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      Long-Term Outcome of 4,040 Children Diagnosed With Pediatric Low-Grade Gliomas: An Analysis of the Surveillance Epidemiology and End Results (SEER) Database

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          Abstract

          Background

          Children with pediatric low-grade gliomas (PLGG) are known to have excellent 10-year survival rates; however the outcomes of adult survivors of PLGG are unknown. We identified patients diagnosed with PLGG diagnosed between 1973 and 2008 through the Surveillance Epidemiology and End Results (SEER) database to examine outcomes of adult survivors of PLGG.

          Procedure

          Four thousand and forty patients with either WHO grade I or II PLGG were identified and outcome data retrieved. Two analyses were performed to assess survival and risk of death from tumor. Competing risks analysis was conducted and cumulative incidence curves of death due to disease were generated. Cox proportional hazards regression was performed, with adjustment for non-disease death. Kaplan–Meier curves for overall cancer specific survival (OS) were also generated.

          Results

          The 20-year OS was 87% ± 0.8% and the 20-year cumulative incidence of death due to glioma was 12% ± 0.8%. The incidence of death after transition to adulthood (age greater than 22 years) was slightly lower, with 20-year cumulative incidence of disease death of 7% ± 1.8%. Year of diagnosis, age of diagnosis, histology, WHO grade, primary site, radiation, and degree of initial resection were prognostic in univariate analysis, while the administration of radiation was the greatest risk of death in multivariate analysis of OS (hazard ratio = 3.9).

          Conclusions

          PLGGs are associated with an excellent long-term survival, with a low likelihood of PLGG related death in adult survivors. Treatment strategies for pediatric tumors should therefore aim for disease control during childhood and adolescence with an emphasis on minimizing long-term treatment induced toxicities.

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          Most cited references23

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          Microstructural maturation of the human brain from childhood to adulthood.

          Brain maturation is a complex process that continues well beyond infancy, and adolescence is thought to be a key period of brain rewiring. To assess structural brain maturation from childhood to adulthood, we charted brain development in subjects aged 5 to 30 years using diffusion tensor magnetic resonance imaging, a novel brain imaging technique that is sensitive to axonal packing and myelination and is particularly adept at virtually extracting white matter connections. Age-related changes were seen in major white matter tracts, deep gray matter, and subcortical white matter, in our large (n=202), age-distributed sample. These diffusion changes followed an exponential pattern of maturation with considerable regional variation. Differences observed in developmental timing suggest a pattern of maturation in which areas with fronto-temporal connections develop more slowly than other regions. These in vivo results expand upon previous postmortem and imaging studies and provide quantitative measures indicative of the progression and magnitude of regional human brain maturation.
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            Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data?

            In the context of competing risks the Kaplan-Meier estimator is often unsuitable for summarizing failure time data. We discuss some alternative descriptive methods including marginal probability and conditional probability estimators. Two-sample test statistics are also presented.
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              Neurocognitive status in long-term survivors of childhood CNS malignancies: a report from the Childhood Cancer Survivor Study.

              To assess neurocognitive functioning in adult survivors of childhood Central Nervous System (CNS) malignancy, a large group of CNS malignancy survivors were compared to survivors of non-CNS malignancy and siblings without cancer on a self-report instrument (CCSS-NCQ) assessing four factors, Task Efficiency, Emotional Regulation, Organization and Memory. Additional multiple linear regressions were used to assess the contribution of demographic, illness, and treatment variables to reported neurocognitive functioning in CNS malignancy survivors and the relationship of reported neurocognitive functioning to socioeconomic indicators. Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all CCSS-NCQ factors than non-CNS cancer survivors or siblings (p < .01). Within the CNS malignancy group, medical complications (hearing deficits, paralysis and cerebrovascular incidents) resulted in a greater likelihood of reported deficits on all CCSS-NCQ factors. Total or partial brain irradiation and ventriculoperitoneal (VP) shunt placement was associated with greater impairment on Task Efficiency and Memory. Female gender was associated with a greater likelihood of impaired scores on Task Efficiency and Emotional Regulation, while diagnosis before age 2 years resulted in less likelihood of reported impairment on the Memory factor. CNS malignancy survivors with more impaired CCSS-NCQ scores demonstrated significantly lower educational attainment (p < .01), less household income (p < .001), less full time employment (p < .001), and fewer marriages (p < .001). Survivors of childhood CNS malignancy were found to be at significant risk for neurocognitive impairment that continues to adulthood and is correlated with lower socioeconomic achievement.
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                Author and article information

                Journal
                Pediatr Blood Cancer
                Pediatr Blood Cancer
                pbc
                Pediatric Blood & Cancer
                Blackwell Publishing Ltd (Oxford, UK )
                1545-5009
                1545-5017
                July 2014
                30 January 2014
                : 61
                : 7
                : 1173-1179
                Affiliations
                [1 ]Division of Pediatric Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital Boston, Massachusetts
                [2 ]Department of Cancer Biology, Dana-Farber Cancer Institute Boston, Massachusetts
                [3 ]Department of Medicine, Boston Children's Hospital Boston, Massachusetts
                [4 ]Department of Pediatric Neurosurgery, Boston Children's Hospital Boston, Massachusetts
                [5 ]Department of Radiation Oncology, Boston Children's Hospital, Dana-Farber Cancer Institute and Brigham and Women's Hospital Boston, Massachusetts
                [6 ]Department of Neurology, Boston Children's Hospital Boston, Massachusetts
                [7 ]Department of Medical Oncology, Dana-Farber Cancer Institute Boston, Massachusetts
                [8 ]Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine Los Angeles, California
                Author notes
                *Correspondence to: Peter Manley, Pediatric Neuro-Oncology Program, D3148, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215., E-mail: Peter_Manley@ 123456dfci.harvard.edu

                Grant sponsor: Stop&Shop Pediatric Brain Tumor Program; Grant sponsor: Andrysiak Fund for LGG, Pediatric Low-Grade Astrocytoma Foundation; Grant sponsor: Friends of DFCI; Grant sponsor: Nuovo-Soldati Foundation; Grant sponsor: Philippe Foundation; Grant sponsor: St Baldrick's Foundation

                [The copyright line for this article was corrected in July 2015 after original online publication.]

                Conflict of interest: Nothing to declare.

                Article
                10.1002/pbc.24958
                4657506
                24482038
                bdd02750-650a-456f-8136-5aa0d75d5da0
                © 2014 The Authors. Pediatric Blood & Cancer Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 01 November 2013
                : 03 January 2014
                Categories
                Research Articles

                Pediatrics
                outcome,pediatric low-grade glioma,seer
                Pediatrics
                outcome, pediatric low-grade glioma, seer

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