Jennifer Q. Lanctot

Pediatric Cancer Survivorship Research: Experience of the Childhood Cancer Survivor Study

The Childhood Cancer Survivor Study (CCSS) is a comprehensive multicenter study designed to quantify and better understand the effects of pediatric cancer and its treatment on later health, including behavioral and sociodemographic outcomes. The CCSS investigators have published more than 100 articles in the scientific literature related to the study. As with any large cohort study, high standards for methodologic approaches are imperative for valid and generalizable results. In this article we describe methodological issues of study design, exposure assessment, outcome validation, and statistical analysis. METHODS for handling missing data, intrafamily correlation, and competing risks analysis are addressed; each with particular relevance to pediatric cancer survivorship research. Our goal in this article is to provide a resource and reference for other researchers working in the area of long-term cancer survivorship.

Lifestyle and metabolic syndrome in adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study.

Childhood cancer survivors (CCS) are at an increased risk of developing metabolic syndrome (MetSyn), which may be reduced with lifestyle modifications. The purpose of this investigation was to characterize lifestyle habits and associations with MetSyn among CCS.

Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: Results from the St. Jude Lifetime Cohort Study

The prevalence of low bone mineral density (BMD) in adult survivors of childhood acute lymphoblastic leukemia (ALL), and the degree of recovery or decline, are not well elucidated.

Assessment of potential bias from non-participation in a dynamic clinical cohort of long-term childhood cancer survivors: results from the St. Jude Lifetime Cohort Study.

To evaluate long‐term health outcomes among childhood cancer survivors, St. Jude Childrens Research Hospital (SJCRH) has established the St. Jude Lifetime Cohort Study (SJLIFE), comprised of adult survivors who undergo risk‐directed clinical assessments. As in any human research study, SJLIFE participants are volunteers who may not represent the source population from which they were recruited. A lack of proportional representation could result in biased estimates of exposure‐outcome associations. We compared available demographic, disease, and neighborhood level characteristics between participants and the source population to assess the potential for selection bias.

Prevalence and Characteristics of Energy Underreporting in African-American Girls

Objective: To determine the frequency and characteristics of energy intake underreporting in African‐American preadolescent girls as part of the Girls health Enrichment Multi‐site Studies (GEMS).

Association Between the Prevalence of Symptoms and Health-Related Quality of Life in Adult Survivors of Childhood Cancer: A Report From the St Jude Lifetime Cohort Study

PURPOSE 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. METHODS 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. RESULTS 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. CONCLUSION A large proportion of survivors suffered from many symptom classes, which was associated with HRQOL impairment.

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.

Self-perception and Body Image Associations with Body Mass Index among 8–10-year-old African American Girls

OBJECTIVES The purpose of this study was to examine relationships among body mass index (BMI), self-perceptions, and body image discrepancy in African American (AA) girls. METHODS Baseline self-perception and BMI data were collected by trained staff from 303 preadolescent AA girls participating in the girls health enrichment multi-site studies. Correlations and multivariable logistic regression analyses were performed to identify relationships of BMI with self-perception factors. RESULTS Girls with a BMI at or above the 85th percentile were more likely to have greater body image discrepancy and participate in weight control behaviors than girls with a BMI below the 85th percentile. Body image discrepancy was not related to self-esteem, but was positively correlated with physical activity self-concept and self-efficacy, and diet self-efficacy. CONCLUSION Girls with higher BMI had greater body image discrepancy and were less confident in abilities to be active and eat healthy. Findings may inform the development of obesity interventions for preadolescents.

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.

Measurement of body composition in 8-10-year-old African-American girls: a comparison of dual-energy X-ray absorptiometry and foot-to-foot bioimpedance methods.

OBJECTIVE The purpose of this study was to evaluate body composition outcomes of foot-to-foot (FF) bioelectrical impedance (BIA) and dual-energy x-ray (DEXA) in 8 to 10-year-old African-American girls and, if different, to develop and cross-validate specific BIA prediction equations for this at-risk group. METHODS DEXA and FF-BIA body composition outcomes were analyzed in 183, 8-10-year-old African-American girls from the Memphis site of the Girls health Enrichment Multi-site Study (GEMS). RESULTS Mean body composition outcomes by FF-BIA and DEXA were significantly different (p<0.0001); therefore, population-specific equations were developed and cross-validated using split-sample, cross-validation methods. When equations were used, BIA and DEXA outcomes were significantly correlated (percent body fat [r=0.931], fat mass [r=0.985], and fat-free mass [r=0.944]). Mean predicted BIA measurements for body fat, fat mass, and fat-free mass were essentially equal to their counterpart DEXA measurements (t[182]=- 0.013, p = 0.897, t[182]=- 0.06, p=0.956, and t[182]=- 0.26, p=0.792, respectively). The Bland-Altman analysis revealed a significant slope for percent fat (p=0.009) and slopes approaching significance for fat mass (p=0.07) and fat-free mass (p=0.06). CONCLUSION Although FF-BIA and DEXA are not directly interchangeable in young African-American girls, these equations accurately estimated average percent fat, fat mass, and fat-free mass of the cross-validation sample of African-American girls. However, the application of this equation may result in potential underestimation or overestimation of fat with respect to DEXA measures in some populations.