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Background: The impact of specific treatment modalities on long-term renal function and blood pressure among adult survivors of Wilms tumor (WT) has not been well documented., Methods: Among 40 WT survivors and 35 noncancer controls, we estimated the glomerular filtration rate (eGFR) using the Chronic Kidney Disease-Epidemiology (CKD-EPI) equations with and without cystatin C, obtained 24-hour ambulatory blood pressure readings, and, among survivors only, measured 99m Tc diethylenetriamine pentaacetic acid (DTPA) plasma clearance. Survivors were treated with unilateral nephrectomy and nonnephrotoxic chemotherapy. Twenty received whole abdomen radiation therapy (WART) [median -16.5 Gray (Gy)], and 20 received no radiation therapy. Pairwise comparisons between survivors treated with and without WART, and each group to controls were performed using two-sample t tests., Results: Twenty-six (65%) WT survivors were female, and 33 (83%) were non-Hispanic white. GFR estimated with creatinine or creatinine + cystatin C was decreased among irradiated survivors compared with controls. No irradiated or unirradiated participant had an eGFR (creatinine + cystatin C) < 60 mL/min/1.73 m 2 . The prevalence of hypertension was significantly increased among unirradiated (25%) and irradiated survivors (35%) compared with controls (0%). Of the 24-hour ambulatory blood pressure monitoring parameters evaluated, only mean sleep period diastolic blood pressure load of those who received WART was significantly different from that of controls., Conclusions: Chronic kidney disease was infrequent in long-term survivors of unilateral nonsyndromic WT, whether treated with WART or no radiation. The prevalence of hypertension was increased in both groups compared with controls, emphasizing the need for ongoing monitoring of renal and cardiovascular health., (© 2020 Wiley Periodicals, Inc.)

We investigated misclassification rates, sensitivity, and specificity of self-reported cigarette smoking through serum cotinine concentration (liquid chromatography tandem mass spectrometry) among 287 adult survivors of childhood cancer. Overall, 2.5-6.7% and 19.7-36.9% of the self-reported never and past smokers had cotinine levels indicative of active smoking. Sensitivity and specificity of self-reported smoking were 57.5-67.1% and 96.6-99.2%. Misclassification was associated with younger age (OR = 3.2; 95% CI = 1.4-7.4), male (OR = 2.1; 95% CI = 1.1-4.0), and past (OR = 2.7; 95% CI = 1.3-5.8) or current (OR = 2.6; 95% CI = 1.0-6.6) marijuana use. After adjusting for tobacco-related variables, current marijuana use remained a significant risk for misclassification. Clinicians/researchers should consider bio-verification to measure smoking status among survivors., (© 2018 Wiley Periodicals, Inc.)

Background: Prevalence of emotional, behavioral, and psychiatric outcomes in child and adolescent survivors of childhood acute lymphoblastic leukemia treated on a chemotherapy-only protocol were not well defined., Methods: Self- and parent-reported emotional and behavioral symptoms were assessed for 161 survivors of childhood acute lymphoblastic leukemia (51.0% female; mean [SD] age 12.1[2.6] years; 7.5[1.6] years post-diagnosis). Age- and sex-adjusted scores were calculated for standardized measures and compared with 90th percentile of norms. Frequencies of survivor psychiatric disorders from structured diagnostic interviews with parents were compared with the general population. Parent emotional distress and post-traumatic stress symptoms were assessed. Associations between child symptoms/disorders and parent distress were examined with log-binomial models, adjusting for highest parent education., Results: Compared with population expectations (10%), more survivors self-reported symptoms of inattention (27.9; 95% CI, 21.0%-35.7%), hyperactivity/impulsivity (26.0%; CI, 19.2%-33.6%), and oppositional-defiant behavior (20.1%; CI, 14.1%-27.3%). Parents reported survivors with more symptoms of inattention (23.6%; CI, 17.2%-31.0%), higher frequencies of obsessive-compulsive disorder (10.3% vs 2%) and oppositional defiant disorder (16.0% vs 9.5%), but not attention-deficit/hyperactivity disorder (7.1% vs 7.8%) or generalized anxiety disorder (3.2% vs 4.1%), compared with national norms. Parent-report of child anxiety disorders was associated with parent self-reported emotional distress but not survivor self-report of anxiety., Conclusion: A significant minority of survivors have long-term psychiatric morbidity, multi-informant assessment is important to understand these symptom profiles and to inform selection of appropriate interventions. Interventions targeting inattention and oppositional behavior in children and emotional distress in parents are warranted in families with survivors who display behavioral problems., (Copyright © 2018 John Wiley & Sons, Ltd.)

Purpose We aimed to predict individual risk of ischemic heart disease and stroke in 5-year survivors of childhood cancer. Patients and Methods Participants in the Childhood Cancer Survivor Study (CCSS; n = 13,060) were observed through age 50 years for the development of ischemic heart disease and stroke. Siblings (n = 4,023) established the baseline population risk. Piecewise exponential models with backward selection estimated the relationships between potential predictors and each outcome. The St Jude Lifetime Cohort Study (n = 1,842) and the Emma Children's Hospital cohort (n = 1,362) were used to validate the CCSS models. Results Ischemic heart disease and stroke occurred in 265 and 295 CCSS participants, respectively. Risk scores based on a standard prediction model that included sex, chemotherapy, and radiotherapy (cranial, neck, and chest) exposures achieved an area under the curve and concordance statistic of 0.70 and 0.70 for ischemic heart disease and 0.63 and 0.66 for stroke, respectively. Validation cohort area under the curve and concordance statistics ranged from 0.66 to 0.67 for ischemic heart disease and 0.68 to 0.72 for stroke. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups. The cumulative incidences at age 50 years among CCSS low-risk groups were < 5%, compared with approximately 20% for high-risk groups ( P < .001); cumulative incidence was only 1% for siblings ( P < .001 v low-risk survivors). Conclusion Information available to clinicians soon after completion of childhood cancer therapy can predict individual risk for subsequent ischemic heart disease and stroke with reasonable accuracy and discrimination through age 50 years. These models provide a framework on which to base future screening strategies and interventions.

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., (© 2017 American Cancer Society.)

Context: Long-term follow-up data on premature ovarian insufficiency (POI) in childhood cancer survivors are limited., Objective: To describe the prevalence of POI, its risk factors, and associated long-term adverse health outcomes., Design: Cross-sectional., Setting: The St. Jude Lifetime Cohort Study, an established cohort in a tertiary care center., Patients: Nine hundred twenty-one participants (median age, 31.7 years) were evaluated at a median of 24.0 years after cancer diagnosis., Main Outcome Measure: POI was defined by persistent amenorrhea combined with a follicle-stimulating hormone level >30 IU/L before age 40. Multivariable Cox regression was used to study associations between demographic or treatment-related risk factors and POI. Multivariable logistic regression was used to study associations between POI and markers for cardiovascular disease, bone mineral density (BMD), and frailty. Exposure to alkylating agents was quantified using the validated cyclophosphamide equivalent dose (CED)., Results: The prevalence of POI was 10.9%. Independent risk factors for POI included ovarian radiotherapy at any dose and CED ≥8000 mg/m2. Patients with a body mass index ≥30 kg/m2 at the time of the St. Jude Lifetime Cohort assessment were less likely to have a diagnosis of POI. Low BMD and frailty were independently associated with POI., Conclusion: High-dose alkylating agents and ovarian radiotherapy at any dose are associated with POI. Patients at the highest risk should be offered fertility preservation whenever feasible. POI contributes to poor general health outcomes in childhood cancer survivors; further studies are needed to investigate the role of sex hormone replacement in improving such outcomes., (Copyright © 2017 Endocrine Society)

Background: Electrocardiography (ECG), predictive of adverse outcomes in the general population, has not been studied in cancer survivors. We evaluated the prevalence of ECG abnormalities and associations with mortality among childhood cancer survivors., Methods: Major and minor abnormalities were coded per the Minnesota Classification system for participants in the St Jude Lifetime Cohort Study (n = 2,715) and community controls (n = 268). Odds ratios (ORs) and 95% CIs were calculated using multivariable logistic regression; and hazard ratios, using Cox proportional hazards regression., Results: Survivors were a median age of 31.3 (range 18.4-63.8) years at evaluation and 7.4 (range 0-24.8) years at diagnosis. Prior therapies included cardiac-directed radiation (29.5%), anthracycline (57.9%), and alkylating (60%) chemotherapies. The prevalence of minor ECG abnormalities was similar among survivors and controls (65.2% vs 67.5%, P = .6). Major ECG abnormalities were identified in 10.7% of survivors and 4.9% of controls (P < .001). Among survivors, the most common major abnormalities were isolated ST/T wave abnormalities (7.2%), evidence of myocardial infarction (3.7%), and left ventricular hypertrophy with strain pattern (2.8%). Anthracyclines ≥300 mg/m 2 (OR 1.7 95% CI 1.1-2.5) and cardiac radiation (OR 2.1 95% CI 1.5-2.9 [1-1,999 cGy], 2.6 95% CI 1.6-3.9 [2,000-2,999 cGy], 10.5 95% CI 6.5-16.9 [≥3,000 cGy]) were associated with major abnormalities. Thirteen participants had a cardiac-related death. Major abnormalities were predictive of all-cause mortality (hazard ratio 4.0 95% CI 2.1-7.8)., Conclusions: Major ECG abnormalities are common among childhood cancer survivors, associated with increasing doses of anthracyclines and cardiac radiation, and predictive of both cardiac and all-cause mortality., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Survivors of childhood non-Hodgkin lymphoma (NHL) are at increased risk for chronic health conditions. The objective of this study was to characterize health conditions, neurocognitive function, and physical performance among a clinically evaluated cohort of 200 childhood NHL survivors., Method: Chronic health and neurocognitive conditions were graded as per a modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and impaired physical function defined as performance < 10th percentile of normative data. Multivariable regression was used to investigate associations between sociodemographic characteristics, therapeutic exposures, and outcomes., Results: Survivors were a median age of 10 years (range 1-19) at diagnosis and 34 years (range 20-58) at evaluation. Eighty-eight (44%) received radiation, 46 (23%) cranial radiation, and 69 (35%) high-dose methotrexate. Most prevalent CTCAE Grades 3-4 (severe life-threatening) conditions were obesity (35%), hypertension (9%), and impairment of executive function (13%), attention (9%), and memory (4%). Many had impaired strength (48%), flexibility (39%), muscular endurance (36%), and mobility (36%). Demographic and treatment-related factors were associated with the development of individual chronic diseases and functional deficits., Conclusions: Clinical evaluation identified a high prevalence of chronic health conditions, neurocognitive deficits, and performance limitations in childhood NHL survivors., (© 2016 Wiley Periodicals, Inc.)

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., (© 2016 American Cancer Society.)

Research has shown that self-esteem and hopefulness are positively related among female childhood cancer survivors (CCS) and contribute to their health-related quality of life (HRQOL). HRQOL remains a significant outcome of treatment for CCS. This study examined the relationships among self-esteem, hopefulness, and HRQOL in young adult female CCS to inform the development of evidence-based practice guidelines for pediatric oncology nursing practice. An online survey was conducted with a sample of young adult female CCS from 58 treatment centers across the United States at 4 time points: at baseline and at 6 weeks, 3 months, and 6 months after initial measurement time. The relationships between self-esteem, hopefulness, and HRQOL were statistically significant (Time 1, P = .05; Times 2, 3, and 4, P = .01) across all measurement times. These findings identify hopefulness and self-esteem as determinants of HRQOL and suggest that caring practices among pediatric oncology nurses that support psychosocial adjustment through promoting self-esteem and hopefulness have the potential to support HRQOL among young adult female CCS. These outcomes support the development of evidence-based practice guidelines to influence HRQOL outcomes among these survivors.

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The effect of temporal changes in cancer therapy on health status among childhood cancer survivors has not been evaluated., Objective: To compare proportions of self-reported adverse health status outcomes among childhood cancer survivors across 3 decades., Design: Cross-sectional. (ClinicalTrials.gov: NCT01120353)., Setting: 27 North American institutions., Participants: 14 566 adults, who survived for 5 or more years after initial diagnosis (median age, 27 years; range, 18 to 48 years), treated from 1970 to 1999., Measurements: Patient report of poor general or mental health, functional impairment, activity limitation, or cancer-related anxiety or pain was evaluated as a function of treatment decade, cancer treatment exposure, chronic health conditions, demographic characteristics, and health habits., Results: Despite reductions in late mortality and the proportions of survivors with severe, disabling, or life-threatening chronic health conditions (33.4% among those treated from 1970 to 1979 and 21.0% among those treated from 1990 to 1999), those reporting adverse health status did not decrease by treatment decade. Compared with survivors diagnosed in 1970 to 1979, those diagnosed in 1990 to 1999 were more likely to report poor general health (11.2% vs. 13.7%; P < 0.001) and cancer-related anxiety (13.3% vs. 15.0%; P < 0.001). From 1970 to 1979 and 1990 to 1999, the proportions of survivors reporting adverse outcomes were higher (P < 0.001) among those with leukemia (poor general health, 9.5% and 13.9%) and osteosarcoma (pain, 23.9% and 36.6%). Temporal changes in treatment exposures were not associated with changes in the proportions of survivors reporting adverse health status. Smoking, not meeting physical activity guidelines, and being either underweight or obese were associated with poor health status., Limitation: Considerable improvement in survival among children diagnosed with cancer in the 1990s compared with those diagnosed in the 1970s makes it difficult to definitively determine the effect of risk factors on later self-reported health status without considering their effect on mortality., Conclusion: Because survival rates after a diagnosis of childhood cancer have improved substantially over the past 30 years, the population of survivors now includes those who would have died in earlier decades. Self-reported health status among survivors has not improved despite evolution of treatment designed to reduce toxicities., Primary Funding Source: The National Cancer Institute., Competing Interests: The authors declare no conflicts of interest.

Purpose/objectives: To document the per survivor and per additional survivor screening costs of a mailed survivorship care plan (SCP) with advanced practice nurse (APN) telephone counseling (SCP+C) or without APN telephone counseling (SCP).
., Design: Randomized, longitudinal clinical trial.
., Setting: St. Jude Children's Research Hospital in Memphis, Tennessee.
., Sample: 411 at-risk pediatric cancer survivors (aged 26-59 years), stratified by age (younger than 30 years versus 30 years or older), recommended screening frequency (every one, two, or five years), gender, and cancer diagnosis (hematologic versus solid tumor).
., Methods: Clinical and resource data costs were derived from trial data and external estimates.
., Main Research Variables: The cost-effectiveness of left ventricular systolic function screening per survivor and per each additional survivor screened.
., Findings: The per-survivor costs of SCP (n = 206) and SCP+C (n = 205) were $74.91 and $224.69, respectively. The estimated costs of SCP and SCP+C per additional survivor screened for two years disseminated in a medium-sized clinic (n = 101 survivors annually) were $345.41 and $293.85, respectively.
., Conclusions: Adding APN counseling to a printed SCP may help preserve cardiac health at little or no cost per additional survivor screened.
., Implications for Nursing: APN counseling is cost-effective and superior to the standard of care in supporting at-risk survivors' cardiac screening participation.

Purpose: Female survivors of childhood, adolescent, and young adult (CAYA) cancer who were treated with alkylating agents and/or radiation, with potential exposure of the ovaries, have an increased risk of premature ovarian insufficiency (POI). Clinical practice guidelines can facilitate these survivors' access to optimal treatment of late effects that may improve health and quality of survival; however, surveillance recommendations vary among the existing long-term follow-up guidelines, which impedes the implementation of screening., Patients and Methods: The present guideline was developed by using an evidence-based approach and summarizes harmonized POI surveillance recommendations for female survivors of CAYA cancer who were diagnosed at age < 25 years. The recommendations were formulated by an international multidisciplinary panel and graded according to the strength of the evidence and the potential benefit gained from early detection and intervention. The harmonized POI surveillance recommendations were developed by using a transparent process and are intended to facilitate care for survivors of CAYA cancer., Results and Conclusion: The harmonized set of POI surveillance recommendations is intended to be scientifically rigorous, to positively influence health outcomes, and to facilitate the care for female survivors of CAYA cancer., (© 2016 by American Society of Clinical Oncology.)

Background: The magnitude of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is not known. Using medically ascertained data, we applied the cumulative burden metric to compare chronic cardiovascular health conditions in survivors of Hodgkin's lymphoma and general population controls., Methods: For this study, participant data were obtained from two ongoing cohort studies at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE) and the St Jude Long-term Follow-up Study (SJLTFU). SJLIFE is a cohort study initiated on April 27, 2007, to enable longitudinal clinical evaluation of health outcomes of survivors of childhood cancer treated or followed at St Jude Children's Research Hospital, and SJLTFU is an administrative system-based study initiated in 2000 to collect outcome and late toxicity data for all patients treated at the hospital for childhood cancer. The patient cohort for our study was defined as patients treated at St Jude Children's Research Hospital who reached 18 years of age and were at least 10 years post-diagnosis of pathologically confirmed primary Hodgkin's lymphoma. Outcomes in the Hodgkin's lymphoma survivors were compared with a sample of SJLIFE community control participants, aged 18 years or older at the time of assessment, frequency-matched based on strata defined by 5-year age blocks within each sex, who were selected irrespective of previous medical history. All SJLIFE participants underwent assessment for 22 chronic cardiovascular health conditions. Direct assessments, combined with retrospective clinical reviews, were used to assign severity to conditions using a modified Common Terminology Criteria of Adverse Events (CTCAE) version 4.03 grading schema. Occurrences and CTCAE grades of the conditions for eligible non-SJLIFE participants were accounted for by multiple imputation. The mean cumulative count (treating death as a competing risk) was used to estimate cumulative burden., Findings: Of 670 survivors treated at St Jude Children's Research Hospital, who survived 10 years or longer and reached age 18 years, 348 were clinically assessed in the St Jude Lifetime Cohort Study (SJLIFE); 322 eligible participants did not participate in SJLIFE. Age and sex frequency-matched SJLIFE community controls (n=272) were used for comparison. At age 50 years, the cumulative incidence of survivors experiencing at least one grade 3-5 cardiovascular condition was 45·5% (95% CI 36·6-54·3), compared with 15·7% (7·0-24·4) in community controls. The survivor cohort at age 50 experienced a cumulative burden of 430·6 (95% CI 380·7-480·6) grade 1-5 and 100·8 (77·3-124·3) grade 3-5 cardiovascular conditions per 100 survivors; these numbers were appreciably higher than those in the control cohort (227·4 [192·7-267·5] grade 1-5 conditions and 17·0 [8·4-27·5] grade 3-5 conditions per 100 individuals). Myocardial infarction and structural heart defects were the major contributors to the excess grade 3-5 cumulative burden in survivors. High cardiac radiation dose (≥35 Gy) was associated with an increased proportion of grade 3-5 cardiovascular burden, whereas increased anthracyline dose was not., Interpretation: The true effect of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is reflected in the cumulative burden. Survivors aged 50 years will experience more than two times the number of chronic cardiovascular health conditions and nearly five times the number of more severe (grade 3-5) cardiovascular conditions compared with community controls and, on average, have one severe, life-threatening, or fatal cardiovascular condition. The cumulative burden metric provides a more comprehensive approach for assessing overall morbidity compared with currently used cumulative incidence based analytic methodologies, and will assist clinical researchers when designing future trials and refining general practice screening guidelines., Funding: US National Cancer Institute, St Baldrick's Foundation, and American Lebanese Syrian Associated Charities., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., Competing Interests: No conflicts of interest to declare., (© 2016 American Cancer Society.)

Purpose: This study describes the prevalence and predisposing factors for potentially modifiable unmet emotional, care/support, and information needs among adult survivors of childhood malignancies., Methods: A randomly selected/stratified sample of participants in the Childhood Cancer Survivor Study (CCSS) responded to the CCSS-Needs Assessment Questionnaire (CCSS-NAQ) (n = 1189; mean [SD] current age, 39.7 [7.7], range = 26-61 years; 60.9 % women; mean [SD] years since diagnosis, 31.6 [4.7]). Survivors self-reported demographic information, health concerns, and needs; diagnosis/treatment data were obtained from medical records. Adjusted proportional risk ratios (prevalence ratios, PRs) were used to evaluate 77 separate needs., Results: Fifty-four percent of survivors reported unmet psycho-emotional, 41 % coping, and 35 % care/support needs; 51, 35, and 33 %, respectively, reported unmet information needs related to cancer/treatment, the health care system, and surveillance. Female sex and annual income <$60K were associated with multiple needs; fewer needs were linked to diagnosis/years since/or age at diagnosis. Having moderate/extreme cancer-related anxiety/fear was associated with all needs, including a >6-fold increased prevalence for help dealing with "worry" (PR = 6.06; 95 % confidence interval [CI], 3.79-9.69) and anxiety (PR = 6.10; 95 % CI, 3.82-9.72) and a >5-fold increased prevalence for "needing to move on with life" (PR = 5.56; 95 % CI, 3.34-9.25) and dealing with "uncertainty about the future" (PR = 5.50; 95 % CI, 3.44-8.77). Radiation exposure and perceived health status were related to 42 and 29 needs, respectively., Conclusions: Demographic factors, disease/treatment characteristics, and intrapersonal factors can be used to profile survivors' unmet emotional, care/support, and information needs., Implications for Cancer Survivors: These data can be used to enhance provider-survivor communication, identify at-risk subsamples, and appraise core intervention content.

Purpose: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for low bone mineral density (BMD) and frail health, outcomes potentially modifiable by altering health behaviors and/or treating endocrine abnormalities. We evaluated associations between lifestyle and hormonal deficits with risk of low BMD and frailty among survivors of ALL., Patients and Methods: Participants included 862 survivors of ALL (median age, 31.3 years [range, 18.4 to 59.7 years]) enrolled in the St Jude Lifetime Cohort study. Bone density was measured using quantitative computed tomography of L1 through L2 vertebrae; low BMD was defined as an age- and sex-standardized z score < -1. The presence of frailty or prefrailty was defined as having at least two of the following: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Hormonal deficiencies were determined according to medical history, medications, and laboratory findings (insulin-like growth factor 1, follicle-stimulating hormone, luteinizing hormone, and testosterone levels). Logistic regression was used to examine associations between lifestyle (smoking, alcohol consumption, and activity levels) and deficiencies in growth hormone (GHD) and/or sex steroids with low BMD and frailty., Results: Thirty percent of survivors met criteria for low BMD, and 18.6% for frailty/prefrailty. After adjusting for body mass index, low BMD was associated with GHD (odds ratio [OR], 1.59; 95% CI, 1.02 to 2.13) and current smoking (OR, 1.71; 95% CI, 1.02 to 2.85) among men; and GHD (OR, 2.18; 95% CI, 1.26 to 3.78) and moderate alcohol consumption (OR, 2.09; 95% CI, 1.14 to 3.83) among women. After adjusting for current age, the odds of frailty/prefrailty were increased among men with GHD (OR, 2.97; 95% CI, 1.56 to 5.67) and those who smoked (OR, 3.26; 95% CI, 1.65 to 6.43); there were no significant associations among women., Conclusion: The findings suggest that survivors of ALL should receive counseling regarding lifestyle and undergo screening for hormonal deficits to minimize the risk of low BMD and frailty., (© 2016 by American Society of Clinical Oncology.)

Purpose: Human papillomavirus (HPV) is a sexually transmitted infection and the cause of cervical and other cancers. Vaccination is available to protect against genital HPV and is recommended for individuals aged 9-26 years. This study aimed to estimate the prevalence of HPV vaccination among childhood cancer survivors and to identify factors associated with vaccine outcomes., Methods: Young adult females with (n = 114; M age = 21.18 years, SD = 2.48) and without (n = 98; M age = 20.65 years, SD = 2.29) a childhood cancer history completed surveys querying HPV vaccination initiation/completion, as well as sociodemographic, medical, and health belief factors. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for vaccine outcomes., Results: Among survivors, 38.6 % (44/114) and 26.3 % (30/114) initiated or completed vaccination compared to 44.9 % (44/98) and 28.6 % (28/98) among controls, respectively. In the combined survivor/control group, physician recommendation (OR = 11.24, 95 % CI 3.15-40.14) and familial HPV communication (OR = 7.28, 95 % CI 1.89-28.05) associated with vaccine initiation. Perceptions of vaccine benefit associated with vaccine completion (OR = 10.55, 95 % CI 1.59-69.92), whereas perceptions of HPV-related severity associated with non-completion (OR = 0.14, 95 % CI 0.03-0.71)., Conclusion: Despite their increased risk for HPV-related complication, a minority of childhood cancer survivors have initiated or completed HPV vaccination. Modifiable factors associated with vaccine outcomes were identified., Implications for Cancer Survivors: HPV vaccination is a useful tool for cancer prevention in survivorship, and interventions to increase vaccine uptake are warranted.

Health utility, a summary measure of quality of life, has not been previously used to compare outcomes among childhood cancer survivors and individuals without a cancer history. We estimated health utility (0, death; 1, perfect health) using the Short Form-6D (SF-6D) in survivors (n = 7105) and siblings of survivors (n = 372) (using the Childhood Cancer Survivor Study cohort) and the general population (n = 12 803) (using the Medical Expenditures Panel Survey). Survivors had statistically significantly lower SF-6D scores than the general population (mean = 0.769, 95% confidence interval [CI] = 0.766 to 0.771, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively, ITALIC! P< .001, two-sided). Young adult survivors (age 18-29 years) reported scores comparable with general population estimates for people age 40 to 49 years. Among survivors, SF-6D scores were largely determined by number and severity of chronic conditions. No clinically meaningful differences were identified between siblings and the general population (mean = 0.793, 95% CI = 0.782 to 0.805, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively). This analysis illustrates the importance of chronic conditions on long-term survivor quality of life and provides encouraging results on sibling well-being. Preference-based utilities are informative tools for outcomes research in cancer survivors., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess the prevalence and severity of neurocognitive impairment in adult survivors of pediatric CNS tumors and to examine associated treatment exposures., Patients and Methods: Participants included 224 survivors of CNS tumors who were treated at St Jude Children's Research Hospital (current median age [range], 26 years [19 to 53 years]; time from diagnosis, 18 years [11 to 42 years]) and completed neurocognitive testing. Information on cranial radiation therapy (CRT) doses and parameters of delivery were abstracted from medical records. The prevalence of severe impairment (ie, at least two standard deviations below normative mean) was compared across radiation treatment groups (no CRT, focal irradiation, craniospinal irradiation) using the χ(2) test. Log-binomial models were used to estimate risk ratios (RRs) and corresponding 95% CIs for severe impairment., Results: In multivariable models, craniospinal irradiation was associated with a 1.5- to threefold increased risk of severe impairment compared with no CRT (eg, intelligence: RR = 2.70; 95% CI, 1.37 to 5.34; memory: RR = 2.93; 95% CI, 1.69 to 5.08; executive function: RR = 1.74; 95% CI, 1.24 to 2.45). Seizures were associated with impaired academic performance (RR = 1.48; 95% CI, 1.02 to 2.14), attention (RR = 1.54; 95% CI, 1.12 to 2.13), and memory (RR = 1.44; 95% CI, 1.04 to 1.99). Hydrocephalus with shunt placement was associated with impaired intelligence (RR = 1.78; 95% CI, 1.12 to 2.82) and memory (RR = 1.42; 95% CI, 1.03 to 1.95). Differential follow-up time contributed to variability in prevalence estimates between survivors treated with older nonconformal and those treated with more contemporary conformal radiation therapy methods. Neurocognitive impairment was significantly associated with lower educational attainment, unemployment, and nonindependent living., Conclusion: Survivors of pediatric CNS tumors are at risk of severe neurocognitive impairment in adulthood. The prevalence of severe impairment is greater than expected in the general population, even in the absence of CRT, and is associated with disrupted attainment of adult social milestones., (© 2016 by American Society of Clinical Oncology.)

Background: Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects., Methods: We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals., Results: Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor., Conclusions: The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer. (Funded by the National Cancer Institute and the American Lebanese-Syrian Associated Charities.).

Purpose: Current information regarding pregnancy-associated cardiomyopathy among women treated for childhood cancer is insufficient to appropriately guide counseling and patient management. This study aims to characterize its prevalence within a large cohort of females exposed to cardiotoxic therapy., Methods: This is a retrospective cohort study of female cancer survivors treated at St. Jude Children's Research Hospital between 1963 and 2006, at least 5 years from diagnosis, ≥13 years old at last follow-up, and with at least one successful pregnancy. Pregnancy-associated cardiomyopathy was defined as shortening fraction <28 % or ejection fraction <50 % or treatment for cardiomyopathy during or up to 5 months after completion of pregnancy., Results: Among the 847 female cancer survivors with 1554 completed pregnancies, only 3 (0.3 %) developed pregnancy-associated cardiomyopathy and 40 developed non-pregnancy-associated cardiomyopathy either 5 months postpartum (n = 14) or prior to pregnancy (n = 26). Among those with cardiomyopathy prior to pregnancy (n = 26), cardiac function deteriorated during pregnancy in eight patients (three patients with normalization of cardiac function prior to pregnancy, three with persistently abnormal cardiac function, and two for whom resolution of cardiomyopathy was unknown prior to pregnancy). Patients that developed cardiomyopathy received a higher median dose of anthracyclines compared to those that did not (321 versus 164 mg/m(2); p < 0.01)., Conclusions: Pregnancy-associated cardiomyopathy in childhood cancer survivors is rare., Implications for Cancer Survivors: Most female childhood cancer survivors will have no cardiac complications during or after childbirth; however, those with a history of cardiotoxic therapies should be followed carefully during pregnancy, particularly those with a history of anthracycline exposures and if they had documented previous or current subclinical or symptomatic cardiomyopathy.

Importance: This study provides the first objective data documenting neurocognitive impairment in long-term survivors of childhood osteosarcoma., Objective: To examine neurocognitive, neurobehavioral, emotional, and quality-of-life outcomes in long-term survivors of childhood osteosarcoma., Design, Setting, and Participants: Cross-sectional cohort study at an academic research hospital, with prospective treatment and chronic health predictors. Outcome data were collected from June 2008 to August 2014. Data analysis was completed in April 2015. Survivors of osteosarcoma recruited from the St Jude Lifetime Cohort Study were compared with community controls., Main Outcomes and Measures: Neurocognitive function, neurobehavioral symptoms, emotional distress, and quality of life. Outcomes were examined in relation to pharmacokinetic indices of methotrexate exposure and current chronic health conditions, which were assessed through medical examination and coded according to Common Terminology Criteria for Adverse Events, Version 4.03., Results: Eighty survivors of osteosarcoma (mean [SD] age, 38.9 [7.6] years; time since diagnosis, 24.7 [6.6] years; 42% female) were compared with 39 community controls (age, 39.0 [11.7] years; 56% female). Survivors demonstrated lower mean scores in reading skills (-0.21 [95% CI, -0.32 to -0.10] vs 0.05 [95% CI, -0.13 to 0.23]; P = .01), attention (-0.78 [95% CI, -1.32 to -0.24] vs 0.24 [95% CI, -0.07 to 0.55]; P = .002), memory (-0.24 [95% CI, -0.48 to 0] vs 0.27 [95% CI, -0.08 to 0.62]; P = .01), and processing speed (-0.15 [95% CI, -0.35 to 0.05] vs 0.74 [95% CI, 0.44 to 1.03]; P < .001). Results of pharmacokinetic analysis showed that high-dose methotrexate maximum plasma concentration (estimate = 0; P = .48), median clearance (estimate = -0.11; P = .76), and median/cumulative exposure (estimate = 0; P = .45) were not associated with neurocognitive outcomes. Any grade 3 or 4 Common Terminology Criteria for Adverse Events cardiac, pulmonary, or endocrine condition was associated with poorer memory (t = 2.93; P = .006) and slower processing speed (t = 3.03; P = .002). Survivor-reported poor general health was associated with decreased sustained attention (estimate = 0.24; P = .05) and processing speed (estimate = 0.34; P = .005)., Conclusions and Relevance: Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. Prospective longitudinal studies are needed to identify onset and progression of impairment to inform optimal interventions.

Background: Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data., Objective: To systematically assess cardiac outcomes among survivors of childhood cancer., Design: Cross-sectional study., Setting: St. Jude Children's Research Hospital., Patients: 1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier., Measurements: Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test., Results: One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in 1.4%). Nearly all survivors were asymptomatic. The prevalence of cardiac conditions increased with age at evaluation, ranging from 3% to 24% among survivors aged 30 to 39 years to 10% to 37% among those aged 40 years or older. In multivariable analysis, survivors exposed to anthracycline doses of 250 mg/m2 or more had greater odds of cardiomyopathy (odds ratio, 2.7 [95% CI, 1.1 to 6.9]) than those who were not exposed. Survivors exposed to heart radiation also had increased odds of cardiomyopathy (odds ratio, 1.9 [CI, 1.1 to 3.7]) compared with those who were not exposed. Radiation exposure greater than 1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings., Limitations: Sixty-one percent of survivors exposed to anthracycline chemotherapy or cardiac-directed radiation participated. A comparison group and longitudinal assessments were not available., Conclusion: Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer., Primary Funding Source: National Cancer Institute, American Lebanese Syrian Associated Charities.

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., (© 2015 American Cancer Society.)

Purpose: Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin has not been rigorously evaluated among survivors of childhood cancer. These risks, which are based on hematologic toxicity, are currently assumed to be approximately equivalent., Patients and Methods: Data from 15,815 survivors of childhood cancer who survived at least 5 years were used. Survivors were from the Emma Children's Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n = 364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40 years for doses of daunorubicin and doxorubicin (per 100-mg/m(2) increments) was estimated by using Cox regression adjusted for sex, age at diagnosis, treatment with other anthracycline agents and chest radiation, and cohort membership., Results: In total, 5,144 (32.5%) patients received doxorubicin as part of their cancer treatment, whereas 2,243 (14.7%) received daunorubicin. On the basis of 271 occurrences of HF during a median follow-up time after cohort entry of 17.3 years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years was 3.2% (95% CI, 2.8% to 3.7%). The average ratio of HRs for daunorubicin to doxorubicin was 0.45 (95% CI, 0.23 to 0.73). A similar ratio was obtained by using a linear dose-response model, which yielded an HR of 0.49 (95% CI, 0.28 to 0.70)., Conclusion: Compared with doxorubicin, daunorubicin was less cardiotoxic among survivors of childhood cancer than most current guidelines suggest. This may have implications for follow-up guidelines. The feasibility of substitution of doxorubicin with daunorubicin in childhood cancer treatment protocols to reduce cardiotoxicity should be additionally investigated., (© 2015 by American Society of Clinical Oncology.)

Background: Women with a history of chest radiotherapy have an increased risk of breast cancer; however, many do not undergo annual recommended screening mammography. We sought to characterize the relationship between mammography and potentially modifiable factors, with the goal of identifying targets for intervention to improve utilization., Methods: Of 625 female participants sampled from the Childhood Cancer Survivor Study, who were treated with chest radiotherapy, 551 responded to a survey about breast cancer screening practices. We used multivariate Poisson regression to assess several lifestyle and emotional factors, health care practices, and perceived breast cancer risk, in relation to reporting a screening mammogram within the last two years., Results: Women who had a Papanicolaou test [prevalence ratio (PR): 1.77; 95% confidence interval (CI) 1.26-2.49], and who perceived their breast cancer risk as higher than the average woman were more likely to have had a mammogram (PR, 1.26; 95% CI, 1.09-1.46). We detected an attenuated effect of echocardiogram screening [PR, 0.70; 95% CI (0.52-0.95)] on having a mammogram among older women compared with younger women. Smoking, obesity, physical activity, coping, and symptoms of depression and somatization were not associated with mammographic screening., Conclusion: Our findings suggest that compliance with routine and risk-based screening can be an important indicator of mammography in childhood cancer survivors. In addition, there is a need to ensure women understand their increased breast cancer risk, as a means to encouraging them to follow breast surveillance guidelines., Impact: Screening encounters could be used to promote mammography compliance in this population., (©2015 American Association for Cancer Research.)

Background: Pediatric cancer patients who received blood transfusions were potentially exposed to hepatitis C virus (HCV) prior to second-generation HCV screening of blood products in 1992. Limited evidence is available about long-term incident cirrhosis in this population., Objectives: We aimed to estimate the overall and sex-specific incidence of cirrhosis among HCV-seropositive survivors of pediatric cancer., Study Design: We identified 113HCV-seropositive pediatric cancer patients treated at St. Jude Children's Research Hospital between 1962 and 1997, who survived ≥5 years post-diagnosis, and were followed through 2014. Our outcome was cirrhosis determined by liver biopsy or diagnostic imaging. We used a competing-risk framework to estimate the overall and sex-specific cumulative incidence and 95% confidence limits (CL) of cirrhosis at 10-year follow-up intervals., Results: The median duration of follow-up was 30 years (interquartile range=28-36) post-cancer diagnosis. Cumulative incidence of cirrhosis increased at each 10-year interval from 0% after 10 years to 13% after 40 years (Ptrend<0.001). The median age at diagnosis of cirrhosis was 30 years (interquartile range=24-38). We observed a linear trend in incidence for males (Ptrend<0.001), with a cumulative incidence of 18% (95% CL: 6.1%, 34%) after 40 years. The cumulative incidence for females was 6.5% (95% CL: 0.42%, 26%) after 40 years, but we did not observe a linear trend (Ptrend=0.99)., Conclusion: Our results suggest that the incidence of cirrhosis is similar between HCV-seropositive pediatric cancer survivors and the general population given similar duration of follow-up, but survivors may be diagnosed with cirrhosis at an earlier age., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Treatment for childhood genitourinary tumors such as Wilms tumor, rhabdomyosarcoma, and germ cell tumors has progressed to the point that cure can be expected in many cases. However, survivorship is often coupled with a variety of late effects, of which subsequent neoplasms may be the most concerning if not the most life threatening. Here, we review current literature to assess and report issues relating to subsequent neoplasms in patients with a history of childhood genitourinary tumors, including causative factors, overall risks, the most prevalent subsequent neoplasms, and current recommendations for surveillance and screening., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Among those 9-26 years of age, vaccination can prevent specific types of genital human papillomavirus (HPV), the most common sexually transmitted infection and cause of cervical and other cancers. The objective of this study was to estimate the prevalence of and factors associated with HPV vaccine initiation and completion among females surviving childhood cancer., Procedure: One-hundred fourteen young adults and 230 mothers with daughters surviving childhood cancer completed surveys querying HPV vaccination history along with medical and sociodemographic factors potentially associated with vaccination outcomes. Vaccination rate differences by age necessitated analysis of outcomes by age group: 9-13 years (preadolescents), 14-17 years (adolescents), and 18-26 years (young adults). Multivariable logistic regression was utilized to identify factors associated with HPV vaccination outcomes., Results: Overall, 34.6% (119/344) of survivors initiated and 20.9% (72/344) completed HPV vaccination. Preadolescents were least likely to have initiated vaccination (P < 0.001). Physician recommendation was associated with initiation across age groups (OR = 6.81-11.96, Ps < 0.001-.01), whereas older age at diagnosis (≥12 years of age) was associated with lower vaccination initiation among young adults only (OR = 0.28; 95%CI, 0.10-0.76, P = 0.012). Physician recommendation (OR = 7.54; 95%CI, 1.19-47.69, P = 0.032; adolescent group) and greater treatment intensity (OR = 5.25; 95%CI, 1.00-27.61, P = 0.050; young adult group) were associated with vaccine completion, whereas being non-White was associated with decreased vaccination completion (OR = 0.17; 95%CI, 0.05-0.66, P = 0.010; adolescent group)., Conclusions: A minority of youths surviving childhood cancer have initiated or completed HPV vaccination. Strategies to increase vaccination among survivors are discussed., (© 2015 Wiley Periodicals, Inc.)

Objectives: Characterize longitudinal changes in the use of medical care in adult survivors of childhood cancer., Data Sources: The Childhood Cancer Survivor Study, a retrospective cohort study of 5+ year survivors of childhood cancer., Study Design: Medical care was assessed at entry into the cohort (baseline) and at most recent questionnaire completion. Care at each time point was classified as no care, general care, or survivor-focused care., Data Collection: There were 6,176 eligible survivors. Multivariable models evaluated risk factors for reporting survivor-focused care or general medical care at baseline and no care at follow-up; and survivor-focused care at baseline and general care at follow-up., Principal Findings: Males (RR, 2.3; 95 percent CI 1.8-2.9), earning <$20,000/year (RR, 1.6; 95 percent CI 1.2-2.3) or ≤ high school education (RR, 2.5; 95 percent CI 1.6-3.8 and RR 2.0; 95 percent CI 1.5-2.7 for

Background: Treatment-related cardiac death is the primary, noncancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction may identify a high-risk subset of survivors for early intervention., Objectives: This study sought to determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies., Methods: Echocardiographic assessment included 3-dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain, and diastolic function, graded per American Society of Echocardiography guidelines in 1,820 adult (median age 31 years; range: 18 to 65 years) survivors of childhood cancer (median time from diagnosis 23 years; range: 10 to 48 years) exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306), or both (n = 464)., Results: Only 5.8% of survivors had abnormal 3D LVEFs (<50%). However, 32.1% of survivors with normal 3D LVEFs had evidence of cardiac dysfunction by global longitudinal strain (28%), American Society of Echocardiography-graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed radiotherapy at 1 to 19.9 Gy (rate ratio [RR]: 1.38; 95% confidence interval [CI]: 1.14 to 1.66), 20 to 29.9 Gy (RR: 1.65; 95% CI: 1.31 to 2.08), and >30 Gy (RR: 2.39; 95% CI: 1.79 to 3.18) and anthracycline dose > 300 mg/m(2) (RR: 1.72; 95% CI: 1.31 to 2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (RR: 1.94; 95% CI: 1.66 to 2.28) and abnormal diastolic function (RR: 1.68; 95% CI: 1.39 to 2.03) but not abnormal 3D LVEFs (RR: 1.07; 95% CI: 0.74 to 1.53)., Conclusions: Abnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: The purpose of this investigation was to determine the efficacy of two evidence-based tobacco quitlines in adult survivors of childhood cancer who regularly smoke cigarettes., Methods: A total of 519 adult survivors of childhood cancer were randomized to either Proactive + 4 weeks of medication (Counselor-initiated intervention, n = 260) or a Reactive + 2 weeks of medication (Participant-initiated intervention, n = 259) condition. Both conditions received telephone counseling to quit smoking as well as nicotine replacement therapy. The primary outcome was biochemically verified (i.e. cotinine) point prevalence smoking cessation at 12 months follow-up., Results: Participants randomized to the Proactive + 4 weeks of medication condition self-reported a higher rate of cessation than those survivors in the Reactive + 2 weeks of medication condition at 8 weeks (33.2% vs. 17.0%, p < .001), but cessation rates were not significantly different at 12 months (23.0% vs. 18.7%, p = .29). However, 80% of participants claiming abstinence failed biochemical verification, indicating marked falsification of self-reported smoking status. Adjusted cessation rates were less than 2% in both intervention conditions., Conclusions: Our results indicate that neither a Proactive + 4 weeks of medication or Reactive + 2 weeks of medication quitline significantly impacted long-term smoking cessation rates. Our results further indicate that self-reports of smoking status are unreliable in survivors of childhood cancer, a population in considerable need of tobacco abstinence. Rates of smoking cessation may be markedly overestimated in studies of childhood cancer survivors that rely on self-reports of tobacco abstinence, and future studies need to include biochemical verification of tobacco status in this population., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

There is limited information on body composition, energy balance, and fitness among survivors of childhood acute lymphoblastic leukemia (ALL), especially those treated without cranial radiation therapy (CRT). This analysis compares these metrics among 365 ALL survivors with a mean age of 28.6 ± 5.9 years (149 treated with and 216 without CRT) and 365 age-, sex-, and race-matched peers. We also report risk factors for outcomes among survivors treated without CRT. Male survivors not exposed to CRT had abnormal body composition when compared with peers (% body fat, 26.2 ± 8.2 vs 22.7 ± 7.1). Survivors without CRT had similar energy balance but had significantly impaired quadriceps strength (-21.9 ± 6.0 Newton-meters [Nm]/kg, 60°/s) and endurance (-11.4 ± 4.6 Nm/kg, 300°/s), exercise capacity (-2.0 ± 2.1 ml/kg per minute), low-back and hamstring flexibility (-4.7 ± 1.6 cm), and dorsiflexion range of motion (-3.1 ± 0.9°) and higher modified total neuropathy scores (+1.6 ± 1.1) than peers. Cumulative asparaginase dose ≥120,000 IU/m(2) was associated with impaired flexibility, vincristine dose ≥39 mg/m(2) with peripheral neuropathy, glucocorticoid (prednisone equivalent) dose ≥8000 mg/m(2) with hand weakness, and intrathecal methotrexate dose ≥225 mg with dorsiflexion weakness. Physical inactivity was associated with hand weakness and decreased exercise capacity. Smoking was associated with peripheral neuropathy. Elimination of CRT from ALL therapy has improved, but not eliminated, body-composition outcomes. Survivors remain at risk for impaired fitness., (© 2015 by The American Society of Hematology.)

Survivors of childhood cancer treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure. In this population, congestive heart failure is well recognised as a progressive disorder, with a variable period of asymptomatic cardiomyopathy that precedes signs and symptoms. As a result, several clinical practice guidelines have been developed independently to help with detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions. Differences between these guidelines could hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonise existing cardiomyopathy surveillance recommendations using an evidence-based approach that relied on standardised definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To create clinically useful models that incorporate readily available demographic and cancer treatment characteristics to predict individual risk of heart failure among 5-year survivors of childhood cancer., Patients and Methods: Survivors in the Childhood Cancer Survivor Study (CCSS) free of significant cardiovascular disease 5 years after cancer diagnosis (n = 13,060) were observed through age 40 years for the development of heart failure (ie, requiring medications or heart transplantation or leading to death). Siblings (n = 4,023) established the baseline population risk. An additional 3,421 survivors from Emma Children's Hospital (Amsterdam, the Netherlands), the National Wilms Tumor Study, and the St Jude Lifetime Cohort Study were used to validate the CCSS prediction models., Results: Heart failure occurred in 285 CCSS participants. Risk scores based on selected exposures (sex, age at cancer diagnosis, and anthracycline and chest radiotherapy doses) achieved an area under the curve of 0.74 and concordance statistic of 0.76 at or through age 40 years. Validation cohort estimates ranged from 0.68 to 0.82. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups, corresponding to cumulative incidences of heart failure at age 40 years of 0.5% (95% CI, 0.2% to 0.8%), 2.4% (95% CI, 1.8% to 3.0%), and 11.7% (95% CI, 8.8% to 14.5%), respectively. In comparison, siblings had a cumulative incidence of 0.3% (95% CI, 0.1% to 0.5%)., Conclusion: Using information available to clinicians soon after completion of childhood cancer therapy, individual risk for subsequent heart failure can be predicted with reasonable accuracy and discrimination. These validated models provide a framework on which to base future screening strategies and interventions., (© 2014 by American Society of Clinical Oncology.)

Purpose: To compare age-dependent changes in health status among childhood cancer survivors and a sibling cohort., Methods: Adult survivors of childhood cancer and siblings, all participants of the Childhood Cancer Survivor Study, completed three surveys assessing health status. At each of three time points, participants were classified as having poor outcomes in general health, mental health, function, or daily activities if they indicated moderate to extreme impairment. Generalized linear mixed models were used to compare survivors with siblings for each outcome as a function of age and to identify host- and treatment-related factors associated with age-dependent worsening health status., Results: Adverse health status outcomes were more frequent among survivors than siblings, with evidence of a steeper trajectory of age-dependent change among female survivors with impairment in at least one health status domain (P = .01). In adjusted models, survivors were more likely than siblings to report poor general health (prevalence ratio [PR], 2.37; 95% CI, 2.09 to 2.68), adverse mental health (PR, 1.66; 95% CI, 1.52 to 1.80), functional impairment (PR, 4.53; 95% CI, 3.91 to 5.24), activity limitations (PR, 2.38; 95% CI, 2.12 to 2.67), and an adverse health status outcome in any domain (PR, 2.10; 95% CI, 1.97 to 2.23). Cancer treatment and health behaviors influence the magnitude of differences by age groups. Chronic conditions were associated with adverse health status outcomes across organ systems., Conclusion: The prevalence of poor health status is higher among survivors than siblings, increases rapidly with age, particularly among female participants, and is related to an increasing burden of chronic health conditions., (© 2014 by American Society of Clinical Oncology.)

Cancer is the leading disease-related cause of death in adolescents and young adults (AYAs). This population faces many short- and long-term health and psychosocial consequences of cancer diagnosis and treatment, but many programs for cancer treatment, survivorship care, and psychosocial support do not focus on the specific needs of AYA cancer patients. Recognizing this health care disparity, the National Cancer Policy Forum of the Institute of Medicine convened a public workshop to examine the needs of AYA patients with cancer. Workshop participants identified many gaps and challenges in the care of AYA cancer patients and discussed potential strategies to address these needs. Suggestions included ways to improve access to care for AYAs, to deliver cancer care that better meets the medical and psychosocial needs of AYAs, to develop educational programs for providers who care for AYA cancer survivors, and to enhance the evidence base for AYAs with cancer by facilitating participation in research., (©AlphaMed Press.)

Objective: Childhood cancer survivors are at risk for neurocognitive impairment related to cancer diagnosis or treatment. This study refined and further validated the Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ; Krull et al., 2008), a scale developed to screen for impairment in long-term survivors of childhood cancer., Method: Items related to task efficiency, memory, organization, and emotional-regulation domains were examined using item response theory (IRT). Data were collected from 833 adult survivors of childhood cancer who completed self-report and direct neurocognitive testing for the St. Jude Lifetime Cohort Study. The revision process included: (a) content-validity mapping of items to domains, (b) constructing a revised CCSS-NCQ, (c) selecting items within specific domains using IRT, and (d) evaluating concordance between the revised CCSS-NCQ and direct neurocognitive assessment., Results: Using content and measurement properties, 32 items were retained (8 items in 4 domains). Items captured low to middle levels of neurocognitive concerns. The latent domain scores demonstrated poor convergent/divergent validity with the direct assessments. Adjusted ESs (ES; Cohen's d) for agreement between self-reported memory and direct memory assessment were moderate for total recall (ES = 0.66), long-term memory (ES = 0.63), and short-term memory (STM; ES = 0.55). ESs between self-rated task efficiency and direct assessment of attention were moderate for focused attention (ES = 0.70) and attention span (ES = 0.50), but small for sustained attention (ES = 0.36). Cranial radiation therapy and female gender were associated with lower self-reported neurocognitive function., Conclusion: The revised CCSS-NCQ demonstrates adequate measurement properties for assessing day-to-day neurocognitive concerns in childhood cancer survivors, and adds useful information to direct assessment., (PsycINFO Database Record (c) 2015 APA, all rights reserved.)

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., (© 2014 American Cancer Society.)

Survivors of childhood acute lymphoblastic leukaemia are at risk for neurocognitive impairment, though little information is available on its association with brain integrity, particularly for survivors treated without cranial radiation therapy. This study compares neurocognitive function and brain morphology in long-term adult survivors of childhood acute lymphoblastic leukaemia treated with chemotherapy alone (n = 36) to those treated with cranial radiation therapy (n = 39) and to healthy control subjects (n = 23). Mean (standard deviation) age at evaluation was 24.9 (3.6) years for the chemotherapy group and 26.7 (3.4) years for the cranial radiation therapy group, while time since diagnosis was 15.0 (1.7) and 23.9 (3.1) years, respectively. Brain grey and white matter volume and diffusion tensor imaging was compared between survivor groups and to 23 healthy controls with a mean (standard deviation) age of 23.1 (2.6) years. Survivors treated with chemotherapy alone had higher fractional anisotropy in fibre tracts within the left (P < 0.05), but not in the right, hemisphere when compared to controls. Survivors of acute lymphoblastic leukaemia, regardless of treatment, had a lower ratio of white matter to intracranial volume in frontal and temporal lobes (P < 0.05) compared with control subjects. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone performed worse in processing speed (P < 0.001), verbal selective reminding (P = 0.01), and academics (P < 0.05) compared to population norms and performed better than survivors treated with cranial radiation therapy on verbal selective reminding (P = 0.02), processing speed (P = 0.05) and memory span (P = 0.009). There were significant associations between neurocognitive performance and brain imaging, particularly for frontal and temporal white and grey matter volume. Survivors of acute lymphoblastic leukaemia treated with chemotherapy alone demonstrated significant long-term differences in neurocognitive function and altered neuroanatomical integrity. These results suggest substantial region-specific white matter alterations in survivors of acute lymphoblastic leukaemia possibly resulting in restricted radial diffusion due to the compaction of neuronal fibres., (© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Adult survivors of childhood brain tumors experience multiple, significant, lifelong deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors' physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggest some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population-based matched controls. Chi-square tests, t tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated that life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors' general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population., (© 2014 by Association of Pediatric Hematology/Oncology Nurses.)

Background: A high proportion of pediatric cancer patients are now surviving into adulthood, but are at increased risk for late morbidity and premature mortality related to their diagnosis and therapeutic exposures. Little is known about the potential success of recruiting adult survivors of childhood cancer into research projects that would require a risk-based health evaluation within a clinical setting., Procedures: Pediatric cancer survivors and siblings eligible for the current study were Childhood Cancer Survivor Study participants who lived within 100 miles of one of five Consortium for Pediatric Intervention Research institutions, regardless of where they were initially diagnosed and treated. A short survey was mailed to 829 survivors and 373 siblings to identify factors that predict interest, potential barriers, and motivators, to participation in research including a risk-based clinical evaluation., Results: Overall, 92% of survivors responding to the survey were very interested/interested in participating in a research study requiring a visit to a local hospital clinic. Siblings of survivors were less interested than survivors in participating in such a study, with only 78% indicating that they were very interested/interested. Potential motivators to participation included visiting their treating hospital and receiving health information. The primary barrier to participation was related to taking time off from work., Conclusions: This study demonstrates that a subgroup of survivors would be willing to return to a long-term follow-up center to participate in intervention-based research. Identified motivating factors and perceived barriers need to be considered in determining the feasibility, design and execution of future research., (© 2014 Wiley Periodicals, Inc.)

Purpose: Survivors of childhood cancer are at an increased risk of developing subsequent neoplasms. In long-term survivors of childhood malignancies treated with and without cranial radiation therapy (CRT), undergoing unenhanced magnetic resonance imaging (MRI) of the brain, we estimated detection of intracranial neoplasms., Methods: To investigate neurocognitive outcomes, 219 survivors of childhood cancer underwent unenhanced screening MRI of the brain. Of the survivors, 164 had been treated for acute lymphoblastic leukemia (ALL) (125 received CRT) and 55 for Hodgkin lymphoma (HL) (none received CRT). MRI examinations were reviewed and systematically coded by a single neuroradiologist. Demographic and treatment characteristics were compared for survivors with and without subsequent neoplasms., Results: Nineteen of the 219 survivors (8.7 %) had a total of 31 subsequent intracranial neoplasms identified by neuroimaging at a median time of 25 years (range 12-46 years) from diagnosis. All neoplasms occurred after CRT, except for a single vestibular schwannoma within the cervical radiation field in a HL survivor. The prevalence of subsequent neoplasms after CRT exposure was 14.4 % (18 of 125). By noncontrast MRI, intracranial neoplasms were most suggestive of meningiomas. Most patients presented with no specific, localizing neurological complaints. In addition to the schwannoma, six tumors were resected based on results of MRI screening, all of which were meningiomas on histologic review., Conclusion: Unenhanced brain MRI of long-term survivors of childhood cancer detected a substantial number of intracranial neoplasms. Screening for early detection of intracranial neoplasms among aging survivors of childhood cancer who received CRT should be evaluated., Implications for Cancer Survivors: The high prevalence of incidentally detected subsequent intracranial neoplasms after CRT in long-term survivors of childhood cancer and the minimal symptoms reported by those with intracranial tumors in our study indicate that brain MRI screening of long-term survivors who received CRT may be warranted. Prospective studies of such screening are needed.

Background: We aimed to identify demographic and health-related predictors of declining physical activity levels over a four-year period among participants in the Childhood Cancer Survivor Study., Methods: Analyses included 7,287 ≥5-year childhood cancer survivors and 2,107 siblings who completed multiple follow-up questionnaires. Participants were classified as active if they met the Centers for Disease Control and Prevention guidelines for physical activity. Generalized linear models were used to compare participants whose physical activity levels declined from active to inactive over the study to those who remained active. In addition, selected chronic conditions (CTCAE v4.03 Grade 3 and 4) were evaluated as risk factors in an analysis limited to survivors only., Results: The median age at last follow-up among survivors and siblings was 36 (range, 21-58) and 38 (range, 21-62) years, respectively. The rate of decline did not accelerate over time among survivors when compared with siblings. Factors that predicted declining activity included body mass index ≥30 kg/m(2) [RR = 1.32; 95% confidence interval (CI), 1.19-1.46, P < 0.01], not completing high school (RR = 1.31; 95% CI, 1.08-1.60, P < 0.01), and female sex (RR = 1.33; 95% CI, 1.22-1.44, P < 0.01). Declining physical activity levels were associated with the presence of chronic musculoskeletal conditions (P = 0.034), but not with the presence of cardiac (P = 0.10), respiratory (P = 0.92), or neurologic conditions (P = 0.21)., Conclusions: Interventions designed to maximize physical activity should target female, obese, and less educated survivors. Survivors with chronic musculoskeletal conditions should be monitored, counseled, and/or referred for physical therapy., Impact: Clinicians should be aware of low activity levels among subpopulations of childhood cancer survivors, which may heighten their risk for chronic illness., (©2014 American Association for Cancer Research.)

Purpose: The purposes of this study were to estimate the prevalence of emotional distress in a large cohort of adult survivors of childhood cancer and to evaluate the interrelationship of risk factors including cancer-related late effects., Methods: Adult survivors of childhood cancer (N = 1,863), median age of 32 years at follow-up, completed comprehensive medical evaluations. Clinically relevant emotional distress was assessed using the Brief Symptom Inventory 18 and was defined as T-scores ≥63. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression models to identify risk factors for distress. Path analysis was used to examine associations among identified risk factors., Results: Elevated global distress was reported by 15.1% of survivors. Cancer-related pain was associated with elevated distress (OR 8.72; 95% CI, 5.32-14.31). Survivors who reported moderate learning or memory problems were more likely to have elevated distress than survivors who reported no learning or memory problems (OR 3.27; 95% CI, 2.17-4.93). Path analysis implied that cancer-related pain has a direct effect on distress symptoms and an indirect effect through socioeconomic status and learning or memory problems. Similar results were observed for learning or memory problems., Conclusions: Childhood cancer-related morbidities including pain and learning or memory problems appear to be directly and indirectly associated with elevated distress symptoms decades after treatment. Understanding these associations may help inform intervention targets for survivors of childhood cancer experiencing symptoms of distress., Implications for Cancer Survivors: A subset of long-term childhood cancer survivors experience significant emotional distress. Physical and cognitive late effects may contribute to these symptoms.

Purpose: The first generation of childhood cancer survivors is now aging into their fourth and fifth decades of life, yet health risks across the aging spectrum are not well established., Methods: Analyses included 14,359 5-year survivors from the Childhood Cancer Survivor Study, who were first diagnosed when they were younger than 21 years old and who received follow-up for a median of 24.5 years after diagnosis (range, 5.0 to 39.3 years) along with 4,301 of their siblings. Among the survivors, 5,604 were at least 35 years old (range, 35 to 62 years) at last follow-up. Severe, disabling, life-threatening, and fatal health conditions more than 5 years from diagnosis were classified using the Common Terminology Criteria for Adverse Events, grades 3 to 5 (National Cancer Institute)., Results: The cumulative incidence of a severe, disabling, life-threatening, or fatal health condition was greater among survivors than siblings (53.6%; 95% CI, 51.5 to 55.6; v 19.8%; 95% CI, 17.0 to 22.7) by age 50 years. When comparing survivors with siblings, hazard ratios (HR) were significantly increased within the age group of 5 to 19 years (HR, 6.8; 95% CI, 5.5 to 8.3), age group of 20 to 34 years (HR, 3.8; 95% CI, 3.2 to 4.5), and the ≥ 35 years group (HR, 5.0; 95% CI, 4.1 to 6.1), with the HR significantly higher among those ≥ 35 years versus those 20 to 34 years old (P = .03). Among survivors who reached age 35 years without a previous grade 3 or 4 condition, 25.9% experienced a subsequent grade 3 to 5 condition within 10 years, compared with 6.0% of siblings (P < .001)., Conclusion: Elevated risk for morbidity and mortality among survivors increases further beyond the fourth decade of life, which affects the future clinical demands of this population relative to ongoing surveillance and interventions.

Purpose: Childhood cancer survivors (CCS) experience late effects that interfere with physical function. Limitations in physical function can affect CCS abilities to actively participate in daily activities. The purpose of this investigation was to evaluate the concordance between self-reported physical performance and clinically evaluated physical performance among adult CCS., Methods: CCS 18 yr or older and 10 yr or older from diagnosis who are participants in the St. Jude Lifetime cohort study responded to the physical function section of the Medical Outcome Survey Short Form (SF-36). Measured physical performance was evaluated using the Physical Performance Test and the 6-Minute Walk Test., Results: Individuals (N = 1778, 50.8% female) with a median time since diagnosis of 24.9 yr (range = 10.9-48.2) and a median age of 32.4 yr (range = 19.1-48.2) completed testing. Limitations in physical performance were self-reported by 14.1% of participants. The accuracy of self-report physical performance was 0.87 when the SF-36 was compared with the 6-Minute Walk Test or the Physical Performance Test. Reporting inaccuracies most often involved reporting a physical performance limitation. Poor accuracy was associated with previous diagnosis of a bone or CNS tumor, lymphoma, older age, and large body size., Conclusions: These results suggest that self-report, using the physical performance subscale of the SF-36, correctly identifies CCS who do not have physical performance limitations. In contrast, this same measure is less able to identify individuals who have performance limitations.