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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.)

Background: Neurocognitive impairment in survivors of childhood cancer may be associated with direct neurotoxicity, as well as indirect effects of systemic health complications. We evaluated associations among treatment exposures, chronic health conditions, and neurocognitive outcomes in adult survivors of childhood cancer., Methods: Participants included 5507 adult survivors of childhood cancer (47.1% male; mean [SD] age = 31.8 [7.6] years at evaluation; 23.1 [4.5] years postdiagnosis) in the Childhood Cancer Survivor Study who completed a self-report measure of neurocognitive function. Cardiac, pulmonary, and endocrine chronic health conditions were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Structural equation modeling was used to examine a priori hypothesized causal pathways among cancer treatment, subsequent chronic health conditions, and neurocognitive outcomes. Multivariable models were used to estimate relative risk for associations of treatments and chronic conditions on neurocognitive function. All statistical tests were two-sided., Results: One-third of survivors with a grade 2 or higher chronic condition reported impairments in task efficiency and memory. In addition to direct effects of cranial radiation, path analyses and multivariable models demonstrated direct effects of cardiopulmonary (β = 0.10, P = .002; relative risk [RR] = 1.27, 95% confidence interval [CI] = 1.12 to 1.44) and endocrine (β = 0.07, P = .04; RR = 1.14, 95% CI = 1.02 to 1.28) conditions on impaired task efficiency. We identified similar effects of cardiopulmonary condition on memory (P = .01) and emotional regulation (P = .01). Thoracic radiation was associated with impaired task efficiency (P = .01) and emotional regulation (P = .01) through endocrine morbidity., Conclusions: Non-neurotoxic exposures, such as thoracic radiation, can adversely impact survivors' neurocognitive function through chronic conditions. Management of chronic diseases may mitigate neurocognitive outcomes among aging survivors of childhood cancer.

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.

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: Over 70% of childhood cancer survivors develop late complications from therapy, many of which can be mitigated by physical activity. Survivors engage in exercise at similar or lower rates than their sedentary healthy peers. We piloted a novel home-based exercise intervention with a motivational activity tracker. We evaluated (i) feasibility, (ii) impact on activity levels and physical fitness, and (iii) barriers, preferences, and beliefs regarding physical activity., Methods: Childhood cancer survivors currently 15 years or older and not meeting the Centers for Disease Control and Prevention physical activity guidelines were enrolled and instructed to wear the Fitbit One, a 4.8 cm × 1.8 cm motivational activity tracker, daily for 6 months. Baseline and follow-up evaluations included self-report surveys, an Actigraph accelerometer for 7 days, and a VO 2 maximum test by cardiac stress test., Results: Nineteen participants were enrolled (13.4% participation rate) with a mean age of 24.3 ± 5.8 years (range 15-35). Four participants withdrew with a 79% retention rate. Participants wore the Fitbit an average of 19.0 ± 4.7 days per month during months 1-3 and 15.0 ± 7.9 days per month during months 4-6. Total weekly moderate to vigorous physical activity increased from 265.6 ± 117.0 to 301.4 ± 135.4 min and VO 2 maximum increased from 25.7 ± 7.7 to 27.2 ± 7.4 ml/kg/min. These changes were not statistically significant (P = 0.47 and 0.30, respectively). Survey responses indicated no change in barriers, preferences, and beliefs regarding physical activity., Conclusions: This pilot study of a motivational activity tracker demonstrated feasibility as measured by participant retention, receptivity, and belief of utility. Future studies with a large sample size are needed to demonstrate the efficacy and sustainability of this intervention., (© 2016 Wiley Periodicals, Inc.)

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.

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.)

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.)

By the middle of this century, racial/ethnic minority populations will collectively constitute 50% of the US population. This temporal shift in the racial/ethnic composition of the US population demands a close look at the race/ethnicity-specific burden of morbidity and premature mortality among survivors of childhood cancer. To optimize targeted long-term follow-up care, it is essential to understand whether the burden of morbidity borne by survivors of childhood cancer differs by race/ethnicity. This is challenging because the number of minority participants is often limited in current childhood cancer survivorship research, resulting in a paucity of race/ethnicity-specific recommendations and/or interventions. Although the overall childhood cancer incidence increased between 1973 and 2003, the mortality rate declined; however, these changes did not differ appreciably by race/ethnicity. The authors speculated that any racial/ethnic differences in outcome are likely to be multifactorial, and drew on data from the Childhood Cancer Survivor Study to illustrate the various contributors (socioeconomic characteristics, health behaviors, and comorbidities) that could explain any observed differences in key treatment-related complications. Finally, the authors outlined challenges in conducting race/ethnicity-specific childhood cancer survivorship research, demonstrating that there are limited absolute numbers of children who are diagnosed and survive cancer in any one racial/ethnic minority population, thereby precluding a rigorous evaluation of adverse events among specific primary cancer diagnoses and treatment exposure groups. Cancer 2016;122:2426-2439. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

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.)

Treatment-related obesity and the metabolic syndrome in adult survivors of childhood acute lymphoblastic leukemia (ALL) are risk factors for cardiovascular disease. Both conditions often begin during therapy. Preventive measures, including dietary counseling and tailored exercise, should be initiated early in the course of survivorship, with referral to specialists to optimize success. However, among adults who develop obesity or the metabolic syndrome and who do not respond to lifestyle therapy, medical intervention may be indicated to manage underlying pathology, such as growth hormone deficiency, or to mitigate risk factors of cardiovascular disease. Because no specific clinical trials have been done in this population to treat metabolic syndrome or its components, clinicians who follow adult survivors of childhood ALL should use the existing American Heart Association/National Heart Lung and Blood Institute Scientific Statement to guide their approach.

Background: The impact of impaired vision on cognitive and psychosocial outcomes among long-term survivors of childhood low-grade gliomas has not been investigated previously but could inform therapeutic decision making., Methods: Data from the Childhood Cancer Survivor Study were used to investigate psychological outcomes (measures of cognitive/emotional function) and socioeconomic outcomes (education, income, employment, marital status, and independent living) among astroglial tumor survivors grouped by 1) vision without impairment, 2) vision with impairment (including unilateral blindness, visual field deficits, and amblyopia), or 3) bilateral blindness. The effect of vision status on outcomes was examined with multivariate logistic regression with adjustments for age, sex, cranial radiation therapy, and medical comorbidities., Results: Among 1233 survivors of childhood astroglial tumors 5 or more years after their diagnosis, 277 (22.5%) had visual impairment. In a multivariate analysis, survivors with bilateral blindness were more likely to be unmarried (adjusted odds ratio (OR), 4.7; 95% confidence interval [CI], 1.5-15.0), live with a caregiver (adjusted OR, 3.1; 95% CI, 1.3-7.5), and be unemployed (adjusted OR, 2.2; 95% CI, 1.1-4.5) in comparison with those without visual impairment. Bilateral blindness had no measurable effect on cognitive or emotional outcomes, and vision with impairment was not significantly associated with any psychological or socioeconomic outcomes., Conclusions: Adult survivors of childhood astroglial tumors with bilateral blindness were more likely to live unmarried and dependently and to be unemployed. Survivors with visual impairment but some remaining vision did not differ significantly with respect to psychological function and socioeconomic status from those without visual impairment. Cancer 2016;122:730-739. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

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.

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.)

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.)

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.)

Young adult childhood cancer survivors are at an increased risk of frailty, a physiologic phenotype typically found among older adults. This phenotype is associated with new-onset chronic health conditions and mortality among both older adults and childhood cancer survivors. Mounting evidence suggests that poor fitness, muscular weakness, and cognitive decline are common among adults treated for childhood malignancies, and that risk factors for these outcomes are not limited to those treated with cranial radiation. Although the pathobiology of this phenotype is not known, early cellular senescence, sterile inflammation, and mitochondrial dysfunction in response to initial cancer or treatment-related insults are hypothesized to play a role. To the authors' knowledge, interventions to prevent or remediate frailty among childhood cancer survivors have not been tested to date. Pharmaceutical, nutraceutical, and lifestyle interventions have demonstrated some promise., (© 2014 American Cancer Society.)

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.)

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.)

Purpose: Survivors of Hodgkin lymphoma (HL) are at increased risk of treatment-related cardiovascular (CV) events; whether exercise modifies this risk is unknown., Methods: Survivors of HL (n = 1,187; median age, 31.2 years) completed a questionnaire evaluating vigorous-intensity exercise behavior. CV events were collected in follow-up questionnaires and graded according to Common Terminology Criteria for Adverse Events (version 4.03). The primary end point was incidence of any major (grade 3 to 5) CV event. Poisson regression analyses were used to estimate the association between exercise exposure (metabolic equivalent [MET] hours/week(-1)) and risk of major CV events after adjustment for clinical covariates and cancer treatment., Results: Median follow-up was 11.9 years (range, 1.7 to 14.3 years). Cumulative incidence of any CV event was 12.2% at 10 years for survivors reporting 0 MET hours/week(-1) compared with 5.2% for those reporting ≥ 9 MET hours/week(-1). In multivariable analyses, the incidence of any CV event decreased across increasing MET categories (Ptrend = .002). Compared with survivors reporting 0 MET hours/week(-1), the adjusted rate ratio for any CV event was 0.87 (95% CI, 0.56 to 1.34) for 3 to 6 MET hours/week(-1), 0.45 (95% CI, 0.26 to 0.80) for 9 to 12 MET hours/week(-1), and 0.47 (95% CI, 0.23 to 0.95) for 15 to 21 MET hours/week(-1). Adherence to national vigorous intensity exercise guidelines (ie, ≥ 9 MET hours/week(-1)) was associated with a 51% reduction in the risk of any CV event in comparison with not meeting the guidelines (P = .002)., Conclusion: Vigorous exercise was associated with a lower risk of CV events in a dose-dependent manner independent of CV risk profile and treatment in survivors of HL., (© 2014 by American Society of Clinical Oncology.)

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.)

The purpose of this study was to identify characteristics associated with health-related quality of life (HRQOL) among long-term survivors of adolescent cancer enrolled in the Childhood Cancer Survivor Study. Thirty percent of survivors reported poor physical and/or mental HRQOL. Race/ethnicity, education, and head/neck disfigurement were significantly associated with poor mental HRQOL, while sex, age, household income, obesity, alkylating agents, pelvic radiation, head/neck or limb disfigurement, and walking with a limp were associated with poor physical HRQOL. Identification of high-risk adolescent cancer patients may facilitate timely intervention to attempt to minimize the impact of cancer and treatment on subsequent quality of life., (© 2014 Wiley Periodicals, Inc.)

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: We sought to identify factors, other than cancer-related treatment and presence/severity of chronic health conditions, which may be associated with late mortality risk among adult survivors of pediatric malignancies., Methods: Using the Childhood Cancer Survivor Study cohort and a case-control design, 445 participants who died from causes other than cancer recurrence/progression or non-health-related events were compared with 7,162 surviving participants matched for primary diagnosis, age at baseline questionnaire, time from diagnosis to baseline questionnaire, and time at-risk. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for overall/cause-specific mortality. Independent measures included number/severity of chronic conditions, medical care, health-related behaviors, and health perceptions/concerns., Results: Adjusting for education, income, chemotherapy/radiation exposures, and number/severity of chronic health conditions, an increased risk for all-cause mortality was associated with exercising fewer than 3 days/week (OR = 1.72, CI 1.27-2.34), being underweight (OR = 2.58, CI 1.55-4.28), increased medical care utilization (P < 0.001), and self-reported fair to poor health (P < 0.001). Physical activity was associated with a higher risk of death among males (OR = 3.26, CI 1.90-5.61) reporting no exercise compared to those who exercised ≥3 times per week. Ever consuming alcohol was associated with a reduced risk of all-cause (OR = 0.61, CI 0.41-0.89) and other nonexternal causes of death (OR = 0.40, CI 0.20-0.79). Concerns/worries about future health (OR = 1.54, CI 1.10-2.71) were associated with increased all-cause mortality., Conclusions: Factors independent of cancer treatment and chronic health conditions modify the risk of death among adult survivors of pediatric cancer., Implications for Cancer Survivors: Continued cohort observation may inform interventions to reduce mortality.

Objective: To identify correlates of risky sexual behavior among adolescents surviving childhood cancer., Methods: The Child Health and Illness Profile-Adolescent Edition (CHIP-AE) was completed by 307 survivors of childhood cancer aged 15-20 years (M age at diagnosis 1.53 years; range 0-3.76). Univariate analyses were performed using χ² and Fisher's Exact tests, and multivariable logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for risky sexual behaviors., Results: Diagnosis of central nervous system cancer (OR = .13, 95% CI: .02-.96, p < .05), no history of beer or wine consumption (OR = .20, CI: .06-.68, p = .01), and fewer negative peer influences (OR = .28, CI: .09-.84, p = .02) associated with decreased likelihood of sexual intercourse. Good psychological health (scores ≥-1.5 SD on the CHIP-AE Emotional Discomfort scale) associated with decreased risk of early intercourse (OR = .19, CI: .05-.77, p = .02), whereas high parental education (≥ college degree) associated with decreased risk of multiple lifetime sexual partners (OR = .25, CI: .09-.72, p = .01). Increased time from diagnosis (OR = .27, CI: .10-.78, p = .02) and psychological health (OR = .09, CI: .02-.36, p < .01) associated with decreased risk of unprotected sex at last intercourse, whereas high parent education associated with increased risk (OR = 4.27, CI: 1.46-12.52, p = .01)., Conclusions: Risky sexual behavior in adolescents surviving childhood cancer is associated with cancer type, time since diagnosis, psychological health, alcohol use, and peer influences. Consideration of these factors may provide direction for future interventions designed to reduce adolescent sexual risk-taking.

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.

Objective: With the growing number of childhood cancer survivors in the US, it is important to assess the well-being of these individuals, particularly during the transitional phase of adolescence. Data about adolescent survivors' overall health and quality of life will help identify survivor subgroups most in need of targeted attention to successfully transition to adulthood., Participants and Methods: This ancillary study to the Childhood Cancer Survivor Study focused on children 15-19 years of age who had been diagnosed with cancer before the age of 4 years. A cohort of siblings of pediatric cancer survivors of the same ages served as a comparison sample. Adolescent health was assessed using the Child Health and Illness Profile-Adolescent Edition (CHIP-AE) survey., Results: The teen survey was sent to 444 survivor teens and 189 siblings. Of these, 307(69%) survivors and 97 (51%) siblings completed and returned the survey. The overall health profiles of siblings and survivors were similar. Among survivors, females scored significantly below males on satisfaction, discomfort, and disorders domains. Survivors diagnosed with central nervous system tumors scored less favorably than leukemia survivors in the global domains of satisfaction and disorders., Conclusion: In general, adolescent survivors fare favorably compared to healthy siblings. However, identification of the subset of pediatric cancer survivors who are more vulnerable to medical and psychosocial disorders in adolescence provides the opportunity for design and implementation of intervention strategies that may improve quality of life., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: Adult survivors of childhood central nervous system (CNS) tumors may be at risk for pulmonary dysfunction. This study enumerates the incidence of pulmonary dysfunction and explores associations between craniospinal irradiation (CSI) and pulmonary dysfunction among survivors of childhood CNS tumors., Methods: Participants included Childhood Cancer Survivor Study (CCSS) cohort members treated for CNS malignancies when 3.0 for asthma, chronic cough and need for extra oxygen. Rates of fibrosis (RR 2.0, 95% CI 1.0-3.9), chest wall abnormalities (RR 19.0, 95% CI 4.2-85.7), chronic cough (RR 1.6, 95% CI 1.2-2.1) and need for supplemental oxygen (RR 2.5, 95% CI 1.9-3.3) were higher among survivors than among siblings. Survivors treated with CSI were 10.4 (95% CI 7.6-14.4) times more likely than those not exposed to report chest wall deformity., Conclusion: Adult survivors of CNS malignancy have high rates of pulmonary dysfunction 5+ years after diagnosis. Survivors treated with CSI should be monitored for pulmonary disease to permit early interventions., (© 2013 Wiley Periodicals, Inc.)

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.

There are almost 14-million cancer survivors in the United States and the population is growing. Almost two-thirds of these survivors are age 65 or older. Given this, it is imperative to understand the impact of cancer and its therapies on the aging process. Childhood cancer survivors, diagnosed with cancer at age 21 or younger, particularly females, have rates of frailty similar to rates in older adults. This phenomenon appears to start early, suggesting an aging phenotype. Frailty among childhood cancer survivors increases risk for chronic disease and mortality. Adults diagnosed with cancer are faced with the effects of cancer and its therapies compounded by the issues of multiple morbidities that occur with the typical aging process. Intervention studies to date have focused on smoking cessation, diet, and exercise, as well as improving rates of late effects surveillance in childhood cancer survivors. No intervention studies have specifically addressed the issue of frailty or multiple morbidities in cancer survivors. Concerted efforts must continue to create and disseminate survivorship care plans to all cancer survivors.

Survivors of childhood cancer are at risk for treatment-related musculoskeletal late effects. Early detection and orthopedic intervention can help ameliorate musculoskeletal late effects and prevent subsequent complications. This systematic review summarizes the literature describing associations between cancer, its treatment, and musculoskeletal late effects. We searched PubMed and Web of Science for English language articles published between January 1970 and December 2012. The search was limited to investigations with at least 15 participants and conducted at least 2 years after completion of therapy for childhood, adolescent, or young adult cancer. Some late skeletal effects, including low bone mineral density, osteonecrosis, slipped capital femoral epiphyses, oncogenic rickets, and hormonerelated growth disturbances have been previously reviewed and were excluded, as were outcomes following amputation and limb-salvage procedures. Of 2347 references identified, 30 met inclusion criteria and were retained. An additional 54 studies that met inclusion criteria were found in reference lists of retained studies. Of 84 studies, 60 focused on associations between radiotherapy, six between chemotherapy, and 18 between surgery and musculoskeletal late effects. We found that younger age, higher radiation dosage, and asymmetric or partial bone radiation volume influences the effects of radiation on the musculoskeletal system. Methotrexate and vincristine are associated with long-term muscular strength and flexibility deficits. Laminectomy and chest wall resection are associated with spinal malalignment, and enucleation is associated with orbital deformities among survivors. Radiotherapy, chemotherapy, and surgery are associated with musculoskeletal late effects independently and additively. Associations are additionally influenced by host and treatment characteristics.

Purpose: Frailty, a phenotype reported among 9.9% of individuals 65 years old and older (9.6% of women; 5.2% of men), has not been assessed among adult childhood cancer survivors (CCS). We estimated the prevalence of frailty and examined associations with morbidity and mortality., Methods: Participants included 1,922 CCS at least 10 years from original cancer diagnosis (men, 50.3%; mean age, 33.6 ± 8.1 years) and a comparison population of 341 participants without cancer histories. Prefrailty and frailty were defined as two and ≥ three of the following conditions: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Morbidity was defined as grade 3 to 4 chronic conditions (Common Terminology Criteria for Adverse Events version 4.0). Fisher's exact tests were used to compare, by frailty status, percentages of those with morbidity. In a subset of 162 CCS who returned for a second visit, Poisson regression was used to evaluate associations between frailty and new onset morbidity. Cox proportional hazards regression was used to evaluate associations between frailty and death., Results: The prevalence of prefrailty and frailty were 31.5% and 13.1% among women and 12.9% and 2.7% among men, respectively, with prevalence increasing with age. Frail CCS were more likely than nonfrail survivors to have a chronic condition (82.1% v 73.8%). In models adjusted for existing chronic conditions, baseline frailty was associated with risk of death (hazard ratio, 2.6; 95% CI, 1.2 to 6.2) and chronic condition onset (relative risk, 2.2; 95% CI, 1.2 to 4.2)., Conclusion: The prevalence of frailty among young adult CCS is similar to that among adults 65 years old and older, suggesting accelerated aging.

Although substantial increases in survival rates among children diagnosed with cancer have been observed in recent decades, survivors are at risk of developing therapy-related chronic health conditions. Among children and adolescents treated for cancer, acquisition of peak bone mass may be compromised by cancer therapies, nutritional deficiencies, and reduced physical activity. Accordingly, failure to accrue optimal bone mass during childhood may place survivors at increased risk for deficits in bone density and fracture in later life. Current recommendations for the treatment of bone density decrements among cancer survivors include dietary counseling and supplementation to ensure adequate calcium and vitamin D intake. Few strategies exist to prevent or treat bone loss. Moving forward, studies characterizing the trajectory of changes in bone density over time will facilitate the development of interventions and novel therapies aimed at minimizing bone loss among survivors of childhood cancer.

Purpose: We investigated the association between prevalence of symptoms and health-related quality of life (HRQOL) in adult survivors of childhood cancer enrolled in the St Jude Lifetime Cohort study., Methods: Eligibility criteria include childhood malignancy treated at St Jude, survival ≥ 10 years from diagnosis, and current age ≥ 18 years. Study participants were 1,667 survivors (response rate = 65%). Symptoms were self-reported by using a comprehensive health questionnaire and categorized into 12 classes: cardiac; pulmonary; motor/movement; pain in head; pain in back/neck; pain involving sites other than head, neck, and back; sensation abnormalities; disfigurement; learning/memory; anxiety; depression; and somatization. HRQOL was measured by using physical/mental component summary (PCS/MCS) and six domain scores of the Medical Outcomes Study 36-Item Short-Form Health Survey. Multivariable regression analysis was performed to investigate associations between symptom classes and HRQOL. Cumulative prevalence of symptom classes in relation to time from diagnosis was estimated., Results: Pain involving sites other than head, neck and back, and disfigurement represented the most frequent symptom classes, endorsed by 58.7% and 56.3% of survivors, respectively. Approximately 87% of survivors reported multiple symptom classes. Greater symptom prevalence was associated with poorer HRQOL. In multivariable analysis, symptom classes explained up to 60% of the variance in PCS and 56% of the variance in MCS; demographic and clinical variables explained up to 15% of the variance in PCS and 10% of the variance in MCS. Longer time since diagnosis was associated with higher cumulative prevalence in all symptom classes., Conclusion: A large proportion of survivors suffered from many symptom classes, which was associated with HRQOL impairment.

Background: Cardiovascular-related toxicities have been reported among survivors of osteosarcoma., Methods: Fasting blood samples from 24 osteosarcoma survivors were analyzed for high-sensitivity C-reactive protein (hsCRP), triglycerides, total cholesterol, high-density lipoprotein (HDL), apolipoprotein-ß, lipoprotein (a), fibrinogen, circulating endothelial cells (CECs), and surface expression of vascular cell adhesion molecule-1 (VCAM-1). Values were compared to subjects in the natural history Coronary Artery Risk Development in Young Adults (CARDIA) cohort study except for CECs and VCAM-1 expression, which were compared to controls studied at the University of Minnesota Lillehei clinical trials unit., Procedure: Survivors (54.2% male), median age 18 years (9-32) at diagnosis, 36.5 years (20-56) at evaluation were treated with a variety of chemotherapeutic exposures, all but one were exposed to doxorubicin (median dose 450 mg/m(2) ; range: 90-645 mg/m(2)), 14 (58.3%) received cisplatin, and 3 (12.5%) were exposed to carboplatin. Two survivors (8.3%) received radiation therapy for disease relapse. Compared to CARDIA subjects, mean hsCRP (3.0 mg/L ± 2.0 vs. 1.6 ± 2.3), triglycerides (151 mg/dl ± 81.7 vs. 95.4 ± 101.3), lipoprotein (a) (34.9 mg/dl ± 17.7 vs. 13.8 ± 22.0), and fibrinogen (315.0 mg/dl ± 49.3 vs. 252.4 ± 61.7) were significantly elevated. The number of CECs (0.47 cells/ml ± 2.5 vs. 0.92 ± 2.5) did not differ while surface expression of VCAM-1 (86.4% ± 34.0 vs. 42.1 ± 33.8) was significantly elevated compared to controls., Conclusions: Among survivors of osteosarcoma, assessed a median of 14 years from diagnosis, there is evidence of vascular inflammation, dyslipidemia, and early atherogenesis., (Copyright © 2013 Wiley Periodicals, Inc.)

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

Cancer survivors experience treatment-related complications that can be exacerbated by tobacco use. This study reports the prevalence of smokeless and dual tobacco use, compares these rates to the U.S. population, and examines tobacco risk factors among males surviving childhood cancer. Data from the Childhood Cancer Survivor Study (CCSS) 2007 survey were used (N = 3378). Standardized incidence ratios (SIR) were obtained by comparing CCSS data with the National Survey on Drug Use and Health. Logistic regression was used to evaluate associations between risk factors and tobacco use. Among male survivors, 8.3% and 2.3% were current smokeless tobacco and dual tobacco users, respectively. Survivors were less likely than population males to report smokeless tobacco [SIR = 0.64; 95% confidence interval (CI), 0.57-0.72) or dual tobacco (SIR = 0.37; CI, 0.29-0.46) use; however, non-White survivors aged 35 to 49 years were more likely to use smokeless tobacco (SIR = 2.32; CI, 1.27-3.90). Smokeless tobacco use was associated (P < 0.05) with younger age at diagnosis, lower education, being married or divorced/separated, and not living in the Northeastern United State, whereas history of cardiovascular- and/or pulmonary-toxic treatment was protective. Dual tobacco use was associated with younger age at diagnosis, lower education, divorce/separation, and high psychologic distress. Having active heart or circulatory conditions was protective. Although smokeless tobacco/dual tobacco use is generally low among childhood cancer survivors, these findings suggest that tobacco use screening should be expanded to include smokeless tobacco use, and that smokeless tobacco-specific education and cessation interventions should be provided to users. Screening and intervening for smokeless tobacco/dual tobacco use in childhood cancer survivors will reduce tobacco-related morbidity and mortality.

Objective: To evaluate health status and participation restrictions in survivors of childhood extremity sarcomas., Design: Members of the Childhood Cancer Survivor Study cohort with extremity sarcomas who completed questionnaires in 1995, 2003, or 2007 were included., Setting: Cohort study of survivors of extremity sarcomas., Participants: Childhood extremity sarcoma survivors (N=1094; median age at diagnosis, 13y (range, 0-20y); current age, 33y (range, 10-53y); 49% male; 87.5% white; 75% had lower extremity tumors) who received their diagnosis and treatment between 1970 and 1986., Interventions: Not applicable., Main Outcome Measures: Prevalence rates for poor health status in 6 domains and 5 suboptimal social participation categories were compared by tumor location and treatment exposure with generalized estimating equations adjusted for demographic/personal factors and time/age., Results: In adjusted models, when compared with upper extremity survivors, lower extremity survivors had an increased risk of activity limitations but a lower risk of not completing college. Compared with those who did not have surgery, those with limb-sparing (LS) and upper extremity amputations (UEAs) were 1.6 times more likely to report functional impairment, while those with an above-the-knee amputation (AKA) were 1.9 times more likely to report functional impairment. Survivors treated with LS were 1.5 times more likely to report activity limitations. Survivors undergoing LS were more likely to report inactivity, incomes <$20,000, unemployment, and no college degree. Those with UEAs more likely reported inactivity, unmarried status, and no college degree. Those with AKA more likely reported no college degree. Treatment with abdominal irradiation was associated with an increased risk of poor mental health, functional impairment, and activity limitation., Conclusions: Treatment of lower extremity sarcomas is associated with a 50% increased risk for activity limitations; upper extremity survivors are at a 10% higher risk for not completing college. The type of local control influences health status and participation restrictions. Both of these outcomes decline with age., (Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The aims of this study are to compare self-reported sleep quality in adult survivors of childhood brain tumors and a population-based comparison group, to identify treatment-related factors associated with sleep disturbances, and to identify the impact of post-treatment obesity and depression on sleep scores in adult survivors of childhood brain tumors., Methods: Randomly selected adult survivors of childhood brain tumors (n = 78) and age-, sex-, and zip code-matched population-group members (n = 78) completed the Pittsburgh Sleep Quality Index and the Brief Symptom Inventory. Sleep quality and the effect of demographic, treatment, and post-treatment characteristics were evaluated with linear and logistic regression analyses., Results: Brain tumor survivors were 2.7 (95% CI, 1.1, 6.5) times more likely than the comparison group to take greater than 30 min to fall asleep. Females in both groups reported worse sleep quality and impaired daytime functioning. Among survivors, post-treatment obesity was associated with daytime dysfunction., Conclusions: These results agree with previous studies associating sleep, sex, and obesity and identified longer sleep latency as being a problem among childhood brain tumor survivors. Further study identifying factors contributing to sleep latency, and its impact on quality of life among adult survivors of childhood brain tumors is needed.

Background: To evaluate long-term health outcomes among childhood cancer survivors, St. Jude Children's Research Hospital (SJCRH) has established the St. Jude Lifetime Cohort Study (SJLIFE), comprised of adult survivors who undergo risk-directed clinical assessments. As in any human research study, SJLIFE participants are volunteers who may not represent the source population from which they were recruited. A lack of proportional representation could result in biased estimates of exposure-outcome associations. We compared available demographic, disease, and neighborhood level characteristics between participants and the source population to assess the potential for selection bias., Procedures: Potentially eligible patients for SJLIFE were enumerated as of October 31, 2011. Data from electronic medical records were combined with geocoded census data to develop an analytic data set of 3,108 patients (the evaluable source population) of whom 1,766 (57%) underwent clinical assessment (participants). The ratio of relative frequencies (RRFs) for characteristics was compared between participants and the source population, where RRF = 1.0 indicates equal frequency of the characteristic., Results: Participants and the source population had similar frequencies for most characteristics. Characteristics with modest relative differences (RRFs between 0.86 and 1.11) included sex, distance from SJCRH, primary diagnosis, median household income, median home value, and urbanicity., Conclusions: Our results indicate a lack of substantive differences in the relative frequencies of demographic, disease, or neighborhood characteristics between participants and the source population in SJLIFE, thus alleviating serious concerns about selective non-participation in this cohort. Bias in specific exposure-outcome relations is still possible and will be considered in individual analyses., (Copyright © 2012 Wiley Periodicals, Inc.)

Adult survivors of childhood cancer are known to be at increased risk of subsequent malignancy, but only limited data exist describing the incidence and risk factors for secondary renal carcinoma. Among 14 358 5-year survivors diagnosed between 1970 and 1986, we estimated standardized incidence ratios (SIRs) for subsequent renal carcinoma and identified associations with primary cancer therapy using Poisson regression. Twenty-six survivors were diagnosed with renal carcinoma (median = 22.6 years from diagnosis; range = 6.3-35.7 years), reflecting a statistically significant excess (SIR = 8.0, 95% confidence interval [CI] = 5.2 to 11.7) compared with the general population. Highest risk was observed among neuroblastoma survivors (SIR = 85.8, 95% CI = 38.4 to 175.2) and, in multivariable analyses, with renal-directed radiotherapy of 5 Gy or greater (relative risk [RR] = 3.8, 95% CI = 1.6 to 9.3) and platinum-based chemotherapy (RR = 3.5, 95% CI = 1.0 to 11.2). To our knowledge, this is the first report of an association between cisplatin and subsequent renal carcinoma among survivors of childhood cancer.

Purpose: To determine the prevalence of pulmonary hypertension, a late effect of cancer therapy not previously identified in aging survivors of childhood cancer, and associations with chest-directed radiation therapy (RT) and measures of current cardiac function, lung function, and exercise capacity., Patients and Methods: Cross-sectional evaluation of 498 survivors at a median age of 38.0 years (range, 20.0 to 59.0 years) and a median of 27.3 years (range, 12.2 to 46.0 years) from primary cancer diagnosis was performed. Abnormal tricuspid regurgitant jet velocity (TRV) was defined as more than 2.8 m/s by Doppler echocardiography., Results: Increased TRV was identified in 25.2% of survivors who received chest-directed RT and 30.8% of those who received more than 30 Gy. In multivariable models, increased TRV was associated with increasing dose of RT (1 to 19.9 Gy: odds ratio [OR], 2.09; 95% CI, 0.63 to 6.96; 20 to 29.9 Gy: OR, 3.46; 95% CI, 1.59 to 7.54; ≥ 30 Gy: OR, 4.54; 95% CI, 1.77 to 11.64 compared with no RT; P for trend < .001), body mass index more than 40 kg/m(2) (OR, 3.89; 95% CI, 1.46 to 10.39), and aortic valve regurgitation (OR, 5.85; 95% CI, 2.05 to 16.74). Survivors with a TRV more than 2.8 m/s had increased odds (OR, 5.20; 95% CI, 2.5 to 11.0) of severe functional limitation on a 6-minute walk compared with survivors with a TRV ≤ 2.8 m/s., Conclusion: A substantial number of adult survivors of childhood cancer who received chest-directed RT have an increased TRV and may have pulmonary hypertension as a result of both direct lung injury and cardiac dysfunction. Longitudinal follow-up and confirmation by cardiac catheterization are warranted.