The burden of cardiovascular disease and risk for subsequent major adverse cardiovascular events in survivors of childhood cancer: a prospective, longitudinal analysis from the St Jude Lifetime Cohort Study.

BACKGROUND: The effect of the increasing lifetime burden of non-major cardiovascular conditions on risk for a subsequent major adverse cardiovascular event among survivors of childhood cancer has not been assessed. We aimed to characterise the prevalence of major adverse cardiovascular events and their association with the cumulative burden of non-major adverse cardiovascular events in childhood cancer survivors. METHODS: This is a longitudinal cohort study with participant data obtained from an ongoing cohort study at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE). Prospective clinical follow-up was of 5-year survivors of childhood cancer who were diagnosed when aged younger than 25 years from 1962 to 2012. Age-frequency, sex-frequency, and race-frequency matched community-control participants completed a similar one-time clinical assessment. 22 cardiovascular events were graded using a St Jude Children's Research Hospital-modified version of the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Cumulative incidence and burden of the primary outcome of major adverse cardiovascular events (cardiomyopathy, myocardial infarction, stroke, and other cardiovascular-related mortality) were estimated. Rate ratios (RR) of the association of major adverse cardiovascular events with 22 non-major adverse cardiovascular events were estimated using multivariable piecewise-exponential regression adjusting for attained age, age at diagnosis, sex, race and ethnicity, treatment era, diagnosis of diabetes, and exposure to cardiotoxic cancer therapies. The St Jude Lifetime Cohort study is registered with ClinicalTrials.gov, NCT00760656, and is ongoing. FINDINGS: 9602 5-year survivors of childhood cancer, and 737 community controls were included in the longitudinal follow-up (from Sept 13, 2007, to Dec 17, 2021). The median follow-up was 20·3 years (IQR 12·0-31·4) from the date of primary cancer diagnosis (4311 [44.9%] were females). By the age of 50 years (analysis stopped at age 50 years due to the low number of participants older than that age), the cumulative incidence of major adverse cardiovascular events among survivors was 17·7% (95% CI 15·9-19·5) compared with 0·9% (0·0-2·1) in the community controls. The cumulative burden of major adverse cardiovascular events in survivors was 0·26 (95% CI 0·23-0·29) events per survivor compared with 0·009 (0·000-0·021) events per community control participant. Increasing cumulative burden of grade 1-4 non-major adverse cardiovascular events was associated with an increased future risk of major adverse cardiovascular events (one condition: RR 4·3, 95% CI 3·1-6·0; p<0·0001; two conditions: 6·6, 4·6-9·5; p<0·0001; and three conditions: 7·7, 5·1-11·4; p<0·0001). Increased risk for major adverse cardiovascular events was observed with specific subclinical conditions (eg, grade 1 arrhythmias [RR 1·5, 95% CI 1·2-2·0; p=0·0017]), grade 2 left ventricular systolic dysfunction (2·2, 1·6-3·1; p<0·0001), grade 2 valvular disorders (2·2, 1·2-4·0; p=0·013), but not grade 1 hypercholesterolaemia, grade 1-2 hypertriglyceridaemia, or grade 1-2 vascular stenosis. INTERPRETATION: Among an ageing cohort of survivors of childhood cancer, the accumulation of non-major adverse cardiovascular events, including subclinical conditions, increased the risk of major adverse cardiovascular events and should be the focus of interventions for early detection and prevention of major adverse cardiovascular events. FUNDING: The US National Cancer Institute and the American Lebanese Syrian Associated Charities.

Risk factors for neurocognitive impairment, emotional distress, and poor quality of life in survivors of pediatric rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Prevalence and risk of poor psychological outcomes following rhabdomyosarcoma (RMS) are not well-established. METHODS: Participants in this cross-sectional, case-control study (n = 713 survivors, 42.5% female; mean [SD] age, 30.5 [6.6] years; n = 706 siblings, 57.2% female; mean age, 32.8,[7.9] years) completed measures of neurocognition, emotional distress, and health-related quality of life (HRQOL). Multivariable logistic regression models identified treatments, health behaviors, and chronic conditions associated with impairment. RESULTS: Relative to siblings, more survivors reported neurocognitive impairment (task efficiency: 21.1% vs. 13.7%, emotional regulation: 16.7% vs. 11.0%, memory: 19.3% vs. 15.1%), elevated emotional distress (somatic distress: 12.9% vs. 4.7%, anxiety: 11.7% vs. 5.9%, depression: 22.8% vs. 16.9%) and poorer HRQOL (physical functioning: 11.1% vs. 2.8%, role functioning due to physical problems: 16.8% vs. 8.2%, pain: 17.5% vs. 10.0%, vitality: 22.3% vs. 13.8%, social functioning: 14.4% vs. 6.8%, emotional functioning: 17.1% vs. 10.6%). Cranial radiation increased risk for impaired task efficiency (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.14-4.63), whereas chest and pelvic radiation predicted increased risk of physical functioning (OR, 2.68; 95% CI, 1.16-6.21 and OR, 3.44; 95% CI, 1.70-6.95, respectively). Smoking was associated with impaired task efficiency (OR, 2.06; 95% CI, 1.14-3.70), memory (OR, 2.23; 95% CI, 1.26-3.95), anxiety (OR, 2.71; 95% CI, 1.36-5.41) and depression (OR, 1.77; 95% CI, 1.01-3.11). Neurologic conditions increased risk of anxiety (OR, 2.30; 95% CI, 1.04-5.10), and hearing conditions increased risk of depression (OR, 1.79; 95% CI, 1.05-3.03). Neurologic and hearing conditions, respectively, were associated with impaired memory (OR, 2.44; 95% CI, 1.20-4.95 and OR, 1.87; 95% CI, 1.05-3.35) and poor health perception (OR, 2.62; 95% CI, 1.62-1.28 and OR, 2.33; 95% CI, 1.34-4.06). CONCLUSIONS: RMS survivors are at significant risk for poor psychological outcomes. Advancing therapies for local control, smoking cessation, and managing chronic medical conditions may mitigate poor outcomes following RMS.

Financial hardship among siblings of long-term survivors of childhood cancer: A Childhood Cancer Survivor Study report.

BACKGROUND: Siblings of children with cancer may experience adverse household economic consequences, but their financial outcomes in adulthood are unknown. METHODS: A total of 880 siblings (aged 18-64 years) of adult-aged childhood cancer survivors were surveyed to estimate the prevalence of financial hardship by three established domains (behavioral, material, and psychological). For individual financial hardship items matching the contemporaneous National Health Interview Survey or Behavioral Risk Factor Surveillance System, siblings were compared with the general population by calculating adjusted prevalence odds ratios (ORs) to sample-weighted responses. Multivariable logistic regression models examined associations between sibling characteristics and each hardship domain and between sibling hardship and survivors' cancer/treatment characteristics. RESULTS: Behavioral, material, and psychological hardship was reported by 24%, 35%, and 28%, respectively. Compared with national survey respondents, siblings were more likely to report worries about medical bills (OR, 1.14; 95% confidence interval [CI], 1.06-1.22), difficulty affording nutritious foods (OR, 1.79; 95% CI, 1.54-2.07), and forgoing needed medical care (OR, 1.38; 95% CI, 1.10-1.73), prescription medications (OR, 2.52; 95% CI, 1.99-3.20), and dental care (OR, 1.34; 95% CI, 1.15-1.57) because of cost. Sibling characteristics associated with reporting financial hardship in one or more domains included female sex, older age, chronic health conditions, lower income, not having health insurance, high out-of-pocket medical expenditures, and nonmedical/nonhome debt. No survivor cancer/treatment characteristics were associated with sibling financial hardship. CONCLUSIONS: Adult siblings of childhood cancer survivors were more likely to experience financial hardship compared with the general population. Childhood cancer may adversely affect entire households, with potentially lasting implications.

Continuity and coordination of care for childhood cancer survivors with multiple chronic conditions: Results from the Childhood Cancer Survivor Study.

INTRODUCTION: Continuity and coordination-of-care for childhood cancer survivors with multiple chronic conditions are understudied but critical for appropriate follow-up care. METHODS: From April through June 2022, 800 Childhood Cancer Survivor Study participants with two or more chronic conditions (one or more severe/life-threatening/disabling) were emailed the "Patient Perceived Continuity-of-Care from Multiple Clinicians" survey. The survey asked about survivors' main (takes care of most health care) and coordinating (ensures follow-up) provider, produced three care-coordination summary scores (main provider, across multiple providers, patient-provider partnership), and included six discontinuity indicators (e.g., having to organize own care). Discontinuity (yes/no) was defined as poor care on one or more discontinuity item. Chi-square tests assessed associations between discontinuity and sociodemographics. Modified Poisson regression models estimated prevalence ratios (PRs) for discontinuity risk associated with the specialty and number of years seeing the main and coordinating provider, and PRs associated with better scores on the three care-coordination summary measures. Inverse probability weights adjusted for survey non-participation. RESULTS: A total of 377 (47%) survivors responded (mean age 48 years, 68% female, 89% non-Hispanic White, 78% privately insured, 74% ≥college graduate); 147/373 (39%) reported discontinuity. Younger survivors were more likely to report discontinuity (chi-square p = .02). Seeing the main provider ≤3 years was associated with more prevalent discontinuity (PR; 95%CI) (1.17; 1.02-1.34 vs ≥ 10 years). Cancer specialist main providers were associated with less prevalent discontinuity (0.81; 0.66-0.99 vs. primary care). Better scores on all three care-coordination summary measures were associated with less prevalent discontinuity: main provider (0.73; 0.64-0.83), across multiple providers (0.81; 0.78-0.83), patient-provider partnership (0.85; 0.80-0.89). CONCLUSIONS: Care discontinuity among childhood cancer survivors is prevalent and requires intervention.

Sugar and sugar-sweetened beverages in relation to premature aging in adult survivors of childhood cancer.

BACKGROUND: Premature aging is a significant concern in adult survivors of childhood cancer as they develop aging-related conditions at a younger age than their peers with no history of childhood cancer. Although modifiable lifestyle factors, such as diet, are postulated to affect aging process, supporting evidence is sparse. METHODS: We examined if the consumption of sugar and sugar-sweetened beverages was related to premature aging in 3322 adult survivors of childhood cancer in the St. Jude Lifetime Cohort. Premature aging was assessed using the Deficit Accumulation Index (DAI) that was a ratio of the number of age-related chronic health conditions each survivor had out of 44 conditions total. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There were 46% of childhood cancer survivors consumed SSBs once or more times per day. High intake of sugar, especially sugars added to foods during preparation or processing, and habitual consumption of sugar-sweetened beverage were associated with an increased risk of premature aging. DISCUSSION: Our findings support a need to include strategies to reduce sugar and sugar-sweetened beverages consumption in lifestyle interventions to promote healthy aging in adult survivors of childhood cancer.

Long-term outcomes among survivors of childhood osteosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

PURPOSE: Treatment strategies for osteosarcoma evolving between 1970 and 1999 improved 5-year survival and continue as standard of care today. This report evaluates the impact of these evolving therapies on long-term health outcomes. METHODS: Five-year survivors of childhood osteosarcoma in CCSS treated from 1970 to 1999 were evaluated for late (>5 years from diagnosis) mortality, chronic health conditions (CHCs), and health status using piecewise-exponential and logistical models. Comparisons were made between survivors and siblings without cancer, and among survivors examining historical and current standard chemotherapies (e.g., methotrexate/doxorubicin/cisplatin [MAP] vs. others), specific chemotherapy agents and surgical approaches (amputation vs. limb salvage [LS]). Models were evaluated adjusting for attained age, sex, race, ethnicity, and age at diagnosis. RESULTS: A total of 1257 survivors of osteosarcoma were followed on average for 24.4 years. Twenty-year all-cause late mortality was 13.3% (95% confidence interval [CI]: 11.7%-14.9%) overall and 11.7% (95% CI: 6.9%-16.5%) for the subset treated with MAP plus LS. Survivors were at higher risk of CHCs (rate ratio [RR] 3.7, 95% CI: 3.2-4.3) than the sibling cohort, most notably having more serious cardiac, musculoskeletal, and hearing CHCs. Within the survivor cohort, the risk of severe CHCs was twice as high with MAP versus no chemotherapy (RR 2.1, 95% CI: 1.3-3.4). Compared with primary amputation, serious musculoskeletal CHCs were higher after LS (RR 6.6, 95% CI: 3.6-13.4), without discernable differences in health status. CONCLUSION: Contemporary osteosarcoma therapy with MAP plus LS, while improving 5-year disease-free survival, continues to be associated with a high burden of late mortality, CHCs, and health status limitations.

Risk of increased mortality in underweight survivors: A brief report from the Childhood Cancer Survivor Study.

BACKGROUND: Approximately 1 in 10 adult survivors of childhood cancer is underweight. Although the consequences of being overweight or obese have been well described, outcomes among childhood cancer survivors who are underweight are unknown. OBJECTIVE: To determine whether underweight status increases the risk of mortality. PROCEDURE: Cohort study: Marginal models with generalized estimating equations to evaluate the associations between body mass index (BMI), serious or life-threatening chronic conditions, and death in the setting of long-term follow-up questionnaires and National Death Index search. PARTICIPANTS: Childhood cancer five-year survivors diagnosed during 1970-1986 in the Childhood Cancer Survivor Study Exposure: Underweight status, defined as body mass index (BMI) < 18.5 kg/m2 compared with ideal body weight. Based on available literature on body weight and mortality from the general population, ideal body weight was defined as BMI 22.0-24.9 kg/m2. MAIN OUTCOMES: Overall mortality and cancer-specific mortality. RESULTS: Of 9454 survivors (median age 35 years old (range, 17-58), an average of 17.5 years from diagnosis), 627 (6.6%) participants were underweight at baseline or follow-up questionnaire. Of 184 deaths, 29 were among underweight survivors. Underweight status was more common among females (9.1% vs. 4.5%, p < .01) and participants with younger age at diagnosis (8.2% for < 5 years vs. 6.1% for ≥5 years, p < .01), lower household income (8.9% for < $20,000 vs. 6.0% for ≥ $20,000, p < .01), or a history of serious chronic condition (p = .05). After adjustment for these factors, in addition to prior smoking and a history of radiation therapy, the risk of all-cause mortality within two years of BMI report was increased (OR 2.85; 95% CI: 1.63-4.97; p < .01) for underweight survivors, compared with ideal-weight survivors. CONCLUSIONS: Childhood cancer survivors who are underweight are at increased risk for late mortality that appears unrelated to smoking status, recognized chronic disease, or subsequent malignancy. Whether targeted nutritional interventions would ameliorate this risk is unknown.

The ENGAGE study: a 3-arm randomized hybrid type 1 effectiveness and implementation study of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic services in childhood cancer survivors.

BACKGROUND: Germline cancer genetic testing has become a standard evidence-based practice, with established risk reduction and screening guidelines for genetic carriers. Access to genetic services is limited in many places, which leaves many genetic carriers unidentified and at risk for late diagnosis of cancers and poor outcomes. This poses a problem for childhood cancer survivors, as this is a population with an increased risk for subsequent malignant neoplasms (SMN) due to cancer therapy or inherited cancer predisposition. The ENGaging and Activating cancer survivors in Genetic services (ENGAGE) study evaluates the effectiveness of an in-home, collaborative PCP model of remote telegenetic services to increase uptake of cancer genetic testing in childhood cancer survivors compared to usual care options for genetic testing. METHODS: The ENGAGE study is a 3-arm randomized hybrid type 1 effectiveness and implementation study within the Childhood Cancer Survivor Study population which tests a clinical intervention while gathering information on its delivery during the effectiveness trial and its potential for future implementation among 360 participants. Participants are randomized into three arms. Those randomized to Arm A receive genetic services via videoconferencing, those in Arm B receive these services by phone, and those randomized to Arm C will receive usual care services. DISCUSSION: With many barriers to accessing genetic services, innovative delivery models are needed to address this gap and increase uptake of genetic services. The ENGAGE study evaluates the effectiveness of an adapted model of remote delivery of genetic services to increase the uptake of recommended genetic testing in childhood cancer survivors. This study assesses the uptake in remote genetic services and identify barriers to uptake to inform future recommendations and a theoretically-informed process evaluation which can inform modifications to enhance dissemination beyond this study population and to realize the benefits of precision medicine. TRIAL REGISTRATION: This protocol was registered at clinicaltrials.gov (NCT04455698) on July 2, 2020.

Statistical analysis of self-reported health conditions in cohort studies: handling of missing onset age.

OBJECTIVES: This paper discusses methodological challenges in epidemiological association analysis of a time-to-event outcome and hypothesized risk factors, where age/time at the onset of the outcome may be missing in some cases, a condition commonly encountered when the outcome is self-reported. STUDY DESIGN AND SETTING: A cohort study with long-term follow-up for outcome ascertainment such as the Childhood Cancer Survivor Study (CCSS), a large cohort study of 5-year survivors of childhood cancer diagnosed in 1970-1999 in which occurrences and age at onset of various chronic health conditions (CHCs) are self-reported in surveys. Simple methods for handling missing onset age and their potential bias in the exposure-outcome association inference are discussed. The interval-censored method is discussed as a remedy for handling this problem. The finite sample performance of these approaches is compared through Monte Carlo simulations. Examples from the CCSS include four CHCs (diabetes, myocardial infarction, osteoporosis/osteopenia, and growth hormone deficiency). RESULTS: The interval-censored method is useable in practice using the standard statistical software. The simulation study showed that the regression coefficient estimates from the 'Interval censored' method consistently displayed reduced bias and, in most cases, smaller standard deviations, resulting in smaller mean square errors, compared to those from the simple approaches, regardless of the proportion of subjects with an event of interest, the proportion of missing onset age, and the sample size. CONCLUSION: The interval-censored method is a statistically valid and practical approach to the association analysis of self-reported time-to-event data when onset age may be missing. While the simpler approaches that force such data into complete data may enable the standard analytic methods to be applicable, there is considerable loss in both accuracy and precision relative to the interval-censored method.

Multilevel Social Determinants of Patient-Reported Outcomes in Young Survivors of Childhood Cancer.

In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving treatment at St. Jude Children's Research Hospital who were <18 years of age during follow-up from 2017 to 2018 and their primary caregivers. Social determinants included family factors (caregiver-reported PROs, family dynamics) and county-level deprivation (socioeconomic status, physical environment via the County Health Rankings & Roadmaps). PROMIS measures assessed survivors' and caregivers' PROs. General linear regression tested associations of social determinants with survivors' PROs. We found that caregivers' higher anxiety was significantly associated with survivors' poorer depression, stress, fatigue, sleep issues, and reduced positive affect (p < 0.05); caregivers' sleep disturbances were significantly associated with lower mobility in survivors (p < 0.05). Family conflicts were associated with survivors' sleep problems (p < 0.05). Residing in socioeconomically deprived areas was significantly associated with survivors' poorer sleep quality (p < 0.05), while higher physical environment deprivation was associated with survivors' higher psychological stress and fatigue and lower positive affect and mobility (p < 0.05). Parental, family, and neighborhood factors are critical influences on young survivors' quality of life and well-being and represent new intervention targets.

Mechanisms of sleep disturbances in long-term cancer survivors: a childhood cancer survivor study report.

BACKGROUND: Sleep problems following childhood cancer treatment may persist into adulthood, exacerbating cancer-related late effects and putting survivors at risk for poor physical and psychosocial functioning. This study examines sleep in long-term survivors and their siblings to identify risk factors and disease correlates. METHODS: Childhood cancer survivors (≥5 years from diagnosis; n = 12 340; 51.5% female; mean [SD] age = 39.4 [9.6] years) and siblings (n = 2395; 57.1% female; age = 44.6 [10.5] years) participating in the Childhood Cancer Survivor Study completed the Pittsburgh Sleep Quality Index (PSQI). Multivariable Poisson-error generalized estimating equation compared prevalence of binary sleep outcomes between survivors and siblings and evaluated cancer history and chronic health conditions (CHC) for associations with sleep outcomes, adjusting for age (at diagnosis and current), sex, race/ethnicity, and body mass index. RESULTS: Survivors were more likely to report clinically elevated composite PSQI scores (>5; 45.1% vs 40.0%, adjusted prevalence ratio [PR] = 1.20, 95% CI = 1.13 to 1.27), symptoms of insomnia (38.8% vs 32.0%, PR = 1.26, 95% CI = 1.18 to 1.35), snoring (18.0% vs 17.4%, PR = 1.11, 95% CI = 1.01 to 1.23), and sleep medication use (13.2% vs 11.5%, PR = 1.28, 95% CI = 1.12 to 1.45) compared with siblings. Within cancer survivors, PSQI scores were similar across diagnoses. Anthracycline exposure (PR = 1.13, 95% CI = 1.03 to 1.25), abdominal radiation (PR = 1.16, 95% CI = 1.04 to 1.29), and increasing CHC burden were associated with elevated PSQI scores (PRs = 1.21-1.48). CONCLUSIONS: Among survivors, sleep problems were more closely related to CHC than diagnosis or treatment history, although longitudinal research is needed to determine the direction of this association. Frequent sleep-promoting medication use suggests interest in managing sleep problems; behavioral sleep intervention is advised for long-term management.

Modifiable Cardiometabolic Risk Factors in Survivors of Childhood Cancer: JACC: CardioOncology State-of-the-Art Review.

The growing community of childhood cancer survivors faces a heavy burden of late onset morbidities and mortality, with cardiovascular diseases being the leading noncancer cause. In addition to demographics and cancer treatment exposures, which cannot be altered, cardiometabolic risk factors (obesity, hypertension, diabetes, and dyslipidemia) and frailty potentiate the risk of morbidity and mortality associated with chronic health conditions. Important opportunities exist to target these risk factors and improve late health outcomes for survivors. Unfortunately, limited evidence exists on the optimal methods to prevent, screen, and treat cardiometabolic risk factors among survivors, resulting in significant underdiagnosis and undertreatment. In this review, we discuss the prevalence of, risk factors for, current survivor-specific recommendations, and gaps in knowledge to mitigate potentially modifiable cardiometabolic risk factors and frailty among survivors of childhood cancer.

Chronic Health Conditions and Longitudinal Employment in Survivors of Childhood Cancer.

Importance: Employment is an important factor in quality of life and provides social and economic support. Longitudinal data on employment and associations with chronic health conditions for adult survivors of childhood cancer are lacking. Objective: To evaluate longitudinal trends in employment among survivors of childhood cancer. Design, Setting, and Participants: Retrospective cohort study of 5-year cancer survivors diagnosed at age 20 years or younger between 1970 and 1986 enrolled in the multi-institutional Childhood Cancer Survivor Study (CCSS). Sex-stratified employment status at baseline (2002 to 2004) and follow-up (2014 to 2016) was compared with general population rates from the Behavioral Risk Factor Surveillance System cohort. Data were analyzed from July 2021 to June 2022. Exposures: Cancer therapy and preexisting and newly developed chronic health conditions. Main Outcomes and Measures: Standardized prevalence ratios of employment (full-time or part-time, health-related unemployment, unemployed, not in labor force) among adult (aged ≥25 years) survivors between baseline and follow-up compared with the general population. Longitudinal assessment of negative employment transitions (full-time to part-time or unemployed at follow-up). Results: Female participants (3076 participants at baseline; 2852 at follow-up) were a median (range) age of 33 (25-53) years at baseline and 42 (27-65) years at follow-up; male participants (3196 participants at baseline; 2557 at follow-up) were 33 (25-54) and 43 (28-64) years, respectively. The prevalence of full-time or part-time employment at baseline and follow-up was 2215 of 3076 (71.3%) and 1933 of 2852 (64.8%) for female participants and 2753 of 3196 (85.3%) and 2079 of 2557 (77.3%) for male participants, respectively, with declining standardized prevalence ratios over time (female participant baseline, 1.01; 95% CI, 0.98-1.03; follow-up, 0.94; 95% CI, 0.90-0.98; P < .001; male participant baseline, 0.96; 95% CI, 0.94-0.97; follow-up, 0.92; 95% CI, 0.89-0.95; P = .02). While the prevalence of health-related unemployment increased (female participants, 11.6% to 17.2%; male participants, 8.1% to 17.1%), the standardized prevalence ratio remained higher than the general population and declined over time (female participant baseline, 3.78; 95% CI, 3.37-4.23; follow-up, 2.23; 95% CI, 1.97-2.51; P < .001; male participant baseline, 3.12; 95% CI, 2.71-3.60; follow-up, 2.61; 95% CI, 2.24-3.03; P = .002). Among survivors employed full-time at baseline (1488 female participants; 1933 male participants), 285 female participants (19.2%) and 248 male participants (12.8%) experienced a negative employment transition (median [range] follow-up, 11.5 [9.4-13.8] years). Higher numbers and grades of chronic health conditions were significantly associated with these transitions. Conclusions and Relevance: In this retrospective analysis of adult survivors of childhood cancer, significant declines in employment and increases in health-related unemployment among cancer survivors compared with the general population were identified. A substantial portion of survivors in the midcareer age range fell out of the workforce. Awareness among clinicians, caregivers, and employers may facilitate clinical counseling and occupational provisions for supportive work accommodations.

Health insurance among survivors of childhood cancer following affordable care act implementation.

BACKGROUND: The Affordable Care Act (ACA) increased private non-employer health insurance options, expanded Medicaid eligibility, and provided pre-existing health conditions protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre/post-ACA implementation. METHODS: Using the multicenter Childhood Cancer Survivor Study, we included participants from two cross-sectional surveys: pre-ACA (2007-2009; survivors: N = 7,505; siblings: N = 2,175) and post-ACA (2017-2019; survivors: N = 4,030; siblings: N = 987). A subset completed both surveys (1,840 survivors; 646 siblings). Multivariable regression models compared post-ACA insurance coverage and type (private/public/uninsured) between survivors and siblings and identified associated demographic and clinical factors. Multinomial models compared gaining and losing insurance vs staying the same among survivors and siblings who participated in both surveys. RESULTS: The proportion with insurance was higher post-ACA (survivors pre-ACA 89.1% to post-ACA 92.0% [+2.9%]; siblings pre-ACA 90.9% to post-ACA 95.3% [+4.4%]). Post-ACA insurance coverage was greater among those age 18-25 (survivors: 15.8% vs < 2.3% ages 26+; siblings +17.8% vs < 4.2% ages 26+). Survivors were more likely to have public insurance than siblings post-ACA (18.4% vs 6.9%; odds ratios [OR]=1.7, 95%CI 1.1-2.6). Survivors with severe chronic conditions (OR = 4.7, 95%CI 3.0-7.3) and those living in Medicaid expansion states (OR = 2.4, 95%CI 1.7-3.4) had increased odds of public insurance coverage post-ACA. Among the subset completing both surveys, low/mid income survivors (<$60,000) experienced both insurance losses and gains in reference to highest household income survivors (≥$100,000), relative to odds of keeping the same insurance status. CONCLUSIONS: Post-ACA, more childhood cancer survivors and siblings had health insurance, although disparities remain in coverage.

Plant Foods Intake and Risk of Premature Aging in Adult Survivors of Childhood Cancer in the St Jude Lifetime Cohort (SJLIFE).

PURPOSE: To identify dietary factors that are related to premature aging in adult survivors of childhood cancer, we examined the associations between plant food intakes and age-related deficit accumulation. METHODS: A total of 3,322 childhood cancer survivors (age 18-65 years, mean = 31, standard deviation = 8.4) in the St Jude Lifetime Cohort had total fruit, total vegetables and subgroups, whole grains, refined grains, nuts/seeds, and nutrients intake assessed using a food frequency questionnaire. Premature aging at baseline was assessed by the deficit accumulation index (DAI) and categorized as low, medium, and high risk. Multinomial logistic regressions (reference: low risk) adjusting for confounders estimated odds ratios (ORs) and 95% CIs. Multivariable linear regression of a continuous intake against a continuous DAI was also performed. RESULTS: Dark green vegetable (ORhigh v low = 0.47 [95% CI, 0.28 to 0.78] per 1/2 cup/1,000 kcal increment) and nuts/seeds intakes (ORhigh v low = 0.71 [95% CI, 0.47 to 1.08] per 1 oz/1,000 kcal increment; coefficientlinear = -0.0115, P = .02) were associated with a lower risk of premature aging. Conversely, refined grain intake was related to an increased risk of premature aging (ORhigh v low = 1.33 [95% CI, 0.99 to 1.78], per 1 oz/1,000 kcal increment; coefficientlinear = 0.0093, P = .005). Fruit and whole grain intakes were not associated with premature aging risk. Among nutrients abundant in plant foods, dietary folate intake was associated with a lower risk of premature aging (ORhigh v low = 0.89 [95% CI, 0.80 to 0.99] per 50 mcg/1,000 kcal increase). Beta-carotene, lutein/zeaxanthin, and vitamin E intakes from foods were also related to a modestly lower, but not statistically significant, risk of premature aging. CONCLUSION: Specific plant foods are associated with lower risk of premature aging, providing targets for the interventions to promote healthy aging in childhood cancer survivors.

Associations of seven measures of biological age acceleration with frailty and all-cause mortality among adult survivors of childhood cancer in the St. Jude Lifetime Cohort.

Survivors of childhood cancer may experience accelerated biological aging, resulting in premature frailty and death. We used seven measures of biological age in the St. Jude Lifetime (SJLIFE) Cohort to compare biological age acceleration between the SJLIFE Cohort and the third United States National Health and Nutrition Examination Survey controls, explore trajectories of biological age according to cancer treatment and type, and test associations of biological age acceleration with frailty and death (mean follow-up of 26.5 years) among survivors. Survivors of cancer aged 5% faster per year and measured, on average, 0.6-6.44 years biologically older compared to controls and 5-16 years biologically older compared to age-matched individuals at the population level. Survivors treated with hematopoietic cell transplant and vinca alkaloid chemotherapy evidenced the fastest trajectories of biological aging. Biologically, older and faster-aging survivors consistently and robustly had a higher risk of frailty and died earlier than those with slower biological aging, suggesting a potential opportunity to intervene on excess aging.

Mortality After Major Cardiovascular Events in Survivors of Childhood Cancer.

BACKGROUND: Adult survivors of childhood cancer are at risk for cardiovascular events. OBJECTIVES: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations. METHODS: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical factors. RESULTS: Among 25,658 childhood cancer survivors (median age at diagnosis 7 years, median age at follow-up or death 38 years) and 5,051 siblings, 1,780 survivors and 91 siblings had a cardiovascular event. After HF, CAD, and stroke, 10-year all-cause mortalities were 30% (95% CI: 26%-33%), 36% (95% CI: 31%-40%), and 29% (95% CI: 24%-33%), respectively, among survivors vs 14% (95% CI: 0%-25%), 14% (95% CI: 2%-25%), and 4% (95% CI: 0%-11%) among siblings. All-cause mortality risks among childhood cancer survivors were increased after HF (HR: 7.32; 95% CI: 2.56-20.89), CAD (HR: 5.54; 95% CI: 2.37-12.93), and stroke (HR: 3.57; 95% CI: 1.12-11.37). CAD-specific mortality risk was increased (HR: 3.70; 95% CI: 1.05-13.02). Among 5,114 CARDIA participants, 345 had a major event. Although CARDIA participants were on average decades older at events (median age 57 years vs 31 years), mortality risks were similar, except that all-cause mortality after CAD was significantly increased among childhood cancer survivors (HR: 1.85; 95% CI: 1.16-2.95). CONCLUSIONS: Survivors of childhood cancer represent a population at high risk for mortality after major cardiovascular events.

Financial hardship and neighborhood socioeconomic disadvantage in long-term childhood cancer survivors.

BACKGROUND: Long-term survivors of childhood cancer face elevated risk for financial hardship. We evaluate whether childhood cancer survivors live in areas of greater deprivation and the association with self-reported financial hardships. METHODS: We performed a cross-sectional analysis of data from the Childhood Cancer Survivor Study between 1970 and 1999 and self-reported financial information from 2017 to 2019. We measured neighborhood deprivation with the Area Deprivation Index (ADI) based on current zip code. Financial hardship was measured with validated surveys that captured behavioral, material and financial sacrifice, and psychological hardship. Bivariate analyses described neighborhood differences between survivors and siblings. Generalized linear models estimated effect sizes between ADI and financial hardship adjusting for clinical factors and personal socioeconomic status. RESULTS: Analysis was restricted to 3475 long-term childhood cancer survivors and 923 sibling controls. Median ages at time of evaluation was 39 years (interquartile range [IQR] = 33-46 years and 47 years (IQR = 39-59 years), respectively. Survivors resided in areas with greater deprivation (ADI ≥ 50: 38.7% survivors vs 31.8% siblings; P < .001). One quintile increases in deprivation were associated with small increases in behavioral (second quintile, P = .017) and psychological financial hardship (second quintile, P = .009; third quintile, P = .014). Lower psychological financial hardship was associated with individual factors including greater household income (≥$60 000 income, P < .001) and being single (P = .048). CONCLUSIONS: Childhood cancer survivors were more likely to live in areas with socioeconomic deprivation. Neighborhood-level disadvantage and personal socioeconomic circumstances should be evaluated when trying to assist childhood cancer survivors with financial hardships.

Lifestyle and Subsequent Malignant Neoplasms in Childhood Cancer Survivors: A Report from the St. Jude Lifetime Cohort Study.

INTRODUCTION: This study aimed to assess longitudinal associations between lifestyle and subsequent malignant neoplasms (SMNs) in young adult childhood cancer survivors. METHODS: Members of the St. Jude Lifetime Cohort (SJLIFE) aged ≥18 years and surviving ≥5 years after childhood cancer diagnosis were queried and evaluated for physical activity, cardiorespiratory fitness (CRF), muscle strength, body mass index (BMI), smoking, risky drinking, and a combined lifestyle score. Time to first SMN, excluding nonmalignant neoplasms and nonmelanoma skin cancer, was the outcome of longitudinal analysis. RESULTS: Survivors (n = 4072, 47% female, 29% smokers, 37% risky drinkers, 34% obese, and 48% physically inactive) had a mean (SD) time between baseline evaluation and follow-up of 7.0 (3.3) years, an age of 8.7 (5.7) years at diagnosis, and an age of 30 (8.4) years at baseline lifestyle assessment. Neither individual lifestyle factors nor a healthy lifestyle score (RR 0.8, 0.4-1.3, p = 0.36) were associated with the risk of developing an SMN. CONCLUSIONS: We did not identify any association between lifestyle factors and the risk of SMN in young adult childhood cancer survivors.