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Purpose: Long-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. Methods: A 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. Results: Among 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. Conclusions: The 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., + ID der Publikation: unilu_56897 + Sprache: Englisch + Letzte Aktualisierung: 2022-01-24 15:04:24

Educational achievement and employment outcomes are critical indicators of quality of life in survivors of childhood, adolescent, and young adult (CAYA) cancer. This review is aimed at providing an evidence-based clinical practice guideline (CPG) with internationally harmonized recommendations for the surveillance of education and employment outcomes in survivors of CAYA cancer diagnosed before the age of 30 years. The CPG was developed by a multidisciplinary panel under the umbrella of the International Late Effects of Childhood Cancer Guideline Harmonization Group. After evaluating concordances and discordances of 4 existing CPGs, the authors performed a systematic literature search through February 2021. They screened articles for eligibility, assessed quality, and extracted and summarized the data from included articles. The authors formulated recommendations based on the evidence and clinical judgment. There were 3930 articles identified, and 83 of them, originating from 17 countries, were included. On a group level, survivors were more likely to have lower educational achievement and more likely to be unemployed than comparisons. Key risk factors for poor outcomes included receiving a primary diagnosis of a central nervous system tumor and experiencing late effects. The authors recommend that health care providers be aware of the risk of educational and employment problems, implement regular surveillance, and refer survivors to specialists if problems are identified. In conclusion, this review presents a harmonized CPG that aims to facilitate evidence-based care, positively influence education and employment outcomes, and ultimately minimize the burden of disease and treatment-related late adverse effects for survivors of CAYA cancers. LAY SUMMARY: A multidisciplinary panel has developed guidelines for the surveillance of education and employment outcomes among survivors of childhood, adolescent, and young adult cancer. On the basis of evidence showing that survivors are at risk for lower educational achievement and unemployment, it is recommended that all survivors receive regular screening for educational and employment outcomes. ispartof: CANCER vol:128 issue:13 pages:2405-2419 ispartof: location:United States status: published

Type 2 diabetes mellitus (T2D) is an established late effect of treatment for childhood cancer. Leveraging detailed cancer treatment and whole-genome sequencing data among survivors of childhood cancer of European (EUR) and African (AFR) genetic ancestry in the St. Jude Lifetime Cohort (N=3,676; 304 cases), five novel diabetes mellitus (DM) risk loci were identified with independent trans-/within-ancestry replication, including in 5,965 survivors of the Childhood Cancer Survivor Study. Among these, common risk variants at 5p15.2 ( LINC02112 ), 2p25.3 ( MYT1L ), and 19p12 ( ZNF492 ) modified alkylating agent-related risks across ancestry groups, but AFR survivors with risk alleles experienced disproportionately greater risk of DM (AFR, variant ORs: 3.95-17.81; EUR, variant ORs: 2.37-3.32). Novel risk locus XNDC1N was identified in the first genome-wide DM rare variant burden association analysis in survivors (OR=8.65, 95% CI: 3.02-24.74, P=8.1×10 (-6) ). Lastly, a general-population 338-variant multi-ancestry T2D polygenic risk score was informative for DM risk in AFR survivors, and showed elevated DM odds after alkylating agent exposures (quintiles: combined OR (EUR) =8.43, P=1.1×10 (-8) ; OR (AFR) =13.85, P=0.033). This study supports future precision diabetes surveillance/survivorship care for all childhood cancer survivors, including those with AFR ancestry.

The dataset contains variables used in the study of "Response-shift effects in childhood cancer survivors: A prospective study" reported in Huang et al., Psycho-Oncology 2023 (In Press). Please cite the appropriate publications in any communications or publications arising directly or indirectly from these data.&nbsp

Additional file 1. Supplementary Information.

Additional file 1: Table S1. Components and standards for scoring for Dietary Approaches to Stop Hypertension, Healthy Eating Index-2015, and Alternate Mediterranean diet. Figure S1. Radar plot showing the mean percentage of each component score received in men and women. Table S2. Characteristics of childhood cancer survivors by cardiovascular diseasestatus in the St. Jude Lifetime Cohort Study. Table S3. Characteristics of childhood cancer survivors by quintiles of DASH in the St. Jude Lifetime Cohort Study. Table S4. Characteristics of childhood cancer survivors by tertiles of Mediterranean Diet in the St. Jude Lifetime Cohort Study. Figure S2. Non-parametric regression curves1 for associations between DASH and risk of CVD in St. Jude Lifetime Cohort Study. Figure S3. Non-parametric regression curves1 for associations between Mediterranean diet and risk of CVD in St. JudeLifetime Cohort Study.

BackgroundGonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported.MethodsLeveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of SNPs on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE).ResultsIn the CCSS cohort, nine SNPs were found to be suggestive (P < 10-7) or statistically significantly (P < 5 × 10-8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures, and birth cohort.ConclusionsWe were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors.ImpactFuture attempts at replication should be considered in cohorts treated in a comparable era. In addition, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.

Educational achievement and employment outcomes are critical indicators of quality of life in survivors of childhood, adolescent, and young adult (CAYA) cancer. This review is aimed at providing an evidence-based clinical practice guideline (CPG) with internationally harmonized recommendations for the surveillance of education and employment outcomes in survivors of CAYA cancer diagnosed before the age of 30 years. The CPG was developed by a multidisciplinary panel under the umbrella of the International Late Effects of Childhood Cancer Guideline Harmonization Group. After evaluating concordances and discordances of 4 existing CPGs, the authors performed a systematic literature search through February 2021. They screened articles for eligibility, assessed quality, and extracted and summarized the data from included articles. The authors formulated recommendations based on the evidence and clinical judgment. There were 3930 articles identified, and 83 of them, originating from 17 countries, were included. On a group level, survivors were more likely to have lower educational achievement and more likely to be unemployed than comparisons. Key risk factors for poor outcomes included receiving a primary diagnosis of a central nervous system tumor and experiencing late effects. The authors recommend that health care providers be aware of the risk of educational and employment problems, implement regular surveillance, and refer survivors to specialists if problems are identified. In conclusion, this review presents a harmonized CPG that aims to facilitate evidence-based care, positively influence education and employment outcomes, and ultimately minimize the burden of disease and treatment-related late adverse effects for survivors of CAYA cancers. Lay Summary A multidisciplinary panel has developed guidelines for the surveillance of education and employment outcomes among survivors of childhood, adolescent, and young adult cancer. On the basis of evidence showing that survivors are at risk for lower educational achievement and unemployment, it is recommended that all survivors receive regular screening for educational and employment outcomes., + ID der Publikation: unilu_58956 + Sprache: Englisch + Letzte Aktualisierung: 2022-05-04 16:54:38

Additional file 1: Fig. S1. The scatter plots between chronological age and epigenetic age based on four epigenetic clocks. Fig. S2. QQ plots of EAA GWAS based on four epigenetic clocks. Fig. S3. Distribution of intrinsic epigenetic age acceleration (IEAA) across five quintiles of polygenic risk score (PRS) for IEAA. Fig. S4. Molecular mechanism for associations between rs732314, chest/abdominal/pelvic-RT and EAA-Horvath. Table S1. SNPs (except the top one) significantly associated with EAA-Horvath and EAA-Hannum among survivors (SJLIFE1, SJLIFE2) and controls. Table S2. Single nucleotide polymorphisms (SNPs) with significant associations with IEAA-Horvath and EEAA-Hannum among survivors (SJLIFE1, SJLIFE2) and controls. Table S3. Differentially methylated regions (DMR) between the SJLIFE1 data set of survivors and controls overlapping with rs28366133 (+/- 500 kb) in HLA region. Table S4. Multivariable linear regression models for the two top SNPs. Table S5. Estimated SNP heritability of EAA based on each of four clock methods using single-trait LD Score Regression of the GWAS of the SJLIFE1 data set. Table S6. Estimated genetic correlation between EAA-Horvath and other traits using LD Score Regression of the GWAS of the SJLIFE1 data set (P

CONTEXT Key Objective: Survivors of childhood cancer are at risk for educational problems and lower educational attainment. This systematic review examined data from 80 studies across 18 countries to characterize the frequency of educational support use and the impact of educational interventions on school outcomes and quality of life among children with cancer, from diagnosis into long-term survivorship. Knowledge Generated: Frequency of educational support use varied between diagnosis groups, with higher use observed among survivors of brain tumors. Although substantial proportions of survivors of childhood cancer receive educational supports during or after their cancer treatment, there was a paucity of intervention research to evaluate the effectiveness of these supports. Relevance: Early and ongoing communication between oncology providers, families, and schools is critical for ensuring survivors' access to needed educational supports. Additional research is needed to develop and evaluate interventions to help survivors overcome educational problems associated with childhood cancer and its treatment., + ID der Publikation: unilu_53988 + Sprache: Englisch + Letzte Aktualisierung: 2021-06-02 12:58:31

Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

Additional file 1 Supplementary material. The supplementary material includes (i) the histograms of the predicted AOF risk obtained from the prescribed-dose model and ovarian-dose model for individuals with and without AOF, respectively, (ii) the procedure of obtaining the true values of the IncV metrics under the distributional assumptions of the numerical study, (iii) the results of the numerical study scenarios in which neither of the working risk models is the true model, including plots of the values of each IncV metric for all the scenarios under different event rates, and the scatter plots of each pair of the IncV metrics, and (iv) the results for the scenarios where the two-marker model is the true model, including plots of the values of each IncV metric for all the scenarios under different event rates, plots of their summary statistics, and a table listing the Pearson correlation of each pair of the IncV metrics. (PDF file)

Additional file 1: Supplementary Methods. Bisulfite treatment, array hybridization, and scanning for DNA Methylation Profiling. Fig. S1. A flow diagram of the study population. Fig. S2. Q-Q plot showing the distribution of the observed versus expected association p-values. Fig. S3. Manhattan plot showing the treatment-specific association of DNA methylation. Fig. S4. The distributions of whole-array and significant treatment-associated CpG sites. Fig. S5. The distribution of beta-values for CpG mediators by groups of CHCs. Table S1. Pairwise correlations among eleven different treatments. Table S2. CpG hits associated with the specific treatment exposure (P

Incremental value (IncV) evaluates the performance change from an existing risk model to a new model. It is one of the key considerations in deciding whether a new risk model performs better than the existing one. Problems arise when different IncV metrics contradict each other. For example, compared with a prescribed-dose model, an ovarian-dose model for predicting acute ovarian failure has a slightly lower area under the receiver operating characteristic curve (AUC) but increases the area under the precision-recall curve (AP) by 48%. This phenomenon of conflicting conclusions is not uncommon, and it creates a dilemma in medical decision making. In this article, we examine the analytical connections and differences between two IncV metrics: IncV in AUC (IncV-AUC) and IncV in AP (IncV-AP). Additionally, since they are both semi-proper scoring rules, we compare them with a strictly proper scoring rule: the IncV of the scaled Brier score (IncV-sBrS), via a numerical study. We demonstrate that both IncV-AUC and IncV-AP are weighted averages of the changes (from the existing model to the new one) in separating the risk score distributions between events and non-events. However, IncV-AP assigns heavier weights to the changes in the high-risk group, whereas IncV-AUC weights the changes equally. In the numerical study, we find that IncV-AP has a wide range, from negative to positive, but the size of IncV-AUC is much smaller. In addition, IncV-AP and IncV-sBr Sare highly consistent, but IncV-AUC is negatively correlated with IncV-sBrS and IncV-AP at a low event rate. IncV-AUC and IncV-AP are the least consistent among the three pairs, and their differences are more pronounced as the event rate decreases., 25 pages, 6 figures, 1 table. Compared to Version 1, the title and overall structure of the manuscript have been changed significantly

Purpose Cancer-related fatigue (CRF) negatively affects the lives of childhood, adolescent, and young adult (CAYA) cancer survivors. We aimed to provide an evidence-based clinical practice guideline (CPG) with internationally harmonized CRF surveillance recommendations for CAYA cancer survivors diagnosed

The purpose of this study was to define the prevalence of and risk factors for elevated serum alanine aminotransferase (ALT) level among adult childhood cancer survivors (CCS). The study cohort comprised 2,751 CCS from the St. Jude Lifetime Cohort Study (10 years postdiagnosis, age ≥18 years). Serum ALT level was graded using the Common Terminology Criteria for Adverse Events v. 4.03. Modified Poisson regression models were used to estimate relative risks and 95% confidence intervals for the association between demographic and clinical factors and grades 1-4 ALT on the selected models. A total of 1,339 (48.7%) CCS were female; 2,271 (82.6%) were non-Hispanic white. Median age at evaluation was 31.4 years (interquartile range [IQR] = 25.8-37.8); median elapsed time from diagnosis to evaluation was 23.2 years (IQR = 17.6-29.7). A total of 1,137 (41.3%) CSS had ALTupper limit of normal (Common Terminology Criteria for Adverse Events v. 4.03 grade 1-1,058 (38.5%); grade 2-56 (2.0%); grade 3-23 (0.8%); grade 4-none). Multivariable models demonstrated non-Hispanic white race/ethnicity, age at evaluation in years, being overweight or obese, presence of the metabolic syndrome, current treatment with atorvastatin or rosuvastatin or simvastatin, hepatitis C virus infection, prior treatment with busulfan or thioguanine, history of hepatic surgery, and the percentage of liver treated with ≥10 Gray, ≥15 Gray, or ≥20 Gray were associated with elevated ALT. Conclusion: Grade 3 or 4 hepatic injury is infrequent in CCS. Mild hepatic injury in this group may be amenable to lifestyle modifications.

Sedentary behaviors are associated with poor health outcomes in the general population, but their clinical impact on adult survivors of childhood acute lymphoblastic leukemia (ALL) has not been characterized to date. In the current study, we described the prevalence of sedentary behaviors in survivors of ALL and examined associations between time spent sedentary and body composition and onset of cardiovascular disease (CVD) risk factors.Participants' self-reported screen time (eg, television, computer) and activity as measured by accelerometer were used to determine activity time (sedentary, light activity, and moderate or vigorous physical activity). The percentage of time spent in each activity was compared between 331 survivors of ALL and 330 controls. Associations between time sedentary and body composition were evaluated in survivors using linear regression models. Cox proportional hazard models were used to examine the association between time sedentary at baseline and CVD risk factor onset during follow-up.Survivors spent approximately 65% of their time sedentary, 32% in light activity, and 2% in moderate or vigorous physical activity compared with 67% (P = .04), 30% (P.01), and 3% (P.01), respectively, in controls. Among survivors, percentage lean body mass decreased by 1.0% ± 0.4% (P = .01) per 10% increase in time sedentary. Survivors who were sedentary ≥60% per day were found to be at an increased risk of high total cholesterol (hazard ratio, 2.52; 95% confidence interval, 1.12-5.64) and any CVD risk factor (hazard ratio, 1.96; 95% confidence interval, 1.16-3.30).Sedentary behavior is associated with low lean mass and CVD risk factor development and should be limited in survivors of childhood ALL. Cancer 2018;124:1036-43. © 2017 American Cancer Society.

Cancer survivors transfused with blood products before reliable screening for hepatitis C virus (HCV) are at risk for infection. This study examined the impact of HCV on neurocognitive function and health-related quality of life (HRQOL) among adult survivors of childhood cancer.Neurocognitive testing was conducted for 836 adult survivors of childhood cancer (mean age, 35 years [standard deviation, 7.4 years]; time since diagnosis, 29 years [standard deviation, 6.2 years]) who received blood products before universal HCV screening. No differences were observed between confirmed HCV-seropositive survivors (n = 79) and HCV-seronegative survivors (n = 757) in the primary diagnosis or neurotoxic therapies. Multivariate regression models were used to compare functional outcomes between seropositive and seronegative survivors.Compared with seronegative survivors, seropositive survivors demonstrated lower performance on measures of attention (P.001), processing speed (P = .008), long-term verbal memory (P = .01), and executive function (P = .001). After adjustments for sex, age at diagnosis, and treatment exposures, seropositive survivors had a higher prevalence of impairment in processing speed (prevalence ratio [PR], 1.3; 95% confidence interval [CI], 1.1-1.6) and executive functioning (PR, 1.3; 95% CI, 1.1-1.6). Differences were not associated with the treatment of HCV or the presence of liver cirrhosis. Seropositive survivors reported worse general HRQOL (PR, 1.6; 95% CI, 1.2-2.1), which was associated with the presence of liver cirrhosis (P = .001).Survivors of childhood cancer with a history of HCV infection are at risk for neurocognitive impairment and reduced HRQOL beyond the known risks associated with neurotoxic cancer therapies. Cancer 2017;123:4498-505. © 2017 American Cancer Society.

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research.

PURPOSE: Despite the significant risk of cardiac disease after pediatric cancer treatment with anthracyclines and radiation, adult survivors are not participating in recommended screening. We documented the per-survivor and per-additional-survivor-screened costs of a mailed survivorship care plan with (SCP+C) or without (SCP) advance practice nurse telephone counseling. DESIGN: Randomized longitudinal clinical trial. SETTING: St. Jude Children’s Research Hospital (SJCRH). SAMPLE: 411 at-risk pediatric cancer survivors (26-59 years old; mean = 41 years, SD = 7.68), stratified by age (

Survivors of pediatric cancer have elevated risks of mortality and morbidity. Many late adverse effects associated with cancer treatment (eg, second cancers and cardiac and pulmonary disease) are also associated with cigarette smoking, and this suggests that survivors who smoke may be at high risk for these conditions.This study examined the self-reported smoking status for 9397 adult survivors of childhood cancer across 3 questionnaires (median time interval, 13 years). The smoking prevalence among survivors was compared with the smoking prevalence among siblings and the prevalence expected on the basis of age-, sex-, race-, and calendar time-specific rates in the US population. Multivariable regression models examined characteristics associated with longitudinal smoking patterns across all 3 questionnaires.At the baseline, 19% of survivors were current smokers, whereas 24% of siblings were current smokers, and 29% were expected to be current smokers on the basis of US rates. Current smoking among survivors dropped to 16% and 14% on follow-up questionnaires, with similar decreases in the sibling prevalence and the expected prevalence. Characteristics associated with consistent never-smoking included a higher household income (relative risk [RR], 1.16; 95% confidence interval [CI], 1.08-1.25), higher education (RR, 1.32; 95% CI, 1.22-1.43), and receipt of cranial radiation therapy (RR, 1.08; 95% CI, 1.03-1.14). Psychological distress (RR, 0.86; 95% CI, 0.80-0.92) and heavy alcohol drinking (RR, 0.64; 95% CI, 0.58-0.71) were inversely associated. Among ever-smokers, a higher income (RR, 1.17; 95% CI, 1.04-1.32) and education (RR, 1.23; 95% CI, 1.10-1.38) were associated with quitting, whereas cranial radiation (RR, 0.86; 95% CI, 0.76-0.97) and psychological distress (RR, 0.80; 95% CI, 0.72-0.90) were associated with not having quit. The development of adverse health conditions was not associated with smoking patterns.Despite modest declines in smoking prevalence, the substantial number of consistent current smokers reinforces the need for continued development of effective smoking interventions for survivors.

The objective of this study was to identify treatment and genetic factors associated with obesity among childhood cancer survivors.Participants included 1996 survivors who previously received treatment for cancer at St. Jude Children's Research Hospital and who survived ≥10 years from diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years). Obesity was defined as a body mass index ≥30 kg/m(2) . The factors associated with adult obesity were identified by subgroup-specific (cranial radiation [CRT] exposure status) multivariable logistic regression. Single nucleotide polymorphisms (SNPs) associated with obesity were identified by subgroup-specific, exploratory, genome-wide association analyses using a 2-stage resampling approach with a type I error rate of 5 × 10(-6) .Forty-seven percent of survivors who received CRT and 29.4% of those who did not receive CRT were obese at evaluation. In multivariable analyses, abdominal/pelvic radiation exposure was associated with decreased prevalence of obesity among survivors regardless of CRT status (P.0001). The odds of obesity were increased among survivors who received CRT who had also received glucocorticoids (P = .014) or who were younger at diagnosis (P = .013). Among the survivors who had received CRT, 166 SNPs were associated with obesity. The strongest association was observed with reference SNP rs35669975 (P = 3.3 × 10(-8) ) on segment 33.3 of the long arm of chromosome 13 (13q33.3), approximately 30 kb downstream of FAM155A (family with sequence similarity 155, member A). SNPs within the glycine receptor α3 (GLRA3) gene and near the sex-determining region Y box 11 (SOX11) and cadherin 18 type 2 (CDH18) genes also were identified. These genes have been implicated in neural growth, repair, and connectivity.Obesity in childhood cancer survivors remains associated with previous exposure to CRT and glucocorticoids. Genetic variants related to neural connectivity may modify the risk of obesity among survivors who receive CRT. Validation of these findings in independent cohorts is required.

Childhood cancer survivors (CCSs) are at risk for obesity. The purpose of this project was to determine which clinical measures of body composition are most accurate among CCSs in comparison with dual-energy x-ray absorptiometry (DXA).The agreement between the body mass index (BMI), skinfold percent body fat, and waist-to-height ratio (WHtR) and DXA was evaluated among 1361 CCSs (mean age, 32.4 ± 7.7 years) 10 or more years after the diagnosis. The sensitivity and specificity of BMI, skinfold, and WHtR obesity classifications were calculated with respect to DXA. Log-binomial regression, stratified by sex, was used to evaluate treatment-related factors for misclassification as nonobese by BMI, skinfolds, and WHtR.The mean body fat values were 23.3% ± 7.7% (males) and 32.3% ± 8.1% (females) for skinfolds and 26.9% ± 7.4% (males) and 38.4% ± 7.7% (females) for DXA. Pearson correlations between skinfolds and DXA were high (R = 0.83 for males, R = 0.84 for females). Skinfolds incorrectly classified 34.5% of obese males and 27.3% of obese females. BMI measures were the least sensitive with false-negative rates of 46.4% (males) and 53.1% (females). Males exposed to abdominal/pelvic radiation were at increased risk for misclassification as nonobese by BMI (relative risk, 1.57; 95% confidence interval, 1.25-1.95). The percentages classified as obese were highest with DXA (males, 63.1%; females, 84.8%) and lowest with BMI (males, 35.7%; females, 39.7%). Although skinfolds and WHtR underestimated the percentage classified as obese in comparison with DXA, the differences were not as large.Findings suggest that skinfolds and WHtR are better than BMI for obesity classification in CCSs. Clinicians should be aware of the high risk of misclassifying obese CCSs as nonobese.

The current study investigated the occurrence of emotional distress in parents of long-term survivors of childhood acute lymphoblastic leukemia (ALL) and identified factors associated with parent emotional distress symptoms.Parents of 127 long-term survivors of childhood ALL treated on a chemotherapy-only protocol at St. Jude Children's Research Hospital participated in the study. Parents completed standard ratings of emotional distress, caregiver strain, and child physical, emotional, and psychosocial functioning. Multivariable hierarchical linear regression analyses were used to examine associations between symptoms of caregiver strain, survivor functioning, and parent emotional distress. Covariates included parent education, survivor age, survivor sex, and time since childhood cancer diagnosis.On average, few parents reported significant symptoms of emotional distress. Clinically significant levels of anxiety and depression were reported by 7.1% and 3.1% of parents, respectively. Only 3.9% of parents endorsed significant symptoms of posttraumatic stress. Perceived caregiver strain was significantly associated with symptoms of parent anxiety, depression, and posttraumatic stress. Parent-report of child emotional functioning was significantly associated with symptoms of parent anxiety.Most parents of long-term survivors of ALL exhibit low levels of emotional distress in the context of rates observed in the general population. Perceived caregiver strain was significantly associated with parent emotional distress. Further research is required to examine specific sources of caregiver strain, as well as other risk and protective factors associated with parent emotional distress symptoms.

Survivors of childhood cancer treated with central nervous system (CNS)-directed therapy may be at risk for poor health care utilization because of neurocognitive deficits. This study examined associations between neurocognitive function and adherence to routine and risk-based medical evaluations in adult survivors exposed to CNS-directed therapy.Neurocognitive function and health care utilization were assessed in 1304 adult survivors of childhood cancer enrolled in the St. Jude Lifetime Cohort Study. Adherence to recommended care was defined as meeting guidelines published by the Children's Oncology Group. Multivariate models were used to evaluate associations between neurocognitive function and health screenings. Established predictors of health care utilization were included as covariates. Odds ratios (ORs) or prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated for variables maintained in the final models.Adherence to recommended medical care was higher for routine care (general physician care, 57.6%; dental care, 49.1%) versus specialized care (survivor-focused care, 21.9%; echocardiogram, 19.9%). Higher intelligence was predictive of general physician care (OR, 1.74; 95% CI, 1.41-2.15) and survivor-focused care (OR, 1.44; 95% CI, 1.13-1.83) in comparison with no care, whereas better executive function skills were associated with reduced dental care (PR, 0.94; 95% CI, 0.91-0.98). Echocardiogram monitoring was not associated with neurocognition. Possible late effects of cancer treatment (pain and reduced cardiorespiratory fitness) were associated with an increased likelihood of receiving specialized medical care.Survivors with reduced global cognition are at risk for poor health care utilization. Educational practices regarding recommended health care should be personalized to ensure comprehension by survivors with neurocognitive impairment.

Survivors of Hodgkin lymphoma (HL) have significant cardiovascular risk and require long-term surveillance. The current study assessed the prevalence of coronary artery disease (CAD) by coronary computed tomography angiography (CCTA) in adult survivors of childhood HL.Thirty-one survivors of HL, 13 of whom (42%) were treated with radiotherapy (RT) only and 18 of whom (58%) were treated with multimodal therapy, underwent CCTA, echocardiography, electrocardiography (ECG), and treadmill stress testing. Obstructive CAD was defined as ≥50% occlusion of the left main or ≥70% occlusion of the left anterior descending, left circumflex, or right coronary arteries on CCTA. Echocardiograms with resting wall motion abnormalities or an ejection fraction50%; ECGs with Q waves, ST abnormalities without Q waves, or T-wave abnormalities without Q waves; and a J-point depression of ≥1 mm with a horizontal or downsloping ST segment on stress testing were considered abnormal.The prevalence of disease in participants (median age, 40 years [range, 26 years-55 years]; median time from cancer diagnosis, 24 years [range, 17 years-39 years]) was 39%, with 39 plaques detected among 12 survivors. Three participants (10%) treated with RT only had 4 obstructive lesions; 9 patients (29%; 5 of whom were treated with RT only and 4 of whom were treated with multimodal therapy) had nonobstructive lesions. Approximately 15% of lesions involved the left main, 21% involved the proximal left anterior descending, 18% involved the proximal right coronary, and 13% involved the proximal left circumflex arteries. Of the 12 participants found to have CAD by CCTA, 7 had a positive ECG, 1 had a positive echocardiogram, and 1 had a positive stress test.CCTA identified CAD in a substantial percentage of survivors of HL and may be an effective screening modality for this population.

Female childhood, adolescent and young adult (CAYA) cancer survivors treated with radiation to fields that include breast tissue (chest radiation) have an increased risk of breast cancer. Clinical practice guidelines are essential to ensure that these survivors receive optimum care, and thereby reduce the detrimental consequences of cancer treatment. However, surveillance recommendations vary among the existing long-term follow-up guidelines. This guideline provides international harmonized breast cancer surveillance recommendations for female CAYA cancer survivors treated with chest radiation prior to age 30 years. We applied evidence-based methods to develop the international harmonized recommendations. The recommendations were formulated by an international multidisciplinary guideline panel and categorized according to a 4-level colour grading schema adapted from existing level of evidence criteria. The harmonized breast cancer surveillance recommendations are based on a transparent process and are intended to be scientifically rigorous, positively influence health outcomes, and facilitate care for CAYA cancer survivors.

Estimation of the risk of adverse long-term outcomes such as second malignant neoplasms and infertility often requires reproducible quantification of exposures. The method for quantification should be easily utilized and valid across different study populations. The widely used Alkylating Agent Dose (AAD) score is derived from the drug dose distribution of the study population and thus cannot be used for comparisons across populations as each will have a unique distribution of drug doses.We compared the performance of the Cyclophosphamide Equivalent Dose (CED), a unit for quantifying alkylating agent exposure independent of study population, to the AAD. Comparisons included associations from three Childhood Cancer Survivor Study (CCSS) outcome analyses, receiver operator characteristic (ROC) curves and goodness of fit based on the Akaike's Information Criterion (AIC).The CED and AAD performed essentially identically in analyses of risk for pregnancy among the partners of male CCSS participants, risk for adverse dental outcomes among all CCSS participants and risk for premature menopause among female CCSS participants, based on similar associations, lack of statistically significant differences between the areas under the ROC curves and similar model fit values for the AIC between models including the two measures of exposure.The CED is easily calculated, facilitating its use for patient counseling. It is independent of the drug dose distribution of a particular patient population, a characteristic that will allow direct comparisons of outcomes among epidemiological cohorts. We recommend the use of the CED in future research assessing cumulative alkylating agent exposure.

Adult survivors of childhood cancer are known to be at risk for treatment-related adverse health outcomes. A large population of survivors has not been evaluated using a comprehensive systematic clinical assessment to determine the prevalence of chronic health conditions.To determine the prevalence of adverse health outcomes and the proportion associated with treatment-related exposures in a large cohort of adult survivors of childhood cancer.Presence of health outcomes was ascertained using systematic exposure-based medical assessments among 1713 adult (median age, 32 [range, 18-60] years) survivors of childhood cancer (median time from diagnosis, 25 [range, 10-47] years) enrolled in the St Jude Lifetime Cohort Study since October 1, 2007, and undergoing follow-up through October 31, 2012.Age-specific cumulative prevalence of adverse outcomes by organ system.Using clinical criteria, the crude prevalence of adverse health outcomes was highest for pulmonary (abnormal pulmonary function, 65.2% [95% CI, 60.4%-69.8%]), auditory (hearing loss, 62.1% [95% CI, 55.8%-68.2%]), endocrine or reproductive (any endocrine condition, such as hypothalamic-pituitary axis disorders and male germ cell dysfunction, 62.0% [95% CI, 59.5%-64.6%]), cardiac (any cardiac condition, such as heart valve disorders, 56.4% [95% CI, 53.5%-59.2%]), and neurocognitive (neurocognitive impairment, 48.0% [95% CI, 44.9%-51.0%]) function, whereas abnormalities involving hepatic (liver dysfunction, 13.0% [95% CI, 10.8%-15.3%]), skeletal (osteoporosis, 9.6% [95% CI, 8.0%-11.5%]), renal (kidney dysfunction, 5.0% [95% CI, 4.0%-6.3%]), and hematopoietic (abnormal blood cell counts, 3.0% [95% CI, 2.1%-3.9%]) function were less common. Among survivors at risk for adverse outcomes following specific cancer treatment modalities, the estimated cumulative prevalence at age 50 years was 21.6% (95% CI, 19.3%-23.9%) for cardiomyopathy, 83.5% (95% CI, 80.2%-86.8%) for heart valve disorder, 81.3% (95% CI, 77.6%-85.0%) for pulmonary dysfunction, 76.8% (95% CI, 73.6%-80.0%) for pituitary dysfunction, 86.5% (95% CI, 82.3%-90.7%) for hearing loss, 31.9% (95% CI, 28.0%-35.8%) for primary ovarian failure, 31.1% (95% CI, 27.3%-34.9%) for Leydig cell failure, and 40.9% (95% CI, 32.0%-49.8%) for breast cancer. At age 45 years, the estimated cumulative prevalence of any chronic health condition was 95.5% (95% CI, 94.8%-98.6%) and 80.5% (95% CI, 73.0%-86.6%) for a serious/disabling or life-threatening chronic condition.Among adult survivors of childhood cancer, the prevalence of adverse health outcomes was high, and a systematic risk-based medical assessment identified a substantial number of previously undiagnosed problems that are more prevalent in an older population. These findings underscore the importance of ongoing health monitoring for adults who survive childhood cancer.

Acute lymphoblastic leukemia (ALL) and brain tumor (BT) survivors are at risk for post-treatment IQ declines. The extent to which lower scores represent global cognitive decline versus domain-specific impairment remains unclear. This study examined discrepancies between processing speed and estimated IQ (EIQ) scores and identified clinical characteristics associated with score discrepancies in a sample of pediatric cancer survivors.Survivors (50 ALL, 50 BT) ages 12-17 years completed cognitive testing. The Wechsler Abbreviated Scale of Intelligence provided an untimed measure of general reasoning ability (EIQ). The age-appropriate Wechsler Intelligence Scale provided a Processing Speed Index (PSI) score. Scores were examined and compared.Survivors' PSI scores were lower than their EIQ scores (BT t(45) =6.3, p0.001; ALL t(49) =6.9, p0.001). For BT survivors, lower PSI scores were associated with history of craniospinal irradiation, t(44) =3.3, p0.01. For ALL survivors, lower PSI scores were associated with male gender, grade retention, and time since diagnosis, F(3, 46) =10.1, p0.001. Clinically significant EIQ-PSI score discrepancies were identified in 41.3% of BT and 14.0% of ALL survivors.Many pediatric BT and ALL survivors exhibit slower processing speed than expected for age, whereas general reasoning ability remains largely intact. Risk factors associated with larger EIQ-PSI discrepancies include the following: BT diagnosis, craniospinal irradiation (BT only), male gender, and younger age at diagnosis (ALL only). Grade retention was frequent and associated with lower EIQ scores (both groups) and PSI scores (ALL only). Describing post-treatment cognitive declines using global measures of intellectual ability may underestimate dysfunction or fail to isolate specific underlying deficits contributing to impairment.

Childhood and young adult cancer survivors should receive optimum care to reduce the consequences of late effects and improve quality of life. We can facilitate achieving this goal by international collaboration in guideline development. In 2010, the International Late Effects of Childhood Cancer Guideline Harmonization Group was initiated. The aim of the harmonization endeavor is to establish a common vision and integrated strategy for the surveillance of late effects in childhood and young adult cancer survivors. With the implementation of our evidence-based methods, we provide a framework for the harmonization of guidelines for the long-term follow-up of childhood and young adult cancer survivors. Pediatr Blood Cancer 2013;60:543-549. (C) 2012 Wiley Periodicals, Inc

To describe alcohol consumption patterns and risk factors for risky and heavy alcohol use among siblings of childhood cancer survivors compared with survivors and national controls.Secondary analysis of prospectively collected data from two national surveys was performed including a cohort of 3034 adult siblings of childhood cancer survivors (age 18-56 years) and 10,398 adult childhood cancer survivors, both from the Childhood Cancer Survivor Study, plus 5712 adult participants from the population-based National Alcohol Survey. Cancer-related experiences, self-reported current health, and mental health were examined in relation to alcohol consumption patterns including heavy and risky drinking.Adult siblings of childhood cancer survivors were more likely to be heavy drinkers (OR adj = 1.3; 1.0-1.6) and risky drinkers (OR adj = 1.3; 1.1-1.6) compared with controls from a national sample. Siblings were also more likely to drink at these two levels compared with survivors. Factors associated with heavy drinking among siblings included being 18-21 years old (OR adj = 2.9; 2.0-4.4), male (OR adj = 2.3; 1.7-3.0), having a high school education or less (OR adj = 2.4; 1.7-3.5), and drinking initiation at a young age (OR adj = 5.1; 2.5-10.3). Symptoms of depression, (OR adj = 2.1; 1.3-3.2), anxiety (OR adj = 1.9; 1.1-3.3), and global psychiatric distress (OR adj = 2.5; 1.5-4.3) were significantly associated with heavy alcohol use.Siblings of children with cancer are more likely to be risky and heavy drinkers as adults compared with childhood cancer survivors or national controls. Early initiation of drinking and symptoms of psychological distress should be identified during early adolescence and effective sibling-specific interventions should be developed and made available for siblings of children with cancer.

To describe the psychological needs of adolescent survivors of acute lymphoblastic leukemia (ALL) or brain tumor (BT), we examined the following: (i) the occurrence of cognitive, behavioral, and emotional concerns identified during a comprehensive psychological evaluation and (ii) the frequency of referrals for psychological follow-up services to address identified concerns.Psychological concerns were identified on measures according to predetermined criteria for 100 adolescent survivors. Referrals for psychological follow-up services were made for concerns previously unidentified in formal assessment or not adequately addressed by current services.Most survivors (82%) exhibited at least one concern across domains: behavioral (76%), cognitive (47%), and emotional (19%). Behavioral concerns emerged most often on scales associated with executive dysfunction, inattention, learning, and peer difficulties. Cranial radiation therapy was associated with cognitive concerns, χ(2) (1, N = 100) = 5.63, p0.05. Lower income was associated with more cognitive concerns for ALL survivors, t(47) = 3.28, p0.01, and more behavioral concerns for BT survivors, t(48) = 2.93, p0.01. Of the survivors with concerns, 38% were referred for psychological follow-up services. Lower-income ALL survivors received more referrals for follow-up, χ(2) (1, N = 41) = 8.05, p0.01. Referred survivors had more concerns across domains than non-referred survivors, ALL: t(39) = 2.96, p0.01; BT: t(39) = 3.52, p0.01. Trends suggest ALL survivors may be at risk for experiencing unaddressed cognitive needs.Many adolescent survivors of cancer experience psychological difficulties that are not adequately managed by current services, underscoring the need for long-term surveillance. In addition to prescribing regular psychological evaluations, clinicians should closely monitor whether current support services appropriately meet survivors' needs, particularly for lower-income survivors and those treated with cranial radiation therapy.

The purpose of this article is to summarize the literature that documents the long-term impact of cancer treatment modalities on pulmonary function among survivors of cancer and to identify potential areas for further research.Systematic reviews of clinical trials, observational studies, case series, and review articles were conducted. Articles were limited to the studies that discussed pulmonary toxicity or late effects among pediatric cancer survivors and to follow-up investigations that were conducted a minimum of 2 years after completion of cancer-related treatment or 1 year after hematopoietic stem cell transplant.Sixty publications (51 clinical studies/reports and nine reviews) published from January 1970 to June 2010 in PubMed met the inclusion criteria. Data showed an association between radiotherapy, alkylating agents, bleomycin, hematopoietic stem cell transplant, and thoracic surgery and pulmonary toxicity, as well as possible interactions among these modalities.Pulmonary toxicity is a common long-term complication of exposure to certain anticancer therapies in childhood and can vary from subclinical to life threatening. Pulmonary function and associated loss of optimal exercise capacity may have adverse effects on long-term quality of life in survivors. Lung function diminishes as a function of normal aging, and the effects of early lung injury from cancer therapy may compound these changes. The information presented in this review is designed to provide a stimulus to promote both observational and interventional research that expands our knowledge and aids in the design of interventions to prevent or ameliorate pulmonary late effects among survivors of childhood cancer.

To determine whether unique groups of adult childhood cancer survivors could be defined on the basis of modifiable cognitive, affective, and motivation indicators. Secondary objectives were to examine to what extent group membership co-varied with more static variables (e.g. demographics, disease, and treatment) and predicted intent for subsequent medical follow-up.Using latent class analysis of data from 978 participants (ages, 18-52 years; mean, 31; and SD, 8) in the Childhood Cancer Survivor Study, we classified survivors according to their worries about health, perceived need for follow-up care, health motivation, and background variables. Intent to participate in medical follow-up, as a function of class membership, was tested using equality of proportions.The best-fitting model (BIC = 18 540.67, BLMRT =0.001) was characterized by three distinctive survivor classes (worried, 19%; self-controlling, 26%; and collaborative, 55%) and three significant class covariates (gender, perceptions of health, and severity of late effects). A smaller proportion of survivors in the self-controlling group (81%) than in the worried (90%) (P = 0.015) and collaborative (88%) (P = 0.015) groups intended to obtain a routine medical checkup. A smaller proportion of survivors in the self-controlling group (32%) than in the collaborative (65%) (P =0.001) and worried (86%) (P =0.001) groups planned a cancer-related check-up. A smaller proportion of survivors in the collaborative group (65%) than in the worried group (86%) (P =0.001) were likely to obtain a cancer-related check-up.Childhood cancer survivors can be classified according to the modifiable indicators. The classification is distinctive, predicts intent for future medical follow-up, and can inform tailored interventions.

Survivors of childhood acute lymphoblastic leukemia (ALL) are vulnerable to exaggeration of the aging process including decreased bone mineral density (BMD). As little is known about their dietary or nutrient intake that may affect their long-term bone health, we examined nutrient intake in long-term survivors of childhood ALL.Survivors (n = 164) of childhood ALL who had completed treatment for at least 5 years and were in continuous remission, completed a 110-item food questionnaire that reflected dietary intake over the previous year. The analyzed cohort comprised 34 females and 38 males younger than 19 years and 45 females and 47 males at least 19 years. Reported nutrient intake and food selection were compared with age-specific Recommended Dietary Allowance and USDA Pyramid Food Guide. Body mass index was compared to the general US population, adjusted for age, gender, Tanner stage and race.Less than 30% of participants met recommended dietary intakes for vitamin D, calcium, potassium, or magnesium regardless of age. Mean daily caloric intake was 2,204 kcal (51% from carbohydrates) for younger and 2,160 kcal (49% from carbohydrates) for older participants. Energy intake from sweets was 70% higher than recommended. Participants19 years were less likely to have a healthy weight (odds ratio 0.48, 95% CI 0.30-0.79);19 years more likely to be overweight (odds ratio 1.95, 95% CI 1.11-3.32, P0.002).Survivors of childhood ALL need careful dietary intervention to optimize long-term health.

Post-treatment attention problems experienced by pediatric cancer survivors have been described as similar to symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) experienced in physically healthy children. Accordingly, the objectives of this study were to: (a) estimate the rate of occurrence of ADHD and secondary ADHD (SADHD) in a sample of pediatric cancer survivors, (b) compare the rate of ADHD/SADHD among survivors to the prevalence of ADHD in the general population, and (c) examine clinical correlates of ADHD/SADHD in this sample.Survivors of pediatric ALL or brain tumor (n = 100) participated in an assessment of attention including a Computerized Performance Measure [Conners' Continuous Performance test-II (CPT-II)], parent and self-report measures (Conners 3), and a structured diagnostic interview for ADHD and other psychological disorders [Diagnostic Interview for Children and Adolescents-IV (DICA-IV)].Binomial tests revealed that the rate of ADHD/SADHD in our sample (9%) was significantly greater than the lower limits of ADHD prevalence among children in the US (3%; P0.001), while no difference was identified compared to the upper limits of ADHD prevalence (7%; P0.05). Many additional survivors (25% of the sample) obtained clinical elevations on Conners 3 scales but did not meet ADHD/SADHD criteria.Attentional deficits experienced by pediatric cancer survivors do not appear to resemble the clinical presentation of ADHD or SADHD. Many survivors with cognitive and behavioral difficulties related to attention were not identified using this diagnostic approach. Findings offer needed clarification to guide researchers and clinicians in conceptualizing, assessing, and intervening on attentional late effects.

Previous research from the Childhood Cancer Survivor Study (CCSS) has shown that risk of skin cancer is strongly associated with exposure to radiation therapy. The potential role of ultraviolet radiation exposure in survivors has not been described.The CCSS is a retrospective cohort study designed to investigate late effects among 5-year survivors of children and adolescents diagnosed with cancer between 1970-1986. Data regarding current sun protection behavior were collected on 9298 survivors and 2950 sibling controls. Median age at follow-up was 31 years (range, 17-54).In this cohort, childhood cancer survivors and siblings showed similar patterns of sunscreen use (67% vs 66%). Survivors were significantly less likely to report having sunbathed in the previous year (none vs any in previous year: relative risk (RR)=0.92; 95% confidence interval (CI)=0.89-0.95) or use artificial tanning (none vs any in previous year: RR=0.76; 95% CI=0.70-0.83). Compared with survivors without radiation therapy, survivors with radiation exposure showed increased use of sunscreen (RR=1.06; 95% CI=1.03-1.10), and less sunbathing (none vs any in previous year: RR=0.89; 95% CI=0.86-0.92) or artificial tanning (none vs any in previous year: RR=0.62; 95% CI=0.56-0.69). In adjusted multivariable analysis, statistically significant factors for regular sunscreen use in the past summer (vs never/rarely) in the survivor population were being female, having lighter skin complexions, having previously been examined for skin cancer, and having skin that burned when in the sun unprotected.Survivors of childhood cancer self-reported lower tanning practices than siblings. However, because of the potential increased risk of skin cancer from therapy-related exposures, future research should be directed at intervention studies to further reduce UV exposures.

We hypothesized that pediatric Hodgkin lymphoma (HL) survivors would have bone mineral density (BMD) deficits compared to their peers because of osteotoxic chemotherapy during the time of greatest BMD accretion.We retrospectively reviewed records of HL survivors returning for follow-up between 1990 and 2002. Of the 133 eligible survivors, 109 who underwent quantitative computed tomography (QCT) comprised the study group. QCT-determined BMD Z-scores were correlated with patient characteristics and therapeutic exposures by Wilcoxon rank sum or Chi-square tests. Logistic regression models were used to explore risk factors for diminished BMD.The study cohort was half male (50.5%) and 85.3% reported their race as white. Participants were representative of all survivors potentially eligible for study, except that more study participants were female, had hypothyroidism, and had received cyclophosphamide. Median age at diagnosis was 15.1 years (range, 3.1-20.7 years); median time between diagnosis and QCT was 7.5 years (range, 5.0-12.4 years). The proportion of HL survivors with BMD below the mean did not significantly differ from the general population (P = 0.503). However, those with BMD -1.5 SD and BMD -2.0 SD or lower (14.7% and 7.3%, respectively) exceeded that in the general population (6.7% and 2.3%, respectively; P0.001 for both degrees of severity). Males, diagnosed at 14 years or older, were at 6.5 times higher risk than females (OR 95% CI: 1.24-34.14; P = 0.027) for BMD deficits.Overall, pediatric HL survivors had negligible BMD deficits. Male gender was associated with an increased risk of developing BMD deficits.

Secondary acute leukemia is a devastating complication in children and adolescents who have been treated for cancer. Secondary acute lymphoblastic leukemia (s-ALL) was rarely reported previously but can be distinguished today from recurrent primary ALL by comparison of immunoglobulin and T-cell receptor rearrangement. Secondary acute myeloid leukemia (s-AML) is much more common, and some cases actually may be second primary cancers. Treatment-related and host-related characteristics and their interactions have been identified as risk factors for s-AML. The most widely recognized treatment-related risk factors are alkylating agents and topoisomerase II inhibitors (epipodophyllotoxins and anthracyclines). The magnitude of the risk associated with these factors depends on several variables, including the administration schedule, concomitant medications, and host factors. A high cumulative dose of alkylating agents is well known to predispose to s-AML. The prevalence of alkylator-associated s-AML has diminished among pediatric oncology patients with the reduction of cumulative alkylator dose and limited use of the more leukemogenic alkylators. The best-documented topoisomerase II inhibitor-associated s-AML is s-AML associated with epipodophyllotoxins. The risk of s-AML in these cases is influenced by the schedule of drug administration and by interaction with other antineoplastic agents but is not consistently found to be related to cumulative dose. The unpredictable risk of s-AML after epipodophyllotoxin therapy may discourage the use of these agents, even in patients at a high risk of disease recurrence, although the benefit of recurrence prevention may outweigh the risk of s-AML. Studies in survivors of adult cancers suggest that, contrary to previous beliefs, the outcome of s-AML is not necessarily worse than that of de novo AML when adjusted for cytogenetic features. More studies are needed to confirm this finding in the pediatric patient population.

BackgroundTreatment-related cardiac death is the primary, noncancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction may identify a high-risk subset of survivors for early intervention.ObjectivesThis study sought to determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies.MethodsEchocardiographic assessment included 3-dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain, and diastolic function, graded per American Society of Echocardiography guidelines in 1,820 adult (median age 31 years; range: 18 to 65 years) survivors of childhood cancer (median time from diagnosis 23 years; range: 10 to 48 years) exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306), or both (n = 464).ResultsOnly 5.8% of survivors had abnormal 3D LVEFs (30 Gy (RR: 2.39; 95% CI: 1.79 to 3.18) and anthracycline dose > 300 mg/m2 (RR: 1.72; 95% CI: 1.31 to 2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (RR: 1.94; 95% CI: 1.66 to 2.28) and abnormal diastolic function (RR: 1.68; 95% CI: 1.39 to 2.03) but not abnormal 3D LVEFs (RR: 1.07; 95% CI: 0.74 to 1.53).ConclusionsAbnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention.

Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems-such as speech and language, social-emotional development, and learning difficulties-for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors.

Childhood, adolescent, and young adult (CAYA) cancer survivors may be at risk for a severe course of COVID-19. Little is known about the clinical course of COVID-19 in CAYA cancer survivors, or if additional preventive measures are warranted. We established a working group within the International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) to summarize existing evidence and worldwide recommendations regarding evidence about factors/conditions associated with risk for a severe course of COVID-19 in CAYA cancer survivors, and to develop a consensus statement to provide guidance for healthcare practitioners and CAYA cancer survivors regarding COVID-19.

10055 Background: Childhood cancer survivors are a growing population who appear to be at higher risk for premature aging and age-related chronic health conditions than their peers with no history of cancer. Diet affects many hallmarks of aging, such as inflammation, metabolic dysfunctions, and molecular and epigenetic changes, leading to impairment in physical and cognitive functions and premature death. High consumption of animal foods that are high in protein and fat increase risk for many age-related chronic diseases. However, some studies found protein intake was beneficial for physical frailty in elderly and cancer survivors. Methods: Adult survivors (> = 18 years old) of childhood cancer survivors enrolled in the SJLIFE Cohort between 2007 and 2017 completed a 110-item food frequency questionnaire at study entry (n = 3,322). Survivors’ sociodemographic, cancer, cancer treatments, and medical history data were abstracted from medical records. Health conditions self-reported after cancer diagnosis were clinically validated. Premature aging was assessed using the Deficit Accumulation Index (DAI) based on 45 aging-related health conditions. DAI is categorized into low (< 0.2), medium (0.2-0.34) and high (> 0.35) aging risk groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multinomial logistic regressions adjusting for potential confounders. Results: The average age of survivors at baseline was 31 years. Approximately half of the survivors were women, and 82% were white, non-Hispanic. 20% and 8% of survivors were at medium and high risk for aging, respectively. Survivors at high risk for aging tended to be female, smokers, have low socioeconomic status, and received radiation therapy to head and neck, chest, spine or abdomen compared to those at low aging risk. Higher protein intake was associated with a less risk of premature aging (OR = 0.74, 95% CI: 0.58-0.95 for high aging risk group; OR = 0.91, 95% CI: 0.78-1.07 for medium aging risk group, per increment of 5% of total energy intake). On the other hand, higher fat intake was related to an increased risk of premature aging (OR = 1.14, 95% CI: 1.01-1.29 for high aging risk group; OR = 0.99, 95% CI: 0.91-1.08 for medium aging risk group, per increment of 5% of total energy intake). However, substituting monounsaturated fat for other types of fat was associated with a lower risk of premature aging (OR = 0.81 95% CI: 0.70-0.95 for high aging risk group). Red meat (OR = 1.11, 95% CI: 0.87-1.42 for high aging risk group) and dairy intake (OR = 0.99, 95% CI: 0.72-1.38 for high aging risk group) was not related to risk of premature aging. Conclusions: Consuming protein and fat from healthy foods may lower the risk of premature aging in childhood cancer survivors.