bluuebunny/crossref_metadata_2025_split huggingface dataset:
EPID-06. PEDIATRIC BRAIN TUMOUR DIAGNOSTIC DELAY DURING COVID-19 PANDEMIC IN A REGIONAL NEURONCOLOGY CENTRE
Authors: Mucelli Martina Pozzi , Toniutti Maristella , Pedicini Sara , Liguoro Ilaria , D’Agostini Serena , De Colle Maria Cristina , Tuniz Francesco , Vindigni Marco , Pegolo Enrico , Coassin Elisa , Mascarin Maurizio , Cogo Paola Elisa , Pilotto Chiara 
Published: June 2024

Abstract

BACKGROUND
The Pediatric Central Nervous System (CNS) tumors incidence has increased in the last decades. A diagnostic delay could be related to adverse effects involving neurosurgical approach. Moreover, many studies report that Coronavirus-19 pandemic has even increased the diagnostic delay of solid tumors, in particular CNS types.

METHODS
We conducted a retrospective study including all pediatric patients who received a diagnosis of CNS tumor at Udine Hospital between January 2020 and December 2021. Our first aim was to assess if there has been a variation in the incidence rate and a possible diagnostic delay of CNS pediatric tumors during 2020-2021. As a secondary objective we evaluated if the Coronavirus-19 pandemic has affected our ability to identify tumor relapses caused by delays in planning follow-up exams and imaging. Data of every patient were recorded and compared with data from a historical cohort recruited between 2000 and 2011.

RESULTS
25 patients were enrolled in the study: 19 (11 males) were diagnosed with a primitive CNS tumor, 7 (3 males) with a secondary lesion. Incidence rate during 2020-2021 was 5.17 per 100.000 inhabitants (age 0-18 years) and median diagnostic interval was 6.7 weeks, both higher than in the historical cohort (but not statistically significant). Median age was 10 +/- 4,7 age (IQR 25°-75°5,9-13,7). No substantial variation of clinical presentation was detected, although some symptoms were found to be more frequent than in the past. A significant rise in the number of high histological grade tumors was recorded (63% vs 12%, p value &lt; 0.001), but there was no difference in tumor relapses diagnostic delay (median 6,7 weeks compared with 5 weeks in historical cohort).

CONCLUSIONS
Coronavirus-19 pandemic had no impact in diagnostic delay, planning and execution of follow-up exams in children with CNS tumors.
EPID-08. PEDIATRIC GLIOMA IN INDONESIA: CLINICAL PROFILES AND OUTCOMES
Authors: Rahmartani Ludi Dhyani , Budiarso Michael Nathaniel , Susanto Eka , Amal Mohamad Yanuar ,   Handoko., Nuryadi Endang , Gunawan Kevin 
Published: June 2024

Abstract

BACKGROUNDS
Gliomas are the most common form of pediatric brain tumor. The primary obstacle to optimizing pediatric brain tumor health services, particularly in LMICs, is the lack of comprehensive epidemiological data. We aim to compile comprehensive data on pediatric gliomas, focusing on clinical profiles and outcomes within a national general hospital in Indonesia.

METHODS
A retrospective observational longitudinal study was performed at Cipto Mangunkusumo National General Hospital, focusing on glioma patients’ profiles and outcomes, registered under the pediatric CNS tumor service from January 2022 to December 2023.

RESULTS
Out of 50 suspected glioma patients, 28 patients (56%) underwent biopsy, 28% underwent other modalities (brainstem location), 12% were scheduled for surgery but had already died, 2% were in a watchful waiting mode, and 2% were scheduled for surgery but were lost to follow-up. Glioma-confirmed patients were predominantly female (57.1%), with a mean age of 7.11 ± 4.98. Low-grade gliomas predominated at 57.1%, a trend we attribute to Cipto Mangunkusumo’s status as a referral national hospital, where low-grade glioma cases may have been managed more frequently at lower-level hospitals. The majority of tumors were supratentorial (53.6%) compared to infratentorial (39.3%) and supra-infratentorial (7.1%). The most common symptoms were seizures (25%), followed by headaches (21.4%), disequilibrium (14.3%), and vomiting (10.7%). Moreover, the latter three symptoms exhibited a longer mean delay between symptom onset and medical consultation, potentially impacting prognosis. In the last follow-up, higher-grade gliomas demonstrated a significantly higher mortality rate at 28.6% compared to low-grade gliomas at 3.6% (P &lt; 0.001).

CONCLUSION
Given the variable clinical characteristics of glioma tumors, these results underscore the urgent need for comprehensive epidemiological data on pediatric gliomas in Indonesia, particularly regarding prognosis-related factors. Such data could serve as a crucial step towards future research and clinical strategies aimed at improving outcomes for children with gliomas.
METB-03. SOLID PEDIATRIC TUMORS IN MICE REVEAL MODEL-SPECIFIC GLOBAL DNA METHYLATION AND CNV PROFILES CORRESPONDING TO HUMAN COUNTERPARTS
Authors: Schoof Melanie , Zheng Tuyu , Sill Martin , Imle Roland , Hofmann Nina , Ernst Kati , Vonficht Dominik , Chan Chun Ho , Cais Alessia , Holland-Letz Tim , Postlmayr Andreas , Shiraishi Ryo , Wang Wanchen , Morcavallo Alaide , Spohn Michael , Göbel Carolin , Niesen Judith , Peter Levke-Sophie , Eckhardt Alicia , Bourdeaut Franck , Han Zhi-Yan , Pei Yanxin , Murad Najiba , Swartling Fredrik J , Taylor Jessica , Gilbertson Richard J , Dottermusch Matthias , Kerl Kornelius , Glass Rainer , Cheng Jiying , Horstmann Martin A , Nollau Peter , Wolters-Eisfeld Gerrit , Zhao Haotian , Sturm Dominik , Chesler Louis , Haas Simon , Weiss William A , Northcott Paul A , Kutscher Lena M , Stücklin Ana Guerreiro , Ayrault Olivier , Neumann Julia E , Kawauchi Daisuke , Jones David , Pfister Stefan M , Pajtler Kristian , Banito Ana , Schüller Ulrich , Zuckermann Marc 
Published: June 2024

Abstract

BACKGROUND
The analysis and comparison of global DNA methylation patterns has become a gold standard in modern neuropathology. For human central nervous system (CNS) tumors and other cancers, the research community has collected thousands of methylation profiles, leading to the discovery and definition of numerous molecularly distinct tumor types and subtypes. Although reliable preclinical mouse models are essential for the understanding of tumor development and the validation of therapeutic approaches, such DNA methylation analyses have so far not been systematically performed for murine tumors owing to technical limitations.

METHODS
We employed the Illumina Bead Chip 285k mouse methylation array to profile ~500 samples covering 90 different mouse models representing 33 pediatric solid tumor types, including CNS tumors and sarcomas from 18 laboratories. We compared DNA methylation profiles of these models between each other and to human CNS tumors, performed immune cell deconvolution and conducted an in-depth analysis of copy number variants (CNVs) during tumor evolution.

RESULTS
Unsupervised clustering showed that mouse models form groups of their presumed tumor types. Using a tailor-made cross-species analysis based on syntenic CpG sites, we found that most tumors also group with their corresponding human counterparts. Immune cell deconvolution revealed distinct tumor microenvironments that showed clear similarities to human tumors. We further identified recurrent, model-specific CNVs that are syntenic to genomic aberrations in respective human tumors, suggesting an essential role of CNVs during tumor initiation or maintenance.

CONCLUSION
We provide a global resource of well characterized pediatric solid cancer models representing numerous different tumor types. Our comparative analyses reveal novel molecular model characteristics and validate their reliability as human disease models. Our data provide new biological insights into immune composition, tumor cell identities and tumor development by identifying model-specific CNV profiles.
METB-06. PEDIATRIC BRAIN TUMOURS: A SINGLE INSTITUTIONAL EXPERIENCE OF NEXT GENERATION SEQUENCING-BASED TARGETED PANEL EVALUATION
Authors: Epari Sridhar , Bapat Prachi , Gurav Mamta , Shetty Omshree , Shah Aekta , Sahay Ayushi , Prasad Maya , Sahu Arpita , Singh Vikash , Shetty Prakash , Moiyadi Aliasgar , Dasgupta Archya , Chatterjee Abhishek , Chinnaswamy Girish , Gupta Tejpal 
Published: June 2024

Abstract

BACKGROUND
Pediatric brain tumours (pBT) are molecularly diverse and with the advent of targeted-therapies it is important to decipher molecularly.

METHODS
Single institutional non-consecutive pBT (&lt;18 years) cohort include – a. high-grade glial tumour (HGG; H3-wildtype, IDH1/2-wildtype, immunohistochemically MMR-protein-proficient, negative for NTRK/ALK-rearrangements by FISH in &lt;3 years), b. high-grade CNS neuroepithelial tumour, NOS (cNET), c & d. pilocytic astrocytoma (LGG-PCA), and low-grade glial/glioneuronal tumour LGG-LGGNT), histologically not typical of PCA nor any defined entity that were negative for BRAFV600mutations, KIAA1549- BRAF (16-9, 15-9, & 16-10) fusions, e. low-grade glial tumour with diffuse architecture (LGG-DLGG) that were negative for IDH1R132/IDH2R172-mutations. These were evaluated for NGS-based-panel (42 genes, 137 RNA fusions, and 24 genes for amplification – STS-plus-panel Sophia Genetics).

RESULTS
41 cases (HGG: 12, cNET:2, LGG-PCA: 10 & 1, LGG-LGGNT: 13 & LGG-DLGG: 3) formed the study-cohort. a. HGG: 5 were &lt;3 years (supratentorial [ST]: 3; posterior-3rd-ventricular [p3v]: 1 & posterior-fossa [PF]: 1), 2 showed mutations in TP53-exons 5 & 6 respectively, one ST case showed SND1-AKT2 (9:7) fusion. Of 6-18 years (all ST location), 3 showed TP53-mutations, one showed PDGFA & KIT-amplification with SF3B1-mutation and one showed BRAFV600E-mutation. b. cNET: BRAFV600E and TP53-mutation was observed in each of the case respectively. c. LGG-PCA: one case showed FAM131B-BRAF (2:9) fusion. One KIAA1549- BRAF (15-9) fusion case was evaluated as it progressed, showed additional TP53-mutation. d. LGG-LGGNT: one (4/F; PF location) showed EGFR-gains with TERT-promoter (C228T) mutation (like adult-type glioma), one showed NF1-exon 12 mutation with KIAA1549-RAD51 (18:4) fusion, one showed CDKN2A-exon 2 mutation and one (midbrain) case showed BRAFV600E-mutation. e. LGG-DLGG: one (11/M, occipital-SOL) showed KEAP1-exon 5 mutation with KIAA1549- BRAF (15:9) fusion.

CONCLUSIONS
TP53-mutations is common in HGG, infantile HGG can show non-ALK/NTRK fusions. LGG can show non-BRAF/KIAA1549-fusions, rarely can show KEAP1 mutations and adult-type-like alterations. Target-panel NGS-based assay can help to molecularly decipher to a certain extent, especially for instituting targeted-therapies.
METB-09. VARIANT WORKBENCH IN THE KIDS FIRST PROGRAM FACILITATES GENOMIC DISCOVERIES IN PEDIATRIC NEURO-ONCOLOGY RESEARCH
Authors: Guo Yiran , Li Qi , Rozowsky Jare , Costanza Jeremy , Mattioni Michele , Thibert Jean-Philippe , Brown Miguel , Higgins David , Zhu Yuankun , Heath Allison , Resnick Adam , Ferretti Vincent 
Published: June 2024

Abstract
The Gabriella Miller Kids First Pediatric Research Program (Kids First) aims at facilitating researchers to uncover new insights into the biology of childhood cancer and structural birth defects, including the discovery of shared genetic pathways between these disorders. Kids First Data Resource Center developed the Kids First Data Resource Portal (KFDRP), which is a centralized data platform for both Kids First and collaborative cohorts. Currently, KFDRP facilitates data access for 40 studies with over 35,500 participants. To assist researchers and clinicians in identifying potential disease-causing germline variants in the human genome, KFDRP released the Variant WorkBench (VWB), which facilitates variant querying, manipulation, analysis, and visualization. Cavatica is a widely used bioinformatics analysis platform developed by Velsera. Compared to a previous version, the Cavatica-based VWB has better support for data import/export, more convenient sharing of notebooks and data, and easier billing details, with the same level of scalable, cloud-based computing. Additionally, Cavatica-based VWB has incorporated multiple public reference databases, including Cancer Hotspots, ClinVar, COSMIC, dbNSFP, gnomAD, TOPMed, as well as gene-phenotype links provided by OMIM, HPO, Orphanet, and the Deciphering Developmental Disorders Project. These databases have been converted to parquet files, reducing process time and memory usage compared to regular text files, thus speeding up data retrieval and querying. Furthermore, Cavatica empowers users to create and share custom analysis workflows tailored to specific research questions and datasets, enhancing data utility and analysis accuracy. Here we present a gene-based variant filtering workflow that aggregates information from dbNSFP, HGMD, TOPMed, gnomAD, and ClinVar. We identified 1202 pathogenic/likely pathogenic variants in NF1, a gene that helps regulate cell growth, across 582 pediatric brain tumor samples within 6 mins. Among the variants, there are 21 protein-altering variants. Overall, the upgraded VWB is more powerful, user-friendly, and adaptable.
METB-12. GIFT FROM A CHILD POSTMORTEM SPECIMEN DATASET EXTENSION OF THE PEDIATRIC BRAIN TUMOR ATLAS EMPOWERS PEDIATRIC BRAIN TUMOR RESEARCH
Authors: Koptyra Mateusz P , Diarra Noni , Rokita Jo Lynne , Chroni Antonia , Frenkel Beth , Anthony Ciana , Kraya Adam , Baubet Valerie , Biluck Ian , Sullivan Catherine , Coleman Noel , Seip Lauren , Lilly Jena , Santi Mariarita , Viaene Angela , Storm Phillip B , Resnick Adam C , Child On Behalf Of Gift From A 
Published: June 2024

Abstract

BACKGROUND
Pediatric brain and spinal cord tumors are the leading cause of cancer-related mortality in children. An incomplete understanding of brain tumor biology and associated limited access to high-quality biological samples for research are the main factors driving the lack of clinical therapeutic development for pediatric brain tumors that recur or progress. Post-mortem tissue donation provides an unprecedented resource for addressing some of these limitations.

METHODS
The Gift from a Child (GFAC) program by the Swifty Foundation has a unique mission to increase post-mortem pediatric brain tissue donations through advocacy as well as the education of clinicians and families. Through GFAC’s strategic collaboration with the Children’s Brain Tumor Network (CBTN), CBTN has leveraged postmortem tissue to expand the Pediatric Brain Tumor Atlas (PBTA), a cross-histology multi-omics atlas resource. As part of the effort CBTN has sequenced and released data for over 350 post-mortem pediatric brain tumor specimens including multiple brain region sampling cases with specimen and sequencing quality metrics.

RESULTS
Here we present an assessment of postmortem samples and available multi-omic data on postmortem samples within the PBTA dataset. Data have been harmonized and released with no publication embargo. To access data, researchers can utilize existing open source data resources and platforms including PedCbioPortal and OpenPedCan to: (1) Identify tumor spatial and temporal specific alterations (2) Establish tumor evolution trajectory leading to therapeutic resistance and tumor progression; (3) Understand tumor heterogeneity longitudinally across multiple ‘omics layers; and (4) Identify and request specimens and derived tumor models.

CONCLUSIONS
Together, we present the largest deeply characterized cohort of postmortem pediatric brain tumor samples as powerful expansion of the PBTA cohort of &gt;3,000 pediatric brain tumors. CBTN’s open-science model supported by the GFAC mission highlights the value and utility of autopsy-based specimen collection on behalf of improving outcomes for children with brain tumors.
METB-15. ROLE OF DNA METHYLATION PROFILING IN THE MANAGEMENT OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS: A SINGLE INSTITUTIONAL SERIES
Authors: Sato Mariko , Sharma Prachi , Navalkele Pournima , Pathare Jody , Abdullae Zied , Aldape Ken , Crawford John 
Published: June 2024

Abstract

BACKGROUND
DNA methylation profiling has now been integrated into the WHO classification of CNS tumors and serves as confirmatory means to diagnose CNS tumors in conjunction with genetic sequencing/microarray analysis. The practical impact on patient care in the retrospective and prospective settings is less known.

METHODS
Methylation analysis was performed on a cohort of previously and newly diagnosed children with CNS tumors at Children’s Hospital Orange County from 2022-2023. Data regarding histologic diagnosis, integrated molecular diagnosis, methylation classification, timing of result completion and functional impact of methylation results on patient diagnosis/management was evaluated.

RESULTS
Forty patients (21 boys, ages 5 weeks-17 years) with previously diagnosed (N=11) or newly diagnosed (N=21) CNS tumors were evaluated by methylation analysis at one or more institutions. The most common tumor types were diffuse type pediatric high-grade glioma (N=6) and ependymoma PFA (n=4). Methylation analysis revealed no match in two cases (ALK-EML4 fusion embryonal tumor and recurrent low grade glioneuronal tumor) and had insufficient DNA extraction in one patient with low grade glioneuronal spinal cord tumor. Among the 5 tumors with duplicate methylation analyses at two institutions, three Ependymoma PFA subgroups were concordant while two showed differing classifications (diffuse type pediatric high-grade glioma RTK1 subtype vs. non- classifiable and medulloblastoma group 4 vs. non-WNT, non-SHH). In patients with previously diagnosed CNS tumors, methylation either led to a change in classification or modification of diagnosis in 7 out of 11 patients. The average time from surgery to the receipt of methylation results for newly diagnosed patients was 24 days (range 4-90 days).

CONCLUSION
Methylation analysis was beneficial in both the previously diagnosed and newly diagnosed setting in patients with previously difficult to classify tumors following conventional molecular analysis. Changes in tumor classification or modifications in diagnosis were observed in the majority of patients.
GCT-10. OUTCOME OF CHILDREN AND ADOLESCENTS DIAGNOSED WITH GERMINOMA WITH HCGΒ VALUES BETWEEN 100-200 MUI/ML TREATED ACCORDING TO THE BRAZILIAN CNS GCT PROTOCOL
Authors: Aguiar Carol S , Dassi Natália , Mançano Bruna , Epelman Sidnei , Aguiar Simone S , Silva Nasjla S , Finlay Jonathan L , Cappellano Andrea M 
Published: June 2024

Abstract

BACKGROUND
Primary central nervous system (CNS) germ cell tumors (GCT) are rare tumors, classified according to histological components and tumor markers (TM) as Germinomas and Non-Germinomatous Germ Cell Tumors (NGGCT). The aim of this study is to assess the outcome of patients with Germinoma and HCGβ levels between 100-200mIU/ml treated according to the Brazilian CNS GCT Consortium Protocol.

METHODS
From 2013 to 2021, forty-three patients presented with histological and/or TM (serum and CSF) consistent with the diagnosis of germinoma, five of them with HCGβ levels between 100-200mIU/ml. The treatment plan performed was four cycles of carboplatin/etoposide followed by whole ventricular field irradiation (WVFI) of 18Gy with a boost to primary site(s) up to 30Gy and 24Gy craniospinal irradiation (CSI) for disseminated disease.

RESULTS
Average age 13.7 years (6.3-20.3 years), four males and one female. Diagnosis was made by TM (n=2), and biopsy +TM (n=3). The primary tumor location was pineal (n=2), suprasellar (n=1), and bifocal (n=2) with 1 case presenting ventricular spread at diagnosis. Three patients achieved complete response (CR) after two cycles of chemotherapy and one after four cycles. One patient showed partial radiological response (PR) with negative TM after four cycles and was submitted to a second-look surgery, with pathological report of residual scar tissue. Radiotherapy was performed as described in all patients with four patients receiving WVFI (18Gy+30Gy) and one CSI (24Gy+30Gy). In a mean follow-up of 64 months, overall and event-free survival was 100%.

CONCLUSION
Despite the small sample, the present study shows effectivity with excellent results and a possibility of increasing the cutoff and therefore reducing treatment for patients with HCGβ at levels up to 200mlU/ml currently treated in some protocols as NGGCT cases.
GCT-12. OUTCOMES OF INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOURS (NGGCT) TREATED AT A SINGLE UK PROTON CENTRE ACCORDING TO UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG) GUIDANCE, INCLUDING EARLY IMPROVED OUTCOMES USING WHOLE VENTRICULAR RADIOTHERAPY (WVRT) FOR LOCALISED DISEASE
Authors: Goyal Love , France Anna , Gaito Simona , Colaco Rovel J , Pan Shermaine , Saunders Daniel , Thorp Nicola , Murray Matthew J , Nicholson James C , Ajithkumar Thankamma V , Whitfield Gillian A 
Published: June 2024

Abstract

BACKGROUND
After SIOP-CNS-GCT-II closed in 2018, the CCLG recommended, with caveats, following standard trial arms: 4 Cisplatin-Etoposide-Ifosfamide (PEI) cycles, then focal radiotherapy (FRT) (54Gy/30fractions) to primary site(s) for localised NGGCT and craniospinal-irradiation (CSI) (30Gy/20fr) + boosts (24Gy/15fr cranial, 20.8Gy/13fr spinal) for metastatic disease. Since 04/2021, the CCLG formally recommended adding WVRT (24Gy/15fr) for localised NGGCT, and considering 2x standard, 2x high-dose PEI for high-risk (HR) cases (diagnostic AFP&gt;1000ng/ml).

METHODS
Retrospective review of all CNS-NGGCT patients referred 12/2018-06/2023. We collected patient, tumour and treatment factors, acute toxicities (CTCAE grade≥3), and event-free survival (EFS) from radiotherapy until 09/2023.

RESULTS
Twenty-four patients (21M:3F) included, 14 localised (4xHR), 10 (including 2 incompletely staged) treated as metastatic (3xHR). Median age 11 years, median follow-up 16 months (m). Primary sites: 13 pineal, 5 pituitary/suprasellar, 6 bifocal. Patients were treated according to CCLG guidance. One received FRT without WVRT. One incompletely staged bifocal standard-risk (SR) NGGCT after partial response to PEI had surgery, local+metastatic progression, then second-line chemotherapy before CSI. All seven HR patients received intensified chemotherapy. Nine had post-chemotherapy surgery for residual, two showing necrosis/inflammation, three mature teratoma, two mixed viable GCT. Three relapses (1/17 SR, 2/7 HR) made early EFS 0.875. Of 13 localised patients receiving WVRT, 2 progressed. One bifocal SR patient developed spinal metastases at 5.0m and died despite chemotherapy+spinal irradiation. One unifocal HR patient developed posterior parafalcine metastasis at 3.9m, received GemPOx (Gemcitabine-Paclitaxel-Oxaliplatin), surgery, high dose Carboplatin-Etoposide-Thiotepa with stem-cell rescue, and photon CSI and remains disease-free at 13.2m. One metastatic HR patient progressed at 0.9m and died at 3.0m despite chemotherapy. Acute toxicities were grade 3 lymphopenia in two CSI patients.

CONCLUSIONS
Despite short follow-up, initial EFS is excellent in SR disease. No localised WRVT-receiving NGGCT patient progressed within the ventricular volume, suggesting benefit of low-dose WVRT.