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Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study.

ABSTRACT: To assess the prevalence and severity of neurocognitive impairment in adult survivors of pediatric CNS tumors and to examine associated treatment exposures.Participants included 224 survivors of CNS tumors who were treated at St Jude Children's Research Hospital (current median age [range], 26 years [19 to 53 years]; time from diagnosis, 18 years [11 to 42 years]) and completed neurocognitive testing. Information on cranial radiation therapy (CRT) doses and parameters of delivery were abstracted from medical records. The prevalence of severe impairment (ie, at least two standard deviations below normative mean) was compared across radiation treatment groups (no CRT, focal irradiation, craniospinal irradiation) using the ?(2) test. Log-binomial models were used to estimate risk ratios (RRs) and corresponding 95% CIs for severe impairment.In multivariable models, craniospinal irradiation was associated with a 1.5- to threefold increased risk of severe impairment compared with no CRT (eg, intelligence: RR = 2.70; 95% CI, 1.37 to 5.34; memory: RR = 2.93; 95% CI, 1.69 to 5.08; executive function: RR = 1.74; 95% CI, 1.24 to 2.45). Seizures were associated with impaired academic performance (RR = 1.48; 95% CI, 1.02 to 2.14), attention (RR = 1.54; 95% CI, 1.12 to 2.13), and memory (RR = 1.44; 95% CI, 1.04 to 1.99). Hydrocephalus with shunt placement was associated with impaired intelligence (RR = 1.78; 95% CI, 1.12 to 2.82) and memory (RR = 1.42; 95% CI, 1.03 to 1.95). Differential follow-up time contributed to variability in prevalence estimates between survivors treated with older nonconformal and those treated with more contemporary conformal radiation therapy methods. Neurocognitive impairment was significantly associated with lower educational attainment, unemployment, and nonindependent living.Survivors of pediatric CNS tumors are at risk of severe neurocognitive impairment in adulthood. The prevalence of severe impairment is greater than expected in the general population, even in the absence of CRT, and is associated with disrupted attainment of adult social milestones.

SUBMITTER: Brinkman TM

PROVIDER: S-EPMC4933131 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study.

Brinkman Tara M TM Krasin Matthew J MJ Liu Wei W Armstrong Gregory T GT Ojha Rohit P RP Sadighi Zsila S ZS Gupta Pankaj P Kimberg Cara C Srivastava Deokumar D Merchant Thomas E TE Gajjar Amar A Robison Leslie L LL Hudson Melissa M MM Krull Kevin R KR

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20160201 12

<h4>Purpose</h4>To assess the prevalence and severity of neurocognitive impairment in adult survivors of pediatric CNS tumors and to examine associated treatment exposures.<h4>Patients and methods</h4>Participants included 224 survivors of CNS tumors who were treated at St Jude Children's Research Hospital (current median age [range], 26 years [19 to 53 years]; time from diagnosis, 18 years [11 to 42 years]) and completed neurocognitive testing. Information on cranial radiation therapy (CRT) dos ...[more]

PMID: 26834063

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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.

Project description:PURPOSE:To examine prevalence and predictors of neurocognitive outcomes, social attainment, emotional distress, and health-related quality of life (HRQOL) in long-term survivors of pediatric Wilms tumor (WT). METHODS:One hundred fifty-eight WT survivors (59% female; mean [SD] age 33 [9.1] years; time since diagnosis 29 [9.1] years) and 354 community controls (55.6% female; 35 [10.2] years) completed comprehensive neuropsychological testing and physical examination, including echocardiography/electrocardiography, pulmonary function tests, and endocrine evaluation. Self-report of emotional distress, HRQOL, and social attainment were collected. Impairment was defined in relation to both controls and normative data. Generalized linear models were developed to examine impact of treatment and chronic health conditions on outcomes. RESULTS:WT survivors performed poorer than norms and controls in 6 of 16 cognitive variables and 1 of 8 HRQOL variables, with scores ranging from - 0.64 (mathematics) to - 0.21 (verbal fluency) standard deviations below expectations. Compared to controls, WT survivors were less likely to graduate college (odds ratio 2.23, 95% confidence interval 1.46-3.41) and had more moderate to severe neurologic conditions (18.4% vs 8.2%, p < 0.001), which were associated with poor memory (β = - 0.90, p < 0.001), attention (β = - 1.02, p < 0.001), and HRQOL general health (β = - 0.80, p = 0.0015). Treatment variables and cardiopulmonary morbidity (higher in survivors) were not associated with outcomes. CONCLUSIONS:Survivors of WT demonstrate impairment in neurocognitive function and have lower social attainment during adulthood, with poorer neurocognitive function associated with neurologic morbidity. IMPLICATIONS FOR CANCER SURVIVORS:Survivors of WT should be offered neurocognitive evaluations and rehabilitation. Neurologic conditions should be routinely assessed, and appropriate support offered to reduce risk for functional limitations.

Project description:BackgroundTo the authors' knowledge, few studies to date have examined long-term neurocognitive outcomes in survivors of childhood soft-tissue sarcoma.MethodsA total of 150 survivors (41% of whom were female with a mean current age of 33 years [SD, 8.9 years] and a time since diagnosis of 24 years [SD, 8.7 years]) and 349 community controls (56% of whom were female with a mean current age of 35 years [SD, 10.2 years]) completed comprehensive neuropsychological testing, echocardiography, electrocardiography, pulmonary function tests, endocrine evaluation, and physical examination. Patient-reported outcomes of health-related quality of life (HRQOL) and social attainment were collected. Survivors were compared with norms and controls on neurocognitive outcomes using general linear models, and on HRQOL and social attainment using modified Poisson models. The impacts of treatment and chronic health conditions on outcomes were examined using multivariable general linear models (effect size was expressed as unstandardized β estimates that reflected the unit of change from a mean of 0 and an SD of 1) and modified Poisson models (effect size expressed as relative risks).ResultsCompared with controls and population norms, survivors demonstrated lower performance on measures of verbal reasoning (mean z score, -0.45 [SD, 1.15]; P < .001) mathematics (mean z score, -0.63 [SD, 1.07]; P < .001), and long-term memory (mean z score, -0.37 [SD, 1.14]; P < .001). Cumulative anthracycline exposure (per 100 mg/m2 ) was found to be associated with poorer verbal reasoning (β = -0.14 z scores; P = .04), reading (β = -0.09 z score; P = .04), and patient-reported vitality (relative risk, 1.32; 95% CI, 1.09-1.59). Neurologic and neurosensory chronic conditions were associated with poorer mathematics (neurologic conditions: β = -0.63 z score [P = 0.02]; and hearing impairment: β = -0.75 z scores [P < 0.01]). Better cognitive performance was associated with higher social attainment.ConclusionsLong-term survivors of soft-tissue sarcoma are at risk of neurocognitive problems and poor HRQOL associated with anthracycline treatment and chronic health conditions.

Project description:BackgroundThe objective of this study was to characterize chronic disease, health-related quality of life (HRQOL), emotional distress, and social attainment among long-term survivors of neuroblastoma.MethodsChronic health conditions among 136 ?10-year neuroblastoma survivors (median age, 31.9 years; range, 20.2-54.6 years) and 272 community controls (median age, 34.7 years; range, 18.3-59.6 years) were graded with a modified version of the Common Terminology Criteria for Adverse Events (version 4.03). HRQOL and emotional distress were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey and the Brief Symptom Inventory-18. Log-binomial regression and logistic regression were used to compare the prevalence of chronic conditions and the frequency of reduced HRQOL, distress, and social attainment between survivors and controls. The cumulative burden approach was used to estimate multimorbidity.ResultsBy the age of 35 years, survivors had experienced, on average, 8.5 grade 1 to 5 conditions (95% confidence interval [CI], 7.6-9.3), which was higher than the average for controls (3.3; 95% CI, 2.9-3.7). Compared with controls, survivors had a higher prevalence of any pulmonary (P = .003), auditory (P < .001), gastrointestinal (P < .001), neurological (P = .003), or renal condition (P < .001); were more likely to report poor physical HRQOL (P = .01) and symptoms of anxiety (P = .01) and somatization (P = .01); and were less likely to live independently (P = .01) or marry (P = .01). In analyses limited to survivors, those with 1 or more grade 3 to 5 conditions were more likely to report reduced general health (odds ratio [OR], 6.6; 95% CI, 1.6-26.9), greater bodily pain (OR, 4.2; 95% CI, 1.0-17.0), and unemployment (OR, 3.2; 95% CI, 1.2-8.5).ConclusionsBecause of the high burden of chronic diseases and the associations of these morbidities with reduced HRQOL and social attainment, screening and interventions that provide opportunities to optimize health are important among neuroblastoma survivors.

Dataset Information

Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study.

Publications

Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study.

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