Progression of Frailty in Survivors of Childhood Cancer: A St. Jude Lifetime Cohort Report.
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ABSTRACT: 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.
SUBMITTER: Delaney A
PROVIDER: S-EPMC8633430 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionThere is a growing population of childhood cancer survivors at risk for adverse outcomes, including sexual dysfunction.AimTo 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).MethodsFemale 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 <10th percentile of controls were classified with sexual dysfunction. Logistic regression evaluated associations between survivor characteristics and sexual dysfunction, and between sexual dysfunction and QOL.OutcomesSexual dysfunction was defined by scores <10th percentile of noncancer controls on the SFQ overall, as well as the domains of arousal, interest, orgasm, and physical problems, while QOL was measured by scores on the SF-36 with both physical and mental summary scales.ResultsSexual 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 <40 on the physical (21.1% vs 12.7%, P = .01) and mental health (36.5% vs 18.2%, P < .01) summary scales of the SF-36. Only 2.9% of survivors with sexual dysfunction reported receiving intervention.Clinical implicationsHealth 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 & limitationsStrengths 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.ConclusionSexual 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. Bjornard KL, Howell CR, Klosky JL, et al. Psychosexual Functioning of Female Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort Study. J Sex Med 2020;17:1981-1994.
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Project description: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.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.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).The prevalence of frailty among young adult CCS is similar to that among adults 65 years old and older, suggesting accelerated aging.
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Project description: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.CCS who were???10 years from diagnosis, aged?>?18 years, and participating in the St. Jude Lifetime Cohort Study completed medical and laboratory tests and a food frequency questionnaire. The Third Report of the National Cholesterol Education Program Adult Treatment Panel criteria were used to classify participants with MetSyn. Anthropometric, food frequency questionnaire, and self-reported physical activity data were used to characterize lifestyle habits according to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations. Those who met???4 of 7 recommendations were classified as having followed guidelines. Sex-stratified log-binomial regression models were used to evaluate associations between dietary/lifestyle habits and MetSyn, adjusted for age, age at cancer diagnosis, receipt of cranial radiotherapy, education, and household income.Among 1598 CCS (49.2% of whom were male, with a median age of 32.7 years [range, 18.9 years-60.0 years]), 31.8% met criteria for MetSyn and 27.0% followed WCRF/AICR guidelines. Females who did not follow WCRF/AICR guidelines were 2.4 times (95% confidence interval, 1.7-3.3) and males were 2.2 times (95% confidence interval, 1.6-3.0) more likely to have MetSyn than those who followed WCRF/AICR guidelines.Adherence to a heart-healthy lifestyle is associated with a lower risk of MetSyn among CCS. There is a need to determine whether lifestyle interventions prevent or remediate MetSyn in CCS.
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Project description:The purpose of this study was to define the prevalence of and risk factors for elevated serum alanine aminotransferase (ALT) level among adult childhood cancer survivors (CCS). The study cohort comprised 2,751 CCS from the St. Jude Lifetime Cohort Study (>10 years postdiagnosis, age ?18 years). Serum ALT level was graded using the Common Terminology Criteria for Adverse Events v. 4.03. Modified Poisson regression models were used to estimate relative risks and 95% confidence intervals for the association between demographic and clinical factors and grades 1-4 ALT on the selected models. A total of 1,339 (48.7%) CCS were female; 2,271 (82.6%) were non-Hispanic white. Median age at evaluation was 31.4 years (interquartile range [IQR] = 25.8-37.8); median elapsed time from diagnosis to evaluation was 23.2 years (IQR = 17.6-29.7). A total of 1,137 (41.3%) CSS had ALT > upper limit of normal (Common Terminology Criteria for Adverse Events v. 4.03 grade 1-1,058 (38.5%); grade 2-56 (2.0%); grade 3-23 (0.8%); grade 4-none). Multivariable models demonstrated non-Hispanic white race/ethnicity, age at evaluation in years, being overweight or obese, presence of the metabolic syndrome, current treatment with atorvastatin or rosuvastatin or simvastatin, hepatitis C virus infection, prior treatment with busulfan or thioguanine, history of hepatic surgery, and the percentage of liver treated with ?10 Gray, ?15 Gray, or ?20 Gray were associated with elevated ALT. Conclusion: Grade 3 or 4 hepatic injury is infrequent in CCS. Mild hepatic injury in this group may be amenable to lifestyle modifications.
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Project description:Background: Hypertension potentiates cardiovascular risk in survivors of childhood cancer previously exposed to cardiotoxic therapies, so it is important to determine the prevalence and risk factors for hypertensive blood pressure in this high-risk group.Methods: Participants included 3,016 adult 10-year survivors of childhood cancer who had resting blood pressure measurements performed at St. Jude Children's Research Hospital (Memphis, TN). We characterized the blood pressure status of participants, calculated standardized prevalence ratios based on U.S. population rates, and examined demographic and treatment factors associated with hypertensive blood pressure using logistic regression.Results: The age-specific cumulative prevalence of hypertension in survivors increased sharply with age, exceeding 70% by age 50, and was substantially higher in all diagnosis groups than expected on the basis of age-, sex-, race/ethnicity-, and BMI-specific population rates. Specific cancer treatments were not significantly associated with hypertension, with the exception of nephrectomy (OR, 1.68; 95% confidence interval, 1.11-2.53). Previously undiagnosed hypertensive blood pressure was identified in 8% of survivors, and uncontrolled hypertension in 22% of those with a previous hypertension diagnosis. In a subset (n = 1,185) with longitudinal blood pressure measurements (mean interval, 3.6 years), 5% and 21% of participants with previously normal blood pressure developed hypertensive and prehypertensive blood pressure, respectively.Conclusions: Survivors of childhood cancer have a higher prevalence of hypertension compared with the general population, and many have uncontrolled hypertension that may exacerbate treatment-related cardiovascular risks.Impact: Our results suggest enhanced clinical attention to blood pressure status is warranted in all survivors, regardless of diagnosis or cancer treatment. Cancer Epidemiol Biomarkers Prev; 26(12); 1705-13. ©2017 AACR.
| S-EPMC5788007 | biostudies-literature
Project description:IntroductionThis study aimed to assess longitudinal associations between lifestyle and subsequent malignant neoplasms (SMNs) in young adult childhood cancer survivors.MethodsMembers of the St. Jude Lifetime Cohort (SJLIFE) aged ≥18 years and surviving ≥5 years after childhood cancer diagnosis were queried and evaluated for physical activity, cardiorespiratory fitness (CRF), muscle strength, body mass index (BMI), smoking, risky drinking, and a combined lifestyle score. Time to first SMN, excluding nonmalignant neoplasms and nonmelanoma skin cancer, was the outcome of longitudinal analysis.ResultsSurvivors (n = 4072, 47% female, 29% smokers, 37% risky drinkers, 34% obese, and 48% physically inactive) had a mean (SD) time between baseline evaluation and follow-up of 7.0 (3.3) years, an age of 8.7 (5.7) years at diagnosis, and an age of 30 (8.4) years at baseline lifestyle assessment. Neither individual lifestyle factors nor a healthy lifestyle score (RR 0.8, 0.4-1.3, p = 0.36) were associated with the risk of developing an SMN.ConclusionsWe did not identify any association between lifestyle factors and the risk of SMN in young adult childhood cancer survivors.
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Project description: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 (? -6.44 ± 2.01, P < 0.01), endurance (? -4.63 ± 1.54, P < 0.01), and neuropathy (? -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.
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Project description:Electrocardiography (ECG), predictive of adverse outcomes in the general population, has not been studied in cancer survivors. We evaluated the prevalence of ECG abnormalities and associations with mortality among childhood cancer survivors.Major and minor abnormalities were coded per the Minnesota Classification system for participants in the St Jude Lifetime Cohort Study (n = 2,715) and community controls (n = 268). Odds ratios (ORs) and 95% CIs were calculated using multivariable logistic regression; and hazard ratios, using Cox proportional hazards regression.Survivors were a median age of 31.3 (range 18.4-63.8) years at evaluation and 7.4 (range 0-24.8) years at diagnosis. Prior therapies included cardiac-directed radiation (29.5%), anthracycline (57.9%), and alkylating (60%) chemotherapies. The prevalence of minor ECG abnormalities was similar among survivors and controls (65.2% vs 67.5%, P = .6). Major ECG abnormalities were identified in 10.7% of survivors and 4.9% of controls (P < .001). Among survivors, the most common major abnormalities were isolated ST/T wave abnormalities (7.2%), evidence of myocardial infarction (3.7%), and left ventricular hypertrophy with strain pattern (2.8%). Anthracyclines ?300 mg/m2 (OR 1.7 95% CI 1.1-2.5) and cardiac radiation (OR 2.1 95% CI 1.5-2.9 [1-1,999 cGy], 2.6 95% CI 1.6-3.9 [2,000-2,999 cGy], 10.5 95% CI 6.5-16.9 [?3,000 cGy]) were associated with major abnormalities. Thirteen participants had a cardiac-related death. Major abnormalities were predictive of all-cause mortality (hazard ratio 4.0 95% CI 2.1-7.8).Major ECG abnormalities are common among childhood cancer survivors, associated with increasing doses of anthracyclines and cardiac radiation, and predictive of both cardiac and all-cause mortality.
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