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Health care systems and providers have a responsibility to ensure that access to cancer clinical trials, opportunities to complete the trial, and access to lifelong survivor care are all thoughtfully examined with an equity lens. This will allow the greatest possible number of pediatric and adolescent and young adult cancer patients to receive the highest quality of care possible, in treatment and beyond. [ABSTRACT FROM AUTHOR]

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

Aims: To estimate the level of alcohol consumption behaviors in adult survivors of childhood cancer and to test associations between alcohol consumption behaviors and symptoms of neurocognitive impairment and emotional distress. Design Retrospective cohort study with longitudinal follow‐up of self‐reported health outcomes. Setting: Childhood Cancer Survivor Study (CCSS), a 26‐center study of ≥ 5‐year survivors of childhood cancer diagnosed ≤ 21 years of age between 1970 and 1986 in the United States and Canada. Participants: A total of 4484 adult survivors of childhood cancer [mean (standard deviation) age at evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651 sibling controls who completed surveys reporting on alcohol use, neurocognitive impairment and emotional distress. Measurements Survivor report of alcohol use included age at drinking initiation and quantity and frequency of alcohol consumption. Neurocognition was assessed using the CCSS Neurocognitive Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms Inventory–18 and the Posttraumatic Stress Diagnostic Scale. Findings After adjustment for childhood cancer treatment exposures, including cranial radiation therapy, drinking initiation prior to 18 years of age was associated with 30% increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95% confidence interval (CI) = 1.1–1.5]. Younger age at drinking initiation was associated with future risk of depression (RR = 1.3; 95% CI = 1.1–1.5), anxiety (RR = 1.6; 95% CI = 1.3–2.1), and somatization (RR = 1.2; 95% CI = 1.1–1.4). Persistent heavy/risky drinking was associated with 80% increased risk of persistent psychological distress (RR = 1.8, 95% CI = 1.4–2.3). Conclusions: Drinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer are at significant risk for serious chronic health conditions and subsequent cancers because of their prior treatment exposures. However, little is known about survivors' perceptions of their future health risks.Methods: This study examined self-reported levels of concern about future health and subsequent cancer in 15,620 adult survivors of childhood cancer (median age, 26 years; median time since diagnosis, 17 years) and 3991 siblings in the Childhood Cancer Survivor Study. The prevalence of concerns was compared between survivors and siblings, and the impact of participant characteristics and treatment exposures on concerns was examined with multivariable modified Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results: A substantial proportion of survivors were not concerned about their future health (31%) or developing cancer (40%). The prevalence of concern in survivors was modestly higher (RR for future health, 1.12; 95% CI, 1.09-1.15) or similar (RR for subsequent cancer, 1.02; 95% CI, 0.99-1.05) in comparison with siblings. Survivors exposed to high doses of radiation (≥20 Gy) were more likely to report concern (RR for future health, 1.13; 95% CI, 1.09-1.16; RR for subsequent cancer, 1.14; 95% CI, 1.10-1.18), but 35% of these high-risk survivors were not concerned about developing cancer, and 24% were not concerned about their future health.Conclusions: A substantial subgroup of survivors were unconcerned about their future health and subsequent cancer risks, even after exposure to treatments associated with increased risk. These survivors may be less likely to engage in beneficial screening and risk-reduction activities. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Anthracycline-induced cardiac toxicity is a cause of significant morbidity and early mortality in survivors of childhood cancer. Current strategies for predicting which children are at greatest risk for toxicity are imperfect and diagnosis of cardiac injury is usually made relatively late in the natural history of the disease. This study aims to identify genomic, biomarker and imaging parameters that can be used as predictors of risk or aid in the early diagnosis of cardiotoxicity.Methods: This is a prospective longitudinal cohort study that recruited two cohorts of pediatric cancer patients at six participating centres: (1) an Acute Cohort of children newly diagnosed with cancer prior to starting anthracycline therapy (n = 307); and (2) a Survivor Cohort of long-term survivors of childhood cancer with past exposure to anthracycline (n = 818). The study team consists of three collaborative cores. The Genomics Core is identifying genomic variations in anthracycline metabolism and in myocardial response to injury that predispose children to treatment-related cardiac toxicity. The Biomarker Core is identifying existing and novel biomarkers that allow for early diagnosis and prognosis of anthracycline-induced cardiac toxicity. The Imaging Core is identifying echocardiographic and cardiac magnetic resonance (CMR) imaging parameters that correspond to early signs of cardiac dysfunction and remodeling and precede global dysfunction and clinical symptoms. The data generated by the cores will be combined to create an integrated risk-prediction model aimed at more accurate identification of children who are most susceptible to anthracycline toxicity.Discussion: We aim to identify genomic risk factors that predict risk for anthracycline cardiotoxicity pre-exposure and imaging and biomarkers that facilitate early diagnosis of cardiac injury. This will facilitate a personalized approach to identifying at-risk children with cancer who may benefit from cardio- protective strategies during therapy, and closer surveillance and earlier initiation of medications to preserve heart function after cancer therapy.Trial Registration: NCT01805778 . Registered 28 February 2013; retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The effect of temporal changes in cancer therapy on health status among childhood cancer survivors has not been evaluated.Objective: To compare proportions of self-reported adverse health status outcomes among childhood cancer survivors across 3 decades.Design: Cross-sectional. (ClinicalTrials.gov: NCT01120353).Setting: 27 North American institutions.Participants: 14 566 adults, who survived for 5 or more years after initial diagnosis (median age, 27 years; range, 18 to 48 years), treated from 1970 to 1999.Measurements: Patient report of poor general or mental health, functional impairment, activity limitation, or cancer-related anxiety or pain was evaluated as a function of treatment decade, cancer treatment exposure, chronic health conditions, demographic characteristics, and health habits.Results: Despite reductions in late mortality and the proportions of survivors with severe, disabling, or life-threatening chronic health conditions (33.4% among those treated from 1970 to 1979 and 21.0% among those treated from 1990 to 1999), those reporting adverse health status did not decrease by treatment decade. Compared with survivors diagnosed in 1970 to 1979, those diagnosed in 1990 to 1999 were more likely to report poor general health (11.2% vs. 13.7%; P < 0.001) and cancer-related anxiety (13.3% vs. 15.0%; P < 0.001). From 1970 to 1979 and 1990 to 1999, the proportions of survivors reporting adverse outcomes were higher (P < 0.001) among those with leukemia (poor general health, 9.5% and 13.9%) and osteosarcoma (pain, 23.9% and 36.6%). Temporal changes in treatment exposures were not associated with changes in the proportions of survivors reporting adverse health status. Smoking, not meeting physical activity guidelines, and being either underweight or obese were associated with poor health status.Limitation: Considerable improvement in survival among children diagnosed with cancer in the 1990s compared with those diagnosed in the 1970s makes it difficult to definitively determine the effect of risk factors on later self-reported health status without considering their effect on mortality.Conclusion: Because survival rates after a diagnosis of childhood cancer have improved substantially over the past 30 years, the population of survivors now includes those who would have died in earlier decades. Self-reported health status among survivors has not improved despite evolution of treatment designed to reduce toxicities.Primary Funding Source: The National Cancer Institute. [ABSTRACT FROM AUTHOR]

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]

By the middle of this century, racial/ethnic minority populations will collectively constitute 50% of the US population. This temporal shift in the racial/ethnic composition of the US population demands a close look at the race/ethnicity-specific burden of morbidity and premature mortality among survivors of childhood cancer. To optimize targeted long-term follow-up care, it is essential to understand whether the burden of morbidity borne by survivors of childhood cancer differs by race/ethnicity. This is challenging because the number of minority participants is often limited in current childhood cancer survivorship research, resulting in a paucity of race/ethnicity-specific recommendations and/or interventions. Although the overall childhood cancer incidence increased between 1973 and 2003, the mortality rate declined; however, these changes did not differ appreciably by race/ethnicity. The authors speculated that any racial/ethnic differences in outcome are likely to be multifactorial, and drew on data from the Childhood Cancer Survivor Study to illustrate the various contributors (socioeconomic characteristics, health behaviors, and comorbidities) that could explain any observed differences in key treatment-related complications. Finally, the authors outlined challenges in conducting race/ethnicity-specific childhood cancer survivorship research, demonstrating that there are limited absolute numbers of children who are diagnosed and survive cancer in any one racial/ethnic minority population, thereby precluding a rigorous evaluation of adverse events among specific primary cancer diagnoses and treatment exposure groups. Cancer 2016;122:2426-2439. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Simple Summary: There are many commonalities between children with cancer and other populations that experience early-life stress. Thus, it is important to review the existing research surrounding the stress response in the pediatric cancer population. In this review, we describe the psychoneuroimmunology behind stress regulation and the differences observed in stress regulatory pathways in childhood cancer patients. Our objective is to provide a clinically relevant summary of the stress pathways contributing to, and exacerbating, childhood illness and outline some potential interventions. Stress is a ubiquitous experience that can be adaptive or maladaptive. Physiological stress regulation, or allostasis, can be disrupted at any point along the regulatory pathway resulting in adverse effects for the individual. Children with cancer exhibit significant changes to these pathways in line with stress dysregulation and long-term effects similar to those observed in other early-life stress populations, which are thought to be, in part, a result of cytotoxic cancer treatments. Children with cancer may have disruption to several steps in the stress-regulatory pathway including cognitive-affective function, neurological disruption to stress regulatory brain regions, altered adrenal and endocrine function, and disrupted tissue integrity, as well as lower engagement in positive coping behaviours such as physical activity and pro-social habits. To date, there has been minimal study of stress reactivity patterns in childhood illness populations. Nor has the role of stress regulation in long-term health and function been elucidated. We conclude that consideration of stress regulation in childhood cancer may be crucial in understanding and treating the disease. [ABSTRACT FROM AUTHOR]

Survivors of childhood, adolescent, and young adult cancer, previously treated with anthracycline chemotherapy (including mitoxantrone) or radiotherapy in which the heart was exposed, are at increased risk of cardiomyopathy. Symptomatic cardiomyopathy is typically preceded by a series of gradually progressive, asymptomatic changes in structure and function of the heart that can be ameliorated with treatment, prompting specialist organisations to endorse guidelines on cardiac surveillance in at-risk survivors of cancer. In 2015, the International Late Effects of Childhood Cancer Guideline Harmonization Group compiled these guidelines into a uniform set of recommendations applicable to a broad spectrum of clinical environments with varying resource availabilities. Since then, additional studies have provided insight into dose thresholds associated with a risk of asymptomatic and symptomatic cardiomyopathy, have characterised risk over time, and have established the cost-effectiveness of different surveillance strategies. This systematic Review and guideline provides updated recommendations based on the evidence published up to September, 2020. [ABSTRACT FROM AUTHOR]

Background: Treatment outcomes among survivors of cancer diagnosed during adolescence and early young adulthood have not been characterised independently of survivors of cancers diagnosed during childhood. We aimed to describe chronic health conditions and all-cause and cause-specific mortality among survivors of early-adolescent and young adult cancer.Methods: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study with longitudinal follow-up of 5-year survivors diagnosed with cancer before the age of 21 years at 27 academic institutions in the USA and Canada between 1970 and 1999. We evaluated outcomes among survivors of early-adolescent and young adult cancer (aged 15-20 years at diagnosis) and survivors diagnosed at age younger than 15 years (matched on primary cancer diagnosis, including leukaemia, lymphoma, CNS tumours, neuroblastoma, Wilms tumour, soft-tissue sarcomas, and bone cancer) by comparing both groups to siblings of the same age. Mortality was ascertained with the National Death Index. Chronic health conditions were classified with the Common Terminology Criteria for Adverse Events. Standardised mortality ratios (SMRs) were estimated with age-specific, sex-specific, and calendar year-specific US rates. Cox proportional hazard models estimated hazard ratios (HRs) for chronic health conditions and 95% CIs.Findings: Among 5804 early-adolescent and young adult survivors (median age 42 years, IQR 34-50) the SMR compared to the general population for all-cause mortality was 5·9 (95% CI 5·5-6·2) and among 5804 childhood cancer survivors (median age 34 years; 27-42), it was 6·2 (5·8-6·6). Early-adolescent and young adult survivors had lower SMRs for death from health-related causes (ie, conditions that exclude recurrence or progression of the primary cancer and external causes, but include the late effects of cancer therapy) than did childhood cancer survivors (SMR 4·8 [95% CI 4·4-5·1] vs 6·8 [6·2-7·4]), which was primarily evident more than 20 years after cancer diagnosis. Early-adolescent and young adult cancer survivors and childhood cancer survivors were both at greater risk of developing severe and disabling, life-threatening, or fatal (grade 3-5) health conditions than siblings of the same age (HR 4·2 [95% CI 3·7-4·8] for early adolescent and young adult cancer survivors and 5·6 [4·9-6·3] for childhood cancer survivors), and at increased risk of developing grade 3-5 cardiac (4·3 [3·5-5·4] and 5·6 [4·5-7·1]), endocrine (3·9 [2·9-5·1] and 6·4 [5·1-8·0]), and musculoskeletal conditions (6·5 [3·9-11·1] and 8·0 [4·6-14·0]) when compared with siblings of the same age, although all these risks were lower for early-adolescent and young adult survivors than for childhood cancer survivors.Interpretation: Early-adolescent and young adult cancer survivors had higher risks of mortality and severe and life threatening chronic health conditions than the general population. However, early-adolescent and young adult cancer survivors had lower non-recurrent, health-related SMRs and relative risks of developing grade 3-5 chronic health conditions than childhood cancer survivors, by comparison with siblings of the same age, which were most notable more than 20 years after their original cancer. These results highlight the need for long-term screening of both childhood and early-adolescent and young adult cancer survivors.Funding: National Cancer Institute and American Lebanese-Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Background: Cancer treatment can cause gonadal impairment. Acute ovarian failure is defined as the permanent loss of ovarian function within 5 years of cancer diagnosis. We aimed to develop and validate risk prediction tools to provide accurate clinical guidance for paediatric patients with cancer.Methods: In this cohort study, prediction models of acute ovarian failure risk were developed using eligible female US and Canadian participants in the Childhood Cancer Survivor Study (CCSS) cohort and validated in the St Jude Lifetime Cohort (SJLIFE) Study. 5-year survivors from the CCSS cohort were included if they were at least 18 years old at their most recent follow-up and had complete treatment exposure and adequate menstrual history (including age at menarche, current menstrual status, age at last menstruation, and menopausal aetiology) information available. Participants in the SJLIFE cohort were at least 10-year survivors. Participants were excluded from the prediction analysis if they had an ovarian hormone deficiency, had missing exposure information, or had indeterminate ovarian status. The outcome of acute ovarian failure was defined as permanent loss of ovarian function within 5 years of cancer diagnosis or no menarche after cancer treatment by the age of 18 years. Logistic regression, random forest, and support vector machines were used as candidate methods to develop the risk prediction models in the CCSS cohort. Prediction performance was evaluated internally (in the CCSS cohort) and externally (in the SJLIFE cohort) using the areas under the receiver operating characteristic curve (AUC) and the precision-recall curve (average precision [AP; average positive predictive value]).Findings: Data from the CCSS cohort were collected for participants followed up between Nov 3, 1992, and Nov 25, 2016, and from the SJLIFE cohort for participants followed up between Oct 17, 2007, and April 16, 2012. Of 11 336 female CCSS participants, 5886 (51·9%) met all inclusion criteria for analysis. 1644 participants were identified from the SJLIFE cohort, of whom 875 (53·2%) were eligible for analysis. 353 (6·0%) of analysed CCSS participants and 50 (5·7%) of analysed SJLIFE participants had acute ovarian failure. The overall median follow-up for the CCSS cohort was 23·9 years (IQR 20·4-27·9), and for SJLIFE it was 23·9 years (19·0-30·0). The three candidate methods (logistic regression, random forest, and support vector machines) yielded similar results, and a prescribed dose model with abdominal and pelvic radiation doses and an ovarian dose model with ovarian radiation dosimetry using logistic regression were selected. Common predictors in both models were history of haematopoietic stem-cell transplantation, cumulative alkylating drug dose, and an interaction between age at cancer diagnosis and haematopoietic stem-cell transplant. External validation of the model in the SJLIFE cohort produced an estimated AUC of 0·94 (95% CI 0·90-0·98) and AP of 0·68 (95% CI 0·53-0·81) for the ovarian dose model, and AUC of 0·96 (0·94-0·97) and AP of 0·46 (0·34-0·61) for the prescribed dose model. Based on these models, an online risk calculator has been developed for clinical use.Interpretation: Both acute ovarian failure risk prediction models performed well. The ovarian dose model is preferred if ovarian radiation dosimetry is available. The models, along with the online risk calculator, could help clinical discussions regarding the need for fertility preservation interventions in girls and young women newly diagnosed with cancer.Funding: Canadian Institutes of Health Research, Women and Children's Health Research Institute, National Cancer Institute, and American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]

Childhood cancer survivors are at risk for a range of cardiovascular diseases (CVD) as a consequence of their cancer therapy.[1] However, most studies have focused on anthracycline-related heart failure (HF) only. Because the prevalence of CVD is expected to increase with age, this study reinforces the need for periodic CVD surveillance, and consideration of all CVD types, in childhood cancer survivors. 1 Mulrooney DA Yeazel MW Kawashima T Mertens AC Mitby P Stovall M Donaldson SS Green DM Sklar CA Robison LL Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort. [Extracted from the article]

Long-term survival for children diagnosed with cancer exceeds 80%. Notably, premature cardiovascular disease has become the leading non-cancer cause of late mortality among these survivors. This randomized controlled trial (RCT; NCT03104543) focuses on adult participants in the Childhood Cancer Survivor Study identified as high risk for ischemic heart disease or heart failure due to their cancer treatment. Participants undergo a home-based evaluation of blood pressure and laboratory tests to determine the prevalence of undiagnosed and/or undertreated hypertension, dyslipidemia, and diabetes. Those with abnormal values are then enrolled in an RCT to test the efficacy of a 12-month personalized, remotely delivered survivorship care plan (SCP) intervention designed to reduce undertreatment of these three target conditions. The intervention approximates a clinical encounter and is based on chronic disease self-management strategies. With a goal of 750, currently 342 out of 742 eligible participants approached have enrolled (46.1%). Initially, we randomized participants to different recruitment strategies, including shorter approach packets and a tiered consent, but did not find significant differences in participation rates (40.7% to 42.9%; p =.95). Subsequently, slightly greater participation was seen with larger upfront unconditional incentive checks ($50 vs. $25: 50.7% vs. 44.1%; p =.10). Overall, the financial impact of the $50 upfront incentive was cost neutral, and possibly cost-saving, vs. a $25 upfront incentive. The overall study will determine if a National Academy of Medicine-recommended SCP intervention can improve cardiovascular outcomes among long-term survivors of childhood cancer. Modifications to the recruitment strategy may improve participation rates over time. [ABSTRACT FROM AUTHOR]