Survivors Of Central Nervous System Tumors Research Articles

Recurrence Patterns and Surveillance Imaging in Pediatric Brain Tumor Survivors.

Surveillance magnetic resonance imaging (MRI) is routinely used to detect recurrence in pediatric central nervous system (CNS) tumors. The frequency of neuroimaging surveillance varies without a standardized approach. A single-institutional retrospective cohort study evaluated the frequency of recurrences. This study included 476 patients with the majority diagnosed with low-grade glioma (LGG) (n=138, 29%), high-grade glioma (HGG) (n=77, 16%), ependymoma (n=70, 15%), or medulloblastoma (n=61, 13%). LGG, HGG, and ependymoma patients more commonly had multiply recurrent disease ( P =0.08), with ependymoma patients demonstrating ≥2 relapses in 47% of cases. Recurrent disease was identified by imaging more often than clinical symptoms (65% vs. 32%; P =<0.01). Patients diagnosed with meningioma demonstrated the longest mean time to first relapse (74.7mo) whereas those with atypical teratoid rhabdoid tumor and choroid plexus carcinoma tended to have the shortest time to relapse (8.9and 9mo, respectively). Overall, 22 patients sustained first relapse >10 years from initial diagnosis. With a higher tendency toward detection of tumor recurrence/progression on MRI surveillance in comparison to clinical progression, surveillance imaging is necessary in routine follow up of pediatric CNS tumor survivors. With some relapses >10 years from initial diagnosis, imaging beyond this time point may be useful in particular tumor types. While the study is limited in outcome analysis, earlier detection of recurrence would lead to earlier initiation of treatment and implementation of salvage treatment regimens which can impact survival and quality of life.

Educational attainment in survivors of childhood cancer in Denmark, Finland, and Sweden.

Survivors of childhood cancer may face difficulties at school. We investigated whether childhood cancer affects attainment of upper secondary education, in a register-based cohort study from Denmark, Finland, and Sweden, where we limit bias from selection and participation. From the national cancer registers, we identified all long-term survivors of childhood cancer diagnosed aged 0-14 years in 1971-2005 (n = 7629), compared them to matched population comparisons (n = 35,411) and siblings (n = 6114), using odds ratios (OR) and 95% confidence intervals (CI). Overall, 6127 survivors (80%) had attained upper secondary education by age 25, compared to 84% among comparison groups. Elevated OR for not attaining this level were mainly confined to survivors of central nervous system (CNS) tumours (ORSurv_PopComp2.05, 95%CI: 1.83-2.29). Other risk groups were survivors who had spent more time in hospital around cancer diagnosis and those who had hospital contacts in early adulthood, particularly psychiatric. Survivors of all cancer types were less likely to have attained upper secondary education without delay. Although survivors of childhood cancer experienced delays in their education, many had caught up by age 25. Except for survivors of CNS tumours, survivors attained upper secondary education to almost the same extent as their peers.

12 Differential Processing Efficiency Skills in Survivors of Pediatric Primary CNS Cancer and Cancers of non-CNS Origin

Objective:Pediatric cancer and cancer-related treatments may disrupt brain development and place survivors at risk for long term problems with cognitive functions. Processing efficiency has been operationalized as a nuanced cognitive skill that reflects both processing speed (PS) and working memory (WM) abilities and is sensitive to neurobiological disruption. Pediatric cancer survivors are at risk for processing efficiency deficits; however, a thorough characterization of processing efficiency skills across pediatric primary central nervous system (CNS) tumor and non-CNS cancer survivors has not yet been reported.Participants and Methods:Participants were selected from a mixed retrospective clinical database of pediatric cancer survivors (Total n=160; primary CNS tumor n=33; Non-CNS n=127). Univariate analyses were conducted to examine differences in processing efficiency mean scores (t-tests) and percent impairment (scores &gt;1 SD below mean; chi-squared tests) between the total sample and normative sample, and across groups (CNS vs. Non-CNS). Multiple linear regressions were utilized to evaluate the relationships between additional risk factors, including biological sex, age at diagnosis, time since treatment, and socioeconomic status, and processing efficiency outcomes.Results:The total sample obtained lower scores on WM (M=90.83, SD=13.35) and PS (M=88.86, SD=14.38) measures than normative samples (M=100, SD=15), p &lt; 0.001. Greater percentage of pediatric cancer survivors demonstrated impairment across all processing efficiency measures (24.8-38.1%) than normative samples (15.9%), p &lt; 0.001. Regarding group differences, the CNS group obtained lower mean WM (M=84.85, SD =11.77) and PS (M=80, SD=14.18) scores than the Non-CNS group (WM M=92.39, SD=13.32; PS M=91.16, SD=13.56), p &lt; 0.001. Rates of impairment between groups only differed for PS scores, with 63.6% of the CNS group and 31.5% of the non-CNS group demonstrating impairment, p &lt; 0.001. Primary CNS tumor cancer type and male biological sex emerged as the only significant risk factors that predicted processing efficiency skills, with male sex predicting lower scores on PS (ß=8.91 p&lt;.001) and semantic fluency (ß=7.59, p=.007).Conclusions:These findings indicate that both pediatric primary CNS tumor and non-CNS cancer survivors exhibit substantial weaknesses in processing efficiency skills after treatment. While both groups demonstrated deficits compared to normative samples, the CNS group was more susceptible to PS impairments than non-CNS group. A basic initial study of the relationships between risk factors and processing efficiency skills revealed that primary CNS cancer was a predictor of lower performance on working memory and processing speed measures, while male biological sex was a significant risk factor for worse performance on processing speed and semantic fluency measures. Continued focus on the construct of processing efficiency in pediatric cancer survivors is warranted. Applying a standardized approach to assessing and communicating this nuanced cognitive skill could contribute to advancing both clinical practice and outcomes research of pediatric cancer survivors.

Social cognition and adjustment in adult survivors of pediatric central nervous system tumors.

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. 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. 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]). 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.

Late-onset Cognitive Impairment and Modifiable Risk Factors in Adult Childhood Cancer Survivors

Long-term survivors of childhood cancer may be at elevated risk for new neurocognitive impairment and decline as they age into adulthood. To determine whether aging adult childhood cancer survivors report more new-onset neurocognitive impairments compared with their siblings and to identify risk factors associated with such impairments. Participants of this cohort study included adult survivors of childhood cancer from the Childhood Cancer Survivor Study and their siblings as a control group. The original cohort included survivors who received a diagnosis between January 1, 1970, and December 31, 1986, for whom longitudinal neurocognitive assessment was available. This study examined the prevalence of new-onset neurocognitive impairment between baseline (23.4 years after diagnosis) and follow-up (35.0 years after diagnosis). The analysis was performed from January 2021 to May 2022. Cancer treatment exposures were abstracted from medical records. Chronic health conditions were graded using Common Terminology Criteria for Adverse Events version 4.03. The primary outcome was new-onset (present at follow-up, but not present at baseline) neurocognitive impairment (defined as a score in the worst 10% of the sibling cohort). Impairment was assessed using the Childhood Cancer Survivor Study Neurocognitive questionnaire. Relative risks (RRs) and 95% CIs were used to estimate associations of neurocognitive impairment with treatment and health behaviors and conditions using generalized linear models. The cohort comprised 2375 survivors (mean [SD] age at evaluation, 31.8 [7.5] years; 1298 women [54.6%]) of childhood cancer, including acute lymphoblastic leukemia (ALL; 1316 participants), central nervous system (CNS) tumors (488 participants), and Hodgkin lymphoma (HL; 571 participants). A total of 232 siblings (mean [SD] age at evaluation, 34.2 [8.4] years; 134 women [57.8%]) were included. Compared with siblings, a higher proportion of survivors with no impairment in memory at baseline had new-onset memory impairment at follow-up: siblings proportion, 7.8% (95% CI, 4.3%-11.4%); ALL survivors treated with chemotherapy only, 14.0% (95% CI, 10.7%-17.4%); ALL survivors treated with cranial radiation (CRT), 25.8% (95% CI, 22.6%-29.0%); CNS tumor survivors, 34.7% (95% CI, 30.0%-39.5%); and HL survivors, 16.6% (95% CI, 13.4%-19.8%). New-onset memory impairment was associated with CRT in CNS tumor survivors (RR, 1.97; 95% CI, 1.33-2.90) and alkylator chemotherapy greater than or equal to 8000 mg/m2 in ALL survivors treated without CRT (RR, 2.80; 95% CI, 1.28-6.12). Neurologic conditions mediated the impact of CRT on new-onset memory impairment in CNS survivors. Smoking, low educational attainment, and low physical activity were associated with elevated risk for new-onset memory impairment. These findings suggest that adult survivors of childhood cancer are at elevated risk for late-onset memory impairment related to modifiable risk factors identified early in survivorship.

Obesity Risk of Pediatric Central Nervous System Tumor Survivors: A Cross-Sectional Study.

Adult survivors of pediatric central nervous system (CNS) tumors are at the highest risk for morbidity and late mortality among all childhood cancers due to a high burden of chronic conditions, and environmental and lifestyle factors. This study aims to epidemiologically characterize young adult survivors of pediatric CNS tumors using body mass index (BMI) to assess risk factors for obesity. Using a cross-sectional design, young adults (18-39 years) previously treated for pediatric CNS tumors and followed in a survivorship clinic during 2016-2021 were examined. Demographic, BMI, and diagnosis information were extracted from medical records of the most recent clinic visit. Data were assessed using a two-sample t-test, Fisher's exact test, and multivariable logistical regression. 198 survivors (53% female, 84.3% White) with a BMI status of underweight (4.0%), healthy weight (40.9%), overweight (26.8%), obesity (20.2%), and severe obesity (8.1%) were examined. Male sex (OR, 2.414; 95% CI, 1.321 to 4.414), older age at follow-up (OR, 1.103; 95% CI, 1.037 to 1.173), and craniopharyngioma diagnosis (OR, 5.764; 95% CI, 1.197 to 27.751) were identified as significant (p < 0.05) obesity-related (≥25.0 kg/m2) risk factors. The majority of patients were overweight or obese. As such, universal screening efforts with more precise determinants of body composition than BMI, risk stratification, and targeted lifestyle interventions are warranted during survivorship care.

Interventions to improve neurocognitive late-effects in pediatric and adolescent CNS tumor patients and survivors - a systematic review.

Survival of children and adolescents diagnosed with central nervous system (CNS) tumors massively improved over the last decades due to better diagnostics, treatment, and supportive care. However, morbidity is still the highest of all cancer entities in this age group with neurocognitive late-effects being one of the most severe. With this systematic review, we aim to summarize interventions designed to prevent or improve neurocognitive late-effects in CNS tumor patients. We searched PubMed on August 16th 2022 and included publications studying interventions for neurocognitive late-effects in pediatric and adolescent patients and survivors diagnosed with a CNS tumor. We included any form of neurocognitive intervention during treatment or following treatment completion. We considered all types of studies except for expert opinions and case reports. The literature search resulted in 735 publications. We included 43 publications in the full text screening and 14 met our inclusion criteria. Of those, two assessed the impact of pharmacological interventions, three of exercise interventions, five of online cognitive training, and four assessed behavioral interventions. Different neuropsychological test batteries and imaging were used to measure the impact of the respective interventions. Most studies showed a positive impact of the interventions in single to several of the subtests used. We found several intervention studies indicating improvement of neurocognitive problems in children and adolescent CNS tumor survivors. In this population exercise interventions or online cognitive training might mitigate or improve neurocognitive late-effects.

Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors.

Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI. Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241). Genotype-by-time interactions were evaluated using mixed-effects linear regression to identify common variants (minor allele frequency > 1%) associated with cognitive performance change. Novel variants associated with cognitive decline (P < 5 × 10-5) in individuals of European ancestry (n = 163) were considered replicated if they demonstrated consistent genotype-by-time interactions (P < .05) in individuals of non-European ancestries (n = 78) and achieved genome-wide statistical significance (P < 5 × 10-8) in a meta-analysis across ancestry groups. Participants were mostly males (65%) diagnosed with embryonal tumors (98%) at a median age of 8.3 years. Overall, 1150 neurocognitive evaluations were obtained (median = 5, range: 2-10 per participant). One of the five loci previously associated with cognitive outcomes in pediatric CNS tumors survivors demonstrated significant time-dependent IQ declines (PPARA rs6008197, P = .004). Two variants associated with IQ in the general population were associated with declines in IQ after Bonferroni correction (rs9348721, P = 1.7 × 10-5; rs31771, P = 7.8 × 10-4). In genome-wide analyses, we identified novel loci associated with accelerated declines in IQ (rs116595313, meta-P = 9.4 × 10-9), WM (rs17774009, meta-P = 4.2 × 10-9), and PS (rs77467524, meta-P = 1.5 × 10-8; rs17630683, meta-P = 2.0 × 10-8; rs73249323, meta-P = 3.1 × 10-8). Inherited genetic variants involved in baseline cognitive functioning and novel susceptibility loci jointly influence the degree of treatment-associated cognitive decline in pediatric CNS tumor survivors.

Barriers to employment for young adult central nervous system tumor survivors: The role of career readiness and core self-evaluations

BACKGROUND: Although the majority of childhood cancer survivors make successful transitions to adulthood, research suggests that a significant group experiences ongoing medical concerns, such as psychological distress, that significantly impact the achievement of crucial social roles including employment. OBJECTIVE: The purpose of this study was to examine the relationship between career decision making, core self-evaluations, and perceived internal and external barriers to employment in a sample of young adult central nervous system tumor survivors. METHOD: A sample of 110 young adult survivors of pediatric central nervous system tumors was surveyed. Mediation analysis with structural equational modeling was used to correlate a number of different measures (Career Decision Making [CTI], Perceived Employment Barriers [PEB], and Core-Self Evaluations [CSE]). RESULTS: The presence of both significant direct and indirect effects of career decision making on perceived employment barriers implied that there was a partial mediating effect of core self-evaluations on the association between career readiness and employment barriers. CONCLUSION: Career decision-making is a robust construct that can be applied to young adult central nervous system tumor survivors in effort to gain more insight into the vocational psychological factors that impact career development and employment in this group. Core self-evaluations was found to be a mediator between career decision making and perceived career barriers.

Pediatric central nervous system tumor survivor and caregiver experiences with multidisciplinary telehealth.

Telehealth use to facilitate cancer survivorship care is accelerating; however, patient satisfaction and barriers to facilitation have not been studied amongst pediatric central nervous system (CNS) tumor survivors. We assessed the telehealth experiences of survivors and caregivers in the Pediatric Neuro-Oncology Outcomes Clinic at Dana-Farber/ Boston Children's Hospital. Cross-sectional study of completed surveys among patients and caregivers with ≥ 1 telehealth multidisciplinary survivorship appointment from January 2021 through March 2022. Thirty-three adult survivors and 41 caregivers participated. The majority agreed or strongly agreed that telehealth visits started on time [65/67 (97%)], scheduling was convenient [59/61 (97%)], clinician's explanations were easy-to-understand [59/61 (97%)], listened carefully/addressed concerns [56/60 (93%)], and spent enough time with them [56/59 (95%)]. However, only 58% (n = 35/60) of respondents agreed or strongly agreed they would like to continue with telehealth and 48% (n = 32/67) agreed telehealth was as effective as in person office visits. Adult survivors were more likely than caregivers to prefer office visits for personal connection [23/32 (72%) vs. 18/39 (46%), p = 0.027]. Offering telehealth multi-disciplinary services may provide more efficient and accessible care for a subset of pediatric CNS tumor survivors. Despite some advantages, patients and caregivers were divided on whether they would like to continue with telehealth and whether telehealth was as effective as office visits. To improve survivor and caregiver satisfaction, initiatives to refine patient selection as well as enhance personal communication through telehealth systems should be undertaken.

DISP-16. NUTRITIONAL SCREENING OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR SURVIVORS REVEALS HIGH PREVALENCE OF MALNOURISHMENT WITH SOCIODEMOGRAPHIC AND CLINICAL RISK FACTORS

Abstract Adult survivors of pediatric central nervous system (CNS) tumors are at the highest risk for morbidity and late mortality among all childhood cancers, partially due to chronic health conditions intersected with environmental and lifestyle factors. We aimed to study the prevalence of and risk factors for malnourishment (underweight, overweight, obese) amongst adult survivors of pediatric CNS tumors. We conducted a cross-sectional study assessing young adults (18-39 years) previously treated for pediatric CNS tumors who were followed in our survivorship clinic during 2016-2021. Sociodemographic, clinical, and treatment information was extracted from medical records with BMI status, per CDC guidelines, obtained from the most recent clinic visit. Data was assessed using one-way ANOVA, fishers exact test, and multivariable logistical regression. We identified 198 survivors (53% female, 84.3% white) categorized as underweight (4.0%), normal weight (40.9%), overweight (26.8%), obese (20.2%), and severely obese (8.1%). Patients were median age 8 years [4-12] at diagnosis and 24 years [20-28] at follow-up. Most common primary diagnosis and tumor location was low grade glioma (50.5%) and posterior fossa (39.4%) with 90.4% receiving surgery, 51.5% chemotherapy, and 52.5% radiotherapy. Male sex (OR 2.376, p = 0.006), hypothalamic/optic pathway tumor location (OR 2.362, P = 0.031), and radiation therapy (OR 2.844, p = 0.005) were associated with increased overweight/obesity risk, while chemotherapy (OR 0.363, p = 0.006) was associated with decreased risk. Male sex (OR 0.511, p = 0.007) and white ‘race’ (OR 0.166, p = 0.022) were associated with decreased underweight risk. The majority of young adult survivors seen in our clinic were not healthy weight by BMI, and the distribution of BMI groups appears comparable to contemporary studies of the general young adult U.S. population. The prevalence of malnourishment amongst PNO survivors warrants universal screening efforts with more accurate determinants of body composition than BMI, risk stratification, as well as targeted interventions.

Employment among Childhood Cancer Survivors: A Systematic Review and Meta-Analysis.

Simple SummaryDespite the improvements in the survival rates and functional outcomes of childhood cancer survivors (CCS), most of them experience late effects with possible consequences to their occupational status. To date, a reliable estimate of the prevalence of employment among this population is still missing. This study aimed to assess, for the first time, the prevalence of employment among CCS and to examine the associations of socio-demographic and clinical factors with employment. Almost 100 cohorts worldwide have been included in this review, highlighting that two-thirds of childhood cancer survivors were employed. Different employment rates depending on socio-demographic and clinical factors were identified. The findings from this study could facilitate the design of targeted interventions aimed at promoting employment among CCS.To date, there are heterogeneous studies related to childhood cancer survivors’ (CCS) employment rates. Given the importance of this topic, we aimed to perform a systematic review and meta-analysis to investigate the prevalence of employment among CCS and to examine its association with socio-demographic and clinical factors. We followed the PRISMA guidelines to search for pertinent articles in relevant electronic databases. Eighty-nine articles comprising 93 cohorts were included. The overall prevalence of employment was 66% (CI: 95% 0.63–0.69). Subgroup meta-analyses showed that lower rates were found for central nervous system tumor survivors (51%, CI: 95% 0.43–0.59), and for CCS treated with cranial-radiotherapy (53%, CI: 95% 0.42–0.64) or haematopoietic stem-cell transplantation (56%, CI: 95% 0.46–0.65). The studies conducted in Asia highlighted employment rates of 47% (CI: 95%, 0.34–0.60). Univariate meta-regressions identified the following socio-demographic factors associated with higher rates of employment: a female gender (p = 0.046), a higher mean age at the time of investigation (p = 0.00), a longer time since diagnosis (p = 0.00), a higher educational level (p = 0.03), and a married status (p = 0.00). In conclusion, this systematic review and meta-analysis provides evidence that two-thirds of CCS are employed worldwide. Identifying vulnerable groups of CCS may allow for the design of multidisciplinary support strategies and interventions to promote employment in this population.

OTHR-16. Nutritional screening of U.S. pediatric central nervous system tumor survivors

INTRODUCTION: Adult survivors of pediatric central nervous system (CNS) tumors are at the highest risk for morbidity and late mortality among all childhood cancers – owed in part to chronic health condition burden, which intersects with environmental and lifestyle factors. Their weight epidemiology has not been previously characterized. METHODS: An institutional, cross-sectional study was carried out amongst young adults ages 18-39 years, previously treated for pediatric CNS tumors and seen in our specialty survivorship clinic from January 2016 to December 2021. Sociodemographic, clinical, and treatment information was extracted from medical records and summarized by descriptive statistics. Anthropometric information extracted from clinical visit records was used to calculate body mass index (BMI) and weight status category according to CDC guidelines. RESULTS: We identified 200 survivors, 47% male and 53% female. Median age was 26 years (range 18-39); patients were median 16.5 years (range 1.5-34.2) from initial diagnosis. Most common primary diagnoses were low grade-glioma (51.0%) and embryonal tumor (20.5%.) One hundred and five (52.5%) survivors had received prior cranial radiation; 81 (40.5%) had an endocrinologic disorder at time of visit. Amongst the entire cohort, 39% were healthy weight, 5% were underweight, 27% overweight, 21% obese, and 8% severely obese. CONCLUSION: The majority of young adult survivors seen in our clinic were not healthy weight by BMI definition. The distribution of BMI groups appears comparable to contemporary studies of the general young adult U.S. population. For those with decreased muscle mass, a previously recognized issue in pediatric CNS tumor survivors, BMI may underestimate body fat. By abstract presentation, univariable analyses will be performed using the Fisher’s exact test or Wilcoxon rank sum test to assess for undernutrition and overnutrition risk factors. Our refined understanding of the nutritional epidemiology in this population will allow for more strategic diet and exercise interventions.

QOL-05. Cardiorespiratory fitness and health-related quality of life amongst survivors of childhood central nervous system tumours.

INTRODUCTION: Due to recent advancements in surgical techniques, imaging and adjuvant therapies, survival rates for children with central nervous system (CNS) tumours have improved. Research priorities have now shifted to focus on late-effects and quality of survivorship amongst childhood CNS tumour survivors. Our study aimed to assess levels of cardiorespiratory fitness and health-related quality of life (HRQoL) amongst survivors of childhood CNS tumours. A secondary aim was to investigate potential relationships between cardiorespiratory fitness and HRQoL. METHODS: Participants were recruited from the National Children’s Cancer Service in CHI Crumlin. Inclusion criteria included: diagnosis of a primary CNS tumour, aged between 6-17 years, between 3 months and 5 years post completion of oncology treatment, independent mobility, 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, both self-report and parent proxy report forms were used. RESULTS: 20 participants (n=9 male) were recruited with a mean age of 12.34 (SD = 3.46) years. Mean time since completion of oncology treatment was 2.31 (SD = 1.38) years. Mean 6-minute walk distance (6MWD) was 482.75 (SD = 50.04) metres, equating to the 5.55th (SD = 6.83th) percentile overall. 6MWD was significantly reduced compared to predicted 6MWD (t = -12.52, p <.001, 95% CI [-163.52, -116.68]). Parent proxy-reported HRQoL was significantly reduced compared to healthy population norms (t = -5.82, p <0.001, 95% CI [-25.76, -12.17]). A strong positive correlation exists between 6MWD and both parent-proxy (Pearson’s r = 0.533, p = 0.015) and child-reported HRQoL (r = 0.580, p = 0.007). CONCLUSION: Survivors of childhood CNS tumours present with impaired levels of cardiorespiratory fitness and HRQoL compared to healthy population norms. Higher levels of cardiorespiratory fitness are associated with higher levels of HRQoL.

Associations between DNA methylation age and chronic health conditions in survivors of childhood leukemia and CNS tumor.

12088 Background: Survivors of childhood cancer are at risk for treatment related morbidities, including an early onset of chronic health conditions (CHC). Survivors are at risk for epigenetic age acceleration (EAA), i.e. when DNA methylation (DNAm)-predicted age exceeds chronologic age. EAA has been associated with treatment exposures and incidence of cardiometabolic, pulmonary, and neurologic CHC. We characterized the burden of CHCs in survivors of acute lymphoblastic leukemia (ALL) and central nervous system (CNS) tumors, two of the most common childhood cancers, and determined the association between EAA, cancer diagnosis, and burden of CHC. Methods: We included survivors of CNS tumor or ALL diagnosed at Texas Children’s Hospital (TCH) between 1992-2013, who were seen at least once in the TCH Long-Term Survivor Clinic. Demographics, diagnosis, treatment data and date of onset and type of CHC were abstracted from the electronic health record. All CHCs required subspecialty care, were present for at least 1 year, and were classified by system into one of 8 categories. Germline samples were obtained at an average of 10.5 years after diagnosis, and at an average age of 15.9 years of age. Samples were analyzed by Illumina MethylationEPIC BeadChip array on an iScan System in the Baylor College of Medicine (BCM) Laboratory for Translational Genomics. Methylation data were processed using minfi, normalized with noob, and EAA estimated using the Horvath calculator. The relationship between EAA, diagnosis, and CHCs was determined by multivariable linear regression. Results: Endocrine (65%), neuropsychiatric (78%), and sensory/motor (73%) CHCs were common in the CNS tumor group (n = 77). Metabolic (22%) and neuropsychiatric (59%) CHCs were common in the ALL group (n = 268). Survivors of CNS tumor had an earlier time of CHC onset, were more likely to have endocrine and sensory motor outcomes, and less likely to have metabolic outcomes vs. ALL survivors. On average, both survivor groups had EAA: 3.3 years (range: -12.2-15.5 years) for 138 ALL survivors and 4.4 years (range: -0.9-10.9 years) for 38 CNS tumor survivors, but EAA did not differ between diagnoses after adjustment for RT (p = 0.75). For CNS tumor survivors, EAA was 0.8 years greater for each system affected by CHC (beta = 0.8, p = 0.043) after adjustment for RT. For ALL survivors, EAA was not associated with CHCs (p = 0.33), but was associated with RT (p = 0.007). Conclusions: CHCs are prevalent in survivors of childhood ALL and CNS tumors, with patterns that differ by cancer diagnosis. In this cohort of relatively young 5 year + survivors of ALL and CNS tumor, all survivors had similar EAA but demonstrated cancer diagnosis-specific differences in associations between EAA, RT and burden of CHC.

Health-related quality of life among Malaysian pediatric survivors of central nervous system tumor

Pediatric central nervous system tumor survivors (CNSTS) experience late effects that may affect their health-related quality of life (HRQOL). The study aims: i) compare HRQOL among Malaysian CNSTS with acute lymphoblastic leukemia survivors (ALLS) and healthy children, and ii) explore factors associated with low HRQOL. We performed a comparative cross-sectional HRQOL study of 46 CNSTS aged 5-18 years and 90 ALLS (age and gender-matched) who completed treatment for >1 year, and a published cohort of healthy children. Pediatric Quality of Life Inventory (PedsQL) was used for all groups and PedsQL Cancer Module for CNSTS and ALLS. Multiple regression analysis was used to determine factors associated with low HRQOL. Mean PedsQL total scale score, physical health score and psychosocial health score of CNSTS were 69.0 (SD 20.3), 68.7 (SD 27.9) and 69.2 (SD 19.2) respectively. These scores were significantly lower in all domains particularly in teenagers compared with healthy children and ALLS. The median PedsQL Cancer Module score of CNSTS was significantly lower than ALLS in total scale, cognitive problems and communication. Physical impairment was associated with lower PedsQL scores in all 3 domains; special education placement was associated with lower PedsQL total scale and physical health scores and clinically significant internalizing behavioral difficulties score was associated with lower PedsQL psychosocial health scores. CNSTS reported lower PedsQL scores in all domains than ALLS and healthy children. Clinicians need to be vigilant of HRQOL needs among CNSTS, especially those with risk factors of special education needs, physical impairment, and internalizing behavioral difficulties.

Sickness absence and disability pension trajectories in childhood cancer survivors and references- a Swedish prospective cohort study.

BackgroundChildhood cancer survivors are at high risk of chronic health conditions. We aimed to explore future long-term sickness absence and disability pension in young adult childhood cancer survivors and matched references.MethodsWe performed a prospective cohort study using microdata from five Swedish nationwide registers. Among all individuals born 1976–1998 and living in Sweden, we included 3632 childhood cancer survivors and 17,468 matched references that could be followed-up for 15, 10, or 5 years, respectively. A group-based trajectory model was applied to identify trajectories of mean annual sickness absence and/or disability pension days (SADP) in each sub-cohort, with 95% confidence intervals (CI). Potential risk factors for trajectory belonging were explored using χ2 test and multinomial logistic regression.ResultsMost young adult childhood cancer survivors (90.2–96.5%) and references (97.4–98.8%) followed a No SADP trajectory. A larger proportion of childhood cancer survivors than references followed a Moderate (33–102 days/year) or High (115–260 days/year) SADP trajectory (15-year follow-up cohorts: Moderate 4.6% versus 1.2%; High 5.1% versus 1.5%). Childhood cancer survivors of central nervous system (CNS) tumors were at higher risk of the High SADP trajectory than childhood cancer survivors of hematological or non-CNS solid tumors (hematological versus CNS: odds ratio = 2.30, 95% CI 1.23–4.30; hematological versus non-CNS: odds ratio = 0.32, 95% CI 0.13–0.79).ConclusionsAlthough most young adult childhood cancer survivors had no SADP during follow-up, 9.7% experienced moderate or high numbers of SADP days/year throughout the 15-year follow-up; compared to 2.7% among references. CNS tumor survivors were at particular risk of SADP long-term and need extra attention in their future work prospect.

Long-Term Follow-Up of Pediatric CNS Tumor Survivors-A Selection of Relevant Long-Term Issues.

Introduction: Survivors of pediatric central nervous system (CNS) tumors are at high risk for late effects and long-term morbidity. The quality of survival became increasingly important, as advances in diagnostics, multimodal treatment strategies, and supportive care have led to significant increases in long-term survival. Aim: This review aims to provide a global overview of the potential late effects and long-term follow-up care of CNS tumor survivors, directed to trainees and practitioners with less targeted training in pediatric oncology. Late effects in CNS tumor survivors: A specific focus on CNS tumor survivors relies on cognitive and psychosocial late effects, as they may have an impact on education, professional career, independent living, and quality of life. Further important late effects in CNS tumor survivors include endocrine, metabolic, cardiovascular, and cerebrovascular diseases. Conclusions: Comprehensive long-term follow-up care is essential for pediatric CNS tumor survivors to improve their quality of survival and quality of life. An individualized approach, taking all potential late effects into account, and carried out by an interdisciplinary team, is recommended, and should continue into adulthood. Existing recommendations and guidelines on long-term follow-up care guide the multidisciplinary teams.

Educational Attainment and Employment Outcome of Survivors of Pediatric CNS Tumors in Switzerland-A Report from the Swiss Childhood Cancer Survivor Study.

Background: Childhood cancer survivors diagnosed with a central nervous system (CNS) tumor are at risk for educational and vocational challenges. This study compared educational attainment and employment outcome in survivors of CNS tumors to survivors of other malignancies. Methods: The questionnaire-based Swiss Childhood Cancer Survivor Study (SCCSS) included cancer patients diagnosed between 1976 and 2010, aged ≤20 years, who survived ≥5 years after diagnosis. We classified participants aged ≥16 years into three groups: CNS tumor and non-CNS malignancy with and without CNS-directed treatment. We analyzed educational attainment, employment outcome and special schooling. Subgroup analyses included survivors aged ≥25 years. Results: We analyzed 2154 survivors, including 329 (15%) CNS tumor survivors, 850 (40%) non-CNS tumor survivors with and 975 (45%) without CNS-directed treatment. Fewer CNS tumor survivors aged ≥25 years reached tertiary education (44%) compared to those without CNS-directed treatment (51%) but performed similar to survivors with CNS-directed treatment (42%). Among CNS tumor survivors, 36 (14%) received special schooling. Higher parental education was associated with higher levels in survivors. Employment outcome did not significantly differ between the three diagnostic groups. A higher proportion of CNS tumor survivors received disability pension or were unemployed. Conclusions: Our findings suggest that CNS tumor survivors need more time to achieve their highest educational level. This should influence clinical care of these survivors by offering vocational counseling.

Accelerated cognitive decline in adult survivors of pediatric central nervous system (CNS) tumors: A report from the Childhood Cancer Survivor Study (CCSS).

10049 Background: Survivors of pediatric CNS tumors may be at elevated risk for accelerated cognitive decline as they age through adulthood relative to the general population, which may be an early risk factor for dementia. Methods: Longitudinal analysis of 512 CNS tumor survivors (52.3% female, mean [SD] 30.6 [7.1] years at T1) and 232 siblings (57.8% female, mean [SD] 34.2 [8.4] years at T1) from the CCSS was conducted using the Neurocognitive Questionnaire (NCQ) to assess task efficiency, emotional regulation, organization and memory at two timepoints separated by a mean of 11.6 [0.7] years. Impairment in each NCQ domain was defined as a score ≥ 90th percentile of the CCSS sibling distribution at each survey, with decline defined as moving from unimpaired at T1 to impaired at T2. Treatment exposures were abstracted from medical records. Chronic health conditions were self-reported at T1 and graded according to CTCAE v4.3. Relative risk of decline for group, treatment and chronic condition predictors was estimated using generalized linear models with robust variance estimates. Mediation analysis examined direct effects of treatments and mediating effects of chronic conditions. All models were adjusted for age, sex, and race. Results: At T1, survivors demonstrated higher frequency of impaired memory (24.5% vs. 6.5%, p &lt; 0.001), emotional regulation (14.3 % vs. 5.6%, p &lt; 0.001), task efficiency (43.3% vs. 13.8%, p &lt; 0.001) and organization (17.7% vs. 10.8%, p = 0.015) than siblings. Among those unimpaired at T1, more survivors vs. siblings declined in memory (34.7% vs. 7.8; RR 4.2, 95% CI 2.6-6.9), emotional regulation (15.5% vs. 5.0%; RR 2.8, 95% CI 1.5-5.3), task efficiency (22.7% vs. 7.0%; RR 2.9, 95% CI 1.7-5.2), and organization (14.5% vs. 2.9%; RR 4.9, 95% CI 2.1-11.0) by T2. Decline in survivor memory was associated with exposure to craniospinal irradiation (RR 1.9, 95% CI 1.3-2.8) and focal irradiation (RR 1.6, 95% CI 1.1-2.3) compared with no radiation, and exposure to Ara-C (RR 1.7, 95% CI 1.0-2.8) and cyclophosphamide (RR 1.7, 95% CI 1.01-2.8). Independent of therapy, serious/disabling or life-threatening cardiopulmonary conditions at T1 predicted future decline in memory (RR 1.5, 95% CI 1.02-2.2) and organization (RR 2.0, 95% CI 1.1-3.6), with the presence of 2 or more cardiopulmonary conditions associated with even higher risk (memory RR 2.6, 95% CI 2.0-3.1; organization RR 3.4, 95% CI 1.1-10.5). Chronic conditions did not mediate associations between treatment exposures and cognitive decline. Conclusions: CNS tumor survivors are at elevated risk for impairment and accelerated cognitive decline compared to siblings. Cranial radiation, Ara-C, cyclophosphamide, and cardiopulmonary morbidity are risk factors for decline. Survivors with these exposures/conditions may benefit from interventions to prevent additional future cognitive decline.