bluuebunny/crossref_metadata_2025_split huggingface dataset:
PATH-11. PROSPECTIVE (EPI-)GENETIC CLASSIFICATION OF &gt; 1,000 PEDIATRIC CNS TUMORS—THE MNP 2.0 STUDY
Authors: Sturm Dominik , Sahm Felix , Andreiuolo Felipe , Capper David , Gessi Marco , Rode Agata , Bison Brigitte , Hirsch Steffen , Gerber Nicolas U , Gottardo Nicholas G , Kramm Christof M , Rutkowski Stefan , von Deimling Andreas , Pietsch Torsten , Pfister Stefan M , Jones David T W 
Published: December 2020

Abstract
The large variety of CNS tumor entities affecting children and adolescents, some of which are exceedingly rare, results in very diverging patient outcomes and renders accurate diagnosis challenging. To assess the diagnostic utility of routine DNA methylation-based CNS tumor classification and gene panel sequencing, the Molecular Neuropathology 2.0 study prospectively integrated these (epi-)genetic analyses with reference neuropathological diagnostics as an international trial for newly-diagnosed pediatric patients. In a four-year period, 1,215 patients with sufficient tissue were enrolled from 65 centers, receiving a reference neuropathological diagnosis according to the WHO classification in &gt;97%. Using 10 FFPE sections as input, DNA methylation analysis was successfully performed in 95% of cases, of which 78% with sufficient tumor cell content were assigned to a distinct epigenetic tumor class. The remaining 22% did not match any of 82 represented classes, indicating novel rare tumor entities. Targeted gene panel sequencing of &gt;130 genes performed for 96% of patients with matched blood samples detected diagnostically, prognostically, or therapeutically relevant somatic alterations in 48%. Germline DNA sequencing data indicated potential predisposition syndromes in ~10% of patients. Discrepant results by neuropathological and epigenetic classification (29%) were enriched in histological high-grade gliomas and implicated clinical relevance in 5% of all cases. Clinical follow-up suggests improved survival for some patients with high-grade glioma histology and lower-grade molecular profiles. Routine (epi-)genetic profiling at the time of primary diagnosis adds a valuable layer of information to neuropathological diagnostics and will improve clinical management of CNS tumors.
PATH-15. PROTEOMIC SIGNATURES PREDICT GRADE IN PEDIATRIC AND YOUNG ADULT INFILTRATIVE ASTROCYTOMAS
Authors: Graham Richard T , Sells Blake E , Fleming Jessica , McElroy Joseph P , Bell Erica H , Haque S Jaharul , Becker Aline P , Boué Daniel R , Finlay Jonathan L , Chakravarti Arnab 
Published: December 2020

Abstract

BACKGROUND
Infiltrative astrocytomas in children and young adults pose a treatment challenge due to the difficulty of achieving gross total resection and tumor resistance to irradiation and chemotherapy. Histopathologic grade is an essential part of determining prognosis and treatment, but it is subjective and provides limited understanding of the molecular mechanisms underlying tumor development and progression.

METHODS
We performed liquid chromatography/mass spectrometry (LC/MS-MS) on 28 FFPE samples of primary infiltrative astrocytomas (10 grade II, 8 grade III and 10 grade IV – WHO classification) from Nationwide Children’s Hospital (NCH). Initial unsupervised clustering was performed. Lasso regression yielded a protein signature separating low- and high-grade tumors which was validated using a similar cohort of pediatric and young adult infiltrative astrocytomas from the Proteomic Data Commons (PDC) (n=28) of the National Cancer Institute.

RESULTS
Unsupervised clustering of NCH samples essentially recapitulated grade and lasso regression yielded a 10-protein signature that distinguished grade II from grade III/IV tumors. This 10-protein signature when applied to the PDC validation dataset, accurately predicted grade for 89.3% of the tumors (p=0.00014).

CONCLUSIONS
We identified a quantitative protein signature that can reliably distinguish between low- and high-grade infiltrative astrocytomas from FFPE tissue. Further validation will enable the development an objective prognostic proteomic clinical test that complements and may outperform current histopathological strategies. Additionally, proteomic profiling of tumors will clarify the molecular mechanisms contributing to treatment resistance and tumor progression and help identify novel treatment targets. Independent functional validation and characterization of proteins is ongoing.
PATH-16. CORRELATION OF PATHOLOGICAL AND RADIOGRAPHICAL DIAGNOSES FOR CHILDREN WITH BRAIN TUMORS AT TWO MAJOR HOSPITAL IN KENYA
Authors: Okemwa Dr Minda , Omouk Dr Simon , Mwangombe Prof Nimrod , Macharia Dr Benson 
Published: December 2020

Abstract

BACKGROUND
Central nervous system (CNS) tumors are the leading solid tumors in the childhood population but vastly underreported in the African population. There’s limited data on childhood brain tumors as well as the histopathological distribution in Kenya. Our study aimed at assessing the spectrum as well as the level of correlation with imaging in diagnosis of brain tumors within two major hospital settings. DESIGN: This was a cross-sectional retrospective descriptive study conducted at the two major hospitals in Kenya: Kenyatta National Hospital (KNH) and Moi Teaching and Referral Hospital (MTRH). Children who underwent treatment for brain tumors between 2015 and 2017 and whose tissue biopsies were available at the laboratory archives were included.

RESULTS
87 cases were available for review, and the majority of the affected population were of ages 5–9 years. The most affected site was infratentorial compartment (48.3%) with gliomas and medulloblastoma being equally distributed. Majority of the gliomas were low grade (69%) with pilocytic astrocytoma being the most common subtype (42.9%). The overall sensitivity for the diagnosis of brain tumors through radiology was 69.4%. The level of correlation of histopathological to radiological diagnosis was statistically insignificant with P and kappa values of 0.814 and -0.024 respectively.

CONCLUSION
Gliomas and medulloblastomas were the commonest tumors at both centers. Histopathological diagnoses have a high concordance of agreement among various morphologists. The level of correlation between histopathological and radiological diagnosis was high. Next steps include standardizing clinical, radiological and pathological details within Kenya.
PATH-21. TELOMERE LENGTH ANALYSIS OF CNS TUMORS IN THE PEDIATRIC BRAIN TUMOR ATLAS
Authors: Rokita Jo Lynn , Gaonkar Krutika , Ijaz Heba , Miller Daniel , Karras Tasso , Santi Mariarita , Martinez Daniel , Koptyra Mateusz , De Raedt Thomas , Mason Jennifer , Appert Elizabeth , Lilly Jena , Zhu Yakun , Waanders Angela , Resnick Adam , Storm Jay , Cole Kristina 
Published: December 2020

Abstract
Subsets of pediatric cancers, including high grade glioma (pHGG), have high rates of uniquely long telomeres, associated with ATRX gene mutations and alternative lengthening of telomeres (ALT). Ultimately, these cancers may benefit from a therapy stratification approach. In order to identify and further characterize pediatric brain tumors with telomere lengthening (TL), we determined the intratelomeric content in silico from paired WGS of 918 tumors from CBTTC Pediatric Brain Tumor Atlas (PBTA). The results were highly concordant with experimental assays to determine ALT in a subset of 45 pHGG tumors from the set. Overall, 13% of the PBTA cohort had telomere lengthening. We confirmed the highest rate of TL (37%) in the pHGG cohort (37/100 tumors; 30/82 patients). There was no statistical difference in age, gender or survival in subset analysis. As expected, the patient pHGG tumors with telomere lengthening were enriched for ATRX mutations (60%, q= 1.76e-3). However, 6 tumors without ATRX mutation also had normal protein expression, suggesting a different mechanism of inactivation or TL. The pHGG tumors with telomere lengthening had increased mutational burden (q=8.98e-3) and included all known pHGG cases (n=6) in the cohort with replication repair deficiencies. Of interest, the second highest rate of telomere lengthening was 9 subjects (24%) in the craniopharyngioma cohort. None of the craniopharyngioma tumors had ATRX mutations or low ATRX expression, and 55% of those with TL had CTNNB1 mutations. Finally, lower rates of telomere lengthening were found in medulloblastoma (10%), ependymoma (10%), low grade astrocytoma (8%) and ganglioglioma (7/47, 15%).
QOL-01. LONGITUDINAL COMPARISON OF NEUROCOGNITIVE TRAJECTORIES IN PEDIATRIC MEDULLOBLASTOMA PATIENTS TREATED WITH PROTON VERSUS PHOTON RADIOTHERAPY
Authors: Kahalley Lisa , Peterson Rachel , Ris M Douglas , Janzen Laura , Okcu M Fatih , Grosshans David , Ramaswamy Vijay , Paulino Arnold , Hodgson David , Mahajan Anita , Tsang Derek , Laperriere Normand , Whitehead William , Dauser Robert , Taylor Michael , Conklin Heather , Bouffet Eric , Chintagumpala Murali , Mabbott Donald 
Published: December 2020

Abstract

PURPOSE
By reducing dose to normal brain tissue, proton radiotherapy (PRT) may lessen neurocognitive risk traditionally associated with photon radiotherapy (XRT). We examined change in neurocognitive scores over time in pediatric medulloblastoma patients treated with PRT versus XRT.

METHODS
Neurocognitive scores from 79 patients (37 PRT, 42 XRT) were examined. Patients were treated between 2007–2018 on the same treatment protocols that differed only by craniospinal modality (PRT versus XRT). Change in scores over time since diagnosis were compared between groups.

RESULTS
Groups were similar on most demographic/clinical variables: sex (67.1% male), age at diagnosis (mean 8.6 years), CSI dose (median 23.4 Gy), length of follow-up (mean 4.3 years), and parental education (mean 14.3 years). Boost dose (p&lt;0.001) and margin (p=0.001) differed between groups. Adjusting for covariates, the PRT group exhibited superior outcomes in global IQ, perceptual reasoning, and working memory versus the XRT group (all p&lt;0.05). The XRT group exhibited significant decline in global IQ, working memory, and processing speed (all p&lt;0.05). The PRT group exhibited stable scores in all domains except processing speed (p=0.003). Posterior fossa syndrome imparted risk independent of modality.

CONCLUSION
This is the first study comparing neurocognitive trajectories between pediatric patients treated for medulloblastoma with PRT versus XRT on comparable, contemporary protocols. PRT was associated with more favorable neurocognitive outcomes in most domains compared to XRT, although processing speed emerged as vulnerable in both groups. This is the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.
QOL-06. QUALITY OF LIFE IN MEDULLOBLASTOMA SURVIVORS IN WESTERN MEXICO
Authors: del Campo Regina M Navarro-Martin , Macias-Toscano Jorge L , Toral-Casillas Erika , Sánchez-Zubieta Fernando , Orozco-Alvarado Ana L 
Published: December 2020

Abstract

BACKGROUND
Treatment of children with medulloblastoma (MB) can lead survivors to lidiate with long term sequelae and affect their quality of life (QoL). This study evaluates QoL in long term MB survivors. DESIGN/

METHODS
Clinical files of MB survivors from 1997 to 2016 were retrospectively analyzed. QoL was defined by Schipper Criteria in a five dimensional evaluation: clinical data, physic effects of treatment, academic develop, functional state and self welfare report.

RESULTS
Clinical data: Twenty eight survivors were identified, mean age at review was 18 years, median follow up was 106 months. Functional state: Last visit Karfnosky/lansky were 90 to 80% in 25% of patients. Physic effects of treatment: Cerebellar Mutism or ataxia were present in 25% of cases. Two patients required external dispositives. Audiometry detected an auditive tonal decrease in 25% of cases. An endocrine disfunction was present in 46% of cases, 32% required hormone replacement and 28% having short size. Renal damage without dialysis was detected in 7% and 10% had a transient tubulopaty. One case had bilateral amaurosis and 14% uses glasses. Three patients had a life partner. One female has offspring and two males had azoospermia. Academic development: While 90% attends to school, 35.7% complained of learning difficulties and 18% needed special education. Self welfare report: Difficulties in social environment were described in 21% and 14% still feeling sick during years.

CONCLUSIONS
Survivors of MB had adverse physical effects, followed by academic development, functional state and self welfare report and all this has a negative impact in their QoL.
QOL-13. NEUROCOGNITIVE OUTCOMES ACCORDING TO RISK-ADAPTED TREATMENT REGIMENS FOR CHILDREN OLDER THAN 4 WITH MEDULLOBLASTOMA AND POSTERIOR FOSSA EPENDYMOMA – RESULTS OF THE HIT2000 TRIAL
Authors: Mynarek Martin , Neumann-Holbeck Anne , Resch Anika , Ottensmeier Holger , von Hoff Katja , Traunwieser Thomas , Kortmann Rolf-Dieter , Obrecht Denise , Warmuth-Metz Monika , Bison Brigitte , Pietsch Torsten , Pfister Stefan M , Sill Martin , Kool Marcel , Sturm Dominik , Jones David , von Deimling Andreas , Sahm Felix , Tischler Tanja , Rutkowski Stefan 
Published: December 2020

Abstract

OBJECTIVES
Reduced neuropsychological outcomes are a major concern in pediatric patients with malignant brain tumors. We aimed to estimate decline in cognitive function according to treatment regimens.

METHODS
Cross-sectional analysis of cognitive functions tested with the Neuropsychological Basic Diagnostic tool (NBD) in 279 patients &gt;4 years at diagnosis (median: 8.66; range: 4.01–18.98) with medulloblastoma (n=110, 23.7–25.0Gy CSI; n=131, &gt;30Gy CSI) or posterior fossa ependymoma (n=38 local radiotherapy) who participated in the HIT-2000 trial. Multivariable regression analysis was conducted to adjust for postoperative cerebellar mutism syndrome, preoperative hydrocephalus, postoperative shunt placement, the interval between diagnosis and assessment, sex and age.

RESULTS
Mean time from diagnosis to assessment was 5.1 years. Increasing CSI-dose was significantly associated with a deterioration in performance of most subtests, particularly in areas of fluid intelligence (mean z-values per test for no CSI/23.4Gy/&gt;30Gy respectively: matrix reasoning:-0.40/-0.52/-0.98, p&lt;.001), short-term memory (number recall: -0.07/-0.58/-0.64, p=.002), visuo-spatial skills (visual-motor integration:-0.49/-0.68/-1.12, p&lt;.001) and fine motor skills (dominant-hand:-1.09/-1.80/-2.12, p=.008; non-dominant-hand:-1.47/-2.59/-2.82, p=.003; bimanual coordination:-1.33/-2.68/-2.76, p=.001). These differences were retained after adjustment for confounding variables. Within medulloblastoma patients treated with &gt;30Gy CSI, selective attention, but no other function was reduced in patients treated with pre-radiotherapy chemotherapy including intraventricular MTX (selective attention (with chemotherapy/without chemotherapy mean z-values: -0.66/0.00, p=.006)). Patients with SHH-activated medulloblastoma did significantly better than WNT or Group3/Group4 medulloblastoma patients in fluid intelligence and fine motor skills.

CONCLUSION
CSI dose among other highly relevant factors had significant effects on neuropsychological outcome. Pre-radiotherapy intraventricular MTX had only minor effects. Patients with SHH-activated medulloblastomas showed a more favorable outcome when compared to patients in the other subgroups.
QOL-14. A BIOPSYCHOSOCIAL APPROACH TO BRAIN INJURY REHABILITATION FOLLOWING TREATMENT FOR PAEDIATRIC BRAIN TUMOURS: CAN PHARMACOTHERAPY AID NEUROPSYCHOLOGICAL OUTCOME?
Authors: Phillips Jo , Brougham Mark 
Published: December 2020

Abstract
Long term survival following paediatric brain tumours has vastly improved in recent decades. Consequently there is a drive towards improved quality of survivorship. Brain tumours, surgical resection and adjuvant therapies represent mechanisms for brain injury and can therefore negatively impact a child’s neuropsychological trajectory; affecting cognition, behaviour, emotional and adaptive functioning and educational/occupational outcomes. A biopsychosocial approach to rehabilitation should target each of these domains through supported remediation, environmental modification and psychoeducation for young people and the key systems around them (e.g. families, education). There is a growing evidence base for the role of concordant psychopharmacologies to improve neuropsychological outcome. Since 2015 children treated at RHSC Edinburgh for brain tumours have been offered pharmacotherapy alongside usual rehabilitation approaches if they demonstrate significant difficulties with Attention, Processing Speed and/or Executive Function on formal neuropsychological assessment. Patients are referred to a Consultant Psychiatrist or Paediatrician (as per local protocol) for medication selection, titration and monitoring. A short case series (N=14) is presented outlining brain tumour pathologies, treatment modalities, neuropsychological profile and rationale for recommending pharmacotherapy. Approximately 50% of patients took up the offer. The treatment/s offered and self or parents reported outcomes is summarised. Pharmacotherapy was broadly effective; “it’s been like night and day”, although for one case (N=1) the side effects outweighed any benefit; “she became even more emotional”. Findings indicate that pharmacotherapy should be considered alongside conventional neurorehabilitation techniques for CYP with specific cognitive difficulties following treatment for paediatric brain tumours.
QOL-15. NEURAL NETWORK INTEGRITY FOR FACIAL AFFECT RECOGNITION IN SURVIVORS OF MEDULLOBLASTOMA
Authors: Brinkman Tara , Krull Kevin , Scoggins Matthew , Li Zhenghong , Glass John , Zou Ping , Ness Kirsten , Sabin Noah , Gajjar Amar , Armstrong Gregory , Robison Leslie , Hudson Melissa , Reddick Wilburn 
Published: December 2020

Abstract

BACKGROUND
Medulloblastoma survivors are at risk for social deficits, yet underlying mechanisms are poorly understood.

METHODS
Facial affect recognition was assessed in 50 medulloblastoma survivors treated with craniospinal radiation (median[range] 21.4[12.5–30.9] years old, 11.0[5.7–22.6] years since diagnosis) and 56 non-cancer age-, sex-, and race-matched controls. Brain activation and connectivity in core regions/nodes of the face perception network (fusiform gyri, occipital gyri, superior temporal sulcus) were examined using structural and functional neuroimaging. Structural networks were constructed from diffusion tensor imaging (DTI) data and individual node strength and efficiency were assessed. Functional MRI (fMRI) was conducted using a 1-back facial affect recognition task with assessment of regional differences in task-related cerebral blood flow (BOLD). Standardized neurocognitive testing was completed with 24 hours of brain imaging.

RESULTS
Medulloblastoma survivors performed worse on a behavioral measure of facial affect recognition (P=0.003) compared to matched controls. During the facial affect recognition task, controls demonstrated greater BOLD activation of the left and right fusiform gyri and the left and right middle occipital gyri compared to survivors (P’s&lt;0.05, corrected for multiple comparisons). DTI indicated weaker core node strength in survivors in the right lateral occipital gyri (P=0.02) and efficiency was lower in the left (P=0.01) and right (P=0.03) occipital gyri compared to controls.

CONCLUSIONS
Medulloblastoma survivors have deficits in facial affect recognition and reduced activation and efficiency in brain regions comprising the face perception network compared to matched controls. Interventions targeting this specific skill and neural network may improve social functioning in survivors.
QOL-21. DEVELOPMENT AND UTILISATION OF A NEURO-ONCOLOGY REHABILITATION TEAM: 2018–2019 UPDATE
Authors: Paisley Helen , Hartley Helen , Kearney Anna , Hagan Alex , Owen Joanne , Pizer Barry , Holman Natalie , Kumar Ram 
Published: December 2020

Abstract

INTRODUCTION
A multi-disciplinary Neuro-Oncology Rehabilitation Team (NORT) was established at our institution in 2014. We reviewed NORT inputs, processes and outputs in 2018 to 2019 compared to our previously presented data from 2015, soon after service inception.

METHODS
Retrospective analysis of patients who received NORT input June 2018 - May 2019 compared to 2015 data. Descriptive analysis of changes to NORT operational processes and structure. Complexity of rehabilitation needs was measured using the Rehabilitation Complexity Scale-Extended V13 (RCS).

RESULTS
54 children received NORT input in 2018–2019 (10 children in 2015) with total of 129 outputs. NORT input was highest in children with high grade glioma (median reviews: 3; median RCS: 5) and ependymoma (median reviews: 3; median RCS: 5). Pilocytic astrocytoma formed the largest tumour group (n = 11; median reviews: 2; median RCS: 7). 11% patients were referred to neurologist (9% already known); 17% referred to community services (44% already known); 31% referred to neuropsychology. In 2015, outputs were predominantly referral to occupational therapy and physiotherapy. 6 patients (11% of 54) were discharged in 2018–2019 (40% of 10 patients in 2015). 4 patients died. Between 2015 and 2019, developments included: clarifying referral and discharge pathways, use of screening measures, neuropsychology integration, therapy-led drop-in clinics, use of RCS-E. DISCUSSION: There has been a clear increase in utilisation and scope of work of NORT over last 4 years. The strength of this team is multidisciplinary working and expertise. Further developments planned: multidisciplinary rehabilitation interventions and NORT outcome tools.
QOL-22. MACHINE-LEARNING INFERENCE MAY PREDICT QUALITY OF LIFE SUBGROUPS OF ADAMANTINOMATOUS CRANIOPHARYNGIOMA
Authors: Hengartner Astrid C , Prince Eric , Staulcup Susan , Vijmasi Trinka , Souweidane Mark , Jackson Eric M , Johnston James M , Anderson Richard C E , Naftel Robert P , Grant Gerald , Niazi Toba N , Dudley Roy , Limbrick David D , Ginn Kevin , Smith Amy , Kilburn Lindsay , Jallo George , Wilkening Greta , Hankinson Todd 
Published: December 2020

Abstract

BACKGROUND
Due to disease and/or treatment-related injury, such as hypothalamic, visual, and endocrine damage, quality of life (QoL) scores after childhood-onset Adamantinomatous Craniopharyngioma (ACP) are among the lowest of all pediatric brain tumors. Decision-making regarding management would be aided by more complete understanding of a patients likely QoL trajectory following intervention.

METHODS
We retrospectively analyzed caregiver and patient-reported QoL-instruments from the first 50 patients (ages 1–17 years at diagnosis) enrolled in the international Advancing Treatment for Pediatric Craniopharyngioma (ATPC) consortium. Surveys included 205 pediatric-relevant questions and were completed at diagnosis, and 1- and 12-months following diagnosis. Using Multiple Correspondence Analysis (MCA), these categorical QoL surveys were interrogated to identify time-dependent patient subgroups. Additionally, custom deep learning classifiers were developed using Google’s TensorFlow framework.

RESULTS
By representing QoL data in the reduced dimensionality of MCA-space, we identified QoL subgroups that either improved or declined over time. We assessed differential trends in QoL responses to identify variables that were subgroup specific (Kolmogorov-Smirnov p-value &lt; 0.1; n=20). Additionally, our optimized deep learning classifier achieved a mean 5-fold cross-validation area under precision-recall curve score &gt; 0.99 when classifying QoL subgroups at 12 month follow-up, using only baseline data.

CONCLUSIONs
This work demonstrates the existence of time-dependent QoL-based ACP subgroups that can be inferred at time-of-diagnosis via machine learning analyses of baseline survey responses. The ability to predict an ACP patient’s QoL trajectory affords caregivers valuable information that can be leveraged to maximize that patient’s psychosocial state and therefore improve overall therapy.