to early detection of the components of metabolic syndrome (MetS). This study aimed at investigating the association of plasma levels of nine diabetes markers with being overweight and components of MetS in ALL survivors. The study included 56 subjects with mean age of 12.36 ± 5.15 years. The commercially available Bio-Plex Pro Human Diabetes 10-Plex Panel kit was used to evaluate levels of diabetes biomarkers. ALL survivors presented statistically higher concentrations of GIP (p = 0.026), glucagon (p = 0.001), leptin (p = 0.022), and PAI-1 (p = 0.047), whereas the concentration of ghrelin was lower (p < 0.001) compared to the control group. Moreover, subjects within normal BMI range showed higher GIP (p = 0.005) and lower ghrelin concentration (p < 0.001) compared to healthy peers. At least one risk factor of MetS was present in 58.9% of participants, who showed significantly higher levels of C-peptide (p = 0.028), leptin (p = 0.003), and PAI-1 (p = 0.034) than survivors who did not meet any MetS criteria. In conclusion, ALL survivors are at greater risk of disturbances in carbohydrate metabolism. Understanding the pathogenesis and applicability of diabetes markers is crucial for developing strategies to prevent metabolic syndrome in ALL survivors. [ABSTRACT FROM AUTHOR]

Purpose: The COVID pandemic has greatly impacted cancer care, with survivorship care being accorded low priority. We aimed to assess the impact of the COVID pandemic on survivorship services at our centre, as well as on survivors of childhood cancer (CCS).Methods: We analyzed the trends in survivorship care at our centre from March 2020 to June 2021 compared to previous years. We also conducted an online survey of adolescent and young adult (AYA-CCS) following up at the After Completion of Treatment Clinic, Mumbai, to assess the impact of the COVID pandemic and ensuing restrictions on our cohort of survivors. Sibling responses were used as comparator (CTRI/2020/11/029029).Results: There was a decrease in in-person follow-ups and increase in remote follow-ups over the first few months of the pandemic. While in-person visits steadily increased after October 2020 and reached pre-pandemic numbers, distant follow-ups continue to be higher than pre-pandemic. Evaluable responses from the survey of 88 AYA-CCS and 25 siblings revealed new-onset health concerns in 29.5% of AYA-CCS, missed follow-up visit in 52% and varying degrees of mental health issues in 12.5%. While most survivors were able to cope with the stresses of the pandemic, 20% of siblings reported being unable to cope.Conclusions: Survivorship services continue to be affected well into the pandemic, with increased use of distant follow-ups. While AYA-CCS experienced significant physical, mental health issues and psychosocial concerns as a result of the COVID pandemic, they coped better than siblings during this stressful time, possibly due to multiple, holistic support systems including family, peer support groups and healthcare team. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCS) experience short- and long-term side effects from cancer treatment that often impair functional capacity. Inspiratory muscle weakness is a potential mechanism for reduced functional capacity. The objective of this pilot study was to examine the relationship between inspiratory muscle strength and functional capacity in 10 CCS. Inspiratory muscle strength was measured by maximal inspiratory pressure (MIP) while functional capacity was measured by the two-minute walk test (2MWT), the physiological cost index and hemodynamic response to exercise according to changes in heart rate, blood pressure and rate-pressure product (RPP). Overall, MIP and 2MWT distance were below predicted values. Hemodynamic responses to the 2MWT were consistent with little variation, except for elevated diastolic blood pressure (DBP) response. MIP had significant relationships with resting DBP (Spearman's rank correlation coefficient [rs] = −0.70; p = 0.03) and DBP response (rs = 0.72; p = 0.02). Time since completion of cancer treatment had a significant positive relationship with RPP response (rs = 0.67; p = 0.03). Inspiratory muscle weakness in childhood cancer could be an indicator of skeletal muscle dysfunction and should be considered when symptoms of dyspnea or poor functional capacity arise. Inspiratory muscle strength was found to be related to changes in blood pressure in CCS. Future studies should further investigate these relationships and the impact of inspiratory muscle training on hemodynamics and functional capacity in CCS. [ABSTRACT FROM AUTHOR]

Treatment of malignant childhood posterior fossa tumors (CPFT) often includes surgical resection and craniospinal radiotherapy (CSI). Nasopharyngeal tumors in childhood (CNPHT) are often treated with surgery and radiotherapy (RT), leading to incidental brain irradiation. RT to the developing brain is associated with risks for cognitive impairments. We studied cognitive functioning, health-related quality of life (HRQOL), fatigue, and psychological distress, in adult survivors of CPFT and CNPHT, representing two groups, which had received high and low radiation dose-exposure to the brain, respectively. Cognitive tests were used to compare CPFT (n = 12) and CNPHT (n = 7) survivors to matched healthy controls (n = 28). HRQOL data was compared to the general population (GP) (n = 1415–1459). Average follow-up was 23 (CPFT) and 19 years (CNPHT). CPFT survivors had significant deficits in all cognitive domains. CNPHT survivors showed results below the control group but differed statistically only on one executive test. HRQOL-ratings indicated that both groups had similar self-reported cognitive problems. CPFT survivors reported more emotional problems and fatigue. Anxiety was seen in both CPFT and CNPHT survivors. This study confirmed long-term cognitive sequelae after RT in adult survivors of CPFT,and possible RT-induced cognitive deficits in adult CNPHT survivors. [ABSTRACT FROM AUTHOR]

Purpose: Echocardiographic surveillance for asymptomatic left ventricular systolic dysfunction (ALVSD) is advised in childhood cancer survivors (CCS), because of their risk of heart failure after anthracycline treatment. ALVSD can be assessed with different echocardiographic parameters. We systematically reviewed the prevalence and risk factors of late ALVSD, as defined by contemporary and more traditional echocardiographic parameters. Methods: We searched databases from 2001 to 2020 for studies on ≥ 100 asymptomatic 5-year CCS treated with anthracyclines, with or without radiotherapy involving the heart region. Outcomes of interest were prevalence of ALVSD—measured with volumetric methods (ejection fraction; LVEF), myocardial strain, or linear methods (fractional shortening; FS)—and its risk factors from multivariable analyses. Results: Eleven included studies represented 3840 CCS. All studies had methodological limitations. An LVEF < 50% was observed in three studies in 1–6% of CCS, and reduced global longitudinal strain (GLS) was reported in three studies in 9–30% of CCS, both after a median follow-up of 9 to 23 years. GLS was abnormal in 20–28% of subjects with normal LVEF. Abnormal FS was reported in six studies in 0.3–30% of CCS, defined with various cut-off values (< 25 to < 30%), at a median follow-up of 10 to 18 years. Across echocardiographic parameters, reported risk factors were cumulative anthracycline dose and radiotherapy involving the heart region, with no 'safe' dose for ALVSD. Conclusions: GLS identifies higher prevalence of ALVSD in anthracycline-treated CCS, than LVEF. Implications for Cancer Survivors: The diagnostic and prognostic value of GLS should be evaluated within large cohorts. Protocol registration: PROSPERO CRD42019126588 [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCS) are at risk for developing complications of the treatment and the disease both early and later in life. These complications may be aggravated with increasing age of the survivor. Adequate surveillance according to guidelines for follow-up is essential for optimal care of CCS both as children and as adults. Involving and educating the survivors is essential to increase awareness and to provide them with the necessary knowledge to manage their own health. Health care authorities and society as a whole has a responsibility to make sure such a follow-up is both provided and sustained.

Abstract Background The successful transition of childhood cancer survivors (CCSs) from pediatric to adult long-term follow-up care is a critical phase, and determining the right time point can be challenging. We assessed the feasibility of the use of existing transition readiness tools in the context of the Swiss health care system, assessed partly transition readiness in Swiss CCSs, and compared our findings with Canadian CCSs for which these tools were originally developed. Methods We officially translated the Cancer Worry Scale (CWS) and Self-Management Skill Scale (SMSS) into German and integrated them into this cross-sectional study. We included CCSs attending the long-term follow-up (LTFU) clinic in the Division of Oncology-Hematology, Department of Pediatrics, Kantonsspital Aarau. We used descriptive statistics to describe transition readiness. Results We randomly recruited 50 CCSs aged ≥18 years at participation. The CCSs had a median CWS score of 62 (interquartile range 55–71), indicating a moderate level of cancer-related worry. Despite high self-management skills, some answers showed a dependency of CCSs on their parents. Our experience shows that the CWS and SMSS are easy for Swiss CCSs to use, understand, and complete. The interpretation of the results must take differences in health care systems between countries into account. Conclusions The translated CWS and SMSS are appropriate additional measures to assess transition readiness in CCSs. These scales can be used longitudinally to find the individual time point for transition and the completion by CCSs enables the health care team to individualize the transition process and to support the CCSs according to their individual needs.

An example of chemotherapy-induced cardiotoxicity in cancer survivors is acquired long QT syndrome (aLQTS), which may cause serious yet preventable life-threatening consequences. Our objective was to identify and characterize childhood acute lymphoblastic leukemia (ALL) survivors with possible aLQTS using maximal exercise testing. In this cross-sectional study with exploratory analysis, a total of 250 childhood ALL survivors were evaluated for abnormal QT interval prolongation using the McMaster cycle exercise test. A total of 198 survivors (102 males; 96 females), having reached their V ̇ O 2 peak (mean 32.1 ± 8.4 mL/kg/min; range 15.5-57.8 mL/kg/min), were included in our analyses. Two survivors were excluded for possible congenital LQTS. QT intervals were corrected for heart rate using the Bazett, Fridericia, and Rautaharju formulas at rest (supine, sitting, and standing positions), at the end of each stage of the CPET, and at 1, 3, and 5 minutes into the recovery period. The corrected QT (QTc) of borderline (n = 37) and long QT survivors (n = 20) was significantly longer than normal survivors (n = 141) at rest, exercise, and recovery. Out of 57 survivors presenting an abnormal QTc prolongation, 40 survivors (70%) showed no QT interval anomalies at rest but developed various anomalies during exercise. No significant differences were found between the groups for any of the measured clinical characteristics or cardiac parameters. The standardization of exercise testing in the regular follow-up of oncology patients is necessary for appropriate cardiac prevention and surveillance to enhance the health and quality of life of the ever-increasing number of cancer survivors., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Objective: Long-term psychological impacts are well--documented among childhood cancer survivors. To our knowledge, however, no research has been conducted to investigate obsessive--compulsive and related disorders (OCRD) among childhood -cancer survivors (CCS)., Methods: Using a large electronic medical record database, relative risk were calculated to examine associations between demographic characteristics and childhood cancer type and OCRDs among childhood cancer survivors., Results: Among 121 survivors of childhood cancer diagnosed with OCRD, 57% were female. The most common childhood cancer diagnoses were leukemia/lymphoma (41%) and central nervous system (CNS) malignancies (38%), and OCRD diagnoses most frequently observed were obsessive-compulsive disorder (OCD; 76%) and excoriation disorder (13%). Female sex (RR= 1.39, 95% confidence interval (CI) 1.17-1.61), White race (RR= 1.28, 95% CI 1.15-1.36) and history of CNS malignancies (RR= 1.36, 95% CI 1.18, 1.92) were associated with OCD., Conclusions: Numerous factors, including sex, race, and cancer type, were seen as contributors to risk variance for OCRDs, particularly OCD, among CCS, compared to CCS with no OCRD diagnosis. This provides an enhanced understanding of risk factors for OCRD development and may help improve early identification and care for at-risk survivors.

Background: Childhood cancer survivors lacking awareness on their potential risks of late effects often fail to seek adequate follow-up care. Patient education matching their preference is of great importance to improve their adherence to survivorship care. In this study, we developed two age-dependent game-based learning programs, which enable continuous approaches for childhood cancer survivors along their intellectual maturation. Then, we assessed the effectiveness of the programs.Methods: Childhood cancer survivors over 10 years of age who regularly visited a long-term follow-up clinic were enrolled in this study. They were requested to play either of two different types of game tools, one for school children and another for adolescents and young adults, for one month at home. To evaluate the educational effects of the programs, they were examined for health management awareness, self-esteem, and knowledge on cancer-related late effects before and after the intervention with age-based questionnaires and knowledge tests.Results: Among 83 participants, 49 (59.0%) completed the assessments over the period of 12 months. The health management awareness and knowledge levels increased significantly at 1-month after the intervention as compared to the baseline in both school children and adolescents/young adults (for health management awareness, p = 0.011 in elementary school children; p = 0.007 in junior high school children; p < 0.001 in adolescents/young adults; for knowledge levels, p < 0.001 in school children; p < 0.001 in adolescents/young adults). The effect was maintained for 12 months in school children while it decreased in adolescents and young adults with time. Self-esteem significantly increased at 1-month (p = 0.002 in school children; p = 0.020 in adolescents/young adults) and was maintained for 12 months in both age groups.Conclusion: The game-based learning programs enhanced health locus of control and self-esteem in childhood cancer survivors. The game-based learning programs could be applied effectively to survivorship care as a new modality of patient education.Trial Registration: This study was retrospectively registered in UMIN-CTR ( UMIN000043603 ) on March 12, 2021. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to compare the health‐related quality of life (HRQOL) of Dutch adult male and female childhood cancer survivors (CCSs) to general population references and to study medical determinants. Methods: CCSs from the Dutch Childhood Cancer Survivor Study LATER cohort (1963‐2001) part 2, who were 18 years old or older (time since diagnosis ≥ 5 years), were invited to complete the TNO‐AZL Questionnaire for Adult Health‐Related Quality of Life. Domain scores and proportions of CCSs with impaired HRQOL (score < 25th percentile of the reference scores) were compared with references via Mann‐Whitney U tests and logistic regression analyses corrected for age and sex (P <.004). Interactions of group with sex were included if they were significant (P <.05). Moreover, medical determinants were analyzed with multivariable logistic regression analyses. Results: HRQOL scores for 1766 CCSs (mean age, 35.9 years [standard deviation, 9.4 years]; male, 51%; response rate, 71%) differed from references on most domains with small effect sizes. Both male and female CCSs were more often impaired in gross and fine motor functioning, cognitive functioning, sleep, and vitality with odds ratios (ORs) > 1.4. In addition, female CCSs were more often impaired in daily activities, pain, and sexuality (ORs, 1.4‐1.9) and were less often aggressive (OR, 0.6). CCCs of central nervous system (CNS) tumors, bone tumors, and retinoblastoma and those with cranial, abdominopelvic, or lower extremity radiotherapy were at increased risk of impairment in 1 or more domains. Conclusions: Dutch adult CCSs, especially females, have impaired HRQOL in several domains; this is most pronounced in cognitive functioning. The vulnerabilities of subgroups at risk, such as CCSs of CNS tumors, were confirmed. Surveillance of HRQOL and multidisciplinary survivor care are recommended. Lay Summary: The health‐related quality of life in a Dutch nationwide cohort of 1766 survivors of childhood cancer was studied.Survivors of childhood cancer were found to have lower health‐related quality of life in several domains (eg, motor functioning and vitality) in comparison with the general population.They most often reported low cognitive functioning (eg, memory and attention).Females had low health‐related quality of life in more domains than males.Survivors of brain tumors had low health‐related quality of life in most domains.Monitoring health‐related quality of life regularly and collaborating between disciplines in survivor care is recommended. Dutch adult survivors of childhood cancer, especially females and central nervous system tumor survivors, have impaired health‐related quality of life in several domains; this is most pronounced in cognitive functioning. Surveillance of health‐related quality of life and multidisciplinary survivor care are recommended. [ABSTRACT FROM AUTHOR]

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. One in 4 childhood cancer survivors reports chronic fatigue. Current health problems increase the risk of reporting chronic fatigue. [ABSTRACT FROM AUTHOR]

Introduction: The number of children and young adults who survive cancer has steadily increased over the past decades. Consequently, life circumstances after cancer have gained increasing importance. The aim of this study was to explore family formation and socio-economic status among 35-year-old men having survived cancer in childhood or early adulthood compared to an age-matched comparison group. Methods: This study is a national, register-based cohort study among 35-year-old men. Men diagnosed with cancer in childhood and early adulthood were registered between 1978 and 2016. At the time of diagnosis, each patient was randomly matched with 150 men without cancer from the background population within the same birth year. Those still alive at the age of 35 years were included in the study population. Results: The study population consisted of 4,222 men diagnosed with cancer in childhood or early adulthood and 794,589 men in the age-matched comparison group. Men who have survived cancer during childhood or early adulthood have a reduced probability of having children, and lower probability of getting married or of cohabitation than those from an age-matched comparison group. Men who have survived CNS cancer also have a lower probability of having a higher education than high school and a higher probability of being outside the workforce than those from an age-matched comparison group. Discussion/Conclusion: Many men who have survived cancer during childhood or early adulthood are influenced by their cancer later in life, which was apparent in family formation, educational achievements, and labour market attachment. Continued focus on rehabilitation and needs for support among the male survivors of childhood and youth cancer is warranted. [ABSTRACT FROM AUTHOR]

In echocardiographic surveillance of anthracycline-treated childhood cancer survivors (CCS), left ventricular ejection fraction (LVEF) has insufficient prognostic value for future cardiac events, whereas longitudinal strain may be more sensitive. We describe the long-term incidence of cardiac events in CCS after previous measurement of LVEF and myocardial strain. Echocardiography, including four-chamber view longitudinal strain (4CH-LS), of 116 anthracycline-treated CCS was obtained between 2005–2009 (index echocardiography). Follow-up was obtained at the late-effects clinic. Primary outcome was occurrence of cardiac events, defined as either symptomatic heart failure, life-threatening arrhythmias, LVEF < 40% or cardiac death, in CCS with normal versus abnormal index 4CH-LS. LVEF from subsequent echocardiograms was obtained to evaluate its natural course as a secondary outcome. After index echocardiography (median 13.1 years since childhood cancer diagnosis), our study added a median follow-up of 11.3 years (median last clinical contact 23.6 years since diagnosis). Only three CCS developed a cardiac event (6.2, 6.4 and 6.7 years after index echocardiography), resulting in a ten-year cumulative incidence of 2.7% (95%CI 0.9–8.2). All three CCS had a clearly reduced index 4CH-LS and relevant cardiovascular risk factors, whereas their index LVEFs were around the lower limit of normal. Index LVEF correlated with index 4CH-LS but mean long-term natural course of LVEF was comparable for CCS with abnormal versus normal index 4CH-LS. Absolute 10-year cumulative incidence of cardiac events in anthracycline-treated CCS during long-term follow-up was low. Sensitive echocardiographic measurements, such as 4CH-LS may be useful to tailor surveillance frequency in a selected group of CCS without cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this secondary analysis was to explore how young cancer survivors and their parents experience and manage treatment-related late effects in daily life post-treatment. Design: A phenomenological-hermeneutic explorative study. Methods: Using purposive sampling, we included 15 childhood cancer survivors (aged 11-18 years) and their parents who participated in semi-structured interviews from September 2019 through May 2020. We analysed the interviews paired using a thematic approach focused on meaning. Results: The central theme, 'Negotiation daily life', emerged as well as three interrelated sub-themes, that is 'A changed everyday life', 'Physical activity as a tool' and 'Friends as a tool'. The childhood cancer survivors and their parents experienced, understood and interpreted the late effects differently. The difference between the survivors' perceptions and those of their parents in managing treatment-related late effects in everyday life resulted in a continuous negotiation process between the parties. Parents highlighted the negative impact of late effects on their child's daily life in relation to physical activity, school and socialization while the survivors wished to leave the cancer experience behind and 'move on' with their friends. As a result, most of the survivors developed strategies to manage their social activities while their parents felt that the survivors neglected the late effects. Conclusion: The ongoing negotiation process between the childhood cancer survivors and their parents show the complexity of the new family dynamics on returning to everyday life post-treatment. For clinical nurses, that means that there should be focus on family dynamics and how the childhood cancer survivors and parents, respectively, manage the childhood cancer survivors' late effects. Impact: Healthcare providers should distinguish between the needs of the survivors and those of their parents as they transition from treatment to everyday life, and especially in the management of late effects caused by the treatment. [ABSTRACT FROM AUTHOR]

Background: Fatigue is often reported by patients with childhood cancer both during and after cancer treatment. Several instruments to measure fatigue exist, although none are specifically validated for use in childhood cancer survivors (CCS). The aim of the current study was to present norm values and psychometric properties of the Checklist Individual Strength (CIS) and Short Fatigue Questionnaire (SFQ) in a nationwide cohort of CCS. Methods: In total, 2073 participants were included from the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort. Normative data, construct validity, structural validity, and internal consistency were calculated for the CIS and SFQ. In addition, reliability and a cutoff score to indicate severe fatigue were determined for the SFQ. Results: Correlations between CIS/SFQ and vitality measures asking about fatigue were high (>0.8). Correlations between CIS/SFQ and measures of different constructs (sleep, depressive emotions, and role functioning emotional) were moderate (0.4-0.6). Confirmatory factor analysis resulted in a four-factor solution for the CIS and a one-factor solution for the SFQ with Cronbach's alpha for each (sub)scale showing good to excellent values (>0.8). Test-retest reliability of the SFQ was adequate (Pearson's correlation = 0.88; ICC = 0.946; weighted Cohen's kappa item scores ranged 0.31-0.50) and a cut-off score of 18 showed good sensitivity and specificity scores (92.6% and 91.3%, respectively). Conclusion: The current study shows that the SFQ is a good instrument to screen for severe fatigue in CCS. The CIS can be used as a tool to assess the multiple fatigue dimensions in CCS. [ABSTRACT FROM AUTHOR]

Purpose: Childhood cancer survivors are at higher risk of human papillomavirus (HPV)-related second cancers than adolescents without cancer, yet their HPV vaccination uptake is lower. Using a statewide sample, we evaluated whether survivors are at higher risk of missed opportunities for concomitant HPV vaccination. Methods: From statewide healthcare data, we identified encounters where vaccines were received. Concomitant HPV vaccine missed opportunities were defined as a vaccine encounter where the HPV vaccine was not administered, although eligibility criteria were met. From these encounters, our sample included 327 survivors identified from the Utah Cancer Registry, diagnosed 2000-2016 at ages 0-9, and a birth year and sex-matched sample without cancer from the general population (n = 1,911). Mixed-effects Poisson regression estimated the rate of concomitant missed opportunities per vaccine encounter and 95% confidence intervals by vaccine encounter type (all vaccines, flu shot only, or adolescent/catch-up) from 2013 to 2016. Results: Survivors had more concomitant HPV vaccine missed opportunities than the population sample (70.0% vs. 59.0%). On average, survivors were 12% more likely to have missed opportunities at vaccine encounters and 4% more likely at flu shot only encounters. The predicted excess risk of concomitant missed opportunities for survivors ranged from 0.5 per10 vaccine encounters to 1.1 per10 vaccine encounters. Higher parental education, rurality, younger first vaccine age, and chemotherapy were associated with missed opportunities. Conclusions: Childhood cancer survivors have more missed opportunities for concomitant HPV vaccination than a population sample. As flu shots should be administered annually, providers have a regular opportunity to recommend and deliver the HPV vaccine to survivors. [ABSTRACT FROM AUTHOR]

Purpose: To examine self-reported (30-day) sleep versus nightly actigraphy-assessed sleep concordance in long-term survivors of childhood cancer. Methods: Four hundred seventy-seven participants enrolled in the St. Jude Lifetime Cohort (53.5% female, median (range) age 34.3 (19.3–61.6) years, 25.4 (10.9–49.3) years from diagnosis) completed the Pittsburgh Sleep Quality Index and ≥ 3 nights of actigraphy. Participants had neurocognitive impairment and/or a self-reported prolonged sleep onset latency (SOL). Self-reported 30-day sleep and nightly actigraphic sleep measures for sleep duration, SOL, and sleep efficiency (SE) were converted into ordinal categories for calculation of weighted kappa coefficients. General linear models estimated associations between measurement concordance and late effects. Results: Agreements between self-reported and actigraphic measures were slight to fair for sleep duration and SOL measures (kw = 0.20 and kw = 0.22, respectively; p < 0.0001) and poor for SE measures (kw = 0.00, p = 0.79). In multivariable models, severe fatigue and poor sleep quality were significantly associated with greater absolute differences between self-reported and actigraphy-assessed sleep durations (B = 26.6 [p < 0.001] and B = 26.8 [p = 0.01], respectively). Survivors with (versus without) memory impairment had a 44-min higher absolute difference in sleep duration (B = 44.4, p < 0.001). Survivors with, versus without, depression and poor sleep quality had higher absolute discrepancies of SOL (B = 24.5 [p = 0.01] and B = 16.4 [p < 0.0001], respectively). Poor sleep quality was associated with a 12% higher absolute difference in SE (B = 12.32, p < 0.0001). Conclusions: Self-reported sleep and actigraphic sleep demonstrated discordance in our sample. Several prevalent late effects were statistically significantly associated with increased measurement discrepancy. Future studies should consider the impacts of late effects on sleep assessment in adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Cancer treatment in childhood may negatively affect survivors' quality of life. In this study, we aimed to determine the contributing factors for health‐related quality of life (HRQOL) in survivors of childhood cancer in Korea using quantile regression analysis. This study was a secondary analysis. Data were collected from 130 childhood cancer survivors (CCS) from November 2018 to July 2019. Participants completed the Memorial Symptom Assessment Scale, Depression Anxiety Stress Scale, Health‐Promoting Lifestyle Profile‐II, and 36‐Item Short Form Health Survey (physical component summary [PCS] and mental component summary [MCS]). Quantile and multiple linear regressions were used to analyze the factors contributing to HRQOL. The quantile and linear regression models revealed different results on the contributing factors to HRQOL in CCS. Mean PCS and MCS scores were 78.55 (SD = 15.08) and 64.02 (SD = 18.00), respectively. Symptoms (e.g., difficulty concentrating, worrying, pain, and lack of energy), physical activity, spiritual growth, interpersonal relationships, stress management, depression, and anxiety were significant influencing factors in some PCS quantiles, while symptoms, spiritual growth, interpersonal relationships, depression, and stress were significant influencing factors in some MCS quantiles. The findings of this study showed specific contributing factors in CCS with different levels of HRQOL. There is a need for targeted interventions related to risk reduction and stratification for CCS with different HRQOL levels. Symptom management strategies, early detection programs for CCS with psychological distress, and clinical and counseling interventions for CCS with poor HRQOL need to be developed. [ABSTRACT FROM AUTHOR]

Background: In childhood cancer survivors (survival of 5 years or more after diagnosis), cardiac toxicity is the most common nonmalignant cause of death attributed to treatment-related consequences. Identifying patients at risk of developing late cardiac toxicity is therefore crucial to improving treatment outcomes. The use of genetic markers has been proposed, together with clinical risk factors, to predict individual risk of cardiac toxicity from cancer therapies, such as doxorubicin. Objective: The primary aim of this study is to evaluate the value of multimarker genetic testing for RARG rs2229774, UGT1A6 rs17863783, and SLC28A3 rs7853758 for predicting doxorubicin-induced cardiotoxicity. The secondary aim is to replicate previously described associations of candidate genetic markers with doxorubicin-induced cardiotoxicity. Moreover, we will evaluate the prevalence of cardiovascular dysfunction in childhood cancer survivors after neuroblastoma or nephroblastoma. Methods: This is the pharmacogenetic substudy of the research project Structural Optimization for Children With Cancer After Anthracycline Therapy (LESS-Anthra). We invited 2158 survivors of childhood neuroblastoma or nephroblastoma treated with doxorubicin according to the trial protocols of SIOP 9/GPOH, SIOP 93-01/GPOH, SIOP 2001/GPOH, NB 90, NB 97, or NB 2004 to participate in this prospective cross-sectional cohort study. The study participants underwent a cardiological examination and were asked to provide a blood or saliva sample for genotyping. The study participants' health statuses and cardiovascular diagnoses were recorded using a questionnaire completed by the cardiologist. Digital echocardiographic data were centrally evaluated to determine the contractile function parameters. Medical data on the tumor diagnosis and treatment protocol were taken from the study documentation. Survivors were screened for variants of several candidate genes by TaqMan genotyping. Results: This study includes 657 survivors treated with doxorubicin for childhood cancer, the largest German cohort assembled to date to investigate cardiovascular late effects. Data analyses are yet to be completed. Conclusions: This study will define the genetic risk related to 3 marker genes proposed in a pharmacogenetic guideline for risk assessment. Moreover, the results of this study will show the prevalence of cardiovascular dysfunction in survivors of pediatric neuroblastoma or nephroblastoma who were treated with doxorubicin. The results will help to improve primary treatment and follow-up care, thus reducing cardiovascular late effects in the growing population of childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Introduction: Childhood cancer is rare; the incidence in Sweden is approximately 16 new cases/100 000 children each year. Reduced reproductive function and fertility are well‐known side effects of cancer treatment. Anti‐Müllerian hormone (AMH) has been shown to correlate well with antral follicle count in healthy women but is currently not recommended as the primary surveillance modality for evaluation of premature ovarian insufficiency in this patient group. Psychological wellbeing related to fertility could affect quality of life and should be included in long‐term follow‐up. The aim of the study is to present the baseline data from inclusion for a prospective follow‐up study of fertility surveillance where both medical and psychological aspects of fertility in female childhood cancer survivors are considered. Material and methods: These are the first results from this longitudinal follow‐up cohort study. Female adolescent and young adult survivors of pediatric cancer in Western Sweden were included from January 2016 to December 2018, a total of 54 participants. Median age at inclusion was 21 (15–29) years and median age at cancer diagnosis was 10 (1–17) years. AMH levels, antral follicle count, and data on fertility were recorded at inclusion and will be prospectively followed up. The study includes questionnaires and interviews concerning quality of life. This study is planned to continue until the participants reach the age of 40 years. Results: Eighteen of 54 (33%) participants had AMH levels below 1.0 µg/L and were considered to have high or very high risk of infertility. Median AMH level was 2.50 µg/L. Six women had immediate need of oocyte cryopreservation. Psychological assessment showed that more than one‐third of participants (n = 20) had elevated anxiety scores. Conclusions: One‐third of female survivors of pediatric cancer in the study had high risk of low ovarian reserve, measured by a combination of AMH and antral follicle count, and many had signs of anxiety. The longitudinal study could contribute to better knowledge in the changes of AMH over time for this patient group. Psychological follow‐up with questionnaires and interviews evaluating signs of depression and anxiety may serve as a model for future screening programs. [ABSTRACT FROM AUTHOR]

Study Question: What are the fertility outcomes of male and female childhood acute lymphoblastic leukaemia (ALL) long-term survivors?Summary Answer: We observed similar fertility outcomes in both male and female childhood ALL survivors compared with the general population, with the exception of a higher proportion of miscarriages among partners of male survivors.What Is Known Already: Survival after childhood ALL is currently >90% and fertility impairments are among the main concerns of the long-term survivors. Few studies have focused on the fertility issues within this selected population and the existing data are difficult to interpret due to the different treatment regimens received by the patients, the small sample sizes and the unavailability of control data in many studies.Study Design, Size, Duration: Childhood ALL patients enrolled in European Organisation for Research and Treatment of Cancer (EORTC) studies between 1971 and 1998 in France and Belgium, <18 years old at diagnosis and alive and ≥18 years at follow-up were eligible. Among 1418 eligible survivors, 507 (35.8%) participated (277 females, 230 males). Controls from the general population matched one to one by age, province, level of urbanization and sex could be identified for 503 survivors.Participants/materials, Setting, Methods: Survivors and controls were invited to fill out a questionnaire including information about their menstrual cycles (for females), intention to have children, having children, use of medical help to become pregnant and occurrence of negative pregnancy outcomes (birth defect, miscarriage, medical abortion or stillbirth). The results were analysed separately for females and males. The association between age at diagnosis and fertility outcomes, adjusted by age at follow-up, study and country were investigated using logistic regression.Main Results and the Role Of Chance: The median time since diagnosis was 20.1 years and the median age at follow-up was 25 years. There were 144 survivors (97 females, 47 males) who wanted to have children. Among these, craniospinal radiotheraphy (CRT) and haematopoietic stem cell transplantation (HSCT) were administered to 18% and 4%, respectively. Of these who tried to have children, 75% of females and 69% of males succeeded, compared with 72% and 61% of the controls, respectively. These differences were not statistically significant (P = 0.73 for females and P = 0.50 for males). Overall, fertility outcomes were comparable between survivors and controls, except that a higher proportion of miscarriages occurred in partners of male survivors (28.1% versus 5.9%, P = 0.021). Among female survivors, an older age at diagnosis (10-17 years) was associated with a greater risk of pregnancy problems (adjusted OR 5.61, P = 0.046).Limitations, Reasons For Caution: The interpretation of the incidence of miscarriage among the partners of male survivors is limited by the lack of data regarding the males' partners and by a possibly higher tendency to recall and disclose fertility issues among male survivors compared with male controls.Wider Implications Of the Findings: Fertility outcomes were similar in childhood ALL survivors and controls, and the low proportion of patients treated with CRT or HSCT might explain this. Further studies should confirm the higher proportion of miscarriages in partners of male survivors.Study Funding/competing Interest(s): This publication was supported by donations from the Fonds Cancer (FOCA) from Belgium and the KU Leuven from Belgium. G.R. has been awarded a fellowship by the EORTC Cancer Research Fund (ECRF). C.P. has been awarded a fellowship by Fonds Cancer (FOCA) from Belgium and the Kinderkankerfonds from Belgium (a non-profit childhood cancer foundation under Belgian law). No competing interests were declared.Trial Registration Number: NCT01298388 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: Incidence rates in Denmark of central nervous system (CNS) tumors remain among the highest in the world. Survival rates, however, have improved in the past decades in high‐income countries. Methods: We analyzed incidence and survival of childhood CNS tumors in Denmark diagnosed from 1997 to 2019 based on data from the Danish Childhood Cancer Registry and information on histological types, tumor localization, and treatment from medical records. Results: From 1997 to 2019, 949 children<15 years were diagnosed with a CNS tumor. Age‐standardized incidence was 42.1 (95% CI, 39.4–44.6) per million person‐years and stable during this period. Age‐specific incidence for children aged 0–4 years was 47.7 per million. More than one‐third (n = 374, 39.4%) were treated with surgery alone. Overall survival rates 5 and 10 years after diagnosis were 77.6% (95% CI, 74.7–80.2) and 74.7% (95% CI, 71.7–77.5). Five‐year overall survival improved from 73.0% (95% CI, 68.9–76.7) in 1997–2008 to 83.2% (95% CI, 79.2–86.4) in 2009–2019 (p‐value < 0.0001) in children aged 0–4 years (p = 0.0006). Conclusion: Incidence rates are stable but remain among the highest in the world. Despite improved survival rates in recent years in younger children, some subtypes still have a poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Childhood cancers affect 2,500-3,000 children each year, and there are approximately 50,000 childhood cancer survivors who have completed therapy for their childhood cancer. The onset of childhood cancer most commonly occurs during the period of infancy to early childhood, and unlike adult-onset cancer, people who have cancer as children are expected to encounter many problems throughout their life. This study aimed to identify the kinds of problems that are faced by childhood cancer survivors on reaching adult age and the kinds of self-care that they perform. Methods: Semi-structured interviews were conducted with nine adult childhood cancer survivors following an interview guide prepared in advance. The data obtained was analyzed using the modified grounded theory approach. Subjects were explained about the study prior to obtaining their consent. Results: The analysis of their problems and self-care resulted in the development of four core categories, eight subcategories, and 39 concepts. The core categories were acceptance of and self-care for sequelae, secondary cancers, and late complications, Problematic situations during their growth and development, proactively obtaining information, and acceptance and appreciation of their own life. Conclusion: Childhood cancer survivors were suffering from sequelae resulting from their treatments for long periods. Although they faced many other issues, they did not talk about them to their mothers or medical staff, leaving them unresolved. Furthermore, these issues evolved as the survivors grew. The amount of information for those who have experienced childhood cancer was small, and effective self-care was not achieved. [ABSTRACT FROM AUTHOR]

Background: Use of complementary and alternative medicine (CAM) by those undergoing cancer treatment is common. While some childhood cancer survivors (CCS) may use CAM to treat late effects, others may lack information about available alternative therapies. We sought to determine characteristics associated with seeking more information about CAM among an ethnically diverse sample of young adult CCS. Methods: Young adult CCS were selected from the population-based Los Angeles SEER cancer registry and surveyed at ages 18 to 39 as part of the Project Forward Cohort. Associations between demographic, clinical, and other factors with seeking information on CAM were examined with t-tests, Chi Square analyses, and logistic regression. Results: Among 1106 participants surveyed, 182 (18%) reported interest in obtaining more information on CAM. Interest in CAM was highest among males, older (vs. younger) participants, those born outside the U.S., those with a history of relapsed/recurrent or second cancers, those with greater depressive symptoms, and those with poorer self-rated health. Among Hispanic/Latino/Latinx respondents, depressive symptoms, birth outside the U.S., and higher Latino culture orientation was positively associated with CAM interest. Discussion: Depressive symptoms and unresolved health problems are associated with a need for information about alternative forms of therapy, particularly in those with born outside the U.S. Healthcare providers caring for CCS can incorporate appropriate CAM information to help address unmet physical and mental health needs. [ABSTRACT FROM AUTHOR]

Cardiac diseases in the growing population of childhood cancer survivors are of major concern. Cardiotoxicity as a consequence of anthracyclines and chest radiotherapy continues to be relevant in the modern treatment era. Mitoxantrone has emerged as an important treatment-related risk factor and evidence on traditional cardiovascular risk factors in childhood cancer survivors is accumulating. International surveillance guidelines have been developed with the aim to detect and manage cardiac diseases early and prevent symptomatic disease. There is growing interest in risk prediction models to individualize prevention and surveillance. This State-of-the-Art Review summarizes literature from a systematic PubMed search focused on cardiac diseases after treatment for childhood cancer. Here, we discuss the prevalence, risk factors, prevention, risk prediction, and surveillance of cardiac diseases in survivors of childhood cancer.

Maximizing accumulation of bone mass during childhood and adolescence is essential to attaining optimal peak bone mass. Childhood cancer survivors (CCS) have lower bone mineral density (BMD) than the general population. Chemotherapeutic agents including steroids and radiotherapy can affect BMD. Cancer itself, hormonal insufficiency, a poor nutritional state, and a deficit of physical activities during or after treatment also influence BMD in CCS, resulting in failure to achieve appropriate peak bone mass. Low BMD in childhood and adolescence can lead to osteoporosis in adult life and complications such as bone pain, bone deformity, and fractures. Thus, BMD in CCS should be monitored with appropriate intervention. Adequate intake of calcium and vitamin D and an increase in physical activity are recommended. Timely supplements of hormones are needed in some cases. Some publications have reported that bisphosphonate therapies using pamidronate or alendronate were well tolerated in CCS and helped increase BMD.

Background As the number of childhood cancer survivors increases, there is a need to affront associated issues in adulthood such as anxiety, depression, and infertility. The aim of this qualitative study was to examine how childhood cancer survivors at the end of their fertile period were informed about fertility earlier in life and to investigate how this information influenced family planning decisions during adulthood. Methods The study included childhood cancer survivors in western Sweden ages 37–45 years identified from the Childhood Cancer Registry. Ten women and eight men ultimately participated in the study. Participants had been treated for cancer at a median age of 14 years (range, 2.5–17.5 years) and the median time since diagnosis was 26.0 years (range, 21.0–44.5 years). The study design consisted of a semi-structured interview and thematic analysis. Results A master theme that emerged from interviews was A long and uncertain road, which was divided into three underlying subthemes: Pictures of fertility e.g., from healthcare providers or parents; Experience of fertility e.g., searching as an adult, feeling like everyone else, not for me; and Emotions and fertility e.g., better not to think about it, cancer will affect my child. Women scored consistently lower than men on questionnaires regarding quality of life. Conclusion Most participants felt that they received insufficient information about fertility after cancer. The present study also highlighted a lack of support for cancer survivors into adulthood, which affected their psychological well-being and their inclination to become parents themselves.

Abstract Background A unique and limiting component in the research on functional impairment among children has been the exclusive use of parent proxy reports about child functioning; and there is limited information regarding the impact of pediatric cancer treatment on children’s day-to-day functioning and how this is related to neurocognitive functioning. The objective of the current study was to examine a novel measure of self-reported functional impairment, and explore the relationship between self-reported and parent-reported child functional impairment in pediatric cancer survivors compared to controls. Methods A cross-sectional cohort of survivors (n = 26) and controls (n = 53) were recruited. Survivors were off treatment an average of 6.35 years (SD = 5.38; range 1–15 years) and demonstrated an average “medium” Central Nervous System treatment intensity score. Participants completed measures of functional impairment (FI), intellectual assessment (RIST) and executive functions (NIH Examiner), while parents reported on children’s functional impairment. Results Survivors were similar to controls in functional impairment. Regardless of group membership, self-reported FI was higher than parent-reported FI, although they were correlated and parent report of FI significantly predicted self-reported FI. Across groups, increased impairment was associated with four of seven Examiner scores. Conclusions Research regarding self-reported functional impairment of cancer survivors and its association with parent-reported functional impairment and neurocognitive deficits has been limited. Our results suggest that self-reported FI appears to be a reasonable and viable outcome measure that corresponds with and adds incremental validity to parent reported FI. While low treatment intensity may confer relative sparing of functional impairment among survivors, children report higher FI levels than parents, suggesting that FI can be of clinical utility. In conclusion, pediatric cancer survivors should be screened for self-reported functional difficulties.

Objective: This cross-sectional study aimed to present how the unique cancer experience in childhood influences young adults' quality of life (QOL). Methods: Qualitative and quantitative methods were used to code and analyze a study-specific questionnaire (133 items). These data are presented in accordance with a conceptual QOL/health-related QOL model. Results: The participants included 34 women and 28 men (n = 62) diagnosed with solid tumors/lymphoma in the period 1983–2003, who had been treated at the same childhood cancer center in Sweden. The current mean age was 28.7 years (range: 18–45, standard deviation [SD]: 6.3, median value: 28.5), the mean age at diagnosis was 12.9 years (range: 8–17, SD: 2.3, median value: 13), and the mean time elapsed since treatment was 15.7 years (range: 4–28, SD: 2.4, median value: 15). The response rate was 65%. Higher levels of psychological maturity were reported by women versus men (P = 0.01) and by survivors diagnosed with cancer during adolescence versus school age (P = 0.04). Male participants reported lower levels of physical limitations (P = 0.03) and emotional distress when being of treatment and in contact with health care services (P = 0.04). The strongest factor influencing QOL during therapy was parental support (97%), while the strongest factors after therapy were to live a life similar to peers (82%) and to be satisfied with one's life situation (81%). During treatment, limitations influencing QOL were related to lack of school support (2%), and after treatment, to deteriorated relationships with siblings (5%). Conclusions: Life-threatening diseases at young ages have long-term psychosocial effects with ambiguous results at multiple levels. To capture these experiences, we recommend clinical studies that are based on conceptual clarifying frameworks and adopt a quantitative and qualitative research approach.

Background: Platinum compounds are a group of fundamental chemotherapeutics used in the treatment of solid tumors, but they are burdened by side effects, such as ototoxicity. The objective of this study was to evaluate the incidence of ototoxicity caused by platinum compounds and the risk factors affecting its appearance/progression. Methods: Data from 53 patients who received platinum compounds and who had been off therapy for at least 5 years were analyzed. We collected data relating to audiometry conducted annually from the end of treatment and for at least 5 subsequent years, as well as information concerning the oncological history and comorbidities. Results: At the end of the treatment, 17 patients (32.08%) presented ototoxicity, according to the Boston SIOP Ototoxicity Scale; the risk factors included a higher serum creatinine value at diagnosis, having undergone cranial radiotherapy, and needing magnesium supplementation. After 5 years from the end of the treatment, the number of patients with exhibiting ototoxicity was 31 (58.5%); the factors that influenced the onset/progression of the damage were having undergone radiotherapy (HR 1.23; p < 0.01) and having received therapy with aminoglycosides (HR 1.27; p < 0.01). Conclusions: Ototoxicity caused by platinum compounds can occur even after the conclusion of the treatments, and the factors affecting its progression are radiotherapy and the aminoglycosides therapy.

It is disheartening for parents to discover that their children have long-term cardiac dysfunction after being cured of life-threatening childhood cancers. As the number of childhood cancer survivors increases, early and late oncology-therapy-related cardiovascular complications continues to rise. It is essential to understand that cardiotoxicity in childhood cancer survivors is persistent and progressive. A child’s cancer experience extends throughout his lifetime, and ongoing care for long-term survivors is recognized as an essential part of the cancer care continuum. Initially, there was a lack of recognition of late cardiotoxicities related to cancer therapy. About 38 years ago, in 1984, pioneers like Dr. Lipshultz and others published anecdotal case reports of late cardiotoxicities in children and adolescents exposed to chemotherapy, including some who ended up with heart transplantation. At that time, cardiac tests for cancer survivors were denied by insurance companies because they did not meet appropriate use criteria. Since then, cardio-oncology has been an emerging field of cardiology that focuses on the early detection of cancer therapy-related cardiac dysfunction occurring during and after oncological treatment. The passionate pursuit of many healthcare professionals to make life better for childhood cancer survivors led to more than 10,000 peer-reviewed publications in the last 40 years. We synthesized the existing evidence-based practice and described our experiences in this review to share our current method of surveillance and management of cardiac dysfunction related to cancer therapy. This review aims to discuss the pathological basis of cancer therapy-related cardiac dysfunction and heart failure, how to stratify patients prone to cardiotoxicity by identifying modifiable risk factors, early detection of cardiac dysfunction, and prevention and management of heart failure during and after cancer therapy in children. We emphasize serial longitudinal follow-ups of childhood cancer survivors and targeted intervention for high-risk patients. We describe our experience with the new paradigm of cardio-oncology care, and collaboration between cardiologist and oncologist is needed to maximize cancer survival while minimizing late cardiotoxicity.

Objective: Children with a supratentorial midline low-grade glioma (LGG) may be at risk for impaired bone health due to hypothalamic-pituitary dysfunction, obesity, exposure to multiple treatment modalities, and/or decreased mobility. The presence of impaired bone health and/or its severity in this population has been understudied. We aimed to identify the prevalence and risk factors for bone problems in children with supratentorial midline LGG., Materials and Methods: A retrospective study was performed in children with supratentorial midline (suprasellar or thalamic) LGG between 1 January 2003 and 1 January 2022, visiting the Princess Máxima Center for Pediatric Oncology. Impaired bone health was defined as the presence of vertebral fractures and/or very low bone mineral density (BMD)., Results: In total, 161 children were included, with a median age at tumor diagnosis of 4.7 years (range: 0.1-17.9) and a median follow-up of 6.1 years (range: 0.1-19.9). Five patients (3.1%) had vertebral fractures. In 99 patients, BMD was assessed either by Dual Energy X-ray Absorptiometry (n = 12) or Bone Health Index (n = 95); 34 patients (34.3%) had a low BMD (≤ -2.0). Impaired visual capacity was associated with bone problems in multivariable analysis (OR: 6.63, 95% CI: 1.83-24.00, P = 0.004)., Conclusion: In this retrospective evaluation, decreased BMD was prevalent in 34.3% of children with supratentorial midline LGG. For the risk of developing bone problems, visual capacity seems highly relevant. Surveillance of bone health must be an aspect of awareness in the care and follow-up of children with a supratentorial midline LGG., Significance Statement: Patients with supratentorial midline LGG may encounter various risk factors for impaired bone health. Bone problems in survivors of childhood supratentorial midline LGG are, however, understudied. This is the first paper to address the prevalence of bone problems in this specific patient population, revealing visual problems as an important risk factor. Diencephalic syndrome historyand/or weight problems associated with hypothalamic dysfunction were related to bone problems in univariate analyses. The results of this study can be used in the development of guidelines to adequately screen and treat these patients to subsequently minimizing bone problems as one of the endocrine complications.

Purpose: Female childhood cancer survivors (CCSs) risk infertility due to gonadotoxic chemotherapy/radiation. Anti-Müllerian hormone (AMH) helps evaluate ovarian reserve, and the 2020 Oncofertility Pediatric Initiative Network (O-PIN) risk stratification is utilized to counsel risk of gonadal dysfunction/infertility. This study analyzed how AMH levels after cancer treatment differ with age and correlate AMH with O-PIN risk level and clinical outcomes. Methods: A literature review and mega-analysis of individual patient data were performed. Females ages 0-20 years at the time of cancer diagnosis with AMH values post-treatment were included. AMH outcomes were compared by O-PIN risk stratification, age at diagnosis, cyclophosphamide equivalent dose (CED), and hematopoietic stem cell transplant (HSCT). Multivariable random effects mixed models correlated AMH with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and pregnancy. Results: In 13 studies with 608 CCSs, the median age (years) at diagnosis was 12.0 (interquartile range [IQR] 5.2-16.2) and 21.1 (IQR 17.1-30.0) at AMH measurement. AMH values were higher with time since treatment and correlated with the O-PIN risk level. Patients with HSCT had very low/undetectable AMH levels regardless of CED; when stratified by CED, AMH levels were lower if treated peripubertally or older. AMH was detectable in 54% (34/63) of patients with POI on hormone replacement. Pregnancy did not correspond to the gonadotoxicity risk level ( p = 0.70). Conclusion: This study supports utilizing the O-PIN risk stratification system in estimating risk of DOR in CCSs and its categorization by pubertal status. AMH levels may return over time even after receiving the highest risk therapy. These findings may help counsel cancer patients pre- and post-therapy.

Background: Patient activation describes a willingness to take action to manage health and is associated with health outcomes. The purpose of this study was to characterize patient activation and its association with psychological outcomes and health behaviors in childhood cancer survivors., Methods: Participants were from the St. Jude Lifetime Cohort Study (SJLIFE). Activation levels (1-4, 4 = highest activation) were measured with the Patient Activation Measure (PAM). Psychological outcomes and health behaviors were obtained via self-report. Cognitive function was assessed by trained examiners. ANOVA or chi-squared tests were utilized to assess group-level differences in activation. Multivariable regression models were used to assess associations between PAM scores and outcomes of interest., Results: Among 2708 survivors and 303 controls, more survivors endorsed lower activation levels than the controls (11.3 vs. 4.7% in level 1) and fewer survivors endorsed the highest level of activation than the controls (45.3 vs. 61.5% in level 4). Not endorsing depression (OR: 2.37, 95% CI 1.87-2.99), anxiety (OR: 2.21, 95% CI 1.73-2.83), and somatization symptoms (OR: 1.99, 95% CI 1.59-2.50), general fear (OR: 1.45, 95% CI 1.23-1.71) and body-focused (OR: 2.21, 95% CI 1.83-2.66), cancer-related worry, and physical (OR: 2.57, 95% CI 2.06-3.20) and mental (OR: 2.08, 95% CI 1.72-2.52) HRQOL was associated with higher levels of activation. Lower activation was associated with not meeting physical activity guidelines (OR: 2.07, 95% CI 1.53-2.80)., Conclusions: Survivors endorsed lower activation levels than peers. Interventions to improve physical and psychological health outcomes could leverage these results to identify survivors who benefit from support in patient activation.

Background/objectives: Human papillomavirus (HPV) vaccinations prevent HPV infection and related cancers. Despite being at higher risk of secondary cancers linked to HPV, childhood cancer survivors (CCS) are undervaccinated. This study aimed to compare pediatric oncology providers' knowledge, attitudes, self-efficacy, and practices regarding HPV vaccination among those who participated in a multilevel educational HPV vaccine program with those of a national sample of oncology providers., Methods: Between February and March 2023, 39 providers from five pediatric oncology clinics in Texas completed online surveys, assessing knowledge about CCS risk for HPV-related cancers, attitudes towards the HPV vaccine, and confidence in recommending the vaccine to CCS. The results were compared with a national survey of providers conducted in 2019 (n = 195)., Results: The findings showed that providers who participated in our program had greater knowledge of CCS increased risk for HPV-related cancers (96% vs. 38%; p < 0.001); greater confidence in discussing and recommending the HPV vaccine (100% vs. 66%, p < 0.001) and addressing parental concerns (100% vs. 69%, p < 0.001); and a more positive attitude about oncology providers than general pediatricians, recommending (96% vs. 71%; p = 0.006) and administering the HPV vaccine to CCS (96% vs. 53%, p < 0.001)., Conclusion: This study underscores the importance of educating oncology providers about the increased risk of CCS and improving their self-efficacy to recommend the HPV vaccine, promoting vaccination in the oncology setting.

Purpose: Childhood Cancer Survivors (CCSs) have an increased risk for treatment-related chronic health conditions, but the adherence to long-term follow-up (LTFU) care decreases over time. We therefore assessed the CCSs' development of cancer knowledge, cancer worries, self-management skills, and expectations for LTFU care in a structured, cancer center-based transition model-a crucial part for maintaining adherence., Methods: Using questionnaire-based surveys, we compared the CCSs' cancer knowledge with medical record data and assessed cancer worries (6 questions), self-management skills (15 questions), and expectations (12 questions) longitudinally by validated scales. We used descriptive statistics for presenting our results., Results: We analyzed 17 CCSs, 71% were female, had a median age of 8 years at diagnosis and 21 years at study enrollment. The knowledge about late effects increased during the transition process, except for the risk of secondary malignancies. Leukemia survivors had a decrease in cancer worries. At least 75% of the CCSs agreed to 11 of 15 self-management questions before and after transition, with the highest increase over time in less parental involvement. The CCSs expected the most, that physicians know the CCSs' cancer history, that the visit starts on time, and that physicians can always be called in case of questions., Conclusions: Our transition model improved cancer knowledge, especially the risk for late effects, decreased cancer worries, and identified expectations for LTFU care which should be considered in the future. A structured transition process with evidence-based tools further increases the knowledge of CCS for LTFU through empowerment., (© 2024. The Author(s).)

Background: Measles is reemerging as a public health threat, raising important questions about disease vulnerability among childhood cancer survivors. This secondary analysis assessed the seroprevalence of anti-measles immunoglobulin G (IgG) antibodies as a marker of immune status in survivors of childhood cancer and associated demographic/treatment variables. Method: Participants were childhood cancer survivors who were free of active disease, having routine blood studies drawn, and could provide documentation of having received two doses of measles, mumps, and rubella vaccine before their cancer diagnosis. Patient record review documented demographic and treatment variables. Antimeasles (rubeola) IgG antibody seroprevalence was assessed by enzyme immunoassay for vaccine-specific antibodies. Results: Of 270 survivors evaluated, 110 (42%) were female, 196 (75%) were White, and 159 (61%) were leukemia/lymphoma survivors. Of these 262, 110 (42%) had negative measles seroprevalence, suggesting loss of immunity. Conclusion: Measles antibody surveillance and the need for reimmunization for survivors of childhood cancer survivors outside the transplant setting remains controversial. Our analysis indicates that a substantial proportion of survivors lose vaccine-related immunity to measles. Pediatric oncology nurses play important roles in educating cancer survivors regarding their risk of measles infection, evaluating the need for reimmunization, correcting misinformation about vaccine safety and effectiveness, and working to optimize community herd-based immunity., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Sexual dysfunction is a significant complication of treatment for many adult-onset cancers. However, comparatively less is known about sexual dysfunction in adult childhood cancer survivors (CCSs). Research has been limited by the exclusion of specific cancers (e.g., central nervous system [CNS] tumors) and the lack of validated measures, which makes it difficult to understand the nature and prevalence of sexual dysfunction in CCSs., Methods: A total of 249 adult CCSs (aged 18-65 years) enrolled in Project REACH, a prospective cohort study, and completed measures of physical and mental health, including sexual dysfunction. Participants scoring ≤19 on the Female Sexual Function Index 6 or ≤21 on the International Index of Erectile Function 5 were classified as experiencing sexual dysfunction. Analyses examined the relationships between sexual dysfunction and demographic, disease, treatment, and health variables., Results: A total of 78 participants (32%) experienced clinically significant sexual dysfunction. In univariate analysis, sexual dysfunction was significantly associated with CNS tumor diagnosis (odds ratio [OR], 2.56) and surgery (OR, 1.96) as well as with health variables such as fatigue (OR, 3.00), poor sleep (OR, 2.84), pain (OR, 2.04), depression (OR, 2.64), poor physical health (OR, 2.45), and poor mental health (OR, 2.21). Adjusted analyses found that CNS tumor diagnosis (p = .001) and health variables (p = .025) contribute significantly to sexual dysfunction in CCSs., Conclusions: Approximately one third of adult CCSs report clinically significant sexual dysfunction, which underscores a significant screening and treatment need. However, because available measures were developed for survivors of adult cancers, research to create a sexual health measure specifically for adult CCSs is necessary to better identify the sexual health concerns of this vulnerable population., (© 2024 American Cancer Society.)

Introduction: Data on ovarian function in neuroblastoma survivors are limited. We sought to determine the prevalence of ovarian dysfunction in a cohort of high-risk neuroblastoma survivors and compare outcomes among survivors treated with and without autologous stem cell rescue (ASCR) preceded by myeloablative chemotherapy., Methods: Retrospective review of female survivors of high-risk neuroblastoma ≥5 years from diagnosis, diagnosed between 1982 and 2014, and followed in a tertiary cancer center. Participants were divided into two groups: individuals treated with conventional chemotherapy ± radiation ("non-ASCR") (n = 32) or with chemotherapy ± radiation followed by myeloablative chemotherapy with ASCR ("ASCR") (n = 51). Ovarian dysfunction was defined as follicle-stimulating hormone ≥15 mU/mL, while premature ovarian insufficiency (POI) was defined as persistent ovarian dysfunction requiring hormone replacement therapy. Poisson models were used to determine prevalence ratios of ovarian dysfunction and POI., Results: Among 83 females (median attained age: 19 years [range, 10-36]; median follow-up: 15 years [range, 7-36]), 49 (59%) had ovarian dysfunction, and 34 (41%) developed POI. Survivors treated with ASCR were 3.2-fold more likely to develop ovarian dysfunction (95% CI: 1.8-6.0; p < 0.001) and 4.5-fold more likely to develop POI (95% CI: 1.7-11.7; p = 0.002) when compared with those treated with conventional chemotherapy, after adjusting for attained age. Two participants in the non-ASCR group and six in the ASCR group achieved at least one spontaneous pregnancy., Discussion: Ovarian dysfunction is prevalent in female high-risk neuroblastoma survivors, especially after ASCR. Longitudinal follow-up of larger cohorts is needed to inform counseling about the risk of impaired ovarian function after neuroblastoma therapy., (© 2024 Wiley Periodicals LLC.)