tbuckley/cabot-search huggingface dataset:
MDB-23. MULTICENTRE EVALUATION OF THE MANAGEMENT OF CHILDREN WITH HIGH RISK MEDULLOBLASTOMA: REAL WORLD PERFORMANCE OF THE SJMB03 AND COG99701 PROTOCOLS
Authors: John R Apps, Shaimaa Sahmoud, Katherine Green, Kriti Hedge, Claire Keeling, Anoop Cherungonath, Banuja Srikumar, Blanche Lumb, Jennifer Whitby, James Hayden, Barry Pizer, Steve Clifford, John-Paul Kilday, Mette Jorgensen, Fernando Carceller, Jenny Adamski
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Several treatment protocols are used in the treatment of patients with high risk medulloblastoma (HRMB). In 2015 the UK Children’s Cancer and Leukaemia Group issued interim guidance recommending treatment as per the SJMB03 protocol, whilst also recognising that the COG99701 protocol may be used. Patients were defined as high risk, if metastatic at presentation, large cell anaplastic histology, MYC amplification, significant residual disease or MYCN amplification, the latter two, more recently only if other adverse features present. METHODS We present a retrospective multi-centre service evaluation of treatment of patients with HRMB at 5 tertiary paediatric oncology centres in the UK. Patients were included if treated for HRMB with SJMB03, COG-99701. Patients were excluded if treated for HRMB on other protocols, including the SIOP HRMB trial, or if initially treated for standard risk medulloblastoma and subsequently treated with these protocols due to upstaging or disease progression. Event free, and overall (EFS and OS) survival analyses were calculated from date of primary resection. RESULTS 59 patients were included (median age 8 years, range 3-19): 26 treated as per SJMB03, 33 as per COG-99701. 5-year OS was 83% (95% Confidence Interval, 73-94%) and 5-year EFS was 66% (54-80%). For patients treated as per SJMB03 5-year OS and EFS was 79% (65-97%) and 70% (55-92%)respectively. and for patients treated as per COG99701, 5-year OS and EFS was 86% (73-99%) and 60% (44-83%). There was a higher incidence of grade 3 &amp; 4 ototoxicity (44% vs 6%) and a higher rate of admission to paediatric intensive care (36% vs 6%) in patients treated as per SJMB03 compared to those treated with COG97701 (p&amp;lt;0.05). CONCLUSIONS These real-world outcomes of patients treated in the UK for HRMB are consistent with the published literature for their outcomes for high risk medulloblastoma.
QOL-22. PARTICIPATION RESTRICTIONS IN DAILY LIVING ACTIVITIES IN CHILDHOOD CANCER SURVIVORS ACCORDING TO BODY COMPOSITON: A DOUBLE-CENTER STUDY
Authors: Müberra Tanrıverdi, Kardelen Yıldırım, Güleser Güney Yılmaz, Sedef Şahin, Fatma Betül Çakır
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Impact of cancer and treatment adverse effects on daily living activities in childhood cancer survivors (CCS) are well known. In our study, we hypothesized that the participation in daily living activities is affected in CCS. METHODS Fifty-eight CCS (10.07±3.83 years) in the 3-97th percentile range were included in the study. Participation of CCS was evaluated by Pediatric Outcomes Data Collection Instrument (PODCI). Body compositions of CCS were grouped according to body mass index (BMI). RESULTS The mean z score was.64±3.22 and BMI was 17.76±3.56. The global functioning score was 80.25±15.23, upper extremity score was 86.52±12.09, transfer and basic mobility score was 92.17±10.95, sports and physical functioning score was 71.31±25.70, pain/comfort score was 72.37±23.31, and happiness score was 81.31±19.19 of PODCI. While there was no relation between PODCI global functioning score and age chemotherapy, surgery (p&amp;gt;0.05); there was a significant relationship between PODCI global functioning score and gender, body mass index, radiotherapy (p&amp;lt;0.05). The significant functional difference detected between these groups was in upper extremity, transfer basic mobility, happiness, and global functioning (p&amp;lt;0.05). There were no differences between the sports and physical functioning and pain/comfort (p&amp;gt;0.05) according to the BMI categories (underweight, normal/healthy, and overweight). CONCLUSIONS Survivors have participation restrictions in activities at earlier period of cessation of treatment. Patient-reported outcomes can be systematically assessed in CCS. We recommend that supportive interventions in terms of physical functioning and participation in daily living activities for CCS.
QOL-29. COGNITIVE DEVELOPMENT WITHIN TWO YEARS AFTER CRANIOSPINAL IRRADIATION IN CHILDREN TREATED FOR MEDULLOBLASTOMA: A COMPREHENSIVE ASSESSMENT USING AGE-APPROPRIATE SCALES
Authors: Camilla Satragno, Virginie Kieffer, Christelle Dufour, Valentine Martin, Noura Sellami, Francesco Lanfranchi, Stephanie Bolle
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma 5-years survival rates range from 50-95% across risk classes, underscoring the need to mitigate treatment-related neurocognitive deficits. This study evaluates cognitive outcomes within 2 years post-radiotherapy, considering treatment modalities and various influencing factors. METHODS We conducted a retrospective monocentric study on patients under 18 years old, treated at our hospital from 2007 to 2020, with histologically and molecularly confirmed medulloblastoma, who underwent craniospinal irradiation. Cognitive function was assessed within 24 months post-therapy using age-appropriate Wechsler scales to evaluate verbal comprehension, perceptual reasoning, working memory, and processing speed. Patients were categorized into two groups based on a threshold score of 80, indicating “neurocognitive normality” if scores were ≥80 in all domains or “neurocognitive deficient” if any domain scored &amp;lt;80. Statistical analyses utilized SPSS for descriptive statistics and tests for categorical and continuous variables. RESULTS Among 100 selected patients, 91 completed the evaluations. The average age at diagnosis was 8.47 years, and at the onset of radiotherapy was 8.83 years. Forty-four patients (48%) scored ≥80 in all domains, indicating ‘neurocognitive normality,’ while 47 patients (52%) scored &amp;lt;80 in at least one domain, classified as ‘neurocognitive deficient’. In the descriptive analysis identifying significant differences in the two groups, no significant differences were observed in age, WHO classification, risk class, or pre-surgical shunt. In contrast, significant differences emerged in posterior fossa syndrome frequency, kinetic (p=0.002) and static forms (p&amp;lt;0.001) and in parental education level(p=0.025). CONCLUSION Our findings highlight the multifactorial nature of neurocognitive development in children with medulloblastoma within 2 years post-radiotherapy, identifying postoperative complications and the social environment as significant factors. Notably, specifics of radiotherapy and high-dose chemotherapy did not show a significant impact in this preliminary analysis. Future studies will further investigate the roles of various variables on neurocognitive outcomes, aiming to extend our understanding beyond two years post-radiotherapy.
ATRT-09. MULTI-OMICS SEQUENCING OF ATYPICAL TERATOID RHABDOID TUMORS UNVEILS A SHARED GROUND-STATE POPULATION PROMOTING SUBGROUP-SPECIFIC DIFFERENTIATION TRAJECTORIES
Authors: Enrique Blanco Carmona, Irene Paassen, Jiayou He, Annette Büllesbach, Juliane L Buhl, Aniello Federico, Ilon Liu, Matthew Young, Gerda Kildisiute, Sam Behjati, Rajeev Vibhakar, Andrew Donson, Nicholas Foreman, Volker Hovestadt, McKenzie Shaw, Susan N Chi, Michael Frühwald, Andrey Korshunov, Martin Hasselblatt, Eelco W Hoving, Natalie Jäger, Pascal D Johann, Stefan M Pfister, Mariella Filbin, Jarno Drost, Marcel Kool
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Atypical teratoid rhabdoid tumors (ATRTs) remain a significant clinical challenge in pediatric neurooncology. Despite the simplicity of the genomic profile, mostly characterized by the functional loss of SMARCB1 and in rare cases SMARCA4, ATRTs are molecularly and epigenetically diverse, with three main molecular subgroups identified: ATRT-TYR, ATRT-SHH and ATRT-MYC. METHODS To address the lack of effective mechanism-of-action based treatments and comprehend the biology of these subgroups, we conducted 10X single-nucleus transcriptome (n = 12) and multiome (transcriptome + ATAC) (n = 7) sequencing on tumor samples (ATRT-TYR = 6, ATRT-SHH = 9, ATRT-MYC = 4). Validation datasets included 10X single-cell transcriptomics (n = 1), 10X single-nucleus transcriptomics of cell lines (n = 5), and single-cell (n = 3) and single-nucleus (n = 9) SMART-seq transcriptomics. Separation of malignant cells from tumor microenvironment (TME) cells was achieved by comparison of expression profiles against literature-based marker genesets of normal cell types. Tumor cell populations were characterized based on enrichment in fetal cell types and recurrent tumor programs across cancer types, coupled with non-negative matrix factorization (NMF) and differential expression analyses. RESULTS ATRT-TYR exhibited choroid plexus-like and cilia-like cell populations, ATRT-SHH displayed radial glia-like, OPC-like and NPC-like cell populations and ATRT-MYC mainly demonstrated a mesenchymal-like cell population. Each subgroup represented unique differentiation trajectories. However, we identified a population of intermediate neuronal precursor-like cells (IPC-like) shared across all subgroups, expressing markers of pluripotent stem cells and cell cycle. RNA + ATAC transcription factor (TF) enrichment analysis for IPC-like cells revealed TFs linked to each subgroup’s differentiation trajectory, suggesting IPC-like cells as a putative ground-state tumor cell population driving differentiation of each subgroup. Functional validation of these findings in ATRT organoid models is currently ongoing. CONCLUSIONS This study elucidates defined ATRT subgroup-specific differentiation trajectories that may provide guidance for the development of subgroup-based therapies.
QOL-34. POST-TRAUMATIC GROWTH AND COPING STRATEGIES AMONG ADOLESCENTS AND YOUNG ADULTS SURVIVORS OF PEDIATRIC BRAIN TUMORS
Authors: Sara De Giuseppe, Claudia Milanaccio, Antonio Verrico, Gianluca Piccolo, Marta Molteni, Sabrina Robotti, Cristina Venturino, Maria Luisa Garrè, Sonia Di Profio
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Pediatric brain tumor survivors (PBTS) often report late psychosocial effects following the disease and the treatments. Recent studies have shown that PBTS can experience growth in their personal and interpersonal dimensions and develop coping strategies that allow them to deal with the stress caused by cancer diagnosis and subsequent therapies. This study aimed to describe post-traumatic growth (PTG) experiences and coping strategies among adolescents and young adults (AYA) survivors of pediatric brain tumors. METHODS AYA survivors were assessed using Post-Traumatic Growth Inventory (PTGI) and Coping Inventory for Stressful Situations (CISS) questionnaires. They received evaluation at a median age of 20.2 years (range 13.6-28.7), with a median of 92 months from diagnosis. RESULTS Among 22 AYA survivors (M =14; F=8), the diagnosed tumor types were: germ cell tumor (10/22), low-grade glioma (4/22), embryonal tumor (3/22), high-grade glioma (2/22), craniopharyngioma (2/22), and mesenchymal tumor of the meninges (1/22).The domains of PTG in which positive changes were most frequently reported were Personal Strength (25%), Appreciation for Life (25%), and New Possibilities (23%). The less impacted domain was Spiritual Growth (9%). As regards the most adopted coping style, 38% showed higher values in the Distraction scale, 31% in the Task-Oriented scale, 15% in the Avoidance scale, and 15% in the Social Diversion scale. CONCLUSIONS PTG and coping are important indicators of psychosocial adaptation to difficult or stressful events. To develop specific interventions that enhance PTG, it is essential to understand which factors influence growth in PBTS. Our preliminary data show that all AYA survivors report PTG after treatments, at least in some domains. Further analysis is needed to identify which coping styles may influence the development of PTG.
MDB-20. TOXICITY PROFILE OF TWO CHEMOTHERAPEUTIC REGIMENS ADOPTED FROM COG A9961 AND ACNS0331 FOR STANDARD-RISK MEDULLOBLASTOMA, A COMPARATIVE STUDY
Authors: Moatasem Mohamed Hatem Elayadi, Sarah Magdy Elsayed, Eslam Maher, Iman Abdelmokhales sidhom, Sherif Aboulnaga Aboulnaga
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma (MB) is classically treated with surgery, irradiation, and chemotherapy (CTH). Cisplatin-based CTH regimens for standard-risk (SR) MB entail significant toxicities particularly ototoxicity which adversely affect patients’ quality of life. We compared the toxicity profile of two regimens in terms of grade 3 or 4 ototoxicity, hematologic toxicity, hepatotoxicity, nephrotoxicity, and neurotoxicity. METHODS SR-MB patients enrolled at Children Cancer Hospital-Egypt (57357) between January 2016 and December 2019 (cohort A) received adjuvant CTH adopted from COG-A9961 protocol (regimen A; 8 cycles of vincristine, cisplatin, and CCNU; cumulative cisplatin dose 600 mg/m2). Starting from January 2020 (cohort B), patients received CTH adopted from ACNS0331 protocol (9 cycles; 2 cycles of vincristine, cisplatin, CCNU followed by 1 cycle of cyclophosphamide and vincristine, for 3 rounds; cumulative cisplatin dose 450 mg/m2). Toxicity grading was done using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS enrolled patients (n=168; cohort A = 112; 67% and cohort B = 56; 33%). Cohort A had significantly higher rate of grade ≥3 ototoxicity at some point during treatment (27% vs 3.6%, p &amp;lt;0.001). Similarly, cohort A had higher grade ≥3 neurotoxicity (26% vs 12%, p =0.046), anaemia and thrombocytopenia (72% vs 56%, p =0.04). Cumulative rate of leukopenia was very high in both cohorts, 98% of all patients, while the rate of febrile neutropenia was much lower in cohort A (38% vs 67%, p &amp;lt;0.001). No toxic deaths were observed in both cohorts. There was no difference in grade ≥3 nephrotoxicity nor hepatotoxicity between the 2 cohorts. The 2-year OS for cohort A and B were 96.4% and 86.6%, respectively, p=0.11. Similarly, the 2-year EFS were 92.9% and 86.8%, p=0.29. CONCLUSION adjuvant CTH from ACNS0331 protocol showed a better toxicity profile particularly for ototoxicity compared to A9961 CTH regimen, while maintaining comparable survival.
BIOM-09. TOWARDS CLINICAL IMPLEMENTATION OF LIQUID BIOPSY ANALYSIS FOR PAEDIATRIC BRAIN TUMOUR PATIENTS – A PAN-EUROPEAN EFFORT FOR STANDARDIZATION
Authors: Nike Simon, Kendra K Maass, Petra Pokorná, Natalia Stepien, Johanna Rettenmeier, Oskar Saijonmaa, Tom T Fischer, Daniel Senfter, Sibylle Madlener, Géraldine Giraud, Emma Tham, Cinzia G Scarpini, Matthew J Murray, Esther Hulleman, Steven C Clifford, Stefan M Pfister, Kristian W Pajtler, Johannes Gojo
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Liquid biopsies (LBs) allow for analysis of tumour-derived molecules, such as cell-free DNA (cfDNA) and microRNAs (miRNAs), complementing cancer diagnostics, therapy monitoring, and minimal residual disease detection. While circulation-based LB has benefit for extracranial tumour entities, peripheral blood has not historically been a reliable source for diagnosis and disease-monitoring in brain tumours. For these tumours, cerebrospinal fluid (CSF) analysis is better suited for detection despite being a more invasive procedure. However, standardized protocols for sample collection and pre-analytical parameters for these LBs currently are limited. AIM We aim to establish an evidence-based gold standard protocol for cfDNA and miRNA analyses from CSF in paediatric brain tumour patients. In addition to higher compliance in trial-related CSF sampling, this initiative seeks to facilitate identification of clinically relevant indications and time-points for collection, thereby paving the way for well-informed, routine CSF molecular diagnostics. METHODS AND RESULTS We have initiated the Liquid Biopsy Working Group within the framework of the International Society of Paediatric Oncology Europe Brain Tumour Group (SIOPE-BTG). Available literature on LB in brain tumours was critically assessed regarding pre-analytical parameters, downstream analyses and LB assay performance. To directly evaluate confounding by pre-analytical factors, we experimentally compared the impact of CSF sampling sites, storage conditions, and different pre-processing protocols. cfDNA and miRNA yields, purity, and the fraction of tumour-derived material were selected as read-outs and correlated with tumour tissue information. To prepare for clinical translation, we consulted clinical paediatric brain tumour trial coordinators to identify major bottlenecks for CSF sampling in routine clinical practice. In addition, clinical practitioners and patient/ parent representatives have been consulted to comprehensively represent the perspectives and needs of all stakeholders. Together, results of this collaborative effort will be fundamental to the successful clinical integration of LBs to improve the future management of paediatric brain tumour patients.
ATRT-05. AGE ABOVE 12 MONTHS, ABSENCE OF SYNCHRONOUS, MULTIFOCAL DISEASE AND PATHOGENIC GERMLINE VARIANTS AT C-TERMINI ARE POSITIVE PROGNOSTIC FACTORS IN CHILDREN WITH RTPS1 (RHABDOID-TUMOR-PREDISPOSITION-SYNDROME)
Authors: Michael C Fruehwald, Matej Boros, Sonja Dahlum, Susanne Bens, Pascal D Johann, Denis Kachanov, Peter Hauser, Christian P Kratz, Pablo Hernaiz-Driever, Matthias Eyrich, David Sumerauer, Till Milde, Harald Reinhard, Marianne van de Wetering, Maria Joao Gil-da-Costa, Schiavello Elisabetta, Kornelius Kerl, Rhoikos Furtwaengler, Uwe Kordes, Joachim Gerss, Martin Hasselblatt, Karsten Nysom, Karolina Nemes
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Rhabdoid-Tumor-Predisposition-Syndrome is due to germline mutations in SMARCB1 (rarely SMARCA4). We pursued a comprehensive clinical and (epi-)genetic characterization of RTPS families. METHODS 90 affected children from 16 countries were compared to 252 with sporadic rhabdoid tumors (01/2004 - 01/2021). Tumors and blood were examined for structural or single nucleotide variants (SV, SNV) in SMARCB1/SMARCA4. In 83% (70/84) of RTPS1-patients complete genetic data were available. Trio-exome (n=25) and 850k-methylation analysis of tumors (52/84) and blood (n=51), parents (n=44) and unaffected siblings (n=4) was performed. RESULTS RTPS1 and 2 were diagnosed in 84 (48 females, 36 males) and 6 patients respectively. Median age at diagnosis (RTPS1 only) was 5 (0 – 203) months (18 months, 0-211 in controls, p&amp;lt;0,001). ATRT were present in 55% (46/84), extracranial, extrarenal malignant RT (eMRT) and RT of the kidney (RTK) in 8% (7/84). 26% (22/84) presented with synchronous tumors (SYN). Homozygous SVs were less frequent in the RTPS-tumors [20% (14/84) vs 47% (82/174), p&amp;lt;0,001]. ATRT-MYC was significantly more common among RTPS1 while ATRT-SHH was less common. Trio blood DNA-methylation analysis separated samples of parents but not siblings from RTPS patients. Likely (DNA-methylation) age was a major confounder. The analysis of trio-exomes is ongoing. 5-year-OS and -EFS in RTPS1-patients were 18,4±4.5% and 14±3,9%, (controls: 48,2 ±3,5%, 40,3±3,2%). VOD (venoocclusive disease) was significant in patients &amp;lt; 2 months [18,5% (12/65) vs. 3,3% (3/92), p=0.005]. RTPS1-patients rarely achieved a CR [32% (27/84) vs. 52% (129/249), p=0,002]. In an adjusted multivariate model prognostic factors were male sex [HR: 1.7 (1.0 – 2.9)], age ≤12 months [HR: 2.1 (1.0 – 4.3)], and diagnosis of ATRT [HR: 0.6 (0.3 – 0.9)]. CONCLUSION We describe significant positive outcome predictors such as age &amp;gt;12 months, absence of SYN, diagnosis of ATRT, localized disease, PGV located at C-termini and female sex in RTPS1-patients.
QOL-37. THE CREATION OF A PLAY PREPARATION CLINIC FOR CHILDREN WITH CENTRAL NERVOUS SYSTEM TUMOURS TO REGAIN CONTROL ONCE MORE
Authors: J Ryles *, L Ternent *, T Arif, G Halliday, R M Hill, S Bailey
Journal: Neuro-Oncology (2024)

Abstract Targeted therapies are becoming more readily available for children with Central Nervous System (CNS) tumours, not only for early phase but also late phase trials. With this knowledge, we have created a play preparation clinic whereby all children with a CNS tumour diagnosis are invited to attend. Initially the play preparation clinic was solely a programme to train children to take tablets using a technique created at The Great North Children’s Hospital called ‘Kidzmeds’. On average children are successful in achieving the ‘Kidzmeds’ technique within ten minutes so we were able to expand the programme and incorporate two other areas of play preparation. Firstly, we have been able to include play preparation for children undergoing procedures without sedation or general anaesthesia such as MRI scans and lumbar punctures. Secondly, we have been able to use play preparation to teach children how to achieve cannulation or blood taking using a specific technique we have called the ‘GNCH way’. Our aim is that children leave our hospital having a positive experience and regain control and choice in how procedures take place, feeling they have ownership of their bodies. There is an added incentive of cost saving for our hospital, for example converting medication from liquid to tablet form. Forty-eight children have took part in the clinic so far. Every child has been able to achieve two of the play preparation techniques we offer and eighty-three percent of children have been successful in achieving all three. The youngest child in achieving all three play preparation techniques has been four years old. All forty-eight children continue to be successful in their achievements. Within our service, the feedback from children and families have been overwhelmingly positive and our hope is that other hospitals across the world can benefit from our experience.
QOL-23. POTENTIAL MYELIN REPAIR AFTER IRRADIATED PEDIATRIC BRAIN TUMOR: A MAGNETIZATION TRANSFER IMAGING ANALYSIS
Authors: Eloïse Baudou, Julie Tseng, Jennifer L Ryan, Eric Bouffet, Ute Bartels, Brian Timmons, Cynthia de Medeiros, Donald J Mabbott
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Exercise training and metformin treatment may improve cognition after cranial irradiation in pediatric brain tumors (PBT), but the neuronal mechanisms underlying the effect of these interventions remains unknown. Magnetization transfer imaging (MTI) is an imaging technique that may be sensitive to white matter microstructure – including myelin. METHODS In this work, we analyzed changes in magnetization transfer ratio (MTR) over a 12-week period in irradiated PBT survivors who participated in pilot clinical trials entailing 12 weeks of exercise training (exercise group, n=17), or metformin treatment (n=12). Pre- and post-intervention assessment included MRI scanning and neurocognitive tests. A no intervention control group, (n=7) was also included and seen before and after a 12 week period of time. We used a longitudinal Tract-Based Spatial Statistics (TBSS) approach to analyze differences in MTR across the 12 weeks in the three groups, using as covariates: age at baseline, sex, handedness, age at diagnosis and delay from diagnosis. Then we performed correlations between mean MTR changes and behavioral outcomes. RESULTS Clusters of significant increase in MTR were observed in the right temporal lobe in the exercise group after intervention and in the right minor forceps in the metformin group after treatment. These changes respectively correlated with higher performance in free recall score in exercise group and with higher performances in inhibitory control and attention in metformin group. There was no difference in MTR changes between groups nor within the control group. DISCUSSION This exploratory work suggests either a 12-week period of exercise training or metformin may promote myelination in PBT survivors in brain regions. These changes appear to be associated with improved memory and executive function, two core domains of neurocognitive deficit in this population.