bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODL-17. The Childhood Brain Cancer Cell Line Atlas: A Resource for Biomarker Identification and Therapeutic Development
Authors: Daniel Paul , Sun Claire , Koptyra Mateusz , Drinkwater Caroline , Chew Nicole , Bradshaw Gabrielle , Loi Melissa , Shi Claire , Tourchi Motahhareh , Parackal Sarah , Chong Wai Chin , Fernando Dasun , Adjumain Shazia , Nguyen Hoang , Habarakada Dilru , Sooraj Dhanya , Crombie Duncan , Zhukova Nataliya , Jones Chris , Rubens Jeffrey , Raabe Eric , Vinci Maria , Dun Matt , Ludlow Louise , Nazarian Javad , Fletcher Jamie , Ekert Paul , Ziegler David , Loh Amos Hong Pheng , Low Sharon Yin Yee , Monje Michelle , Neeman Naama , Williams Bryan , Resnick Adam , Gough Daniel , Cain Jason , Firestein Ron 
Published: June 2022

Abstract
Cell lines represent the most versatile and widely used models of cancer and, as such, are critical for identifying and advancing new therapies. Strikingly, there is a significant gap in both the number of childhood brain cancer cell lines and their characterisation compared to their adult counterparts. To address this inequity, we established a childhood brain cancer cell line atlas (publicly available at vicpcc.org.au/dashboard) encompassing over 180 childhood CNS-derived cell lines, representing 20 tumour types and 11 molecular subtypes. Cell lines are characterized by whole genome, RNA-sequencing, phospho- and total proteomics, DNA methylation and ATAC-seq analyses. Multi-omic factor analysis revealed distinct lineage-specified classification of our cell line cohort. In parallel, high throughput drug and CRISPR/Cas9 screens were conducted to map the functional dependencies in over 70 childhood CNS cell lines, including 47 paediatric high grade glioma models. These screens identified both lineage and molecular-subtype specific genetic and drug dependencies, underscoring the utility of this wide-scale approach. Machine based learning approaches to predict genotype-phenotype correlations uncovered distinct paediatric-specific biomarkers of growth dependency, highlighting the unique genetic wiring underlying paediatric CNS tumours. Finally, by integrating functional, molecular and drug profiles of paediatric CNS cell lines, we construct a system to prioritize investigation of novel therapeutic target-biomarkers pairs in specific CNS tumour types.
RONC-05. Peri-transplant Radiation Therapy for Young Children Treated with High-Dose Chemotherapy for Primary Brain Tumors
Authors: Milgrom Sarah , Koo Jane , Foreman Nicholas , Liu Arthur , Campbell Kristen , Dorris Kathleen , Green Adam , Dahl Nathan , Donson Andrew , Vibhakar Rajeev , Mulcahy-Levy Jean 
Published: June 2022

Abstract
PURPOSE: The role of peri-transplant radiation therapy (RT) in young children with primary brain tumors is unclear. We characterized our institutional practice patterns and patient outcomes. MATERIALS AND METHODS: The cohort included all patients treated with high-dose chemotherapy for primary brain tumors at our institution from 2011-2017. Rates of local control (LC), progression-free survival (PFS), overall survival (OS), and radiation-associated injury were assessed. RESULTS: Of 37 eligible patients, 29 (78%) received peri-transplant RT at a median age of 4 years. Patients treated with RT were more likely to have metastatic (p=0.0121) and incompletely resected (p=0.056) disease, and to have high-risk histologies including atypical teratoid rhabdoid tumor, nongerminomatous germ cell tumor, pineoblastoma, primitive neuro-ectodermal tumor, glioneuronal tumor and group 3 medulloblastoma. Of those treated with RT, 13 (45%) received craniospinal irradiation (CSI) and 16 (55%) received focal RT. The median CSI dose was 23.4 Gy (IQR: 18-36; boost median 54 Gy [IQR: 53.7-55.8]) and focal RT dose was 50.4 Gy (IQR: 50.4-54.5). Compared to the focal RT group, patients treated with CSI were older (p=0.0499) and more likely to have metastatic disease (p=0.0004). For the complete cohort, at a median follow-up of 3.8 years, the 2-year rate of LC was 82% (95% CI: 70-96%), PFS was 63% (95% CI: 49-81%), and OS was 65% (95% CI: 51-82%). These rates did not differ significantly between patients treated with and without peri-transplant RT. Two cases of fatal myelopathy were observed after spinal cord doses within the highest tertile (41.4 CGE and 36 Gy); both cases occurred in patients who received RT before high-dose chemotherapy. CONCLUSION: Peri-transplant RT was used for high-risk disease. Oncologic outcomes after RT were encouraging. However, 2 cases of grade 5 myelopathy were observed. If used cautiously, RT may contribute to durable remission in patients at high risk of relapse.
RONC-11. Permanent alopecia in pediatric patients with medulloblastoma treated by craniospinal irradiation: looking for a threshold dose
Authors: Satragno Camilla , Verrico Antonio , Giannelli Flavio , Ferrero Alfonso , Cavagnetto Francesca , Schiavetti Irene , Garrè Maria Luisa , Garibotto Federica , Milanaccio Claudia , Ramaglia Antonia , Profio Sonia Di , Belgioia Liliana , Barra Salvina 
Published: June 2022

Abstract
BACKGROUND: Permanent alopecia in adult survivors of childhood cancer is a late effect that has a negative impact on vitality and social function, and it is not clear if it is only associated with radiotherapy or also with high-dose chemotherapy. In this study, we analysed a cohort of medulloblastoma survivors treated with craniospinal irradiation (CSI) with long follow-up looking for radiotherapy parameters associated with permanent hair loss. METHODS: We retrospectively analysed 42 patients with medulloblastoma with median follow up of 10 years. In 27 pts, Eclipse subgroup, the scalp was accurately re-contoured and were estimated specifics dosimetric parameters. Any relationship between presence of alopecia and other characteristics was investigated by univariate and multivariate analysis, in both groups. For each significant predictor variable, a Receiver Operating Characteristic curve was drawn for calculating the Area Under the Curve and identifying the optimal dose discriminatory cut-off value for prediction of alopecia. RESULTS: The best predictor for the occurrence of permanent alopecia was the dose of CSI (OR: 1.002; 95%CI: 1.001-1.003; p=0.003), with a cut-off value of 30.9 Gy. In Eclipse subgroup median Dose hair skin was statistically significant, (OR: 1.216; 95%CI: 1.030-1.435; p=0.021), with a cut-off value of 28.7 Gy. If the median dose of each Gy unit of D median is exceeded, the probability of alopecia increases by 21.6% (3.0% - 43.5%), with a specificity of 90.9%. None of the other variables was statistically significant. CONCLUSIONS: Pediatric Medulloblastoma survivors have a high risk of developing permanent alopecia.Our study supports the finding that permanent hair loss is dose-dependent and identified a threshold dose, the median dose of 28.7 Gy, to prevent the occurrence of permanent alopecia in paediatric patients undergoing radiotherapy. Therefore, we suggest that this dosimetric parameter should be evaluated when planning radiation treatment, especially when planning CSI in low- and standard-risk medulloblastoma.
SWK-03. Neuroimaging in CNS tumours: To GA , or not to GA, that is the question.
Authors: Ryles Jade , Ternent Lisa , Halliday Gail , Hill Rebecca M , Bailey Simon 
Published: June 2022

Abstract
Children with a Central Nervous System (CNS) tumour have frequent magnetic resonance imaging (MRI) scans during their disease trajectory. Younger children routinely have these performed under general anaesthetic (GA) with an associated risk and inconvenience. Our project over a two-year period was to introduce a structured programme to any child over the age of five years old to achieve an MRI scan without the need for a GA. Thirty-six patients took part. The motivation behind this project was to enhance the hospital experience for patients and their families, lessen time spent in hospital and minimise risk. In addition, there was an added incentive of cost saving and increased availability of GA scans for other specialities within the hospital setting. During the COVID pandemic, it has also resulted in a reduction of our patients requiring COVID swabs, and isolation and in turn a reduction in aerosol generating procedures. As part of the structured programme, each child had an initial assessment with the nurse specialist followed by a minimum of one play preparation session with the play specialist. Children were required to demonstrate they could follow simple instructions, engage in social stories and role-play with hospital equipment and specialised resources. During these sessions, the children visited the MRI department where they practiced lying flat on the MRI bed as it moved into the scanner. Over the two-year period, of the total number of MRI scans performed, the amount of MRI scans requiring a GA reduced from 41% to 31%. The quality of the MRI scans was scrutinised and shown not to be significantly affected. In summary, by introducing a structured programme, it is possible to significantly reduce the need for GA in children requiring CNS imaging as part of their tumour journey.
SWK-06. Structured transition from pediatric neuro-oncology to adult survivorship follow-up care - Can we close the gap?
Authors: Krottendorfer Kerstin , Baumgartner Alicia-Christina , Boehm Alexandra , Ziomek Sabina , Peyrl Andreas , Gsell Hannah , Schneider Carina , Rosenmayr Verena , Gojo Johannes Salomon , Azizi Amedeo , Rinner Sarah , Burger Sabine , Huemer Marlene , Pucher Anna , Leiss Ulrike 
Published: June 2022

Abstract
PURPOSE: Advances in treatment have increased survival rates and quality of life of pediatric CNS tumor patients leading to a growing number of long-term survivors. However, there is sufficient clinical and scientific evidence for the need of a highly specialized lifelong follow-up care due to multidimensional late effects. Furthermore, adolescence and young adulthood are challenging age periods when patients frequently get lost to follow-up potentially having severe impact on health and well-being. Since 2020, we have established a structured transfer of long-term survivors older than 18 years to a newly founded highly specialized adult care follow-up setting for childhood cancer survivors (IONA). The aim of this study was to evaluate the current transition process. RESEARCH DESIGN: The standard of care transition process at the neuro-oncology unit of the MUV includes a joint appointment with the patient, a pediatric neuro-oncologist, psychologist and/or social worker and the team of the adult care facility (physician, psychologist). Different elements are used to end care safely in the pediatric structure and building trust in the upcoming out-patient-department at the same time. The transition process was evaluated statistically and analyzed qualitatively with regard to the factors that define a safe transition. RESULTS: After two years (01/2020-12/2021) 114 patients had a joint transition appointment, two patients contacted IONA directly. Shortly after the joint appointment all patients had a scheduled follow-up meeting at IONA. 102 patients (87.9%) showed up, seven patients (6%) already had a planned appointment, two patients (1.7%) were in contact with IONA but had no possibility to show up in person. Only five patients (4.3%) did not attend the appointment and were lost to follow-up. CONCLUSION: A structured interdisciplinary transition concept is a successful option to establish controlled and patient-safe transition from pediatric to adult care setting.
TBIO-01. Mutation Profiling of Paediatric Solid Tumours in a Cohort of South African Patients
Authors: Lamola Lindiwe , Manolas Erin , Krause Amanda 
Published: June 2022

Abstract
BACKGROUND: The incidence of childhood cancer incidence is increasing gradually in low-middle income countries, such as South Africa. Globally, there is an extensive range of familial- and hereditary-cancer syndromes, where underlying germline variants increase the likelihood of developing cancer in childhood. Next-Generation Sequencing (NGS) technologies have been key in determining the occurrence and genetic contribution of germline variants to paediatric cancer development. We aimed to design and evaluate a candidate gene panel, specific to inherited cancer-predisposing genes to provide a comprehensive insight into the contribution of germline variants to childhood cancer. METHODS: 32 paediatric patients (aged 0-18 years) diagnosed with a malignant tumour were recruited and biological samples were obtained. After quality control, DNA was sequenced using an ion Ampliseq 50 candidate gene panel design and Ion Torrent S5 technologies. Sequencing variants were called using Ion Torrent Suite software and were subsequently annotated using Ion Reporter and Ensembl's VEP. High priority variants were manually analysed using tools such as MutationTaster, SIFT-INDEL and VarSome. Putative identified candidates were validated via Sanger Sequencing. RESULTS: The patients studied had a variety of cancers, the most common being nephroblastoma (13), followed by osteosarcoma (4) and astrocytoma (3). We identified 10 pathogenic / likely pathogenic variants in 10 patients, most of which were novel. CONCLUSIONS: According to literature, we expected ~10% of our patient population to harbour pathogenic or likely pathogenic germline variants, however we reported about 3 times (~30%) more than we expected. Majority of the identified variants are novel; this may be because this is the first study of its kind in an understudied South African population
TBIO-12. Screening for Cancer Predisposition Syndromes in Pediatric Neuro-Oncology Patients: a Single Institution Experience
Authors: Johns Claire , Kline Cassie , Solomon David , Mueller Sabine , Banerjee Anu , Gupta Nalin , Reddy Alyssa 
Published: June 2022

Abstract
BACKGROUND: Traditional screening for cancer predisposition syndromes centers on family history, phenotypic features, and tumor histology. With expanded accessibility of next generation sequencing, identification of de novo germline mutations is increasing and the predictive value of family history has become less clear. While identification of germline mutations often affects care of pediatric neuro-oncology patients, germline sequencing is not currently standard of care. We hypothesize that routine screening for germline mutations in pediatric neuro-oncology patients reveals unsuspected cancer predisposition syndromes and impacts care. METHODS: A retrospective analysis was performed on pediatric neuro-oncology patients at a single institution who had targeted next generation sequencing of approximately 500-cancer associated genes (UCSF500) on tumor and paired germline DNA. We determined the proportion of patients with germline mutations and assessed impact on future screening and current tumor treatment. We interrogated clinical notes, family history, and interviewed treating physicians to determine if predispositions were previously suspected. RESULTS: Between June 2015-December 2019, 187 patients had paired testing; of these 29 (16%) harbored germlines mutations that were pathogenic or likely pathogenic. Germline mutations were found in patients with high-grade glioma (n=12), low-grade glioma (n=7), medulloblastoma (n=4), ATRT (n=2), and choroid plexus papilloma (n=1). Known cancer predisposition syndromes were identified or confirmed in 18 patients. Of these, the most common alterations were in TP53 (n=6), CHEK2 (2), NF1 (n=2), SMARCB1 (n=2), and PTEN (n=2). Patients were referred to genetic counseling in 26 cases and malignancy screenings were implemented in 25 cases. Germline findings affected malignancy treatment in 10 cases, most often through use of targeted therapeutics or avoidance of radiation. CONCLUSIONS: In our series, we found that 16% of pediatric neuro-oncology patients harbored germline mutations, the majority of which were associated with cancer predisposition syndromes. These results support standardizing screening for pathogenic germline mutations in pediatric neuro-oncology patients.
INSP-01. What to do when you cannot randomize? Leveraging Historical Data in Efficient Study Designs for Pediatric Neuro-Oncology.
Authors: Onar-Thomas Arzu 
Published: June 2022

Abstract
BACKGROUND: Randomized phase III studies represent the gold standard in clinical trial design for many good reasons. They control bias and the effects of known and unknown covariates on outcomes of interest. Recent examples from Children’s Oncology Group Medulloblastoma studies have demonstrated their utility in providing insights that likely would not have been possible otherwise. However, experience with these trials also reaffirmed that large, randomized studies often take too long to keep up with the ever-changing landscape in pediatric Neuro-Oncology, and the rarity of these tumors is a significant barrier in utilizing such designs effectively. METHODS: Recent global efforts in pediatric Neuro-Oncology have led to rich, well annotated repositories that contain patient-level data. While these data suffer from the well-known limitations when used as sole comparison cohorts for ongoing studies, they also offer an opportunity to design more efficient studies in ultra-rare patient populations that trialists in pediatric neuro-oncology often face. Therefore, there is renewed effort in the statistical community in devising methodologies that can effectively utilize external data in the design of prospective studies. These approaches include incorporating external data as a supplement to a small fraction of patients randomized to standard of care arms and prospectively assessing similarity with an intent to minimize overall sample size. Others focus on patient selection methodologies from external controls with an intent to optimize matching between the retrospective and prospective cohorts to control for known covariates. Additional considerations include incorporating arms into the study that retain standard of care treatments to capture the magnitude of drift in outcome over time due to improved supportive care.
CONCLUSIONS: While there are important limitations to designs based on external controls, judicious choice of design parameters and careful selection of controls could provide a viable alternative when rarity of patient populations make randomized designs infeasible.
INSP-02. WHO 2021 classification of CNS tumors
Authors: Wesseling Pieter 
Published: June 2022

Abstract
In line with recommendations of the cIMPACT-NOW consortium, the fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5 classification) is substantially different from the previous (revised 4th) edition. Salient changes include the separation of pediatric-type low- and high-grade diffuse gliomas from adult-type diffuse gliomas, refinement of the classification of ependymal tumors, and the addition of a newly recognized embryonal CNS tumors. Furthermore, for some tumors the name was changed. For example, diffuse midline glioma (DMG), H3K27M-mutant is now DMG, H3K27-altered (because there are H3-wildtype DMGs that do show loss of nuclear H3K27me3 staining and with a similar prognosis as DMGs, H3K27M-mutant), and supratentorial ependymoma, RELA fusion-positive was changed into ZFTA fusion-positive (as ZFTA (‘zinc finger translocation associated’, the new name for c11orf95) is the more frequent fusion partner in these tumors). The WHO CNS5 tumor classification certainly is an improvement, but it brings several (new) challenges as well. For example, for more CNS tumors it is now impossible to reach a state-of-the-art ‘histomolecular’ diagnosis in case molecular tools for assessment of essential diagnostic characteristics are not available. In those situations, adding NOS (not otherwise specified) to the histology-based diagnosis is the way to go. Furthermore, designing the optimal therapeutic management for newly defined tumor types is challenging. And while a more precise classification facilitates enrollment of more homogeneous populations of patients in clinical studies, the higher granularity of CNS tumor taxonomy makes it more difficult to perform studies on a large number of patients for particular tumor types. Still, one would like to think that patients suffering from a CNS tumor are better served by a more precise diagnosis because this allows for a better estimation of prognosis and, hopefully sooner than later, for a more tailored and effective therapeutic approach.
INSP-03. Neuronal regulation of glioma progression
Authors: Monje Michelle 
Published: June 2022

Abstract
The nervous system regulates stem and precursor cell behavior across a range of tissues. In the central nervous system, neuronal activity is a critical regulator of development and plasticity. Activity-dependent proliferation of healthy glial progenitors, oligodendrocyte precursor cells (OPCs), and the consequent generation of new oligodendrocytes contributes to adaptive myelination. This plasticity of myelin tunes neural circuit function and contributes to healthy cognition. The robust mitogenic effect of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, suggests that dysregulated or “hijacked” mechanisms of myelin plasticity might similarly promote malignant cell proliferation in this devastating group of brain cancers. Indeed, neuronal activity regulates initiation and promotes progression of gliomas in preclinical models. Crucial mechanisms mediating activity-regulated glioma progression include secretion of BDNF and the synaptic protein neuroligin-3 (NLGN3). NLGN3 induces multiple oncogenic signaling pathways in the cancer cell, and also promotes glutamatergic synapse formation between neurons and glioma cells. This synaptic and electrical integration of glioma into neural circuits is central to tumor progression in preclinical models. NLGN3 is necessary for the growth of gliomas in a range of preclinical models, and therapeutic targeting of NLGN3 is presently under clinical investigation. Thus, neuron-glial interactions not only modulate neural circuit structure and function in the healthy brain, but paracrine and synaptic neuron-glioma interactions also play important roles in the pathogenesis of glial cancers. The mechanistic parallels between normal and malignant neuron-glial interactions underscores the extent to which mechanisms of neurodevelopment and plasticity are subverted by malignant gliomas, and the importance of understanding the neuroscience of cancer.
INSP-06. Recent advances in improving neuropsychological outcomes for paediatric brain tumour patients - Are we entering a new era?
Authors: Mabbott Donald 
Published: June 2022

Abstract
Children and youth treated for brain tumours can sustain a brain injury as a consequence of the tumour and curative therapy leaving them with significant cognitive challenges. Advances in treatment for paediatric brain tumours – particularly the delivery of radiotherapy – have been associated with improved neuropsychological outcome in survivors, however. This presentation will first focus on work documenting the impact of changes in cranial radiotherapy delivery and modality on neuropsychological late effects in children treated for medulloblastoma. Outcomes in patients treated on modern protocols are substantially improved relative to prior therapy, however challenges remain. Second, novel approaches for cognitive recovery and brain repair in survivors of paediatric brain tumours will be discussed, with a focus on novel approaches for fostering endogenous neuroplasticity for cognitive recovery and brain repair in children and youth treated for paediatric brain tumours.