Carrie R. Howell

Physical performance limitations among adult survivors of childhood brain tumors.

Young adult survivors of childhood brain tumors (BTs) may have late effects that compromise physical performance and everyday task participation. The objective of this study was to evaluate muscle strength, fitness, physical performance, and task participation among adult survivors of childhood BTs.

Risky Health Behavior Among Adolescents in the Childhood Cancer Survivor Study Cohort

OBJECTIVE To report the prevalence and comparison of cancer-linked health behaviors and identify risk factors associated with unhealthy behavior among adolescent siblings and cancer survivors. METHODS The Child Health and Illness Profile--Adolescent Edition (CHIP--AE) was completed by 307 survivors and 97 sibling controls 14-20 years of age. RESULTS Risky behavior ranged from 0.7% to 35.8% for survivors and 1.0% to 41.2% for siblings. Comparisons of sexual behavior, tobacco, alcohol, or illicit drug use utilizing continuous data revealed no differences between groups. Categorically, survivors were less likely to report past smokeless tobacco use or current use of beer/wine or binge drinking (p-values range from .01 to .04). Survivors with better mental health were at lower risk for poor behavioral outcomes. CONCLUSIONS Adolescent survivors engage in risky health behaviors at rates generally equivalent to their siblings. Aggressive health education efforts should be directed toward this high-risk population.

The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE).

Background Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity among survivors, however, has not been described. Methods Among 5,522 patients treated for childhood cancer at St. Jude Children’s Research Hospital who survived ≥10 years and were ≥18 years old, 3,010 underwent prospective clinical assessment and retrospective medical validation of health records as part of the St. Jude Lifetime Cohort Study. Age- and sex-frequency-matched community-controls (n=272) were used for comparison. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs among the 2512 survivors not clinically evaluated. Mean cumulative count and marked-point-process regression were used for descriptive and inferential cumulative burden analyses, respectively. Findings The cumulative incidence of any grade CHC at age 50 was 99·9%; 96·0% (95·3%–96·8%) for severe/disabling, life-threatening or fatal CHCs. By age 50, a survivor experienced, on average, 17·1 (16·2–18·0) CHCs including 4·7 (4·6–4·9) graded as severe/disabling, life-threatening or fatal. The cumulative burden among survivors was nearly 2-fold greater than matched community-controls (p<0·001). Second neoplasms, spinal disorders and pulmonary disease were major contributors to the excess total cumulative burden. Significant heterogeneity in CHCs among survivors with differing primary cancer diagnoses was observed. Multivariable analyses demonstrated that age at diagnosis, treatment era and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. Interpretation The burden of surviving childhood cancer is substantial and highly variable. The total cumulative burden experienced by survivors of pediatric cancer, in conjunction with detailed characterization of long-term CHCs, provide data to better inform future clinical guidelines, research investigations and health services planning for this vulnerable, medically-complex population.

Energy balance and fitness in adult survivors of childhood acute lymphoblastic leukemia.

There is limited information on body composition, energy balance, and fitness among survivors of childhood acute lymphoblastic leukemia (ALL), especially those treated without cranial radiation therapy (CRT). This analysis compares these metrics among 365 ALL survivors with a mean age of 28.6 ± 5.9 years (149 treated with and 216 without CRT) and 365 age-, sex-, and race-matched peers. We also report risk factors for outcomes among survivors treated without CRT. Male survivors not exposed to CRT had abnormal body composition when compared with peers (% body fat, 26.2 ± 8.2 vs 22.7 ± 7.1). Survivors without CRT had similar energy balance but had significantly impaired quadriceps strength (-21.9 ± 6.0 Newton-meters [Nm]/kg, 60°/s) and endurance (-11.4 ± 4.6 Nm/kg, 300°/s), exercise capacity (-2.0 ± 2.1 ml/kg per minute), low-back and hamstring flexibility (-4.7 ± 1.6 cm), and dorsiflexion range of motion (-3.1 ± 0.9°) and higher modified total neuropathy scores (+1.6 ± 1.1) than peers. Cumulative asparaginase dose ≥120,000 IU/m(2) was associated with impaired flexibility, vincristine dose ≥39 mg/m(2) with peripheral neuropathy, glucocorticoid (prednisone equivalent) dose ≥8000 mg/m(2) with hand weakness, and intrathecal methotrexate dose ≥225 mg with dorsiflexion weakness. Physical inactivity was associated with hand weakness and decreased exercise capacity. Smoking was associated with peripheral neuropathy. Elimination of CRT from ALL therapy has improved, but not eliminated, body-composition outcomes. Survivors remain at risk for impaired fitness.

Effect of Low-Magnitude, High-Frequency Mechanical Stimulation on BMD Among Young Childhood Cancer Survivors: A Randomized Clinical Trial

IMPORTANCE Bone accrual during youth is critical to establish sufficient strength for lifelong skeletal health. Children with cancer may develop low bone mineral density (BMD) any time before or after diagnosis. OBJECTIVE To evaluate the ability of low-magnitude, high-frequency mechanical stimulation to enhance BMD among childhood cancer survivors. DESIGN, SETTING, AND PARTICIPANTS Double-blind randomized clinical trial conducted at St Jude Childrens Research Hospital from June 1, 2010, to January 22, 2013, using cancer survivors, ages 7 to 17 years, who were previously treated at St Jude Childrens Research Hospital, were in remission, and at least 5 years from diagnosis, with whole-body or lumbar spine BMD z scores of -1.0 or lower. Participants were randomized (stratified by sex and Tanner stage) to either a placebo device or low-magnitude, high-frequency mechanical stimulation device, which was used at home. INTERVENTIONS Placebo or low-magnitude, high-frequency mechanical stimulation (0.3 g; 32-37 Hz) for 2 sessions lasting 10 minutes each, 7 days per week for 1 year. All participants were prescribed daily cholecalciferol (vitamin D) and calcium. MAIN OUTCOMES AND MEASURES Changes in areal and volumetric BMD and bone biomarkers were compared by analysis of variance, adjusted for strata. RESULTS Of the 65 participants, 32 were randomized to the intervention group (mean [SD] age was 13.6 [3.7] years, 18 [56.2%] were male, and 27 [84.4%] were white), and 33 were randomized to the placebo group (mean [SD] age was 13.6 [2.9] years, 17 [51.5%] were male, and 26 [78.8%] were white). Forty-eight participants completed the trial, 22 in the intervention group and 26 in the placebo group with median adherence of 70.1% for intervention and 63.7% for placebo groups. With intention-to-treat analysis, mean (SD) whole-body BMD 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 = .05). Circulating osteocalcin at 12 months correlated with change in total body BMD (r = 0.35, P = .02). Tibial trabecular bone among participants completing 70% or more of the prescribed sessions increased by a mean of 11.2% (95% CI, 5.2 to 17.2%) compared with those completing less than 70% who decreased by a mean of -1.3% (95% CI, -7.3 to 4.7%; P = .02). Change in circulating receptor activator of nuclear factor κ-B ligand was higher in the intervention than in the placebo group (0.06 [0.16] vs -0.04 [0.17] pmol/L) (P = .04). CONCLUSIONS AND RELEVANCE Pediatric cancer survivors with low BMD may benefit from low-magnitude, high-frequency mechanical stimulation as a novel and safe intervention to optimize peak bone mass during youth, alone or in conjunction with other therapies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01010230.

Risky Sexual Behavior in Adolescent Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study

OBJECTIVE To identify correlates of risky sexual behavior among adolescents surviving childhood cancer. METHODS The Child Health and Illness Profile-Adolescent Edition (CHIP-AE) was completed by 307 survivors of childhood cancer aged 15-20 years (M age at diagnosis 1.53 years; range 0-3.76). Univariate analyses were performed using χ² and Fishers Exact tests, and multivariable logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for risky sexual behaviors. RESULTS Diagnosis of central nervous system cancer (OR = .13, 95% CI: .02-.96, p < .05), no history of beer or wine consumption (OR = .20, CI: .06-.68, p = .01), and fewer negative peer influences (OR = .28, CI: .09-.84, p = .02) associated with decreased likelihood of sexual intercourse. Good psychological health (scores ≥-1.5 SD on the CHIP-AE Emotional Discomfort scale) associated with decreased risk of early intercourse (OR = .19, CI: .05-.77, p = .02), whereas high parental education (≥ college degree) associated with decreased risk of multiple lifetime sexual partners (OR = .25, CI: .09-.72, p = .01). Increased time from diagnosis (OR = .27, CI: .10-.78, p = .02) and psychological health (OR = .09, CI: .02-.36, p < .01) associated with decreased risk of unprotected sex at last intercourse, whereas high parent education associated with increased risk (OR = 4.27, CI: 1.46-12.52, p = .01). CONCLUSIONS Risky sexual behavior in adolescents surviving childhood cancer is associated with cancer type, time since diagnosis, psychological health, alcohol use, and peer influences. Consideration of these factors may provide direction for future interventions designed to reduce adolescent sexual risk-taking.

Responsiveness to Change in PROMIS® Measures among Children with Asthma: A Report from the PROMIS® Pediatric Asthma Study

OBJECTIVE To compare the responsiveness to change of the Patient-Reported Outcomes Measurement Information System (PROMIS(®)) asthma impact, pain interference, fatigue, depressive symptoms, mobility, and peer relationship scales to a legacy scale, the Paediatric Asthma Quality of Life Questionnaire (PAQLQ). METHODS Two hundred and twenty-nine child-parent dyads from public insurance programs were enrolled. PROMIS pediatric short forms (SFs) and the PAQLQ were used to measure health-related quality of life across four time points (T1-T4) over 2 years. The Asthma Control and Communication Instrument was used to measure the change in asthma control, and the Global Rating of Change (GRC) Index for breathing problems and overall health was used to measure the change in health status. Responsiveness was tested by comparing the changes in health-related quality of life with the changes in asthma control and health status over time using t tests, generalized estimating equations, and relative validity approaches. Magnitudes of the responsiveness between the Pediatric PROMIS and PAQLQ were assessed through statistical significance, Cohens d effect size (ES), and standardized response mean (SRM). RESULTS The PROMIS asthma impact scale and all PAQLQ scales exhibited significant responsiveness (ps<0.05) and small to medium ES/SRM when anchored to asthma control, GRC breathing problems, and overall health. Relative validity, especially related to change in asthma control status and GRC breathing problems, was equivalent. PROMIS pain interference, fatigue, and mobility SFs also indicated adequate responsiveness. CONCLUSIONS The PROMIS asthma impact SF indicated similar responsiveness to the PAQLQ scales. Due to its brevity and responsiveness, the PROMIS asthma impact SF is useful for clinical practice or research.

Dietary Protein Intake and Lean Muscle Mass in Survivors of Childhood Acute Lymphoblastic Leukemia: Report From the St. Jude Lifetime Cohort Study.

Background Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for low lean muscle mass and muscle weakness, which may contribute to inactivity and early development of chronic diseases typically seen in older adults. Although increasing protein intake, in combination with resistance training, improves lean muscle mass in other populations, it is not known whether muscular tissue among survivors of ALL, whose impairments are treatment-related, will respond similarly. Objective The aim of this study was to evaluate associations among dietary protein intake, resistance training, and lean muscle mass in survivors of ALL and age-, sex-, and race-matched controls. Design This was a cross-sectional study. Methods Lean muscle mass was determined with dual-energy x-ray absorptiometry, dietary information with 24-hour recalls, and participation in resistance training with a questionnaire. Participants were 365 survivors of ALL (52% male; 87% white; median age=28.5 years, range=23.6–31.7) and 365 controls with no previous cancer. Results Compared with controls, survivors of ALL had lower lean muscle mass (55.0 versus 57.2 kg, respectively) and lower percentage of lean muscle mass (68.6% versus 71.4%, respectively) than controls. Similar proportions of survivors (71.1%) and controls (69.7%) met recommended dietary protein intake (0.8 g/kg/d). Survivors (45.4%) were less likely to report resistance training than controls (53.8%). In adjusted models, 1-g higher protein intake per kilogram of body mass per day was associated with a 7.9% increase and resistance training ≥1×wk, with a 2.8% increase in lean muscle mass. Limitations The cross-sectional study design limits temporal evaluation of the association between protein intake and lean muscle mass. Conclusions The findings suggest that survivors of childhood ALL with low lean muscle mass may benefit from optimizing dietary protein intake in combination with resistance training. Research is needed to determine whether resistance training with protein supplementation improves lean muscle mass in survivors of childhood ALL.

Fingernail and toenail clippings as a non-invasive measure of chronic cortisol levels in adult cancer survivors

PurposeCancer survivors are at greater risk of comorbidities and functional decline due to physiological and psychological stress which can be measured by salivary cortisol. If saliva is used, multiple samples must be collected to accurately quantify long-term stress; however, fingernail (FN) and toenail (TN) clippings offer an opportunity to measure retrospective cortisol levels in a non-invasive manner.MethodsThree sets of FN and TN clippings were collected at 12-month intervals in conjunction with saliva samples from cancer survivors (n = 109) participating in two clinical trials. FN and TN samples were stored at room temperature (RT); a subset underwent additional processing and freezing before analysis. Cortisol levels were determined via enzyme immunoassay, and correlation coefficients were generated to determine overall correspondence of the individual measures.ResultsMatched RT and frozen samples were highly correlated for TN (r = 0.950, p = 5.44 × 10−37) and FN (r = 0.784, p = 1.05 × 10−10). Correlations between RT FN and TN were statistically significant (r = 0.621, p = 3.61 × 10− 17), as were frozen FN and TN (r = 0.310, p = 0.0283). RT, but not frozen TN and FN correlated with salivary cortisol (r = 0.580, p = 1.65 × 10− 16 and r = 0.287, p = 0.00042 for TN and FN, respectively).ConclusionsFN and TN cortisol levels correlate with salivary cortisol in adult cancer survivors and may offer a less invasive and convenient means for measuring chronic cortisol levels.

Clinical impact of sedentary behaviors in adult survivors of acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort study: Sedentary Behaviors in Survivors of Leukemia

Sedentary behaviors are associated with poor health outcomes in the general population, but their clinical impact on adult survivors of childhood acute lymphoblastic leukemia (ALL) has not been characterized to date. In the current study, we described the prevalence of sedentary behaviors in survivors of ALL and examined associations between time spent sedentary and body composition and onset of cardiovascular disease (CVD) risk factors.