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Purpose: Childhood cancer survivors are at risk for cardiac dysfunction and impaired physical performance, though underlying cellular mechanisms are not well studied. In this cross-sectional study, we examined the association between peripheral blood mitochondrial DNA copy number (mtDNA-CN, a proxy for mitochondrial function) and markers of performance impairment and cardiac dysfunction. Methods: Whole-genome sequencing, validated by quantitative polymerase chain reaction, was used to estimate mtDNA-CN in 1720 adult survivors of childhood cancer (48.5% female; mean age = 30.7 years, standard deviation (SD) = 9.0). Multivariable logistic regression was performed to evaluate the associations between mtDNA-CN and exercise intolerance, walking inefficiency, and abnormal global longitudinal strain (GLS), adjusting for treatment exposures, age, sex, and race and ethnicity. Results: The prevalence of exercise intolerance, walking inefficiency, and abnormal GLS among survivors was 25.7%, 10.7%, and 31.7%, respectively. Each SD increase of mtDNA-CN was associated with decreased odds of abnormal GLS (adjusted odds ratio (OR) = 0.88, p = 0.04) but was not associated with exercise intolerance (OR = 1.02, p = 0.76) or walking inefficiency (OR = 1.06, p = 0.46). Alkylating agent exposure was associated with increased odds of exercise intolerance (OR = 2.25, p < 0.0001), walking inefficiency (OR = 2.37, p < 0.0001), and abnormal GLS (OR = 1.78, p = 0.0002). Conclusions: Increased mtDNA-CN is associated with decreased odds of abnormal cardiac function in childhood cancer survivors. Implications for Cancer Survivors: These findings demonstrate a potential role for mtDNA-CN as a biomarker of early cardiac dysfunction in this population. [ABSTRACT FROM AUTHOR]

Purpose: To investigate racial/ethnic-related disparities by insurance status in "forgoing needed medical care in the last year due to finances" in childhood cancer survivors. Methods: Our study included 3310 non-Hispanic/Latinx White, 562 non-Hispanic/Latinx Black, and 92 Hispanic/Latinx survivors from the St. Jude Lifetime Cohort Study. Logistic regression analyses, guided by Andersen's Healthcare Utilization Model, were adjusted for "predisposing" (survey age, sex, childhood cancer diagnosis and treatment, and treatment era) and "need" (perceived health status) factors. Additional adjustment for household income/education and chronic health conditions was considered. Results: 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 household 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 chronic health condition adjustment did not alter these results. Conclusions: 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. Implications for Cancer Survivors: Under public insurance, childhood cancer survivors had low risk of forgoing care, at the similar level to privately insured non-Hispanic/Latinx Whites, regardless of race/ethnicity. [ABSTRACT FROM AUTHOR]

Purpose: The study aims were to determine the prevalence of balance impairments in adult survivors of pediatric central nervous system (CNS) tumors, and to identify predictors of and limitations associated with balance impairments. Methods: Participants were adult survivors (N = 329) of pediatric CNS tumors. Balance was considered impaired among those with composite scores < 70 on the sensory organization test. Potential predictors of impaired balance were evaluated with generalized linear regression. Multivariable logistic regression was used to evaluate associations between balance impairment and function. Results: Balance impairment was observed in 48% of survivors, and associated with infratentorial tumor location (OR = 4.0, 95% CI, 2.0–7.6), shunt placement (OR = 3.5, 95% CI, 1.8–6.7), increased body fat percentage (OR = 1.1, 95% CI, 1.0–1.1), hearing loss (OR = 11.1, 95% CI, 5.6–22.2), flexibility limitations (OR = 2.0, 95% CI, 1.0–3.9), peripheral neuropathy (OR = 2.4, 95% CI, 1.2–4.5), and cognitive deficits (OR = 2.2, 95% CI, 1.1–4.7). In adjusted models, impaired balance was associated with limitations in overall physical performance (OR = 3.6, 95% CI, 2.0–6.3), mobility (OR = 2.6, 95% CI, 1.5–4.4), diminished walking endurance (OR = 2.9, 95% CI, 1.7–5.0), and non-independent living (OR = 2.0, 95% CI, 1.0–4.3). Conclusions: Nearly half of adult survivors of pediatric CNS tumors have impaired balance, which is associated with mobility and physical performance limitations. Interventions to address the complex needs of this population should be prioritized. Implications for Cancer Survivors: Survivors with identified risk factors should be closely evaluated for presence of balance impairment. Interventions tailored to improve balance also can positively affect function and mobility in survivors. [ABSTRACT FROM AUTHOR]

Purpose: Cancer-related fatigue (CRF) negatively affects the lives of childhood, adolescent, and young adult (CAYA) cancer survivors. We aimed to provide an evidence-based clinical practice guideline (CPG) with internationally harmonized CRF surveillance recommendations for CAYA cancer survivors diagnosed < 30 years.Methods: This CPG was developed by a multidisciplinary panel under the umbrella of the International Late Effects of Childhood Cancer Guideline Harmonization Group. After evaluating concordances and discordances of four existing CPGs, we performed systematic literature searches. We screened articles for eligibility, assessed quality, extracted, and summarized the data from included articles. We formulated recommendations based on the evidence and clinical judgment.Results: Of 3647 articles identified, 70 articles from 14 countries were included. The prevalence of CRF in CAYA cancer survivors ranged from 10-85%. We recommend that healthcare providers are aware of the risk of CRF, implement regular screening with validated measures, and recommend effective interventions to fatigued survivors.Conclusions: A considerable proportion of CAYA cancer survivors suffers from CRF even years after the end of treatment.Implications For Cancer Survivors: We recommend that healthcare providers adopt regular screening to detect and treat CRF early and positively influence survivors' health and quality of life. [ABSTRACT FROM AUTHOR]

Purpose: The majority of research examining posttraumatic stress symptoms/disorder (PTSS/PTSD) among adult survivors of childhood cancer has been oriented to cancer, assuming that cancer has been the most traumatic experience in their lives. Whether that assumption is valid, and how it might impact assessment of PTSS, is unknown.Methods: Survivors in the St. Jude Lifetime Cohort study completed an assessment of PTSS without cancer orientation, global psychological functioning, perceived stress, and cancer-related anxiety.Results: Participants (n = 2969; Mage = 32.5 ± 8.5 years, 24.1 years since diagnosis, 49.1% female) obtained a mean score on the PTSD Checklist of 27.7, which is comparable to a normative population. Using established cutoffs, 11.8% obtained scores in the at-risk range. Multivariable modeling indicated that psychological factors [global distress (p < 0.0001), perceived stress (p = 0.001), cancer-related anxiety (p < 0.0001)] and demographic variables [female gender (p < 0.0001), survivors with less than a college education (p = 0.002)] were risk factors for increased PTSS. Only 14.5% identified a cancer-related traumatic event, and there was no difference in PTSS scores between those who identified cancer vs. non-cancer events as most stressful (28.4 ± 12.6 vs. 28.5 ± 12.7, p = 0.93).Conclusion: One in eight adult long-term survivors of childhood cancer had PTSS above the cutoff, though subgroups (e.g., females and those with lower education) report more distress symptoms. Most adult survivors do not identify cancer as their most stressful event.Implications For Cancer Survivors: Screening for distress in survivorship clinics should not assume that distress is directly related to the survivor's cancer experience. [ABSTRACT FROM AUTHOR]

Purpose: Human papillomavirus (HPV) is a sexually transmitted infection and the cause of cervical and other cancers. Vaccination is available to protect against genital HPV and is recommended for individuals aged 9-26 years. This study aimed to estimate the prevalence of HPV vaccination among childhood cancer survivors and to identify factors associated with vaccine outcomes.Methods: Young adult females with (n = 114; M age = 21.18 years, SD = 2.48) and without (n = 98; M age = 20.65 years, SD = 2.29) a childhood cancer history completed surveys querying HPV vaccination initiation/completion, as well as sociodemographic, medical, and health belief factors. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs) for vaccine outcomes.Results: Among survivors, 38.6 % (44/114) and 26.3 % (30/114) initiated or completed vaccination compared to 44.9 % (44/98) and 28.6 % (28/98) among controls, respectively. In the combined survivor/control group, physician recommendation (OR = 11.24, 95 % CI 3.15-40.14) and familial HPV communication (OR = 7.28, 95 % CI 1.89-28.05) associated with vaccine initiation. Perceptions of vaccine benefit associated with vaccine completion (OR = 10.55, 95 % CI 1.59-69.92), whereas perceptions of HPV-related severity associated with non-completion (OR = 0.14, 95 % CI 0.03-0.71).Conclusion: Despite their increased risk for HPV-related complication, a minority of childhood cancer survivors have initiated or completed HPV vaccination. Modifiable factors associated with vaccine outcomes were identified.Implications For Cancer Survivors: HPV vaccination is a useful tool for cancer prevention in survivorship, and interventions to increase vaccine uptake are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Current information regarding pregnancy-associated cardiomyopathy among women treated for childhood cancer is insufficient to appropriately guide counseling and patient management. This study aims to characterize its prevalence within a large cohort of females exposed to cardiotoxic therapy.Methods: This is a retrospective cohort study of female cancer survivors treated at St. Jude Children's Research Hospital between 1963 and 2006, at least 5 years from diagnosis, ≥13 years old at last follow-up, and with at least one successful pregnancy. Pregnancy-associated cardiomyopathy was defined as shortening fraction <28 % or ejection fraction <50 % or treatment for cardiomyopathy during or up to 5 months after completion of pregnancy.Results: Among the 847 female cancer survivors with 1554 completed pregnancies, only 3 (0.3 %) developed pregnancy-associated cardiomyopathy and 40 developed non-pregnancy-associated cardiomyopathy either 5 months postpartum (n = 14) or prior to pregnancy (n = 26). Among those with cardiomyopathy prior to pregnancy (n = 26), cardiac function deteriorated during pregnancy in eight patients (three patients with normalization of cardiac function prior to pregnancy, three with persistently abnormal cardiac function, and two for whom resolution of cardiomyopathy was unknown prior to pregnancy). Patients that developed cardiomyopathy received a higher median dose of anthracyclines compared to those that did not (321 versus 164 mg/m(2); p < 0.01).Conclusions: Pregnancy-associated cardiomyopathy in childhood cancer survivors is rare.Implications For Cancer Survivors: Most female childhood cancer survivors will have no cardiac complications during or after childbirth; however, those with a history of cardiotoxic therapies should be followed carefully during pregnancy, particularly those with a history of anthracycline exposures and if they had documented previous or current subclinical or symptomatic cardiomyopathy. [ABSTRACT FROM AUTHOR]