Neurocognitive functioning in adult survivors of childhood non-central nervous system cancers.
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ABSTRACT:
SUBMITTER: Kadan-Lottick NS
PROVIDER: S-EPMC2886093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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?<?.001). After adjustment for neurotoxic treatment exposures, insomnia (vs healthy sleepers with no daytime fatigue or sleepiness) was associated with worse neurocognitive performance in the domains of verbal reasoning, memory, attention, executive function, and processing speed (verbal reasoning: males ? = -0.34, P?=?.04, females ? = -0.57, P?<?.001; long-term memory: males ? = -0.60, P?<?.001, females ? = -0.36, P?=?.02; sustained attention: males ? = -0.85, P?<?.001, females ? = -0.42, P?=?.006; cognitive flexibility: males ? = -0.70, P?=?.002, females ? = -0.40, P?=?.02). Self-reported sleep disturbance without daytime fatigue or sleepiness or daytime fatigue or sleepiness alone were not consistently associated with poorer neurocognitive performance. 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.
| S-EPMC7197383 | biostudies-literature
Project description:BackgroundAdult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups.MethodsWe collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided.ResultsAmong all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage.ConclusionsSurvivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines.
| S-EPMC2704230 | biostudies-literature
Project description:ObjectiveBrain tumors during childhood may disrupt the development and maintenance of friendships due to the impact of disease- and treatment-related factors on functioning. The goal of this study was to determine if children treated for either a brain tumor or a non-central nervous system (CNS) solid tumor could name a friend and to evaluate the social information processes associated with the ability to name a friend.MethodYouth (ages 7-14) treated for either a brain tumor (n = 47; mean age = 10.51 years) or a non-CNS solid tumor (n = 34; mean age = 11.29) completed an assessment within 6 months of the conclusion of treatment that included asking participants to name a friend and completing measures of social information processing (SIP). Rates of self-reported friendship were compared between groups and correlates of being able to name a friend were evaluated.ResultsYouth treated for a brain tumor (61.7%) were significantly less likely to name a friend compared with youth treated for a non-CNS solid tumor (85.3%). Diagnosis type (brain vs. non-CNS), relapse status, attribution style, and facial affect recognition were significant predictors of being able to name a friend or not in a logistic regression model.ConclusionsYouth treated for a brain tumor and those who experienced a disease relapse are at risk for impairments in friendships; difficulties with SIP may increase this risk. Targeted screening and intervention efforts for children diagnosed with brain tumors and those who have relapsed could address difficulties with peers.
| S-EPMC7029689 | biostudies-literature
Project description:Background:A comprehensive overview of neurologic complications among survivors of central nervous system (CNS) tumors in childhood is lacking. We aimed to investigate the risk for these disorders in a large, population-based study with outcome measures from nationwide hospital registries. Methods:We identified 4858 five-year survivors with diagnoses of CNS tumor in childhood in Denmark, Iceland, Finland, and Sweden in 1943-2007, and 166658 matched population comparison subjects. Inpatient discharge diagnoses of neurologic disorders were used to calculate relative risks (RRs) and absolute excess risks (AERs). Results:A neurologic disorder was verified in 1309 survivors, while 92.4 were expected, yielding an overall RR of 14.2 (95% confidence interval [CI]: 13.3-15.1) and an AER of 20 hospitalizations per 1000 persons per year. The risks remained increased more than 20 years after diagnosis (RR: 6.3, 95% CI: 5.6-7.2; AER: 11, 9-12). The most frequent diagnoses were epilepsy (affecting 14.1% of all survivors) followed by hydrocephalus (9.5%) and paralytic syndromes (4.2%), with RRs of 28.7 (95% CI: 26.0-31.6), 243 (95% CI: 190-311), and 40.3 (95% CI: 33.1-49.2), respectively. Of these outcomes, 30%-40% were diagnosed prior to or synchronously with the CNS tumor. The survivors had highly increased RRs for infectious diseases of the CNS, disorders of cranial nerves, and degenerative diseases of the nervous system. Conclusions:Survivors of childhood CNS tumors are at markedly increased risk for neurologic disorders throughout their lives. Health care professionals must be aware of survivors who might benefit from preventive interventions and intensive follow-up.
| S-EPMC6303468 | biostudies-literature
Project description:IntroductionIn recent years, growing attention has been given to the study of the impact of cancer-related cognitive impairment (CRCI) in working non-central nervous system (CNS) cancer survivors. Available literature has shown that working cancer survivors identify cognitive problems at work as very problematic and worrisome. Some reviews have discussed the association between CRCI and work-related outcomes; however, none to date have investigated this association through comprehensive systematic review with meta-analysis. Hence, this work will comprehensively summarise existing evidence from quantitative studies assessing the relationship between CRCI and work-related outcomes of adult non-CNS cancer survivors at working age.Methods and analysisThe systematic review procedures and its report will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Electronic searches in the databases Web of Science, Scopus, PubMed, ProQuest, PsycINFO and CINAHL, complemented by a manual search of other relevant articles, will be performed from 2000 onwards to identify relevant publications. Two independent reviewers will assess studies for inclusion and extract data from each article using a standardised form. Studies eligible for inclusion must be quantitative, contain adult non-CNS cancer survivors with CRCI, and a measure of cognitive functioning and work-related outcomes. To assess risk of bias, the Joanna Briggs Institute Critical Appraisal Tool Studies checklists will be independently used by the two researchers. Synthesis of the included articles will be conducted using a narrative method and through meta-analysis. Meta-analysis will be reported via correlation for the association between CRCI and work-related outcomes. The cumulative evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation system.Ethics and disseminationEthics approval is not required since individual patient data will not be collected. The findings will be published in a peer-review indexed journal, presented at scientific meetings and included in a chapter of a Doctoral thesis.Prospero registration numberCRD42020165458.
| S-EPMC9277407 | biostudies-literature
Project description:BACKGROUND:Children with non-Hodgkin lymphoma (NHL) undergo treatment with central nervous system-directed therapy, the potentially neurotoxic effects of which have not been reported in NHL survivors. METHODS:NHL survivors (n?=?187) participating in the St. Jude Lifetime Cohort who were 10 or more years from their diagnosis and were 18 years old or older underwent neurocognitive, emotional distress (Brief Symptom Inventory 18), and health-related quality of life (HRQOL) assessments (36-Item Short Form Health Survey). Age-adjusted z scores were compared with community controls (n?=?181) and normative data. Treatment exposures were abstracted from medical records. Models adjusted for the age, sex, and time from diagnosis were used to calculate the risk of impairment. RESULTS:The mean ages at evaluation were similar for the survivors and the controls (35.7?±?8.9 vs 35.5?±?11.0 years; P?=?.86). Survivors were 25.2?±?8.8 years from their diagnosis: 43 (23%) received cranial radiation, 70 (37%) received high-dose methotrexate, 40 (21%) received high-dose cytarabine, and 151 (81%) received intrathecal chemotherapy. Survivors' intelligence and attention were within normal limits; however, their memory, executive function, processing speed, and academics were impaired in comparison with both population norms and community controls (P values?<?.05). Treatment-related exposures were not associated with neurocognitive function; however, neurocognitive impairment was associated with lower educational attainment, unemployment, and occupational status (P values?<?.03). Slower processing speed and worse self-reported executive function were associated with symptoms of depression (P values???.003) and poorer HRQOL (P values?<?.05). CONCLUSIONS:Adult survivors of childhood NHL experience impaired neurocognitive function, which is associated with lower social attainment and poor HRQOL. Early-detection and intervention strategies are recommended. Cancer 2017. © 2017 American Cancer Society.
| S-EPMC5760296 | biostudies-literature
Project description:Multimodal therapy has improved survival for some childhood CNS tumors. However, whether risk for subsequent neoplasms (SNs) also increases is unknown. We report the cumulative incidence of, and risk factors for, SNs after a childhood primary CNS tumor and determine whether treatment that combines radiation therapy (RT) with chemotherapy increases risk for SNs.Analyses included 2779 patients with a primary CNS tumor treated at St Jude Children's Research Hospital between 1985 and 2012. Cumulative incidence and standardized incidence ratios (SIRs) were estimated for SNs confirmed by pathology report. Cumulative incidence among the 237 five-year medulloblastoma survivors treated with multimodal therapy (RT + chemotherapy) was compared with a historical cohort of 139 five-year survivors treated with RT but no chemotherapy in the Childhood Cancer Survivor Study.Eighty-one survivors had 97 SNs. The cumulative incidence of first SN was 3.0% (95% CI: 2.3%-3.9%) at 10 years, and 6.0% (95% CI: 4.6%-7.7%) at 20 years from diagnosis. Risks were highest for subsequent glioma, all grades (SIR = 57.2; 95% CI: 36.2-85.8) and acute myeloid leukemia (SIR = 31.8; 95% CI: 10.2-74.1). Compared with RT alone, RT + chemotherapy did not increase risk for SNs (hazard ratio: 0.64; 95% CI: 0.38-1.06). Among five-year survivors of medulloblastoma treated with multimodal therapy, cumulative incidence of SN was 12.0% (95% CI: 6.4%-19.5%) at 20 years, no different than survivors treated with RT alone (11.3%, P = .44).The cumulative incidence of SNs continues to increase with time from treatment with no obvious plateau, but the risk does not appear to be higher after exposure to multimodal therapy compared with RT alone. Continued follow-up of survivors as they age is essential.
| S-EPMC4483102 | biostudies-literature
Project description:PurposeA growing number of young patients with central nervous system (CNS) tumour survived for more than five years. However, these long-term survivors might be at risk of multiple late effects thus leading to a higher risk of late mortality. We aimed to explore the risk of late mortality and the pattern of mortality among long-term survivors of childhood or adolescent CNS tumour.MethodsWe identified 5-year survivors with childhood or adolescent CNS tumour before age 20 years through the Swedish Cancer Registry. Five controls were randomly matched for each patient to generate the reference group. We retrieved information about death via Cause of Death Register. We calculated the absolute excess risk (AER) of death and the hazard ratio (HR) of death using Cox proportional hazard model.ResultsLong-term survivors with CNS tumour suffered a significant higher risk of overall mortality (HR 6.56, 95% CI 5.71-7.53; AER 5.89, 95% CI 5.03-6.87). The mortality rate declined with the increasing survival time, but it was still higher even after 30 years of follow-up. Malignant neoplasms contributed mostly to late mortality with an AER of 3.75 (95% CI 2.95-4.75). Female survivors, survivors diagnosed at a younger age and survivors with medulloblastoma were particularly strongly associated with a higher risk of death.ConclusionsLong-term survivors of childhood and adolescent CNS tumours are at a higher risk of late mortality, and the risk of death is affected by gender, age at diagnosis and types of CNS tumour.
| S-EPMC6881431 | biostudies-literature
Project description:PurposeWe assessed cardiorespiratory fitness and health-related quality of life (HRQoL) in survivors of childhood central nervous system (CNS) tumours.MethodsParticipants were recruited from the National Children's Cancer Service in Children's Health Ireland at Crumlin. Inclusion criteria included diagnosis of a primary CNS tumour, aged between 6 and 17 years, between 3 months and 5 years post completion of oncology treatment, independently mobile, and deemed clinically appropriate to participate by treating oncologist. Cardiorespiratory fitness was assessed using the six-minute walk test. HRQoL was assessed with the PedsQL Generic Core Scales, Version 4.0.ResultsThirty-four participants (n = 16 male) were recruited, with a mean age of 12.21 ± 3.31 years and a mean time since completion of oncology treatment of 2.19 ± 1.29 years. Mean six-minute walk distance (6MWD) achieved was 489.56 ± 61.48 m, equating to the 8th percentile overall. 6MWD was significantly reduced when compared to predicted population norms (p < 0.001). PedsQL parent proxy-report and child-report scores were significantly lower when compared to healthy paediatric norms (p < 0.001 - p = 0.011). A significant positive correlation was found between 6MWD and both parent proxy-report (r = 0.55, p < 0.001) and child-report (r = 0.48, p = 0.005) PedsQL total scores.ConclusionSurvivors of childhood CNS tumours present with impaired cardiorespiratory fitness and HRQoL. Higher levels of cardiorespiratory fitness are associated with higher levels of HRQoL.Implications for cancer survivorsRoutine screening of cardiorespiratory fitness and HRQoL in survivors of childhood CNS tumours may be beneficial. Healthcare providers should encourage and provide education on the potential benefits of physical activity to improve overall quality of life.
| S-EPMC10272264 | biostudies-literature
Project description:This study provides the first objective data documenting neurocognitive impairment in long-term survivors of childhood osteosarcoma.To examine neurocognitive, neurobehavioral, emotional, and quality-of-life outcomes in long-term survivors of childhood osteosarcoma.Cross-sectional cohort study at an academic research hospital, with prospective treatment and chronic health predictors. Outcome data were collected from June 2008 to August 2014. Data analysis was completed in April 2015. Survivors of osteosarcoma recruited from the St Jude Lifetime Cohort Study were compared with community controls.Neurocognitive function, neurobehavioral symptoms, emotional distress, and quality of life. Outcomes were examined in relation to pharmacokinetic indices of methotrexate exposure and current chronic health conditions, which were assessed through medical examination and coded according to Common Terminology Criteria for Adverse Events, Version 4.03.Eighty survivors of osteosarcoma (mean [SD] age, 38.9 [7.6] years; time since diagnosis, 24.7 [6.6] years; 42% female) were compared with 39 community controls (age, 39.0 [11.7] years; 56% female). Survivors demonstrated lower mean scores in reading skills (-0.21 [95% CI, -0.32 to -0.10] vs 0.05 [95% CI, -0.13 to 0.23]; P =?.01), attention (-0.78 [95% CI, -1.32 to -0.24] vs 0.24 [95% CI, -0.07 to 0.55]; P =?.002), memory (-0.24 [95% CI, -0.48 to 0] vs 0.27 [95% CI, -0.08 to 0.62]; P =?.01), and processing speed (-0.15 [95% CI, -0.35 to 0.05] vs 0.74 [95% CI, 0.44 to 1.03]; P <?.001). Results of pharmacokinetic analysis showed that high-dose methotrexate maximum plasma concentration (estimate = 0; P =?.48), median clearance (estimate =?-0.11; P =?.76), and median/cumulative exposure (estimate = 0; P =?.45) were not associated with neurocognitive outcomes. Any grade 3 or 4 Common Terminology Criteria for Adverse Events cardiac, pulmonary, or endocrine condition was associated with poorer memory (t = 2.93; P =?.006) and slower processing speed (t?=?3.03; P?=?.002). Survivor-reported poor general health was associated with decreased sustained attention (estimate = 0.24; P =?.05) and processing speed (estimate = 0.34; P =?.005).Long-term survivors of osteosarcoma are at risk for neurocognitive impairment, which is related to current chronic health conditions and not to original treatment with high-dose methotrexate. Prospective longitudinal studies are needed to identify onset and progression of impairment to inform optimal interventions.
| S-EPMC4752424 | biostudies-literature