Insomnia and Neurocognitive Functioning in Adult Survivors of Childhood Cancer.
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ABSTRACT:
SUBMITTER: Tonning Olsson I
PROVIDER: S-EPMC7197383 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Insomnia and Neurocognitive Functioning in Adult Survivors of Childhood Cancer.
Tonning Olsson Ingrid I Lubas Margaret M MM Li Chenghong C Mandrell Belinda N BN Banerjee Pia P Howell Carrie R CR Ness Kirsten K KK Srivastava Deokumar D Robison Leslie L LL Hudson Melissa M MM Krull Kevin R KR Brinkman Tara M TM
JNCI cancer spectrum 20200219 3
<h4>Background</h4>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.<h4>Methods</h4>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 ex ...[more]
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Project description:BACKGROUND We sought to measure self-reported neurocognitive functioning among survivors of non-central nervous system (CNS) childhood cancers, overall and compared with a sibling cohort, and to identify factors associated with worse functioning. METHODS In a retrospective cohort study, 5937 adult survivors of non-CNS cancers and 382 siblings completed a validated neuropsychological instrument with subscales in task efficiency, emotional regulation, organization, and memory. Scores were converted to T scores; scores in the worst 10% of siblings' scores (ie, T score > or =63) were defined as impaired. Non-CNS cancer survivors and siblings were compared with multivariable linear regression and log-binomial regression. Among survivors, log-binomial models assessed the association of patient and treatment factors with neurocognitive dysfunction. All statistical tests were two-sided. RESULTS Non-CNS cancer survivors had similar or slightly worse (<0.5 standard deviation) mean test scores for all four subscales than siblings. However, frequencies of impaired survivors were approximately 50% higher than siblings in task efficiency (13.0% of survivors vs 7.3% of siblings), memory (12.5% vs 7.6%), and emotional regulation (21.2% vs 14.4%). Impaired task efficiency was most often identified in patients with acute lymphoblastic leukemia who received cranial radiation therapy (18.1% with impairment), myeloid leukemia who received cranial radiation therapy (21.2%), and non-Hodgkin lymphoma (13.9%). In adjusted analysis, diagnosis age of younger than 6 years, female sex, cranial radiation therapy, and hearing impairment were associated with impairment. CONCLUSION A statistically and clinically significantly higher percentage of self-reported neurocognitive impairment was found among survivors of non-CNS cancers than among siblings.
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Project description:BACKGROUND:Cancer survivors transfused with blood products before reliable screening for hepatitis C virus (HCV) are at risk for infection. This study examined the impact of HCV on neurocognitive function and health-related quality of life (HRQOL) among adult survivors of childhood cancer. METHODS:Neurocognitive testing was conducted for 836 adult survivors of childhood cancer (mean age, 35 years [standard deviation, 7.4 years]; time since diagnosis, 29 years [standard deviation, 6.2 years]) who received blood products before universal HCV screening. No differences were observed between confirmed HCV-seropositive survivors (n = 79) and HCV-seronegative survivors (n = 757) in the primary diagnosis or neurotoxic therapies. Multivariate regression models were used to compare functional outcomes between seropositive and seronegative survivors. RESULTS:Compared with seronegative survivors, seropositive survivors demonstrated lower performance on measures of attention (P < .001), processing speed (P = .008), long-term verbal memory (P = .01), and executive function (P = .001). After adjustments for sex, age at diagnosis, and treatment exposures, seropositive survivors had a higher prevalence of impairment in processing speed (prevalence ratio [PR], 1.3; 95% confidence interval [CI], 1.1-1.6) and executive functioning (PR, 1.3; 95% CI, 1.1-1.6). Differences were not associated with the treatment of HCV or the presence of liver cirrhosis. Seropositive survivors reported worse general HRQOL (PR, 1.6; 95% CI, 1.2-2.1), which was associated with the presence of liver cirrhosis (P = .001). CONCLUSIONS:Survivors of childhood cancer with a history of HCV infection are at risk for neurocognitive impairment and reduced HRQOL beyond the known risks associated with neurotoxic cancer therapies. Cancer 2017;123:4498-505. © 2017 American Cancer Society.
| S-EPMC5673503 | 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
Project description:Adult survivors of childhood cancer are at risk for long-term morbidities, which may be managed pharmacologically. Psychoactive medication treatment has been associated with adverse effects on specific neurocognitive processes in non-cancer populations, yet these associations have not been examined in adult survivors of childhood cancer.Outcomes were evaluated in 7,080 adult survivors from the Childhood Cancer Survivor Study (CCSS) using a validated self-report Neurocognitive Questionnaire. Multivariable logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for neurocognitive impairment using demographic and treatment factors and survivors' report of prescription medication use.Controlling for cranial radiation, pain, psychological distress, and stroke/seizure, use of antidepressant medications was associated with impaired task efficiency (OR?=?1.80, 95% CI?=?1.47-2.21), organization (OR?=?1.83, 95% CI?=?1.48-2.25), memory (OR?=?1.53, 95% CI?=?1.27-1.84), and emotional regulation (OR?=?2.06, 95% CI?=?1.70-2.51). Neuroleptics and stimulants were associated with impaired task efficiency (OR?=?2.46, 95% CI?=?1.29-4.69; OR?=?2.82, 95% CI?=?1.61-4.93, respectively) and memory (OR?=?2.08, 95% CI?=?1.13-3.82; OR?=?2.69, 95% CI?=?1.59-4.54, respectively). Anticonvulsants were associated with impaired task efficiency, memory, and emotional regulation, although survivors who use these medications may be at risk for neurocognitive impairment on the basis of seizure disorder and/or underlying tumor location (CNS).These findings suggest that specific psychoactive medications and/or mental health conditions may be associated with neurocognitive function in adult survivors of childhood cancer. The extent to which these associations are causal or indicative of underlying neurological impairment for which the medications are prescribed remains to be ascertained.
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Project description:PurposeLong-term survivors of childhood Hodgkin lymphoma (HL) are at risk for cardiopulmonary complications and CNS stroke, although neurocognitive function has not been previously examined. The aim of this study was to examine neurocognitive and brain imaging outcomes in adult survivors of childhood HL.Patients and methodsIn all, 62 adult survivors (mean age, 42.2 years; standard deviation [SD], 4.77; mean age at diagnosis, 15.1 years; SD, 3.30) were identified by stratified random selection from a large cohort treated with either high-dose (≥ 30 Gy) thoracic radiation (n = 38) or lower-dose (< 30 Gy) thoracic radiation combined with anthracycline (n = 24). Patients underwent neurocognitive evaluations, brain magnetic resonance imaging (MRI), echocardiograms, pulmonary function tests, and physical examinations.ResultsCompared with national age-adjusted norms, HL survivors demonstrated lower performance on sustained attention (P = .004), short-term memory (P = .001), long-term memory (P = .006), working memory (P < .001), naming speed (P < .001), and cognitive fluency (P = .007). MRI revealed leukoencephalopathy in 53% of survivors, and 37% had evidence of cerebrovascular injury. Higher thoracic radiation dose was associated with impaired cardiac diastolic function (E/E'; ratio of peak mitral flow velocity of early rapid filling [E] to early diastolic velocity of the mitral annulus [E']; P = .003), impaired pulmonary function (diffusing capacity of lungs for carbon monoxide [DL(co)(corr); P = .04), and leukoencephalopathy (P = .02). Survivors with leukoencephalopathy demonstrated reduced cognitive fluency (P = .001). Working memory impairment was associated with E/E', although impaired sustained attention and naming speed were associated with DL(co)(corr). Neurocognitive performance was associated with academic and vocational functioning.ConclusionThese results suggest that adult long-term survivors of childhood HL are at risk for neurocognitive impairment, which is associated with radiologic indices suggestive of reduced brain integrity and which occurs in the presence of symptoms of cardiopulmonary dysfunction.
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Project description:AimsTo estimate the level of alcohol consumption behaviors in adult survivors of childhood cancer and to test associations between alcohol consumption behaviors and symptoms of neurocognitive impairment and emotional distress.DesignRetrospective cohort study with longitudinal follow-up of self-reported health outcomes.SettingChildhood Cancer Survivor Study (CCSS), a 26-center study of ≥ 5-year survivors of childhood cancer diagnosed ≤ 21 years of age between 1970 and 1986 in the United States and Canada.ParticipantsA total of 4484 adult survivors of childhood cancer [mean (standard deviation) age at evaluation = 34.8 (6.1) years; time from diagnosis = 24.8 (4.4) years] and 1651 sibling controls who completed surveys reporting on alcohol use, neurocognitive impairment and emotional distress.MeasurementsSurvivor report of alcohol use included age at drinking initiation and quantity and frequency of alcohol consumption. Neurocognition was assessed using the CCSS Neurocognitive Questionnaire. Emotional distress symptoms were measured using the Brief Symptoms Inventory-18 and the Posttraumatic Stress Diagnostic Scale.FindingsAfter adjustment for childhood cancer treatment exposures, including cranial radiation therapy, drinking initiation prior to 18 years of age was associated with 30% increased risk of subsequent memory problems [risk ratio (RR) = 1.3; 95% confidence interval (CI) = 1.1-1.5]. Younger age at drinking initiation was associated with future risk of depression (RR = 1.3; 95% CI = 1.1-1.5), anxiety (RR = 1.6; 95% CI = 1.3-2.1), and somatization (RR = 1.2; 95% CI = 1.1-1.4). Persistent heavy/risky drinking was associated with 80% increased risk of persistent psychological distress (RR = 1.8, 95% CI = 1.4-2.3).ConclusionsDrinking initiation during adolescence is associated with modest increased risk for memory impairment and emotional distress in adult survivors of childhood cancer.
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Project description:BackgroundThe impact of growth hormone deficiency (GHD) on neurocognitive function is poorly understood in survivors of childhood acute lymphoblastic leukemia (ALL). This study examined the contribution of GHD to functional outcomes while adjusting for cranial radiation therapy (CRT).MethodsAdult survivors of ALL (N = 571; 49% female; mean age, 37.4 years; age range, 19.4-62.2 years) completed neurocognitive tests and self-reported neurocognitive symptoms, emotional distress, and quality of life. GHD was defined as a previous diagnosis of GHD or a plasma insulin-like growth factor1 level less than -2.0 standard deviations for sex and age at the time of neurocognitive testing. Hypothyroidism, hypogonadism, sex, age at diagnosis, CRT dose, and intrathecal and high-dose intravenous methotrexate were included as covariates in multivariable linear regression models.ResultsOf the 571 survivors, 298 (52%) had GHD, and those with GHD received higher doses of CRT (P = .002). Survivors who had GHD, irrespective of prior growth hormone treatment, demonstrated poorer vocabulary (z-score, -0.84 vs -0.61; P = .02), processing speed (z-score, -0.49 vs -0.30; P = .04), cognitive flexibility (z-score, -1.37 vs -0.94; P = .01), and verbal fluency (z-score, -0.74 vs -0.44; P = .001), and they self-reported more neurocognitive problems and poorer quality of life compared with survivors who did not have GHD. Multivariable and mediation models revealed that GHD was associated with small effects on quality of life (general health, P = .01; vitality, P = .01; mental health, P = .01); and CRT dose accounted for the lower neurocognitive outcomes.ConclusionsAdult survivors of childhood ALL who receive CRT are at risk for GHD, although poor neurocognitive outcomes are determined by CRT dose and not by the presence of GHD.
| S-EPMC6486430 | biostudies-literature
Project description:IntroductionLittle is known about the impact of childhood cancer on the personal income of survivors. We compared income between survivors and siblings, and determined factors associated with income.MethodsAs part of the Swiss Childhood Cancer Survivor Study (SCCSS), a questionnaire was sent to survivors, aged ?18 years, registered in the Swiss Childhood Cancer Registry (SCCR), diagnosed at age <21 years, who had survived ?5 years after diagnosis of the primary tumor. Siblings were used as a comparison group. We asked questions about education, profession and income and retrieved clinical data from the SCCR. We used multivariable logistic regression to identify characteristics associated with income.ResultsWe analyzed data from 1'506 survivors and 598 siblings. Survivors were less likely than siblings to have a high monthly income (>4'500 CHF), even after we adjusted for socio-demographic and educational factors (OR = 0.46, p<0.001). Older age, male sex, personal and parental education, and number of working hours were associated with high income. Survivors of leukemia (OR = 0.40, p<0.001), lymphoma (OR = 0.63, p = 0.040), CNS tumors (OR = 0.22, p<0.001), bone tumors (OR = 0.24, p = 0.003) had a lower income than siblings. Survivors who had cranial irradiation, had a lower income than survivors who had no cranial irradiation (OR = 0.48, p = 0.006).DiscussionEven after adjusting for socio-demographic characteristics, education and working hours, survivors of various diagnostic groups have lower incomes than siblings. Further research needs to identify the underlying causes.
| S-EPMC4877063 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES: Because little is known about long-term treatment-related nephrotoxicity, the aim was to determine risk factors for renal impairment long after childhood cancer treatment. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from 763 adult childhood cancer survivors (414 men) were obtained during regular visits at the late-effects clinic between 2003 and 2009. Median follow-up time was 18.3 years (range=5.0-58.2). Glomerular function was assessed by estimated GFR (using the Modification of Diet in Renal Disease formula), urinary albumin creatinine ratio, and tubular function by urinary ?2-microglobulin creatinine ratio. The association with treatment factors was analyzed with covariance analysis for estimated GFR and logistic regression for urinary albumin and urinary ?2-microglobulin creatinine ratios. RESULTS: Survivors treated with nephrectomy and abdominal irradiation had significantly lower estimated GFR than survivors not treated with nephrectomy/abdominal irradiation (estimated mean=90 ml/min per 1.73 m(2) versus 106, P<0.001). Estimated GFR was significantly lower in survivors after treatment with high-dose ifosfamide (88 versus 98, P=0.02) and high-dose cisplatin (83 versus 101, P=0.004) compared with survivors not treated with these regimen. Nephrectomy combined with abdominal radiotherapy (odds ratio=3.14, 95% confidence interval=1.02; 9.69) and high-dose cisplatin (odds ratio=5.19, 95% confidence interval=1.21; 22.21) was associated with albuminuria. High-dose ifosfamide (odds ratio=6.19, 95% confidence interval=2.45; 15.67) was associated with increased urinary ?2-microglobulin creatinine ratio. Hypertension was present in 23.4% of survivors and 31.4% of renal tumor survivors. CONCLUSIONS: Treatment with unilateral nephrectomy, abdominal radiotherapy, cisplatin, and ifosfamide was associated with lower estimated GFR. Persisting tubular damage was related to ifosfamide treatment.
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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.
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