tbuckley/cabot-search huggingface dataset:
QOL-33. CANCER WORRY AND PSYCHOPATHOLOGICAL SYMPTOMS IN ADOLESCENTS AND YOUNG ADULTS SURVIVORS OF PEDIATRIC BRAIN TUMORS
Authors: Sonia Di Profio, Sara De Giuseppe, Antonio Verrico, Gianluca Piccolo, Marta Molteni, Cristina Venturino, Maria Luisa Garrè, Claudia Milanaccio
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Adolescent and young adult (AYA) survivors of pediatric brain tumors may experience cancer-related worries, defined as concerns about relapse and late effects of treatment. Late psychological effects include psychological distress, depression, immaturity, and poor development of social skills. Furthermore, pediatric brain tumor survivors (PBTS) are more vulnerable to developing long-term neurocognitive and psychosocial consequences compared both to the general population and survivors of other types of childhood cancer. The purpose of the study was to identify the presence of cancer worry and psychopathological symptoms in AYA survivors of pediatric brain tumors. METHODS AYA survivors were assessed using the Cancer Worry Scale and Child Behavior Checklist questionnaires. Neurocognitive evaluation was performed using the age-appropriate Wechsler Scale. 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). Survivors received the assessment at a median age of 20.2 years (range 13.6-28.7), with a median of 92 months after diagnosis. Cancer worry was reported in 50% of patients. The psychological evaluation showed clinical levels of internalizing problems in 17% and externalizing problems in 8%. Depressive and anxiety problems were reported in 25% of our cohort. Neurocognitive assessment demonstrated an average tIQ of 104. CONCLUSIONS As reported in the literature, cancer worry can influence the psychosocial adjustment process, alter self-image, and influence lifestyle decisions in PBTS. These concerns can affect their life prospects and their ability to successfully complete developmental tasks. Therefore, these issues must be early identified to prevent, through targeted psychosocial interventions, the onset of troubles in having romantic relationships, finishing school, entering the job market, and obtaining a good quality of life.
QOL-35. ANALYSIS ON THE EVOLUTIONARY PATTERN OF COGNITIVE FUNCTIONS IN CHILDREN ON FOLLOW-UP FOR BRAIN TUMORS
Authors: Ilaria Liguoro, Maristella Toniutti, Francesco Tuniz, Marco Vindigni, Enrico Pegolo, Serena D’Agostini, Maria Cristina De Colle, Maurizio Mascarin, Elisa Coassin, Paola Elisa Cogo, Chiara Pilotto, Tiziana Zilli
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Long-term cognitive sequelae of paediatric brain tumors are of increasing interest. The role of histology and surgery remains still unclear. Our study aimed to evaluate children cognitive functioning before and after brain tumors surgery, and at the end of additional treatments. METHODS New diagnoses of paediatric primary brain tumors were prospectively assessed. Neurocognitive evaluations were performed at diagnosis (T0), within 7-10 days from surgery (T1) and 12-18 months after the end of treatments (T2). Language, learning and memory, attention, executive functions, visuo-constructional and sensorimotor skills were evaluated at T0 and T1, Intelligent Quotient (IQ) was explored at T0 and T2. RESULTS Twenty-five patients (M:F=15:10, mean age 10.9±3.4 years) were enrolled between January 2019 and December 2022. In comparison to normal values (&amp;gt;7.0), at baseline patients showed major deficits in narrative memory (6.6±3.7, p&amp;lt;0.001) and visuo-spatial memory (copy design tasks: general 6.8±3.9, p&amp;lt;0.001, specific 6.2±3.3, p&amp;lt;0.001, motor 5.2±3.2, p&amp;lt;0.001). At T1 assessment, significant deficits remained in narrative memory (6.2±3.3, p&amp;lt;0.001) and visual-motor coordination (copy design tasks: specific 5.9±3.0, p&amp;lt;0.001 and motor 4.8±4.3 p&amp;lt;0.001); attention and visual-constructional abilities significantly improved (p=0.04 and p=0.001). On the visual construction test, children with high-grade histology scored lower than the low-grade group (Rey- Osterrieth complex figure-copy 5.1±4.4 vs 11.0±4.3; p=0.019). At T2 evaluation children showed persistent deficits in visuo-spatial processing and a possible decline in IQ scores, with lower scores compared with T0 (93 vs 100, p=0.05). CONCLUSIONS Children with brain tumors may present several neuropsychological impairments at diagnosis, particularly those with high-grade diseases. Surgery may have a positive effect on the recovery of some cognitive functions. However, cognitive decline may worsen over time. Baseline and periodic neurocognitive evaluations should be encouraged to identify functional difficulties and to develop a tailored treatment approach for the patient.
MDB-19. THE 3D CHROMATIN LANDSCAPE OF MEDULLOBLASTOMA
Authors: Stephanie C Wu, Eduardo Ferreira Martins Diaz, Enrichetta Mileti, Laure Bihannic, Kyle S Smith, Francisco G Rodríguez-González, Nicos Sidiropoulos, Joachim Weischenfeldt, Paul A Northcott
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma (MB) is a highly malignant childhood cerebellar tumor comprised of four molecularly and clinically distinct subgroups. Sporadic yet subgroup-specific genetic and epigenetic landscapes suggest that higher-order chromatin topology may contribute to distinct subgroup identities and disease biology. Herein, we investigated the 3D chromatin landscape of MB by performing genome-wide chromosome conformation capture (Hi-C) across molecular subgroups using a cohort of n=24 patient-derived xenografts and primary tumor specimens, aiming to elucidate regulatory mechanisms facilitated by genome organization. METHODS Integrative analyses were adapted to incorporate a wide variety of sample-paired datasets. Chromatin contact matrices generated from Hi-C allowed for the mapping of active/inactive compartments (A/B compartments), topologically associated domains (TADs), and distal pairwise chromatin contacts (loops). Topological insights of chromatin architecture were complemented with whole-genome sequencing, RNA-seq, ATAC-seq, DNA methylation, CTCF and histone modification (H3K27ac/H3K27me3) ChIP-seq datasets to dissect mechanisms of gene regulation. RESULTS Unsupervised analysis revealed that chromatin compartmentalization is subgroup stratified. Gene loci contained in subgroup-unique active compartments correspondingly exhibited subgroup-specific chromatin contact patterns, adopted open chromatin conformations, and remained transcriptionally active. As an example, LIN28B resides within a Group 3-specific ‘A’ compartment where its local topology displays higher complexity compared to that of other subgroups. This consequentially facilitates a Group 3-unique loop connecting the LIN28B promoter with a distal enhancer, resulting in subgroup-specific transcriptional upregulation. Targeted displacement of CTCF that anchors and stabilizes chromatin looping at the LIN28B locus was sufficient to alter its transcriptional activity. Using similar lines of investigation, mechanistic insights into the topological determinants of known enhancer-hijacking events, including GFI1, GFI1B and PRDM6, were resolved. CONCLUSIONS Pioneering this integrative approach centered on comprehensive Hi-C maps, our study provides a high-resolution blueprint of the 3D chromatin landscape defining MB subgroups, informing the mechanistic basis of recurrent driver gene activation, and disclosing putative subgroup-specific vulnerabilities.
QOL-31. NEUROPSYCHOLOGICAL FUNCTIONING AND QUALITY OF LIFE IN INFANT AT/RT SURVIVORS: FOCUS ON FLUID INTELLIGENCE AND VISUAL PROCESSING
Authors: Thomas Traunwieser, Elena Loos, Holger Ottensmeier, Martin Mynarek, Brigitte Bison, Daniela Kandels, Anne Rossius, Peggy Lüttich, Katja Baust, Kristin Faulstich-Ritter, Rainer John, Andrea Kreisch, Judyta Landmann, Eva Manteufel, Alexandra Nest, Jenny Prüfe, Lisa Schubert, Walther Stamm, Beate Timmermann, Joachim Gerss, Stefan Rutkowski, Paul-Gerhardt Schlegel, Matthias Eyrich, Astrid K Gnekow, Michael C Frühwald
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Understanding the long-term cognitive sequelae in infant brain tumor survivors remains incomplete, particularly regarding the impact of tumor type, multimodal treatment, and other patient-related factors. This retrospective analysis explores neuropsychological and quality of survival (QoS) outcomes in survivors of atypical teratoid/rhabdoid tumors (AT/RT) and extracranial malignant rhabdoid tumors of soft tissues (eMRT) and kidneys (RTK), all treated within the same framework. Neuropsychological data from children with AT/RT were compared to data from children with non-irradiated low-grade glioma (LGG). METHODS Patients (0 - 36 months at diagnosis) underwent various treatments, including radio-chemotherapy for AT/RT (n = 13) and eMRT/RTK (n = 7), chemotherapy only for LGG (n = 4) and eMRT/RTK (n = 1), or observation for LGG (n = 11). Neuropsychological evaluations were conducted at a median of 6.8 years (AT/RT), 6.6 years (eMRT/RTK), and 5.2 years (LGG) post-diagnosis. RESULTS Impairments were observed for all tumour types. Patients with AT/RT exhibited impairments in fluid intelligence (p =.041; d = 1.11) and visual processing (p =.001; d = 2.09) when compared to LGG-patients. Both groups demonstrated deficits in psychomotor speed and attention abilities (p &amp;lt;.001–.019; d = 0.79–1.90). Diagnosis significantly predicted cognitive outcomes, whereas gender and age-related variables did not. QoS outcomes for all rhabdoid patients indicated lower scores in psychosocial functioning (p =.023; d = 0.78) and quality of life (p =.006; d = 0.79) compared to healthy controls. CONCLUSIONS Infant rhabdoid tumor survivors experience cognitive and quality-of-life sequelae. Patients with AT/RT are especially vulnerable to impairments in fluid intelligence and visual processing, while infant LGG-patients without radiotherapy demonstrated comparable deficits in psychomotor and attention abilities. Close monitoring of neuropsychological and quality of life outcomes is crucial for early onset and multimodal treatment.
QOL-27. EARLY CHEMOTHERAPY-INDUCED HEARING LOSS IN CHILDREN WITH MEDULLBLASTOMA AND EMBRYONAL BRAIN TUMOURS
Authors: Maya Prasad, Vikas Patil, Jitesh Prasad sahoo, Badira Parambil, Venkata Ramamohan Gollamudi, Archya Dasgupta, Abhishek Chatterji, Tejpal Gupta, Girish Chinnaswamy
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The purpose of this study was to examine the prevalence, severity and time to develop Chemotherapy-induced hearing loss (HL) in a cohort of embryonal brain tumors(ET) treated with cisplatin and cranial radiation(RT). METHODS Our cohort included children 3-15years treated between January2022 and June2023 for medulloblastoma and other ETs with surgery, craniospinal RT and 6 cycles of CET chemotherapy (cyclophosphamide,vincristine,cisplatin). Cisplatin 75mg/m2 was given in alternate cycles with a cumulative dose of 225 mg/m2. Children underwent clinical evaluation and age-appropriate audiological assessment at diagnosis,every 1-2cycles of cisplatin and end-of-treatment. Grading of ototoxicity was done per SIOP-Boston grading. Children with grade2 and above HL did not receive further cisplatin.Children with grade1HL underwent frequent monitoring.For this study, pure-tone-audiometry from start of treatment to end of treatment were analyzed and ≥Grade2HL was considered significant. RESULTS A total of 63 children were included in the study, 28(44.%)female, median age 7years (range 3-15years). Twenty (31.7%) children developed &amp;gt;grade2HL; the worse ear had grade 4 HL in 1(1.6%),grade 3 in 13(20.6%) and grade 2 in 6(9.5%).One had grade 2HL and 4 had grade 1HL even prior to start of cisplatin.The median cumulative cisplatin dose at developing &amp;gt;grade2HL was 0mg/m2(n=1), 75mg/m2(n=8), 150mg/m2(n=3) and 225mg/m2(n=9; 5 at end-of-treatment and 4 at follow-up). Age, gender and diagnosis were not associated with development of HL. CONCLUSION The high prevalence of early-onset ototoxicity in children with embryonal brain tumours is concerning.We recommend close monitoring of hearing function,at least every 2 cycles of cisplatin chemotherapy, if not more frequently. Incorporation of pharmacogenomics to identify highly susceptible individuals and therapeutic interventions such as cessation of cisplatin or replacement with alternatives in early ototoxicity would help reduce a potentially life-altering and long-term health concern.
MDB-22. DECIPHERING MEDULLOBLASTOMA’S MOSAIC: UNVEILING SUBGROUP CLASSIFICATION THROUGH METHYLATION PROFILING
Authors: Nader Ashraf, Amani Al Kofide, Tarek Arabi, Belal Sabbah, Mariam Aboian, Abderrahman Ouban
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Medulloblastoma represents the most prevalent malignant brain tumor in children, posing significant treatment challenges despite advances in multimodal therapies. The heterogeneity of medulloblastomas necessitates precise classification to improve therapeutic outcomes. This study explores the utility of genome-wide DNA methylation profiling in categorizing medulloblastomas into molecular subgroups, aiming to refine diagnostic and treatment strategies. METHODS This investigation involved the analysis of medulloblastoma samples from pediatric patients at the King Faisal Hospital and Research Centre. We employed the Illumina Infinium 850K EPIC assay to assess the CpG methylation status in six medulloblastoma cases. The methylation data were then compared with immunohistochemical findings to validate the methylation-based subgroup classification. RESULTS The Infinium 850K EPIC assay successfully classified all six medulloblastoma cases into the recognized subgroups: WNT, SHH, Group 3, and Group 4. This classification was further supported by immunohistochemical analysis, demonstrating the assay’s robustness in accurately identifying the molecular subtypes. Notably, the assay also distinguished a control case within the cohort, illustrating its potential for widespread clinical application. The study highlights the feasibility of using formalin-fixed, paraffin-embedded (FFPE) tissues, which offers a practical advantage by eliminating the need for fresh tissue samples. CONCLUSIONS Genome-wide methylation profiling emerges as a superior method for the classification of pediatric medulloblastomas, facilitating the identification of molecular subgroups with distinct prognostic and therapeutic implications. The ability to utilize FFPE tissues broadens the applicability of this approach, particularly in settings where fresh samples are not readily available. This advancement holds significant promise for enhancing the clinical management of medulloblastoma in pediatric populations.
QOL-25. DETERMINING THE BURDEN OF SLEEP PATHOLOGY AMONG PEDIATRIC NEURO-ONCOLOGY PATIENTS
Authors: Lanipua Yeh-Nayre, Jennifer Elster, Sunita Sridhar, Megan Paul
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Children with brain and spinal cord tumors are at higher risk for sleep disruption. The incidence and characteristics of sleep difficulties in this population is not well understood. Our aim is to use survey and chart review to retrospectively and prospectively evaluate the frequency, severity, and types of sleep difficulties experienced by pediatric patients who have brain and spine tumors. METHODS Pediatric patients with a diagnosis of a brain or spinal cord tumor and their parents were surveyed at three time points during routine visits with their neuro-oncology team. Parents and children completed the following self-reported standardized surveys: The San Diego Pediatric Sleep Survey (Child) and The San Diego Pediatric Sleep Survey (Parent). RESULTS Identified sleep disturbances include difficulty initiating sleep, excessive movement while asleep, increased incidence of nocturnal awakening, and snoring. We identified high rates of behavioral and environmental modifiers of sleep quality including sleeping in a shared bed with another family member and poor sleep hygiene. CONCLUSIONS Identification of sleep disruption and factors contributing to sleep difficulties in this high risk population will encourage proactive screening and recognition of these issues in future patients. Next steps include implementation of interventions such as referral to appropriate specialists, sleep hygiene modification, and parent/patient education. Early intervention may lead to overall improvement in quality of life and health, including increased academic success and job productivity in children and their caregivers.
ATRT-19. CELL SURFACE PROTEOME ANALYSIS OF ATRT IDENTIFIES CD44V6 AS A CAR TARGET
Authors: Allison Cole, Eric Hoffmeyer, Enrique Grimaldo, Andrew Donson, Rajeev Vibhakar, Anandani Nellan, Siddhartha S Mitra
Journal: Neuro-Oncology (2024)

Abstract Atypical teratoid rhabdoid tumor (ATRT) is an uncommon, aggressive tumor affecting the brain and spinal cord primarily in children. Despite significant strides in understanding cancer biology through DNA and RNA sequencing, nearly 90% of ATRTs exhibit a crucial deletion that triggers rampant tumor growth. The absence of easily targetable genetic mutations in ATRT complicates the development of effective treatments, necessitating innovative strategies for therapy. Evading immune system detection is a key feature of cancer cells. In our study, we conducted an exhaustive, unbiased examination of 350 surface receptors through high-throughput multicolor flow cytometry on samples from ATRT surgeries, cell lines, and xenograft models derived from patients. By using a combination of antibodies targeting CD31, CD45, CD11b, CCR2, Cx3CR1, CD4, and CD8, we could identify immune cell populations within the tumors. Our findings revealed a heightened presence of CD44, CD146, CD59, CD151, and CD276 on the surface. Using qPCR we identified CD44V6 a variant isoform of the CD44 molecule, which is a cell surface glycoprotein involved in cell-cell interactions, cell adhesion, and migration. CD44 has multiple isoforms generated through alternative splicing, with CD44V6 being one of these variants. This specific isoform includes an additional variable exon (exon v6) in its extracellular domain. CD44v6-directed CAR-T cells effectively controlled tumor growth in multiple myeloma and solid tumors such as HNSCC, lung and ovarian adenocarcinomas. We developed CD44V6-directed CAR-T cells and investigated the capacity of Anti-CD44v6 CAR-T cells to execute cytotoxicity against ATRT tumor cells. We see significant cell killing by Anti-CD44v6 CAR-T cells in vitro and a significant increase in the survival of ATRT tumor-bearing mice.
MDB-24. SHH MEDULLOBLASTOMA WITH SMO MUTATION BEFORE THE AGE OF 5YEARS OLD
Authors: Gwenaelle Duhil de Bénazé, Julien Masliah Planchon, Arnault Tauziede Espariat, Liesbeth Cardoen, Léa Guerrini Rousseau, Olivier Ayrault, Pascale Blouin, Christelle Dufour, Natacha Entz-Werle, Marion Yvert, Franck Bourdeaut
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND SHH medulloblastomas represent around 30% of MB’s and occur mostly in infants and adults with an intermediate prognosis. The driving mutations concern mostly PTCH1(43%), SUFU(10%) or SMO(9%). SMO activating mutations have been described almost exclusively in adults, and is extremely rare in infants. The features and outcome of SMO mutated infant MB are not known so far. PATIENTS AND METHODS We did a national retrospective analysis of children under 5 years with a SHH medulloblastoma and a somatic SMO mutation. We collected clinical, radiological and biological data (centralised reviews) with addition of methyloma, aiming to depict the clinico-molecular features and the outcome of these rare MB. RESULTS We identified 6 patients from 2014 to 2020. The median age at diagnosis was 3.2years. No evidence of metastatic disease was found for 5/6 patients and one had a positive CSF cytology. All patients underwent a complete removal. All had an extensive nodularity histologic subtype, no specific alterations in CGH apart from gains of all chromosomes 2,7 and,15. Methyloma classified 4/6 in subgroup SHH-1 and 2 in subgroup SHH-2. One patient had a second cerebellar lesion with a different radiological aspect; histological analysis and methylation profiling revealed a subependymoma, sharing the same SMO mutation than the MB ((c.1604G&amp;gt;T/p.(Trp535Leu)), suggesting a mosaicism. Another patient presented a polymalformative disorder diagnosed as a Curry-Jones syndrome, in agreement with the finding of mosaic SMO variant (c.1234C&amp;gt;T(p.Leu412Phe)). All patients received several cycles of chemotherapy, and no radiotherapy. With a median follow-up of 3.9 years, all patients were alive in complete remission with no relapse. CONCLUSION This data suggests that an underlying mosaicism must be sought in these very rare patients, and that the outcome seems overall similar to other infants with SHH medulloblastoma and more classical SUFU or PTCH1 mutations.
QOL-26. SYTHESIS OF THE LITERATURE REVIEW ON PHYSICAL ACTIVITY IN PEDIATRIC NEURO-ONCOLOGY
Authors: Seda YILDIZ, Müberra TANRIVERDİ
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Physical Activity plays a vital role in physical, social, phychological wellbeing of pediatric neuro-oncologic group. However, the researches investigating the effects of physical activity on this group have been sparse. The purpose of this study was to identify studies conducted about the effects of physical activity on this population. METHODS PRISMA statement conduct review was followed in electronic database of Journal of Neuro-oncology. Two authors (SY, MT) independently conducted systematic literature searches February 2024. Keywords/Mesh terms: “physical activity’’. Randomized controlled English clinical trials are included; Studies that were published as “review”, “protocol”, “books”, “news”, not reach full text and not related to physical activity excluded. After articles had been reached, used QUADAS-2 checklist for methodological quality. RESULTS 29 articles were identified from 1721 articles, and 2 of them (published 2014-2023) were about pediatric age group. One of them was assessment (50%), while the other one was interventional study (50%). Assessment study was measured by using Bruininks-Osteretsky Test of Motor Performance, Second Edition (BOT-2) and online surveys. Interventional study analyzed the effects of aerobic exercises of three 90-minute sessions per week for 12 consecutive weeks primarily on cortical thickness, white matter, hippocampal volume and secondarily reaction time, accuracy across tests of attention, processing speed, and short term memory. CONCLUSION This abstract provides an initial scoping review of physical activity in pediatric neuro-oncology group. It demonstrates limited range of assessments, and interventions which highlights the lack of clinical evidence in this specific area. The results raise the need for further research in this field to help the development of physical activity guidelines for evaluation and physical activity methods in children with ataxia, and tumours expecially posterior fossa brain tumors. Investigation of different physical activity methods in a group of neuro-oncology children in need of support is major importance.