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Background: Survivors of pediatric central nervous system (CNS) tumors are at risk for neurocognitive and social difficulties throughout childhood. This study characterized social cognition (perception and reasoning from social cues) and adjustment in adulthood. Methods: A total of 81 adult survivors of pediatric CNS tumors (51% female; mean [SD] age, 28.0 [5.8] years), were recruited across four groups: (1) no radiation therapy (RT) [n = 21], (2) infratentorial (IT) tumors + focal RT [n = 20], (3) IT tumors + craniospinal irradiation [n = 20], and (4) supratentorial tumors + focal RT [n = 20]. Prevalence of social cognitive and adjustment impairments was compared to test norms. Multivariable models examined clinical and neurocognitive predictors of social cognition and its impact on functional outcomes. Results: Survivors demonstrated elevated risk of severe social cognitive impairments (social perception Morbidity Ratio [95% CI] 5.70 [3.46–9.20]), but self‐reported few social adjustment problems. Survivors of IT tumors treated with craniospinal irradiation performed nearly 1 SD worse than survivors treated without RT on multiple measures of social cognition (e.g., social perception: β = −0.89, p =.004). Impaired executive functioning and nonverbal reasoning were associated with worse social cognitive performance (e.g., social perception: β = −0.75, p <.001; β = –0.84, p <.001, respectively). Better social perception was associated with higher odds of attaining full‐time employment (odds ratio, 1.52 [1.17–1.97]) and at least some college education (odds ratio, 1.39 [1.11–1.74]). Conclusions: Adult survivors of CNS tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Better understanding of potential mechanisms underlying social cognitive deficits may inform intervention targets to promote better functional outcomes for at‐risk survivors. Adult survivors of childhood central nervous system tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Infratentorial tumor survivors treated with craniospinal radiation demonstrated worse social cognition, which was in turn associated with reduced social attainment. [ABSTRACT FROM AUTHOR]

Background: There is limited understanding of associations between a combination of health behaviors (physical activity, sedentary/screen‐time, diet) and cardiometabolic health risk factors, physical performance, and emotional health among young (<18) childhood cancer survivors (CCS). The aims of this research were to address this gap by 1) deriving health behavior adherence profiles among CCS, and 2) examining associations among demographic, diagnosis and/or treatment exposures, cardiometabolic, physical performance, and emotional functioning with health behavior profile membership. Methods: Participants included 397 CCS (≥5 years post‐diagnosis; 10–17 years old) enrolled in the St. Jude Lifetime Cohort Study who completed physical health evaluations and questionnaires assessing health behaviors and psychological functioning. Latent profile analysis was used to derive profiles of health behavior adherence. Logistic regression and t‐tests were used to examine mean‐level differences and associations between profile membership with demographic, diagnosis, treatment exposures, cardiometabolic health, psychological functioning, and physical performance. Results: Two profiles emerged: inactive‐unhealthy‐diet ("IU") and active‐sedentary‐unhealthy‐diet ("ASU") to guidelines. More participants in IU demonstrated higher resting heart rate (mean [M], 76.54; SD = 12.00) and lower motor proficiency scores (M = 34.73; SD = 29.15) compared to ASU (resting heart rate, M = 71.95, SD = 10.74; motor proficiency, M = 50.40, SD = 31.02). Conclusions: CCS exhibited low adherence to multiple health behavior guidelines, with adherence patterns differentially associated with cardiometabolic health (i.e., resting heart rate) and physical performance. However, robust protection against all health variables was not observed. Findings suggest interventions designed to improve health outcomes should target multiple health behaviors simultaneously. Plain Language Summary: Pediatric cancer survivors are at‐risk for detrimental health outcomes associated with cancer and treatment.Engagement in healthy lifestyle behaviors serves to reduce health vulnerabilities among adult survivors but less is known about associations with lifestyle behaviors on young survivors.This study documents patterns of lifestyle behaviors among survivors of pediatric cancer, factors that increase susceptibility to nonadherence, and associations among lifestyle behaviors and health indicators. Young (<18 years of age) survivors of pediatric cancer exhibit poor adherence to diet and physical activity guidelines. Adherence is associated with clinical health outcomes. [ABSTRACT FROM AUTHOR]

Background: Adult survivors of childhood cancer have poor adherence to nutrition guidelines and inadequate intake of dietary vitamins D and E, potassium, fiber, magnesium, and calcium. The contribution of vitamin and mineral supplement use to total nutrient intake in this population is unclear. Methods: We examined the prevalence and dose of nutrient intake among 2570 adult survivors of childhood cancer participating in the St. Jude Lifetime Cohort Study, and the association of dietary supplement use with treatment exposures, symptom burden, and quality of life. Results: Nearly 40% of the adult survivors of cancer survivors reported regular use of dietary supplements. Although cancer survivors who used dietary supplements were less likely to have inadequate intake of several nutrients, they were also more likely to have excessive intake (total nutrient intake ≥ tolerable upper intake levels) of folate (15.4% vs. 1.3%), vitamin A (12.2% vs. 0.2%), iron (27.8% vs. 1.2%), zinc (18.6% vs. 1%), and calcium (5.1% vs. 0.9%) compared with survivors who did not use dietary supplements (all p < 0.05). Treatment exposures, symptom burden, and physical functioning were not associated with supplement use, whereas emotional well‐being and vitality were positively associated with supplement use among childhood cancer survivors. Conclusions: Supplement use is associated with both inadequate and excessive intake of specific nutrients, but positively impacts aspects of quality of life among childhood cancer survivors. Adult survivors of childhood cancer who used dietary supplements were less likely to have inadequate intake of several nutrients but were also more likely to have excessive intake of specific nutrients compared with those who did not use dietary supplements. Health care providers need to monitor dietary supplement use among long‐term survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Cancer survivors are at risk for developing subsequent human papillomavirus (HPV)–related malignancies. HPV vaccination rates among survivors remain low, and the reasons for refusal of the vaccine are unclear in this population. Methods: The authors conducted a secondary analysis of data from an open‐label clinical trial evaluating the immunogenicity and safety of the HPV vaccine among vaccine‐naive cancer survivors who were 9–26 years old and 1–5 years from the completion of their cancer treatment. Survivors/parents who declined trial participation were asked their reasons for declining. Refusal reasons were categorized, and multivariable logistic regression models were developed to identify associations between survivor characteristics and primary refusal reasons. Results: Among the 301 survivors who refused participation in the clinical trial, 215 (71.4%) refused for reasons related to the HPV vaccine. Reasons for vaccine‐related refusal included safety concerns, vaccine hesitancy/disinterest, external influences, vaccine‐related information deficits, and health beliefs/family decisional processes. Compared with males, females were more likely to refuse for reasons related to health beliefs/family decisional processes (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.12–3.93; p =.022) and were less likely to do so because of external influences (OR, 0.43; 95% CI, 0.19–0.92; p =.035). Survivors approached about participation during the latter years of the trial were more likely to refuse because of safety concerns (OR, 3.33; 95% CI, 1.55–7.69; p =.003). Conclusions: Cancer survivors refused participation in an open‐label trial evaluating the immunogenicity and safety of the HPV vaccine primarily because of vaccine‐related concerns that were unrelated to the research study. Many of these concerns are potentially addressable by health care providers using evidence‐based messages tailored to the cancer survivor population. Reasons for the refusal of the human papillomavirus vaccine among young cancer survivors include safety concerns, vaccine hesitancy/disinterest, external influences, vaccine‐related information deficits, and health beliefs/family decisional processes. Many of these concerns are potentially actionable and can be addressed by health care providers using evidence‐based messages tailored to enhance the relevancy to the cancer survivor population. [ABSTRACT FROM AUTHOR]

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. A systematic review of the literature indicates that survivors of childhood, adolescent, and young adult cancer are at risk for lower educational achievement and unemployment. It is recommended that all survivors receive regular screening for educational and employment outcomes. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine the impact of seizure‐related factors on neurocognitive, health‐related quality of life (HRQOL), and social outcomes in survivors of childhood cancer. Methods: Survivors of childhood cancer treated at St. Jude Children's Hospital (n = 2022; 48.3% female; median age, 31.5 years; median time since diagnosis, 23.6 years) completed neurocognitive testing and questionnaires. The presence, severity, resolution, and treatment history of seizures were abstracted from medical records. Adjusting for the age at diagnosis, sex, and prior cancer therapy, multivariable models examined the impact of seizures on neurocognitive and HRQOL outcomes. Mediation analyses were conducted for social outcomes. Results: Seizures were identified in 232 survivors (11.5%; 29.9% of survivors with central nervous system [CNS] tumors and 9.0% of those without CNS tumors). In CNS tumor survivors, seizures were associated with poorer executive function and processing speed (P <.02); in non‐CNS tumor survivors, seizures were associated with worse function in every domain (P <.05). Among non‐CNS survivors, seizure severity was associated with worse processing speed (P =.023), and resolution was associated with better executive function (P =.028) and attention (P =.044). In CNS survivors, seizure resolution was associated with improved attention (P =.047) and memory (P <.02). Mediation analysis revealed that the impact of seizures on social outcomes was mediated by neurocognitive function. Conclusions: Seizures in cancer survivors adversely affect long‐term functional and psychosocial outcomes independently of cancer therapy. The resolution of seizure occurrence is associated with better outcomes. Seizure severity is associated with poorer outcomes and should be a focus of clinical management and patient education. Adult survivors of childhood cancer are at risk for poorer cognitive, health‐related quality of life, and social outcomes. Seizure frequency, independently of the underlying etiology, is associated with poorer outcomes in non–brain tumor survivors, and this implies that they may be a more vulnerable population with a lower threshold for impact from seizures of any severity. [ABSTRACT FROM AUTHOR]

Background: Limited data exist regarding left ventricular remodeling patterns observed in adult survivors of childhood cancer after therapy. Methods: Among 1190 adult survivors diagnosed with childhood cancer (median age at diagnosis, 9 years [interquartile range (IQR), 3.8‐14.4 years]; age at evaluation, 35.6 years [IQR, 29.5‐42.8 years]), treatment exposures included anthracyclines (n = 346), chest radiotherapy (n = 174), both (n = 245), or neither (n = 425). Prospective echocardiographic assessment compared survivors with 449 noncancer controls classified according to left ventricle geometric patterns. Associations between left ventricle geometric patterns and decreased exercise tolerance were assessed. Results: Overall, 28.2% of survivors (95% confidence interval [CI], 25.6%‐30.8%) exhibited concentric remodeling, 2.4% (95% CI, 1.6%‐3.5%) exhibited eccentric hypertrophy, and 1.1% (95% CI, 0.6%‐1.9%) exhibited concentric hypertrophy. A greater proportion of survivors who received only chest radiotherapy (41%) had concentric remodeling compared with those who received only anthracyclines (24%), both (27%), or neither (27%; all P <.001), and all were greater than the proportions in noncancer controls (18%; all P <.05). Concentric remodeling was associated with radiation exposure, but not with anthracycline exposure, in multivariable models. Survivors who had concentric remodeling were more likely to have a maximal oxygen uptake peak <85% compared with those who had normal geometry (81.0% vs 66.3%; odds ratio, 1.75; 95% CI, 1.15‐2.68). Conclusions: Chest radiation therapy, but not anthracycline therapy, increased the risk for concentric remodeling in survivors of childhood cancer. The presence of concentric remodeling was associated with increased exercise intolerance. Chest radiation therapy increases the risk of concentric left ventricular remodeling as assessed by echocardiography, but anthracycline therapy does not increase the risk of concentric remodeling. Adult survivors of childhood cancer who have concentric remodeling are more likely to have a relative peak oxygen uptake <85% compared with survivors who have normal left ventricular geometry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cranial radiation therapy (CRT) is associated with ototoxicity, which manifests as hearing loss and tinnitus. The authors sought to identify clinical determinants and genetic risk factors for ototoxicity among adult survivors of pediatric cancer treated with CRT. METHODS: Logistic regression evaluated associations of tinnitus (n = 1991) and hearing loss (n = 2198) with nongenetic risk factors and comorbidities among CRT‐treated survivors in the Childhood Cancer Survivor Study. Genome‐wide association studies (GWASs) of CRT‐related tinnitus and hearing loss were also performed. RESULTS: Males were more likely to report CRT‐related tinnitus (9.4% vs 5.4%; P = 5.1 × 10−4) and hearing loss (14.0% vs 10.7%; P =.02) than females. Survivors with tinnitus or hearing loss were more likely to experience persistent dizziness or vertigo (tinnitus: P < 2 × 10−16; hearing loss: P = 6.4 × 10−9), take antidepressants (tinnitus: P =.02; hearing loss: P =.01), and report poorer overall health (tinnitus: P = 1.5 × 10−6; hearing loss: P = 1.7 × 10−6) in comparison with controls. GWAS of CRT‐related tinnitus revealed a genome‐wide significant signal in chromosome 1 led by rs203248 (P = 1.5 × 10−9), whereas GWAS of CRT‐related hearing loss identified rs332013 (P = 5.8 × 10−7) in chromosome 8 and rs67522722 (P = 7.8 × 10−7) in chromosome 6 as nearly genome‐wide significant. A replication analysis identified rs67522722, intronic to ATXN1, as being significantly associated with CRT‐related hearing loss (P =.03) and de novo hearing loss (P = 3.6 × 10−4). CONCLUSIONS: CRT‐associated ototoxicity was associated with sex, several neuro‐otological symptoms, increased antidepressant use, and poorer self‐reported health. GWAS of CRT‐related hearing loss identified rs67522722, which was supported in an independent cohort of survivors. LAY SUMMARY: Hearing loss and subjective tinnitus (the perception of noise or ringing in the ear) are long‐term side effects of cancer treatment and are common in children treated with radiation to the brain.These toxicities can affect childhood development and potentially contribute to serious learning and behavioral difficulties.This study's data indicate that males are at greater risk for hearing loss and tinnitus than females after radiation therapy to the brain.Those who develop these toxicities are more likely to use antidepressants and report poorer overall health.Health care providers can improve the management of survivors by informing patients and/or their parents of these risks. Health care providers can improve the management of survivors of childhood cancer by informing patients of ototoxicity risk and associated comorbidities (dizziness and vertigo) after the completion of cranial radiation therapy. Genome‐wide association studies reveal genetic variants in ATXN1, a gene associated with spinocerebellar ataxia type 1, to be significantly associated with cranial radiation therapy–related hearing loss. [ABSTRACT FROM AUTHOR]

Background: Neurocognitive impairment and obesity are common adverse sequelae in survivors of childhood acute lymphoblastic leukemia (ALL); however, the association has not been investigated. Methods: Neurocognitive function was evaluated once in survivors of ALL who were at least 8 years old and 5 years from their diagnosis. In a cross‐sectional analysis, the associations with the body mass index (BMI) category and Z score were examined. A longitudinal analysis used the overweight/obesity area under the curve (AUC), which was determined via the trapezoidal rule by a sum of the integrals defined by the BMI Z score at each time point and the time intervals of the BMI measurement. Results: For 210 survivors, the median BMI Z score at diagnosis was 0.17, which increased to 0.54 at the end of induction and to 0.74 at the neurocognitive assessment. In the cross‐sectional analysis, overweight/obese survivors scored significantly lower than others on the measures of executive function (cognitive flexibility, planning, verbal fluency, working memory, and spatial construction; all P <.05), attention (attention span and risk taking; all P <.05), and processing speed (visual motor coordination, visual speed, and motor speed; all P <.05). In the longitudinal analysis, when the treatment period was subdivided into 4 time periods (induction, consolidation, early maintenance, and late maintenance), a greater overweight/obesity AUC during induction therapy was associated with worse cognitive flexibility (P =.01) and slower motor speed (P =.02), which persisted throughout the treatment. Conclusions: Overweight/obesity was significantly associated with neurocognitive impairment during long‐term follow‐up, and this association started early in treatment for ALL. Novel early interventions to provide cognitive training and prevent weight gain are required for patients at risk. In a cohort of 210 children with acute lymphoblastic leukemia (ALL) at a median follow‐up of 7.5 years from diagnosis, overweight/obese survivors score significantly worse than others on measures of neurocognitive performance. This association with overweight/obesity status is already seen during induction therapy, and this suggests that early multidisciplinary interventions should be implemented to prevent obesity and to alleviate adverse neurocognitive sequelae in survivors of ALL. [ABSTRACT FROM AUTHOR]

Background: Cancer‐related worry (CRW) is common among cancer survivors; however, little is known about factors associated with CRW or its impact on health behaviors in adult survivors of childhood cancer. Methods: Survivors in the St. Jude Lifetime Cohort Study (n = 3211; 51% male; mean age, 31.2 years [SD, 8.4 years]; mean time after diagnosis, 22.8 years [SD, 8.3 years]) underwent medical evaluations and completed ratings of CRW, psychological symptoms, and health behaviors. Multivariable modified Poisson regression models examined associations between CRW and treatment exposures, chronic health conditions, psychological symptoms, and health behaviors. Results: Sixty‐four percent of survivors (95% confidence interval [CI], 62.6‐65.9) reported worry about subsequent malignancy, 45% (95% CI, 43.5‐46.9) reported worry about physical problems related to cancer, and 33% (95% CI, 31.2‐34.4) reported worry about relapse. Multiple psychological symptoms, treatment exposures, and chronic conditions significantly increased the risk of CRW. Survivors reporting CRW were at increased risk for substance use, inadequate physical activity, and increased health care utilization after adjustments for chronic conditions. For example, with adjustments for chronic conditions, those who endorsed CRW were more likely to have ≥5 cancer‐related physician visits, ≥5 physician visits related to cancer, and ≥5 calls to a physician's office in the previous 2 years in comparison with survivors who were not worried. CRW was also associated with an increased risk of current tobacco use, past marijuana use, and current marijuana use. Conclusions: A substantial proportion of adult survivors of childhood cancer reported CRW associated with increased health care utilization. CRW may serve as an intervention target to promote well‐being and adaptive health behaviors. Cancer‐related worry is common among long‐term survivors of childhood cancer. It is associated with treatment exposures, chronic medical conditions, psychological and somatic symptoms, and maladaptive health behaviors. Cancer‐related worry is a modifiable construct that can be targeted via psychosocial interventions. [ABSTRACT FROM AUTHOR]

Background: Although survivors of childhood cancer are at risk of chronic pain, the impact of pain on daily functioning is not well understood. Methods: A total of 2836 survivors (mean age, 32.2 years [SD, 8.5 years]; mean time since diagnosis, 23.7 years [SD, 8.2 years]) and 343 noncancer community controls (mean age, 35.5 years [SD, 10.2 years]) underwent comprehensive medical, neurocognitive, and physical performance assessments, and completed measures of pain, health‐related quality of life (HRQOL), and social functioning. Multinomial logistic regression models, using odds ratios and 95% confidence intervals (95% CIs), examined associations between diagnosis, treatment exposures, chronic health conditions, and pain. Relative risks (RRs) between pain and neurocognition, physical performance, social functioning, and HRQOL were examined using modified Poisson regression. Results: Approximately 18% of survivors (95% CI, 16.1%‐18.9%) versus 8% of controls (95% CI, 5.0%‐10.9%) reported moderate to very severe pain with moderate to extreme daily interference (P <.001). Severe and life‐threatening chronic health conditions were associated with an increased likelihood of pain with interference (odds ratio, 2.03; 95% CI, 1.62‐2.54). Pain with daily interference was found to be associated with an increased risk of impaired neurocognition (attention: RR, 1.88 [95% CI, 1.46‐2.41]; and memory: RR, 1.65 [95% CI, 1.25‐2.17]), physical functioning (aerobic capacity: RR, 2.29 [95% CI, 1.84‐2.84]; and mobility: RR, 1.71 [95% CI, 1.42‐2.06]), social functioning (inability to hold a job and/or attend school: RR, 4.46 [95% CI, 3.45‐5.76]; and assistance with routine and/or personal care needs: RR, 5.64 [95% CI, 3.92‐8.10]), and HRQOL (physical: RR, 6.34 [95% CI, 5.04‐7.98]; and emotional: RR, 2.83 [95% CI, 2.28‐3.50]). Conclusions: Survivors of childhood cancer are at risk of pain and associated functional impairments. Survivors should be screened routinely for pain and interventions targeting pain interference are needed. Adult survivors of childhood cancer are at an increased risk of moderate to very severe pain compared with community controls. In long‐term survivors, pain significantly interferes with multiple aspects of daily functioning. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown. Methods: N‐terminal pro–B‐type natriuretic peptide (NT‐proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest‐directed radiation therapy (RT). NT‐proBNP values above age‐ and sex‐specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross‐sectional associations between abnormal NT‐proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death. Results: At a median age of 35.5 years (interquartile range, 29.8‐42.5 years), NT‐proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose‐dependent increased risk for abnormal NT‐proBNP (P for trend <.0001). Among exposed survivors with no history of Common Terminology Criteria for Adverse Events–graded cardiomyopathy and with normal systolic function, survivors with abnormal NT‐proBNP had higher rates per 1000 person‐years of cardiac mortality (2.93 vs 0.96; P <.0001) and future cardiomyopathy (32.10 vs 15.98; P <.0001) and an increased risk of future cardiomyopathy (HR, 2.28; 95% CI, 1.28‐4.08) according to a multivariable assessment. Conclusions: Abnormal NT‐proBNP values were prevalent and, among survivors who were exposed to cardiotoxic therapy but did not have a history of cardiomyopathy or current systolic dysfunction, identified those at increased risk for future cardiomyopathy. Further longitudinal studies are needed to confirm this novel finding. In this longitudinal cohort study including 1213 adult survivors of childhood cancer, nearly 25% have an abnormal N‐terminal pro–B‐type natriuretic peptide (NT‐proBNP) value for age and sex at the baseline. Among survivors exposed to cardiotoxic therapy who have a normal ejection fraction at the baseline, those with an abnormal NT‐proBNP value have more than twice the risk of future cardiomyopathy; this is a significant finding. [ABSTRACT FROM AUTHOR]

Background: Treatment characteristics such as cranial radiation therapy (CRT) do not fully explain adiposity risk in childhood acute lymphoblastic leukemia (ALL) survivors. This study was aimed at characterizing genetic variation related to adult body mass index (BMI) among survivors of childhood ALL. Methods: Genetic associations of BMI among 1458 adult survivors of childhood ALL (median time from diagnosis, 20 years) were analyzed by multiple approaches. A 2‐stage genome‐wide association study in the Childhood Cancer Survivor Study (CCSS) and the St. Jude Lifetime Cohort Study (SJLIFE) was performed. BMI was a highly polygenic trait in the general population. Within the known loci, the BMI percent variance explained was estimated, and additive interactions (chi‐square test) with CRT in the CCSS were evaluated. The role of DNA methylation in CRT interaction was further evaluated in a subsample of ALL survivors. Results: In a meta‐analysis of the CCSS and SJLIFE, 2 novel loci associated with adult BMI among survivors of childhood ALL (LINC00856 rs575792008 and EMR1 rs62123082; PMeta < 5E–8) were identified. It was estimated that the more than 700 known loci explained 6.2% of the variation in adult BMI in childhood ALL survivors. Within the known loci, significant main effects for 23 loci and statistical interactions with CRT at 9 loci (P < 7.0E–5) were further identified. At 2 CRT‐interacting loci, DNA methylation patterns may have differed by age. Conclusions: Adult survivors of childhood ALL have genetic heritability for BMI similar to that observed in the general population. This study provides evidence that treatment with CRT can modify the effect of genetic variants on adult BMI in childhood ALL survivors. Adult survivors of childhood acute lymphoblastic leukemia, particularly those treated with cranial radiation, are at increased risk for obesity. This study provides evidence that the body mass index in adult survivors of childhood acute lymphoblastic leukemia is a genetically heritable trait similar to that in the general population and that the effect of genetic loci from the general population may be modified by treatment with cranial radiation. [ABSTRACT FROM AUTHOR]

Background: Suicide is a serious public health concern. An increased risk of suicide ideation previously has been reported among survivors of childhood cancer. Methods: Suicide mortality was assessed for all potentially eligible survivors (those aged ≥18 years who were ≥5 years after their cancer diagnosis; 7312 survivors). Risk factors for acute suicidal ideation were assessed among clinically evaluated survivors (3096 survivors) and the prevalence of acute ideation was compared with that of community controls (429 individuals). The prevalence of 12‐month suicidality was assessed among survivors who could be compared with population data (1255 survivors). Standardized mortality ratios compared rates of suicide mortality among survivors with those of the general population. Risk ratios (RRs) and 95% confidence intervals (95% CIs) derived from generalized linear models identified risk factors associated with acute suicidal ideation. Standardized incidence ratios (SIRs) compared the prevalence of 12‐month suicidality among survivors with that of a matched sample from the general population. Results: Survivors reported a similar 12‐month prevalence of ideation compared with the general population (SIR, 0.68; 95% CI, 0.35‐1.01) and a lower prevalence of suicidal behaviors (planning: SIR, 0.17 [95% CI, 0.07‐0.27]; attempts: SIR, 0.07 [95% CI, 0.00‐0.15]) and mortality (standardized mortality ratio, 0.60; 95% CI, 0.34‐0.86). Among survivors, depression (RR, 12.30; 95% CI, 7.89‐19.11), anxiety (RR, 2.19; 95% CI, 1.40‐3.40), and financial stress (RR, 1.47; 95% CI, 1.00‐2.15) were found to be associated with a higher prevalence of acute suicidal ideation. Conclusions: Survivors of childhood cancer were found to be at a lower risk of suicidal behaviors and mortality, yet endorsed a prevalence of ideation similar to that of the general population. These results are in contrast to previous findings of suicidal ideation among survivors and support the need for further research to inform screening strategies and interventions. Lay Summary: The purpose of the current study was to compare the risk of suicidal ideation, behaviors, and mortality in adult survivors of childhood cancer with those of the general population. Risk factors associated with suicidal ideation among survivors of childhood cancer also were examined.Survivors of childhood cancer reported a similar risk of ideation compared with the general population, but a lower risk of suicidal behaviors and mortality. Psychological health and financial stressors were found to be risk factors associated with suicidal ideation.Although adult survivors of childhood cancer did not report a greater risk of suicidality compared with the general population, psychosocial care in survivorship remains essential. Long‐term survivors of childhood cancer do not appear to be at an increased risk of suicidality. However, despite its low prevalence, death by suicide can be prevented and the development of interventions to address suicidality remains important for survivors. [ABSTRACT FROM AUTHOR]

Background: Anthracycline-related cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Glutathione S-transferases (GSTs) are a class of phase II detoxification enzymes that facilitate the elimination of anthracyclines. As free-radical scavengers, GSTs could play a role in oxidative damage-induced cardiomyopathy. Associations between the GSTμ1 (GSTM1) null genotype and iron-overload-related cardiomyopathy have been reported in patients with thalassemia.Methods: The authors sought to identify an association between the GSTM1 null genotype and anthracycline-related cardiomyopathy in childhood cancer survivors and to corroborate the association by examining GSTM1 gene expression in peripheral blood and human-induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) from survivors with and without cardiomyopathy. GSTM1 gene deletion was examined by polymerase chain reaction in 75 survivors who had clinically validated cardiomyopathy (cases) and in 92 matched survivors without cardiomyopathy (controls). Conditional logistic regression analysis adjusting for sex, age at cancer diagnosis, chest radiation, and anthracycline dose was used to assess the association between genotype and cardiomyopathy. Proprietary bead array technology and quantitative real-time polymerase chain reaction were used to measure GSTM1 expression levels in samples from 20 cases and 20 matched controls. hiPSC-CMs from childhood cancer survivors (3 with cardiomyopathy, 3 without cardiomyopathy) also were examined for GSTM1 gene expression levels.Results: A significant association was observed between the risk of cardiomyopathy and the GSTM1 null genotype (odds ratio, 2.7; 95% CI, 1.3-5.9; P = .007). There was significant downregulation of GSTM1 expression in cases compared with controls (average relative expression, 0.67 ± 0.57 vs 1.33 ± 1.33, respectively; P = .049). hiPSC-CMs from patients who had cardiomyopathy revealed reduced GSTM1 expression (P = .007).Conclusions: The current findings could facilitate the identification of childhood cancer survivors who are at risk for anthracycline-related cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, few studies to date have examined long-term neurocognitive outcomes in survivors of childhood soft-tissue sarcoma.Methods: A total of 150 survivors (41% of whom were female with a mean current age of 33 years [SD, 8.9 years] and a time since diagnosis of 24 years [SD, 8.7 years]) and 349 community controls (56% of whom were female with a mean current age of 35 years [SD, 10.2 years]) completed comprehensive neuropsychological testing, echocardiography, electrocardiography, pulmonary function tests, endocrine evaluation, and physical examination. Patient-reported outcomes of health-related quality of life (HRQOL) and social attainment were collected. Survivors were compared with norms and controls on neurocognitive outcomes using general linear models, and on HRQOL and social attainment using modified Poisson models. The impacts of treatment and chronic health conditions on outcomes were examined using multivariable general linear models (effect size was expressed as unstandardized β estimates that reflected the unit of change from a mean of 0 and an SD of 1) and modified Poisson models (effect size expressed as relative risks).Results: Compared with controls and population norms, survivors demonstrated lower performance on measures of verbal reasoning (mean z score, -0.45 [SD, 1.15]; P < .001) mathematics (mean z score, -0.63 [SD, 1.07]; P < .001), and long-term memory (mean z score, -0.37 [SD, 1.14]; P < .001). Cumulative anthracycline exposure (per 100 mg/m2 ) was found to be associated with poorer verbal reasoning (β = -0.14 z scores; P = .04), reading (β = -0.09 z score; P = .04), and patient-reported vitality (relative risk, 1.32; 95% CI, 1.09-1.59). Neurologic and neurosensory chronic conditions were associated with poorer mathematics (neurologic conditions: β = -0.63 z score [P = 0.02]; and hearing impairment: β = -0.75 z scores [P < 0.01]). Better cognitive performance was associated with higher social attainment.Conclusions: Long-term survivors of soft-tissue sarcoma are at risk of neurocognitive problems and poor HRQOL associated with anthracycline treatment and chronic health conditions. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to characterize chronic disease, health-related quality of life (HRQOL), emotional distress, and social attainment among long-term survivors of neuroblastoma.Methods: Chronic health conditions among 136 ≥10-year neuroblastoma survivors (median age, 31.9 years; range, 20.2-54.6 years) and 272 community controls (median age, 34.7 years; range, 18.3-59.6 years) were graded with a modified version of the Common Terminology Criteria for Adverse Events (version 4.03). HRQOL and emotional distress were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey and the Brief Symptom Inventory-18. Log-binomial regression and logistic regression were used to compare the prevalence of chronic conditions and the frequency of reduced HRQOL, distress, and social attainment between survivors and controls. The cumulative burden approach was used to estimate multimorbidity.Results: By the age of 35 years, survivors had experienced, on average, 8.5 grade 1 to 5 conditions (95% confidence interval [CI], 7.6-9.3), which was higher than the average for controls (3.3; 95% CI, 2.9-3.7). Compared with controls, survivors had a higher prevalence of any pulmonary (P = .003), auditory (P < .001), gastrointestinal (P < .001), neurological (P = .003), or renal condition (P < .001); were more likely to report poor physical HRQOL (P = .01) and symptoms of anxiety (P = .01) and somatization (P = .01); and were less likely to live independently (P = .01) or marry (P = .01). In analyses limited to survivors, those with 1 or more grade 3 to 5 conditions were more likely to report reduced general health (odds ratio [OR], 6.6; 95% CI, 1.6-26.9), greater bodily pain (OR, 4.2; 95% CI, 1.0-17.0), and unemployment (OR, 3.2; 95% CI, 1.2-8.5).Conclusions: Because of the high burden of chronic diseases and the associations of these morbidities with reduced HRQOL and social attainment, screening and interventions that provide opportunities to optimize health are important among neuroblastoma survivors. [ABSTRACT FROM AUTHOR]

Background: Greater than one-half of children who are treated for acute lymphoblastic leukemia (ALL) develop ≥1 treatment-related medical conditions in their lifetime, many of which are known risk factors for diabetes mellitus. In the current study, the authors evaluated the prevalence and risk factors of diabetes mellitus among clinically assessed adult survivors of childhood ALL METHODS: The authors performed a retrospective evaluation of data from survivors of ALL and community controls who were enrolled in the St. Jude Lifetime Cohort Study between October 1, 2007, and June 30, 2016. Participants were adults with ≥10 years of survival of childhood ALL and community controls who completed clinical and laboratory evaluations. Data for the current analysis were abstracted from medical records. Exposures evaluated herein included chemotherapy and radiation exposures and medical history, including drug-induced diabetes mellitus.Results: Of 1360 eligible adults who were ≥10-year survivors of childhood ALL, a total of 1044 completed the evaluations; these individuals had a mean age of 33.97±9.14 years and 50.86% were male. The 368 controls, 45.65% of whom were male, had a mean age of 35.33±10.21 years. Type 2 diabetes mellitus (T2DM) was found in approximately 7.47% of survivors and 3.80% of controls (odds ratio [OR], 2.07; 95% CI, 1.11-3.87). In adjusted models, among survivors, older age (OR, 1.05 for each additional year; 95% CI, 1.02-1.08), body mass index ≥30 kg/m2 (OR, 7.40; 95% CI, 2.61-20.97), and drug-induced diabetes mellitus occurring during ALL therapy (OR, 4.67; 95% CI, 2.53-8.61) were found to be associated with T2DM.Conclusions: Adult survivors of childhood ALL are at an increased risk of T2DM. Adult survivors of childhood ALL who are of older age, with an overweight or obese body mass index, and/or who developed drug-induced diabetes mellitus during treatment should be closely monitored for T2DM during long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Optimal risk-based survivor health care includes surveillance for late effects and education targeted at reducing or preventing risky health behaviors. Understanding the reasons for a lack of risk-based follow-up care is essential.Methods: Adult participants from the Childhood Cancer Survivor Study were surveyed about having a cancer-related visit in the past 2 years and the likelihood of having a cancer-related visit in the future. Additional factors thought to be related to the primary outcomes were also assessed.Results: Nine hundred seventy-five survivors completed the survey. Twenty-seven percent (95% confidence interval [CI], 24%-30%) had a cancer-related medical visit in the previous 2 years, and 41% (95% CI, 38%-44%) planned to have such a visit within the next 2 years. The likelihood of having had a cancer-related visit within the last 2 years was higher among survivors assigning greater importance to these visits (relative risk [RR], 1.2; 95% CI, 1.1-1.3), perceiving greater susceptibility to health problems (RR, 1.2; 95% CI, 1.1-1.3), having a moderate to life-threatening chronic health problem related to their cancer (RR, 2.1; 95% CI, 1.7-2.7), seeing a primary care provider for a cancer-related problem (RR, 1.3; 95% CI, 1.0-1.6), having a cancer treatment summary (RR, 1.3; 95% CI, 1.0-1.6), and endorsing greater confidence in physicians' abilities to address questions and concerns (RR, 1.2; 95% CI, 1.0-1.3).Conclusions: Educational interventions improving awareness of treatment history and susceptibility to cancer-related late effects and corresponding risk-based care are likely to be beneficial for survivors of childhood cancers. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for both treatment-related exercise intolerance and neurocognitive deficits. This analysis aimed to identify the association between exercise intolerance and neurocognitive impairments in ALL survivors.Methods: Cardiopulmonary exercise testing, results from a 2-hour standardized neuropsychological assessment, and self-report questionnaires were obtained for 341 adult survivors of childhood ALL and 288 controls. Multivariable modeling was used to test associations between oxygen uptake at 85% estimated heart rate (rpkVO2 ) and neuropsychological test and self-reported questionnaire domains, adjusted for sex, age at diagnosis, cranial radiation, anthracycline, and methotrexate exposure and tobacco smoking status.Results: Compared with controls, survivors had worse rpkVO2 and performance on verbal intelligence, focused attention, verbal fluency, working memory, dominant/nondominant motor speed, visual-motor speed, memory span, and reading and math measures (all P < .001). In adjusted models, exercise intolerance was associated with decreases in performance of verbal ability, focused attention, verbal fluency, working memory, dominant motor speed, nondominant motor speed, visual-motor speed, memory span, reading academics, and math academics in survivors.Conclusion: This study demonstrates an association between exercise intolerance and neurocognitive outcomes. Research is needed to determine whether interventions that improve exercise tolerance impact neurocognitive function in ALL survivors. [ABSTRACT FROM AUTHOR]

Background: Despite an increased risk of subsequent human papillomavirus (HPV)-related malignancies, HPV vaccine initiation rates among cancer survivors remain critically low. The purpose of this study was to determine the relationship between HPV vaccine intent and subsequent vaccine initiation among cancer survivors by linking data from a cross-sectional survey with state-based immunization registry records.Methods: Cancer survivors who were 9 to 26 years old were surveyed 1 to 5 years after their treatment to assess their HPV vaccine initiation status, HPV vaccine intent, sociodemographic factors, and vaccine-related health beliefs. HPV vaccine doses/dates were abstracted from the Georgia Registry for Immunization Transactions for 3.5 years after survey participation. Logistic regression models identified factors associated with vaccine intent and subsequent vaccine initiation.Results: Among survivors who were HPV vaccine-naive at survey participation (n = 103), factors associated with vaccine intent included the following: 1) provider recommendation for the HPV vaccine (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.4-18.1; P = .014), 2) positive general attitude toward vaccines (OR, 4.8; 95% CI, 2.0-11.2; P < .001), and 3) perceived severity of HPV disease (OR, 3.5; 95% CI, 1.2-9.9; P = .02). Of the vaccine-naive patients, 28 initiated the HPV vaccine at a median of 1.1 years after the survey. Initiation was more likely among survivors who had reported vaccine intent (OR, 3.9; 95% CI, 1.2-12.5; P = .02) and was less likely among older survivors (OR per year, 0.7; 95% CI, 0.6-0.9; P < .001).Conclusions: These findings suggest that provider recommendation for the HPV vaccine plays a role in establishing intent, which then translates into subsequent initiation. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer are at risk of neurocognitive impairment, emotional distress, and poor health-related quality of life (HRQOL); however, the effect of race/ethnicity is understudied. The objective of this study was to identify race/ethnicity-based disparities in neurocognitive, emotional, and HRQOL outcomes among survivors of childhood cancer.Methods: Self-reported measures of neurocognitive function, emotional distress (the Brief Symptom Inventory-18), and HRQOL (the Medical Outcomes Study Short Form-36 health survey) were compared between minority (Hispanic, n = 821; non-Hispanic black [NHB], n = 600) and non-Hispanic white (NHW) (n = 12,287) survivors from the Childhood Cancer Survivor Study (median age, 30.9 years; range, 16.0-54.1 years). By using a sample of 3055 siblings, the magnitude of same-race/same-ethnicity survivor-sibling differences was compared between racial/ethnic groups, adjusting for demographic and treatment characteristics and current socioeconomic status (SES).Results: No clear pattern of disparity in neurocognitive outcomes by race/ethnicity was observed. The magnitude of the survivor-sibling difference in the mean score for depression was greater in Hispanics than in NHWs (3.59 vs 1.09; P = .004). NHBs and Hispanics had greater survivor-sibling differences in HRQOL than NHWs for mental health (NHBs: -5.78 vs -0.69; P = .001; Hispanics: -3.87 vs -0.69; P = .03), and social function (NHBs: -7.11 vs -1.47; P < .001; Hispanics: -5.33 vs -1.47; P = .001). NHBs had greater survivor-sibling differences in physical subscale scores for HRQOL than NHWs. In general, the findings were not attenuated by current SES.Conclusions: Although no pattern of disparity in neurocognitive outcomes was observed, differences across many HRQOL outcomes among minorities compared with NHWs, not attenuated by current SES, were identified. This suggests that further research into environmental and sociocultural factors during and immediately after treatment is needed. [ABSTRACT FROM AUTHOR]

Background: The impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT).Methods: Adult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4-62.2 years) completed neurocognitive tests and self-reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin-like growth factor1 level less than -2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high-dose intravenous methotrexate were included as covariates in multivariable linear regression models.Results: Of the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT (P = .002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z-score, -0.84 vs -0.61; P = .02), processing speed (z-score, -0.49 vs -0.30; P = .04), cognitive flexibility (z-score, -1.37 vs -0.94; P = .01), and verbal fluency (z-score, -0.74 vs -0.44; P = .001), and they self-reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P = .01; vitality, P = .01; mental health, P = .01); and CRT dose accounted for the lower neurocognitive outcomes.Conclusions: Adult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer report poor health-related quality of life (HRQOL). Modifiable lifestyle factors such as nutrition and physical activity represent opportunities for interventions to improve HRQOL.Methods: The authors examined the association between modifiable lifestyle factors and HRQOL among 2480 adult survivors of childhood cancer in the St. Jude Lifetime Cohort Study. Dietary intake, physical activity, cigarette smoking, and alcohol consumption were assessed through questionnaires. Weight and height were measured in the clinic. HRQOL was evaluated using the Medical Outcome Study 36-Item Short Form Survey. The physical component summary (PCS), mental component summary (MCS), and 8 domain scores of HRQOL were calculated. Multivariable linear regression models were used to estimate regression coefficients (β) associated with HRQOL differences.Results: Being physically active (PCS β = 3.10; and MCS β = 1.48) was associated with higher HRQOL whereas current cigarette smoking (PCS β = -2.30; and MCS β = -6.49) and obesity (body mass index ≥30 kg/m2 ) (PCS β = -3.29; and MCS β = -1.61) were associated with lower HRQOL in both the physical and mental domains. Better diet (Healthy Eating Index-2015) was associated with higher physical HRQOL (PCS β = 1.79). Moderate alcohol consumption was associated with higher physical (PCS β = 1.14) but lower mental (MCS β = -1.13) HRQOL (all P <.05). Adherence to multiple healthy lifestyle factors demonstrated a linear trend with high scores in both physical and mental HRQOL (highest vs lowest adherence: PCS β = 7.60; and MCS β = 5.76 [P for trend, <.0001]).Conclusions: The association between healthy lifestyle factors and HRQOL is cumulative, underscoring the importance of promoting multiple healthy lifestyles to enhance HRQOL in long-term survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer are at significant risk for serious chronic health conditions and subsequent cancers because of their prior treatment exposures. However, little is known about survivors' perceptions of their future health risks.Methods: This study examined self-reported levels of concern about future health and subsequent cancer in 15,620 adult survivors of childhood cancer (median age, 26 years; median time since diagnosis, 17 years) and 3991 siblings in the Childhood Cancer Survivor Study. The prevalence of concerns was compared between survivors and siblings, and the impact of participant characteristics and treatment exposures on concerns was examined with multivariable modified Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results: A substantial proportion of survivors were not concerned about their future health (31%) or developing cancer (40%). The prevalence of concern in survivors was modestly higher (RR for future health, 1.12; 95% CI, 1.09-1.15) or similar (RR for subsequent cancer, 1.02; 95% CI, 0.99-1.05) in comparison with siblings. Survivors exposed to high doses of radiation (≥20 Gy) were more likely to report concern (RR for future health, 1.13; 95% CI, 1.09-1.16; RR for subsequent cancer, 1.14; 95% CI, 1.10-1.18), but 35% of these high-risk survivors were not concerned about developing cancer, and 24% were not concerned about their future health.Conclusions: A substantial subgroup of survivors were unconcerned about their future health and subsequent cancer risks, even after exposure to treatments associated with increased risk. These survivors may be less likely to engage in beneficial screening and risk-reduction activities. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, social network status in adolescent and young adult (AYA) cancer survivors has not been adequately studied to date. The authors developed and validated a functional social network index (FSNI) for AYA survivors, and compared its performance with that of 2 traditional indices (density and betweenness centrality).Methods: A total of 102 AYA survivors and 102 noncancer controls who were matched for age, sex, and race were recruited from an Internet panel. Each participant reported relationships with up to 25 close friends and/or relatives. The authors developed a FSNI with reported marital status, contact frequency with friends/relatives, available resources for emotional and tangible support, and available resources for physical activity and weight management advice. Linear regression was used to analyze associations between the FSNI and cancer diagnoses, treatments, and coping skills.Results: Based on the FSNI, survivors were found to have more available resources for emotional support (beta [b] = 3.02; P = .003), tangible support (b = 4.17; P<.001), physical activity advice (b = 3.94; P<.001), and weight management advice (b = 4.10; P<.001) compared with noncancer controls. Survivors of lymphoma had the largest FSNI, whereas survivors of central nervous system malignancies had the smallest (b = 2.77; P = .02). A higher FSNI was associated with better coping skills: less denial (b = 0.10; P = .01), using emotional support (b = 0.08; P = .04), using instrumental support (b = 0.12; P<.001), less behavioral disengagement (b = 0.08; P = .04), venting of emotions (b = 0.10; P = .004), positive reframing (b = 0.12; P = .003), planning for the future (b = 0.08; P = .03), and religious engagement (b = 0.16; P<.001). Density and betweenness centrality indices demonstrated neither significant differences in social networks between cancer survivors and controls (all P values >.05) nor significant associations with coping skills (all P values >.05).Conclusions: The FSNI appears to provide a better social network assessment for AYA cancer survivors than traditional indices. Cancer 2018;124:2220-7. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Children with non-Hodgkin lymphoma (NHL) undergo treatment with central nervous system-directed therapy, the potentially neurotoxic effects of which have not been reported in NHL survivors.Methods: NHL survivors (n = 187) participating in the St. Jude Lifetime Cohort who were 10 or more years from their diagnosis and were 18 years old or older underwent neurocognitive, emotional distress (Brief Symptom Inventory 18), and health-related quality of life (HRQOL) assessments (36-Item Short Form Health Survey). Age-adjusted z scores were compared with community controls (n = 181) and normative data. Treatment exposures were abstracted from medical records. Models adjusted for the age, sex, and time from diagnosis were used to calculate the risk of impairment.Results: The mean ages at evaluation were similar for the survivors and the controls (35.7 ± 8.9 vs 35.5 ± 11.0 years; P = .86). Survivors were 25.2 ± 8.8 years from their diagnosis: 43 (23%) received cranial radiation, 70 (37%) received high-dose methotrexate, 40 (21%) received high-dose cytarabine, and 151 (81%) received intrathecal chemotherapy. Survivors' intelligence and attention were within normal limits; however, their memory, executive function, processing speed, and academics were impaired in comparison with both population norms and community controls (P values < .05). Treatment-related exposures were not associated with neurocognitive function; however, neurocognitive impairment was associated with lower educational attainment, unemployment, and occupational status (P values < .03). Slower processing speed and worse self-reported executive function were associated with symptoms of depression (P values ≤ .003) and poorer HRQOL (P values < .05).Conclusions: Adult survivors of childhood NHL experience impaired neurocognitive function, which is associated with lower social attainment and poor HRQOL. Early-detection and intervention strategies are recommended. Cancer 2017. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: Long-term survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive impairment, which may be associated with fatigue, sleep problems, systemic inflammation, and oxidative stress. We examined these associations among survivors of childhood ALL treated with chemotherapy only.Methods: Survivors of childhood ALL (male, n = 35 and female, n = 35; mean age, 14.3 years [standard deviation, 4.7 years] and mean years from diagnosis, 7.4 years [standard deviation, 1.9 years]) completed neurocognitive testing, behavioral ratings, and reported sleep quality and fatigue symptoms 5 years after diagnosis. Serum was collected concurrently and assayed for interleukin (IL)-1β and IL-6, tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hsCRP), malondialdehyde, myeloperoxidase, and oxidized low-density lipoprotein. General linear modeling was used to assess associations among biomarkers and functional outcomes, adjusting for age and stratified by sex.Results: Survivors performed worse than population norms on executive function and processing speed and reported more behavioral problems (P < .05 adjusted for multiple comparison). In female survivors, fatigue was associated with poor executive function (r = 0.41; P = .02), processing speed (r = 0.56; P < .001), and attention (r = 0.36-0.55; P < .05). Female survivors with frequent nighttime awakening displayed more inattention (P = .01), hyperactivity (P = .03), and aggression (P = .01). Worse executive function, processing speed, and behavioral symptoms were observed in female survivors with higher levels of IL-6, IL-1β, and hsCRP (P < .05). Male survivors with high levels of TNF-α demonstrated worse organization (P = .03), but no significant associations between neurocognitive outcomes and sleep/fatigue measures were observed.Conclusion: Neurocognitive function in female survivors of childhood ALL appears more susceptible to the effects of sleep disturbance and fatigue. Systemic inflammation may play a role in neurocognitive impairment and behavioral symptoms. Cancer 2017;123:3410-9. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to describe perceptions and associated risk factors of the impact of cancer on functional outcomes, including social relationships, exercise, finances, and religion, among adult survivors of childhood cancer.Methods: Evaluable participants included 3001 adult survivors (mean age, 32.5 years; range, 18.3-63.8 years; 24.1 years from diagnosis; 50.8% male; 84.9% Caucasian) who were enrolled in the St. Jude Lifetime Cohort study. Perceptions of the impact of cancer were assessed using the Brief Cancer Impact Assessment (BCIA). Regression models were used to evaluate risk factors for functional outcomes.Results: The median response on the BCIA was a perception that cancer had minimal impact on the domains assessed. Approximately 33.1% to 46.6% of survivors indicated this response across the 4 subscales, although responses ranged from very positive to very negative impact. Other than diagnosis (with survivors of brain tumors generally indicating a more negative impact of cancer, with subscale estimates of -1.25 for caregiving and finance and -1.01 for social and emotional and an odds ratio of 1.83 for exercise and diet), most variability was because of demographic factors, including sex, age, race, education, and employment.Conclusions: The current findings highlight that many long-term adult survivors perceive minimal impact of childhood cancer on functional aspects of adulthood, including caregiving, finances, exercise, social-emotional relationships, and religion. This suggests that survivors may not be focusing on the influence of likely physical and psychological late effects of their disease in their day-to-day lives. For those who do perceive a negative impact, variability in responses suggests that there are of survivors who may benefit from interventions focused on the achievement of functional goals. Cancer 2017;123:1625-1634. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Health complications related to childhood cancer may be influenced by risky health behaviors (RHBs), particularly when RHBs co-occur. To the authors' knowledge, only limited information is available describing how RHBs cluster among survivors of childhood cancer and their siblings and the risk factors for co-occurring RHBs.Methods: Latent class analysis was used to identify RHB clusters using longitudinal survey data regarding smoking, alcohol use, and physical activity from adult survivors (4184 survivors) and siblings (1598 siblings) in the Childhood Cancer Survivor Study. Generalized logistic regression was used to evaluate associations between demographic characteristics, treatment exposures, psychological distress, health conditions, and cluster membership.Results: Three RHB clusters were identified: a low-risk cluster, an insufficiently active cluster, and a high-risk cluster (tobacco and risky alcohol use and insufficient activity). Compared with siblings, survivors were more likely to be in the insufficiently active cluster (adjusted odds ratio [ORadj ], 1.17; 95% confidence interval [95% CI], 1.06-1.27) and were less likely to be in the high-risk cluster (ORadj , 0.79; 95% CI, 0.69-0.88). Risk factors for membership in the high-risk cluster included psychological distress (ORadj , 2.76; 95% CI, 1.98-3.86), low educational attainment (ORadj , 7.49; 95% CI, 5.15-10.88), income <$20,000 (ORadj , 2.62; 95% CI, 1.93-3.57), being divorced/separated or widowed (ORadj , 1.36; 95% CI, 1.03-1.79), and limb amputation (ORadj , 1.52; 95% CI, 1.03-2.24). Risk factors for the insufficiently active cluster included chronic health conditions, psychological distress, low education or income, being obese or overweight, female sex, nonwhite race/ethnicity, single marital status, cranial radiation, and cisplatin exposure.Conclusions: RHBs co-occur in survivors of childhood cancer and their siblings. Economic and educational disadvantages and psychological distress should be considered in screening and interventions to reduce RHBs. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2747-2756. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Fertility preservation care for children, adolescents, and young adults (CAYAs) with cancer is not uniform among practitioners. To ensure high-quality care, evidence-based clinical practice guidelines (CPGs) are essential. The authors identified existing CPGs for fertility preservation in CAYAs with cancer, evaluated their quality, and explored differences in recommendations.Methods: A systematic search in PubMed (January 2000-October 2014); guideline databases; and Web sites of oncology, pediatric, and fertility organizations was performed. Two reviewers evaluated the quality of the identified CPGs using the Appraisal of Guidelines for Research and Evaluation II Instrument (AGREE II). From high-quality CPGs, the authors evaluated concordant and discordant areas among the recommendations.Results: A total of 25 CPGs regarding fertility preservation were identified. The average AGREE II domain scores (scale of 0%-100%) varied from 15% on applicability to 100% on clarity of presentation. The authors considered 8 CPGs (32%) to be of high quality, which was defined as scores ≥60% in any 4 domains. Large variations in the recommendations of the high-quality CPGs were observed, with 87.2% and 88.6%, respectively, of discordant guideline areas among the fertility preservation recommendations for female and male patients with cancer.Conclusions: Only approximately one-third of the identified CPGs were found to be of sufficient quality. Of these CPGs, the fertility preservation recommendations varied substantially, which can be a reflection of inadequate evidence for specific recommendations, thereby hindering the ability of providers to deliver high-quality care. CPGs including a transparent decision process for fertility preservation can help health care providers to deliver optimal and uniform care, thus improving the quality of life of CAYAs with cancer and cancer survivors. Cancer 2016;122:2216-23. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer who are treated with platinum-based chemotherapy and/or cranial radiation are at risk of treatment-induced hearing loss. However, the effects of such hearing loss on adult social attainment have not been well elucidated.Methods: Adult survivors of pediatric central nervous system (CNS) solid tumors (180 survivors) and non-CNS solid tumors (226 survivors) who were treated with potentially ototoxic cancer therapy completed audiologic evaluations and questionnaires assessing their perception of social functioning and social attainment (ie, independent living, marriage, and employment). Audiograms were graded with the Chang ototoxicity grading scale. Analyses were stratified by tumor type (ie, CNS vs non-CNS). Multivariable logistic regression models were conducted with adjustment for age; sex; chronic health conditions; and, for the CNS group, IQ. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were reported.Results: Serious hearing loss (that requiring a hearing aid or deafness) was detected in 36% of survivors of CNS tumors and 39% of survivors of non-CNS tumors. Serious hearing loss was associated with an increased risk of perceived negative impact in ≥1 areas of social functioning (survivors of non-CNS tumors: OR, 1.83 [95% CI, 1.00-3.34]). Among survivors of non-CNS tumors, serious hearing loss was associated with 2-fold increased risk of nonindependent living (OR, 2.19; 95% CI, 1.19-4.04) and unemployment or not graduating from high school (OR, 1.85; 95% CI, 1.00-3.34).Conclusions: A substantial proportion of adult survivors of childhood cancer treated with potentially ototoxic therapy have serious hearing loss. Treatment-induced hearing loss was found to be associated with reduced social attainment, both perceived and actual, in this study sample. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: Partial nephrectomy is considered by some for children with unilateral Wilms tumor (UWT) to avoid the theoretical complication of renal insufficiency. In the current study, the authors evaluated the prevalence of hypertension and impaired renal function in long-term survivors of nonsyndromic UWT who were treated without nephrotoxic chemotherapy or ionizing radiation. METHODS: Eligibility included age ≤15 years at the time of diagnosis of nonsyndromic UWT, treatment receipt before 2002, and maintenance of disease remission after unilateral nephrectomy without receipt of abdominal irradiation or nephrotoxic chemotherapy. Renal function was assessed by urinalysis and estimated glomerular filtration rate (eGFR). Patients receiving antihypertensive medication or those with blood pressure readings of >140/90 mm Hg were considered to be hypertensive. RESULTS: A total of 75 patients with a median age at diagnosis of 3.2 years (range, 0.2-12.1 years) met eligibility criteria. The median length of follow-up was 19.6 years (range, 10.0-32.8 years). All but 1 patient had stage I/II disease. Sixty-eight patients (90.7%) patients had WT with favorable histology and 7 patients had anaplastic histology. Sixteen patients (21.3%) had an eGFR <90 mL/minute/1.73m², 2 of whom also had proteinuria (12.5%). No patient had an eGFR <60 mL/minute/1.73m². Five patients (6.7%) had hypertension, 3 of whom were receiving antihypertensive medications. At the time of last follow-up, no patient had developed end-stage renal disease. CONCLUSIONS: Patients with UWT who were treated with unilateral radical nephrectomy without nephrotoxic chemotherapy or ionizing radiation appear to be at low risk of developing significant long-term renal dysfunction. For this patient population, the routine use of partial nephrectomy does not appear justified. However, monitoring and counseling are important for identifying the rare patient who develops subtle renal insufficiency and therefore might be at an increased risk of adverse cardiovascular sequelae. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to identify treatment and genetic factors associated with obesity among childhood cancer survivors.Methods: 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) .Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

BACKGROUND 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). METHODS 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. RESULTS 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. CONCLUSIONS 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. Cancer 2015;121:2036-2043. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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. Cancer 2015;121:774-782. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Retinoblastoma has a 5-year survival rate exceeding 95%, yet little is known about long-term functional outcomes for these patients. METHODS Sixty-nine adult survivors of retinoblastoma (mean age, 33 years; mean years post-diagnosis, 31) who had enrolled in the St. Jude Lifetime Cohort Study completed clinical cognitive evaluations and questionnaires assessing adult social attainment. Scores on all cognitive measures were converted to z-scores (M = 0, SD = 1) using age-adjusted normative data. Multivariable linear regression analyses, adjusted for age at diagnosis and disease laterality, were used to examine associations between disease and treatment exposures and cognitive outcomes. RESULTS Retinoblastoma survivors performed within normative expectations across most cognitive domains. In multivariable models, adjusted for disease laterality, survivors diagnosed at ≤1 year of age performed significantly better on measures of short-term verbal memory (β = 0.87, P<.01), long-term verbal memory (β = 0.66, P = .02), verbal learning (β = 0.67, P = .02), and verbal reasoning abilities (β = 0.79, P<.01) compared with survivors diagnosed at >1 year of age. In multivariable models, restricted to bilateral survivors and adjusted for age at diagnosis, whole brain radiation exposure was significantly associated with poorer performance on tasks of short-term verbal memory (β = −0.003, P = .03) and long-term verbal memory (β = −0.003, P = .01). Reported social attainment was consistent with adult developmental expectations. CONCLUSIONS Adult survivors of retinoblastoma demonstrate few cognitive or social attainment deficits decades following diagnosis and treatment. Findings suggest the potential for neural reorganization following early insult to the visual system as well as vulnerability of the developing brain to low dose radiation exposure. Early intervention and rehabilitation will be important for these patients. Cancer 2015;121:123-131. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND 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. METHODS 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 fraction <50%; 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. RESULTS 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. CONCLUSIONS CCTA identified CAD in a substantial percentage of survivors of HL and may be an effective screening modality for this population. Cancer 2014;120:3536-3544. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Childhood cancer survivors (CCS) are at an increased risk of developing metabolic syndrome (MetSyn), which may be reduced with lifestyle modifications. The purpose of this investigation was to characterize lifestyle habits and associations with MetSyn among CCS. METHODS CCS who were ≥ 10 years from diagnosis, aged > 18 years, and participating in the St. Jude Lifetime Cohort Study completed medical and laboratory tests and a food frequency questionnaire. The Third Report of the National Cholesterol Education Program Adult Treatment Panel criteria were used to classify participants with MetSyn. Anthropometric, food frequency questionnaire, and self-reported physical activity data were used to characterize lifestyle habits according to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations. Those who met ≥ 4 of 7 recommendations were classified as having followed guidelines. Sex-stratified log-binomial regression models were used to evaluate associations between dietary/lifestyle habits and MetSyn, adjusted for age, age at cancer diagnosis, receipt of cranial radiotherapy, education, and household income. RESULTS Among 1598 CCS (49.2% of whom were male, with a median age of 32.7 years [range, 18.9 years-60.0 years]), 31.8% met criteria for MetSyn and 27.0% followed WCRF/AICR guidelines. Females who did not follow WCRF/AICR guidelines were 2.4 times (95% confidence interval, 1.7-3.3) and males were 2.2 times (95% confidence interval, 1.6-3.0) more likely to have MetSyn than those who followed WCRF/AICR guidelines. CONCLUSIONS Adherence to a heart-healthy lifestyle is associated with a lower risk of MetSyn among CCS. There is a need to determine whether lifestyle interventions prevent or remediate MetSyn in CCS. Cancer 2014;120:2742-2750. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although whole lung irradiation is used to treat pulmonary metastases of pediatric solid malignancies, few studies have addressed its long-term pulmonary consequences. METHODS: The authors conducted a retrospective study of longitudinal changes in 171 pulmonary function tests (PFTs) and their relation with clinical features in 48 survivors of pediatric malignant solid tumors treated with whole lung irradiation. RESULTS: Although active respiratory symptoms were seen in only 9 patients (18.8%), abnormalities in forced vital capacity (FVC; 58.3%), forced expiratory volume in 1 second (FEV1; 64.6%), total lung capacity (TLC; 72.9%), and diffusion capacity of the lung for carbon monoxide corrected for hemoglobin (DLCOcorr; 70.8%) were common. At a median follow-up of 9.7 years after whole lung irradiation, FVC, FEV1, and TLC significantly declined longitudinally ( P = .04, .03, and .02, respectively). Focal pulmonary boost irradiation was significantly associated with abnormal FEV1/FVC ( P = .03), forced expiratory flow between 25% and 75% forced vital capacity ( P = .005), residual volume (RV; P = .005), and RV/TLC ( P = .002). Ten patients had baseline PFTs, and FVC, FEV1, TLC, and DLCOcorr worsened immediately after radiation, followed by transient improvement but subsequent decline. Thirteen of 32 (40.6%) patients aged >18 years were smokers. CONCLUSIONS: Pulmonary dysfunction was prevalent after whole lung irradiation and worsened over time, although most patients were asymptomatic. Boost irradiation impaired pulmonary function, and a significant proportion of patients were smokers. Further studies are planned to assess the predictors and clinical consequences of progressive PFT abnormalities and to evaluate educational interventions. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Treatment regimens for childhood acute lymphoblastic leukemia (ALL) contain neurotoxic agents that may interfere with neuromuscular health. In this study, the authors examined associations between neuromuscular impairments and physical function and between neuromuscular impairments and doses of vincristine and intrathecal methotrexate used to treat leukemia among survivors of childhood ALL. METHODS: ALL survivors >10 years from diagnosis participated in neuromuscular performance testing. Treatment data were abstracted from medical records. Regression models were used to evaluate associations between treatment factors, neuromuscular impairments, and physical performance. RESULTS: Among 415 survivors (median age, 35 years; age range, 21-52 years), balance, mobility, and 6-minute walk (6MW) distances were 1.3 standard deviations below age-specific and sex-specific values in 15.4%, 3.6%, and 46.5% of participants, respectively. Impairments included absent Achilles tendon reflexes (39.5%), active dorsiflexion range of motion (ROM) <5 degrees (33.5%), and impaired knee extension strength (30.1%). In adjusted models (including cranial radiation), survivors who received cumulative intrathecal methotrexate doses ≥215 mg/m2 were 3.4 times more likely (95% confidence interval, 1.2-9.8 times more likely) to have impaired ROM than survivors who received no intrathecal methotrexate, and survivors who received cumulative vincristine doses ≥39 mg/m2 were 1.5 times more likely (95% CI, 1.0-2.5 times more likely) to have impaired ROM than survivors who received lower cumulative doses of vincristine. Higher intrathecal methotrexate doses were associated with reduced knee extension strength and 6MW distances. CONCLUSIONS: Neuromuscular impairments were prevalent in childhood ALL survivors and interfered with physical performance. Higher cumulative doses of vincristine and/or intrathecal methotrexate were associated with long-term neuromuscular impairments, which have implications on future function as these survivors age. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The authors examined whether survivors from the Childhood Cancer Survivor Study were less likely to be in higher-skill occupations than a sibling comparison and whether certain survivors were at higher risk for lower-skill jobs.Methods: The authors created 3 mutually exclusive occupational categories for participants aged ≥ 25 years: Managerial/Professional, Nonphysical Service/Blue Collar, and Physical Service/Blue Collar. The authors examined currently employed survivors (4845) and their siblings (1727) in multivariable generalized linear models to evaluate the likelihood of being in 1 of the 3 occupational categories. Multinomial logistic regression was used among all participants to examine the likelihood of these outcomes compared to being unemployed (survivors, 6671; siblings, 2129). Multivariable linear models were used to assess survivor occupational differences by cancer-  and treatment-related variables. Personal income was compared by occupation.Results: Employed survivors were less often in higher-skilled Managerial/Professional occupations (relative risk, 0.93; 95% confidence interval 0.89-0.98) than their siblings. Survivors who were black, were diagnosed at a younger age, or had high-dose cranial radiation were less likely to hold Managerial/Professional occupations than other survivors. In multinomial models, female survivors' likelihood of being in full-time Managerial/Professional occupations (27%) was lower than male survivors (42%) and female (41%) and male (50%) siblings. Survivors' personal income was lower than siblings within each of the 3 occupational categories in models adjusted for sociodemographic variables.Conclusions: Adult childhood cancer survivors are employed in lower-skill jobs than siblings. Survivors with certain treatment histories are at higher risk for lower-skill jobs and may require vocational assistance throughout adulthood. [ABSTRACT FROM AUTHOR]

The majority of children, adolescents, and young adults diagnosed with cancer will become long-term survivors with many potential years of life ahead of them. Their journey from health through diagnosis and treatment to survivorship involves multiple transitions. Transitional services that should be available throughout this journey include health-related education, health surveillance and screening, management of cancer-related complications, and psychosocial support relevant to their developmental needs. Survivors require lifelong care that focuses not only on the medical risks arising from their cancer therapy, but also the psychosocial, educational, and vocational implications of surviving cancer. Because many community health care providers lack familiarity with the health risks associated with childhood or adolescent/young adult cancer, survivors must have sufficient health knowledge to advocate for risk-based cancer-related follow-up; the provision of a treatment summary and care plan at the conclusion of their cancer therapy is an important tool for facilitating this process. The availability of resources for survivors varies by geography, health care system, and survivor characteristics. Adolescents and young adults who receive their care outside of a pediatric cancer center have particularly limited access. The limitations in cancer center resources (along with survivor preference) strongly suggest that the long-term care of survivors will need to be shared between the cancer centers and primary care providers in survivors' communities. Cancer 2011;117(10 suppl):2335-41. © 2011 American Cancer Society. Survivors of cancer in childhood, adolescence, or young adult life require lifelong care that focuses not only on the medical risks that arise from their cancer therapy but also on the psychosocial, educational, and vocational implications of surviving cancer. Limitations in cancer center resources (along with survivor preference) strongly suggest that this care will need to be shared between cancer centers and primary care providers in survivors' communities. [ABSTRACT FROM AUTHOR]

Background: Lack of health insurance is a key barrier to accessing care for chronic conditions and cancer screening. The influence of insurance type (private, public, none) on survivor-focused and general preventive health care in adult survivors of childhood cancer was examined.Methods: The Childhood Cancer Survivor Study is a retrospective cohort study of childhood cancer survivors diagnosed between 1970 and 1986. Among 8425 adult survivors, the relative risk (RR) and 95% confidence interval (CI) of receiving survivor-focused and general preventive health care were estimated for uninsured (n = 1390) and publicly insured (n = 640), compared with for the privately insured (n = 6395)Results: Uninsured survivors were less likely than those privately insured to report a cancer-related visit (adjusted RR, 0.83; 95% CI, 0.75-0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71-0.98). Uninsured survivors had lower levels of utilization in all measures of care in comparison with privately insured. In contrast, publicly insured survivors were more likely to report a cancer-related visit (adjusted RR, 1.22; 95% CI, 1.11-1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18-1.70) than were privately insured survivors. Although publicly insured survivors had similar utilization of general health examinations, they were less likely to report a Papanicolaou test or a dental examinationsConclusions: Among this large, socioeconomically diverse cohort, publicly insured survivors utilize survivor-focused health care at rates at least as high as survivors with private insurance. Uninsured survivors have lower utilization of both survivor-focused and general preventive health care. [ABSTRACT FROM AUTHOR]

The article examines the factors that predicted outcome in pediatric Hodgkin lymphoma (HL) patients who progressed or relapsed after initial treatment with a combined-modality therapy regimen consisting of both chemotherapy and radiation therapy. It was found out that an inadequate response to initial salvage therapy was a significant variable in the analysis of overall survival. It was concluded that there is a very poor prognosis for pediatric patients with relapsed HL who have an inadequate response after initial primary salvage chemotherapy.

Background: Pediatric cancer survivors who were treated before routine hepatitis C virus (HCV) screening of blood donors in 1992 have an elevated risk of transfusion-acquired HCV.Methods: To assess long-term pediatric cancer survivors' knowledge of HCV testing and blood transfusion history, a questionnaire was administered to 9242 participants in the Childhood Cancer Survivor Study who are at risk for transfusion-acquired HCV after cancer therapy from 1970 to 1986.Results: More than 70% of survivors reported either no prior HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting prior testing. One half recalled having a treatment-related blood transfusion; those who recalled a transfusion were more likely to report HCV testing (39%) than those who did not (18%) or were unsure (20%). In multivariate models, survivors who reported no prior HCV testing were more likely to be older (odds ratio [OR] per 5-year increase, 1.1; 95% confidence interval [CI], 1.0-1.1) and to report no care at a cancer center within the past 2 years (OR, 1.2; 95% CI, 1.0-1.4), no cancer treatment summary (OR, 1.3; 95% CI, 1.2-1.5), and no transfusions (OR, 2.6; 95% CI, 2.3-3.0) or uncertainty about transfusions (OR, 2.2; 95% CI, 1.9-2.6), and less likely to be racial/ethnic minorities (OR, 0.9; 95% CI, 0.8-1.0) or survivors of acute myeloid leukemia (OR, 0.7; 95% CI, 0.5-1.0).Conclusions: Many pediatric cancer survivors at risk for transfusion-acquired HCV are unaware of their transfusion history and prior testing for HCV and would benefit from programs to increase HCV knowledge and screening. [ABSTRACT FROM AUTHOR]

Background: The current study was performed to describe frequencies and risk factors of altered oral health and odontogenesis in childhood cancer survivors.Methods: In total, 9308 survivors who were diagnosed between 1970 and 1986 and 2951 siblings from the Childhood Cancer Survivor Study completed a survey that contained oral-dental health information. The authors analyzed treatment impact, socioeconomic data, and patient demographics on dental outcomes using univariate and multivariate logistic regression models to estimate odds ratios (ORs).Results: In multivariate analysis, survivors were more likely to report microdontia (OR, 3.0; 95% confidence interval [95% CI], 2.4-3.8), hypodontia (OR, 1.7; 95% CI, 1.4-2.0), root abnormalities (OR, 3.0; 95% CI, 2.2-4.0), abnormal enamel (OR, 2.4; 95% CI, 2.0-2.9), teeth loss>or=6 (OR, 2.6; 95% CI, 1.9-3.6), severe gingivitis (OR, 1.2; 95% CI, 1.0-1.5), and xerostomia (OR, 9.7; 95% CI, 4.8-19.7). Controlling for chemotherapy and socioeconomic factors, radiation exposure of >or=20 Gray to dentition was associated significantly with an increased risk of >or=1 dental abnormality. Dose-dependent alkylating agent therapy significantly increased the risk of >or=1 anatomic/developmental dental abnormalities in survivors who were diagnosed at age<5 years (OR, 1.7, 2.7, and 3.3 for alkylating agent scores of 1, 2, and 3, respectively).Conclusions: Radiation and chemotherapy were independent risk factors for adverse oral-dental sequelae among childhood cancer survivors. The authors concluded that patients who received receiving alkylating agents at age<5 years should be closely monitored. [ABSTRACT FROM AUTHOR]