Outcomes In Survivors Of Childhood Cancer Research Articles

Human papillomavirus-associated subsequent malignant neoplasms among childhood cancer survivors

ObjectiveEmerging evidence suggests a higher risk of human papillomavirus-associated subsequent malignant neoplasms (HPV-SMNs) in childhood cancer survivors. However, comprehensive population-based risk estimates for HPV-SMNs are lacking. MethodsWe utilized longitudinal data obtained from the Surveillance, Epidemiology, and End Results program between 1975 and 2018 to establish a cohort comprising childhood cancer individuals who survived for at least 5 years. Standardized incidence ratio (SIR) with corresponding 95 % confidence interval (95 %CI) was used to evaluate the relative risk of HPV-SMNs. The competing risk regression model was performed to identify risk factors associated with HPV-SMNs. ResultsA total of 35,397 childhood cancer survivors were included. Among them, 42 individuals subsequently developed HPV-SMNs (median time from primary cancer, 25 years). HPV-SMN anatomic sites included cervix (N=16), oropharynx (N=15), anus (N=5), vulva\\vagina (N=5), and penis (N=1). The 40-year cumulative incidence rate of HPV-SMNs was estimated to be 0.51 %. All survivors had a 10-fold increased risk of developing HPV-SMNs compared to individuals of similar age in the general population (SIR 10.1, 95 %CI 7.3–13.6). The competing risk regression model indicted that age at diagnosis and the type of primary malignancy could potentially influence the development of HPV-SMNs. Furthermore, multivariable Cox regression analysis confirmed that the presence of HPV-SMNs significantly increased the risk of mortality for survivors (hazard ratio 2.63, 95 %CI 1.68–4.14). ConclusionsChildhood cancer survivors have a significantly elevated risk of developing HPV-SMNs, accompanied by poor survival outcomes. Encouraging HPV vaccination and robust surveillance protocols may improve long-term health outcomes in childhood cancer survivors.

Pharmacogenomic studies of fertility outcomes in pediatric cancer survivors - A systematic review.

For the same age, sex, and dosage, there can be significant variation in fertility outcomes in childhood cancer survivors. Genetics may explain this variation. This study aims to: (i) review the genetic contributions to infertility, (ii) search for pharmacogenomic studies looking at interactions of cancer treatment, genetic predisposition and fertility-related outcomes. Systematic searches in MEDLINE Ovid, Embase Classic+Embase, and PubMed were conducted using the following selection criteria: (i) pediatric, adolescent, and young adult cancer survivors, below 25 years old at the time of diagnosis, (ii) fertility outcome measures after cancer therapy, (iii) genetic considerations. Studies were excluded if they were (i) conducted in animal models, (ii) were not published in English, (iii) editorial letters, (iv) theses. Articles were screened in Covidence by at least two independent reviewers, followed by data extraction and a risk of bias assessment using the Quality in Prognostic Studies tool. Eight articles were reviewed with a total of 29 genes. Outcome measures included sperm concentration, azoospermia, AMH levels, assessment of premature menopause, ever being pregnant or siring a pregnancy. Three studies included replication cohorts, which attempted replication of SNP findings for NPY2R, BRSK1, FANCI, CYP2C19, CYP3A4, and CYP2B6. Six studies were rated with a high risk of bias. Differing methods may explain a lack of replication, and small cohorts may have contributed to few significant findings. Larger, prospective longitudinal studies with an unbiased genome-wide focus will be important to replicate significant results, which can be applied clinically.

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

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. The authors invited 5925 5-year survivors from the Dutch Childhood Cancer Survivor Study (DCCSS LATER) cohort and their 1066 siblings to complete aquestionnaire 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. At median 18.5years 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. 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.

Assisted reproductive technology use and outcomes in childhood cancer survivors.

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

Educational outcomes in childhood cancer survivors: A Scotland-wide record-linkage study of 766,217 schoolchildren.

A cancer diagnosis during childhood greatly disrupts the lives of those affected, causing physical and psychological challenges. We aim to investigate educational outcomes among schoolchildren with a previous cancer diagnosis compared to their peers. Individual records from four national education databases and three national health databases were linked to construct a cohort of all singleton schoolchildren born in Scotland attending Scottish local-authority schools between 2009-2013. Pupils previously diagnosed with any cancer, haematological cancers, and central nervous system (CNS) cancers, were compared to their unaffected peers with respect to five educational outcomes: special educational need (SEN), absenteeism, school exclusion, academic attainment, and unemployment. Analyses were adjusted for sociodemographic and maternity factors and chronic conditions. Of 766,217 pupils, 1,313 (0.17%) had a previous cancer diagnosis. Children with any cancer had increased odds of SEN (OR 3.26, 95% CI 2.86-3.71), absenteeism (IRR 1.82, 95% CI 1.70-1.94), and low attainment (OR 2.15, 95% CI 1.52-3.03) compared to their peers. Similar findings were observed for haematological (SEN OR 2.62, 95% CI 2.12-3.24; absenteeism IRR 2.04, 95% CI 1.85-2.25; low attainment OR 2.17, 95% CI 1.31-3.61) and CNS (SEN OR 6.44, 95% CI 4.91-8.46; absenteeism IRR 1.75, 95% CI 1.51-2.04; low attainment OR 3.33, 95% CI 1.52-7.30) cancers. Lower exclusions were observed among children with any cancer (IRR 0.51, 95% CI 0.31-0.83) and CNS cancer (IRR 0.20, 95% CI 0.06-0.61). No associations were observed with unemployment. This study highlights the wider impacts of childhood cancer on educational outcomes. These children need to be supported, as poor educational outcomes can further impact later health.

OUTC-09. PEDIATRIC LOW GRADE GLIOMA SURVIVORS’ NEED FOR SURVIVORSHIP CARE: ‘ENGAGE’ A MULTIDISCIPLINARY, E-HEALTH INTERVENTION

Abstract Higher survival rates for children diagnosed with low-grade gliomas (LGG), compared to other brain cancers, often limit the survivorship resources afforded this cohort, despite potential long-term physical, functional and psychological impacts. We conducted a two-phase program of research, first evaluating LGG survivors’ need for support during the survivorship phase, followed by the development and pilot evaluation of a multidisciplinary, telehealth, survivorship program. Phase 1: We conducted a retrospective cohort study of children aged 0-16 years at diagnosis, diagnosed between 2000-2015, assessing psychosocial impact and quality of life. Phase 2: We developed ‘Engage Brain’, a multidisciplinary, telehealth program, designed to improve medical and psychosocial outcomes for childhood cancer survivors throughout their lifespan. Key components of Engage’s design include distance-delivered care to ensure access for all survivors irrespective of whether they live close to a tertiary, survivorship center; hospital-based expertise integrated with local, primary care services to ensure a model of care which is sustainable long-term; nurse-led care providing tailored education to encourage adoption of a prevention-focused healthy lifestyle to mitigate survivors’ personal risk and reduce ongoing costs to the individual and healthcare system; psychosocial focus, incorporating allied health staff (psychologist/social worker) as an integral aspect of care. Phase 1: 45 survivors participated (36% female, mean age 14.8 years, average 7.5 years post-treatment). Survivors reported high levels of anxiety (23%), depression (14%), fatigue (62%). Phase 2: 30 LGG survivors completed Engage Brain intervention (50% female, mean age 21 years, average 11.5 years post-treatment). 64% uptake, 10% attrition. Most (78%) of participants ‘agree’-‘greatly agree’ that Engage Brain provides ‘high-quality survivorship care’ and ‘help accessing survivorship care’. This program of research illustrates the long-term needs of LGG survivors, despite their lower risk status compared to other brain cancers, and the feasibility of providing a multidisciplinary, telehealth intervention to support them.

Outcomes among survivors of childhood cancer in low- and middle-income countries: A systematic review.

10057 Background: Low- and middle-income countries (LMICs) account for most of the global childhood cancer burden. Though cure rates lag behind those in high-income countries (HICs), a substantial proportion of LMIC children do survive. Long-term side effects of cancer or cancer therapy (late effects) are well-documented among childhood cancer survivors (CCS) in HICs, but whether prevalence and risk factors of late effects are comparable in LMICs is unclear. We thus conducted a systematic review to assess LMIC CCS outcomes. Methods: Five major health sciences databases were searched from inception to November 2022 in all languages. We included observational studies conducted in LMICs (World Bank 2021 classification) that evaluated outcomes in CCSs diagnosed with any malignancy. Mean or median length of follow-up must have been ≥ 5 years from original cancer diagnosis. Meta-analyses were precluded by cohort and outcome heterogeneity. Results: Of 1,994 studies identified, 113 underwent full-text review and 21 met inclusion criteria (16 full articles and 5 conference abstracts). Studies were conducted in lower-middle income (N = 12, 57%) or upper-middle income (N = 9, 43%) countries; no low-income country data were found. Study regions were mainly South and East Asia (N = 10, 48%) and the Americas (N = 8, 38%). Almost half (N = 9, 43%) of studies were conducted in India and only one African study from Cameroon was identified. Over half (N = 12, 57%) of studies were cross-sectional in design. Only five (24%) cohorts were comprised entirely of 5-year survivors. CCS of all childhood cancer types were evaluated in 12 (57%) cohorts, and 9 (43%) were specific to one cancer type. Ten (48%) studies were conducted in a survivorship clinic. Second cancers, followed by endocrine, reproductive, and cardiovascular late effects were most frequently assessed. Second cancers were reported in 1%–11% of CCS cohorts (N = 10 studies). The prevalence of hypothyroidism and metabolic syndrome ranged from 2%-49% (N = 6 studies) and 4%-17% (N = 5 studies), respectively. Gonadal dysfunction ranged from 2%-82% (N = 6 studies). Cardiac dysfunction and hypertension ranged from 1%-16% (N = 3 studies) and 5-19% (N = 3 studies), respectively. Late effects of the musculoskeletal (N = 4 studies) and urinary (N = 4 studies) systems were least investigated. Conclusions: Substantial knowledge gaps exist in LMIC childhood cancer survivorship. Few LMIC-based studies were identified, with no low-income country data available. In middle-income countries, variability existed in how late effects were defined and assessed; data was also limited by selection bias and small sample sizes. Additional systematically collected data on LMIC CCS cohorts are urgently needed.

Self-reported physical activity behaviors of childhood cancer survivors: comparison to a general adolescent population in Korea

Adequate physical activity (PA) can significantly contribute to the prevention of undesirable health outcomes in childhood cancer survivors (CCS). This study aimed to identify the patterns of PA and related factors in Korean CCS. Study subjects were 184 adolescents selected from an ongoing cohort study of Korean CCS and 1,840 sex- and school grade-matched controls randomly selected from the participants of the 2019 Korea Youth Risk Behavior Web-based Survey. Information on PA and sedentary behaviors was collected by self-administered questionnaire. We estimated body mass index (BMI)-adjusted odds ratio (OR) and 95% confidence interval (CI) for the advisable healthy behaviors of CCS compared with healthy controls using conditional logistic regression analysis. In addition, the associations of advisable healthy behaviors of CCS with sociodemographic and clinical factors were estimated using multiple logistic regression analysis. CCS were less likely to be physically active than controls, but this finding was evident only in males. The ORs (95% CIs) for regular exercise, moderate intensity PA, vigorous intensity PA, and walking were 0.42 (0.27-0.65), 0.39 (0.24-0.63), 0.53 (0.33-0.84), and 0.64 (0.42-0.98), respectively, in male CCS compared with same-sex controls. Compared with same-sex controls, male CCS were 4.60 times and female survivors were 15.19 times more likely to sleep longer than 8h a day. Among CCS, males were 2.92 times and 3.07 times more likely to perform moderate intensity PA and muscle-strengthening exercise, respectively, than female. Higher BMI (OR: 1.16), highest family income (OR: 3.98), and a caregiver who performed regular exercise (OR: 2.08) were positively associated with vigorous intensity PA of CCS. With increasing time after treatment completion, the probability of engaging in sedentary activity for less than 6h per day decreased (OR = 0.89, 95% CI 0.79-1.00). Korean adolescent CCS were physically inactive compared with control adolescents. Several sociodemographic factors such as sex, family income, caregiver PA, and obesity level were associated with PA behaviors of CCS. Strategic effort would be needed to increase physical activity of childhood cancer survivors in adolescent period with consideration of various sociodemographic factors found in this study.

Risk of Renal or Urinary Related Hospitalization in Survivors of Childhood Cancer: Results from the French Childhood Cancer Survivor Study.

Hospitalization rates can be used as an indirect indicator of the burden and severity of adverse health outcomes in childhood cancer survivors (CCS). We aimed to determine the long-term risks of hospitalization related to renal and urinary diseases among 5-year CCS. The French Childhood Cancer Survivor Study cohort was linked with data from the French National Healthcare System database, which enabled the identification of hospitalizations related to renal or urinary diseases. Clinical and detailed treatment data were collected from medical records. Dose-volume histograms were estimated for all patients treated with radiotherapy. Standardized Hospitalization Ratios and absolute excess risks (AER) were calculated. Relative risks were estimated using Poisson regression. A total of 5,498 survivors were followed for 42,118 person-years (PY). Survivors experience 2.9 times more renal hospitalizations than expected in the general population, with an AER of 21.2/10,000 PY. Exposing more than 10% of the kidneys' volume to at least 20 Gray increases the risk of being hospitalized for renal causes by 2.2 (95% confidence interval, 1.3-3.6). Nephrectomized survivors treated with high doses of ifosfamide (>60 g/m²) have an extremely high risk of hospitalization for renal causes. Patients with comorbidities have about a 3-fold higher risk, and nephrectomized patients a 2-fold higher risk of being hospitalized for renal causes compared with other subjects. In the case of hospitalization for urinary causes, treatment by anthracycline administration was found to be associated with an almost 2-fold higher risk of hospitalization compared with the general population. These results support the need for careful monitoring of long-term renal diseases in survivors who have undergone nephrectomy, those treated with high doses of radiation (≥20 Gy) even to small volumes of the kidneys, and those with predisposing risk factors. This study provides new evidence with potential impact on surveillance guidelines related to dose-volume indicators associated with renal toxicity.

Identifying the important social outcomes for childhood cancer survivors: an e-Delphi study protocol

IntroductionOptimising the health of childhood cancer survivors is important given the high long-term survival rate coupled with a significant late effects burden. Included within the WHO’s definition of ‘Health’ are...

Risk Factors for Long-Term Kidney Outcomes in Childhood Cancer Survivors

Risk Factors for Long-Term Kidney Outcomes in Childhood Cancer Survivors

Employment among Childhood Cancer Survivors: A Systematic Review and Meta-Analysis.

Simple SummaryDespite the improvements in the survival rates and functional outcomes of childhood cancer survivors (CCS), most of them experience late effects with possible consequences to their occupational status. To date, a reliable estimate of the prevalence of employment among this population is still missing. This study aimed to assess, for the first time, the prevalence of employment among CCS and to examine the associations of socio-demographic and clinical factors with employment. Almost 100 cohorts worldwide have been included in this review, highlighting that two-thirds of childhood cancer survivors were employed. Different employment rates depending on socio-demographic and clinical factors were identified. The findings from this study could facilitate the design of targeted interventions aimed at promoting employment among CCS.To date, there are heterogeneous studies related to childhood cancer survivors’ (CCS) employment rates. Given the importance of this topic, we aimed to perform a systematic review and meta-analysis to investigate the prevalence of employment among CCS and to examine its association with socio-demographic and clinical factors. We followed the PRISMA guidelines to search for pertinent articles in relevant electronic databases. Eighty-nine articles comprising 93 cohorts were included. The overall prevalence of employment was 66% (CI: 95% 0.63–0.69). Subgroup meta-analyses showed that lower rates were found for central nervous system tumor survivors (51%, CI: 95% 0.43–0.59), and for CCS treated with cranial-radiotherapy (53%, CI: 95% 0.42–0.64) or haematopoietic stem-cell transplantation (56%, CI: 95% 0.46–0.65). The studies conducted in Asia highlighted employment rates of 47% (CI: 95%, 0.34–0.60). Univariate meta-regressions identified the following socio-demographic factors associated with higher rates of employment: a female gender (p = 0.046), a higher mean age at the time of investigation (p = 0.00), a longer time since diagnosis (p = 0.00), a higher educational level (p = 0.03), and a married status (p = 0.00). In conclusion, this systematic review and meta-analysis provides evidence that two-thirds of CCS are employed worldwide. Identifying vulnerable groups of CCS may allow for the design of multidisciplinary support strategies and interventions to promote employment in this population.

Can We Compare the Health-Related Quality of Life of Childhood Cancer Survivors Following Photon and Proton Radiation Therapy? A Systematic Review.

Simple SummaryProton radiation therapy is a radiation oncology innovation expected to produce superior health-related quality of life (HRQoL) outcomes for children with cancer, compared to conventional photon radiation therapy. The review aim is to identify if clinical evidence exists to support the anticipated HRQoL improvements for children receiving proton radiation therapy. HRQoL outcomes of 1986 childhood cancer survivors are described. There is insufficient quality evidence to compare HRQoL outcomes between proton and photon radiation therapy. Therefore, the current state of the literature does not conclude that proton radiation therapy produces superior HRQoL outcomes for childhood cancer survivors. Despite recommendations, no evidence of routine HRQoL assessment using patient-reported outcomes in paediatric radiation oncology are identified. Further rigorous collection and reporting of HRQoL data is essential to improve patient outcomes, and to adequately compare HRQoL between radiation therapy modalities.Paediatric cancer patients have a risk of late side effects after curative treatment. Proton radiation therapy (PRT) has the potential to reduce the incidence and severity of toxicities produced by conventional photon radiation therapy (XRT), which may improve the health-related quality of life (HRQoL) in children. This systematic review aimed to identify the evidence of HRQoL outcomes in childhood cancer survivors following XRT and PRT. Medline, Embase, and Scopus were systematically searched. Thirty studies were analysed, which described outcomes of 1986 childhood cancer survivors. Most studies (n = 24) described outcomes for children with a central nervous system (CNS) tumour, four studies reported outcomes for children with a non-CNS tumour, and two studies combined CNS and non-CNS diagnoses within a single cohort. No studies analysed routine HRQoL collection during paediatric radiation oncology clinical practice. There is insufficient quality evidence to compare HRQoL outcomes between XRT and PRT. Therefore, the current state of the literature does not conclude that PRT produces superior HRQoL outcomes for childhood cancer survivors. Standardised clinical implementation of HRQoL assessment using patient-reported outcomes is recommended to contribute to improvements in clinical care whilst assisting the progression of knowledge comparing XRT and PRT.

Personal and Social Resources Are Linked to Cognition and Health-Related Quality of Life in Childhood Cancer Survivors.

Personal and social resources may buffer the adverse effects of childhood cancer and its impact on cognition and quality of life. While childhood cancer survivors show domain-specific cognitive difficulties, little is known about their personal and social resources. We therefore investigated personal and social resources and their association with cognitive and quality-of-life outcomes in childhood cancer survivors. Seventy-eight survivors of childhood cancer of different etiologies (aged 7–16 years; ≥one year since treatment) and fifty-six healthy controls were included. Cognitive outcome was assessed by neuropsychological tests; personal and social resources, as well as health-related quality of life, were assessed by standardized questionnaires. In the social resource domain, peer integration was worse in survivors than in controls (puncorr < 0.04, d = 0.33). Personal resources and all other subscales of social resources did not significantly differ between survivors and controls. In survivors, the global resource score was significantly correlated with processing speed (r = 0.39, pcorr < 0.001) and quality of life (parent: r = 0.44; self-report: r = 0.46; pscorr < 0.001). In controls, no association occurred between resources and cognitive outcome, and the correlation between the global resource score and quality of life did not withstand correction for multiple comparison (parent: r = 0.28; self-report: r = 0.40, psuncorr < 0.001). After an adverse event such as childhood cancer, resources might play a particularly buffering role on cognitive performance and quality of life (when compared to the everyday life of healthy controls). This highlights the importance of interventions that strengthen the resources of children and their families, even years after cancer. Such resource-focused intervention could help to counteract long-term sequelae in cognitive outcomes and health-related quality of life.

Influence of Body Mass Index, Cancer Type and Treatment on Long-Term Metabolic and Liver Outcomes in Childhood Cancer Survivors.

In the last decade, the survival of subjects affected by cancer in childhood has significantly improved. The increased lifespan of childhood cancer survivors (CCS) led to a greater risk for long-term, therapy-related morbidity. To identify the clinical predictors of metabolic adverse outcomes in CCS (average off-therapy period: 12 years), we recruited 126 survivors of different childhood cancers (86.5% hematological cancers) who received at least anticancer chemotherapy, consecutively approached during their annual oncohematological outpatient visit. At examination, anthropometric measures and cancer-related history were collected. Moreover, a fasting venous sample was carried out for measuring fasting plasma glucose and insulin, glycated hemoglobin, lipid panel, and transaminases. We calculated the indexes of insulin resistance (HOMA-IR, McAuley, and QUICKI) and secretion (HOMA-β), liver steatosis (Hepatic Steatosis Index) and fibrosis (FIB-4 and NAFLD fibrosis score), and visceral fat dysfunction (Visceral Adiposity Index). More than one-third of the subjects (37.3%) did not have normal weight, with 11.1% of them affected by obesity. At recruitment, obese subjects were at significantly higher risk for impaired fasting glucose, metabolic syndrome, visceral adipose dysfunction, and liver steatosis/fibrosis. Subjects who received bone marrow transplantation were prone to insulin resistance, while survivors of lymphoma presented a visceral adipose dysfunction These results suggest a carefully metabolic monitoring of CCS, particularly in subgroups at higher risk, to early detect these conditions, promptly begin therapeutic interventions, and mitigate the dysmetabolic-related health burden.

Childhood cancer survivorship care during the COVID-19 pandemic: an international report of practice implications and provider concerns.

PurposeLong-term follow-up (LTFU) care is essential to optimise health outcomes in childhood cancer survivors (CCS). We aimed to assess the impact of the COVID-19 pandemic on LTFU services and providers.MethodsA COVID-19 working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) distributed a questionnaire to LTFU service providers in 37 countries across Europe, Asia, North America, Central/South America, and Australia. The questionnaire assessed how care delivery methods changed during the pandemic and respondents’ level of worry about the pandemic’s impact on LTFU care delivery, their finances, their health, and that of their family and friends.ResultsAmong 226 institutions, providers from 178 (79%) responded. Shortly after the initial outbreak, 42% of LTFU clinics closed. Restrictions during the pandemic resulted in fewer in-person consultations and an increased use of telemedicine, telephone, and email consultations. The use of a risk assessment to prioritise the method of LTFU consultation for individual CCS increased from 12 to 47%. While respondents anticipated in-person consultations to remain the primary method for LTFU service delivery, they expected significantly increased use of telemedicine and telephone consultations after the pandemic. On average, respondents reported highest levels of worry about psychosocial well-being of survivors.ConclusionsThe pandemic necessitated changes in LTFU service delivery, including greater use of virtual LTFU care and risk-stratification to identify CCS that need in-person evaluations.Implications for Cancer Survivors Increased utilisation of virtual LTFU care and risk stratification is likely to persist post-pandemic.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11764-021-01120-9.

KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors: Description of Clinical Research Protocol of the KINDEST-CCS Study.

Approximately 30% of childhood cancer survivors (CCSs) will develop chronic kidney disease (CKD) or hypertension 15 to 20 years after treatment ends. The incidence of CKD and hypertension in the 5-year window after cancer therapy is unknown. Moreover, extent of monitoring of CCS with CKD and associated complications in current practice is underexplored. To inform the development of new and existing care guidelines for CCS, the epidemiology and monitoring of CKD and hypertension in the early period following cancer therapy warrants further investigation. To describe the design and methods of the KIdney aNd blooD prESsure ouTcomes in Childhood Cancer Survivors study, which aims to evaluate the burden of late kidney and blood pressure outcomes in the first ~10 years after cancer therapy, the extent of appropriate screening and complications monitoring for CKD and hypertension, and whether patient, disease/treatment, or system factors are associated with these outcomes. Two distinct, but related studies; a prospective cohort study and a retrospective cohort study. Five Ontario pediatric oncology centers. The prospective study will involve 500 CCS at high risk for these late effects due to cancer therapy, and the retrospective study involves 5,000 CCS ≤ 18 years old treated for cancer between January 2008 and December 2020. Chronic kidney disease is defined as Estimated glomerular filtration rate <90 mL/min/1.73 m2 or albumin-to-creatinine ratio ≥ 3mg/mmol. Hypertension is defined by 2017 American Academy of Pediatrics guidelines. Prospective study: we aim to investigate CKD and hypertension prevalence and the extent to which they persist at 3- and 5-year follow-up in CCS after cancer therapy. We will collect detailed biologic and clinical data, calculate CKD and hypertension prevalence, and progression at 3- and 5-years post-therapy. Retrospective study: we aim to investigate CKD and hypertension monitoring using administrative and health record data. We will also investigate the validity of CKD and hypertension administrative definitions in this population and the incidence of CKD and hypertension in the first ~10 years post-cancer therapy. We will investigate whether patient-, disease/treatment-, or system-specific factors modify these associations in both studies. Results from the prospective study may not be generalizable to non-high-risk CCS. The retrospective study is susceptible to surveillance bias. Our team and knowledge translation plan is engaging patient partners, researchers, knowledge users, and policy group representatives. Our work will address international priorities to improve CCS health, provide the evidence of new disease burden and practice gaps to improve CCS guidelines, implement and test revised guidelines, plan trials to reduce CKD and hypertension, and improve long-term CCS health.

Disparities in cardiovascular risk factors by race/ethnicity among adult survivors of childhood cancer: A report from the Childhood Cancer Survivorship Study (CCSS).

10017 Background: Racial, ethnic, and socioeconomic disparities are documented in outcomes for childhood cancer survivors. Understanding whether childhood cancer modifies established disparities in cardiovascular risk factors (CVRFs) in the general population would inform strategies to reduce health inequities among survivors. Methods: The CCSS is a retrospectively constructed cohort with prospective follow-up consisting of 25,579 five year survivors of childhood cancer diagnosed between 1970 and 1999. We estimated the incidence of self-reported Common Terminology Criteria for Adverse Events (CTCAE) grade &gt;2 CVRFs (hypertension, diabetes, dyslipidemia, and obesity) and multiple (&gt;2) CVRFs among survivors. Multivariable Poisson regression estimated the rate ratios (RR) of CVRFs by race/ethnicity, adjusted for key treatment exposures and sociodemographics. Results: Within the CCSS cohort, there were 20,416 non-Hispanic White (NHW), 1625 non-Hispanic Black (NHB), and 2043 Hispanic survivors with the cumulative incidence estimates of each CVRF at age 40 displayed in Table. Survivors who self-reported “Other” or mixed race were excluded for this analysis (n=1495). NHB survivors were more likely to report hypertension (unadjusted RR 1.3; 95% Confidence Interval [CI] 1.0-1.6), diabetes (RR 1.6; 95% CI 1.0-2.4), obesity (RR 1.6; 95% CI 1.4-1.9), and multiple CVRF (RR 1.3; 95% CI 1.2-1.5), whereas Hispanic survivors were more likely to report diabetes (RR 1.7; 95% CI 1.2-2.4), obesity (RR 1.4; 95% CI 1.2-1.5), and multiple CVRFs (RR 1.1; 95% CI 1.0-1.3) compared with NHW survivors. These observed disparities in risks of CVRFs remained nearly unchanged even after adjustment for sociodemographic factors (age, sex, household income, education, marital status, employment, and insurance) and treatment exposures (Yes/No for anthracyclines, alkylators, and chest radiation). Conclusions: NHB and Hispanic adult survivors demonstrate a higher burden of CVRF compared with NHW survivors, particularly diabetes and obesity. The associated morbidity of these conditions and established increase they incur in risk of more severe cardiovascular disease emphasizes the need for interventions to mitigate CVRFs to promote health equity among these survivors.[Table: see text]

Determinants of symptom clusters and associations with health outcomes in childhood cancer survivors: A report from the St. Jude Lifetime Cohort (SJLIFE).

10046 Background: Childhood cancer survivors experience concurrent symptoms, but associations with health outcomes are unknown. We characterize symptom clusters among adult survivors of childhood cancer in SJLIFE and tests associations with health-related quality of life (HRQL) and clinically assessed physical and neurocognitive performance. Methods: This cross-sectional study includes survivors diagnosed when &lt;18 years of age, ≥10 years off-therapy, and ≥18 years of age at evaluation. Survivors rated 37 symptoms over 10 domains (cardiac, pulmonary, sensory, motor, nausea, pain, fatigue, memory, anxiety, depression), representing 3 broader symptom groups (physical, somatic, psychological). They also underwent a rating of HRQL (SF-36 PCS/MCS) and testing of physical performance (quantitative sensory, motor, endurance, mobility) and neurocognition (processing speed, executive function, attention, memory problems). Latent class analysis determined survivors with distinct symptom burden. Polytomous logistic regression identified risk factors of symptom clusters; multivariable regression tested associations of symptom clusters with health outcomes. Results: Among 3,085 survivors, mean [SD] age at evaluation was 31.9 [8.3] years, time from diagnosis was 28.1 [9.1] years, 49.7% were female, 37.1% were treated for leukemia and 33.0% for solid tumors. Four groups of survivors with distinct symptom burden were found: Cluster 1 (52%, low prevalence in all 3 symptom groups); Cluster 2 (16%, low in physical, moderate in somatic, high in psychological); Cluster 3 (18%; high in physical, moderate in somatic, low in physiological); and Cluster 4 (14%, high in all 3 symptom groups). Compared to the lowest symptom burden (Cluster 1), survivors with highest burden (Cluster 4) were significantly more likely to be female (OR 2.5; 95%CI 1.9, 3.4), have below a high school education (OR 7.7; 95%CI 4.5, 13.3), no insurance (OR 1.5; 95%CI 1.1, 2.3) and previous exposure to corticosteroids (OR 1.8; 95%CI 1.0, 3.0). High physical, moderate somatic and low psychological symptom burden (Cluster 3) was associated with below high school education (OR 2.7; 95%CI 1.4, 5.0), exposure to platinum agents (OR 2.2; 95%CI 1.4, 3.7) and brain radiation ≥30Gy (OR 4.0; 95%CI 2.3, 6.9) in contrast to Cluster 1. Survivors in Cluster 4 had the poorest PCS, MCS, physical and neurocognitive outcomes vs in Clusters 2 or 3, whereas those in Cluster 1 had the best outcomes (F-values for 4 clusters: 291.4 [PCS], 269.2 [MCS], 61.5 [physical], 36.9 [neurocognitive], p-values &lt;0.001; effect sizes for Clusters 4 vs 1: 0.4-2.0 [4 outcomes]). Conclusions: Nearly 50% of survivors belong to symptom clusters with ≥1 moderate/high burden groups, associated with the socio-demographic and treatment exposures. Survivors in the highest symptom burden cluster had the poorest HRQL and functional outcomes.

Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report.

Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors. Family history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0-23); age at last follow-up, 35 years (range, 18-66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events grade 2-4 events) and cardiovascular risk factors. Among survivors exposed to chest-directed radiation and/or anthracycline chemotherapy (n = 824), 7% reported a first-degree family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01-1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26-1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06-1.59; P = 0.01)]. Family history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies. These data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer.