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Background Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors. Methods Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls. Results Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non–high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy. Conclusions Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population. [ABSTRACT FROM AUTHOR]

Background: Prior studies have identified that survivors of childhood acute lymphoblastic leukemia (ALL) report poor health status. It is unknown how risk-stratified therapy impacts the health status of ALL survivors. Methods: We estimated and compared the prevalence of self-reported poor health status among adult (=18 years) survivors of childhood ALL diagnosed at age <21 years from 1970 to 1999 and sibling controls, excluding proxy reports. Therapy combinations defined treatment groups representative of 1970s therapy (70s), standard- and high-risk 1980s and 1990s therapy (80sSR, 80sHR, 90sSR, 90sHR), and relapse/bone marrow transplant (R/BMT). Log-binomial models, adjusted for clinical and demographic factors, compared outcomes between groups using prevalence ratios (PR) with 95% confidence intervals (CI). Results: Among 5,119 survivors and 4,693 siblings, survivors were more likely to report poor health status in each domain including poor general health (13.5% vs. 7.4%; PR = 1.92; 95% CI, 1.69-2.19). Compared with 70s, 90sSR and 90sHR were less likely to report poor general health (90sSR: PR = 0.75; 95% CI, 0.57-0.98; 90sHR: PR = 0.58; 95% CI, 0.39-0.87), functional impairment (90sSR: PR = 0.56; 95% CI, 0.42-0.76; 90sHR: PR = 0.63; 95% CI, 0.42-0.95), and activity limitations (90sSR: 0.61; 95% CI, 0.45-0.83; 90sHR: PR = 0.59; 95% CI, 0.38-0.91). An added adjustment for chronic conditions in multivariable models partially attenuated 90sSR risk estimates. Conclusions: Risk-stratified ALL therapy has succeeded in reducing risk for poor general health, functional impairment, and activity limitations among more recent survivors of standard- and high-risk therapy. Impact: Future research into the relationship between risk-stratified therapy, health status, and late health outcomes may provide new opportunities to further improve late morbidity among survivors. [ABSTRACT FROM AUTHOR]

Background: The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only.Methods: This cross-sectional study included 1207 ALL survivors (54.0% female; mean age 30.6 years) and 2273 siblings (56.9% female; mean age 47.6 years), who completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were 2-sided.Results: Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs 16.9%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.31 to 2.74; females: 12.5% vs 17.6%; OR = 1.50, 95% CI = 1.07 to 2.14), as well as impaired memory (males: 11.6% vs 19.9%, OR = 1.89, CI = 1.31 to 2.74; females: 14.78% vs 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), and impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92).Conclusion: Neurocognitive impairment is associated with methotrexate, dexamethasone, and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship. [ABSTRACT FROM AUTHOR]

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

Background: Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors., Methods: Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls., Results: Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non-high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy., Conclusions: Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only., Methods: This cross-sectional study included 1207 ALL survivors (54.0% female; mean age 30.6 years) and 2273 siblings (56.9% female; mean age 47.6 years), who completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were 2-sided., Results: Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs 16.9%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.31 to 2.74; females: 12.5% vs 17.6%; OR = 1.50, 95% CI = 1.07 to 2.14), as well as impaired memory (males: 11.6% vs 19.9%, OR = 1.89, CI = 1.31 to 2.74; females: 14.78% vs 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), and impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92)., Conclusion: Neurocognitive impairment is associated with methotrexate, dexamethasone, and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)