bluuebunny/crossref_metadata_2025_split huggingface dataset:
MBRS-44. TIME, PATTERN AND OUTCOME OF MEDULLOBLASTOMA RELAPSE ARE ASSOCIATED WITH TUMOUR BIOLOGY AT DIAGNOSIS AND UPFRONT THERAPY: A COHORT STUDY
Authors: Hill Rebecca , Richardson Stacey , Schwalbe Edward , Hicks Debbie , Lindsey Janet , Crosier Stephen , Rafiee Gholamreza , Grabovska Yura , Wharton Stephen , Jacques Thomas , Michalski Anthony , Joshi Abhijit , Pizer Barry , Williamson Daniel , Bailey Simon , Clifford Steven 
Published: December 2020

Abstract
Disease relapse occurs in ~30% of children with medulloblastoma, and is fatal in the majority. We sought to establish whether clinico-molecular characteristics at diagnosis are associated with the nature of relapse, subsequent disease-course, and whether these associations could inform clinical management. We surveyed the clinical features of medulloblastoma relapse (time-to-relapse, pattern-of-relapse, time-to-death and overall outcome) in 247 centrally-reviewed patients who relapsed following standard-upfront-therapies. We related these to clinico-molecular features at diagnosis, prognostic factors, and first-line/relapse treatment. Patients who received upfront craniospinal irradiation (CSI-treated) displayed prolonged time-to-relapse compared to CSI naïve patients (p&lt;0.001). Similarly, in CSI naïve patients, CSI at relapse, alongside re-resection and desmoplastic/nodular histology, were associated with long-term survival. In CSI-treated patients, the nature of relapse was subgroup-dependent. Local-nodular relapse patterns were enriched in relapsed-MBSHH patients (p&lt;0.001), but a notable proportion (65%) also acquired distant-diffuse disease (p=0.010). MBGroup3 relapsed quickly (median 1.3 years), MBGroup4 slowly (median 2.1 years). Distant-disease was prevalent in MBGroup3 and MBGroup4 relapses (90%) but, in contrast to relapsed-MBSHH, nodular and diffuse patterns of distant-disease were observed. Furthermore, nodular disease was associated with a prolonged time-to-death post-relapse (p=0.006). Investigation of second-generation MBGroup3/4 subtypes refined our understanding of heterogeneous relapse characteristics. Subtype VIII had prolonged time-to-relapse; subtype II a rapid time-to-death. Subtypes II/III/VIII developed a significantly higher incidence of distant-disease at relapse, whereas subtypes V/VII did not. The nature of medulloblastoma relapse are biology and therapy-dependent, providing immediate translational opportunities for improved disease management through biology-directed surveillance, post-relapse prognostication and risk-stratified selection of second-line treatment.
MODL-12. DEVELOPMENT OF A NOVEL IMMUNOCOMPETENT MOUSE MODEL FOR DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Seblani Maggie , Zannikou Markella , Pituch Katarzyna , Ilut Liliana , Becher Oren , Balyasnikova Irina 
Published: December 2020

Abstract
Diffuse intrinsic pontine glioma (DIPG) is a devastating brain tumor affecting young children. Immunotherapies hold promise however the lack of immunocompetent models recreating a faithful tumor microenvironment (TME) remains a challenge for development of targeted immunotherapeutics. We propose to generate an immunocompetent DIPG mouse model through induced overexpression of interleukin 13 receptor alpha 2 (IL13Rα2), a tumor-associated antigen overexpressed by glioma cells. A model with an intact TME permits comprehensive preclinical assessment of IL13Rα2-targeted immunotherapeutics. Our novel model uses the retroviral avian leucosis and sarcoma virus (RCAS) for in vivo gene delivery leading to IL13Rα2 expression in proliferating progenitor cells. Transfected cells expressing IL13Rα2 and PDGFB, a ligand for platelet derived growth factor receptor, alongside induced p53 loss via the Cre-Lox system are injected in the fourth ventricle in postnatal pups. We validated the expression of PDGFB and IL13Rα2 transgenes in vitro and in vivo and will characterize the TME through evaluation of the peripheral and tumor immunologic compartments using immunohistochemistry and flow cytometry. We confirmed expression of transgenes via flow cytometry and western blotting. Comparison of survival dynamics in mice inoculated with PDGFB alone with PDGFB+IL13Rα2 demonstrated that co-expression of IL13Rα2 did not significantly affect mice survival compared to the PDGFB model. At time of application, we initiated experiments to characterize the TME. Preliminary data demonstrate establishment of tumors within and adjacent to the brainstem and expression of target transgenes. Preclinical findings in a model recapitulating the TME may provide better insight into outcomes upon translation to clinical application.
NFB-08. PHASE II STUDY OF AXITINIB IN PATIENTS WITH NEUROFIBROMATOSIS TYPE 2 AND PROGRESSIVE VESTIBULAR SCHWANNOMAS
Authors: Phadnis Sheetal , Hagiwara Mari , Yaffe Anna , Mitchell Carole , Nicolaides Theodore , Akshintala Srivandana , Hochman Tsivia , Goldberg Judith , Allen Jeffrey , Karajannis Matthias 
Published: December 2020

Abstract

INTRODUCTION
Vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor (PDGFR), and c-KIT represent clinically and/or preclinically validated molecular targets in vestibular schwannomas. We conducted a single institution, prospective, open-label, two-stage phase II study (ClinicalTrials.gov identifier NCT02129647) to estimate the response rate to axitinib, an oral multi-receptor tyrosine kinase inhibitor targeting VEGFR, PDGFR and c-KIT, in neurofibromatosis type 2 (NF2) patients with progressive vestibular schwannomas (VS).

METHODS
NF2 patients older than 5 years with at least one volumetrically measurable, progressive VS were eligible. The primary endpoint was to estimate the objective volumetric response rates to axitinib. Axitinib was given continuously in 28-day cycles for up to of 12 cycles. Response was assessed every 3 months with MRI using 3-D volumetric tumor analysis and audiograms. Volumetric response and progression were defined as ≥20% decrease or increase in VS volume, respectively.

RESULTS
Twelve eligible patients (ages: 14–56 years) were enrolled on this study. Seven of twelve patients completed 12 cycles (range: 2 to 12 cycles). We observed two imaging and three hearing responses. Best volumetric response was -53.9% after nine months on axitinib. All patients experienced drug-related toxicities, the most common adverse events were diarrhea, hematuria and skin toxicity, not exceeding grade 2 and hypertension, not exceeding grade 3.

CONCLUSIONS
While axitinib has modest anti-tumor activity in NF2 patients, it is more toxic and appears to be less effective compared to bevacizumab. Based on these findings, further clinical development of axitinib for this indication does not appear warranted.
PATH-13. PLEOMORPHIC XANTHOASTROCYTOMA INTEGRATED GENOMIC CHARACTERIZATION - WHAT HAVE WE LEARNED?
Authors: Vaubel Rachael , Zschernack Valentina , Caron Alissa , Milosevic Dragana , Jenkins Robert , Kipp Benjamin , Rodriguez Fausto , Tran Quynh , Orr Brent , Pietsch Torsten , Giannini Caterina 
Published: December 2020

Abstract
Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma occurring predominantly in children and young adults. It is characterized histologically by large pleomorphic, spindled and lipidized cells with frequent eosinophilic granular bodies and pericellular reticulin deposition. BRAF p.V600E mutation and CKDN2A/B deletion are the most common genetic alterations. We report the integrated genomic characterization of a cohort of 67 patients (37 F, 30 M; median age 20.3 years (interquartile 13.4–32.9) with histologically defined PXA (52, 78%) or anaplastic PXA (A-PXA) (15, 22%), using genome-wide cytogenetic (ThermoFisher Oncoscan, n=67), methylation profiling (Illumina EPIC array, n=43), and targeted next generation sequencing (n=32). BRAF p.V600E mutation (n=51, 76.1%) and CDKN2A/B deletion (n=63; 94%) were the most frequent alterations. Of 16 BRAF p.V600E negative cases, 7 showed an alternative BRAF activating mutation (n=2), NF1 (n=3) mutation or ATG7-RAF1 fusion (n=2). Targeted TERT analysis found promoter mutations in 3 (of 58) cases, but TERT amplification was absent. Supervised and unsupervised methylation profiling against a comprehensive reference cohort demonstrated consensus grouping with the PXA class in 36 of 43 cases; while the minority grouped with a ganglioglioma class (n=3), with reactive brain or had no resolvable subgroup (n=4). Follow-up was available in 61 patients (91.0%) (median 63 months). Overall survival was significantly different between PXA and A-PXA (5-year:80.4% vs. 55.1%; p=0.001), but not progression-free survival (5-year:61.7% vs. 39.8%; p=0.128). Our data confirm the high frequency of MAP-K abnormalities and CDKN2A/B deletion in PXA. WHO grade remains a strong predictor of patient overall survival.
QOL-26. I’VE GOT FRIENDS NOW: PAEDIATRIC PATIENTS’ EXPERIENCES OF METHYLPHENIDATE TREATMENT FOR NEUROCOGNITIVE LATE-EFFECTS ASSOCIATED WITH BRAIN TUMOUR
Authors: Verity Sarah , Hill Rebecca , Halliday Gail , Ryles Jade , Bailey Simon 
Published: December 2020

Abstract

BACKGROUND
Whilst rates of survival following paediatric brain tumour have increased, quality of survival continues to present a significant challenge to children and their families. The neurocognitive impact of cranial radiotherapy (CRT) in childhood upon future intellectual development is well established. Both CRT and chemotherapy are associated with medium-term slowed speed of cognitive processing, attention, and memory impairment, and with longer-term failure to achieve pre-morbid intellectual potential and low Health-Related Quality of Life (HRQoL).Methylphenidate is a psychostimulant drug shown to be effective in alleviating some of the neurocognitive symptoms of cancer treatment, however the subjective experience of paediatric participants is not reported. AIM: The current study aimed to explore the subjective experience of HRQoL in paediatric neuro-oncology patients currently receiving methylphenidate.

METHODS
A retrospective audit was conducted on 12 paediatric neuro-oncology patients in receipt of methylphenidate. Both standardised and novel measures were used to assess aspects of HRQoL, specifically; social life, perceived independence, mood, confidence, school life, self-esteem, interpersonal relationships and fatigue levels. Data collected were analysed using Thematic Analysis.

RESULTS
Five key themes were identified; physical, emotional, social, academic and neuropsychological impact.

CONCLUSION
The current findings evidence the perception of patients that methylphenidate supported them to regain previously lost functionality. Methylphenidate has the potential to increase HRQoL in this population and to provide children with the opportunity to regain a sense of normality in their lives.
QOL-41. CARDIAC DYSFUNCTION IN MEDULLOBLASTOMA SURVIVORS TREATED WITH PHOTON IRRADIATION
Authors: Cacciotti Chantel , Chordas Christine , Valentino Kate , Allen Rudy , Manley Peter , Pillay-Smiley Natasha 
Published: December 2020

Abstract

BACKGROUND
Medulloblastoma is an aggressive central nervous system (CNS) tumor that occurs mostly in the pediatric population. Treatment includes surgical resection, craniospinal radiation (CSI) and chemotherapy. Children who receive standard photon radiation (RT) are at risk for cardiac toxicities. Potential late effects include coronary artery disease, left ventricular scarring and dysfunction, valvular damage and atherosclerosis. Current survivorship guidelines recommend routine ECHO surveillance for these patients but this comes at significant health care costs over a lifetime. We describe the experience of cardiac dysfunction in medulloblastoma survivors in a multi-institution study.

METHODS
A retrospective chart review of medulloblastoma patients treated between 1980 and 2010 with radiation at Lurie Children’s Hospital and Dana-Farber/ Boston Children’s Hospital who had an echocardiogram done following completion of therapy.

RESULTS
168 patients were treated for medulloblastoma during the study time. Of whom, 80 patients had echocardiogram follow up and 76 received photon irradiation. The latter were included in the study. The mean age at CSI was 8.6 years (range 2.9- 20), and mean number of years post RT at echocardiogram 7.4 years (range 2–16). Mean ejection fraction (EF) was 60.03% and shortening fraction (SF) 33.8%. Four patients (5%) had abnormal results, all of which had EF&lt;50%.

CONCLUSION
Patients who received craniospinal irradiation for medulloblastoma therapy have relatively normal echocardiograms post treatment. Although RT may result in cardiac risks, echocardiograms may not be the most cost effective or efficacious mode to evaluate the risk in these survivors long term.
RARE-12. VASCULOPATHY IN PEDIATRIC CRANIOPHARYNGIOMA PATIENTS TREATED WITH SURGERY AND RADIOTHERAPY
Authors: Lucas John , LeVine David , Ismael Yousef , Hsu Chi-Yang , Darrow Kaleb , Faught Austin , Moskvin Vadim , Pilepesov Fakhriddin , Sabin Noah , Boop Frederick , Klimo Paul , Elijovich Lucas , Merchant Thomas 
Published: December 2020

Abstract

PURPOSE
As much as 40% of pediatric brain tumor patients will experience varied levels of Vasculopathy (VS), however few predictive factors have been described. Here we describe the type and timing of VS and explore the relationship between treatment modality and the timing, location, and distribution of VS.

METHODS
94 pediatric Craniopharyngioma patients underwent surgery and proton radiotherapy. Pre- and post-treatment imaging, cumulative physical and biological proton dose maps, clinical characteristics, and measures of dyslipidemia were evaluated. MR and MRAs were evaluated for pre- and post-radiotherapy VS (type, workup, location, and severity). VS events were segmented and described according to their normal brain region, and vascular territory.

RESULTS
47 patients were found to have 154 confirmed VS of varying severity with a median time to event of 3.41 years 95% CI 3.08–3.88. 22% (N=21) of patients had ≥1 pre-existing instances of VS and 26.6% (N=25) had a dyslipidemia at diagnosis. Forty-six (48.9%) patients had evidence of VS post-RT with 9.5% (N=9) being clinically significant. Aspirin was recommended in 10.6% (N=10) patients. Only 4 (4.2%) patients required revascularization. Clinical characteristics were not predictive of VS. An increased frequency of VS were observed along the operative corridor and high-dose radiotherapy field.

CONCLUSIONS
VS often precedes radiotherapy necessitating appropriate baseline imaging. Surgery type and extent are interrelated to the risk for radiotherapy-induced VS. While the spatial radiotherapy dose distribution approximated most vascular injury events, it was not all-inclusive. Spatial modeling of biological and physical dose may offer insights into therapy related vascular injury.
RARE-39. MOLECULARLY CONFIRMED ATYPICAL CHOROID PLEXUS PAPILLOMA WITH INTRACRANIAL DISSEMINATION
Authors: Yanagi Masato , Fukuoka Kohei , Matsushita Yuko , Hibiya Yuko , Honda Satoko , Mori Makiko , Arakawa Yuki , Ichimura Koichi , Tanami Yutaka , Nakazawa Atsuko , Kurihara Jun , Ko Katsuyoshi 
Published: December 2020

Abstract

INTRODUCTION
Among choroid plexus tumors (CPTs), metastasis occurs more frequently as pathological grading increases. There could be an underestimation of pathological diagnosis if disseminated CPTs are diagnosed with lower grade tumors such as choroid plexus papilloma (CPP) or atypical choroid plexus papilloma (aCPP). Thus, molecular diagnosis using genome-wide DNA methylation profiling may be useful to clarify malignant potential among thetumor entity. Here, we report about a case of aCPP with intracranial dissemination that was molecularly diagnosed by methylation profiling. CASE DESCRIPTION: A 2-year-old girl presented with a history of vomiting. Brain magnetic resonance imaging showed a large tumor mass in the right lateral ventricle and diffuse enhancement surrounding her brainstem, which suggested dissemination. Gross total resection of the mass was performed. Intraoperative findings revealed multiple spot metastatic lesions on the inner wall of lateral ventricle. The pathological diagnosis was aCPP owing to the presence of a glandular structure with a papillary pattern suggesting a neoplasm of epithelial origin, increased cellularity, several necrotic areas, and an intermediate number of mitoses. The CPT-SIOP-2000 treatment protocol was followed without radiation therapy, and the disseminated lesion was disappeared during the chemotherapy. Methylation data of the current case was entered into a recently published classifier, and the tumor was classified as methylation class “plexus tumor, subclass pediatric A” with high confidence (calibrated score 0.96), which includes cases diagnosed as CPP and aCPPs.

CONCLUSION
Our case indicates the clinical significance of molecular confirmation of diagnosis among CPTs, particularly lower grade tumors with dissemination.
RONC-03. NEUROCOGNITIVE CHANGES AFTER RADIATION FOR PEDIATRIC BRAIN TUMOURS: WHICH BRAIN SUBSTRUCTURES ARE MOST IMPORTANT?
Authors: Tsang Derek S , Kim Laurence , Mabbott Donald , Khandwala Mohammad , Liu Zhihui Amy , Laperriere Normand , Janzen Lauran , Dama Hitesh , Ramaswamy Vijay , Keilty Dana , Bouffet Eric , Hodgson David C 
Published: December 2020

Abstract

INTRODUCTION
The contribution of different intracranial structures on neurocognitive decline after radiation therapy (RT) in children is unclear.

METHODS
This was a retrospective study of children with brain tumours treated from 2005 to 2017. Patients with longitudinal neurocognitive assessments and photon dosimetric data (if RT given) were included. Full scale intelligence quotient (FSIQ) was the primary endpoint; sub-indices of neurocognition were modelled separately (perceptual reasoning [PRI], processing speed [PSI], verbal comprehension [VCI] and working memory [WMI]). Multivariable linear mixed effects models were used to model endpoints, with age at diagnosis & dose to different brain regions as fixed effects and patient-specific random intercepts.

RESULTS
Sixty-nine patients were included; ten patients did not receive any RT (i.e. low-grade glioma). Median neurocognitive follow-up was 3.2 years. Right hippocampus mean dose was a strong predictor of declines in FSIQ (p &lt; .001), VCI (p = 0.002) and PRI (p = 0.049). Dose to 50% of the supratentorial brain (D50) was the strongest predictor for WMI (p &lt; .001) and PSI (p &lt; .001). Each gray increase in mean right hippocampus dose resulted in a decrease of 0.038 FSIQ points/year. After adjusting for dose to brain substructures, younger age & presence of a ventriculoperitoneal shunt were also associated with decreased FSIQ.

CONCLUSIONS
Mean dose to the right hippocampus was associated with declines in FSIQ, VCI and PRI, while supratentorial brain D50 was associated with WMI and PSI. Efforts should be made to reduce unnecessary dose to these brain structures.
SURG-15. THE SURGERY OF THALAMIC LESIONS IN PEDIATRIC BRAIN TUMORS
Authors: Shimizu Yuzaburo , Akiyama Osamu , Kondo Akihide 
Published: December 2020

Abstract

BACKGROUND
Pediatric brain tumors are occurred in the center of central nervous system. Since mid-line glioma has defined in the new classification, thalamus has attracted attention as a site that requires surgical intervention. However, the surgery for thalamus is a challenging procedure for neurosurgeons. In this study, we studied our surgical cases of patients suffering from pediatric brain tumors in thalamus and/or thalamic regions to evaluate the safety of surgeries and the consideration of appropriate surgical approaches.

METHODS
We reviewed neuroradiological images, medical record, and, surgical videos for the assessment of surgical fields in patients under the age of 15 who had surgical treatments at our institution.

RESULTS
We had six cases that could be analyzed. The lesions in the posterior parts of the thalamus had been operated by the occipital transtentorial approach. The lesions in the superior parts of thalamus were treated with transcortical transventricle approach. It was possible to achieve sufficient removal of tumors and have good surgical view. The monitoring of motor function and visual function was used in all cases. After removal, we could have a nice view of the important structures around thalamus.

CONCLUSIONS
The surgeries for thalamus and thalamic regions were safety with enough considerations for neurological examinations and radiological imaging. The intra operative monitoring for motor and visual function should be used.
TBIO-17. INTEGRATIVE ANALYSES OF BRAFv600e MUTATED GLIOMAS: FROM MOLECULAR BIOLOGY TO RADIOLOGY AND TREATMENTS
Authors: Lhermitte Benoit , Guerin Eric , Ruhland Elisa , Sebastia Consuelo , Chammas Agathe , Fuchs Quentin , Bund Caroline , Namer Izzie Jacques , Dontenwill Monique , Entz-Werle Natacha 
Published: December 2020

Abstract
BRAFv600e mutation is encountered mostly in low-grade pediatric gliomas (LGG) and epileptogenic glioneuronal tumors, such as gangliogliomas (GG). Less frequently this mutation is present in high-grade glial (HGG) or glioneuronal tumors. Recent publications were highlighting BRAF mutation and CDKN2A deletion, as independent prognostic factors linked to a worst outcome in LGGs. We studied retrospectively a monocentric cohort of 12 LGGs (9 GG and 3 pilocytic astrocytomas) and 9 HGG (5 “de novo” tumors and 4 with a long past of LGG evolution) with BRAFv600e positivity. The patients were aged from 1 to 47 years. LGGs were under 20 years and only 3 patients with HGGs had less than 18 years. We focused on extended tumors’ biology assessment by DNA single-cell analyses, RNAsequencing, NGS, metabolomics, radiology (MRI, PET-scanning and spectroscopy) and correlated them to tumor’s data. One LGG had a CDKN2A deletion. Six had a complete surgical resection, 2 had a minimal residue and 4 had chemotherapies after partial surgery and relapsed. All HGGs had a surgical resection followed by chemotherapy and radiotherapy and additional CDKN2A deletion. Two pediatric HGGs relapsed rapidly. Only one benefited positively from targeted therapy. Specific radiological and spectroscopic signs were linked to the BRAF mutation itself and those different groups (LGGs, HGGs and LGGs with long term evolution of HGG), where specific molecular pathways and metabolomic profiles are associated. Currently, we are going further in the correlations to be able to predict in LGG their potential long-term evolution, where MAPK pathway modulations might be involved.