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Background: Estimates indicate that nearly 8% of the over 500,000 survivors of childhood cancer living in the United States are frail in their fourth and fifth decades of life, a phenotype typically seen in geriatric populations. Participation in regular physical activity to improve physical fitness in healthy and diseased populations reduces risk for frail health by increasing physiologic reserve. However, physical activity may not have the same effects on fitness in childhood cancer survivors as it does among their peers with no cancer history. Aims: This scoping review seeks to describe associations between physical activity, physical fitness, chronic disease, and mortality in childhood cancer survivors. Methods: Relevant literature was identified through a comprehensive search in the PubMed, Web of Science, CINAHL, and Cochrane databases. A narrative synthesis was performed on observational studies that had physical activity or physical fitness clearly defined and compared with chronic disease outcomes. Results: A total of 595 studies were screened, and results from 11 studies are presented. Childhood cancer survivors who participate in regular physical activity have improved markers of cardiovascular health, decreased risk of overt cardiovascular disease, and decreased risk of all-cause mortality compared to survivors who are not physically active. Childhood cancer survivors who are physically fit have increased neurocognition, and decreased risk of all-cause mortality compared to survivor's who are not fit. The differential effects of physical activity on fitness and health among childhood cancer survivors when compared to peers is potentially related to treatment exposures that damage cardiovascular tissue and impact regenerative potential. Conclusion:Research is needed to determine the optimal timing, frequency, intensity, and duration of physical activity necessary to optimize fitness in childhood cancer survivors.

Background There are limited data describing fitness and associated health‐related quality of life (HRQoL) in survivors of childhood Hodgkin lymphoma (HL). Procedure Fitness was evaluated among 336 adult survivors of childhood‐onset HL treated at St. Jude Children's Research Hospital and 327 controls who never had childhood cancer. The controls were frequency matched on age, sex, and race. Associations were examined between chronic disease and fitness and between fitness and HRQoL using a multivariable linear and logistic regression. Results Male survivors had lower endurance (6‐min walk [6MW] distance 604.4 ± 7.9 m vs 637.0 ± 7.5 m, P < 0.01), and worse neuropathy (modified Total Neuropathy Score [mTNS] 2.7 ± 0.2 vs 1.4 ± 0.2, P < 0.01) compared to controls. Female survivors had lower endurance (6MW distance 564.5 ± 6.9 m vs 590.6 ± 7.0 m, P < 0.01), quadriceps strength (145.7 ± 4.0 vs 163.4 ± 4.0 N·m per kilogram, P < 0.01), and worse neuropathy (mTNS 3.2 ± 0.2 vs 1.4 ± 0.3, P < 0.01) compared to controls. Moderate, severe/disabling, or life‐threatening (grades 2‐4) neurological conditions were associated with impaired quadriceps strength (odds ratio [OR] 2.94, 99% confidence interval [CI] 1.24‐6.96) and impaired endurance (OR 2.96, 99% CI 1.28‐6.69). Cardiovascular (OR 2.36, 99% CI 1.00‐5.61) and pulmonary (OR 2.78, 99% CI 1.30‐5.94) conditions were associated with impaired endurance. Quadriceps strength (β –6.44 ± 2.01, P < 0.01), endurance (β –4.63 ± 1.54, P < 0.01), and neuropathy (β –4.98 ± 1.14, P < 0.01) were associated with a lower physical component summary on the HRQoL. Conclusion Survivors of childhood HL, particularly those with neurological, cardiac, and pulmonary chronic conditions, are at risk for impaired fitness and HRQoL.

Purpose Children diagnosed with craniopharyngioma are vulnerable to adverse health outcomes. Characterization of body mass index (BMI), physical function, and cardiopulmonary fitness in those treated with proton radiotherapy (PRT) will serve to design interventions to improve outcomes. Methods Ninety-four children with craniopharyngioma completed physical function testing prior to PRT and annually for 5 years. For each outcome, age- and sex-specific z-scores were calculated using normative values. Participants with z-scores > 1.5 or < − 1.5 were classified as impaired. Those with z-scores > 2.0 or < − 2.0 were classified as significantly impaired. Descriptive statistics were used to describe study outcomes and change in prevalence of impairments from 2 to 5 years after treatment. Results Nearly half of participants [45.2%, 95% confidence interval (CI) 39.4, 51.0] had mean BMI z-scores > 1.5 at baseline, with prevalence increasing to 66.7% (95% CI 61.5, 71.9) at 5 years. More than half of participants (54.2%, 95% CI 48.4, 60.0) had knee extension strength z-scores < − 1.5 at baseline, with prevalence increasing to 81.3% (95% CI 77.7, 84.9) at 5 years. BMI and knee extension strength had the largest proportion of participants impaired at both 2 and 5 years (53.2% and 62.3%, respectively). Resting heart rate had the highest proportion of participants not impaired at 2 years but became impaired at 5 years (26.6%). Conclusions Children with craniopharyngioma have BMI and fitness abnormalities at diagnosis and continue 5 years after treatment. This cohort may benefit from interventions designed to improve BMI, strength, and resting indicators of cardiopulmonary fitness. Supplementary Information The online version contains supplementary material available at 10.1007/s11060-022-04116-2.

BackgroundOver 50% of childhood cancer survivors are exercise intolerant, with maximal aerobic capacities comparable to individuals decades older, suggesting early physiologic ageing. In addition, 36% of survivors are obese. Optimal exercise capacity provides a foundation to support daily function and healthy body habitus and is associated with benefits to cognition, cardiovascular health, and longevity. Cellular senescence and inflammation are key mechanisms that drive age-related disease, quantifiable as biomarkers in peripheral blood.AimsThis study aimed to evaluate associations between p16INKa, a biomarker of cellular senescence, and inflammation and exercise capacity among adult survivors of childhood cancer.Materials and methodsEligible survivors were recruited from the St. Jude Lifetime (SJLIFE) Cohort Study. Exercise capacity was assessed by maximal oxygen uptake (VO2, ml/kg/min) obtained via cardiopulmonary exercise testing using a modified Bruce protocol. Body fat (%) was determined from dual energy x-ray absorptiometry (DEXA). Peripheral blood samples were used to evaluate log2 p16INK4a mRNA expression, a biomarker of cellular senescence, and inflammation with high sensitivity C-reactive protein (hs-CRP) levels. Multivariable regression evaluated associations between p16INK4a, hs-CRP, body fat, and exercise capacity.ResultsParticipants included 185 five-year childhood cancer survivors (mean age 36.6 [range 20.1 - 55.7] years, 44% male, 77% non-Hispanic white, 53% leukemia/lymphoma). Compared to males, females had lower peak VO2 (mean ± SD, 22.5 ± 8.2 vs. 28.8 ± 7.7 ml/kg/min, p&lt;0.01), higher p16INK4a expression (9.6 ± 1.2 vs. 9.2 ± 1.2 fold, p=0.02), and hs-CRP concentration (5.9 ± 8.4 vs. 3.3 ± 3.9 mg/L, p=0.01). Among females (n=103), hs-CRP concentration (β -0.2, 95% CI -0.34 to -0.05, p=0.01) and p16INK4a expression (β-5.32, 95% CI 10.42 to -0.22, p=0.04) were inversely associated and statistically significant with peak exercise capacity, with a significant interaction between p16INK4a expression and body fat (β 0.15, 95% CI 0.02 to 0.28, p=0.03). Among males (n=82), p16INK4a expression (β -1.01, 95% CI -2.14 to 0.12, p=0.08), and body fat (β -0.54, 95% CI -0.70 to -0.38, p&lt;0.01) were inversely associated with peak exercise capacity.ConclusionInflammation and p16INK4a expression, a biomarker of cellular senescence, are associated with lower exercise capacity in childhood cancer survivors, suggesting potential targets or outcome measures for interventions designed to prevent or remediate accelerated physiologic ageing in this population.