Self protective health care in childhood cancer survivors from the perspective of survivors, parents, and professionals: a qualitative study.

INTRODUCTION: Childhood cancer survivors experience many health problems that they must protect themselves from their destructive physical and psychological effects. Understanding experiences of children about self-protective care will help health care providers manage long-term care plans. Therefore, this study was conducted with the aim of exploring self-protection care in childhood cancer survivors. METHODS: This is a phenomenological study that was conducted in the clinics and cancer care centers of Urmia and Khoy in Iran. 27 participants were selected by purposive sampling until data saturation. The data was collected using a semi-structured and in-depth face to face interview. Content analysis approach used for data analysis and MAXQUDA 10 software used for data management. RESULTS: Data analysis led to the emergence of "self-protection health care" as a main category, two categories "maintaining physical health" and "keeping a strong mindset" and 9 sub-categories including "abstain activities that may cause harm", "refusing contact with others for possible infection", "monitoring symptoms and side-effects of cancer coming back", "avoiding unhealthy diet", "knowing about cancer from similar others", "keep away negative thoughts and emotions", "drawing on spiritual resources", "creating a bridge to life again" and "being healthy for the sake of one's family". CONCLUSION: According to the results of this study, self-protection is one of the most important cares for childhood cancer survivors. Over time, the influence of the clinical team and parents on children's health care diminishes. Therefore, they should promote their health and well-being behaviors and use a variety of protective approaches to self-care.

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

OBJECTIVE: This study examines the association between psychosocial risk and protective factors and a wide range of psychosocial outcomes including emotional, social, cognitive, and physical domains in childhood cancer survivors (CCS). METHODS: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed 1963-2001) part 2 (age ≥ 18 years, diagnosed < 18 years, ≥ 5 years since diagnosis) completed questionnaires on psychosocial risk and protective factors (Benefit and Burden Scale, Illness Cognition Questionnaire, Rosenberg Self-Esteem Scale, and Impact of Cancer Scale), and psychosocial outcomes (Hospital Anxiety and Depression Scale, Self-Rating Scale for Post-Traumatic Stress Disorder, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and Short Form-36). Associations were assessed with regression analysis, adjusting for attained age, sex, number of health conditions, and time since diagnosis, while correcting for multiple testing (p < 0.004). RESULTS: A total of 1382 CCS participated, all diagnosed ≥ 15 years ago. The mean age of participating CCS was 36 years, and 51% were female. Perceived benefit and burden, acceptance, and helplessness, self-esteem and social support were associated with the psychosocial outcomes. In the models including all psychosocial factors, most associations with psychosocial outcomes were seen for self-esteem (10×), and perceived burden (9×). Self-esteem (all ß ≤ 0.47) and perceived burden (all ß ≤ 0.38) demonstrated strongest associations of medium/large size. CONCLUSIONS: Perceptions of childhood cancer, illness cognitions, self-esteem, and social support play a role in explaining psychosocial functioning in CCS, outweighing the influence of socio-demographic and medical variables. Addressing negative perceptions and reducing feelings of helplessness, while promoting acceptance, self-esteem, and social support, could provide intervention targets for CCS who encounter psychosocial challenges.

Autonomic Dysfunction Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort Study.

Background: The burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown. Objectives: We evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors. Methods: We conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression tested associations with impaired cardiorespiratory fitness (peak Vo2 < 80% predicted). Results: Survivors (50.7% female) were 9.0 ± 5.8 years at cancer diagnosis and 35.5 ± 8.9 years at evaluation. Prevalence (survivors vs control subjects) of elevated resting heart rate (17.9% vs 7.0%), decreased heart rate reserve (21.7% vs 9.1%), decreased systolic blood pressure response to exercise (25.3% vs 12.6%), and delayed heart rate recovery (24.3% vs 10.6%) was more than 2-fold higher among survivors (P < 0.001 for all). Carboplatin (adjusted OR: 2.50; 95% CI: 1.42-4.40; P = 0.001), chest-directed radiation therapy (adjusted OR: 2.06; 95% CI: 1.52-2.75; P < 0.001), and cranial radiation (adjusted OR: 1.49; 95% CI: 1.08-2.05; P = 0.015) were associated with an increased likelihood of having ≥2 measures of autonomic dysfunction. Survivors with ≥2 measures of autonomic dysfunction were at increased risk for impaired cardiorespiratory fitness (adjusted OR: 2.71; 95% CI: 1.82-4.02; P < 0.001). Conclusions: Survivors of childhood cancer manifest a higher prevalence of autonomic dysfunction associated with impaired cardiorespiratory fitness.

Neighborhood Vulnerability and Associations with Poor Health-Related Quality-of-Life Among Adult Survivors of Childhood Cancer.

BACKGROUND: Few studies investigate the relationship between neighborhood vulnerability and health-related quality-of-life (HRQOL) in the childhood cancer population. This study evaluated the impact of neighborhood vulnerability on HRQOL among adult survivors of childhood cancer. METHODS: This cross-sectional study included 4,393 adult survivors of childhood cancer from the St Jude Lifetime Cohort Study. At the baseline (2007-2020), HRQOL was assessed using the SF36v2's physical/mental components summaries (PCS/MCS). Neighborhood vulnerability was assessed using the overall, domain, and indicator-specific scores of the Social Vulnerability Index (SVI) and Minority Health SVI (MHSVI). Multivariable logistic regression was used to evaluate associations of neighborhood vulnerability (quartiles: Q1-Q4) with impaired HRQOL (1SD below the norm), adjusting for diagnosis, demographics, personal socioeconomic status (SES), lifestyle, and chronic health condition burden. Interactions of SVI/MHSVI with personal SES on impaired HRQOL were analyzed. RESULTS: Among survivors, 51.9% were male, averaging 30.3 years of age at evaluation and 21.5 years since diagnosis. Comparing neighborhoods with higher vs lower vulnerability (Q4 vs Q1), overall (OR = 1.60, 95%CI = 1.19-2.16) and domain-specific vulnerability (socioeconomic: OR = 1.59, 95%CI = 1.18-2.15; household composition: OR = 1.54, 95%CI = 1.16-2.06; housing/transportation: OR = 1.33, 95%CI = 1.00-1.76; medical vulnerability: OR = 1.60, 95%CI = 1.22-2.09) were significantly associated with impaired PCS, but not MCS. Residing in neighborhoods lacking urgent care clinics was significantly associated with impaired PCS (OR = 1.39, 95%CI = 1.08-1.78). Having lower vs higher personal education and living in higher vulnerability neighborhoods were associated with more impaired PCS (P  interaction=0.021). CONCLUSIONS: Specific aspects of neighborhood vulnerability increase the risk for impaired physical HRQOL. Addressing these neighborhood factors is essential to enhance the HRQOL of survivors.

Uncovering possible silent acquired long QT syndrome using exercise stress testing in long-term pediatric acute lymphoblastic leukemia survivors.

An example of chemotherapy-induced cardiotoxicity in cancer survivors is acquired long QT syndrome (aLQTS), which may cause serious yet preventable life-threatening consequences. Our objective was to identify and characterize childhood acute lymphoblastic leukemia (ALL) survivors with possible aLQTS using maximal exercise testing. In this cross-sectional study with exploratory analysis, a total of 250 childhood ALL survivors were evaluated for abnormal QT interval prolongation using the McMaster cycle exercise test. A total of 198 survivors (102 males; 96 females), having reached their V ̇ O 2 $$ \dot{\mathrm{V}}{\mathrm{O}}_2 $$ peak (mean 32.1 ± 8.4 mL/kg/min; range 15.5-57.8 mL/kg/min), were included in our analyses. Two survivors were excluded for possible congenital LQTS. QT intervals were corrected for heart rate using the Bazett, Fridericia, and Rautaharju formulas at rest (supine, sitting, and standing positions), at the end of each stage of the CPET, and at 1, 3, and 5 minutes into the recovery period. The corrected QT (QTc) of borderline (n = 37) and long QT survivors (n = 20) was significantly longer than normal survivors (n = 141) at rest, exercise, and recovery. Out of 57 survivors presenting an abnormal QTc prolongation, 40 survivors (70%) showed no QT interval anomalies at rest but developed various anomalies during exercise. No significant differences were found between the groups for any of the measured clinical characteristics or cardiac parameters. The standardization of exercise testing in the regular follow-up of oncology patients is necessary for appropriate cardiac prevention and surveillance to enhance the health and quality of life of the ever-increasing number of cancer survivors.

Using mHealth Technology to Evaluate Daily Symptom Burden among Adult Survivors of Childhood Cancer: A Feasibility Study.

BACKGROUND: Cancer therapies predispose survivors to a high symptom burden. This study utilized mobile health (mHealth) technology to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer to evaluate symptom fluctuation and associations with future health-related quality-of-life (HRQOL). METHODS: This prospective study used an mHealth platform to distribute a 20-item cancer-related symptom survey (5 consecutive days each month) and an HRQOL survey (the day after the symptom survey) over 3 consecutive months to participants from the Childhood Cancer Survivor Study. These surveys comprised a PROMIS-29 Profile and Neuro-QOL assessed HRQOL. Daily symptom burden was calculated by summing the severity (mild, moderate, or severe) of 20 symptoms. Univariate linear mixed-effects models were used to analyze total, person-to-person, day-to-day, and month-to-month variability for the burden of 20 individual symptoms. Multivariable linear regression was used to analyze the association between daily symptom burden in the first month and HRQOL in the third month, adjusted for covariates. RESULTS: Out of the 60 survivors invited, 41 participated in this study (68% enrollment rate); 83% reported their symptoms ≥3 times and 95% reported HRQOL in each study week across 3 months. Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Higher first-month symptom burden was associated with poorer HRQOL related to anxiety (regression coefficient: 6.56; 95% CI: 4.10-9.02), depression (6.32; 95% CI: 3.18-9.47), fatigue (7.93; 95% CI: 5.11-10.80), sleep (6.07; 95% CI: 3.43-8.70), pain (5.16; 95% CI: 2.11-8.22), and cognitive function (-6.89; 95% CI: -10.00 to -3.79) in the third month. CONCLUSIONS: Daily assessment revealed fluctuations in symptomology, and higher symptom burden was associated with poorer HRQOL in the future. Utilizing mHealth technology for daily symptom assessment improves our understanding of symptom dynamics and sources of variability.

Pediatric Oncology Providers' HPV Vaccine Knowledge, Attitude, Self-Efficacy, and Practice after Communication Training: A Comparison with a National Survey.

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

Characterization of Patient Activation among Childhood Cancer Survivors in the St. Jude Lifetime Cohort Study (SJLIFE).

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

Longitudinal needs and cancer knowledge in Swiss childhood cancer survivors transitioning from pediatric to adult follow-up care: results from the ACCS project.

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

A Mega-Analysis of Anti-Müllerian Hormone Levels in Female Childhood Cancer Survivors Based on Treatment Risk, Time since Treatment, and Pubertal Status.

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

Associations between perceived cancer impact and measures of health behavior in survivors of childhood cancer.

PURPOSE: Perceived cancer impact (PCI) is the degree to which one feels cancer has impacted one's life. It is unknown if PCI is associated with health behaviors. The aim of this study is to determine associations between PCI and health behaviors in childhood cancer survivors. METHODS: Participants were ≥ 5-year survivors enrolled in the St. Jude Lifetime (SJLIFE) cohort. The Brief Cancer Impact (BCIA) assessed PCI across four domains (caregiving/finances, diet/exercise, social/emotional functioning, religiosity). Responses were categorized as negative, neutral, or positive impact. Smoking, risky drinking, illicit drug use, and diet quality data were obtained via self-report. Physical activity (PA) was assessed via self-report and actigraphy. Cross-sectional and longitudinal associations between PCI and health behaviors were evaluated via multivariable logistic regression. RESULTS: A total of 3623 participants (mean age 30.4 ± 8.3 years, 49.6% female, 81.5% NH White) were included in baseline cross-sectional analysis; 1709 had a second visit 5.0 ± 1.4 years later and were included in longitudinal analysis. At baseline, the percentage of participants who endorsed cancer as having a negative impact on caregiving/finances was 37.5%, diet/exercise 30.5%, social/emotional functioning 40.6%, and religiosity 8.7%. Negative and neutral PCI across all four domains were cross-sectionally associated with all behaviors except illicit drug use. Negative and neutral PCI at the first time point across all four domains were associated with smoking, diet quality, and PA (ORs ranging from 1.35 to 2.41) in longitudinal analyses. CONCLUSIONS: Endorsing negative or neutral PCI is associated with adverse health behaviors. IMPLICATIONS FOR CANCER SURVIVORS: Promoting optimal health behavior should include addressing PCI.

Bone health in childhood low-grade glioma: an understudied problem.

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

Continuity and coordination of care for childhood cancer survivors with multiple chronic conditions: Results from the Childhood Cancer Survivor Study.

INTRODUCTION: Continuity and coordination-of-care for childhood cancer survivors with multiple chronic conditions are understudied but critical for appropriate follow-up care. METHODS: From April through June 2022, 800 Childhood Cancer Survivor Study participants with two or more chronic conditions (one or more severe/life-threatening/disabling) were emailed the "Patient Perceived Continuity-of-Care from Multiple Clinicians" survey. The survey asked about survivors' main (takes care of most health care) and coordinating (ensures follow-up) provider, produced three care-coordination summary scores (main provider, across multiple providers, patient-provider partnership), and included six discontinuity indicators (e.g., having to organize own care). Discontinuity (yes/no) was defined as poor care on one or more discontinuity item. Chi-square tests assessed associations between discontinuity and sociodemographics. Modified Poisson regression models estimated prevalence ratios (PRs) for discontinuity risk associated with the specialty and number of years seeing the main and coordinating provider, and PRs associated with better scores on the three care-coordination summary measures. Inverse probability weights adjusted for survey non-participation. RESULTS: A total of 377 (47%) survivors responded (mean age 48 years, 68% female, 89% non-Hispanic White, 78% privately insured, 74% ≥college graduate); 147/373 (39%) reported discontinuity. Younger survivors were more likely to report discontinuity (chi-square p = .02). Seeing the main provider ≤3 years was associated with more prevalent discontinuity (PR; 95%CI) (1.17; 1.02-1.34 vs ≥ 10 years). Cancer specialist main providers were associated with less prevalent discontinuity (0.81; 0.66-0.99 vs. primary care). Better scores on all three care-coordination summary measures were associated with less prevalent discontinuity: main provider (0.73; 0.64-0.83), across multiple providers (0.81; 0.78-0.83), patient-provider partnership (0.85; 0.80-0.89). CONCLUSIONS: Care discontinuity among childhood cancer survivors is prevalent and requires intervention.

Feasibility, reproducibility, and accuracy of echocardiographic right ventricular systolic function assessments in childhood cancer survivors at risk for heart failure.

PURPOSE: We sought to assess the feasibility, reproducibility, and accuracy of conventional and newer echocardiographic measures of right ventricular (RV) systolic function in adolescent and young adult childhood cancer survivors treated with anthracyclines. METHODS: Echocardiography and cardiac magnetic resonance imaging (CMR) were acquired ≤60 days apart in prospectively recruited survivors and RV functional measures were quantitated by blinded observers. Repeat quantitation was performed in a subset to evaluate reproducibility. For each echocardiographic measure, Spearman correlations with CMR measures were calculated, and values in participants with CMR RV ejection fraction (RVEF) ≥48% and RVEF <48% were compared using two sample Wilcoxon rank-sum tests. RESULTS: Among 58 participants, mean age was 18.2 years (range 13.1-25.2) and five participants had CMR RVEF <48%. Intra- and inter-observer coefficients of variation were 8.2%-10.1% and 10.5%-12.0% for adjusted automated strain measures, and 5.2%-8.7% and 2.7% for 3D RVEF, respectively. No echocardiographic measures were significantly correlated with CMR RVEF; only tricuspid annular plane systolic excursion was correlated with CMR RV stroke volume (r = .392, p = .003). Participants with RV dysfunction had worse automated global longitudinal strain (-20.3% vs. -23.9%, p = .007) and free wall longitudinal strain (-23.7% vs. -26.7%, p = .09). CONCLUSIONS: Echocardiographic strain and 3D RV function measurements were feasible and reproducible in at-risk childhood cancer survivors. Although not associated with CMR RVEF in this population with predominantly normal RV function, automated strain measurements were more abnormal in participants with RV dysfunction, suggesting potential clinical utility of these measures.

Treatments affecting splenic function as a risk factor for valvular heart disease in Childhood Cancer Survivors: A DCCSS-LATER study.

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

Statistical analysis of self-reported health conditions in cohort studies: handling of missing onset age.

OBJECTIVES: This paper discusses methodological challenges in epidemiological association analysis of a time-to-event outcome and hypothesized risk factors, where age/time at the onset of the outcome may be missing in some cases, a condition commonly encountered when the outcome is self-reported. STUDY DESIGN AND SETTING: A cohort study with long-term follow-up for outcome ascertainment such as the Childhood Cancer Survivor Study (CCSS), a large cohort study of 5-year survivors of childhood cancer diagnosed in 1970-1999 in which occurrences and age at onset of various chronic health conditions (CHCs) are self-reported in surveys. Simple methods for handling missing onset age and their potential bias in the exposure-outcome association inference are discussed. The interval-censored method is discussed as a remedy for handling this problem. The finite sample performance of these approaches is compared through Monte Carlo simulations. Examples from the CCSS include four CHCs (diabetes, myocardial infarction, osteoporosis/osteopenia, and growth hormone deficiency). RESULTS: The interval-censored method is useable in practice using the standard statistical software. The simulation study showed that the regression coefficient estimates from the 'Interval censored' method consistently displayed reduced bias and, in most cases, smaller standard deviations, resulting in smaller mean square errors, compared to those from the simple approaches, regardless of the proportion of subjects with an event of interest, the proportion of missing onset age, and the sample size. CONCLUSION: The interval-censored method is a statistically valid and practical approach to the association analysis of self-reported time-to-event data when onset age may be missing. While the simpler approaches that force such data into complete data may enable the standard analytic methods to be applicable, there is considerable loss in both accuracy and precision relative to the interval-censored method.

Design and methods of the StepByStep randomized trial of a mobile health and social media physical activity intervention among adolescent and young adult survivors of childhood cancer: A report from the Children's Oncology Group.

BACKGROUND: Interventions to increase physical activity are needed in adolescent and young adult survivors of childhood cancer who are largely inactive but at lifelong elevated risk of multiple chronic conditions improved by physical activity. The goals of the StepByStep study are to evaluate the effects of a 48-week distance-based, multi-component mobile health and social media behavioral intervention on physical activity, biomarkers of cardiometabolic health, and health-related quality of life. METHODS: This ongoing study is a two-arm, prospective, multi-site randomized controlled trial. 384 childhood cancer survivors age ≥ 15 years and < 21 years who were 3-36 months off therapy and not meeting physical activity guidelines were enrolled. The trial will test the efficacy of a 24-week intensive multi-component physical activity intervention combining a wearable physical activity tracker, social media peer support group, and individualized goal setting followed by a 24-week maintenance phase of the intervention to improve outcomes. The control group receives the wearable physical activity tracker only. CONCLUSION: There is a growing need for novel, developmentally appropriate interventions to increase physical activity and improve the health trajectory of adolescent and young adult survivors of childhood cancer. If efficacious, this portable and scalable intervention would be a much-needed tool to reduce the morbidity from cancer treatment and improve quality of life among survivors after treatment ends. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04089358; COG Identifier: ALTE2031.

Research progress on sexual functioning and associated factors in childhood cancer survivors: a scoping review.

Background: Childhood Cancer Survivors (CCSs) are more likely to report sexual dysfunction than people without cancer history. Sexual functioning encompasses more than just sexual dysfunction. The scarcity of information regarding the status and influencing factors of sexual functioning in CCSs, hampers to devise suitable screening or interventions. This review aims to summarize research progress on sexual functioning and associated factors among CCSs. Methods: This review protocol is registered in PROSPERO(CRD42023427939) and performed according to PRISMA guidelines. From inception to November 15, 2023, a comprehensive search was conducted in PubMed, EMBASE, CINAHL, Web of Science, SCOPUS, PsycINFO, CNKI Database, Wanfang of Chinese Database, SinoMed Database and Cochrane Library on sexual functioning and childhood cancer survivors. Inclusion criteria were English or Chinese studies focusing on sexual functioning and related factors of cancer survivors, who diagnosed with cancer before 18 years old, and were adult and disease-free when participating in the study. Studies were excluded if the focus was on adult cancer patients or without age information. Findings: 395 records were retrieved, and 22 studies were finally included in this review. Results suggest that CCSs experience a substantial burden of sexual issues, including delayed psychosexual development, low satisfaction, and high prevalence of dysfunction. Underlying factors related to sexual functioning of CCSs were identified, including demographic, cancer treatment-related, psychological, and physiological factors. The historical change in research on sexual functioning was summarized. Interpretation: Research on sexual functioning among CCSs is limited. The extent to which cancer and related treatments affect sexual functioning remains largely unknown. The relationships between various factors and mechanisms underlying sexual functioning need to be confirmed by more rigorous studies to enable effective interventions to be developed. Funding: None.

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.

Pediatric Cardio-Oncology: Screening, Risk Stratification, and Prevention of Cardiotoxicity Associated with Anthracyclines.

Anthracyclines have significantly improved the survival of children with malignant tumors, but the associated cardiotoxicity, an effect now under the purview of pediatric cardio-oncology, due to its cumulative and irreversible effects on the heart, limits their clinical application. A systematic screening and risk stratification approach provides the opportunity for early identification and intervention to mitigate, reverse, or prevent myocardial injury, remodeling, and dysfunction associated with anthracyclines. This review summarizes the risk factors, surveillance indexes, and preventive strategies of anthracycline-related cardiotoxicity to improve the safety and efficacy of anthracyclines.