OBJECTIVE: 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: 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.

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.
CONCLUSIONS: 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.
BACKGROUND: ClinicalTrials.gov Identifier: NCT04089358; COG Identifier: ALTE2031.

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

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.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: None.

BACKGROUND: Interpersonal communication is a crucial component of the cancer experience that can contribute to managing cancer care and improving cancer survivors\' and caregivers\' quality of life. Cultural and contextual factors may impact Hispanic childhood cancer survivor (CCS) and parent caregiver relationships and communication. This study sought to describe the healthcare communication experiences of Hispanic parents with CCS, families, and medical providers.
METHODS: We conducted 15 semi-structured interviews with Hispanic caregivers from a safety-net hospital in Los Angeles County. Interviews were conducted in English and Spanish, audio-recorded and professionally transcribed, and analyzed using a thematic approach.
RESULTS: Caregivers shared the importance and impact of medical communication when exploring the \"first big talk\" of the diagnosis, uncertainty about treatment, navigating multiple providers, therapeutic communication (i.e., providing emotional reassurance), and current and lingering effects of cancer. All caregivers shared \"good communication\" experiences, while others shared various barriers to communication, including a lack of understanding of the cancer diagnosis and caregiver experience, psychological challenges impacting communication, cultural and language differences, physical factors that limit communication, and young age of child impacting communication with caregivers.
CONCLUSIONS: Our findings suggest that a strong interpersonal communication skill set for clinicians can contribute to managing cancer care and improving caregivers\' psychological adjustment.

OBJECTIVE: 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.
METHODS: 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.
CONCLUSIONS: 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.

BACKGROUND: 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.
CONCLUSIONS: 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.

OBJECTIVE: Investigate the association between presence, number and type of clinically relevant health conditions and a range of psychosocial outcomes (emotional, social, cognitive, physical) in survivors of childhood cancer (CCS).
METHODS: CCS from the Dutch Childhood Cancer Survivor Study (DCCSS)-LATER cohort (diagnosed between 1963-2001, attained age ≥ 18, diagnosed < 18, ≥ 5 years since diagnosis) completed a questionnaire on health conditions (2013-2014), and questionnaires on psychosocial outcomes (2017-2020): Hospital Anxiety and Depression Scale, Short form 36, TNO-AZL Questionnaire for Adult Health-Related Quality of Life, and the Self-Rating Scale for Post-Traumatic Stress Disorder. Associations among health conditions and psychosocial outcomes were assessed with regression analysis, adjusting for attained age, sex, and time since diagnosis, and adjusting for multiple testing (p < 0.004).
RESULTS: A total of 1437 CCS, mean age 36.3 years, 51.1% female, ≥ 15 years since diagnosis, completed questionnaires on health and psychosocial outcomes. CCS with a clinically relevant health condition, and those with more conditions had worse emotional, social, and physical outcomes; regression coefficients were small to moderate. CCS with gastro-intestinal conditions, endocrine, nervous systems, eye, or ear conditions, and especially those with secondary malignant neoplasms, reported worse psychosocial functioning; regression coefficients were small/moderate to large.
CONCLUSIONS: Health care professionals should be aware of the increased risk for psychosocial problems among CCS with health conditions, especially for survivors with secondary malignant neoplasms, gastro-intestinal, endocrine, nervous system, eye, and ear conditions. CCS may benefit from psychological interventions to develop coping strategies to manage health conditions and psychosocial consequences of the cancer trajectory.

UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.