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Background We aimed to characterize premature aging as an accumulation of deficits in survivors of pediatric cancer compared with community controls and examine associations with host and treatment factors, neurocognition, and mortality. Methods Pediatric cancer survivors (n = 4000, median age = 28.6, interquartile range [IQR] = 23-35 years; 20 years postdiagnosis: IQR = 15-27), and community participants without a history of cancer serving as controls (n = 638, median age = 32, IQR = 25-40 years) completed clinical assessments and questionnaires and were followed for mortality through April 30, 2020 (mean [SD] follow-up = 7.0 [3.4] years). A deficit accumulation index (DAI) score was calculated from 44 aging-related items including self-reported daily function, psychosocial symptoms, and health conditions. Items were weighted from 0 (absent) to 1 (present and/or most severe), summed and divided by the total yielding a ratio (higher = more deficits). Scores less than 0.20 are robust, and 0.06 is a clinically meaningful difference. Linear regression compared the DAI in survivors and controls with an age*survivor or control interaction. Logistic regression and Cox-proportional hazards estimated the risk of neurocognitive impairment and death. Models were minimally adjusted for age, sex, and race and ethnicity. Results The adjusted mean DAI among survivors at age 30 years was 0.16 corresponding to age 63 years in controls (33 years premature aging; β = 0.07, 95% confidence interval [CI] = 0.06 to 0.08; P Conclusion Pediatric cancer survivors experience clinically significant premature aging. The DAI may be used to identify survivors at greatest risk of poor health outcomes.

Background Adult childhood cancer survivors are at risk for frailty, including low muscle mass and weakness (sarcopenia). Using peripheral blood mitochondrial DNA copy number (mtDNAcn) as a proxy for functional mitochondria, this study describes cross-sectional associations between mtDNAcn and sarcopenia among survivors. Methods Among 1762 adult childhood cancer survivors (51.6% male; median age = 29.4 years, interquartile range [IQR] = 23.3-36.8), with a median of 20.6 years from diagnosis (IQR = 15.2-28.2), mtDNAcn estimates were derived from whole-genome sequencing. A subset was validated by quantitative polymerase chain reaction and evaluated cross-sectionally using multivariable logistic regression for their association with sarcopenia, defined by race-, age-, and sex-specific low lean muscle mass or weak grip strength. All statistical tests were 2-sided. Results The prevalence of sarcopenia was 27.0%, higher among female than male survivors (31.5% vs 22.9%; P Conclusions A growing body of evidence supports peripheral blood mtDNAcn as a biomarker for adverse health outcomes; however, this study is the first to report an association between mtDNAcn and sarcopenia among childhood cancer survivors.

Background Some adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at 10 or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail. Methods Frailty was measured at study entry and 5 years later. Logistic regression tested the associations of several factors with having frailty at 5 years for all participants and separately by sex and by study entry frailty status. Cox models evaluated the hazard of death associated with entry frailty considering covariates. Results Cancer survivors (range = 0-22 years at diagnosis, median = 7 years) were ages 18-45 years (median = 30 years) at study entry. Frailty prevalence increased from 6.2% (95% confidence interval [CI] = 5.0% to 7.5%) to 13.6% (95% CI = 11.9% to 15.4%) at 5 years. Risk factors for frailty at follow-up among all survivors included chest radiation 20 Gy or higher (odds ratio [OR] = 1.98, 95% CI = 1.29 to 3.05), cardiac (OR = 1.58, 95% CI = 1.02 to 2.46), and neurological (OR = 2.58, 95% CI = 1.69 to 3.92) conditions; lack of strength training (OR = 1.74, 95% CI = 1.14 to 2.66); sedentary lifestyle (OR = 1.75, 95% CI = 1.18 to 2.59); and frailty at study entry (OR = 11.12, 95% CI = 6.64 to 18.61). The strongest risk factor for death during follow-up was prior frailty (OR = 3.52, 95% CI = 1.95 to 6.32). Conclusions Prevalent frailty more than doubled at 5 years after study entry among adult childhood cancer survivors. Frailty at entry was the strongest risk factor for death. Because treatment exposures cannot be changed, mitigation of other risk factors for frailty, including lack of strength training and sedentary lifestyle, may decrease risk of adverse health events and improve longevity in survivors.

Background Mounting evidence supports the occurrence of accelerating aging among long-term survivors of childhood cancer. We aimed to investigate epigenetic age acceleration (EAA) in survivors and evaluate associations between EAA, treatment exposures, health behaviors, and chronic health conditions (CHCs). Methods Genome-wide methylation data were generated with Infinium EPIC BeadChip on blood-derived DNA from 2139 survivors and 282 frequency matched controls from the St Jude Lifetime Cohort Study. EAAs were estimated as residuals from a linear regression of epigenetic age (Levine’s clock) against chronological age. Adjusted least square mean (ALSM) of EAA was calculated and compared between survivors and controls, across treatment exposures and health behaviors. Associations of EAA with 20 clinically assessed CHCs were evaluated with multivariable piecewise-exponential models. All statistical tests for P values below were 2-sided. Results EAA was statistically significantly higher in survivors than controls (ALSM = 0.63, 95% confidence interval [CI] = 0.26 to 1.01 vs −3.61, 95% CI = −4.43 to 2.80). In a multivariable model among survivors, statistically significantly higher EAA (P Conclusions EAA is statistically significantly higher in survivors of childhood cancer than in noncancer controls and is associated with specific treatment exposures, unfavorable health behaviors, and presence of specific CHCs.

Introduction There is a growing population of childhood cancer survivors at risk for adverse outcomes, including sexual dysfunction. Aim To estimate the prevalence of and risk factors for sexual dysfunction among adult female survivors of childhood cancer and evaluate associations between dysfunction and psychological symptoms/quality of life (QOL). Methods Female survivors (N = 936, mean 7.8 ± 5.6 years at diagnosis; 31 ± 7.8 years at evaluation) and noncancer controls (N = 122) participating in the St. Jude Lifetime Cohort Study completed clinical evaluations, Sexual Functioning Questionnaires (SFQ), and Medical Outcomes Survey Short Forms 36 (SF-36). Linear models compared SFQ scores between sexually active survivors (N = 712) and controls; survivors with scores Outcomes Sexual dysfunction was defined by scores Results Sexual dysfunction was prevalent among 19.9% (95% CI 17.1, 23.1) of survivors. Those diagnosed with germ cell tumors (OR = 8.82, 95% CI 3.17, 24.50), renal tumors (OR = 4.49, 95% CI 1.89, 10.67), or leukemia (OR = 3.09, 95% CI 1.50, 6.38) were at greater risk compared to controls. Age at follow-up (45–54 vs 18–24 years; OR = 5.72, 95% CI 1.87, 17.49), pelvic surgery (OR = 2.03, 95% CI 1.18, 3.50), and depression (OR = 1.96, 95% CI 1.10, 3.51) were associated with sexual dysfunction. Hypogonadism receiving hormone replacement (vs nonmenopausal/nonhypogonadal; OR = 3.31, 95% CI 1.53, 7.15) represented an additional risk factor in the physical problems (eg, vaginal pain and dryness) subscale. Survivors with sexual dysfunction, compared to those without sexual dysfunction, were more likely to score Clinical Implications Health care providers should be aware of the increased risk of sexual dysfunction in this growing population, inquire about symptomology, and refer for appropriate intervention. Strengths & Limitations Strengths of this study include the use of a validated tool for evaluating sexual function in a large population of clinically assessed female childhood cancer survivors. Limitations include potential for selection bias, and lack of clinically confirmed dysfunction. Conclusion Sexual dysfunction is prevalent among female childhood cancer survivors and few survivors receive intervention; further research is needed to determine if those with sexual dysfunction would benefit from targeted interventions.

Background Glucocorticoids used to treat childhood leukemia and lymphoma can result in osteonecrosis, leading to physical dysfunction and pain. Improving survival rates warrants research into long-term outcomes among this population. Objective The objective of this study was to compare the physical function and quality of life (QOL) of survivors of childhood cancer who had an osteonecrosis history with that of survivors who had no osteonecrosis history and with that of people who were healthy (controls). Design This was a cross-sectional study. Methods This study included St Jude Lifetime Cohort Study participants who were ≥ 10 years from the diagnosis of childhood leukemia or lymphoma and ≥ 18 years old; 135 had osteonecrosis (52.5% men; mean age = 27.7 [SD = 6.08] years) and 1560 had no osteonecrosis history (52.4% men; mean age = 33.3 [SD = 8.54] years). This study also included 272 people who were from the community and who were healthy (community controls) (47.7% men; mean age = 35.1 [SD = 10.46] years). The participants completed functional assessments and questionnaires about QOL. Results Survivors with osteonecrosis scored lower than other survivors and controls for dorsiflexion strength (mean score = 16.50 [SD = 7.91] vs 24.17 [SD = 8.61] N·m/kg) and scored lower than controls for flexibility with the sit-and-reach test (20.61 [SD = 9.70] vs 23.96 [SD = 10.73] cm), function on the Physical Performance Test (mean score = 22.73 [SD = 2.05] vs 23.58 [SD = 0.88]), and mobility on the Timed “Up & Go” Test (5.66 [SD = 2.25] vs 5.12 [SD = 1.28] seconds). Survivors with hip osteonecrosis requiring surgery scored lower than survivors without osteonecrosis for dorsiflexion strength (13.75 [SD = 8.82] vs 18.48 [SD = 9.04] N·m/kg), flexibility (15.79 [SD = 8.93] vs 20.37 [SD = 10.14] cm), and endurance on the 6-minute walk test (523.50 [SD = 103.00] vs 572.10 [SD = 102.40] m). Limitations Because some eligible survivors declined to participate, possible selection bias was a limitation of this study. Conclusions Survivors of childhood leukemia and lymphoma with and without osteonecrosis demonstrated impaired physical performance and reported reduced QOL compared with controls, with those requiring surgery for osteonecrosis most at risk for impairments. It may be beneficial to provide strengthening, flexibility, and endurance interventions for patients who have pediatric cancer and osteonecrosis for long-term function.

PURPOSE: Pediatric low-grade glioma therapy has evolved to delay or eliminate radiation. The impact of therapy changes on long-term outcomes remains unknown. METHODS: Cumulative incidence of late mortality (death >5 years from diagnosis), subsequent neoplasms (SNs), and chronic health conditions (CHCs, CTCAE grading criteria) were evaluated in the Childhood Cancer Survivor Study among 5-year survivors of glioma diagnosed 1970-1999. Outcomes were evaluated by diagnosis decade and by treatment exposures received ≤5 years following diagnosis (surgery-only, chemotherapy ± surgery, and cranial radiation ± surgery or chemotherapy). Relative risk (RRs) with 95%CIs estimated long-term outcomes using multivariable piecewise exponential models. RESULTS: Among 2,684 eligible survivors (age at diagnosis (median [range]), 7 years [0-20 years]; time from diagnosis, 24 years [5-48 years]), exposure to cranial radiation decreased [51% (1970s), 45% (1980s), 25% (1990s)] along with late tumor recurrence (>5 & ≤15 years from diagnosis) [9.8% (1970s), 8.8% (1980s), 5.0% (1990s)]. The 15-year cumulative incidence of late mortality was 10.3% (1970s), 6.5% (1980s), and 6.0% (1990s) (p

Background Among adult childhood cancer survivors, the relationship between race/ethnicity and health insurance status, as a contributor to disparities in healthcare utilization, is poorly understood. Methods We examined racial/ethnic-related disparities by insurance status in “forgoing needed medical care in the last year due to finances” using 3,964 adult childhood cancer survivors (3310 non-Hispanic/Latinx White, 562 non-Hispanic/Latinx Black, and 92 Hispanic/Latinx) participating in the St. Jude Lifetime Cohort Study (SJLIFE). Multivariable logistic regression analyses, guided by Andersen’s Healthcare Utilization Model, were adjusted for “predisposing” (age, sex, childhood cancer diagnosis, cancer treatment, surgery, and treatment era) and “need” (perceived health status) factors. Additional adjustment for income/education and chronic health conditions was considered. Results The risk of forgoing care was highest among non-Hispanic/Latinx Blacks and lowest among Hispanics/Latinxs for each insurance status. Among privately-insured survivors, relative to non-Hispanic/Latinx Whites, non-Hispanic/Latinx Blacks were more likely to forgo care (adjusted OR: 1.82, 95% CI: 1.30–2.54): this disparity remained despite additional adjustment for income/education (adjusted OR: 1.43, 95% CI: 1.01–2.01). In contrast, publicly-insured survivors, regardless of race/ethnicity, had similar risk of forgoing care as privately-insured non-Hispanic/Latinx Whites. All uninsured survivors had high risk of forgoing care. Additional adjustment for chronic health conditions did not alter these results. Conclusions The findings of this study show that provision of public insurance to all childhood cancer survivors may diminish racial/ethnic disparities in forgoing care that exist among the privately-insured and reduce the risk of forgoing care among uninsured survivors to that of privately-insured non-Hispanic/Latinx Whites. Key messages Providing publicly funded health insurance coverage to childhood cancer survivors can reduce disparities in forgoing medical care.

This review focuses on diet and exercise interventions that have been conducted in pediatric cancer and pediatric stem cell transplant patients. It examines the different reasons for conducting lifestyle interventions with attention to the different outcome measurements and feasibility of these measures with an argument toward a need for standardization to move the field forward.

Observational data have shown that some cancer survivors develop chronic conditions like frailty, sarcopenia, cardiac dysfunction, and mild cognitive impairment earlier and/or at a greater burden than similarly aged individuals never diagnosed with cancer or exposed to systemic or targeted cancer therapies. In aggregate, cancer- and treatment-related physical, cognitive, and psychosocial late- and long-term morbidities experienced by cancer survivors are hypothesized to represent accelerated or accentuated aging trajectories. However, conceptual, measurement, and methodological challenges have constrained efforts to identify, predict, and mitigate aging-related consequences of cancer and cancer treatment. In July 2018, the National Cancer Institute convened basic, clinical, and translational science experts for a think tank titled “Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors.” Through the resulting deliberations, several research and resource needs were identified, including longitudinal studies to examine aging trajectories that include detailed data from before, during, and after cancer treatment; mechanistic studies to elucidate the pathways that lead to the emergence of aging phenotypes in cancer survivors; long-term clinical surveillance to monitor survivors for late-emerging effects; and tools to integrate multiple data sources to inform understanding of how cancer and its therapies contribute to the aging process. Addressing these needs will help expand the evidence base and inform strategies to optimize healthy aging of cancer survivors.

Background In noncancer populations, insomnia is known to affect neurocognitive processes. Although the prevalence of insomnia appears to be elevated in survivors of childhood cancer, relatively little is known about its association with neurocognitive performance in this at-risk population. Methods A total of 911 survivors (51.9% female; mean [SD] age, 34 [9.0] years; time since diagnosis, 26 [9.1] years) completed direct assessments of attention, memory, processing speed, and executive functioning and self-reported symptoms of sleep (Pittsburgh Sleep Quality Index), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue), and daytime sleepiness (Epworth Sleepiness Scale). Sex-stratified general linear models were used to examine associations between insomnia and neurocognitive performance, with adjustment for treatment exposures and chronic health conditions. All statistical tests were two-sided. Results Insomnia was reported by 22.1% of females and 12.3% of males (P Conclusions Insomnia was highly prevalent and contributed to the neurocognitive burden experienced by adult survivors of childhood cancer. Treatment of insomnia may improve neurocognitive problems in survivors.

In May 2018, the National Cancer Policy Forum (NCPF) of the National Academies of Sciences, Engineering, and Medicine (formerly the Institute of Medicine) released a report, Long-Term Survivorship Care After Cancer Treatment: Proceedings of Workshop. NCPF-published reports have historically played a significant role in driving policy and payment model changes in oncology care, in addition to raising awareness about the needs of individuals with cancer. This 2018 report provides a specific set of recommendations for improving symptom management and rehabilitation that suggest the integration of rehabilitation services at the point of cancer diagnosis and throughout the continuum of cancer care to effectively screen for and manage the anticipated functional morbidity associated with cancer treatment. The specificity of these recommendations is of significant relevance to the physical therapy profession and should encourage bold steps to effectively increase the presence of physical therapists as members of interdisciplinary cancer care teams. The profession must act to implement models of prospective care, develop targeted education and training initiatives to assure the knowledge and skills of our workforce for this complex population, and augment the current evidence base with greater attention to health services research aiming to understand the effectiveness of rehabilitation services in improving costs, utilization, and meaningful functional outcomes.

Background Neurocognitive impairment in survivors of childhood cancer may be associated with direct neurotoxicity, as well as indirect effects of systemic health complications. We evaluated associations among treatment exposures, chronic health conditions, and neurocognitive outcomes in adult survivors of childhood cancer. Methods Participants included 5507 adult survivors of childhood cancer (47.1% male; mean [SD] age = 31.8 [7.6] years at evaluation; 23.1 [4.5] years postdiagnosis) in the Childhood Cancer Survivor Study who completed a self-report measure of neurocognitive function. Cardiac, pulmonary, and endocrine chronic health conditions were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Structural equation modeling was used to examine a priori hypothesized causal pathways among cancer treatment, subsequent chronic health conditions, and neurocognitive outcomes. Multivariable models were used to estimate relative risk for associations of treatments and chronic conditions on neurocognitive function. All statistical tests were two-sided. Results One-third of survivors with a grade 2 or higher chronic condition reported impairments in task efficiency and memory. In addition to direct effects of cranial radiation, path analyses and multivariable models demonstrated direct effects of cardiopulmonary (β = 0.10, P = .002; relative risk [RR] = 1.27, 95% confidence interval [CI] = 1.12 to 1.44) and endocrine (β = 0.07, P = .04; RR = 1.14, 95% CI = 1.02 to 1.28) conditions on impaired task efficiency. We identified similar effects of cardiopulmonary condition on memory (P = .01) and emotional regulation (P = .01). Thoracic radiation was associated with impaired task efficiency (P = .01) and emotional regulation (P = .01) through endocrine morbidity. Conclusions Non-neurotoxic exposures, such as thoracic radiation, can adversely impact survivors' neurocognitive function through chronic conditions. Management of chronic diseases may mitigate neurocognitive outcomes among aging survivors of childhood cancer.

Introduction Sleep disturbances are prevalent among adult survivors of childhood cancer, though little is known about associations between sleep and health in this vulnerable population. Methods Survivors recruited from the St. Jude Lifetime Cohort (n=911; 52% female; mean age 34 years; 26 years post-diagnosis) completed surveys assessing habitual sleep patterns and mental health and underwent comprehensive physical examinations. A subset of survivors (n=491) completed sleep actigraphy. Short sleep duration was defined as sleeping Results Self-report and actigraphy-assessed short sleep was identified in 44% and 42% of survivors, respectively. However, these measures were weakly correlated (r=0.23). In adjusted multivariable models, self-reported short sleep was associated with higher risk of pulmonary conditions (RR=1.3, 95% CI=1.1-1.7), depression (OR=2.6, 95% CI=1.4-5.1) and anxiety (OR=3.4, 95% CI=1.6-6.8), while associations with cardiac (RR=1.10, 95% CI=0.94-1.30) and renal conditions (OR=1.30, 95% CI=0.79-2.13) were not significant. There were no significant associations between actigraphy-assessed short sleep and any of the health outcomes. Conclusion Habitual self-reported short sleep was associated with clinically ascertained adverse health outcomes. Although the temporality of these associations cannot be determined in this cross-sectional study, sleep is a modifiable health behavior and improving sleep may improve health in survivors. Measures of self-reported sleep may have unique value when assessing the relationship between sleep and health. Support CA225590, K. Krull Principal Investigator; CA195547, M. Hudson and L. Robison Principal Investigators; CA21765, C. Roberts, Principal Investigator

Young adults were the only age group to defy the downward trend in cigarette use seen in the 1980s and 1990s. To help explain this phenomenon, we conducted an exploratory study to examine the association between the sociocultural contexts of young adults' everyday lives and their smoking attitudes and behaviors. "Context" was operationalized by (a) including students and nonstudents in the study population, and (b) selecting two distinctly different areas of Minnesota for examination. The study sites were Hibbing and environs (Range), the sparsely populated hub of the state's once-thriving iron ore industry, and the Twin Cities metropolitan area (Metro), center of state government, finance, transportation, education, and industry. This report focuses on the first phase of the study, which consisted of a computer-assisted telephone interview of 995 randomly selected young adults, aged 18-24. Approximately equal numbers of students and nonstudents were selected from each site. Exploratory factor analysis yielded four distinct scales related to alcohol consumption and partying (Drinking Behavior), the social attractiveness and utility of smoking (Social Utility), outdoor recreation (Outdoor Rec), and media use and hours of free time. We decided not to use the media and free time scale, however, because of its low Cronbach alpha (.42). We used polynomial logistic regression to evaluate the association between smoking status, gender, student status, location (Range vs. Metro), and the three retained scales. Results indicated that living on the Iron Range (OR = 2.6), being female (OR = 1.3), and scoring higher on the Social Utility scale (OR = 3.06) increased the risk of smoking, whereas being a student (OR = 0.53) decreased the risk substantially.

Background and Purpose. Because of the high risk of falling and the recognition that falling is a “geriatric syndrome,” screening for risk of falls has become popular at community health fairs. The purposes of this study were to determine whether health fair screening and educational intervention would result in behaviors that could reduce the risk of falls and to determine whether adoption of risk-reduction behaviors differed between people over age 65 years screened as being at high risk for falls and those screened as being at lower risk for falls. Subjects and Methods. The Berg Balance Test was used to classify fall risk in 68 individuals aged 57 to 89 years who were attending a community health fair. A score of 45 or lower led to a categorization of the person being at high risk for falls. All subjects were provided recommendations intended to reduce fall risk. Participants were interviewed by telephone 30 days after the screening to assess implementation of these recommendations. Results. Seventy-two percent of the participants reported implementing at least one risk-reduction behavior. The high-risk group was more likely to implement risk-reduction behaviors than the low-risk group. Discussion and Conclusion. Screening and education in a health fair setting appear to promote behaviors that could reduce fall risk among elderly people. Future study with a control group that does not receive an educational intervention is needed to draw more definite conclusions about the value of this health promotion activity for fall prevention.