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Background: Subsequent short‐latency leukemias are well‐described among survivors of childhood cancer. However, late (5–14.9 years from diagnosis, LL) and very late (≥15 years from diagnosis, VLL) subsequent leukemias have not been well studied. We assessed risk factors, prevalence, and outcomes for LL and VLL in the Childhood Cancer Survivor Study cohort. Methods: Subsequent leukemias, among 25,656 five‐year survivors, were self‐reported and confirmed by pathology review. Standardized incidence ratios (SIR) and cumulative incidences were calculated, and relative risks (RR) were estimated using Cox regression for exposures. Results: Seventy‐seven survivors developed subsequent leukemia, 49 survivors with LL (median time from diagnosis 7.8 years, range 5.0–14.5 years) and 28 with VLL (median time from diagnosis 25.4 years, range 15.9–42.8 years), with a cumulative incidence of 0.23% (95% CI 0.18%–0.30%) 20 years from diagnosis for all subsequent leukemias. The most common leukemia subtypes were acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. Compared to the general population, survivors were at increased risk, for developing LL (SIR 9.3, 95% CI 7.0–12.1) and VLL (SIR 5.9, 95% CI 3.9–8.4). In multivariable relative risk analyses, cumulative epipodophyllotoxin dose >4000 mg/m2 was associated with increased risk for LL and VLL (RR 4.5, 95% CI 2.0–9.9). Conclusions: In this large series of late subsequent leukemias, survivors of childhood cancer are at increased risk, with no evidence of plateau over time. We observed most risk among survivors who received high cumulative doses of epipodophyllotoxins. Ongoing consideration for this late effect should continue beyond 10 years. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. Methods: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0–53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0–70.0] years, 55.7% female) completed in‐person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form‐36 physical/mental summary scores, social attainment). Results: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%–29.4%) than controls (2.9%, CI 1.4–4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06–18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19–72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01–1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68–11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10–0.84, Sensory: OR 0.35, CI 0.13–0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22–5.72). Conclusions: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL. [ABSTRACT FROM AUTHOR]

Summary: Children with acute lymphoblastic leukaemia (ALL) are at risk for obesity and cardiometabolic diseases. To gain insight into body composition changes among children with ALL, we assessed quantitative computed tomography (QCT) data for specific body compartments (subcutaneous adipose tissue [SAT], visceral adipose tissue [VAT], total adipose tissue [TAT], lean tissue [LT], LT/TAT and VAT/SAT at lumbar vertebrae L1 and L2) at diagnosis and at off‐therapy for 189 children with ALL and evaluated associations between body mass index (BMI) Z‐score and clinical characteristics. BMI Z‐score correlated positively with SAT, VAT and TAT and negatively with LT/TAT and VAT/SAT. At off‐therapy, BMI Z‐score, SAT, VAT and TAT values were higher than at diagnosis, but LT, LT/TAT and VAT/SAT were lower. Patients aged ≥10 years at diagnosis had higher SAT, VAT and TAT and lower LT and LT/TAT than patients aged 2.0–9.9 years. Female patients had lower LT and LT/TAT than male patients. Black patients had less VAT than White patients. QCT analysis showed increases in adipose tissue and decreases in LT during ALL therapy when BMI Z‐scores increased. Early dietary and physical therapy interventions should be considered, particularly for patients at risk for obesity. [ABSTRACT FROM AUTHOR]

In health‐science research, outcomes ascertained through surveys and interviews are subject to potential bias with respect to the true outcome status, which is only ascertainable with clinical and laboratory assessment. This measurement error may lead to biased inference when evaluating associations between exposures and outcomes of interest. Here, we consider a cohort study in which the outcome of interest is ascertained via questionnaire, subject to imperfect ascertainment, but where a subset of participants also have a clinically assessed, validated outcome available. This presents a methodological opportunity to address potential bias. Specifically, we constructed the likelihood in two parts, one using the validated subset and the other using a subset without validation. This work expands on that proposed by Pepe and enables inference with standard statistical software. Weighted generalized linear model estimates for our method and maximum likelihood estimates (MLE) for Pepe's method were computed, and the statistical inference was based on the standard large‐sample likelihood theory. We compare the finite sample performance of two approaches through Monte Carlo simulations. This methodological work was motivated by a large cohort study of long‐term childhood cancer survivors, allowing us to provide a relevant application example where we examined the association between clinical factors and chronic health conditions. [ABSTRACT FROM AUTHOR]

Objective: To examine associations between neurologic late effects and attainment of independence in adult survivors of childhood cancer treated with central nervous system (CNS)‐directed therapies. Methods: A total of 7881 survivors treated with cranial radiation therapy (n = 4051; CRT) and/or intrathecal methotrexate (n = 4193; IT MTX) ([CNS‐treated]; median age [range] = 25.5 years [18–48]; time since diagnosis = 17.7 years [6.8–30.2]) and 8039 without CNS‐directed therapy reported neurologic conditions including stroke, seizure, neurosensory deficits, focal neurologic dysfunction, and migraines/severe headaches. Functional independence was assessed using latent class analysis with multiple indicators (independent living, assistance with routine and personal care needs, ability to work/attend school, attainment of driver's license, marital/partner status). Multivariable regression models, adjusted for age, sex, race/ethnicity, and chronic health conditions, estimated odds ratios (OR) or relative risks (RR) for associations between neurologic morbidity, functional independence, and emotional distress. Results: Among CNS‐treated survivors, three classes of independence were identified: (1) moderately independent, never married, and non‐independent living (78.7%); (2) moderately independent, unable to drive (15.6%); and (3) non‐independent (5.7%). In contrast to 50% of non‐CNS‐treated survivors and 60% of siblings, a fourth fully independent class of CNS‐treated survivors was not identified. History of stroke (OR = 2.50, 95% CI: 1.70–3.68), seizure (OR = 9.70, 95% CI: 7.37–12.8), neurosensory deficits (OR = 2.67, 95% CI: 2.16–3.31), and focal neurologic dysfunction (OR = 3.05, 95% CI: 2.40–3.88) were associated with non‐independence among CNS‐treated survivors. Non‐independence was associated with emotional distress symptoms. Interpretation: CNS‐treated survivors do not attain full independence comparable to non‐CNS‐treated survivors or siblings. Interventions to promote independence may be beneficial for survivors with treatment‐related neurological sequalae. [ABSTRACT FROM AUTHOR]

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

Background: Treatment‐related late effects can worsen over time among cancer survivors. Such worsening health states may trigger changes in internal standards, values, or conceptualization of quality‐of‐life (QOL). This "response‐shift" phenomenon can jeopardize the validity of QOL assessment, and misrepresent QOL comparisons over time. This study tested response‐shift effects in reporting future‐health concerns among childhood cancer survivors who experienced progression in chronic health conditions (CHCs). Methods: 2310 adult survivors of childhood cancer from St. Jude Lifetime Cohort Study completed a survey and clinical assessment at two or more timepoints. Based on 190 individual CHCs graded for adverse‐event severity, global CHC burden was classified as "progression" or "non‐progression". QOL was assessed using the SF‐36TM eight domains and physical‐ and mental‐component summary scores (PCS, MCS). A single global item measured concerns about future health. Random‐effects models comparing survivors with and without progressive global CHC burden (progressors vs. non‐progressors) evaluated response‐shift effects (recalibration, reprioritization, reconceptualization) in reporting future‐health concerns. Results: Compared with non‐progressors, progressors were more likely to de‐emphasize (or downplay) overall physical and mental health in evaluating future‐health concerns (p‐values<0.05), indicating recalibration response‐shift, and more likely to de‐emphasize physical health earlier rather than later in follow‐up (p‐value<0.05), indicating reprioritization response‐shift. There was evidence for a reconceptualization response‐shift with progressor classification associated with worse‐than‐expected future‐health concerns and physical health, and better‐than‐expected pain and role‐emotional functioning (p‐values<0.05). Conclusion: We identified three types of response‐shift phenomena in reporting concerns about future health among childhood cancer survivors. Survivorship care or research should consider response‐shift effects when interpreting changes in QOL over time. [ABSTRACT FROM AUTHOR]

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

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

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

Objective: This study used childhood cancer survivors as a novel model to study whether children who experience central nervous system (CNS) injury are at higher risk for neurocognitive impairment associated with subsequent late onset chronic health conditions (CHCs). Methods: Adult survivors of childhood cancer (n = 2,859, ≥10 years from diagnosis, ≥18 years old) completed a comprehensive neurocognitive battery and clinical examination. Neurocognitive impairment was defined as age‐adjusted z score < 10th percentile. Participants impaired on ≥3 tests had global impairment. CHCs were graded using the Common Terminology Criteria for Adverse Events v4.3 (grade 1, mild; 2, moderate; 3, severe/disabling; 4, life‐threatening) and were combined into a severity/burden score by frequency and grade (none/low, medium, high, and very high). A total of 1,598 survivors received CNS‐directed therapy including cranial radiation, intrathecal methotrexate, or neurosurgery. Logistic regression estimated the odds of neurocognitive impairment associated with severity/burden score and grade 2 to 4 conditions, stratified by CNS treatment. Results: CNS‐treated survivors performed worse than non–CNS‐treated survivors on all neurocognitive tests and were more likely to have global neurocognitive impairment (46.9% vs 35.3%, p < 0.001). After adjusting for demographic and treatment factors, there was a dose–response association between severity/burden score and global neurocognitive impairment, but only among CNS‐treated survivors (high odds ratio [OR] = 2.24, 95% confidence interval [CI] = 1.42–3.53; very high OR = 4.07, 95% CI = 2.30–7.17). Cardiovascular and pulmonary conditions were associated with processing speed, executive function, and memory impairments in CNS‐treated but not non–CNS‐treated survivors who were impacted by neurologic conditions. Interpretation: Reduced cognitive/brain reserve associated with CNS‐directed therapy during childhood may make survivors vulnerable to adverse cognitive effects of cardiopulmonary conditions during adulthood. ANN NEUROL 2021;89:534–545 [ABSTRACT FROM AUTHOR]

Cardiovascular disease is up to 10 times more likely among childhood cancer survivors compared to siblings. Low cardiorespiratory fitness is a modifiable risk‐factor for cardiovascular diseases. Yet, cardiorespiratory fitness is not routinely screened in pediatric oncology, and healthy VO2max cut‐points are unavailable. We aimed to predict cardiorespiratory fitness by developing a simple algorithm and establish cut‐points identifying survivors' cardiovascular fitness health‐risk zones. We recruited 262 childhood cancer survivors (8–18 years old, ≥1‐year posttreatment). Participants completed gold‐standard cardiorespiratory fitness assessment (Cardiopulmonary Exercise Test [CPET; VO2max]) and 6‐minute walk test (6MWT). Associations with VO2max were included in a linear regression algorithm to predict VO2max, which was then cross‐validated. We used Bland–Altman's limits of agreement and Receiver Operating Characteristic curves using FITNESSGRAM's "Healthy Fitness Zones" to identify cut‐points for adequate cardiorespiratory fitness. A total of 199 participants (aged 13.7 ± 2.7 years, 8.5 ± 3.5 years posttreatment) were included. We found a strong positive correlation between VO2max and 6MWT distance (r = 0.61, r2 = 0.37, p < 0.001). Our regression algorithm included 6MWT distance, waist‐to‐height ratio, age and sex to predict VO2max (r = 0.79, r2 = 0.62, p < 0.001). Forty percentages of predicted VO2max values were within ±3 ml/kg/min of measured VO2max. The cut‐point for FITNESSGRAM's "health‐risk" fitness zone was 39.8 ml/kg/min (males: AUC = 0.88), and 33.5 ml/kg/min (females: AUC = 0.82). We present an algorithm to reasonably predict cardiorespiratory fitness for childhood cancer survivors, using inexpensive measures. This algorithm has useful clinical application, particularly when CPET is unavailable. Our algorithm has the potential to assist clinicians to identify survivors below the cut‐points with increased cardiovascular disease‐risk, to monitor and refer for tailored interventions with exercise specialists. What's new? Survivors of childhood cancer experience increased rates of cardiovascular disease later in life. Screening for cardiorespiratory fitness could help patients improve their risk of later CV disease. Here, the authors developed an algorithm to predict cardiorespiratory fitness. They enrolled 262 childhood cancer survivors and had them take both the standard Cardiopulmonary Exercise Test (CPET) and the 6‐minute walk test. They developed an algorithm incorporating the 6‐minute walk test, waist‐to‐height ratio, age, and sex, by which doctors can evaluate cardiorespiratory fitness when the CPET is unavailable. The algorithm provides an inexpensive way to identify at‐risk patients before symptoms develop. [ABSTRACT FROM AUTHOR]

Survivors of childhood cancer are at risk for obesity, a condition potentially modifiable if dietary intake and physical activity are optimized. These health behaviors are likely influenced by neighborhood of residence, a determinant of access to healthy, affordable food and safe and easy exercise opportunities. We examined associations between neighborhood level factors and obesity among survivors in the St. Jude Lifetime cohort and community comparison group members. Persons with residential addresses available for geocoding were eligible for analysis (n = 2,265, mean age 32.5 [SD 9.1] years, 46% female, 85% white). Survivors completed questionnaires regarding individual behaviors; percent body fat was assessed via dual X‐ray absorptiometry (obesity: ≥25% males; ≥35% females); neighborhood effect was characterized using census tract of residence (e.g., neighborhood socioeconomic status [SES], rurality). Structural equation modeling was used to determine associations between neighborhood effect, physical activity, diet, smoking, treatment exposures and obesity. Obese survivors (n = 1,420, 62.7%) were more likely to live in neighborhoods with lower SES (RR: 1.23, 95% CI: 1.10–1.38) and rural areas (RR: 1.22, 95% CI: 1.07–1.39) compared to survivors with normal percent body fat. Resource‐poor neighborhoods (standardized effect: 0.06, p < 0.001) and cranial radiation (0.16, p < 0.001) had direct effects on percent body fat. Associations between neighborhood of residence and percent body fat were increased (0.01, p = 0.04) among individuals with a poor diet. Neighborhoods where survivors reside as an adult is associated with obesity. Interventions targeting survivors should incorporate strategies that address environmental influences on obesity. What's new? The neighborhood where a childhood cancer survivor resides likely influences obesity risk and obesity‐related health behaviors. Little is known, however, about the impact of the so‐called neighborhood effect, which is driven by factors such as socioeconomic status (SES), access to healthy foods, and exercise opportunities, on obesity risk among survivors of childhood cancer. Here, investigation of survivors in the St. Jude Lifetime cohort shows that obesity risk is significantly increased in particular among survivors living in rural areas or in neighborhoods with relatively low SES. Obesity risk was further linked to age, exposure to cranial radiation, and inadequate physical activity. [ABSTRACT FROM AUTHOR]

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

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

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

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

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

Background: Childhood cancer survivors are at risk for adverse psychological outcomes. Whether exercise can attenuate this risk is unknown.Methods: In total, 6199 participants in the Childhood Cancer Survivor Study (median age, 34.3 years [range, 22.0-54.0 years]; median age at diagnosis, 10.0 years [range, 0-21.0 years]) completed a questionnaire assessing vigorous exercise and medical/psychological conditions. Outcomes were evaluated a median of 7.8 years (range, 0.1-10.0 years) later and were defined as: symptom level above the 90th percentile of population norms for depression, anxiety, or somatization on the Brief Symptom Inventory-18; cancer-related pain; cognitive impairment using a validated self-report neurocognitive questionnaire; or poor health-related quality of life. Log-binomial regression estimated associations between exercise (metabolic equivalent [MET]-hours per week-1 ) and outcomes adjusting for cancer diagnosis, treatment, demographics, and baseline conditions.Results: The prevalence of depression at follow-up was 11.4% (95% CI, 10.6%-12.3%), anxiety 7.4% (95% CI, 6.7%-8.2%) and somatization 13.9% (95% CI, 13.0%-14.9%). Vigorous exercise was associated with lower prevalence of depression and somatization. The adjusted prevalence ratio for depression was 0.87 (95% CI, 0.72-1.05) for 3 to 6 MET hours per week-1 , 0.76 (95% CI, 0.62-0.94) for 9 to 12 MET-hours per week-1 , and 0.74 (95% CI, 0.58-0.95) for 15 to 21 MET-hours per week-1 . Compared with 0 MET hours per week-1 , 15 to 21 MET-hours per week-1 were associated with an adjusted prevalence ratio of 0.79 (95% CI, 0.62-1.00) for somatization. Vigorous exercise also was associated with less impairment in the physical functioning, general health and vitality (Ptrend  < .001), emotional role limitations (Ptrend  = .02), and mental health (Ptrend  = .02) domains as well as higher cognitive function in the domains of task completion, organization, and working memory (P < .05 for all), but not in the domain of cancer pain.Conclusions: Vigorous exercise is associated with less psychological burden and cognitive impairment in childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Children with acute lymphoblastic leukemia (ALL) have an increased risk of obesity and short stature. To the authors' knowledge, data regarding patients treated on contemporary protocols without cranial irradiation are limited.Methods: Changes in z scores for body mass index (BMI), height, and weight from the time of diagnosis to 5 years off therapy were evaluated using multivariable analysis in 372 children with ALL who were aged 2 to 18 years at the time of diagnosis and were enrolled on the St. Jude Children's Research Hospital Total XV protocol from 2000 through 2007.Results: The percentage of overweight/obese patients increased from 25.5% at the time of diagnosis to approximately 50% during the off-therapy period. Median BMI z scores increased significantly during glucocorticoid therapy (induction: ∆0.56; 95% confidence interval [95% CI], 0.29-0.64 [P<.001]; and reinduction II: ∆0.22; 95% CI, 0.13-0.49 [P=.001]) and during the first year after therapy (∆0.18; 95% CI, 0.08-0.46 [P=.006]). Among patients who were of healthy weight/underweight at the time of diagnosis, those aged 2 to <10 years at diagnosis had a significantly higher risk of becoming overweight/obese during or after therapy compared with those aged ≥10 years (P=.001). Height z scores declined during treatment and improved after therapy. Being aged 2 to <10 years at the time of diagnosis, being of low-risk status, having a white blood cell count < 50×109 /L at the time of diagnosis, and having negative central nervous system disease were associated with significantly better improvements in z scores for height during the off-therapy period compared with being aged ≥10 years, being of standard-risk/high-risk status, having a white blood cell count  ≥ 50×109 /L, and having positive central nervous system disease, respectively.Conclusions: The results of the current study demonstrate that obesity is prevalent, and height growth, especially in patients with identified risk factors, appears compromised. Multidisciplinary intervention should begin during induction therapy and continue during the off-therapy period. [ABSTRACT FROM AUTHOR]

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

BACKGROUND: The purpose of this study was to examine the prevalence and predictors of social difficulties in adolescent survivors of central nervous system (CNS) tumors. METHODS: Six hundred sixty‐five survivors of CNS tumors (53.8% male and 51.7% treated with cranial radiation therapy [CRT]), who had a current median age of 15.0 years (range, 2.0‐17.0 years) and were a median of 12.1 years (range, 8.0‐17.7 years) from their diagnosis, were compared with 1376 survivors of solid tumors (50.4% male), who had a median age of 15.0 years (range, 12.0‐17.0 years) and were a median of 13.2 years (range, 8.3‐17.9 years) from their diagnosis, and 726 siblings (52.2% male), who had a median age of 15.0 years (range, 12.0‐17.0 years). Social adjustment was measured with parent‐proxy responses to the Behavior Problems Index. Latent profile analysis defined social classes. Multinomial logistic regression, adjusted for age, sex, and age at diagnosis, identified predictors of class membership. Path analyses tested mediating effects of physical limitations, sensory loss, and cognitive impairment on social outcomes. RESULTS: Caregivers reported that survivors of CNS tumors were more likely to have 0 friends (15.3%) and to interact with friends less than once per week (41.0%) in comparison with survivors of solid tumors (2.9% and 13.6%, respectively) and siblings (2.3% and 8.7%, respectively). Latent profile analysis identified 3 social classes for survivors of CNS tumors: well‐adjusted (53.4%), social deficits (16.2%), and poor peer relationships (30.4%). However, 2 classes were identified for survivors of solid tumors and siblings: well‐adjusted (86.2% and 91.1%, respectively) and social deficits (13.8% and 8.9%, respectively). CRT predicted class membership for CNS survivors (odds ratio [OR] for poor peer relationships, 1.16/10 Gy; 95% confidence interval [CI], 1.08‐1.25; OR for social deficits 1.14/10 Gy; 95% CI, 1.04‐1.25; reference, well‐adjusted). Cognitive impairment mediated the association between all social outcomes and CRT (P values <.001). CONCLUSION: Almost 50% of survivors of CNS tumors experience social difficulties; the pattern is unique in comparison with solid tumor and sibling groups. Cognitive impairment is associated with increased risk, and this highlights the need for multitargeted interventions. Almost 50% of survivors of pediatric central nervous system tumors experience social difficulties; the pattern is unique in comparison with solid tumor and sibling groups. Cognitive impairment is associated with increased risk, and this highlights the need for multitargeted interventions. [ABSTRACT FROM AUTHOR]

Objective: Epidemiologic analyses indicate a lack of association between BMI (kg/m2 ) and mortality among Hispanic adults. Because BMI provides only a surrogate for the real variable of interest, adiposity, this study evaluated associations between measures of body composition and mortality.Methods: Using data from US-residing Mexican Americans in the National Health and Nutrition Examination Survey (NHANES) III (n = 4,480) and NHANES 1999-2010 (n = 5,849), the association between seven measures of body composition measured via anthropometry and bio-electrical impedance analysis (i.e., waist circumference, waist-to-height ratios [WHtR], skinfolds, lean mass, fat mass, percent body fat, and BMI) and all-cause and cardiovascular and diabetes mortality were examined. Additional analyses were stratified by gender.Results: Waist circumference (hazard ratio [HR]: 1.04, 95% CI: 1.01-1.07) and WHtR (HR: 1.08, 95% CI: 1.03-1.14) were weakly associated with an increased all-cause mortality, while WHtR was associated with an increased risk of diabetes-related death (HR: 1.26, 95% CI: 1.07-1.49). In gender-stratified analyses, there was an increased risk of mortality in females who had increases in WHtR and waist circumference for all-cause mortality and cardiovascular deaths.Conclusions: Waist circumference and WHtR were associated with increased risk of all-cause and diabetes-related mortality in US-residing Mexican American adults. [ABSTRACT FROM AUTHOR]

The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Children with acute lymphoblastic leukemia (ALL) can develop reduced bone mineral density (BMD). However, data from patients who received treatment on a frontline regimen without cranial irradiation are limited, and no genome-wide analysis has been reported.Methods: Lumbar BMD was evaluated by quantitative computed tomography at diagnosis, after 120 weeks of continuation therapy, and after 2 years off therapy in pediatric patients with ALL (ages 2-18 years at diagnosis) who were treated on the St. Jude Total XV Protocol. Clinical, pharmacokinetic, and genetic risk factors associated with decreased BMD Z-scores were evaluated.Results: The median BMD Z-score in 363 patients was 0.06 at diagnosis, declined to -1.08 at week 120, but partly recovered to -0.72 after 2 years off therapy; BMD in patients with low BMD Z-scores at diagnosis remained low after therapy. Older age (≥10 years vs 2-9.9 years at diagnosis; P < .001), a higher BMD Z-score at diagnosis (P = .001), and a greater area under the plasma drug concentration-time curve for dexamethasone in weeks 7 and 8 of continuation therapy (P = .001) were associated with a greater decrease in BMD Z-score from diagnosis to week 120. Single-nucleotide polymorphisms in 2 genes important in osteogenesis and bone mineralization (COL11A1 [reference single-nucleotide polymorphism rs2622849]; P = 2.39 × 10-7 ] and NELL1 [rs11025915]; P = 4.07 × 10-6 ]) were associated with a decreased BMD Z-score. NELL1 (P = .003) also was associated with a greater dexamethasone area under the plasma drug concentration-time curve.Conclusions: BMD Z-scores decreased during therapy, especially in patients who had clinical, pharmacokinetic, and genetic risk factors. Early recognition of BMD changes and strategies to optimize bone health are essential. Cancer 2018;124:1025-35. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

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

Objective: To evaluate concurrent and longitudinal associations between psychosocial functioning and physical activity in adolescent and young adult survivors of early childhood cancer.Methods: Adolescent survivors of early childhood cancer (diagnosed before age four) participating in the Childhood Cancer Survivor Study completed the Coping Health and Illness Profile-Adolescent Edition (CHIP-AE; n = 303; mean age at survey: 17.6 years). A subset of these survivors (n = 248) completed a follow-up survey an average of 6.0 years later (range: 4-10). Logistic regression identified associations between psychosocial functioning in adolescence and physical activity levels in adolescence and young adulthood.Results: Survivors reported low physical activity as adolescents (46.1% scored below CHIP-AE cut-point) and young adults (40.8% below Centers for Disease Control guidelines). Poor physical activity during adolescence was associated with female sex (OR = 2.06, 95% CI, 1.18-3.68), parents with less than a college education (OR = 1.91, 95% CI, 1.11-3.32), previous treatment with cranial radiation (OR = 3.35, 95% CI, 1.69-6.88), TV time (OR = 1.77, 95% CI, 1.00-3.14), and limitations of activity due to health or mobility restrictions (OR = 8.28, 95% CI, 2.87-30.34). Poor diet (OR = 1.84, 95% CI, 1.05-3.26) and low self-esteem (OR = 1.80, 95% CI, 0.99-3.31) during adolescence were associated with lower odds of meeting Centers for Disease Control physical activity guidelines in young adulthood.Conclusion: These findings provide targets for future interventional studies to improve physical activity in this high-risk population. [ABSTRACT FROM AUTHOR]

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

Background: Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown.Methods: This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03).Results: Among 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively.Conclusions: With extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551-60. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]