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Alterations in treatment intensity and decreased use of radiation therapy have reduced the risk of late treatment-related death in long-term survivors of childhood cancer. In the 1960s, fewer than half the children in whom cancer was diagnosed were still alive 5 years later. 1 Now, more than 83% of patients with a childhood cancer in the United States become 5-year survivors of the disease. 2 As a result, in 2013 it was estimated that there were more than 420,000 survivors of childhood cancer in the United States and that by the year 2020 this number would surpass 500,000. 3 Increased success in the treatment of childhood cancers has been achieved through the systematic conduct of clinical trials to assess the efficacy of multimodal approaches involving combination chemotherapy, . . .

The Childhood Cancer Survivor Study found a high rate of illness owing to chronic health conditions among more than 10,000 adult survivors of childhood cancer. The Childhood Cancer Survivor Study found a high rate of illness owing to chronic health conditions among more than 10,000 adult survivors of childhood cancer. As a result of advances in treatment, almost 80% of children and adolescents who receive a diagnosis of cancer become long-term survivors. 1 In the United States, there are approximately 270,000 survivors of pediatric cancer, or about 1 of every 640 adults between the ages of 20 and 39 years. 2 The large number of survivors has prompted studies of the long-term health consequences of treatments for childhood cancer. 2 – 4 It is now clear that damage to the organ systems of children caused by chemotherapy and radiation therapy may not become clinically evident for many years. To understand fully the health risks . . .

Female cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health needs of emerging adult female survivors of childhood cancer and to identify decisional and contextual factors that influence pursuit of FSA using an explanatory sequential quantitative to qualitative mixed methods design. This study will enroll 325 female survivors (aged 18 to 29 years and >1-year post treatment; diagnosed with cancer < age 21 years) from four cancer centers in the United States. Sociodemographic and developmental factors, reproductive knowledge and values, decisional needs, and receipt of an FSA will be assessed through a web-based survey. Informed by survey findings, a subset of participants will be recruited for qualitative interviews to explore decisional factors associated with uptake of an FSA. Clinical data will be abstracted from the medical records. Multivariable logistic regression models will be developed to identify factors associated with FSA and qualitative descriptive analysis will be used to develop themes from the interviews. Quantitative and qualitative findings will be merged using a joint display to develop integrated study conclusions and direct future interventional research.

Previous studies have indicated that thyroid cancer risk after a first childhood malignancy is curvilinear with radiation dose, increasing at low to moderate doses and decreasing at high doses. Understanding factors that modify the radiation dose response over the entire therapeutic dose range is challenging and requires large numbers of subjects. We quantified the long-term risk of thyroid cancer associated with radiation treatment among 12,547 5-year survivors of a childhood cancer (leukemia, Hodgkin lymphoma and non-Hodgkin lymphoma, central nervous system cancer, soft tissue sarcoma, kidney cancer, bone cancer, neuroblastoma) diagnosed between 1970 and 1986 in the Childhood Cancer Survivor Study using the most current cohort follow-up to 2005. There were 119 subsequent pathologically confirmed thyroid cancer cases, and individual radiation doses to the thyroid gland were estimated for the entire cohort. This cohort study builds on the previous case-control study in this population (69 thyroid cancer cases with follow-up to 2000) by allowing the evaluation of both relative and absolute risks. Poisson regression analyses were used to calculate standardized incidence ratios (SIR), excess relative risks (ERR) and excess absolute risks (EAR) of thyroid cancer associated with radiation dose. Other factors such as sex, type of first cancer, attained age, age at exposure to radiation, time since exposure to radiation, and chemotherapy (yes/no) were assessed for their effect on the linear and exponential quadratic terms describing the dose–response relationship. Similar to the previous analysis, thyroid cancer risk increased linearly with radiation dose up to approximately 20 Gy, where the relative risk peaked at 14.6-fold (95% CI, 6.8–31.5). At thyroid radiation doses >20 Gy, a downturn in the dose–response relationship was observed. The ERR model that best fit the data was linear-exponential quadratic. We found that age at exposure modified the ERR linear dose term (higher radiation risk with younger age) (P < 0.001) and that sex (higher radiation risk among females) (P  =  0.008) and time since exposure (higher radiation risk with longer time) (P < 0.001) modified the EAR linear dose term. None of these factors modified the exponential quadratic (high dose) term. Sex, age at exposure and time since exposure were found to be significant modifiers of the radiation-related risk of thyroid cancer and as such are important factors to account for in clinical follow-up and thyroid cancer risk estimation among childhood cancer survivors.

The reproductive implications of mutagenic treatments given to children with cancer are not clear. By studying the risk of untoward pregnancy outcomes, we indirectly assessed the risk of transmission of germline damage to the offspring of survivors of childhood cancer who were given radiotherapy and chemotherapy. We did a retrospective cohort analysis, within the Childhood Cancer Survivor Study (CCSS), of the risk of stillbirth and neonatal death among the offspring of men and women who had survived childhood cancer. Patients in CCSS were younger than 21 years at initial diagnosis of an eligible cancer, were treated at 25 US institutions and one Canadian institution, and had survived for at least 5 years after diagnosis. We quantified the chemotherapy given to patients, and the preconception radiation doses to the testes, ovaries, uterus, and pituitary gland, and related these to the risk of stillbirth or neonatal death using Poisson regression analysis. Among 1148 men and 1657 women who had survived childhood cancer, there were 4946 pregnancies. Irradiation of the testes (16 [1%] of 1270; adjusted relative risk 0·8 [95% CI 0·4–1·6]; mean dose 0·53 Gy [SD 1·40]) and pituitary gland (17 [3%] of 510, 1·1 [0·5–2·4] for more than 20·00 Gy; mean dose 10·20 Gy [13·0] for women), and chemotherapy with alkylating drugs (26 [2%] of 1195 women, 0·9 [0·5–1·5]; ten [1%] of 732 men, 1·2 [0·5–2·5]) were not associated with an increased risk of stillbirth or neonatal death. Uterine and ovarian irradiation significantly increased risk of stillbirth and neonatal death at doses greater than 10·00 Gy (five [18%] of 28, 9·1 [3·4–24·6]). For girls treated before menarche, irradiation of the uterus and ovaries at doses as low as 1·00–2·49 Gy significantly increased the risk of stillbirth or neonatal death (three [4%] of 69, 4·7 [1·2–19·0]). Our findings do not support concern about heritable genetic changes affecting the risk of stillbirth and neonatal death in the offspring of men exposed to gonadal irradiation. However, uterine and ovarian irradiation had serious adverse effects on the offspring that were probably related to uterine damage. Careful management is warranted of pregnancies in women given high doses of pelvic irradiation before puberty. Westlakes Research Institute, National Cancer Institute, and Children's Cancer Research Fund.

Background The Children's Oncology Group Guidelines recommend a cardiacechocardiogram, or comparable functional imaging, following therapy completion in survivors of childhood/adolescent cancers exposed to anthracyclines. Methods Using the 2009–2019 Merative™ MarketScan® Commercial Database, we examined real‐world utilization of cardiac testing among 1609 anthracycline‐treated survivors of childhood/adolescent cancers. Results The cumulative incidence of receiving an initial cardiac test by 5.25 years from the index date (six months after end‐of‐therapy) was 62.3% (95% CI = 57.5%–66.7%), with median time to initial test being 2.7 years (95% CI = 2.5%–3.1%). Young adults (18–28 years) were less likely than children (≤17 years) to receive cardiac testing (hazard ratio [HR] = 0.42, 95% CI = 0.3%–0.49%). More likely to receive cardiac testing were survivors receiving hematopoietic stem cell transplantation versus chemotherapy only (HR = 2.23, 95% CI = 1.63%–3.03%), and survivors with bone or soft tissue versus hematologic cancer (HR = 1.64, 95% CI = 1.30%–2.07%). Conclusions Nearly 40% of anthracycline‐treated survivors of childhood/adolescent cancers had not received cardiac testing within 5.25 years post‐index date, with young adults least likely to receive a test. In this nationwide, insurance claims data‐based study, we examined the real‐world utilization of cardiac tests after therapy completion among anthracycline‐treated survivors of childhood and adolescent cancer. We found that nearly 40% of anthracycline‐treated survivors at risk of cardiac dysfunction had not received any cardiac test within 5.25 years from 6 months after end‐of‐therapy, despite national guidelines detailing the importance of timely screening for early detection of cardiac dysfunction. Young adult survivors were least likely to receive cardiac testing despite having insurance.

Background Vaccination against COVID‐19 is recommended for childhood cancer survivors (CCS). This study aimed to identify antecedents contributing to caregivers' decisions to vaccinate CCS aged 5–17 years against COVID‐19 by applying the Theory of Planned Behavior. Methods Participants in this cross‐sectional study completed an online survey assessing caregiver attitudes, subjective norms, perceived behavioral control, intention to vaccinate CCS, CCS vaccination status, COVID‐19 health literacy, and frequency of COVID‐19 information‐seeking. Surveys were completed between May and June 2022 following approval for the emergency use of COVID‐19 vaccines among children aged ≥5 years in the U.S. Data were analyzed using unadjusted linear regressions and structural equation modeling. Results Participants were caregivers (n = 160, 87.5% biological mothers, 75.6% white/non‐Hispanic) of CCS (n = 160, 44.4% female, mean (M) = 12.5 years old, M = 8.0 years off treatment). 70.0% (n = 112) of caregivers and 53.8% (n = 86) of CCS received a COVID‐19 vaccine. Over one‐third (37.5%) of caregivers reported disagreement or indecision about future COVID‐19 vaccination for the CCS. Caregivers' intention (β = 0.962; standard error [S.E.] = 0.028; p < 0.001) was highly related to CCS vaccination status. Attitudes (β = 0.568; S.E. = 0.078; p < 0.001) and subjective norms (β = 0.322; S.E. = 0.062; p < 0.001) were associated with intention. Higher frequency of COVID‐19 information‐seeking (β = 0.313; S.E. = 0.063; p < 0.001) and COVID‐19 health literacy (β = 0.234; S.E. = 0.059; p < 0.001) had a positive indirect effect on intention through attitudes and subjective norms. Conclusions Caregivers' vaccination intentions for minor CCS are highly related to vaccination behavior and shaped by attitudes, subjective norms, COVID‐19 health literacy, and frequency of COVID‐19 information‐seeking. Promoting tailored communication with caregivers of CCS and encouraging them to review reputable sources of information can address their vaccine hesitancy.

Survivors of childhood cancer may experience important disease- and treatment-related late effects, including functional limitations. This study evaluated performance limitations and restricted abilities to participate in personal care, to engage in routine activities like shopping or housework, and to attend work or school (participation restrictions) in a cohort of survivors of childhood cancer. Epidemiologic survey and 26 institutions that treat childhood cancer. Participants included 11 481 persons who were treated for primary brain cancer, leukemia, Hodgkin disease, non-Hodgkin lymphoma, kidney tumor, neuroblastoma, soft-tissue sarcoma, or malignant bone tumor before the age of 21 years and who survived at least 5 years after diagnosis. The comparison group included 3839 siblings of survivors of childhood cancer. Medical data were abstracted, and participants or parents (if the participants were <18 years of age at survey completion) completed a 24-page questionnaire. Compared with siblings, survivors were more likely to report performance limitations (risk ratio, 1.8 [95% CI, 1.7 to 2.0]) and to report restricted participation in personal care skills (risk ratio, 4.7 [CI, 3.0 to 7.2]), routine activities (risk ratio, 4.7 [CI, 3.6 to 6.2]), and the ability to attend work or school (risk ratio, 5.9 [CI, 4.5 to 7.6]). Survivors of brain (26.6%) and bone (36.9%) cancer were most likely to report performance limitations, restricted ability to do routine activities (20.9% and 8.5%, respectively), and restricted ability to attend work or school (20.0% and 11.2%, respectively). Survivors of brain cancer were also most likely to report restricted abilities to perform personal care (10.5%). There was the potential for participants to be healthier or more physically capable than nonparticipants or for persons to be more motivated to participate in this study if they had functional deficits. In addition, the nature of the questionnaire did not allow specific physical limitations to be measured. Long-term survivors of childhood cancer are at increased risk for functional limitations in physical performance and in participation in activities needed for daily living.

5-year survival after childhood cancer does not fully describe life-years lost due to childhood cancer because there are a large number of deaths occurring beyond 5-years (late mortality) related to cancer and cancer treatment. Specific causes of health-related (non-recurrence, non-external) late mortality and risk reduction through modifiable lifestyle and cardiovascular risk factors are not well described. Through using a well-characterised cohort of 5-year survivors of the most common childhood cancers, we evaluated specific health-related causes of late mortality and excess deaths compared with the general US population and identified targets to reduce future risk. In this multi-institutional, hospital-based, retrospective cohort study, late mortality (death ≥5 years from diagnosis) and specific causes of death were evaluated in 34 230 5-year survivors of childhood cancer diagnosed at an age younger than 21 years from 1970 to 1999 at 31 institutions in the USA and Canada; median follow-up from diagnosis was 29 years (range 5–48) in the Childhood Cancer Survivor Study. Demographic, self-reported modifiable lifestyle (ie, smoking, alcohol, physical activity, and BMI) and cardiovascular risk factors (ie, hypertension, diabetes, and dyslipidaemia) associated with health-related mortality (which excludes death from primary cancer and external causes and includes death from late effects of cancer therapy) were evaluated. 40-year cumulative all-cause mortality was 23·3% (95% CI 22·7–24·0), with 3061 (51·2%) of 5916 deaths from health-related causes. Survivors 40 years or more from diagnosis experienced 131 excess health-related deaths per 10 000 person-years (95% CI 111–163), including those due to the top three causes of health-related death in the general population: cancer (absolute excess risk per 10 000 person-years 54, 95% CI 41–68), heart disease (27, 18–38), and cerebrovascular disease (10, 5–17). Healthy lifestyle and absence of hypertension and diabetes were each associated with a 20–30% reduction in health-related mortality independent of other factors (all p values ≤0·002). Survivors of childhood cancer are at excess risk of late mortality even 40 years from diagnosis, due to many of the leading causes of death in the US population. Modifiable lifestyle and cardiovascular risk factors associated with reduced risk for late mortality should be part of future interventions. US National Cancer Institute and the American Lebanese Syrian Associated Charities.

The COVID-19 pandemic propelled telemental health utilization among children seeking mental health (MH) services. We examined racial and ethnic disparities in telemental health use among publicly insured children before and following COVID-19. We identified 36,877,141 child-year observations among publicly insured children aged 3 to 17 years with MH-related encounters in a given year from 2016 to 2020. Multivariable linear regressions controlling for individual- and county-level confounders estimated changes in telemental health use before (2016-2019) and following the pandemic (2020) and how these changes differed by individual- and county-level race and ethnicity. The percentage of publicly insured children using telemental health increased from 2.74% pre-COVID-19 to 35.90% in 2020. Among non-Hispanic White children, 3.41% used telemental health care pre-COVID-19, which increased by 36.49 percentage points (PP) in 2020. Non-Hispanic Black children had a lower percentage of telemental health use (2.50%) pre-COVID-19, which increased by 31.20 PP in 2020, resulting in a 5.39 PP smaller increase than non-Hispanic White children (P < .001). Similarly, Hispanic, non-Hispanic Asian, and non-Hispanic Pacific Islander children had 6.19 PP, 15.45 PP, and 12.10 PP smaller increases in telemental health use in 2020 compared with non-Hispanic White children (all P < .001). Moreover, children in counties with the highest (vs lowest) quartiles of non-Hispanic Black and Hispanic populations had lower pre-COVID-19 telemental health use and smaller increases in 2020 (all P < .001). Racial and ethnic disparities in telemental health use widened following COVID-19. Future research should evaluate how telemental health use impacted MH care quality and outcomes among publicly insured children.