Reproductive late effects and testosterone replacement therapy in male childhood cancer survivors: A population-based study (the Fex-Can study).

Childhood cancer survivors are at risk of various endocrine late effects affecting their quality of life. The aim of this study was to assess the prevalence and predictors of endocrine and reproductive outcomes in young adult survivors. A secondary aim was to assess possible associations between testosterone replacement therapy (TRT) and other endocrine, cardiovascular and psychosocial late effects. This nationwide study comprised 1212 male childhood cancer survivors aged 19-40 years, identified through the National Quality Registry for Childhood Cancer in Sweden. Median age at diagnosis during 1981-2017 was 7 (range 0-17) and at study 29 (19-40) years. The study combined self-report survey data with cancer treatment data from the national registry. Hormone-induced puberty was self-reported by 3.8% of the survivors and ongoing TRT by 6.0%. In separate logistic regression analyses, these treatments were associated with hematopoietic stem cell transplantation and cranial radiotherapy. Hormone-induced puberty was additionally associated with younger age at diagnosis. Men with TRT had a higher prevalence of other endocrine deficiencies, cholesterol medication, depressive symptoms and fatigue as well as a lower probability of living with a partner, having a biological child or current occupation. In the total male cohort, 28.2% reported having a biological child. Reassuring reproductive outcomes after less intensive therapies and low frequency of TRT were observed in young adult male childhood cancer survivors treated in the most recent treatment era. However, men with TRT suffered from several other endocrine, cardiovascular and psychosocial late effects, indicating a need for long-term monitoring of this high-risk group.

Reproductive outcomes and reproductive health care utilization among male survivors of childhood cancer: A DCCSS-LATER study.

BACKGROUND: Treatment-related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings. METHODS: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study. RESULTS: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p < .001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p = .86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p < .001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p = .001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p = .001). CONCLUSIONS: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists.

Effect of a 1-year physical activity intervention on quality of life, fatigue, and distress in adult childhood cancer survivors-A randomized controlled trial (SURfit).

INTRODUCTION: Childhood cancer survivors (CCS) are at risk of experiencing lower quality-of-life, fatigue, and depression. Few randomized controlled trials have studied the effect of physical activity (PA) on these in adult long-term CCS. This study investigated the effect of a 1-year individualized PA intervention on health-related quality-of-life (HRQOL), fatigue, and distress symptoms in adult CCS. METHODS: The SURfit trial randomized 151 CCS ≥16 years old, <16 at diagnosis and ≥5 years since diagnosis, identified through the Swiss Childhood Cancer Registry. Intervention participants received personalized PA counselling to increase intense PA by ≥2.5 h/week for 1 year. Controls maintained usual PA levels. The authors assessed physical- and mental-HRQOL, fatigue, and distress symptoms at baseline, 3, 6, and 12 months. T-scores were calculated using representative normative populations (mean = 50, standard deviation = 10). Generalized linear mixed-effects models with intention-to-treat (ITT, primary), and three per-protocol allocations were used. RESULTS: At 12 months, ITT (-3.56 larger decrease, 95% confidence interval -5.69 to -1.43, p = .001) and two per-protocol analyses found significantly lower fatigue. Physical-HRQOL improved significantly in two per-protocol analyses at 12 months. No other effects were found. CONCLUSION: SURfit showed that increased intense PA over 1 year improved fatigue in adult CCS. Survivors should be recommended PA to reduce the burden of late-effects.

Sexual health in adult survivors of childhood cancer: A Project REACH study.

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

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

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

Health-related risk behaviors among U.S. childhood cancer survivors: a nationwide estimate.

BACKGROUND: Childhood cancer survivors (CCS) are subject to a substantial burden of treatment-related morbidity. Engaging in health protective behaviors and eliminating risk behaviors are critical to preventing chronic diseases and premature deaths. This study is aimed to provide updated information on currently smoking, physical inactivity, binge drinking patterns and associated factors among CCS using a nationwide dataset. METHODS: We constructed a sample of CCS (cancer diagnosis at ages < 21y) and healthy controls (matched on age, sex, residency, race/ethnicity) using 2020 Behavioral Risk Factor Surveillance System. We used Chi-square tests and Wilcoxon rank-sum test to examine differences in sociodemographics and clinical characteristics between two groups. Logistic, ordinal regression and multivariable models (conditional models for matching) were used to determine factors associated with risk behaviors. RESULTS: The final sample (18-80y) included 372 CCS and 1107 controls. Compared to controls, CCS had a similar proportion of binge drinking (~ 18%) but higher prevalence of currently smoking (26.6% vs. 14.4%, p < 0.001), physical inactivity (23.7% vs. 17.7%, p = 0.012), and of having 2-or-3 risk behaviors (17.2% vs. 8.1%, p < 0.001). Younger age, lower educational attainment, and having multiple chronic health conditions were associated with engaging in more risk behaviors among CCS. Females, compared to male counterparts, had lower odds of binge drinking (adjusted odds ratio (aOR) = 0.30, 95% confidence interval (CI): 0.16-0.57) among CCS but not in all sample. Having multiple chronic health conditions increased odds of both currently smoking (aOR = 3.52 95%CI: 1.76-7.02) and binge drinking (aOR = 2.13 95%CI: 1.11-4.08) among CCS while it only increased odds of currently smoking in all sample. DISCUSSION: Our study provided risk behavior information for wide age-range CCS, which is currently lacking. Every one in four CCS was currently smoking. Interventions targeting risk behavior reduction should focus on CCS with multiple chronic health conditions.

Post-treatment sperm cryopreservation practices in childhood and young adult cancer survivors.

RESEARCH QUESTION: What are current practices of post-treatment fertility preservation in male childhood cancer survivors (CCS) who have not benefitted from pre-therapeutic fertility preservation in France and other European countries? DESIGN: A survey was conducted of all fertility preservation centres in France (n = 30) and European fertility specialists (n = 9) in five European countries. Eight clinical cases and 40 questions were included to assess the effect of age at diagnosis, type of treatment (alkylating-agents, orchidectomy, testicular radiotherapy) and sperm parameters on the probability of a post-treatment fertility preservation proposal. Demographic characteristics of the responding practitioner were also collected. RESULTS: Post-treatment sperm cryopreservation was proposed by 100% of fertility specialists in cases of severe oligoasthenoteratozoospermia, 77-88% in cases of moderate oligoasthenoteratozoospermia and in 65-77% in cases of sperm motility and vitality impairment. In cases of normal sperm parameters, 27-54% of fertility specialists would propose post-treatment sperm cryopreservation. These results did not differ significantly according to the type of treatment received or to responder-related factors. Practices of European specialists were also guided by sperm parameter results; 44-67% of specialists responding that they would propose sperm cryopreservation in cases of moderate to severe sperm parameter alterations. CONCLUSION: Post-treatment semen analysis could be widely proposed to CCS who have not benefitted from pre-therapeutic fertility preservation. Post-treatment fertility preservation could be proposed in cases of persistent moderate to severe sperm parameter alterations. Guidelines would be important to homogenize practices and to encourage oncologists to refer CCS for fertility assessments.

Association analysis of self-reported outcomes with a validated subset.

In health-science research, outcomes ascertained through surveys and interviews are subject to potential bias with respect to the true outcome status, which is only ascertainable with clinical and laboratory assessment. This measurement error may lead to biased inference when evaluating associations between exposures and outcomes of interest. Here, we consider a cohort study in which the outcome of interest is ascertained via questionnaire, subject to imperfect ascertainment, but where a subset of participants also have a clinically assessed, validated outcome available. This presents a methodological opportunity to address potential bias. Specifically, we constructed the likelihood in two parts, one using the validated subset and the other using a subset without validation. This work expands on that proposed by Pepe and enables inference with standard statistical software. Weighted generalized linear model estimates for our method and maximum likelihood estimates (MLE) for Pepe's method were computed, and the statistical inference was based on the standard large-sample likelihood theory. We compare the finite sample performance of two approaches through Monte Carlo simulations. This methodological work was motivated by a large cohort study of long-term childhood cancer survivors, allowing us to provide a relevant application example where we examined the association between clinical factors and chronic health conditions.

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

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

Ovarian function in female survivors of high-risk neuroblastoma.

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

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

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

Assessment of anthracycline-induced cardiotoxicity in childhood cancer survivors during long-term follow-up using strain analysis and intraventricular pressure gradient measurements.

BACKGROUND: Cardiac dysfunction due to cardiotoxicity from anthracycline chemotherapy is a leading cause of morbidity and mortality in childhood cancer survivors (CCS), and the cumulative incidence of cardiac events has continued to increase. This study identifies an adequate indicator of cardiac dysfunction during long-term follow-up. PROCEDURE: In total, 116 patients (median age: 15.5 [range: 4.7-40.2] years) with childhood cancer who were treated with anthracycline were divided into three age groups for analysis (C1: 4-12 years of age, C2: 13-18 years of age, C3: 19-40 years of age), and 116 control patients of similar ages were divided into three corresponding groups (N1, N2, and N3). Layer-specific strains were assessed for longitudinal strain (LS) and circumferential strain (CS). The total and segmental intraventricular pressure gradients (IVPG) were also calculated based on Doppler imaging of the mitral inflow using Euler's equation. RESULTS: Conventional echocardiographic parameters were not significantly different between the patients and controls. All layers of the LS and inner and middle layers of the basal and papillary CS in all ages and all IVPGs in C2 and C3 decreased compared to those of corresponding age groups. Interestingly, basal CS and basal IVPG in CCS showed moderate correlation and both tended to rapidly decrease with aging. Furthermore, basal IVPG and anthracycline dose showed significant correlations. CONCLUSIONS: Basal CS and total and basal IVPGs may be particularly useful indicators of cardiotoxicity in long-term follow-up.

Utility of apical four-chamber longitudinal strain in the assessment of childhood cancer survivors: A multicenter study.

BACKGROUND: A previous multicenter study showed that longitudinal changes in standard cardiac functional parameters were associated with the development of cardiomyopathy in childhood cancer survivors (CCS). Evaluation of the relationship between global longitudinal strain (GLS) changes and cardiomyopathy risk was limited, largely due to lack of quality apical 2- and 3-chamber views in addition to 4-chamber view. We sought to determine whether apical 4-chamber longitudinal strain (A4LS) alone can serve as a suitable surrogate for GLS in this population. METHODS: A4LS and GLS were measured in echocardiograms with acceptable apical 2-, 3-, and 4-chamber views. Correlation was evaluated using Pearson and Spearman coefficients, and agreement was evaluated with Bland-Altman plots. The ability of A4LS to identify normal and abnormal values compared to GLS as the reference was evaluated. RESULTS: Among a total of 632 reviewed echocardiograms, we identified 130 echocardiograms from 56 patients with adequate views (38% female; mean age at cancer diagnosis 8.3 years; mean follow-up 9.4 years). Correlation coefficients between A4LS and GLS were .89 (Pearson) and .85 (Spearman), with Bland-Altman plot of GLS-A4LS showing a mean difference of -.71 ± 1.8. Compared with GLS as the gold standard, A4LS had a sensitivity of 86% (95% CI 79%-93%) and specificity of 82% (69%-95%) when using normal range cutoffs and 90% (82%-97%) and 70% (58%-81%) when using ±2 standard deviations. CONCLUSION: A4LS performs well when compared with GLS in this population. Given the more recent adoption of apical 2- and 3-chamber views in most pediatric echocardiography laboratories, A4LS is a reasonable stand-alone measurement in retrospective analyses of older study cohorts and echocardiogram biorepositories.

The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.

BACKGROUND: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. The ENGaging and Activating cancer survivors in Genetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing. METHODS: The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services. DISCUSSION: With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.

Factors That Influence Physical Activity Behavior in Children and Adolescents During and After Cancer Treatment: A Qualitative Systematic Review of the Literature.

PURPOSE: The aim of this systematic review is to reveal the social, personal, and contextual factors that influence physical activity (PA) in children and adolescents during and after cancer treatment. METHOD: SPORTDiscus, Cochrane, Web of Science, PubMed, and FIS Education electronic database were systematically searched. RESULTS: The 13 included studies show that social support (parents, siblings, and friends) in particular is rated as important by cancer survivors; for example, doing PA together. Depending on the treatment status and state of health, particularities arise. During the acute treatment phase, parents issued more prohibitions regarding PA than after treatment. The state of health and concern about infections are described as inhibiting factors. Not all hospitals generally offer special exercise programs for cancer patients, and in some cases, only sporadic exercise sessions were conducted by specialized staff. In addition, the hospital atmosphere, such as cramped rooms, tends to be associated with demotivating effects. CONCLUSIONS: Both inhibiting and promoting factors in the area of social, personal, and contextual factors could be identified. The most fundamental factor for PA is the physical condition. Social factors, such as parents or friends, often have a motivating effect and can promote PA. Inhibiting factors are mainly context-related, such as an environment unsuitable for PA. Although the review highlights interesting aspects, further treatment-related and longitudinal studies could provide deeper insights.

Circulating leptin is associated with adverse vascular changes in young adult survivors of childhood cancer.

INTRODUCTION: Proteomics may help discover novel biomarkers and underlying mechanisms for cardiovascular disease. This could be useful for childhood cancer survivors as they show an increased risk of cardiovascular disease. The aim of this study was to investigate circulating cardiovascular proteins in young adult survivors of childhood cancer and their relationship to previously reported subclinical cardiovascular disease. METHODS: Ninety-two cardiovascular proteins were measured in 57 childhood cancer survivors and in 52 controls. For proteins that were significantly different between childhood cancer survivors and controls, we performed correlations between protein levels and measures of peripheral arterial stiffness (carotid distensibility and stiffness index, and augmentation index) and endothelial dysfunction (reactive hyperemia index). RESULTS: Leptin was significantly higher in childhood cancer survivors compared to controls (normalized protein expression units: childhood cancer survivors 6.4 (1.5) versus 5.1 (1.7), p < 0.0000001) after taking multiple tests into account. Kidney injury molecule-1, MER proto-oncogene tyrosine kinase, selectin P ligand, decorin, alpha-1-microglobulin/bikunin precursor protein, and pentraxin 3 showed a trend towards group differences (p < 0.05). Among childhood cancer survivors, leptin was associated with anthracycline treatment after adjustment for age, sex, and body mass index (p < 0.0001). Higher leptin correlated with lower carotid distensibility after adjustment for age, sex, body mass index, and treatments with radiotherapy and anthracyclines (p = 0.005). CONCLUSION: This proteomics approach identified that leptin is higher in young asymptomatic adult survivors of childhood cancer than in healthy controls and is associated with adverse vascular changes. This could indicate a role for leptin in driving the cardiovascular disease burden in this population.

And what about today? Burden and support needs of adolescent childhood cancer survivors in long-term follow-up care-A qualitative content analysis.

PURPOSE: Childhood cancer affects approximately 2000 children annually in Germany, and there is an increasing number of long-term childhood cancer survivors. Due to developmental tasks, adolescent survivors in long-term follow-up (LTFU) care may face specific challenges and perceive different burden due to their disease. The current study explored (a) the impact of cancer and burden regarding survivorship and (b) supportive needs of adolescent childhood cancer survivors in LTFU care. METHODS: Semistructured qualitative interviews were conducted with 18 adolescent childhood cancer survivors in LTFU care aged 14-18 years (average age 16.4 years). Interviews were transcribed verbatim and analysed using content analysis. RESULTS: Based on the exploratory research questions, two key categories were generated: (1) The impact and burden on survivors' lives during LTFU care and (2) support needs of adolescent childhood cancer survivors in LTFU care. The four subcategories that emerged regarding the impact and burden on survivors' lives during LTFU care were (1) physical consequences, (2) cognitive impairments, (3) difficulties in social interactions, and (4) psychosocial burden. Additionally, two subcategories, (1) practical and (2) emotional support needs of adolescent childhood cancer survivors were identified. CONCLUSIONS: Our results indicate that childhood cancer influences adolescent survivors' life in a negative way even many years after the end of treatment. Furthermore, parents seem to play a crucial role in the survivorship experience of childhood cancer survivors, as they remain keep responsible for most cancer-related concerns even during LTFU care, causing adolescents to persist in the child role. A family systemic approach to care is suggested to facilitate development-specific tasks and to enable adolescents to become autonomous adults. Still, the question remains as to who in the health care system could take over the family systemic tasks.

Investigating and quantifying obsessive-compulsive and related disorders among childhood cancer survivors: a brief report.

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

Clinical, demographic factors, and substance use among Hispanic and non-Hispanic young adult childhood cancer survivors.

PURPOSE: The purpose of this study is to examine the protective and risk factors of substance use behaviors (tobacco, marijuana, e-cigarette, and alcohol) among young adult childhood cancer survivors. The study focused on clinical (receipt of cancer-related follow-up care, treatment intensity, late effects, depressive symptoms, self-rated health) and demographic (race/ethnicity, neighborhood socioeconomic status) factors and their associations with substance use. METHODS: Participants were from the Project Forward cohort, a population-based study of young adult survivors of childhood cancers. Participants (N = 1166, Mage = 25.1 years) were recruited through the Los Angeles Cancer Surveillance Program (Cancer Registry covering Los Angeles County, California). Multivariate path analyses were performed with substance use as the outcome variables and clinical and demographic factors as independent variables. Covariates included age and sex. FINDING: Substance use was positively associated with depressive symptoms, and inversely associated with cancer-related follow-up care, female sex, age, Hispanic ethnicity, treatment intensity, and self-rated health. Neighborhood SES was inversely associated with tobacco use, while being positively associated with binge drinking and e-cigarette use. The results highlight the interrelationship between the clinical and demographic variables and their associations with different substance use. CONCLUSION: Findings support the need for effective interventions targeting substance use behavior among CCS. This will help improve long-term outcomes and mitigate the risk for early morbidity.

Quality of life of adolescent and adult survivors of childhood cancer in Europe-A systematic review.

Advances in diagnostics and treatment of childhood cancer during the past few decades have substantially increased survival, resulting in a growing population of survivors of childhood cancer. Somatic and mental late effects of the cancer and the treatment may impact the quality of life (QoL). Previous reviews of QoL in survivors of childhood cancer have shown contradictory findings across studies and the majority of studies included have been based on data from North America and may not be directly comparable to a European setting. The aim of our study was to critically evaluate and summarise the latest evidence on the QoL of childhood cancer survivors in Europe and to identify survivors at particular risk. The eligible studies were published between 2008 and 2022, conducted in Europe and included participants who had survived at least 5 years after diagnosis of a childhood cancer. The main outcome of interest was QoL of survivors which was measured with validated qualitative and quantitative QoL questionnaires. A systematic literature search conducted in PubMed, EMBASE, PsycINFO and CINALH resulted in inclusion of 36 articles with a total of 14 342 survivors of childhood cancer. The majority of included studies found that childhood cancer survivors reported poorer QoL than comparisons. Female gender, treatment with haematopoietic stem cell transplantation and a brain tumour diagnosis were associated with lower QoL. With a growing population of childhood cancer survivors with many years ahead of them, targeted interventions and optimal follow-up care are important to improve the QoL of survivors.