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Background: Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the United States.Methods: We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material [eg, problems paying bills], psychological [eg, distress], and behavioral [eg, forgoing care due to cost]) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately.Results: A total of 2588 AYA cancer survivors (median = 31 [interquartile range = 26-35] years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior.Conclusions: Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors' health, and multifaceted interventions are necessary to address underlying causes. [ABSTRACT FROM AUTHOR]

The article focuses on the socioeconomic and health system factors of the population on childhood cancer medical care and screening including enrollment in the Childhood Cancer Survivor Study (CCSS) and individual-level factors from U.S. Area Health Resource File was reported.

Background: Health complications related to childhood cancer may be influenced by risky health behaviors (RHBs), particularly when RHBs co-occur. To the authors' knowledge, only limited information is available describing how RHBs cluster among survivors of childhood cancer and their siblings and the risk factors for co-occurring RHBs.Methods: Latent class analysis was used to identify RHB clusters using longitudinal survey data regarding smoking, alcohol use, and physical activity from adult survivors (4184 survivors) and siblings (1598 siblings) in the Childhood Cancer Survivor Study. Generalized logistic regression was used to evaluate associations between demographic characteristics, treatment exposures, psychological distress, health conditions, and cluster membership.Results: Three RHB clusters were identified: a low-risk cluster, an insufficiently active cluster, and a high-risk cluster (tobacco and risky alcohol use and insufficient activity). Compared with siblings, survivors were more likely to be in the insufficiently active cluster (adjusted odds ratio [ORadj ], 1.17; 95% confidence interval [95% CI], 1.06-1.27) and were less likely to be in the high-risk cluster (ORadj , 0.79; 95% CI, 0.69-0.88). Risk factors for membership in the high-risk cluster included psychological distress (ORadj , 2.76; 95% CI, 1.98-3.86), low educational attainment (ORadj , 7.49; 95% CI, 5.15-10.88), income <$20,000 (ORadj , 2.62; 95% CI, 1.93-3.57), being divorced/separated or widowed (ORadj , 1.36; 95% CI, 1.03-1.79), and limb amputation (ORadj , 1.52; 95% CI, 1.03-2.24). Risk factors for the insufficiently active cluster included chronic health conditions, psychological distress, low education or income, being obese or overweight, female sex, nonwhite race/ethnicity, single marital status, cranial radiation, and cisplatin exposure.Conclusions: RHBs co-occur in survivors of childhood cancer and their siblings. Economic and educational disadvantages and psychological distress should be considered in screening and interventions to reduce RHBs. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2747-2756. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: To compare antimüllerian hormone (AMH) patterns by cancer status and treatment exposures across 6 years after incident breast cancer using administrative data.Design: In a cross-sectional design, AMH levels in patients who developed incident breast cancer between ages 15-39 years during 2005-2019 were matched 1:10 to levels in females without cancer in the OptumLabs Data Warehouse. Modeled AMH patterns were compared among cyclophosphamide-based chemotherapy, non-cyclophosphamide-based chemotherapy, no chemotherapy, and no breast cancer groups.Setting: Commercially insured females in the United States.Patient(s): Females with and without breast cancer.Exposure(s): Breast cancer, cyclophosphamide- and non-cyclophosphamide-based chemotherapy.Main Outcome Measure(s): AMH levels.Result(s): A total of 233 patients with breast cancer (mean age, 34 years; standard deviation, 3.7 years) contributed 278 AMH levels over a median of 2 years (range, 0-6.7 years) after diagnosis; 52% received cyclophosphamide-based chemotherapy, 17% received non-cyclophosphamide-based chemotherapy (80% platinum-based), and 31% received no chemotherapy. A total of 2,777 matched females without cancer contributed 2,780 AMH levels. The pattern of AMH levels differed among the 4 groups. Among females without cancer and breast cancer survivors who did not undergo chemotherapy, AMH declined linearly over time. In contrast, among those who received cyclophosphamide-based and noncyclophosphamide-based chemotherapy, a nonlinear pattern of AMH level of initial fall during chemotherapy, followed by an increase over 2-4 years, and then by a plateau over 1-2 years before a decline was observed.Conclusion(s): In breast cancer survivors, AMH levels from administrative data supported ovarian toxicity of non-cyclophosphamide-based chemotherapy in breast cancer and efficiently depicted the timing and duration of changes in ovarian reserve to reflect the residual reproductive lifespan. [ABSTRACT FROM AUTHOR]

Background: Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.Methods: We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk.Findings: Among 23 601 survivors with a median follow-up of 21 years (IQR 15-25), the 20-year cumulative incidence of at least one grade 3-5 chronic condition decreased significantly from 33·2% (95% CI 32·0-34·3) in those diagnosed 1970-79 to 29·3% (28·4-30·2; p<0·0001) in 1980-89, and 27·5% (26·4-28·6; p=0·012 vs 1980-89) in 1990-99. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition in 5051 siblings was 4·6% (95% CI 3·9-5·2). The 15-year cumulative incidence of at least one grade 3-5 condition was lower for survivors diagnosed 1990-99 compared with those diagnosed 1970-79 for Hodgkin lymphoma (17·7% [95% CI 15·0-20·5] vs 26·4% [23·8-29·1]; p<0·0001), non-Hodgkin lymphoma (16·9% [14·0-19·7] vs 23·8% [19·9-27·7]; p=0.0053), astrocytoma (30·5% [27·8-33·2] vs 47·3% [42·9-51·7]; p<0·0001), Wilms tumour (11·9% [9·5-14·3] vs 17·6% [14·3-20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5-33·1] vs 36·5% [31·5-41·4]; p=0·021), and osteosarcoma (65·6% [60·6-70·6] vs 87·5% [84·1-91·0]; p<0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-99 vs 1970-79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4-63·3] vs 42·9% [34·9-50·9]; p=0·00060), and neuroblastoma (25·0% [21·8-28·2] vs 18·0% [14·5-21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64-0·92; HR with treatment in the model=0·89, 95% CI 0·72-1·11; pmediation=0·0085) and Hodgkin lymphoma (HR without treatment=0·75, 95% CI 0·65-0·85; HR with treatment=0·91, 95% CI 0·73-1·12; pmediation=0·024). Temporal decreases in 15-year cumulative incidence comparing survivors diagnosed 1970-79 to survivors diagnosed 1990-99 were noted for endocrinopathies (5·9% [5·3-6·4] vs 2·8% [2·5-3·2]; p<0·0001), subsequent malignant neoplasms (2·7% [2·3-3·1] vs 1·9% [1·6-2·2]; p=0·0033), musculoskeletal conditions (5·8% [5·2-6·4] vs 3·3% [2·9-3·6]; p<0·0001), and gastrointestinal conditions (2·3% [2·0-2·7] vs 1·5% [1·3-1·8]; p=0·00037), while hearing loss increased (3·0% [2·6-3·5] vs 5·7% [5·2-6·1]; p<0·0001).Interpretation: Our results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population.Funding: National Cancer Institute and the American Lebanese-Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

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

Background: The Affordable Care Act (ACA) increased private nonemployer health insurance options, expanded Medicaid eligibility, and provided preexisting health condition protections. We evaluated insurance coverage among long-term adult survivors of childhood cancer pre- and post-ACA implementation., Methods: Using the multicenter Childhood Cancer Survivor Study, we included participants from 2 cross-sectional surveys: pre-ACA (2007-2009; survivors: n = 7505; siblings: n = 2175) and post-ACA (2017-2019; survivors: n = 4030; siblings: n = 987). A subset completed both surveys (1840 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 increase in coverage was higher among those aged 18-25 years (survivors: +15.8% vs +2.3% or less ages 26 years and older; siblings +17.8% vs +4.2% or less ages 26 years and older). Survivors were more likely to have public insurance than siblings post-ACA (18.4% vs 6.9%; odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.1 to 2.6). Survivors with severe chronic conditions (OR = 4.7, 95% CI = 3.0 to 7.3) and those living in Medicaid expansion states (OR = 2.4, 95% CI = 1.7 to 3.4) had increased odds of public insurance coverage post-ACA. Among the subset completing both surveys, low- and mid-income survivors (<$40 000 and <$60 000, respectively) experienced 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., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described., Methods: Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings., Results: Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1])., Conclusion: Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions., Design: Retrospective cohort study., Setting: US administrative database., Patients: We identified incident breast, colorectal, and ovarian cancer cases in females aged 15-39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer., Intervention: Platinum-based chemotherapy., Main Outcome Measures: We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries)., Results: There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42-0.82) and 0.70 (95% CI 0.51-0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97-1.15) and 1.42 (95% CI 1.31-1.53), respectively., Conclusions: Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

It is unknown how common job lock (i.e., staying at job to maintain health insurance) remains among childhood cancer survivors after Affordable Care Act (ACA) implementation in 2010. We examined prevalence of and factors associated with job lock using a cross-sectional survey from the Childhood Cancer Survivor Study (3503 survivors; 942 siblings). Survivor, spousal, and any survivor/spouse job lock were more frequently reported by survivors than siblings. Survivor job lock/any job lock was associated with older age, low income, severe chronic conditions, and debt/inability to pay debt. Job lock remains more common among survivors than siblings after ACA implementation., (© 2023 Wiley Periodicals LLC.)

Purpose: To estimate the prevalence of financial hardship among adult survivors of childhood cancer compared with siblings and identify sociodemographic, cancer diagnosis, and treatment correlates of hardship among survivors in the era after implementation of the Affordable Care Act., Methods: A total of 3,555 long-term (≥ 5 years) survivors of childhood cancer and 956 siblings who completed a survey administered in 2017-2019 were identified from the Childhood Cancer Survivor Study. Financial hardship was measured by 21 survey items derived from US national surveys that had been previously cognitively tested and fielded. Principal component analysis (PCA) identified domains of hardship. Multiple linear regression examined the association of standardized domain scores (ie, scores divided by standard deviation) with cancer and treatment history and sociodemographic characteristics among survivors., Results: Survivors were more likely than siblings to report hardship in ≥ 1 item (63.4% v 53.7%, P < .001). They were more likely to report being sent to debt collection (29.9% v 22.3%), problems paying medical bills (20.7% v 12.8%), foregoing needed medical care (14.1% v 7.8%), and worry/stress about paying their rent/mortgage (33.6% v 23.2%) or having enough money to buy nutritious meals (26.8% v 15.5%); all P < .001. Survivors reported greater hardship than siblings in all three domains identified by principal component analysis: behavioral hardship (mean standardized domain score 0.51 v 0.35), material hardship/financial sacrifices (0.64 v 0.46), and psychological hardship (0.69 v 0.44), all P < .001. Sociodemographic (eg, 2 anthracycline chemotherapy, or chest radiation) were statistically significantly associated with increased hardship., Conclusion: Survivors of childhood cancer were more likely to experience financial hardship than siblings. Correlates of hardship can inform survivorship care guidelines and intervention strategies.

Background: Non-white patients with childhood cancer have worse survival than Non-Hispanic (NH) White patients for many childhood cancers in the United States. We examined the contribution of socioeconomic status (SES) and health insurance on racial/ethnic disparities in childhood cancer survival., Methods: We used the National Cancer Database to identify NH White, NH Black, Hispanic, and children of other race/ethnicities (<18 years) diagnosed with cancer between 2004 and 2015. SES was measured by the area-level social deprivation index (SDI) at patient residence and categorized into tertiles. Health insurance coverage at diagnosis was categorized as private, Medicaid, and uninsured. Cox proportional hazard models were used to compare survival by race/ethnicity. We examined the contribution of health insurance and SES by sequentially adjusting for demographic and clinical characteristics (age group, sex, region, metropolitan statistical area, year of diagnosis, and number of conditions other than cancer), health insurance, and SDI., Results: Compared with NH Whites, NH Blacks and Hispanics had worse survival for all cancers combined, leukemias and lymphomas, brain tumors, and solid tumors (all P < 0.05). Survival differences were attenuated after adjusting for health insurance and SDI separately; and further attenuated after adjusting for insurance and SDI together., Conclusions: Both SES and health insurance contributed to racial/ethnic disparities in childhood cancer survival., Impact: Improving health insurance coverage and access to care for children, especially those with low SES, may mitigate racial/ethnic survival disparities., (©2021 American Association for Cancer Research.)

Background: Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the United States., Methods: We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material [eg, problems paying bills], psychological [eg, distress], and behavioral [eg, forgoing care due to cost]) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately., Results: A total of 2588 AYA cancer survivors (median = 31 [interquartile range = 26-35] years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior., Conclusions: Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors' health, and multifaceted interventions are necessary to address underlying causes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Children treated for cancer are at risk for neuromuscular dysfunction, but data are limited regarding prevalence, longitudinal patterns, and long-term impact., Methods: Longitudinal surveys from 25,583 childhood cancer survivors ≥5 years from diagnosis and 5,044 siblings from the Childhood Cancer Survivor Study were used to estimate the prevalence and cumulative incidence of neuromuscular dysfunction. Multivariable models adjusted for age, sex, race, and ethnicity estimated prevalence ratios (PR) of neuromuscular dysfunction in survivors compared with siblings, and associations with treatments and late health/socioeconomic outcomes., Results: Prevalence of neuromuscular dysfunction was 14.7% in survivors 5 years postdiagnosis versus 1.5% in siblings [PR, 9.9; 95% confidence interval (CI), 7.9-12.4], and highest in survivors of central nervous system (CNS) tumors (PR, 27.6; 95% CI, 22.1-34.6) and sarcomas (PR, 11.5; 95% CI, 9.1-14.5). Cumulative incidence rose to 24.3% in survivors 20 years postdiagnosis (95% CI, 23.8-24.8). Spinal radiotherapy and increasing cranial radiotherapy dose were associated with increased prevalence of neuromuscular dysfunction. Platinum exposure (vs. none) was associated with neuromuscular dysfunction (PR, 1.8; 95% CI, 1.5-2.1), even after excluding survivors with CNS tumors, cranial/spinal radiotherapy, or amputation. Neuromuscular dysfunction was associated with concurrent or later obesity (PR, 1.1; 95% CI, 1.1-1.2), anxiety (PR, 2.5; 95% CI, 2.2-2.9), depression (PR, 2.1; 95% CI, 1.9-2.3), and lower likelihood of graduating college (PR, 0.92; 95% CI, 0.90-0.94) and employment (PR, 0.8; 95% CI, 0.8-0.9)., Conclusions: Neuromuscular dysfunction is prevalent in childhood cancer survivors, continues to increase posttherapy, and is associated with adverse health and socioeconomic outcomes., Impact: Interventions are needed to prevent and treat neuromuscular dysfunction, especially in survivors with platinum and radiation exposure., (©2021 American Association for Cancer Research.)

Purpose: To determine the incidence of serious chronic health conditions among survivors of pediatric Hodgkin lymphoma (HL), compare by era of therapy and by selected cancer therapies, and provide estimates of risks associated with contemporary therapy., Methods: Assessing 2,996 5-year HL survivors in the Childhood Cancer Survivor Study diagnosed from 1970 to 1999, we examined the cumulative incidence of severe to fatal chronic conditions (grades 3-5) using self-report conditions, medically confirmed subsequent malignant neoplasms, and cause of death based on the National Death Index. We used multivariable regression models to estimate hazard ratios (HRs) per decade and by key treatment exposures., Results: HL survivors were of a mean age of 35.6 years (range, 12-58 years). The cumulative incidence of any grade 3-5 condition by 35 years of age was 31.4% (95% CI, 29.2 to 33.5). Females were twice as likely (HR, 2.1; 95% CI, 1.8 to 2.4) to have a grade 3-5 condition compared with males. From the 1970s to the 1990s, there was a 20% reduction (HR, 0.8; 95% CI, 0.7 to 0.9) in decade-specific risk of a grade 3-5 condition ( P trend = .002). In survivors who had a recurrence and/or hematopoietic cell transplant, the risk of a grade 3-5 condition was substantially elevated, similar to that of survivors treated with high-dose, extended-field radiotherapy (HR, 1.2; 95% CI, 0.9 to 1.5). Compared with survivors treated with chest radiotherapy ≥ 35 Gy in combination with an anthracycline or alkylator, a contemporary regimen for low-intermediate risk HL was estimated to lead to a 40% reduction in risk of a grade 3-5 condition (HR, 0.6; 95% CI, 0.4 to 0.8)., Conclusion: This study demonstrates that risk-adapted therapy for pediatric HL has resulted in a significant reduction in serious long-term outcomes.

Background: Individuals diagnosed with acute lymphoblastic leukemia (ALL) between the ages of 22 and 39 years experience worse outcomes than those diagnosed when they are 21 years old or younger. Treatment at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) mitigates these disparities but may be associated with higher expenditures., Methods: Using deidentified administrative claims data (OptumLabs Data Warehouse), the cancer-related expenditures were examined among patients with ALL diagnosed between 2001 and 2014. Multivariable generalized linear model with log-link modeled average monthly health-plan-paid (HPP) expenditures and amount owed by the patient (out-of-pocket [OOP]). Cost ratios were used to calculate excess expenditures (CCC vs non-CCC). Incidence rate ratios (IRRs) compared CCC and non-CCC monthly visit rates. Models adjusted for sociodemographics, comorbidities, adverse events, and months enrolled., Results: Clinical and sociodemographic characteristics were comparable between CCC (n = 160) and non-CCC (n = 139) patients. Higher monthly outpatient expenditures in CCC patients ($15,792 vs $6404; P < .001) were driven by outpatient hospital HPP expenditures. Monthly visit rates and per visit expenditures for nonchemotherapy visits (IRR = 1.6; P = .001; CCC = $8247, non-CCC = $1191) drove higher outpatient hospital expenditures among CCCs. Monthly OOP expenditures were higher at CCCs for outpatient care (P = .02). Inpatient HPP expenditures were significantly higher at CCCs ($25,918 vs $13,881; ꞵ = 0.9; P < .001) before accounting for adverse events but were no longer significant after adjusting for adverse events (ꞵ = 0.4; P = .1). Hospitalizations and length of stay were comparable., Conclusions: Young adults with ALL at CCCs have higher expenditures, likely reflecting differences in facility structure, billing practices, and comprehensive patient care. It would be reasonable to consider CCCs comparable to the oncology care model and incentivize the framework to achieve superior outcomes and long-term cost savings., Lay Summary: Health care expenditures in young adults (aged 22-39 years) with acute lymphoblastic leukemia (ALL) are higher among patients at National Cancer Institute-designated Comprehensive Cancer Centers (CCC) than those at non-CCCs. The CCC/non-CCC differences are significant among outpatient expenditures, which are driven by higher rates of outpatient hospital visits and outpatient hospital expenditures per visit at CCCs. Higher expenditures and visit rates of outpatient hospital visits among CCCs may also reflect how facility structure and billing patterns influence spending or comprehensive care. Young adults at CCCs face higher inpatient HPP expenditures; these are driven by serious adverse events., (© 2021 American Cancer Society.)

Background: Anthracycline-induced cardiotoxicity is a major cause of morbidity and mortality in childhood cancer survivors (CCSs). Echocardiographic myocardial strain imaging is recommended in adult patients with cancer, but its role in pediatric CCSs has not been well established. Aims of this study were to determine the prevalence of abnormalities in left ventricular strain in pediatric CCSs, to compare strain with other echocardiographic measurements and blood biomarkers, and to explore risk factors for reduced strain., Methods: CCSs ≥3 years from their last anthracycline treatment were enrolled in this multicenter study and underwent a standardized functional echocardiogram and biomarker collection. Regression analysis was used to identify factors associated with longitudinal strain (LS)., Results: Five hundred forty-six pediatric CCSs were compared with 134 healthy controls. Abnormal left ventricular ejection fraction (<50%) and mean LS ( Z score, <-2) was found in 0.8% and 7.7% of the CCSs, respectively. LS was significantly lower in CCSs than in controls, but the absolute difference was small (0.7%). Lower LS in CCSs was associated with older current age and higher body surface area. Sex, cumulative anthracycline dose, radiotherapy, and biomarkers were not independently associated with LS. Circumferential strain, diastolic parameters, and biomarkers were not significantly different in pediatric CCSs., Conclusions: Global systolic function and LS are only mildly reduced in pediatric CCSs, and most LS values are within normal range. This makes single LS measurements of limited added value in identifying CCSs at risk for cardiac dysfunction. The utility of strain imaging in the long-term follow-up of CCS remains to be demonstrated.

Importance: Adult survivors of childhood cancer are at excess risk for mortality compared with the general population. Whether exercise attenuates this risk is not known., Objective: To examine the association between vigorous exercise and change in exercise with mortality in adult survivors of childhood cancer., Design, Setting, and Participants: Multicenter cohort analysis among 15 450 adult cancer survivors diagnosed before age 21 years from pediatric tertiary hospitals in the United States and Canada between 1970 and 1999 enrolled in the Childhood Cancer Survivor Study, with follow-up through December 31, 2013., Exposures: Self-reported vigorous exercise in metabolic equivalent task (MET) hours per week. The association between vigorous exercise and change in vigorous exercise and cause-specific mortality was assessed using multivariable piecewise exponential regression analysis to estimate rate ratios., Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary end points were cause-specific mortality (recurrence/progression of primary malignant neoplasm and health-related mortality). Outcomes were assessed via the National Death Index., Results: The 15 450 survivors had a median age at interview of 25.9 years (interquartile range [IQR], 9.5 years) and were 52.8% male. During a median follow-up of 9.6 years (IQR, 15.5 years), 1063 deaths (811 health-related, 120 recurrence/progression of primary cancer, 132 external/unknown causes) were documented. At 15 years, the cumulative incidence of all-cause mortality was 11.7% (95% CI, 10.6%-12.8%) for those who exercised 0 MET-h/wk, 8.6% (95% CI, 7.4%-9.7%) for 3 to 6 MET-h/wk, 7.4% (95% CI, 6.2%-8.6%) for 9 to 12 MET-h/wk, and 8.0% (95% CI, 6.5%-9.5%) for 15 to 21 MET-h/wk (P < .001). There was a significant inverse association across quartiles of exercise and all-cause mortality after adjusting for chronic health conditions and treatment exposures (P = .02 for trend). Among a subset of 5689 survivors, increased exercise (mean [SD], 7.9 [4.4] MET-h/wk) over an 8-year period was associated with a 40% reduction in all-cause mortality rate compared with maintenance of low exercise (rate ratio, 0.60; 95% CI, 0.44-0.82; P = .001)., Conclusions and Relevance: Vigorous exercise in early adulthood and increased exercise over 8 years was associated with lower risk of mortality in adult survivors of childhood cancer.

Background: Childhood cancer survivors treated with radiotherapy to a field including the colon or rectum have an elevated risk of developing radiation-induced colorectal cancer (CRC). The Children's Oncology Group recommends colonoscopy every 5 years beginning at age 35 years for at-risk survivors., Methods: Analyses included 702 five-year survivors (Childhood Cancer Survivor Study) aged ≥36 years who received ≥30 gray of abdominal, pelvic, or spinal radiotherapy. Multivariate generalized linear models were used to calculate relative risks (RR) with 95% confidence intervals (95% CI) for adherence to the Children's Oncology Group's CRC surveillance recommendations., Results: With a median age of 43 years (range, 36-58 years), 29.5% of the survivors (207 of 702 survivors) met surveillance recommendations. In multivariate analyses, age ≥50 years versus age 36 to 49 years (RR, 2.6; 95% CI, 2.0-3.4), reporting a routine cancer follow-up visit within 1 year before the study (RR, 1.5; 95% CI, 1.0-2.2), reporting ≥10 physician visits within the past year versus 0 to 9 visits (RR, 1.4; 95% CI, 1.1-1.7), and discussing future cancer risk with a physician at the time of the most recent follow-up visit (RR, 1.4; 95% CI, 1.1-1.7) were found to be associated with adherence to CRC surveillance recommendations., Conclusions: Greater than 70% of survivors at an increased risk of CRC were not screened as recommended. Regular physician contact and discussion of screening were associated with a 60% increase in CRC surveillance. Educational interventions targeted at survivors and their primary care physicians are needed to heighten knowledge of CRC risk after radiotherapy and the importance of appropriate surveillance., (© 2015 American Cancer Society.)

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

Background: Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols., Methods: We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population., Findings: We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living., Interpretation: The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted., Funding: National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Childhood cancer survivors develop gastrointestinal cancer more frequently and at a younger age than the general population, but the risk factors have not been well-characterized., Objective: To determine the risk and associated risk factors for gastrointestinal subsequent malignant neoplasms (SMNs) in childhood cancer survivors., Design: Retrospective cohort study., Setting: The Childhood Cancer Survivor Study, a multicenter study of childhood cancer survivors diagnosed between 1970 and 1986., Patients: 14 358 survivors of cancer diagnosed when they were younger than 21 years of age who survived for 5 or more years after the initial diagnosis., Measurements: Standardized incidence ratios (SIRs) for gastrointestinal SMNs were calculated by using age-specific population data. Multivariate Cox regression models identified associations between risk factors and gastrointestinal SMN development., Results: At median follow-up of 22.8 years (range, 5.5 to 30.2 years), 45 cases of gastrointestinal cancer were identified. The risk for gastrointestinal SMNs was 4.6-fold higher in childhood cancer survivors than in the general population (95% CI, 3.4 to 6.1). The SIR for colorectal cancer was 4.2 (CI, 2.8 to 6.3). The highest risk for gastrointestinal SMNs was associated with abdominal radiation (SIR, 11.2 [CI, 7.6 to 16.4]). However, survivors not exposed to radiation had a significantly increased risk (SIR, 2.4 [CI, 1.4 to 3.9]). In addition to abdominal radiation, high-dose procarbazine (relative risk, 3.2 [CI, 1.1 to 9.4]) and platinum drugs (relative risk, 7.6 [CI, 2.3 to 25.5]) independently increased the risk for gastrointestinal SMNs., Limitation: This cohort has not yet attained an age at which risk for gastrointestinal cancer is greatest., Conclusion: Childhood cancer survivors, particularly those exposed to abdominal radiation, are at increased risk for gastrointestinal SMNs. These findings suggest that surveillance of at-risk childhood cancer survivors should begin at a younger age than that recommended for the general population., Primary Funding Source: National Cancer Institute.

Background: The 5-year survival rate for individuals with neuroblastoma is approaching 70%. Few data exist, however, on the long-term outcomes of these patients, who are often treated at a very young age., Methods: Outcome data were obtained for 954 5-year neuroblastoma survivors who were diagnosed in 1970-1986 and enrolled in the Childhood Cancer Survivor Study (CCSS). Late mortality, second malignant neoplasms, and chronic health conditions were analyzed in relation to treatment factors using Poisson regression models and their modification with generalized estimating equations. Neuroblastoma survivors were compared with a cohort of 3899 siblings of CCSS participants for risk of chronic health conditions and selected sociodemographic outcomes. All statistical tests were two-sided., Results: Six percent of patients died more than 5 years after their diagnosis (standardized mortality ratio = 5.6; 95% confidence interval [CI] = 4.4 to 6.9). The most common causes of death were disease recurrence (n = 43) and second malignant neoplasms (n = 13). The cumulative incidence of second malignant neoplasms was 3.5% at 25 years and 7.0% at 30 years after diagnosis. Compared with the sibling cohort, survivors had an increased risk of selected chronic health conditions (risk ratio [RR] = 8.3; 95% CI = 7.1 to 9.7) with a 20-year cumulative incidence of 41.1%. The most prevalent outcomes involved the neurological, sensory, endocrine, and musculoskeletal systems, with 20-year cumulative incidences of 29.8%, 8.6%, 8.3%, and 7.8%, respectively. Neuroblastoma survivors who were treated with multimodality therapy were more likely to develop a chronic health condition than survivors treated with surgery alone (RR = 2.2; 95% CI = 1.6 to 3.0). Neuroblastoma survivors were less likely than siblings to have ever been employed (P = .04) or to be married (P < .001) and had a lower personal income (P = .009)., Conclusions: Neuroblastoma survivors have an increased rate of mortality and second malignant neoplasms, relative to the age- and sex-comparable US population, and of chronic health conditions, relative to their siblings, which underscores the need for long-term medical surveillance.

Survival for childhood cancer has increased dramatically over the last 40 years with 5-year survival rates now approaching 80%. For many diagnostic groups, rapid increases in survival began in the 1970s with the broader introduction of multimodality approaches, often including combination chemotherapy with or without radiation therapy. With this increase in rates of survivorship has come the recognition that survivors are at risk for adverse health and quality-of-life outcomes, with risk being influenced by host-, disease-, and treatment-related factors. In 1994, the US National Cancer Institute funded the Childhood Cancer Survivor Study, a multi-institutional research initiative designed to establish a large and extensively characterized cohort of more than 14,000 5-year survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. This ongoing study, which reflects the single most comprehensive body of information ever assembled on childhood and adolescent cancer survivors, provides a dynamic framework and resource to investigate current and future questions about childhood cancer survivors.

Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.

With modern therapies and supportive care, survival of childhood cancer has increased considerably. Patients who have survived cancers involving the central nervous system or who have received therapy toxic to the developing brain are at risk of long-term neurocognitive sequelae. Negative outcomes are observed most frequently in survivors of acute lymphoblastic leukemia and brain tumors. The Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer has generated risk-based, exposure-related guidelines designed to direct the follow-up care of survivors of pediatric malignancies based on a comprehensive literature review and expert opinion. This article expands on these guidelines by reviewing the risk factors for the development of neurocognitive sequelae and describing the expected pattern of these disabilities. We herein present recommendations for the screening and management of neurocognitive late effects and outline important areas of school and legal advocacy for survivors with disabilities. Finally, we list resources that can guide patients, their parents, and their medical caregivers as they face the long-term neurocognitive consequences of cancer therapy.