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Purpose: Childhood cancer survivors (CCS) are at risk for therapy-related late effects. Physical activity (PA) can minimize some late effects risk, but rates of PA are low in CCS. We aimed to determine how perception of survivor health status and presence of chronic conditions are associated with patient- or proxy-reported PA. Methods: This cross-sectional, retrospective study of CCS (6–25 years; ≥ 1 year off-therapy) defined low PA as < 5 days per week with ≥ 60 minutes/day of patient- or proxy-reported activity. Participants completed PROMIS Global Health questions assessing perceptions of overall, physical, and mental health. Presence of chronic conditions was abstracted from the health record and defined as ≥ 2 late effects. Multivariable logistic regressions were performed to identify associations between physical activity and health status or chronic conditions. Results: Of 284 CCS, 71.8% reported low PA. Negative perceived overall, physical, and mental health status were present in 5.6%, 10.6%, and 15.9% of CCS, respectively, with presence of chronic conditions in 49.7%. Low PA was directly associated with female sex (p = 0.002) and poor physical (p = 0.01) and mental (p = 0.02) health status, and inversely associated with relapsed/refractory disease (p = 0.03). Presence of chronic conditions was not associated with low PA (p = 0.68); however, all CCS with chronic graft-versus-host disease or vision impairment had low PA. Conclusion: Low PA is an issue for CCS, especially females, and is associated with negative perceived physical and mental health. Future PA interventions for CCS should address perceived physical and mental health, and focus on specific at-risk sub-groups. [ABSTRACT FROM AUTHOR]

Background: Because the occurrence of metabolic syndrome (MetS) might contribute to childhood cancer survivor's excess risk of cardiovascular disease, the authors assessed the prevalence and determinants of MetS in the Dutch Childhood Cancer Survivor Study (DCCSS‐LATER2) cohort. Methods: In total, 2338 adult childhood cancer survivors (CCS) were cross‐sectionally assessed for the prevalence of MetS, using the Lifelines cohort (N = 132,226 adults without a history of cancer) as references. The prevalence of MetS was clinically assessed using existing classifications, as well as an alternative method using dual‐energy x‐ray absorptiometry fat% instead of waist circumference to define abdominal adiposity. Logistic regression models, adjusted for age and sex, were used to investigate the association between the presence of MetS and both cohorts. Demographic, lifestyle, and treatment determinants of MetS were identified through multivariable logistic regression. Results: The survivor cohort (median age, 34.7 years, median follow‐up time, 27.1 years) showed increased adjusted odds ratio (aOR) for MetS (modified National Cholesterol Education Program Adult Treatment Panel III criteria), as compared to the reference cohort (aOR, 2.07; 95% confidence interval [CI], 1.85–2.32). Compared to these criteria, the alternative method identified 57 additional survivors with MetS (395 of 2070 [19.1%] vs. 452 of 1960 [23.1%], respectively). Age (odds ratio [OR], 1.07; 95% CI, 1.04–1.10, per year increase), smoking (OR, 1.46; 95% CI, 1.04–2.04), low physical activity (OR, 1.48; 95% CI, 1.05–2.09), abdominal radiotherapy (OR, 2.13; 95% CI, 1.01–4.31; >30 Gy), cranial radiotherapy (OR, 2.89; 95% CI, 1.67–4.96; 1–25 Gy; and OR, 2.44; 95% CI, 1.30–4.47; >25 Gy), total body irradiation (OR, 6.17; 95% CI, 3.20–11.76), and underlying central nervous system tumor (OR, 1.78; 95% CI, 1.21–2.60) were associated with MetS. Conclusion: The high risk of MetS in CCS, combined with several potential modifiable factors, underscores the need for timely identification and intervention strategies to mitigate the long‐term cardiovascular risks in CCS. The prevalence of metabolic syndrome in the recruited nationwide childhood cancer survivor cohort was high and inconsistent with the chronological age, suggesting a substantial future health burden. Nonmodifiable determinants, including cranial, abdominal, and total body irradiation, as well as modifiable determinants, including smoking and physical activity, were associated with metabolic syndrome in this nationwide childhood cancer survivor cohort. [ABSTRACT FROM AUTHOR]

Objective Childhood cancer survivors (CCS) face an increased risk of early cardiovascular disease (CVD). In our nationwide CCS cohort, we assessed the prevalence and determinants of dyslipidemia, a well-established risk factor for accelerated atherosclerosis and CVD. Methods Prevalence of dyslipidemia was cross-sectionally assessed in 2338 adult CCS and compared to adults with no cancer history (Lifelines, n = 132 226). Dyslipidemia was defined by multiple classifications as well as lipid abnormalities to investigate the impact on prevalence and determinants. Logistic regression models, adjusted for age, sex, and BMI, were used to assess the cohort effect on presence of dyslipidemia. Determinants of dyslipidemia were identified through multivariable logistic regression. Results CCS (median age 34.7 year, median follow-up 27.1 year) had significantly increased odds of dyslipidemia compared to the reference cohort according to all classifications (NCEP-ATP-III, WHO, EGIR, CTCAEv.4.03). In survivors without lipid-lowering agents (n = 2007), lipid abnormalities were present in 20.6% (triglycerides > 1.7 mmol/L), 30.3% (HDL-c < 1.0/1.3 mmol/L (male/female)), 29.9% (total cholesterol > 5.2 mmol/L), 7.3% (LDL-c > 4.1 mmol/L), and 7.7% (apolipoprotein-B > 130 mg/dL). Compared to references without lipid-lowering agents (n = 126 631), survivors had increased odds of high triglycerides (aOR = 1.89, 95% CI = 1.68-2.13), low HDL-c (aOR = 2.73, 95% CI = 2.46-3.03), and high apolipoprotein-B (aOR = 1.84, 95% CI = 1.53-2.20). Sex, age, BMI, physical activity, abdominal/pelvic, cranial, and total body irradiation, alkylating agents, smoking, growth hormone deficiency, and diabetes mellitus were associated with (≥1 definition of) dyslipidemia in CCS. Conclusions CCS is at increased risk of dyslipidemia, with various modifiable and non-modifiable determinants identified, underscoring the importance of survivor-specific risk assessment tools to control cardiovascular morbidity and mortality in this high-risk population. [ABSTRACT FROM AUTHOR]

Simple Summary: Because of the treatments they have undergone, survivors of childhood brain tumors have a greater risk of cardiovascular disease and sarcopenia compared to the general population. The objective of this study was to analyze differences in a bioelectrical impedance analysis (BIA) of body composition between male childhood brain tumor cancer survivors and healthy controls and to evaluate the correlation between the BIA results and the treatments performed (chemotherapy, radiotherapy, and steroid therapy). Our analysis indicates the presence of several body composition indexes at the BIA that point towards the presence of sarcopenia in childhood brain tumor survivors, showing also a significant correlation between some of these indexes and total dose of carboplatin received. Background. Childhood brain tumor survivors (CCSs) are at high risk of developing metabolic syndrome (MetS) and sarcopenia. To date, a tool able to predict any body composition changes or detect them early and increased adiposity (and, therefore, increased likelihood of MetS onset) is still lacking in this population. Objective. The objective was to analyze differences in a bioelectrical impedance analysis (BIA) of body composition between male childhood brain tumor cancer survivors and healthy controls. Methods. In this pilot, prospective, observational study, 14 male CCSs were compared to 14 healthy controls matched for sex and age. Results. CCSs showed statistically significant lower mean values in terms of their body metabolic rate (BMR), body cell mass index (BCMI), fat-free mass (FFM), skeleton muscle mass (SM), skeletal muscle mass index (SMI), and appendicular skeletal muscular mass (ASMM). CCSs also showed a statistically significantly higher mean value of resistance when compared with controls. The BMR, BCM, FFM, and ASMM were significantly correlated with total doses of carboplatin (Tau = −0.601; p = 0.018; Tau = −0.599, p = 0.025; Tau = −0.601, p = 0.018; Tau = −0.509, p = 0.045, respectively). Conclusion. A BIA allows for the detection of changes in body composition in survivors of childhood brain tumors, revealing either the presence of central obesity correlated with the risk of MetS or signs of sarcopenia that deserve early treatment. [ABSTRACT FROM AUTHOR]

Abstract Purpose Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). Methods We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. Results The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5–31.2 and RHR = 5.1, 95%CI 4.4–5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7–13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7–3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3–4.7) compared to those who did not receive radiotherapy. Conclusions Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals.

Purpose: Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). Methods: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. Results: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5–31.2 and RHR = 5.1, 95%CI 4.4–5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7–13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7–3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3–4.7) compared to those who did not receive radiotherapy. Conclusions: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals. [ABSTRACT FROM AUTHOR]

Abstract Cardiovascular complications related to cancer therapies are broad and variable in onset. These complications are the leading cause of non-cancer related morbidity and mortality in childhood cancer survivors and can also impact ongoing cancer treatment. Despite this understanding, dedicated cardio-oncology programs are lacking in pediatric cardiology. In an attempt to respond to these concerns, a risk-stratified, comprehensive cardio-oncology program was established to address the cardiovascular needs including prevention, early diagnosis, and management of patients with and at risk for cardiovascular complications of cancer therapy. This manuscript describes a single institution’s experience of building and managing a multidisciplinary pediatric cardio-oncology program with close collaboration among cardiologists, oncologists, advanced cardiology and oncology practice providers, and allied health providers such as a dietitian and psychologist to provide comprehensive cardiovascular care for childhood cancer patients and survivors. In developing this program, emphasis was on the childhood cancer survivor population, as various cardiovascular complications can present many years after cancer treatment.

Background: Childhood cancer survivors (CCS) exposed to platinum chemotherapy are at an increased risk of developing hearing loss and reporting decreased quality of life (QOL). This study compared two QOL measures; one developed for children with hearing loss, The Hearing Environments and Refection on Quality of Life (HEAR-QL), and one validated in CCS, the Patient-Reported Outcomes Measurement Information System (PROMIS), to assess their ability to evaluate QOL deficits in this population. Methods: Subject eligibility were restricted to CCS exposed to platinum-based chemotherapy but who were free of known risk factors for cognitive impairment, (non-central nervous system tumor, no cranial radiation, or intrathecal chemotherapy). Participants had to be between 8-17 years, have completed anti-cancer therapy for at least 6 months, and have an audiogram within 1 year, Participants completed the HEAR-QL-26 (7-12 years) or the HEAR-QL-28 (13-18 years) and the PROMIS. Independent samples and/or one sample T-tests were utilized to compare participants with normal hearing and hearing loss, and to compare outcome measures to normative HEAR-QL and PROMIS data. Non-parametric correlations were utilized to evaluate the relationship between QOL and demographic and medical variables, and QOL and severity of hearing loss. Results: Fifty-four CCS were evaluable. The mean age was 12.0 years. Twenty-eight participants (51.9%) received cisplatin, 30 (55.6%) carboplatin, and 4 (7.4%) received both. Twenty participants (37%) demonstrated hearing loss. Participants with hearing loss scored significantly lower on the HEAR-QL than those with normal hearing (mean: 70.3, SD: 21.7, vs mean: 88.0, SD: 9.3, p =.004 for the HEAR-QL-26; mean: 84.7, SD: 10.2 vs mean: 94.8, SD: 3.4, p =.040 for the HEARQL-28). Participants with normal hearing scored significantly lower on the HEARQL-26 than the normative mean (mean: 88, SD: 9.3, normative mean: 98, SD: 5, p =.000). The PROMIS failed to identify any differences in QOL between participants based on hearing status, or when compared to the normative mean. Conclusion: The HEAR-QL was more sensitive than the PROMIS in identifying QOL deficits in CCS at risk for hearing loss. The HEAR-QL should be considered in studies seeking to improve the QOL of CCS with hearing loss. [ABSTRACT FROM AUTHOR]

Background: Childhood, adolescent and young-adult (AYA) cancer survivors often experience health problems due to late or long-term effects of their cancer or the treatment thereof. The general population gains health benefits from immersion in nature, and nature-based programmes seem to be an intervention that can promote health among childhood and AYA cancer survivors. Objective: To explore the impact of the WAYA wilderness programme on the health of childhood and AYA cancer survivors. Methods: The study had a qualitative approach, with data from individual interviews (n = 18) 3 months after completion of the WAYA programme. In addition, case report data was collected during follow-up talks (1, 2 and 12 months after the programme) (n = 19). The WAYA programme consisted of an 8-day expedition, followed 3 months later by a 4-day base camp. The programme included activities such as hiking, backpacking, kayaking, rock climbing, bushcraft and mindfulness. Data was analysed according to a qualitative content analysis. The consolidated criteria for reporting qualitative research (COREQ) were followed. Results: An overarching theme was identified: "Personal growth from challenges in nature supported by deep connections with others". In 4 additional themes, participants' experiences describe how deep personal connections arose, as they developed a feeling of being able and competent in nature. Nature provided a space that supported relaxation and respite from everyday challenges and stimuli, which also led to an experience of being more connected to nature. Conclusion: The WAYA programme was experienced as being of support to childhood and AYA cancer survivors. The programme provided them with skills and tools to be safe in nature. When connected to nature, the participants developed trust and self-confidence, personal growth, relaxation and recovery from stress. Their engagement in outdoor activities continued after completion of the programme, when they returned to everyday life at home. [ABSTRACT FROM AUTHOR]

Along with improvements in cancer treatment over time, the number of childhood cancer survivors has been growing. Survivors are at risk for serious medical complications, and growth impairment is among the most common. There are multiple factors that may cause impaired growth among survivors. In this article, we review the impact of cancer on growth in children and adolescents. We first provide an overview of growth disturbance among childhood cancer patients and survivors due to nonhormonal causes, including a recent understanding of the effect of targeted cancer therapies (eg, tyrosine kinase inhibitors and immune checkpoint inhibitors) on growth. Then we describe the hormonal causes of growth impairment among survivors, focusing on growth hormone deficiency, including the prevalence, risk factors, and treatment. Lastly, we briefly summarize overgrowth and tall stature in childhood cancer. It is critical to assess the linear growth of children and adolescents, especially in cancer survivors who are at risk for growth disturbance, since growth is an important measure of their health. [ABSTRACT FROM AUTHOR]

Background. Childhood brain tumor survivors (CCSs) are at high risk of developing metabolic syndrome (MetS) and sarcopenia. To date, a tool able to predict any body composition changes or detect them early and increased adiposity (and, therefore, increased likelihood of MetS onset) is still lacking in this population. Objective. The objective was to analyze differences in a bioelectrical impedance analysis (BIA) of body composition between male childhood brain tumor cancer survivors and healthy controls. Methods. In this pilot, prospective, observational study, 14 male CCSs were compared to 14 healthy controls matched for sex and age. Results. CCSs showed statistically significant lower mean values in terms of their body metabolic rate (BMR), body cell mass index (BCMI), fat-free mass (FFM), skeleton muscle mass (SM), skeletal muscle mass index (SMI), and appendicular skeletal muscular mass (ASMM). CCSs also showed a statistically significantly higher mean value of resistance when compared with controls. The BMR, BCM, FFM, and ASMM were significantly correlated with total doses of carboplatin (Tau = −0.601; p = 0.018; Tau = −0.599, p = 0.025; Tau = −0.601, p = 0.018; Tau = −0.509, p = 0.045, respectively). Conclusion. A BIA allows for the detection of changes in body composition in survivors of childhood brain tumors, revealing either the presence of central obesity correlated with the risk of MetS or signs of sarcopenia that deserve early treatment.

BackgroundChildhood cancer survivors (CCS) exposed to platinum chemotherapy are at an increased risk of developing hearing loss and reporting decreased quality of life (QOL). This study compared two QOL measures; one developed for children with hearing loss, The Hearing Environments and Refection on Quality of Life (HEAR-QL), and one validated in CCS, the Patient-Reported Outcomes Measurement Information System (PROMIS), to assess their ability to evaluate QOL deficits in this population.MethodsSubject eligibility were restricted to CCS exposed to platinum-based chemotherapy but who were free of known risk factors for cognitive impairment, (non-central nervous system tumor, no cranial radiation, or intrathecal chemotherapy). Participants had to be between 8-17 years, have completed anti-cancer therapy for at least 6 months, and have an audiogram within 1 year, Participants completed the HEAR-QL-26 (7-12 years) or the HEAR-QL-28 (13-18 years) and the PROMIS. Independent samples and/or one sample T-tests were utilized to compare participants with normal hearing and hearing loss, and to compare outcome measures to normative HEAR-QL and PROMIS data. Non-parametric correlations were utilized to evaluate the relationship between QOL and demographic and medical variables, and QOL and severity of hearing loss.ResultsFifty-four CCS were evaluable. The mean age was 12.0 years. Twenty-eight participants (51.9%) received cisplatin, 30 (55.6%) carboplatin, and 4 (7.4%) received both. Twenty participants (37%) demonstrated hearing loss. Participants with hearing loss scored significantly lower on the HEAR-QL than those with normal hearing (mean: 70.3, SD: 21.7, vs mean: 88.0, SD: 9.3, p =.004 for the HEAR-QL-26; mean: 84.7, SD: 10.2 vs mean: 94.8, SD: 3.4, p =.040 for the HEAR-QL-28). Participants with normal hearing scored significantly lower on the HEAR-QL-26 than the normative mean (mean: 88, SD: 9.3, normative mean: 98, SD: 5, p =.000). The PROMIS failed to identify any differences in QOL between participants based on hearing status, or when compared to the normative mean.ConclusionThe HEAR-QL was more sensitive than the PROMIS in identifying QOL deficits in CCS at risk for hearing loss. The HEAR-QL should be considered in studies seeking to improve the QOL of CCS with hearing loss.

Simple Summary: Survivors of childhood brain tumors, because of the treatments they have undergone, have a greater risk of dying earlier from cardiovascular causes compared to the general population. The objective of this study was to evaluate differences between cardiovascular risk biomarkers and cardiopulmonary exercise test (CPET) results from childhood brain tumor survivors and healthy controls. We found worse CPET performance in survivors associated with higher endothelin-1 values compared to controls. Correlation analysis showed an inverse relationship between CPET results and leptin, emphasizing the role of radiotherapy as a possible cause in the genesis of a greater cardiovascular risk in survivors of childhood brain tumors. In recent decades, the improvement of treatments and the adoption of therapeutic protocols of international cooperation has led to an improvement in the survival of children affected by brain tumors. However, in parallel with the increase in survival, long-term side effects related to treatments have been observed over time, including the activation of chronic inflammatory processes and metabolic alterations, which can facilitate the onset of metabolic syndrome and increased cardiovascular risk. The aim of this study was to find possible statistically significant differences in the serum concentrations of early biomarkers of metabolic syndrome and in the results of cardiopulmonary exercise testing between survivors of childhood brain tumors and healthy controls. This is a prospective and observational study conducted on a group of 14 male patients who survived childhood brain tumors compared with the same number of healthy controls. The concentrations of early metabolic syndrome biomarkers [adiponectin, leptin, TNF-α, IL-1, IL-6, IL-10, endothelin-1, apolipoprotein B, and lipoprotein (a)] were measured and a cardiopulmonary exercise test (CPET) was performed. Results: Childhood brain tumor survivors performed worse on average than controls on the CPET. Furthermore, they showed higher endothelin-1 values than controls (p = 0.025). The CPET results showed an inverse correlation with leptin. The differences found highlight the greater cardiovascular risk of brain tumor survivors, and radiotherapy could be implicated in the genesis of this greater cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Recently, while the overall survival rate of childhood cancer has improved, research has highlighted a high incidence of comorbidities in childhood cancer survivors (CCSs). However, it is likely that many asymptomatic comorbidities go unnoticed. The purpose of the current study was to identify comorbidities unique to Japanese CCSs through comparisons with a general population that underwent comparable comprehensive medical checkups. Methods: The patient group included CCSs who had completed their cancer treatment, were aged 16 years or older, and underwent the comprehensive medical checkups at the University of Tsukuba Hospital between 2018 and 2020. The control group included members of the general population who underwent comprehensive medical checkups at the same hospital in 2018. Results: Seventeen CCSs and 59 controls were included. Among the CCSs, the median ages at medical checkup and diagnosis were 22.1 years (range, 16–39) and 8.7 years (range, 1.3–14.8), respectively. Incidence of abnormalities in respiratory function, hearing function, and body mass index was higher in CCSs (52.9%, p = 0.013; 17.6%, p < 0.001; and 41.2%, p = 0.080, respectively) compared with controls. Conclusion: Asymptomatic pulmonary dysfunction was detected in the comprehensive medical checkup as a unique comorbidity in CCSs. Because the odds ratio of mortality due to respiratory failure is high in CCSs, as previously reported, we believe that detection of pulmonary dysfunction and the promotion of a healthy lifestyle are important. The evaluation of the pulmonary function may not typically be included in routine clinical visits, but it could be necessary for comprehensive medical evaluation in CCSs. [ABSTRACT FROM AUTHOR]

Background: Treatment exposures for childhood cancer reduce ovarian reserve. However, the success of assisted reproductive technology (ART) among female survivors is not well established. Methods: Five‐year survivors of childhood cancer in the Childhood Cancer Survivor Study were linked to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System, which captures national ART outcomes. The authors assessed the live birth rate, the relative risk (RR) with 95% confidence intervals (95% CIs), and associations with treatment exposure using generalized estimating equations to account for multiple ovarian stimulations per individual. Siblings from a random sample of survivors were recruited to serve as a comparison group. Results: Among 9885 female survivors, 137 (1.4%; median age at diagnosis, 10 years [range, 0–20 years]; median years of follow‐up after age 18 years, 11 years [range, 2–11 years]) underwent 224 ovarian stimulations using autologous or donor eggs and/or gestational carriers (157 autologous ovarian stimulation cycles, 67 donor ovarian stimulation cycles). In siblings, 33 (1.4%) underwent 51 autologous or donor ovarian stimulations. Of those who used embryos from autologous eggs without using gestational carriers, 97 survivors underwent 155 stimulations, resulting in 49 live births, for a 31.6% chance of live birth per ovarian stimulation (vs. 38.3% for siblings; p =.39) and a 43.9% chance of live birth per transfer (vs. 50.0%; p =.33). Prior treatment with cranial radiation therapy (RR, 0.44; 95% CI, 0.20–0.97) and pelvic radiation therapy (RR, 0.33; 95% CI, 0.15–0.73) resulted in a reduced chance of live birth compared with siblings. The likelihood of live birth after ART treatment in survivors was not affected by alkylator exposure (cyclophosphamide‐equivalent dose, ≥8000 mg/m2 vs. none; RR, 1.04; 95% CI, 0.52–2.05). Conclusions: Childhood cancer survivors are as likely to undergo treatment using ART as sibling controls. The success of ART treatment was not reduced after alkylator exposure. The results from the current study provide needed guidance on the use of ART in this population. Linking the Childhood Cancer Survivor Study database to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System revealed that childhood cancer survivors are as likely to undergo treatment with assisted reproductive technology as their siblings. The success of assisted reproductive technology was not reduced after alkylator exposure. [ABSTRACT FROM AUTHOR]

Purpose: Treatment sequelae compromising reproductive health are highly prevalent in childhood cancer survivors, and a main determinant of health and quality of life. Follicular reserve determines ovarian function life span; thus, its preservation is important in the care of female survivors. Anti-Müllerian hormone (AMH) is a biomarker to measure functional ovarian reserve. We aimed to evaluate the effect of leuprolide during gonadotoxic therapy on pubertal females' post-treatment functional ovarian reserve using AMH levels. Methods: We conducted a single-center retrospective study including all pubertal females who had undergone gonadotoxic treatments between January 2010 and April 2020, and had an AMH level after completion of therapy. We used multivariable linear regressions to compare AMH-level beta coefficients in patients stratified by gonadotoxic risk, adjusting for leuprolide use. Results: Fifty-two females meeting study eligibility were included, of which 35 received leuprolide. The use of leuprolide was associated with higher post-treatment AMH levels in the lower gonadotoxic risk group (beta 2.74, 95% CI 0.97–4.51; p = 0.004). This association was lost in the higher gonadotoxic risk groups. Conclusions: Leuprolide may have a protective effect on the functional ovarian reserve. However, this is limited by increasing treatment gonadotoxicity. Larger, prospective studies are needed to elucidate the potential benefits of gonadotropin-releasing hormone agonist on preservation of ovarian reserve among children receiving gonadotoxic therapies, as cancer survivors. [ABSTRACT FROM AUTHOR]

Abstract Background Whether diet has beneficial effects on cardiovascular disease (CVD) in childhood cancer survivors as in the general population is unknown. Therefore, we examined associations between dietary patterns and risk of CVD in adult survivors of childhood cancer. Methods Childhood cancer survivors, 18–65 years old in the St Jude Lifetime Cohort (1882 men and 1634 women) were included in the analysis. Dietary patterns were defined by the adherence to the Healthy Eating Index (HEI)–2015, Dietary Approaches to Stop Hypertension (DASH), and alternate Mediterranean diet (aMED) based on a food frequency questionnaire at study entry. CVD cases (323 in men and 213 in women) were defined as participants with at least one grade 2 or higher CVD-related diagnosis at baseline. Multivariable logistic regression adjusted for confounders was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of CVD. Results Greater adherence to HEI-2015 (OR=0.88, 95% CI: 0.75–1.03, per 10 score increment), DASH (OR=0.85, 95% CI: 0.71–1.01, per 10 score increment), and aMED (OR=0.92, 95% CI: 0.84–1.00, each score increment) were, albeit trending towards significance, associated with a lower risk of CVD in women. HEI-2015 was associated with a non-significantly lower risk of CVD in men (ORQ5 vs. Q1=0.80, 95% CI: 0.50–1.28). These dietary patterns were also associated with a lower risk of CVD in survivors with high underlying CVD risk. Conclusions As recommended to the general population, a diet rich in plant foods and moderate in animal foods needs to be a part of CVD management and prevention in childhood cancer survivors.

Simple Summary: Childhood cancer survivors have an increased lifetime risk of cardiac problems due to the cardiotoxic effects of cancer treatments. While most research has focused on the left side of the heart, little is known about the effects of these treatments on the right-side chambers. We used cardiac ultrasound to examine the right ventricle in 90 long-term survivors of childhood leukemia and a control group of 58 healthy siblings. Our findings showed that a noticeable number of survivors had subtle alterations in the pump function of the right ventricle, especially when measured using a novel parameter called a free-wall strain. Alterations in free-wall strain were more common in the survivors who were obese or smoked. This study underscores the importance of incorporating right ventricular strain assessment into routine cardiac surveillance and promoting healthy lifestyle habits among survivors. There are limited data regarding right ventricle (RV) impairment in long-term survivors of childhood acute lymphoblastic leukemia (CLS). The aim of this study was to assess RV function in these patients using echocardiographic conventional measurements and automated RV strain. Echocardiographic recordings of 90 CLS and 58 healthy siblings from the CTOXALL cohort were analyzed. For group comparisons, inverse probability weighting was used to reduce confounding. The CLS group (24.6 ± 9.7 years, 37.8% women) underwent an echocardiographic evaluation 18 (11–26) years after the diagnosis. RV systolic dysfunction was found in 16.7% of CLS individuals using RV free-wall strain (RVFWS) compared to 2.2 to 4.4% with conventional measurements. RV systolic function measurements were lower in the CLS than in the control group: TAPSE (23.3 ± 4.0 vs. 25.2 ± 3.4, p = 0.004) and RVFWS (24.9 ± 4.6 vs. 26.8 ± 4.7, p = 0.032). Modifiable cardiovascular risk factors such as obesity (p = 0.022) and smoking (p = 0.028) were independently associated with reduced RVFWS. In conclusion, RV systolic function impairment was frequent in long-term survivors of childhood leukemia, underscoring the importance of RV assessment, including RVFWS, in the cardiac surveillance of these patients. [ABSTRACT FROM AUTHOR]

Background: Timely diagnosis of treatment-related chronic health conditions in childhood cancer survivors (CCS) may result in reduced long-term morbidity and mortality. Evidence-based guidelines serve as a tool to implement risk-adapted screening examinations in long-term follow-up (LTFU) of CCS. Summary: New international LTFU guidelines from the last 3 years have been reviewed and included into a practical LTFU tool in order to provide an updated summary of LTFU recommendations. The inclusion of 13 new LTFU guidelines as well as 25 pragmatic recommendations resulted in an updated LTFU plan for implantation in daily practice. Special consideration of psychosocial and mental health aspects as well as recommendations for pregnant CCS complement holistic LTFU care. Key Messages: Risk-adapted LTFU in CCS offers the possibility for early detection and treatment of late effects. As these LTFU recommendations aim at asymptomatic individuals, benefits and potential risks of regular screening examinations have to be carefully balanced. Implementation of current evidence-based guidelines in clinical practice as well as the development of new application tools such as the Survivorship Passport can contribute to an individualized LTFU approach in order to ensure long-term health and quality of life in CCS. [ABSTRACT FROM AUTHOR]

Background: Whether diet has beneficial effects on cardiovascular disease (CVD) in childhood cancer survivors as in the general population is unknown. Therefore, we examined associations between dietary patterns and risk of CVD in adult survivors of childhood cancer. Methods: Childhood cancer survivors, 18–65 years old in the St Jude Lifetime Cohort (1882 men and 1634 women) were included in the analysis. Dietary patterns were defined by the adherence to the Healthy Eating Index (HEI)–2015, Dietary Approaches to Stop Hypertension (DASH), and alternate Mediterranean diet (aMED) based on a food frequency questionnaire at study entry. CVD cases (323 in men and 213 in women) were defined as participants with at least one grade 2 or higher CVD-related diagnosis at baseline. Multivariable logistic regression adjusted for confounders was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of CVD. Results: Greater adherence to HEI-2015 (OR=0.88, 95% CI: 0.75–1.03, per 10 score increment), DASH (OR=0.85, 95% CI: 0.71–1.01, per 10 score increment), and aMED (OR=0.92, 95% CI: 0.84–1.00, each score increment) were, albeit trending towards significance, associated with a lower risk of CVD in women. HEI-2015 was associated with a non-significantly lower risk of CVD in men (ORQ5 vs. Q1=0.80, 95% CI: 0.50–1.28). These dietary patterns were also associated with a lower risk of CVD in survivors with high underlying CVD risk. Conclusions: As recommended to the general population, a diet rich in plant foods and moderate in animal foods needs to be a part of CVD management and prevention in childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Treatment‐related late effects can worsen over time among cancer survivors. Such worsening health states may trigger changes in internal standards, values, or conceptualization of quality‐of‐life (QOL). This "response‐shift" phenomenon can jeopardize the validity of QOL assessment, and misrepresent QOL comparisons over time. This study tested response‐shift effects in reporting future‐health concerns among childhood cancer survivors who experienced progression in chronic health conditions (CHCs). Methods: 2310 adult survivors of childhood cancer from St. Jude Lifetime Cohort Study completed a survey and clinical assessment at two or more timepoints. Based on 190 individual CHCs graded for adverse‐event severity, global CHC burden was classified as "progression" or "non‐progression". QOL was assessed using the SF‐36TM eight domains and physical‐ and mental‐component summary scores (PCS, MCS). A single global item measured concerns about future health. Random‐effects models comparing survivors with and without progressive global CHC burden (progressors vs. non‐progressors) evaluated response‐shift effects (recalibration, reprioritization, reconceptualization) in reporting future‐health concerns. Results: Compared with non‐progressors, progressors were more likely to de‐emphasize (or downplay) overall physical and mental health in evaluating future‐health concerns (p‐values<0.05), indicating recalibration response‐shift, and more likely to de‐emphasize physical health earlier rather than later in follow‐up (p‐value<0.05), indicating reprioritization response‐shift. There was evidence for a reconceptualization response‐shift with progressor classification associated with worse‐than‐expected future‐health concerns and physical health, and better‐than‐expected pain and role‐emotional functioning (p‐values<0.05). Conclusion: We identified three types of response‐shift phenomena in reporting concerns about future health among childhood cancer survivors. Survivorship care or research should consider response‐shift effects when interpreting changes in QOL over time. [ABSTRACT FROM AUTHOR]

With advancements in cancer treatment and supportive care, there is a growing population of childhood cancer survivors who experience a substantial burden of comorbidities related to having received cancer treatment at a young age. Despite an overall reduction in the incidence of most chronic health conditions in childhood cancer survivors over the past several decades, the cumulative incidence of certain late effects, in particular diabetes mellitus (DM), has increased. The implications are significant, because DM is a key risk factor for cardiovascular disease, a leading cause of premature death in childhood cancer survivors. The underlying pathophysiology of DM in cancer survivors is multifactorial. DM develops at younger ages in survivors compared to controls, which may reflect an “accelerated aging” phenotype in these individuals. The treatment-related exposures (i.e., chemotherapy, radiation) that increase risk for DM in childhood cancer survivors may be more than additive with established DM risk factors (e.g., older age, obesity, race, and ethnicity). Emerging research also points to parallels in cellular processes implicated in aging- and cancer treatment-related DM. Still, there remains marked inter-individual variability regarding risk of DM that is not explained by demographic and therapeutic risk factors alone. Recent studies have highlighted the role of germline genetic risk factors and epigenetic modifications that are associated with risk of DM in both the general and oncology populations. This review summarizes our current understanding of recognized risk factors for DM in childhood cancer survivors to help inform targeted approaches for disease screening, prevention, and treatment. Furthermore, it highlights the existing scientific gaps in understanding the relative contributions of individual therapeutic exposures and the mechanisms by which they exert their effects that uniquely predispose this population to DM following cancer treatment.

BackgroundBeing diagnosed with cancer in childhood often has a direct impact on the child's opportunities to participate in activities and the child's sense of belonging in different life situations. Experiences of illness in youth affect the lives of these individuals in numerous ways and they need pronounced support to regain their normal life after treatment.PurposeTo illustrate how childhood cancer survivors describe the role of the caring support provided by healthcare professionals at diagnosis and during the cancer trajectory.MethodsA mixed methods approach was applied. Swanson's Theory of Caring was used to deductively analyze the answers in a study-specific questionnaire with Likert scales (1–5). Descriptive and comparative statistics and exploratory factor analyses were performed.ResultsSixty-two former patients, diagnosed with solid tumors/lymphoma in 1983 to 2003 in Sweden, participated. The mean time passed since treatment was 15.7 years. Swanson's caring processes Being with and Doing for were the most prominent loading categorical factor indicators. Higher scores for healthcare professionals being emotionally present (Being with), doing for others what they would do for themselves (Doing for) and being willing to understand the sick child's situation (Knowing) were highlighted by survivors older than 30 years, compared to those younger than 30 years (p = 0.041, p = 0.045, and p = 0.013, respectively). An increased vulnerability regarding their ability to cope with difficulties (Maintain belief) was found among participants who were treated during adolescence, related to schoolchildren (p = 0.048), and among those who had been treated with extra-cranial irradiation in comparison with no extra-cranial irradiation (p = 0.004). The role of having a partner in comparison with being single was underlined among those who felt they had acquired the tools they needed to take care of themselves (Enabling) (p = 0.013). The total explained variance was 63%.ConclusionsA person-centered care approach during treatment for childhood cancer, reflected by a caring model, highlights the role of healthcare professionals being emotionally present, involving children, performing actions, and with an approach that has potential long-term implications. Childhood cancer patients and survivors need not only clinically competent professionals, but professionals who provide caring interactions with compassion.

Purpose : Using the International Standard Classification of Education (ISCED), we examined the educational and vocational pathways of two comparable, parental cohorts: childhood cancer survivors (CCS) and their siblings. Both cohorts had previously entered parenthood. The aim of the study was to elucidate whether childhood cancer and treatment affect the educational pathways chosen by parents who are former patients. Methods: We analysed data that was collected from childhood cancer survivors and their siblings regarding their offspring's health within the FeCt Multicentre Offspring Study (conducted 2013–2016). We evaluated and compared the professional pathways of (i) all participating survivors and all participating siblings and those of (ii) survivors and their biological siblings. Results: Overall information on parental gender, age, and education were available from 1077 survivors and 246 siblings (group (i)). The majority of participants were female with a mean age of 35.2 (survivor) and 37.9 (sibling) years at time of survey. For subgroup (ii), analysis information was available on 191 survivors and 210 siblings. Fathers achieved university degrees significantly more often than mothers (p = 0.003 (i), p < 0.001 (ii)). The distribution of professional education was not significantly different between cancer survivors and siblings in either cohort (i) or (ii). Conclusions: Regarding our research on the educational and vocational trajectory of CCS, patients can be reassured that family planning and vocational education are well compatible. Inequalities regarding gender-specific educational pathways remain to be addressed. Implications for Cancer Survivors: CCS should monitor their fertility status regularly and, if necessary, cryopreserve germ cells or tissue in order to optimize their family planning. Educational opportunities should be pursued as desired and with confidence. Local as well as European aftercare programs can assist with family planning and education. [ABSTRACT FROM AUTHOR]

Posttraumatic growth (PTG) represents positive changes following a trauma, crisis, and/or psychologically distressing event. Experiencing cancer can serve as a traumatic event for patients, resulting in life changes among survivors. Various PTG measures have been used to assess post-cancer change among childhood cancer survivors (CCS), but few have been evaluated for use in this population. This study examined the factor structure of an adapted, 11-item version of the Posttraumatic Growth Inventory (PTGI) among CCS. A randomly selected subgroup of participants (N = 332) was selected from the Los Angeles Cancer Surveillance Program (mean age of 26.5 years at time of survey, mean age at diagnosis of 12 years, primarily male [53.6%], and Hispanic [51.5%]). Participants indicated the degree to which they experienced positive, negative, or no change in their life because of their cancer experience. An exploratory factor analysis (EFA) identified two factors: Appreciation of New Possibilities and Spiritual Change. The adapted, 11-item PTGI was deemed appropriate for use among CCS. Additional research is needed to confirm the use of the two-factor model with confirmatory factor analysis in an independent sample. Future research on PTG among CCS can consider spiritual change as a potential independent factor. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors (CCS) are at risk of polyneuropathy due to chemotherapy, but studies in young survivors are scarce and diagnosis is challenging. We aimed to study the presence of polyneuropathy and the possible effect of cumulative doses of chemotherapeutic agents in a representative group of adolescent survivors. CCS aged nine to 18 years and age- and sex-matched controls were recruited from the cross-sectional Physical Activity and Fitness among Childhood Cancer Survivors (PACCS) study. CCS with various cancer diagnoses who had ended cancer treatment one year or more before study were included. Polyneuropathy was evaluated clinically and with nerve conduction studies (NCSs) in three motor and five sensory nerves. We used mixed-effects linear regression models to compare CCS and controls, and investigate possible associations between cumulative chemotherapy doses and NCS amplitudes. A total of 127 CCS and 87 controls were included, with 14% CCS having probable or confirmed polyneuropathy. NCS amplitudes were lower in survivors compared with controls in all nerves. The largest mean difference was 3.47 μV (95% confidence interval [CI], 2.18 to 4.75) in the tibial plantar medial sensory and 1.91 mV (95% CI, 0.78 to 3.04) in the tibial motor nerve. The cumulative dose of platinum derivatives was associated with lower tibial motor nerve amplitude (−0.20; 95% CI, −0.35 to −0.04 mV for 100 mg/m2 dose increase) but not in other nerves. We found no significant associations between vinca alkaloids cumulative dose and amplitudes. CCS without clinical signs or symptoms of polyneuropathy may have subtle nerve affection. The clinical long-term impact of this novel observation should be evaluated in larger, longitudinal studies. [ABSTRACT FROM AUTHOR]

IntroductionSubsequent breast cancer (SBC) represents a major complication in childhood cancer survivors and screening for SBC in survivors after incidental irradiation of breasts is recommended. In this article, we report the results and discuss benefits of SBC screening in female pts treated for Hodgkin's lymphoma (HL) in Slovenia in a period of 45 years.MethodsBetween 1966 and 2010, 117 females were treated for HL under the age of 19 in Slovenia. One hundred five of them survived for 5 years and were included in our study. They were 3–18 (med. 15) years old at diagnosis and followed for 6–52 (med. 28) years. Eighty-three percent of them had chest RT with a median dose of 30 Gy. Ninety-seven (92%) of 105 pts were regularly followed according to the international guidelines including yearly screening mammography/breast MRI in those who received chest RT.ResultsWe diagnosed 10 SBCs in eight pts 14–39 (med. 24) years after diagnosis at the age of 28–52 (med. 42) years. At 40 years of follow-up, cumulative incidence of SBCs in females who got chest RT was 15.2%. Seven of eight patients (with 9 SBCs) got chest RT with 24–80 (med. 36) Gy at the age of 12 to 18 (median 17) years. Two patients in this group got bilateral SBC. One patient got invasive SBC after being treated with ChT containing high-dose of anthracyclines without chest RT at the age of 13. All eight invasive SBCs were invasive ductal cancers, HER2 receptors negative, all but one with positive hormonal receptors. Six invasive cancers were of stage T1N0, one T1N1mi, only one, diagnosed before era of screening, was of T2N1. None of 8 pts died of SBC.ConclusionAfter introduction of regular breast screening in our female patients, who received chest RT in childhood, all SBCs were of early stage and no patients died of SBC. Survivors of pediatric HL should be informed about the risk of late sequelae of treatment for HL, including SBC. Regular follow-up with breast cancer screening and breast self-examination is of vital importance in those treated with chest RT.

Background: Along with improvements in curative treatment for childhood cancer, childhood cancer survivors (CCSs) often face numerous problems such as late complications of cancer treatment, social issues at school, struggles in employment, and financial difficulties. These children have received a wide range of support from the medical, educational, and administrative sectors. However, it was unclear how this multifaceted support contributed to quality of life (QOL) of CCSs in Japan. Methods: The subjects were 46 CCSs of 16 years of age or older at the time of the survey, who had been diagnosed and treated for pediatric cancer. A self‐administered questionnaire survey was conducted to investigate the in‐hospital status during treatment, adjustment when returning to school, and administrative social support. The QOL of CCSs was also evaluated by the Medical Outcome Study 36‐Item Short‐Form Health Survey. Results: Twenty‐four CCSs answered the questions. The respondents who had experienced school‐life problems tended to have lower role/social QOL scores (p = 0.046), whereas the CCSs who had experienced administrative counseling tended to have lower physical QOL scores (p = 0.036). The mental QOL scores tended to be higher in respondents who were informed of the exact diagnosis of cancer during hospitalization. The role/social QOL scores tended to be lower in respondents who advanced to their preferred career path. Conclusions: It is essential for three stakeholders—health‐care providers, education offices, and public administrative agencies—to collaborate to share long‐term psychosocial issues or concerns related to employment or daily living that CCSs may encounter, and to establish a coordinated approach to support CCSs. [ABSTRACT FROM AUTHOR]

Background: Although premature aging is a significant concern in adult survivors of childhood cancer, little is known about the role of diet in premature aging in this vulnerable population. Therefore, we examined whether dietary patterns specific to childhood cancer survivors are associated with premature aging., Methods: This cross-sectional study included 2904 adult survivors of childhood cancer (mean age = 31 years, SD = 8 years) in the St. Jude Lifetime Cohort. Diet was assessed using a food frequency. Four dietary patterns were identified: (1) plant-based diet pattern high in whole grains, fruit, and vegetables; (2) fast-food diet pattern high in processed meat, high-fat dairy, and sweets and desserts; (3) Western contemporary diet pattern high in red meat, pasta/rice, French fries, and salty snacks; and (4) animal-based diet pattern high in all meats. The deficit accumulation index (DAI), a proxy measure of premature aging, was estimated as the ratio of the number of age-related items out of 44 total conditions and categorized into low, medium, and high deficit accumulation groups. Multivariable multinomial logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of medium and high DAI groups (reference: low group)., Results: Compared to survivors consuming a plant-based diet, those who consume a fast-food (OR high vs. low DAI  = 1.82, 95% CI: 1.12‒2.96), a Western contemporary (OR = 2.12, 95% CI: 1.31‒3.43), or an animal-based diet (OR = 2.10, 95% CI: 1.15‒3.84) had approximately a twofold higher odds of being in the high DAI group. In contrast, survivors with a plant-based diet had almost 50% lower odds of being in the high DAI group, compared to those with other dietary patterns (OR ranges 0.47‒0.55)., Conclusions: A plant-based diet may promote healthy aging, whereas a fast-food, a Western contemporary, and an animal-based diet may have detrimental effects on aging. Adult survivors of childhood cancer may benefit from nutrition education and interventions for healthy aging., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the St. Jude Children’s Research Hospital Institutional Review Board (#00000029 FWA00004775; IRB number: SJLIFE; reference number: 027446), and all participants provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Context/objective: Diabetes mellitus (DM), a possible adverse effect of childhood cancer treatment, is strongly associated with cardiovascular disease and early mortality in adult childhood cancer survivors (CCS). Here, we assess the prevalence and determinants of DM in our nationwide CCS cohort., Design/methods: In this cross-sectional study, the prevalence of DM was assessed in 2,338 CCS, using the Lifelines cohort (n=132,226 adults with no history of cancer) as a reference. DM was defined through serum glucose measurement (fasting glucose ≥7.0mmol/L or non-fasting ≥11.1mmol/L) and/or self-report (previous diagnosis and/or medication use). Multivariable logistic regression models, adjusted for age, sex, and BMI, were used to assess the cohort effect on the presence of DM. Multivariable logistic regression analysis was used to identify determinants of DM in CCS., Results: Survivors (median age 34.7 years, median follow-up time 27.1 years) showed increased odds for hyperglycemia (aOR=2.72, 95%CI=2.06-3.59), previous DM diagnosis (aOR=3.03, 95%CI=2.33-3.95), and anti-diabetic medication use (aOR=2.94, 95%CI=2.17-3.99), compared to the reference cohort. Age (OR=4.32, 95%CI=1.84-10.15, >35 versus 18-35 years), BMI (OR=1.12, 95%CI=1.08-1.16, per point), family history of DM (OR=2.38, 95%CI=1.51-3.76), prior abdominal/pelvic radiotherapy (OR=4.19, 95%CI=2.32-7.55), total body irradiation (OR=14.31, 95%CI=6.98-29.34), hypogonadism (OR=2.40, 95%CI=1.15-4.99), hypertension (OR=1.71, 95%CI=1.06-2.76), and dyslipidemia (OR=3.81, 95%CI=2.15-6.75) were associated with DM in CCS. A significant interaction between age and sex on the development of DM in survivors was identified., Conclusions: The identified three-fold increased risk of DM in CCS, along with the clinically relevant -and some modifiable- determinants, underscores the importance of early risk-based screening and the exploration of lifestyle interventions in this population., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Parents of children treated for cancer may experience psychological difficulties including depression, anxiety, and posttraumatic stress. Digital interventions, such as internet-administered cognitive behavioral therapy, offer an accessible and flexible means to support parents. However, engagement with and adherence to digital interventions remain a significant challenge, potentially limiting efficacy. Understanding factors influencing user engagement and adherence is crucial for enhancing the acceptability, feasibility, and efficacy of these interventions. We developed an internet-administered, guided, low-intensity cognitive behavioral therapy (LICBT)-based self-help intervention for parents of children treated for cancer, (EJDeR [internetbaserad självhjälp för föräldrar till barn som avslutat en behandling mot cancer or internet-based self-help for parents of children who have completed cancer treatment]). EJDeR included 2 LICBT techniques-behavioral activation and worry management. Subsequently, we conducted the ENGAGE feasibility trial and EJDeR was found to be acceptable and feasible. However, intervention adherence rates were marginally under progression criteria., Objective: This study aimed to (1) describe user engagement with the EJDeR intervention and examine whether (2) sociodemographic characteristics differed between adherers and nonadherers, (3) depression and anxiety scores differed between adherers and nonadherers at baseline, (4) user engagement differed between adherers and nonadherers, and (5) user engagement differed between fathers and mothers., Methods: We performed a secondary analysis of ENGAGE data, including 71 participants. User engagement data were collected through log-data tracking, for example, communication with e-therapists, homework submissions, log-ins, minutes working with EJDeR, and modules completed. Chi-square tests examined differences between adherers and nonadherers and fathers and mothers concerning categorical data. Independent-samples t tests examined differences regarding continuous variables., Results: Module completion rates were higher among those who worked with behavioral activation as their first LICBT module versus worry management. Of the 20 nonadherers who opened the first LICBT module allocated, 30% (n=6) opened behavioral activation and 70% (n=14) opened worry management. No significant differences in sociodemographic characteristics were found. Nonadherers who opened behavioral activation as the first LICBT module allocated had a significantly higher level of depression symptoms at baseline than adherers. No other differences in depression and anxiety scores between adherers and nonadherers were found. Minutes working with EJDeR, number of log-ins, days using EJDeR, number of written messages sent to e-therapists, number of written messages sent to participants, and total number of homework exercises submitted were significantly higher among adherers than among nonadherers. There were no significant differences between fathers and mothers regarding user engagement variables., Conclusions: Straightforward techniques, such as behavioral activation, may be well-suited for digital delivery, and more complex techniques, such as worry management, may require modifications to improve user engagement. User engagement was measured behaviorally, for example, through log-data tracking, and future research should measure emotional and cognitive components of engagement., Trial Registration: ISRCTN Registry 57233429; https://doi.org/10.1186/ISRCTN57233429., (©Christina Reuther, Louise von Essen, Mudassir Imran Mustafa, Markus Saarijärvi, Joanne Woodford. Originally published in JMIR Formative Research (https://formative.jmir.org), 28.01.2025.)

Background: Childhood cancer survivors (CCS) have a 50% higher risk of diabetes mellitus (DM) compared with the general population. Interventions in survivors with prediabetes (fasting glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) may mitigate the development of DM and its attendant morbidity, but there is limited information on the feasibility of secondary prevention in this setting., Methods: This 6-week pilot feasibility 1:1 randomized controlled trial enrolled 20 CCS on a structured telehealth exercise program ± nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor. Feasibility metrics were: (1) ≥50% of eligible CCS enrolled onto study; (2) ≥70% of participants completed baseline and end-of-study assessments; (3) ≥70% compliance with exercise and NR. Secondary endpoints included changes in biomarkers associated with glucose homeostasis and muscle health., Results: Median age (years) at cancer diagnosis was 16.5 (range, 1.5-21.5) and 35.5 (range, 18.0-67.0) at study enrollment. Enrollment rate was 87%, and 85% of participants completed baseline and end-of-study assessments. The mean percentage of exercise sessions completed was 86.6%; NR compliance was > 90%. There were no severe adverse events attributable to study interventions. Secondary endpoints were not significantly different between study arms at study completion. Myostatin decrease was observed in participants who completed a higher median number of exercise sessions and was associated with decreased intramuscular adipose tissue and increased lower extremity muscle cross-sectional area., Conclusions: A telehealth exercise intervention ± NR supplementation was feasible in CCS with prediabetes. Future studies in larger cohorts may be needed to evaluate their beneficial effects on muscle health and DM risk among CCS., (© 2024 Wiley Periodicals LLC.)

Endocrine disorders in survivors of childhood, adolescent, and young adult (CAYA) cancers are associated with substantial adverse physical and psychosocial effects. To improve appropriate and timely endocrine screening and referral to a specialist, the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) aims to develop evidence and expert consensus-based guidelines for healthcare providers that harmonize recommendations for surveillance of endocrine disorders in CAYA cancer survivors. Existing IGHG surveillance recommendations for premature ovarian insufficiency, gonadotoxicity in males, fertility preservation, and thyroid cancer are summarized. For hypothalamic-pituitary (HP) dysfunction, new surveillance recommendations were formulated by a guideline panel consisting of 42 interdisciplinary international experts. A systematic literature search was performed in MEDLINE (through PubMed) for clinically relevant questions concerning HP dysfunction. Literature was screened for eligibility. Recommendations were formulated by drawing conclusions from quality assessment of all evidence, considering the potential benefits of early detection and appropriate management. Healthcare providers should be aware that CAYA cancer survivors have an increased risk for endocrine disorders, including HP dysfunction. Regular surveillance with clinical history, anthropomorphic measures, physical examination, and laboratory measurements is recommended in at-risk survivors. When endocrine disorders are suspected, healthcare providers should proceed with timely referrals to specialized services. These international evidence-based recommendations for surveillance of endocrine disorders in CAYA cancer survivors inform healthcare providers and highlight the need for long-term endocrine follow-up care in subgroups of survivors and elucidate opportunities for further research. [ABSTRACT FROM AUTHOR]

To evaluate the prevalence of and risk factors for hypertension in childhood cancer survivors (CCSs) who were treated with potentially nephrotoxic therapies. In the Dutch Childhood Cancer Survivor Study LATER cohort part 2 renal study, 1024 CCS ≥5 years after diagnosis, aged ≥18 years at study participation, treated between 1963 and 2001 with nephrectomy, abdominal radiotherapy, total body irradiation (TBI), cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide (≥1 g/m2 per single dose or ≥10 g/m2 total) or haematopoietic stem cell transplantation participated and 500 controls from Lifelines. Hypertension was defined as blood pressure (BP) (mmHg) systolic ≥140 and/or diastolic ≥90 or receiving medication for diagnosed hypertension. At the study visit, the CKD-EPI 2012 equation including creatinine and cystatin C was used to estimate the glomerular filtration rate (GFR). Multivariable regression analyses were used. For ambulatory BP monitoring (ABPM), hypertension was defined as BP daytime: systolic ≥135 and/or diastolic ≥85, night time: systolic ≥120 and/or diastolic ≥70, 24-h: systolic ≥130 and/or diastolic ≥80. Outcomes were masked hypertension (MH), white coat hypertension and abnormal nocturnal dipping (aND). Median age at cancer diagnosis was 4.7 years (interquartile range, IQR 2.4–9.2), at study 32.5 years (IQR 27.7–38.0) and follow-up 25.5 years (IQR 21.4–30.3). The prevalence of hypertension was comparable in CCS (16.3%) and controls (18.2%). In 12% of CCS and 17.8% of controls, hypertension was undiagnosed. A decreased GFR (<60 ml/min/1.73 m2) was associated with hypertension in CCS (OR 3.4, 95% CI 1.4–8.5). Risk factors were abdominal radiotherapy ≥20 Gy and TBI. The ABPM-pilot study (n = 77) showed 7.8% MH, 2.6% white coat hypertension and 20.8% aND. The prevalence of hypertension was comparable among CCS who were treated with potentially nephrotoxic therapies compared to controls, some of which were undiagnosed. Risk factors were abdominal radiotherapy ≥20 Gy and TBI. Hypertension and decreased GFR were associated with CCS. ABPM identified MH and a ND. • Prevalence of hypertension is comparable in childhood cancer survivors and controls. • Risk factors for hypertension are abdominal radiotherapy and total body irradiation. • Hypertension is associated with decreased glomerular filtration rate in childhood cancer survivors. • Ambulatory blood pressure monitoring has added value for childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Abstract Background Emerging research suggests that survivors of childhood and adolescent cancers are at risk for morbidity and mortality associated with air pollutants. However, caregiver perceptions of the effects of air pollution are unknown. Thus, to address this gap we described caregivers’ perceptions of air pollution’s impact on general population health and specifically on childhood cancer survivors, and caregivers’ air pollution information-seeking and exposure reduction behaviors. Methods Participants were Utah residents, ≥18 years, and caregiver of a childhood cancer survivor who had completed treatment. Semi-structured interviews were conducted with caregivers to describe their perspectives on air quality, how air pollution impacts health (general population and survivor health), and their information seeking and exposure reduction behaviors. Interviews were recorded, transcribed, and analyzed through two rounds of structured coding. Results Caregivers (N = 13) were non-Hispanic white and primarily females (92.3%) between 30 and 49 years old (46.2%). Most families lived within the Wasatch Front (69.2%), the main metropolitan of Utah. Two categories emerged pertaining to caregiver’s perceptions of air pollution: 1) Limited awareness about the health effects of air pollution, and 2) Unsuccessful information seeking and minimal exposure reduction behaviors. All caregivers held negative perceptions of air pollution in Utah, but most were unaware of how pollution affects health. While some families limited air pollution exposure by avoiding outdoor activity or physically leaving the region, few practiced survivor-specific exposure reduction. Nearly half of caregivers worried about potential effects of air pollution on survivor health and wanted more information. Conclusions Despite negative perceptions of air pollution, caregivers were divided on whether air pollution could impact survivor health. Few caregivers engaged in exposure reduction for their cancer survivor. As air pollution levels increase in the U.S., continued research on this topic is essential to managing cancer survivor respiratory and cardiovascular health.

BackgroundChildhood cancer survivors (CCSs) have a lifelong increased risk of chronic health problems, most of which are associated with the curative therapies. Recent studies have suggested that prospective active screening using comprehensive assessments for CCSs is superior in identifying undiagnosed chronic health problems.MethodsTo assess the significance of active screening using comprehensive medical examinations for detecting chronic health problems in multiple organ systems in CCSs, we retrospectively compared the frequency and severity of health problems between two different cohorts of CCSs in a single institution: 110 CCSs who visited the outpatient clinic for regular follow-ups between December 2010 and December 2015 (regular follow-up group) vs. 58 CCSs who underwent comprehensive medical examinations between February 2016 and September 2019 (active screening group). CCSs were defined as patients aged ≥ 18 years who had been diagnosed as having childhood cancer ≥ 10 years before and had survived without cancer for ≥ 5 years.ResultsPatient characteristics were similar between the two groups except for primary diagnosis (more brain tumors and embryonal tumors in the active screening group) and treatment history (more alkylating agents used and surgical interventions performed in the active screening group). The prevalence and the median number of health problems were significantly higher in the active screening group than in the regular follow-up group: 93% vs. 67% and 1.0 [0.0–8.0] vs. 2.0 [0.0–7.0] respectively. In term of organ-specific health problems, pulmonary dysfunction, neurocognitive impairment, ocular abnormalities, and dental abnormalities were identified more in the active screening group, partly because these problems had not been assessed in the regular follow-up group. Nevertheless, the prevalence of grade 3–5 health problems was similar between the two groups, except for pulmonary dysfunction.ConclusionActive screening using comprehensive medical examinations was effective for identifying health problems in CCSs. Although the prevalence of severe problems identified by both approaches was similar, comprehensive medical examinations could detect overlooked problems such as severe pulmonary dysfunction, dental maldevelopment, and borderline intellectual functioning, which might have an impact on quality of life in CCSs.

Objective: Increased survival rates in childhood cancers have led the researchers to focus on long-term side effects and possible risk factors for late nephrotoxicity related to the treatment regimens applied. Our aim is to evaluate drug-induced nephrotoxicity in survivors of childhood cancer and to investigate the compatibility of creatinine clearance with the estimated glomerular filtration rate. Methods: The presence of glomerular and tubular dysfunction has been screened among 59 childhood cancer survivors who had completed their treatment regimens with cisplatin, carboplatin, ifosfamide, and /or high dose methotrexate. Results: The mean age of patients was 10.7+-5.5 years (2.5-23), and mean follow-up time was 2.6+-2.1 years (0.5-8). Renal dysfunction was detected in 65% of the patients. The most prevalent manifestation of renal dysfunction was decreased glomerular filtration rate (n: 19, 32.2%), and increased urinary β2-microglobulin excretion (n: 12, 20.4%), followed by microalbuminuria (n: 6, 10.1%). Survivors treated with combined chemotherapy regimens (cisplatin, carboplatin, ifosfamide) had significantly lower tubular reabsorption of phosphate than those treated with high dose of methotrexate. The glomerular filtration rate analysis was performed using different methods, and a moderate correlation (r=0.563, p=0.00) was found between estimated glomerular filtration rates calculated according to cystatin-C-based equations and Schwartz formula. Conclusion: Childhood cancer survivors demonstrated a high frequency of renal complications in the current study. We have shown that the calculation of the estimated glomerular filtration rate using the Schwartz formula or cystatin-C-based equations is compatible with the creatinine clearance in this specific patient group. In survivors of childhood cancer who cannot perform 24-hour urine collection, determination of estimated glomerular filtration rate is a more practical approach.

Childhood cancer survivors are at risk for chemotherapy-induced peripheral neuropathy (CIPN). Physical therapy (PT) improves CIPN symptoms, but little is known about survivors' PT utilization. We described characteristics of survivors with ≥ grade 2 CIPN, investigated PT referral and attendance, and described characteristics of survivors who attended and did not attend PT. Childhood cancer survivors <21 years old at cancer diagnosis and ≥2 years posttherapy, living in the United States, evaluated at a regional survivorship clinic were included in this retrospective analysis if they had motor CIPN. Symptomatic CIPN (≥grade 2 by Common Terminology Criteria for Adverse Events) and PT referral/attendance were tabulated. Patient characteristics from the medical record, and neighborhood characteristics (retrieved using survivors' zip code from the National Neighborhood Data Archive) were described by group. Among 91 survivors with CIPN (median 17.5 years old, 8.1 years postcancer diagnosis, 45.1% female), 35 (38.5%) had ≥ grade 2 CIPN. Survivors with ≥ grade 2 CIPN were 28.6% female, and 45.7% were <13 years old. Twenty-four (68.6%) survivors with ≥ grade 2 CIPN agreed to PT referral, and 15 (42.9%) attended PT. Among survivors who attended PT, 73.3% were <13 years old. Neighborhood characteristics of survivors included median percentage of adults without a high school diploma (6.7% PT attendees, 12.5% nonattendees), median percentage of adults who are foreign-born (11.5% PT attendees, 16.4% nonattendees), and median percentage of households with an annual income of <$15,000 (3.2% PT attendees, 6.5% nonattendees). While 68.6% of survivors with ≥ grade 2 CIPN were referred to PT, only 42.9% attended. Studies to better understand barriers to PT attendance and interventions to improve attendance are needed, especially in older survivors. Nurses can play a key role in survivor education and care coordination to help optimize PT attendance. [ABSTRACT FROM AUTHOR]

Female childhood cancer survivors with history of bone marrow transplant with or without total body irradiation have increased pregnancy risks. Preconception counselling and early referral to appropriate clinical pathways may improve pregnancy outcomes.UK-wide survey of clinicians, promoted via social media and conferences, jointly funded by Action Medical Research/Borne.Forty responses received between 22 October 2020 and 21 October 2021: 43% reviewed this group monthly, 15% annually, 15% less than annually, and 27% never (for O & G only: 13%, 13%, 26%, and 48%, respectively). Pre-pregnancy, most discussed potential fertility/pregnancy implications. Early pregnancy discussions included late miscarriage (34%), preterm birth (44%), fetal growth restriction (31%), and health risks other than cancer (30%). During pregnancy: 80% refer to specialist clinics; 87% offer extra investigations; 33% prescribed aspirin; 20% offered cervical cerclage; and 13% prescribed progesterone. 43% reviewed this group monthly, 15% annually, 15% less than annually, and 27% never (for O & G only: 13%, 13%, 26%, and 48%, respectively).Pre-pregnancy, most discussed potential fertility/pregnancy implications.Early pregnancy discussions included late miscarriage (34%), preterm birth (44%), fetal growth restriction (31%), and health risks other than cancer (30%).During pregnancy: 80% refer to specialist clinics; 87% offer extra investigations; 33% prescribed aspirin; 20% offered cervical cerclage; and 13% prescribed progesterone.Evidence of variation in care. As previous observations suggest pregnancy outcomes improve when managed in specialist clinics, clearer guidance is required. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer are at lifelong risk of morbidity (such as new cancers or heart failure) and premature mortality due to their cancer treatment. These are termed late effects. Therefore, they require lifelong, risk-tailored surveillance. However, most adult survivors of childhood cancer do not complete recommended surveillance tests such as mammograms or echocardiograms. Objective: In partnership with survivors, family physicians, and health system partners, we are designing a provincial support system for high-priority tests informed by principles of implementation science, behavioral science, and design thinking. Methods: Our multiphase process was structured as follows. Step 1 consisted of a qualitative study to explore intervention components essential to accessing surveillance tests. Step 2 comprised a workshop with childhood cancer survivors, family physicians, and health system stakeholders that used the Step 1 findings and “personas” (a series of fictional but data-informed characters) to develop and tailor the intervention for different survivor groups. Step 3 consisted of intervention prototype development, and Step 4 involved iterative user testing. Results: The qualitative study of 30 survivors and 7 family physicians found a high desire for information on surveillance for late effects. Respondents indicated that the intervention should help patients book appointments when they are due in addition to providing personalized information. Insights from the workshop included the importance of partnering with both family physicians and survivorship clinics and providing emotional support for survivors who may experience distress upon learning of their risk for late effects. In our user-testing process, prototypes went through iterations that incorporated feedback from users regarding acceptability, usability, and functionality. We sought to address the needs of survivors and physicians while balancing the capacity and infrastructure available for a lifelong intervention via our health system partners. Conclusions: In partnership with childhood cancer survivors, family physicians, and health system partners, we elucidated the barriers and enablers to accessing guideline-recommended surveillance tests and designed a multifaceted solution that will support survivors and their family physicians. The next step is to evaluate the intervention in a pragmatic randomized controlled trial. [ABSTRACT FROM AUTHOR]

Simple Summary: We studied survivors of childhood cancer who received cancer treatment that might affect the kidneys and compared them to controls from the general population. We investigated if there was a difference in the occurrence of tubular dysfunction. The tubules are the part of the kidney responsible for reabsorption of needed substances to the blood and the removal of wastes. After around 25 years since their cancer diagnosis, we found that in general there were no differences between survivors and controls, but survivors more often had losses of small proteins in the urine. Yet, some survivors of childhood cancer were found to have an increased risk of tubular dysfunction. Namely, survivors treated with the chemotherapeutic agents ifosfamide, cisplatin or carboplatin. Therefore, these patients should be monitored during their follow-up. The aim of this nationwide cross-sectional cohort study was to determine the prevalence of and risk factors for tubular dysfunction in childhood cancer survivors (CCS). In the DCCSS-LATER 2 Renal study, 1024 CCS (≥5 years after diagnosis), aged ≥ 18 years at study, treated between 1963 and 2001 with potentially nephrotoxic therapy (i.e., nephrectomy, abdominal radiotherapy, total body irradiation, cisplatin, carboplatin, ifosfamide, high-dose cyclophosphamide, or hematopoietic stem cell transplantation) participated, and 500 age- and sex-matched participants from Lifelines acted as controls. Tubular electrolyte loss was defined as low serum levels (magnesium < 0.7 mmol/L, phosphate < 0.7 mmol/L and potassium < 3.6 mmol/L) with increased renal excretion or supplementation. A α1-microglobulin:creatinine ratio > 1.7 mg/mmol was considered as low-molecular weight proteinuria (LMWP). Multivariable risk analyses were performed. After median 25.5 years follow-up, overall prevalence of electrolyte losses in CCS (magnesium 5.6%, potassium 4.5%, phosphate 5.5%) was not higher compared to controls. LMWP was more prevalent (CCS 20.1% versus controls 0.4%). LMWP and magnesium loss were associated with glomerular dysfunction. Ifosfamide was associated with potassium loss, phosphate loss (with cumulative dose > 42 g/m2) and LMWP. Cisplatin was associated with magnesium loss and a cumulative dose > 500 mg/m2 with potassium and phosphate loss. Carboplatin cumulative dose > 2800 mg/m2 was associated with potassium loss. In conclusion, long-term tubular dysfunction is infrequent. Yet, ifosfamide, cisplatin and carboplatin are risk factors. [ABSTRACT FROM AUTHOR]

Background Childhood cancer survivors (CCSs) show relevant cardiac morbidity and mortality throughout life. Early detection is key for optimal support of patients at risk. The aim of this study was to evaluate 2‐dimensional speckle‐tracking echocardiography strain analysis during semisupine exercise stress in CCSs for detection of subclinical left ventricular dysfunction after cancer treatment. Methods and Results Seventy‐seven CCSs ≥1‐year postchemotherapy were prospectively examined at rest, low, and submaximal stress level and compared with a cohort of healthy adolescents and young adults (n=50). Global longitudinal strain (GLS), short axis circumferential strain, and corresponding strain rates were analyzed using vendor‐independent software. CCSs at median 7.8 years postchemotherapy showed comparable left ventricular GLS, circumferential strain, and strain rate values at all stress stages to healthy controls. Yet, prevalence of abnormal GLS (defined as

Abstract Background Childhood cancer survivors (CCS) have high prevalence of obesity vitamin D (VD) deficiency together with dyslipidemia. We aimed to evaluate lipid profile and the effect of VD supplementation in CCS. Results VD deficiency was more frequent among obese CCS and their lipid profiles, TC, and LDL-C levels were significantly higher compared to non-obese patients. After VD supplementation trials, VD levels increased among obese and non-obese children albeit it was significantly higher in non-obese subjects while the lipid profile of obese patients significantly decreased. Also, parathyroid hormone levels were persistently elevated among VD-deficient obese patients. Yet, the weight of obese patients remained unchanged. Conclusion VD deficiency was more prevalent among obese CCS. VD supplementation helped in normalization of the lipid profile of obese CCS. Regular measurement of PTH and 25OH-VD is recommended for CCS especially obese ones who may need VD supplementation.

Simple Summary: Heart failure is a major problem that affects childhood cancer survivors. Thus, early detection of cardiotoxicity before the onset of symptoms is imperative. Global longitudinal strain (GLS) is an echocardiographic tool that can be used to detect subclinical changes in cardiac function. However, its utility in long-term cardiac monitoring is unclear, and its application in routine practice is limited in this setting. We aimed to assess the prevalence of cardiotoxicity in 90 long-term childhood leukemia survivors (CLSs) using conventional echocardiography and automated software that simplifies GLS measurement. Additionally, we compared these measurements and biomarkers with a control group made up of 58 healthy siblings. Our results show that automated GLS outperforms conventional echocardiography in the early detection of cardiotoxicity, emerging as a promising tool in the long-term cardiac surveillance of CLSs. There is limited evidence that supports the use of the global longitudinal strain (GLS) in long-term cardiac monitoring of childhood acute lymphoblastic leukemia survivors (CLSs). Our aim was to assess the utility of automated GLS to detect left ventricular systolic dysfunction (LVSD) in long-term CLSs. Asymptomatic and subclinical LVSD were defined as LVEF < 50% and GLS < 18.5%, respectively. Echocardiographic measurements and biomarkers were compared with a control group. Inverse probability weighting was used to reduce confounding. Regression models were used to identify factors associated with LVEF and GLS in the survivors. Ninety survivors with a median follow-up of 18 (11–26) years were included. The prevalence of LVSD was higher using GLS than with LVEF (26.6% vs. 12.2%). The measurements were both reduced as compared with the controls (p < 0.001). There were no differences in diastolic parameters and NT-ProBNP. Survivors were more likely to have Hs-cTnI levels above the detection limit (40% vs. 17.2%, p = 0.006). The dose of anthracycline was associated with LVEF but not with GLS in the survivors. Biomarkers were not associated with GLS or LVEF. In conclusion, LVSD detection using automated GLS was higher than with LVEF in long-term CLSs. Its incorporation into clinical routine practice may improve the surveillance of these patients. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse. Objective: The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4). Methods: The PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with ≥1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures. Results: Ethical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published. Conclusions: The PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation. [ABSTRACT FROM AUTHOR]

Purpose: Augmented survival of childhood nephroblastoma and neuroblastoma has increased long-term side effects such as metabolic syndrome (Met S). Risk stratification is difficult after abdominal radiation because waist circumferenc e underestimates adiposity. We aimed to develop a strategy for determining MetS in irradiated survivors using an integrated biomarker profile and vascular ultrasonograp hy. Methods: The NCEP-ATPIII MetS-components, 14 additional serum biomarker s and 9 vascular measurements were assessed in a single-centre cohort of childhood nephroblastoma (n = 67) and neuroblastoma (n = 36) survivors and controls (n = 61). Multivariable regression models were used to study treatment eff ects. Principal component analysis (PCA) was used to study all biomarkers in a combined analysis, to identify patterns and correlations. Results: After 27.5 years of follow-up, MetS occurred more often in sur vivors (14%) than controls (3%). Abdominal radiotherapy and nephrectomy, to a lesser extent, were associated with MetS and separate components and with seve ral biomarker abnormalities. PCA of biomarkers revealed a pattern on PC1 from favourable lipid markers (HDL-cholesterol, adiponectin) towards unfavourable markers (triglycerides, LDL-cholesterol, apoB, uric acid). Abdominal radiotherapy was a ssociated with the unfavourable biomarker profile (β = 1.45, P = 0.001). Vascular measurements were not of added diagnostic value. Conclusions: Long-term childhood nephro- and neuroblastoma survivors freque ntly develop MetS. Additional assessment of biomarkers identified in PCA – adiponectin, LDL, apoB, and uric acid – may be used especially in abdominally irr adiated survivors, to classify MetS as alternative for waist circumference. Vascular ultrasono graphy was not of added value.

Long-term follow-up (LTFU) care, although endorsed, is not available for the majority of adult survivors of childhood, adolescence and young adult (CAYA) cancer. Barriers to implementation include lack of time, knowledge, personnel and funding. Sustainable solutions are urgently needed to address the needs of CAYA cancer survivors to improve the quality of life and reduce the burden of late effects on survivors, health care systems and society. The European Union–funded PanCareFollowUp project, initiated by the Pan-European Network for Care of Survivors after Childhood and Adolescent Cancer, was established to facilitate the implementation of person-centred survivorship care across Europe. The PanCareFollowUp Care Intervention was co-developed with survivors as part of the PanCareFollowUp project. It is a person-centred approach to survivorship care, supported by guidelines and with flexibility to adapt to local health care settings. The Care Intervention consists of three steps: (1) previsit completion of a Survivor Questionnaire (by the survivor) and Treatment Summary (by the health care provider [HCP]), (2) a clinic visit including shared decision-making, and (3) a follow-up call to finalise the individualised Survivorship Care Plan. We developed the key components of the PanCareFollowUp Care Intervention : a PanCareFollowUp Survivor Questionnaire , Treatment Summary template, Survivorship Care Plan template, and educational materials for HCPs and survivors. Wide implementation of the PanCareFollowUp Care Intervention will be supported with a freely distributed Replication Manual on completion of the PanCareFollowUp project. The PanCareFollowUp Care Intervention will support the implementation of person-centred, guideline-based LTFU care in different health care settings across Europe to improve survivors' health and well-being. • Long-term follow-up care is essential for the health of childhood cancer survivors. • PanCareFollowUp Care Intervention is suitable for all health care systems. • Treatment summary, Survivorship Care Plan, recommendations and health information. • Evaluation of feasibility and effectiveness of Care Intervention in four European countries. • Replication manual for implementation at institutions will be available postproject. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors (CCSs) may have comorbidities including a long-term abnormality in the immune system. Immune reconstitution in CCSs after treatment for acute leukemia has been reported previously, while analyses of immune reconstitution in CCSs with solid tumors have been limited. Methods: Childhood cancer survivors who received chemotherapy for solid tumors and who visited University of Tsukuba Hospital between November 2019 and March 2021 were included the study. Peripheral blood was collected for flow cytometry analysis. Results: Forty-nine samples from 35 CCSs (18 male, 17 female) were included in the study. High-dose chemotherapy and cerebral spinal irradiation were conducted in 14 CCSs (40%) and in five CCSs (14%), respectively. The median time between the completion of chemotherapy and the collection of the present samples was 15.0 months (range, 0–286 months). The total lymphocyte count, B cells, and CD8-positive T cells recovered to the normal range of controls (NR-CTLs) in 0 (0%), four (66.7%), and four (66.7%) of six samples at 0–3 months after the completion of chemotherapy, and in three (60%), four (80%), and three (60%) of five samples at 3–12 months after the completion of chemotherapy, respectively. Meanwhile, CD4-positive T cells remained lower than NR-CTLs in 0 (0%) of six samples, one (20%) of five samples, and seven (63.7%) of 11 samples at 0–3, 3–12 and 12–60 months after the completion of chemotherapy, respectively. Conclusions: Recovery to the NR-CTLs was rapidly achieved in B cells and CD8-positive T cells, while the recovery was slower and incomplete in CD4-positive T cells. Careful observation of infection in long-term follow-up clinics is needed. [ABSTRACT FROM AUTHOR]