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.
In this report from the Childhood Cancer Survivor Study, vigorous exercise is associated with a lower risk of subsequent depression and somatization; even small amounts of vigorous exercise appear to be beneficial.
We investigated the association between prevalence of symptoms and health-related quality of life (HRQOL) in adult survivors of childhood cancer enrolled in the St Jude Lifetime Cohort study.
...Eligibility criteria include childhood malignancy treated at St Jude, survival ≥ 10 years from diagnosis, and current age ≥ 18 years. Study participants were 1,667 survivors (response rate = 65%). Symptoms were self-reported by using a comprehensive health questionnaire and categorized into 12 classes: cardiac; pulmonary; motor/movement; pain in head; pain in back/neck; pain involving sites other than head, neck, and back; sensation abnormalities; disfigurement; learning/memory; anxiety; depression; and somatization. HRQOL was measured by using physical/mental component summary (PCS/MCS) and six domain scores of the Medical Outcomes Study 36-Item Short-Form Health Survey. Multivariable regression analysis was performed to investigate associations between symptom classes and HRQOL. Cumulative prevalence of symptom classes in relation to time from diagnosis was estimated.
Pain involving sites other than head, neck and back, and disfigurement represented the most frequent symptom classes, endorsed by 58.7% and 56.3% of survivors, respectively. Approximately 87% of survivors reported multiple symptom classes. Greater symptom prevalence was associated with poorer HRQOL. In multivariable analysis, symptom classes explained up to 60% of the variance in PCS and 56% of the variance in MCS; demographic and clinical variables explained up to 15% of the variance in PCS and 10% of the variance in MCS. Longer time since diagnosis was associated with higher cumulative prevalence in all symptom classes.
A large proportion of survivors suffered from many symptom classes, which was associated with HRQOL impairment.
Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin ...has not been rigorously evaluated among survivors of childhood cancer. These risks, which are based on hematologic toxicity, are currently assumed to be approximately equivalent.
Data from 15,815 survivors of childhood cancer who survived at least 5 years were used. Survivors were from the Emma Children's Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n = 364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40 years for doses of daunorubicin and doxorubicin (per 100-mg/m(2) increments) was estimated by using Cox regression adjusted for sex, age at diagnosis, treatment with other anthracycline agents and chest radiation, and cohort membership.
In total, 5,144 (32.5%) patients received doxorubicin as part of their cancer treatment, whereas 2,243 (14.7%) received daunorubicin. On the basis of 271 occurrences of HF during a median follow-up time after cohort entry of 17.3 years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years was 3.2% (95% CI, 2.8% to 3.7%). The average ratio of HRs for daunorubicin to doxorubicin was 0.45 (95% CI, 0.23 to 0.73). A similar ratio was obtained by using a linear dose-response model, which yielded an HR of 0.49 (95% CI, 0.28 to 0.70).
Compared with doxorubicin, daunorubicin was less cardiotoxic among survivors of childhood cancer than most current guidelines suggest. This may have implications for follow-up guidelines. The feasibility of substitution of doxorubicin with daunorubicin in childhood cancer treatment protocols to reduce cardiotoxicity should be additionally investigated.
Adolescents, regardless of medical history, may face behavioral and social challenges. Cancer and related treatments represent additional challenges for teens navigating the transition from childhood ...to adulthood. This study was conducted to evaluate behavioral and social outcomes of adolescent childhood cancer survivors using data from the Childhood Cancer Survivor Study.
We evaluated 2,979 survivors and 649 siblings of cancer survivors to determine the incidence of difficulty in six behavioral and social domains (depression/anxiety, headstrong, attention deficit, peer conflict/social withdrawal, antisocial behaviors, and social competence). Outcomes were determined by calculating parent-reported scores to questions from the behavior problem index.
Survivors and siblings were similar in age at the time of interview (mean: 14.8, survivors; 14.9, siblings; range, 12 to 17 years). Overall, multivariate analyses showed that survivors were 1.5 times (99% CI, 1.1 to 2.1) more likely than siblings to have symptoms of depression/anxiety and 1.7 times (99% CI, 1.3 to 2.2) more likely to have antisocial behaviors. Scores in the depression/anxiety, attention deficit, and antisocial domains were significantly elevated in adolescents treated for leukemia or CNS tumors when compared with siblings. In addition, survivors of neuroblastoma had difficulty in the depression/anxiety and antisocial domains. Treatments with cranial radiation and/or intrathecal methotrexate were specific risk factors.
Adolescent survivors of childhood cancer, especially those with a history of leukemia, CNS tumors, or neuroblastoma, may be at increased risk for adverse behavioral and social outcomes. Increased surveillance of this population, in combination with development of interventional strategies, should be a priority.
Childhood cancer survivors are at higher risk of morbidity and mortality from cardiovascular disease compared with the general population.
Eight thousand five hundred ninety-nine survivors (52% male) ...and 2,936 siblings (46% male) from the Childhood Cancer Survivor Study, a retrospectively ascertained, prospectively followed study of persons who survived 5 years after childhood cancer diagnosed from 1970 to 1986, were evaluated for body mass index of > or =30 kg/m(2) based on self-reported heights and weights and self-reported use of medications for hypertension, dyslipidemia, and impaired glucose metabolism. The presence of three or more of the above constituted Cardiovascular Risk Factor Cluster (CVRFC), a surrogate for Metabolic Syndrome.
Survivors were more likely than siblings to take medications for hypertension odds ratio (OR), 1.9; 95% confidence interval (95% CI), 1.6-2.2, dyslipidemia (OR, 1.6; 95% CI, 1.3-2.0) or diabetes (OR, 1.7; 95% CI, 1.2-2.3). Among these young adults (mean age of 32 years for survivors and 33 years for siblings), survivors were not more likely than siblings to be obese or have CVRFC. In a multivariable logistic regression analysis, factors associated with having CVRFC included older age at interview > or =40 versus <30 years of age (OR, 8.2; 95% CI, 3.5-19.9), exposure to total body irradiation (OR, 5.5; 95% CI, 1.5-15.8) or radiation to the chest and abdomen (OR, 2.3; 95% CI, 1.2-2.4), and physical inactivity (OR, 1.7; 95% CI, 1.1-2.6).
Among adult survivors of pediatric cancer, older attained age, exposure to total body irradiation or abdominal plus chest radiation, and a sedentary life-style are associated with CVRFC.
Purpose Beyond survival, achieving independence is a primary goal for adult survivors of pediatric CNS tumors. However, the prevalence of and risk factors for failure to achieve independence, ...assessed with multiple concurrent indicators, have not been examined. Patients and Methods Functional and social independence was assessed in 306 survivors (astrocytoma n = 130, medulloblastoma n = 77, ependymoma n = 36, and other n = 63; median current age, 25.3 years range, 18.9 to 53.1 years; time since diagnosis, 16.8 years range, 10.6 to 41.8 years). Six observed indicators were used to identify latent classes of independence, which included employment, living independently, assistance with personal care, assistance with routine needs, obtaining a driver's license, and marital status. Physical performance impairments were defined as scores < 10th percentile on measures of aerobic capacity, strength, flexibility, balance, mobility, and adaptive function. Multinomial logistic regression estimated odds ratios (ORs) and 95% CIs were calculated for associations of disease/treatment exposures and impairments in physical performance with nonindependence. Results Three classes of independence were identified as independent (40%), moderately independent (34%), and nonindependent (26%). In multivariable models, craniospinal irradiation (OR, 4.20; 95% CI, 1.69 to 10.44) and younger age at diagnosis (OR, 1.24; 95% CI, 1.14 to 1.35) were associated with risk of nonindependence versus independence. Beyond impaired IQ, limitations in aerobic capacity (OR, 5.47; 95% CI, 1.78 to 16.76), flexibility (OR, 3.66; 95% CI, 1.11 to 12.03), and adaptive physical function (OR, 11.54; 95% CI, 3.57 to 37.27) were associated with nonindependence versus independence. Nonindependent survivors reported reduced physical but not mental health-related quality of life compared with independent survivors. Conclusion Sixty percent of survivors of pediatric CNS tumors do not achieve complete independence as adults. Reduction in intensity of primary therapies and interventions that target physical performance and adaptive deficits may help survivors to achieve greater independence.
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.
To evaluate whether childhood cancer survivors receive regular medical care focused on the specific morbidities that can arise from their therapy.
We conducted a cross-sectional survey of health care ...use in 8,522 participants in the Childhood Cancer Survivor Study, a multi-institutional cohort of childhood cancer survivors. We assessed medical visits in the preceding 2 years, whether these visits were related to the prior cancer, whether survivors received advice about how to reduce their long-term risks, and whether screening tests were discussed or ordered. Completion of echocardiograms and mammograms were assessed in patients at high risk for cardiomyopathy or breast cancer. We examined the relationship between demographics, treatment, health status, chronic medical conditions, and health care use.
Median age at cancer diagnosis was 6.8 years (range, 0 to 20.9 years) and at interview was 31.4 years (range, 17.5 to 54.1 years). Although 88.8% of survivors reported receiving some form of medical care, only 31.5% reported care that focused on their prior cancer (survivor-focused care), and 17.8% reported survivor-focused care that included advice about risk reduction or discussion or ordering of screening tests. Among survivors who received medical care, those who were black, older at interview, or uninsured were less likely to have received risk-based, survivor-focused care. Among patients at increased risk for cardiomyopathy or breast cancer, 511 (28.2%) of 1,810 and 169 (40.8%) of 414 had undergone a recommended echocardiogram or mammogram, respectively.
Despite a significant risk of late effects after cancer therapy, the majority of childhood cancer survivors do not receive recommended risk-based care.
Childhood cancer survivors carry a high burden of treatment-related morbidity; however, race/ethnicity-specific risks of adverse outcomes are not well understood.
Data from the Childhood Cancer ...Survivor Study, a cohort of survivors of at least 5 years, were used to compare Hispanic (n = 750, 5.4%) and non-Hispanic black (NHB: n = 694, 5.0%) survivors to non-Hispanic white patients (NHW: n = 12,397, 89.6%) for late mortality, subsequent neoplasms, and chronic health conditions.
NHBs and Hispanics reported lower socioeconomic status (SES) and higher prevalence of obesity, and NHBs reported higher prevalence of hypertension. NHBs had higher rate of all-cause mortality (relative rate RR, 1.4; 95% CI, 1.1 to 1.9; P = .008), which was abrogated (RR, 1.0; 95% CI, 0.8 to 1.4; P = .9) after adjusting for SES. Nonmelanoma skin cancer was not observed among irradiated NHBs, and the risk was lower among Hispanic survivors (RR, 0.3; 95% CI, 0.1 to 0.7) compared with NHWs. Both NHBs and Hispanics demonstrated elevated risks for diabetes; these risks persisted after adjusting for SES and obesity (NHBs: RR, 2.8; 95% CI, 1.1 to 6.7; Hispanics: RR, 3.1; 95% CI, 1.5 to 6.4). NHBs were more likely to report cardiac conditions (RR, 1.8; 95% CI, 1.1 to 2.7), but the risk was attenuated after adjusting for cardiovascular risk factors. Therapeutic exposures did not affect racial/ethnic differences in mortality (all cause or cause specific), chronic health conditions, or subsequent neoplasms.
By and large, NHB and Hispanic childhood cancer survivors experience a comparable burden of morbidity and mortality to their NHW counterparts. The few differences in risk were explained by the racial/ethnic differences in socioeconomic status and/or cardiovascular risk factors.
Studies of cardiac disease among adult survivors of childhood cancer have generally relied on self-reported or registry-based data.
To systematically assess cardiac outcomes among survivors of ...childhood cancer.
Cross-sectional study.
St. Jude Children's Research Hospital.
1853 adult survivors of childhood cancer, aged 18 years or older, who received cancer-related cardiotoxic therapy at least 10 years earlier.
Baseline history and physical examination, fasting metabolic and lipid panels, echocardiography, electrocardiography, and 6-minute walk test.
One half of the survivors (52.3%) were men with a median age of 8 years (range, 0 to 24 years) at cancer diagnosis and 31 years (range, 18 to 60 years) at evaluation. Cardiomyopathy was present in 7.4% survivors (newly identified at the time of evaluation in 4.7%), coronary artery disease in 3.8% (newly identified in 2.2%), valvular regurgitation or stenosis in 28.0% (newly identified in 24.8%), and conduction or rhythm abnormalities in 4.4% (newly identified in 1.4%). Nearly all survivors were asymptomatic. The prevalence of cardiac conditions increased with age at evaluation, ranging from 3% to 24% among survivors aged 30 to 39 years to 10% to 37% among those aged 40 years or older. In multivariable analysis, survivors exposed to anthracycline doses of 250 mg/m2 or more had greater odds of cardiomyopathy (odds ratio, 2.7 95% CI, 1.1 to 6.9) than those who were not exposed. Survivors exposed to heart radiation also had increased odds of cardiomyopathy (odds ratio, 1.9 CI, 1.1 to 3.7) compared with those who were not exposed. Radiation exposure greater than 1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings.
Sixty-one percent of survivors exposed to anthracycline chemotherapy or cardiac-directed radiation participated. A comparison group and longitudinal assessments were not available.
Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood cancer.
National Cancer Institute, American Lebanese Syrian Associated Charities.
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