Search

Simple Summary: This cross-sectional study analyzed how multilevel social factors affect patient-reported outcomes in children under 18 who survived cancer. Study participants include 293 pairs of these survivors who received survivorship care at a U.S.-based comprehensive cancer center between 2017 and 2018 and their primary caregivers. Findings indicate that higher caregiver anxiety is linked to worse depression, stress, fatigue, sleep problems, and lower positive affect in survivors of pediatric cancer. The study also found that family conflicts are associated with sleep issues in childhood cancer survivors. Furthermore, survivors living in socioeconomically deprived areas experience poorer sleep quality, and those residing in environments with high physical deprivation experience more psychological stress and fatigue, alongside reduced positivity and mobility. These results highlight the significant impact of parental, familial, and neighborhood factors on a range of patient-reported outcomes among young cancer survivors, suggesting these social factors as crucial targets for intervention. In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving treatment at St. Jude Children's Research Hospital who were <18 years of age during follow-up from 2017 to 2018 and their primary caregivers. Social determinants included family factors (caregiver-reported PROs, family dynamics) and county-level deprivation (socioeconomic status, physical environment via the County Health Rankings & Roadmaps). PROMIS measures assessed survivors' and caregivers' PROs. General linear regression tested associations of social determinants with survivors' PROs. We found that caregivers' higher anxiety was significantly associated with survivors' poorer depression, stress, fatigue, sleep issues, and reduced positive affect (p < 0.05); caregivers' sleep disturbances were significantly associated with lower mobility in survivors (p < 0.05). Family conflicts were associated with survivors' sleep problems (p < 0.05). Residing in socioeconomically deprived areas was significantly associated with survivors' poorer sleep quality (p < 0.05), while higher physical environment deprivation was associated with survivors' higher psychological stress and fatigue and lower positive affect and mobility (p < 0.05). Parental, family, and neighborhood factors are critical influences on young survivors' quality of life and well-being and represent new intervention targets. [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]

Background: The objective of this study was to identify treatment and genetic factors associated with obesity among childhood cancer survivors.Methods: Participants included 1996 survivors who previously received treatment for cancer at St. Jude Children's Research Hospital and who survived ≥10 years from diagnosis (median age at diagnosis, 7.2 years; median age at follow-up, 32.4 years). Obesity was defined as a body mass index ≥30 kg/m(2) . The factors associated with adult obesity were identified by subgroup-specific (cranial radiation [CRT] exposure status) multivariable logistic regression. Single nucleotide polymorphisms (SNPs) associated with obesity were identified by subgroup-specific, exploratory, genome-wide association analyses using a 2-stage resampling approach with a type I error rate of 5 × 10(-6) .Results: Forty-seven percent of survivors who received CRT and 29.4% of those who did not receive CRT were obese at evaluation. In multivariable analyses, abdominal/pelvic radiation exposure was associated with decreased prevalence of obesity among survivors regardless of CRT status (P < .0001). The odds of obesity were increased among survivors who received CRT who had also received glucocorticoids (P = .014) or who were younger at diagnosis (P = .013). Among the survivors who had received CRT, 166 SNPs were associated with obesity. The strongest association was observed with reference SNP rs35669975 (P = 3.3 × 10(-8) ) on segment 33.3 of the long arm of chromosome 13 (13q33.3), approximately 30 kb downstream of FAM155A (family with sequence similarity 155, member A). SNPs within the glycine receptor α3 (GLRA3) gene and near the sex-determining region Y box 11 (SOX11) and cadherin 18 type 2 (CDH18) genes also were identified. These genes have been implicated in neural growth, repair, and connectivity.Conclusions: Obesity in childhood cancer survivors remains associated with previous exposure to CRT and glucocorticoids. Genetic variants related to neural connectivity may modify the risk of obesity among survivors who receive CRT. Validation of these findings in independent cohorts is required. [ABSTRACT FROM AUTHOR]

Background: Although pediatric lower extremity sarcoma once was routinely treated with amputation, multiagent chemotherapy as well as the evolution of tumor resection and reconstruction techniques have enabled the wide adoption of limb salvage surgery (LSS). Even though infection and tumor recurrence are established risk factors for early amputation (< 5 years) after LSS, the frequency of and factors associated with late amputation (≥ 5 years from diagnosis) in children with sarcomas are not known. Additionally, the resulting psychosocial and physical outcomes of these patients compared with those treated with primary amputation or LSS that was not complicated by subsequent amputation are not well studied. Studying these outcomes is critical to enhancing the quality of life of patients with sarcomas., Questions/purposes: (1) How have treatments changed over time in patients with lower extremity sarcoma who are included in the Childhood Cancer Survivor Study (CCSS), and did primary treatment with amputation or LSS affect overall survival at 25 years among patients who had survived at least 5 years from diagnosis? (2) What is the cumulative incidence of amputation after LSS for patients diagnosed with pediatric lower extremity sarcomas 25 years after diagnosis? (3) What are the factors associated with time to late amputation (≥ 5 years after diagnosis) in patients initially treated with LSS for lower extremity sarcomas in the CCSS? (4) What are the comparative social, physical, and emotional health-related quality of life (HRQOL) outcomes among patients with sarcoma treated with primary amputation, LSS without amputation, or LSS complicated by late amputation, as assessed by CCSS follow-up questionnaires, the SF-36, and the Brief Symptom Inventory-18 at 20 years after cancer diagnosis?, Methods: The CCSS is a long-term follow-up study that began in 1994 and is coordinated through St. Jude Children's Research Hospital. It is a retrospective study with longitudinal follow-up of more than 38,000 participants treated for childhood cancer when younger than 21 years at one of 31 collaborating institutions between 1970 and 1999 in the United States and Canada. Participants were eligible for enrollment in the CCSS after they had survived 5 years from diagnosis. Within the CCSS cohort, we included participants who had a diagnosis of lower extremity sarcoma treated with primary amputation (547 patients with a mean age at diagnosis of 13 ± 4 years) or primary LSS (510 patients with a mean age 14 ± 4 years). The LSS cohort was subdivided into LSS without amputation, defined as primary LSS without amputation at the time of latest follow-up; LSS with early amputation, defined as LSS complicated by amputation occurring less than 5 years from diagnosis; or LSS with late amputation, defined as primary LSS in study patients who subsequently underwent amputation 5 years or more from cancer diagnosis. The cumulative incidence of late amputation after primary LSS was estimated. Cox proportional hazards regression with time-varying covariates identified factors associated with late amputation. Modified Poisson regression models were used to compare psychosocial, physical, and HRQOL outcomes among patients treated with primary amputation, LSS without amputation, or LSS complicated by late amputation using validated surveys., Results: More study participants were treated with LSS than with primary amputation in more recent decades. The overall survival at 25 years in this population who survived 5 years from diagnosis was not different between those treated with primary amputation (87% [95% confidence interval [CI] 82% to 91%]) compared with LSS (88% [95% CI 85% to 91%]; p = 0.31). The cumulative incidence of amputation at 25 years after cancer diagnosis and primary LSS was 18% (95% CI 14% to 21%). With the numbers available, the cumulative incidence of late amputation was not different among study patients treated in the 1970s (27% [95% CI 15% to 38%]) versus the 1980s and 1990s (19% [95% CI 13% to 25%] and 15% [95% CI 10% to 19%], respectively; p = 0.15). After controlling for gender, medical and surgical treatment variables, cancer recurrence, and chronic health conditions, gender (hazard ratio [HR] 2.02 [95% CI 1.07 to 3.82]; p = 0.03) and history of prosthetic joint reconstruction (HR 2.58 [95% CI 1.37 to 4.84]; p = 0.003) were associated with an increased likelihood of late amputation. Study patients treated with a primary amputation (relative risk [RR] 2.04 [95% CI 1.15 to 3.64]) and LSS complicated by late amputation (relative risk [RR] 3.85 [95% CI 1.66 to 8.92]) were more likely to be unemployed or unable to attend school than patients treated with LSS without amputation to date. The CCSS cohort treated with primary amputation and those with LSS complicated by late amputation reported worse physical health scores than those without amputation to date, although mental and emotional health outcomes did not differ between the groups., Conclusion: There is a substantial risk of late amputation after LSS, and both primary and late amputation status are associated with decreased physical HRQOL outcomes. Children treated for sarcoma who survive into adulthood after primary amputation and those who undergo late amputation after LSS may benefit from interventions focused on improving physical function and reaching educational and employment milestones. Efforts to improve the physical function of people who have undergone amputation either through prosthetic design or integration into the residuum should be supported. Understanding factors associated with late amputation in the setting of more modern surgical approaches and implants will help surgeons more effectively manage patient expectations and adjust practice to mitigate these risks over the life of the patient., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)

Importance: This study provides the first objective data documenting neurocognitive impairment in long-term survivors of childhood osteosarcoma., Objective: To examine neurocognitive, neurobehavioral, emotional, and quality-of-life outcomes in long-term survivors of childhood osteosarcoma., Design, Setting, and Participants: Cross-sectional cohort study at an academic research hospital, with prospective treatment and chronic health predictors. Outcome data were collected from June 2008 to August 2014. Data analysis was completed in April 2015. Survivors of osteosarcoma recruited from the St Jude Lifetime Cohort Study were compared with community controls., Main Outcomes and Measures: Neurocognitive function, neurobehavioral symptoms, emotional distress, and quality of life. Outcomes were examined in relation to pharmacokinetic indices of methotrexate exposure and current chronic health conditions, which were assessed through medical examination and coded according to Common Terminology Criteria for Adverse Events, Version 4.03., Results: Eighty survivors of osteosarcoma (mean [SD] age, 38.9 [7.6] years; time since diagnosis, 24.7 [6.6] years; 42% female) were compared with 39 community controls (age, 39.0 [11.7] years; 56% female). Survivors demonstrated lower mean scores in reading skills (-0.21 [95% CI, -0.32 to -0.10] vs 0.05 [95% CI, -0.13 to 0.23]; P = .01), attention (-0.78 [95% CI, -1.32 to -0.24] vs 0.24 [95% CI, -0.07 to 0.55]; P = .002), memory (-0.24 [95% CI, -0.48 to 0] vs 0.27 [95% CI, -0.08 to 0.62]; P = .01), and processing speed (-0.15 [95% CI, -0.35 to 0.05] vs 0.74 [95% CI, 0.44 to 1.03]; P < .001). Results of pharmacokinetic analysis showed that high-dose methotrexate maximum plasma concentration (estimate = 0; P = .48), median clearance (estimate = -0.11; P = .76), and median/cumulative exposure (estimate = 0; P = .45) were not associated with neurocognitive outcomes. Any grade 3 or 4 Common Terminology Criteria for Adverse Events cardiac, pulmonary, or endocrine condition was associated with poorer memory (t = 2.93; P = .006) and slower processing speed (t = 3.03; P = .002). Survivor-reported poor general health was associated with decreased sustained attention (estimate = 0.24; P = .05) and processing speed (estimate = 0.34; P = .005)., Conclusions and Relevance: Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. Prospective longitudinal studies are needed to identify onset and progression of impairment to inform optimal interventions.

Background: Childhood cancer survivors (CCSs) are at risk for obesity. The purpose of this project was to determine which clinical measures of body composition are most accurate among CCSs in comparison with dual-energy x-ray absorptiometry (DXA)., Methods: The agreement between the body mass index (BMI), skinfold percent body fat, and waist-to-height ratio (WHtR) and DXA was evaluated among 1361 CCSs (mean age, 32.4 ± 7.7 years) 10 or more years after the diagnosis. The sensitivity and specificity of BMI, skinfold, and WHtR obesity classifications were calculated with respect to DXA. Log-binomial regression, stratified by sex, was used to evaluate treatment-related factors for misclassification as nonobese by BMI, skinfolds, and WHtR., Results: The mean body fat values were 23.3% ± 7.7% (males) and 32.3% ± 8.1% (females) for skinfolds and 26.9% ± 7.4% (males) and 38.4% ± 7.7% (females) for DXA. Pearson correlations between skinfolds and DXA were high (R = 0.83 for males, R = 0.84 for females). Skinfolds incorrectly classified 34.5% of obese males and 27.3% of obese females. BMI measures were the least sensitive with false-negative rates of 46.4% (males) and 53.1% (females). Males exposed to abdominal/pelvic radiation were at increased risk for misclassification as nonobese by BMI (relative risk, 1.57; 95% confidence interval, 1.25-1.95). The percentages classified as obese were highest with DXA (males, 63.1%; females, 84.8%) and lowest with BMI (males, 35.7%; females, 39.7%). Although skinfolds and WHtR underestimated the percentage classified as obese in comparison with DXA, the differences were not as large., Conclusions: Findings suggest that skinfolds and WHtR are better than BMI for obesity classification in CCSs. Clinicians should be aware of the high risk of misclassifying obese CCSs as nonobese., (© 2015 American Cancer Society.)

Purpose: Frailty, a phenotype reported among 9.9% of individuals 65 years old and older (9.6% of women; 5.2% of men), has not been assessed among adult childhood cancer survivors (CCS). We estimated the prevalence of frailty and examined associations with morbidity and mortality., Methods: Participants included 1,922 CCS at least 10 years from original cancer diagnosis (men, 50.3%; mean age, 33.6 ± 8.1 years) and a comparison population of 341 participants without cancer histories. Prefrailty and frailty were defined as two and ≥ three of the following conditions: low muscle mass, self-reported exhaustion, low energy expenditure, slow walking speed, and weakness. Morbidity was defined as grade 3 to 4 chronic conditions (Common Terminology Criteria for Adverse Events version 4.0). Fisher's exact tests were used to compare, by frailty status, percentages of those with morbidity. In a subset of 162 CCS who returned for a second visit, Poisson regression was used to evaluate associations between frailty and new onset morbidity. Cox proportional hazards regression was used to evaluate associations between frailty and death., Results: The prevalence of prefrailty and frailty were 31.5% and 13.1% among women and 12.9% and 2.7% among men, respectively, with prevalence increasing with age. Frail CCS were more likely than nonfrail survivors to have a chronic condition (82.1% v 73.8%). In models adjusted for existing chronic conditions, baseline frailty was associated with risk of death (hazard ratio, 2.6; 95% CI, 1.2 to 6.2) and chronic condition onset (relative risk, 2.2; 95% CI, 1.2 to 4.2)., Conclusion: The prevalence of frailty among young adult CCS is similar to that among adults 65 years old and older, suggesting accelerated aging.

Purpose: Childhood cancer survivors are at risk for late effects which may be managed pharmacologically. The purposes of this study were to estimate and compare the prevalence of psychoactive medication use of adult survivors of childhood cancer and sibling controls, identify predictors of medication use in survivors, and investigate associations between psychoactive medications and health-related quality of life (HRQOL)., Methods: Psychoactive medication use from 1994 to 2010 was evaluated in 10,378 adult survivors from the Childhood Cancer Survivor Study. A randomly selected subset of 3,206 siblings served as a comparison group. Multivariable logistic regression models were used to calculate odds ratios (OR) for baseline and new onset of self-reported psychoactive medication use and HRQOL., Results: Survivors were significantly more likely to report baseline (22 vs. 15 %, p < 0.001) and new onset (31 vs. 25 %, p < 0.001) psychoactive medication use compared to siblings, as well as use of multiple medications (p < 0.001). In multivariable models, controlling for pain and psychological distress, female survivors were significantly more likely to report baseline and new onset use of antidepressants (OR = 2.66, 95 % CI = 2.01-3.52; OR = 2.02, 95 % CI = 1.72-2.38, respectively) and multiple medications (OR = 1.80, 95 % CI = 1.48-2.19; OR = 1.77, 95 % CI = 1.48-2.13, respectively). Non-cranial radiation and amputation predicted incident use of analgesics >15 years following diagnosis. Antidepressants were associated with impairment across all domains of HRQOL, with the exception of physical function., Conclusions: Prevalence of psychoactive medication use was higher among survivors for most medication classes, as was the use of multiple medications. Clinicians should be aware of the possible contribution of psychoactive medications to HRQOL., Implications for Cancer Survivors: Survivors of childhood cancer are more likely to be prescribed psychoactive medication than their sibling counterparts, though use of such medication does not appear to normalize quality of life. Survivors are encouraged to consider additional interventions, including psychosocial support and physical exercise.

Purpose: Many Childhood Cancer Survivor Study (CCSS) participants are at increased risk for obesity. The etiology of their obesity is likely multifactorial but not well understood., Patients and Methods: We evaluated the potential contribution of demographic, lifestyle, treatment, and intrapersonal factors and self-reported pharmaceutical use to obesity (body mass index ≥ 30 kg/m2) among 9,284 adult (> 18 years of age) CCSS participants. Independent predictors were identified using multivariable regression models. Interrelationships were determined using structural equation modeling (SEM)., Results: Independent risk factors for obesity included cancer diagnosed at 5 to 9 years of age (relative risk [RR], 1.12; 95% CI, 1.01 to 1.24; P = .03), abnormal Short Form-36 physical function (RR, 1.19; 95% CI, 1.06 to 1.33; P < .001), hypothalamic/pituitary radiation doses of 20 to 30 Gy (RR, 1.17; 95% CI, 1.05 to 1.30; P = .01), and paroxetine use (RR, 1.29; 95% CI, 1.08 to 1.54; P = .01). Meeting US Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR, 0.90; 95% CI, 0.82 to 0.97; P = .01) and a medium amount of anxiety (RR, 0.86; 95% CI, 0.75 to 0.99; P = .04) reduced the risk of obesity. Results of SEM (N = 8,244; comparative fit index = 0.999; Tucker Lewis index = 0.999; root mean square error of approximation = 0.014; weighted root mean square residual = 0.749) described the hierarchical impact of the direct predictors, moderators, and mediators of obesity., Conclusion: Treatment, lifestyle, and intrapersonal factors, as well as the use of specific antidepressants, may contribute to obesity among survivors. A multifaceted intervention, including alternative drug and other therapies for depression and anxiety, may be required to reduce risk.