An interactive, rewards-based intervention designed to increase MVPA is feasible in adolescent survivors of childhood cancer.

PURPOSE Exercise intolerance, associated with heart failure and death in general populations, is not well studied in survivors of childhood cancer. We examined prevalence of exercise intolerance in survivors exposed or not to cardiotoxic therapy, and associations among organ system function, exercise intolerance, and mortality. METHODS Participants consisted of 1,041 people who had survived cancer ≥ 10 years (and had or did not have exposure to anthracyclines and/or chest-directed radiation) and 285 control subjects. Exercise intolerance was defined as peak oxygen uptake < 85% predicted from maximal cardiopulmonary exercise testing; organ functions were ascertained with imaging or clinical testing. Multivariable regression of the data was performed to compare exercise capacity between survivors exposed or unexposed to cardiotoxic therapy and control subjects, and to evaluate associations between treatment and organ function, and organ function and exercise intolerance. Propensity score methods in time-to-event analyses evaluated associations between exercise intolerance and mortality. RESULTS Survivors (mean age ± standard deviation [SD], 35.6 ± 8.8 years) had lower mean (± SD) peak oxygen uptake (exposed: 25.74 ± 8.36 mL/kg/min; unexposed: 26.82 ± 8.36 mL/kg/min) than did control subjects (32.69 ± 7.75 mL/kg/min; P for all < .001). Exercise intolerance was present in 63.8% (95% CI, 62.0% to 65.8%) of exposed survivors, 55.7% (95% CI, 53.2% to 58.2%) of unexposed survivors, and 26.3% (95% CI, 24.0% to 28.3%) of control subjects, and was associated with mortality (hazard ratio, 3.9; 95% CI, 1.09 to 14.14). Global longitudinal strain (odds ratio [OR], 1.71; 95% CI, 1.11 to 2.63), chronotropic incompetence (OR, 3.58; 95% CI, 1.75 to 7.31); forced expiratory volume in 1 second < 80% (OR, 2.59; 95% CI, 1.65 to 4.09), and 1 SD decrease in quadriceps strength (OR, 1.49; 95% CI, 1.23 to 1.82) were associated with exercise intolerance. Ejection fraction < 53% was not associated with exercise intolerance. CONCLUSION Exercise intolerance is prevalent among childhood cancer survivors and associated with all-cause mortality. Treatment-related cardiac (detected by global longitudinal strain), autonomic, pulmonary, and muscular impairments increased risk. Survivors with impairments may require referral to trained specialists to learn to accommodate specific deficits when engaging in exercise.

Importance Bone accrual during youth is critical to establish sufficient strength for lifelong skeletal health. Children with cancer may develop low bone mineral density any time before or after diagnosis. Objective To evaluate the ability of low magnitude, high frequency mechanical stimulation to enhance bone mineral density among childhood cancer survivors. Design Double-blind randomized controlled trial from June 1, 2010-January 22, 2013. Participants were randomized (stratified by sex and Tanner stage) to either a placebo device or low magnitude, high frequency mechanical stimulation. Setting St. Jude Children’s Research Hospital; intervention completed at home. Participants Survivors, ages 7-17 years, previously treated at St. Jude Children’s Research Hospital, in remission, at least five years from diagnosis, with whole body or lumbar spine bone mineral density Z-scores ≤−1.0. Intervention Placebo or low magnitude, high frequency mechanical stimulation (0.3 g, 32-37Hz) for two 10-minute sessions, seven days a week for one year. All participants were prescribed daily vitamin D and calcium. Main outcome measures Changes in areal and volumetric bone mineral density and bone biomarkers were compared by analysis of variance, adjusted for strata. Results Forty-eight of 65 randomized participants completed this double-blind study with median adherence of 70.1% for intervention and 63.7% for placebo groups. With intention-to-treat analysis, mean whole body bone mineral density Z-score by dual x-ray absorptiometry improved by 0.25±0.78 in the intervention (N=22), but decreased by −0.19±0.79 in the placebo group (N=26) p=0.05). Circulating osteocalcin at 12 months correlated with change in total body bone mineral density (r=0.35, p=0.02). Participants completing ≥70% of prescribed sessions increased 11.2±11.3% in tibial trabecular bone volume compared to those completing <70% who decreased −1.3±9.9% (p=0·02). Change in circulating receptor activator of nuclear factor kappa-B ligand was higher in the intervention than in the placebo group (0.06±0.16 vs. −0.04±0.17 pmol/L, p=0.04). Conclusions and relevance Pediatric cancer survivors with low bone mineral density may benefit from low magnitude, high frequency mechanical stimulation as a novel, safe, and convenient intervention to optimize peak bone mass during youth, alone or in conjunction with other therapies. Trial Registration NCT01010230. Vibration Intervention For Bone Enhancement In Childhood Cancer Survivors, www.clincialtrials.gov

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.