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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.

Purpose: Childhood cancer survivors experience interconnected symptoms, patterns of which can be elucidated by network analysis. However, current symptom networks are constructed based on the average survivors without considering individual heterogeneities. We propose to evaluate personal symptom network estimation using the Ising model with covariates through simulations and estimate personal symptom network for adult childhood cancer survivors. Patients and Methods: We adopted the Ising model with covariates to construct networks by employing logistic regressions for estimating associations between binary symptoms. Simulation experiments assessed the robustness of this method in constructing personal symptom network. Real-world data illustration included 1708 adult childhood cancer survivors from the St. Jude Lifetime Cohort Study (SJLIFE), a retrospective cohort study with prospective follow-up to characterize the etiology and late effects for childhood cancer survivors. Patients' baseline symptoms in 10 domains (cardiac, pulmonary, sensation, nausea, movement, pain, memory, fatigue, anxiety, depression) and individual characteristics (age, sex, race/ethnicity, attained education, personal income, and marital status) were self-reported using survey. Treatment variables (any chemo or radiation therapy) were obtained from medical records. Personal symptom network of 10 domains was estimated using the Ising model, incorporating individual characteristics and treatment data. Results: Simulations confirmed the robustness of the Ising model with covariates in constructing personal symptom networks. Real-world data analysis identified age, sex, race/ethnicity, education, marital status, and treatment (any chemo and radiation therapy) as major factors influencing symptom co-occurrence. Older childhood cancer survivors showed stronger cardiac-fatigue associations. Survivors of racial/ethnic minorities had stronger pain-fatigue associations. Female survivors with above-college education demonstrated stronger pain-anxiety associations. Unmarried survivors who received radiation had stronger association between movement and memory problems. Conclusion: The Ising model with covariates accurately estimates personal symptom networks. Individual heterogeneities exist in symptom co-occurrence patterns for childhood cancer survivors. The estimated personal symptom network offers insights into interconnected symptom experiences. [ABSTRACT FROM AUTHOR]

Background Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown. Methods Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions. Multivariable models evaluated associations between changes in treatment exposures (surgery only, chemotherapy [with or without surgery], cranial radiation [with or without chemotherapy and/or surgery]), and neurocognitive impairment. Latent class analysis with 5 indicators (employment, independent living, assistance with routine and/or personal care needs, driver's license, marital or partner status) identified classes of functional independence. Path analysis tested associations among treatment exposures, neurocognitive impairment, chronic health conditions, and functional independence. Statistical tests were 2-sided. Results Cranial radiation exposure decreased over time (51%, 1970s; 46%, 1980s; 27%, 1990s]. However, compared with siblings, survivors with any treatment exposure were at elevated risk for neurocognitive impairment, including surgery only (eg, memory: relative risk = 2.22; task efficiency: relative risk = 1.88; both P  < .001). Three classes of functional independence were identified: independent (58%), moderately independent (20%), and nonindependent (22%). Cranial radiation was associated with nonindependence through impaired task efficiency (β = 0.06), sensorimotor (β = 0.06), and endocrine (β = 0.10) chronic health conditions and through the associations between these conditions and task efficiency (each β = 0.04). Sensorimotor and endocrine chronic health conditions were associated with nonindependence through memory. Conclusion Most long-term glioma survivors achieve adult independence. However, functional nonindependence is associated with treatment-related neurocognitive impairment and chronic health conditions. [ABSTRACT FROM AUTHOR]

Background: Survivors of pediatric central nervous system (CNS) tumors are at risk for neurocognitive and social difficulties throughout childhood. This study characterized social cognition (perception and reasoning from social cues) and adjustment in adulthood. Methods: A total of 81 adult survivors of pediatric CNS tumors (51% female; mean [SD] age, 28.0 [5.8] years), were recruited across four groups: (1) no radiation therapy (RT) [n = 21], (2) infratentorial (IT) tumors + focal RT [n = 20], (3) IT tumors + craniospinal irradiation [n = 20], and (4) supratentorial tumors + focal RT [n = 20]. Prevalence of social cognitive and adjustment impairments was compared to test norms. Multivariable models examined clinical and neurocognitive predictors of social cognition and its impact on functional outcomes. Results: Survivors demonstrated elevated risk of severe social cognitive impairments (social perception Morbidity Ratio [95% CI] 5.70 [3.46–9.20]), but self‐reported few social adjustment problems. Survivors of IT tumors treated with craniospinal irradiation performed nearly 1 SD worse than survivors treated without RT on multiple measures of social cognition (e.g., social perception: β = −0.89, p =.004). Impaired executive functioning and nonverbal reasoning were associated with worse social cognitive performance (e.g., social perception: β = −0.75, p <.001; β = –0.84, p <.001, respectively). Better social perception was associated with higher odds of attaining full‐time employment (odds ratio, 1.52 [1.17–1.97]) and at least some college education (odds ratio, 1.39 [1.11–1.74]). Conclusions: Adult survivors of CNS tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Better understanding of potential mechanisms underlying social cognitive deficits may inform intervention targets to promote better functional outcomes for at‐risk survivors. Adult survivors of childhood central nervous system tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Infratentorial tumor survivors treated with craniospinal radiation demonstrated worse social cognition, which was in turn associated with reduced social attainment. [ABSTRACT FROM AUTHOR]

Background: We aimed to characterize premature aging as an accumulation of deficits in survivors of pediatric cancer compared to community controls and examine associations with host/treatment factors, neurocognition, and mortality.Methods: Pediatric cancer survivors (N = 4,000, median age 28.6 [IQR 23-35], 20 [15-27] years post-diagnosis) and community controls (N = 638, median age 32 [25-40]) completed clinical assessments, questionnaires, and were followed for mortality through April 30th, 2020 (mean [SD] follow-up 7.0 [3.4] years). A deficit accumulation index (DAI) score was calculated from 44 aging-related items including: self-reported daily function, psychosocial symptoms, and health conditions. Items were weighted from 0 (absent) to 1 (present/most severe), summed and divided by the total yielding a ratio (higher=more deficits). Scores <0.20 are robust and 0.06 is a clinically meaningful difference. Linear regression compared the DAI in survivors and controls with an age*survivor/control interaction. Logistic regression and Cox-proportional hazards estimated the risk of neurocognitive impairment and death. Models were minimally adjusted for age, sex, and race andethnicity.Results: The adjusted mean DAI among survivors at age 30 years was 0.16 corresponding to age 63 in controls (33 years premature aging; β = 0.07 95%CI 0.06-0.08; p<.001). Cranial/abdominal radiation, alkylators, platinum, and neurosurgery were associated with worse DAI (p's≤.001). Higher scores were associated with increased risk of neurocognitive impairment in all domains (p's<.001) and increased risk of death (DAI 0.20-0.35 HR = 2.80, 95%CI 1.97-3.98; DAI ≥0.35 HR = 5.08, 95%CI 3.52-7.34).Conclusion:  Pediatric cancer survivors experience significant premature aging. The DAI may be used to identify survivors at greatest risk of poor health outcomes. [ABSTRACT FROM AUTHOR]