bluuebunny/crossref_metadata_2025_split huggingface dataset:
MEDB-89. Elucidation of the Oncogenic role of Nuclear Factor I/B (NFIB) in group 3 medulloblastoma
Authors: Perumal Naveenkumar , Kanchan Ranjana , Doss David , Thapa Ishwor , Nasser Mohd W , Batra Surinder , Mahapatra Sidharth 
Published: June 2022

Abstract
Amongst the 4 subgroups of medulloblastoma (MB), tumors falling into group 3 are the most aggressive and associated with increased incidence of aberrations on chromosome 17p, c-Myc amplification, metastases at diagnosis, and rapid tumor relapse. Thus, patients with group 3 tumors suffer the worst prognosis with a 5-year survival rate of &lt;50%. We have prior identified a novel tumor-suppressive microRNA, miR-212, silenced on chromosome 17p and its deregulated oncoprotein target, Nuclear Factor I/B (NFIB). Here, we sought to identify the role of NFIB in group 3 MB pathophysiology. NFIB is a transcription factor that regulates chromosomal gene accessibility and expression of pro-metastatic genes in various cancers. Transcriptomic interrogation of group 3 tumors revealed deregulated expression of NFIB. Kaplan-Meier survival analysis confirmed poorer survival in NFIB high-expressing patients. Using inducible silencing of NFIB in a classic group 3 MB cell line, HDMB03, we observed downregulation of key driver genes (49 genes, Log2 fold change &lt; -0.5, p &lt; 0.001) associated with group 3 MB pathogenesis by RNA sequencing. NFIB expression knockdown (NFIBKD) further reduced tumor cell growth and aggressiveness, as evidenced by reduced proliferation, colony formation, migration, and invasion. NFIBKD also affected group 3 MB stemness, with attenuation of medullospheres and a reduction in stem cell markers (Nanog, Oct4, Sox2, CD133). Moreover, NFIBKD destabilized c-Myc phosphorylation at serine-62, resulting in reduced total c-Myc levels and subsequent cellular apoptosis. Concurrently, NFIBKD decreased the expression of upstream activators of c-Myc such as p-Akt and p-Erk. Taken together, these results validate the oncogenic role of NFIB in group 3 medulloblastomas and provide a potential new therapeutic target.
NFB-05. A family-centered neurocutaneous syndrome clinic in the age of targeted therapies
Authors: Marks Asher , Antaya Richard , Balsamo Lyn , Cardinale Kathleen , Cheron Rebecca , Frumberg David , Gentile Victoria , Habib Larissa , Puthenpura Vidya , Zhang Hui 
Published: June 2022

Abstract
On April 10, 2020, the FDA approved selumetinib for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. This, combined with the 2016 EXIST-3 data showing the efficacy of adjunctive everolimus in the treatment of tuberous sclerosis associated seizures, have resulted in the re-imagining of the treatment of these neurocutaneous syndromes and subsequently, the multidisciplinary clinics in which they are treated. In early 2021, this reshaping resulted in the launch of a unique, family-centered clinic at Yale New Haven Children’s Hospital serving children and young adults up to 30 years of age in the management of NF1, NF2, tuberous sclerosis and schwannomatosis. Here we present the clinical reasoning and benefit of a multidisciplinary, family-centered clinic that manages to combine on-site, real-time access to neuro-oncology, neurology, psychology, dermatology, orthopedics, genetics, and ophthalmology. We will describe how the collaboration of these specialists is essential for providing high-quality, easy-access care to patients and families with the above noted syndromes – particularly with the advent of effective, readily available targeted therapies that carry their own side effects requiring further subspecialty consultation. Furthermore, we will describe previous and ongoing challenges to the creation of such a clinic and offer solutions based on our experience.
NFB-12. Effect of trametinib on leg length discrepancy in a child with NF1 related plexiform neurofibroma
Authors: Pradeep Celia , Abouassaly Marcel , Assis Zarina , Finkbeiner Melanie , Lafay-Cousin Lucie 
Published: June 2022

Abstract
INTRODUCTION: Plexiform neurofibroma(PN) is a challenging benign tumor. Recently, MEK inhibitors (MEKi) showed encouraging tumor response. We report the observed effect of Trametinib on leg length discrepancy (LLD) in a child with NF1. CASE DESCRIPTION: A 4 year old girl with sporadic NF1, developed progressive bilateral L1-L5 paraspinal PN extending to the left thigh resulting in hypertrophy of left leg and associated with LLD. At 33 months of age, length difference of 2.8 cm between both femurs was described on scanogram with a projected LLD of at 6.1- 6.2 cm LLD at bone maturity using the multiplier method, a common method of predicting LLD. At 36 months of age, treatment with Trametinib was initiated for her large PN. Ten months into therapy, parents reported impression of decrease swelling of her left thigh enlargement. MRI evaluation showed stable measurement of PN using the RECIST criteria. Repeat measurement on scanogram at 46 months of age disclosed a stable difference of 2.8 cm between both femurs, with a LLD projected at 5.2-5.3 cm at maturity by multiplier method. Bone age at study entry and at 11 months into therapy (Greulich-Pyle) was reported normal for chronologic age. DISCUSSION/CONCLUSION: LLD has not been commonly described in association with NF1 related PN. Given the PN involved mainly the left thigh in our patient, it is reasonable to suggest common underlying mechanism for the PN and faster growth of her left femur. Although with limited time point’s measurements, the early observation of stabilization of the LLD, 10 months into Trametinib therapy suggesting a final discrepancy in femurs length less than initially predicted, is encouraging. Further evaluation at completion of treatment and on follow-up are needed. Larger case series will be useful to explore this unexpected and possible clinical effect of MEKi in NF1 children.
NFB-20. Pre-clinical models of Mismatch Repair Deficient Gliomas
Authors: Putnam Ethan , Yadavilli Sridevi , Dawood Adam , Mizoguchi Sean , Subramaniam Bavani , Bornhorst Miriam , Nazarian Javad 
Published: June 2022

Abstract
INTRODUCTION: Lynch syndrome and Biallelic Mismatch Repair Deficiency (BMMRD) are hereditary tumor predisposition syndromes, resulting from one or two (respectively) germline alterations in DNA mis-match repair (MMR) genes. Currently, there are few treatments for mismatch repair deficient (MMRD) gliomas, in part due to a lack of suitable pre-clinical models for drug testing. The purpose of this study is to develop and characterize pre-clinical models of MMRD gliomas. METHODS: Primary cells were developed from patients diagnosed with MMRD gliomas and characterized through immunofluorescence staining (IF) for different cell type markers, western blot assays, and genome and transcriptome analysis. Murine models were generated through intracranial injection of mCherry-luciferase reporter expressing primary cells, and mice were monitored for evidence of engraftment and clinical symptoms. Drug screening on the cell lines was performed to identify potential therapeutic agents for in-vivo testing. RESULTS: The cell lines had similar characteristics as the primary glial tumors by IF staining and genome and transcriptome analysis. Adult NSG mice developed tumors around three weeks after intercranial transplantation of the tumor cells. These tumors closely resembled the primary patient tumors on histology. Preliminary drug testing on the cell lines showed efficacy of ONC201, ONC206, and RM006 against MMRD gliomas with IC50 concentrations of 1.77 μM, 185 nM, and 699 nM respectively. CONCLUSION: The generation of pre-clinical MMRD glioma models can lead to improved understanding of tumorigenesis, allowing for the identification of targetable molecules, and supporting novel treatment development.
QOL-03. Beyond Survival: Clinical Rehabilitation and Functional Optimization Pearls for the Neuro-Oncologist
Authors: Rosenberg Nathan 
Published: June 2022

Abstract
Over the past decades, major advances in treatment for pediatric brain tumors have led to higher survival rates. Management including surgical resection, chemotherapy and radiation have led to prolonged survival though each comes with potential deleterious impact upon a child's level of function. While function-sparing treatments continue to be developed and utilized each year, the standard of care for many conditions leaves our patients with the potential for worsening function. The areas of mobility, activities of daily living, cognition, communication and swallow are all potentially impacted. Rehabilitation medicine specialists focus on detecting impairments, addressing them with practical interventions and improving the function our shared patients. Unfortunately, there is a worldwide scarcity of rehabilitation medicine physicians and the role of improving function often falls into the hands of the neuro-oncologist. A number of practical clinical assessments and interventions utilized by rehabilitation medicine specialists can be translated to the toolbox of the neuro-oncoligst. The aim of this presentation is to provide the neuro-oncologist with further abilities to enhance function with interventions that typically require low time investment. Topics covered will include the following: 1. What is spasticity, when is it necessary to treat and how is it treated? 2. Leg braces -- who needs them, who doesn't and what are the goals? 3. What physical exam signs can be utilized to detect peripheral neuropathy early and inform further treatment decisions with agents such as Vincristine. 4. What aspects of a gait assessment are high yield in detecting concern for clinical progression? The goal of this talk is high yield and low time investment.. It is unfortunately not applicable for a poster presentation. A minimum amount of time would be 15 minutes. If less time is available for the this presentation, a photo/video-based, rapid-fire format (similar to Tik-Tok content) could be utilized.
QOL-05. Cardiorespiratory fitness and health-related quality of life amongst survivors of childhood central nervous system tumours.
Authors: Keating Rachael , Curry Sarah , Hussey Juliette 
Published: June 2022

Abstract
INTRODUCTION: Due to recent advancements in surgical techniques, imaging and adjuvant therapies, survival rates for children with central nervous system (CNS) tumours have improved. Research priorities have now shifted to focus on late-effects and quality of survivorship amongst childhood CNS tumour survivors. Our study aimed to assess levels of cardiorespiratory fitness and health-related quality of life (HRQoL) amongst survivors of childhood CNS tumours. A secondary aim was to investigate potential relationships between cardiorespiratory fitness and HRQoL. METHODS: Participants were recruited from the National Children’s Cancer Service in CHI Crumlin. Inclusion criteria included: diagnosis of a primary CNS tumour, aged between 6-17 years, between 3 months and 5 years post completion of oncology treatment, independent mobility, deemed clinically appropriate to participate by treating oncologist. Cardiorespiratory fitness was assessed using the six-minute walk test. HRQoL was assessed with the PedsQL Generic Core Scales, Version 4.0, both self-report and parent proxy report forms were used. RESULTS: 20 participants (n=9 male) were recruited with a mean age of 12.34 (SD = 3.46) years. Mean time since completion of oncology treatment was 2.31 (SD = 1.38) years. Mean 6-minute walk distance (6MWD) was 482.75 (SD = 50.04) metres, equating to the 5.55th (SD = 6.83th) percentile overall. 6MWD was significantly reduced compared to predicted 6MWD (t = -12.52, p &lt;.001, 95% CI [-163.52, -116.68]). Parent proxy-reported HRQoL was significantly reduced compared to healthy population norms (t = -5.82, p &lt;0.001, 95% CI [-25.76, -12.17]). A strong positive correlation exists between 6MWD and both parent-proxy (Pearson’s r = 0.533, p = 0.015) and child-reported HRQoL (r = 0.580, p = 0.007). CONCLUSION: Survivors of childhood CNS tumours present with impaired levels of cardiorespiratory fitness and HRQoL compared to healthy population norms. Higher levels of cardiorespiratory fitness are associated with higher levels of HRQoL.
QOL-09. SyMon-SAYS: A symptom monitoring and reporting program for children with cancer
Authors: Lai Jin-Shei , Jensen Sally , Urban Megan , Goldman Stewart , Lenzen Alicia 
Published: June 2022

Abstract
Unrelieved symptom burden due to cancer treatments can lead to poor psychosocial functioning and decreased health-related quality of life (HRQOL) for patients and their families. Barriers at the patient, healthcare provider and system levels can contribute to poor symptom management. Funded by the US National Cancer Institute, we have developed the Symptom Monitoring & Systematic Assessment and Reporting System in Young Survivors (SyMon-SAYS) program. SyMon-SAYS is a technology-based program with the potential to minimize symptom management barriers by routinely collecting and interpreting patient-reported outcomes in pediatric oncology ambulatory settings in a manner that is efficient, actionable by clinicians, supports engagement of patients and families with their health and care, and improves clinical processes and outcomes. This is a single institution modified waitlist control 16-week randomized trial of 200 children (ages 8-17) with cancer and their parents/guardians. Participants in the intervention phase will complete a symptom checklist weekly via the electronic health record patient portal. Scores exceeding a pre-defined threshold will trigger an alert to the treatment team, which will review the report and take appropriate actions. Participants will complete a separate battery of questionnaires assessing HRQOL at baseline and weeks 8 and 16. The recruitment is in progress. As of today, we have recruited 57 patients/parents. 29 completed 16-week study (15 intervention & 14 wait-list). Preliminary results showed SyMon-SAYS system was easy (92%) and convenient (85%) to use. Parents were satisfied (74.1%) with the SyMon-SAYS program. Comparing to the waitlist control, intervention group parents reported significantly less concerns on not having enough time to discuss their child’s symptoms with treating clinicians (p=0.0022), and disagreed that it is not necessary to treat their child’s symptoms as they will go away (p=0.04). We anticipate completing the recruitment by the end of 2023.
QOL-11. Comparison of Neuropsychological Functioning in Pediatric Posterior Fossa Tumor Survivors: Medulloblastoma, Low-Grade Astrocytoma, and Healthy Controls
Authors: Levitch Cara , Holland Alice Ann , Bledsoe Jesse , Kim Soo Young , Barnett Marie , Ramjan Sameera , Sands Stephen 
Published: June 2022

Abstract
BACKGROUND: Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. PROCEDURE: Forty-two children (16 MB, 9 LGA, 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. RESULTS: MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors’ mean scores were below normative expectations in working memory, processing speed, and fine motor functioning. Additionally, parents of LGA survivors reported the most difficulty with behavior and cognitive regulation compared to healthy controls and medulloblastoma survivors. In this overall sample, processing speed difficulties were independent of fine motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. CONCLUSION: The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.
QOL-14. Long term neurocognitive and psychosocial outcomes among adolescents and young adults survivors of paediatric brain tumour.
Authors: Profio Sonia Di , De Giuseppe Sara , Robotti Sabrina , Uccello Miriana , Crocco Marco , Verrico Antonio , Piccolo Gianluca , Satragno Camilla , Milanaccio Claudia , Venturino Cristina , Garrè Maria Luisa 
Published: June 2022

Abstract
PURPOSE: The aim of the study was to describe neurocognitive and psychological outcomes among adolescents and young adults (AYA) survivors of paediatric brain tumour (BT). METHODS: neurocognitive and psychological assessment of 45 AYA (M = 30; F = 15), treated for paediatric BT at our institution between 1978 and 2018, were retrospectively collected. Survivors received psychological and neurocognitive assessment at a mean age of 21.4 years (range 15.11-39.4) after a median of 120 months from diagnosis. The assessment was carried out using the following self-report questionnaires: Beck Depression Inventory, State-Trait Anxiety Inventory, Body Uneasiness Test, Multidimensional Fatigue Inventory, European Organization for the Research and Treatment of Cancer Quality of LifeQuestionnaire. Neurocognitive evaluation was carried out using Wechsler Adult Intelligence Scale. RESULTS: 18/45 survivors had received a diagnosis of germ cell tumor, 12 of low grades glioma, 10 of embryonal tumor, 3 of high-grade glioma, 2 of meninges and mesenchymal tumor. Thirty-four patients received neurosurgery, 34 patients chemotherapy, 44 patients cranial radiotherapy. Fatigue was reported in 56% of the patients, 15% of them also showed low level of QoL. The psychological assessment showed clinical levels of anxiety in 56% of AYA, depression in 41% and body image problems in 29%. Neurocognitive assessment showed that 73% has an average tIQ (tIQ ≥ 80). CONCLUSIONS: The psychological evaluation showed that 77% of our cohort had at least one clinically significant distress symptom as fatigue, depressive symptoms, anxiety and body image problems, compared to 23% who did not report any problem. Further analysis is needed to identify any possible psychopathological risk factors. It is essential to provide an accurate and comprehensive assessment and effective psychological support to these patients, to help them better manage the late effects of cancer and therapies at different levels: physical, psychological and neurocognitive.
QOL-22. Neurocognitive performance in survivors of pediatric brain tumors with neurocutaneous syndromes
Authors: Tonning Olsson Ingrid 
Published: June 2022

Abstract
BACKGROUND: Pediatric brain tumors (PBT) in children with neurocutaneous syndromes are typically low-grade and survival rates are close to 100%. Neurocutaneous syndromes are associated with neurocognitive and behavioral problems, and a diagnosis of brain tumor adds to the total neurocognitive burden. The aim of this study was to describe neurocognitive performance in survivors of PBT with a neurocutaneous syndrome and to find associated factors. METHOD: Neurocognitive data (verbal and non-verbal reasoning, cognitive processing speed, working memory, and executive function) on 20 survivors of brain tumors with neurocutaneous syndromes were collected from medical logs. Results were converted to z-scores (m=0, sd=1) using age-adjusted national norms. Generalized linear models were built to find factors associated with neurocognitive performance. Most survivors had received several assessments and all assessments were added to the model together with time since diagnosis at assessment. RESULTS: Seventeen of the survivors (85%) had undergone 1-3 assessments and 3 survivors had undergone 4-5 assessments. Six survivors (30%) had a diagnosis of intellectual disability, and neurocognitive scores were low at all assessment points: average z-score across all datapoints(sd): verbal reasoning -1.1(1.2); non-verbal reasoning -1.2(0.9); working memory -1.9(0.7); cognitive processing speed -1.0 (1.0); executive function -0.6 (1.0)). Factors associated with worse neurocognitive performance were young age at brain tumor diagnosis, larger tumors, epilepsy, and longer time span between diagnosis and assessment. CONCLUSIONS: Survivors of PBT with neurocutaneous syndromes are at risk for neurocognitive deficits that might worsen over time. These survivors need personalized neurocognitive follow-up. When examining neurocognitive performance and associated factors in survivors of PBT special consideration needs to be taken to survivors with neurocutaneous syndrome since these survivors receive limited cancer treatment and still have neurocognitive deficits.
QOL-23. Expanded protocols for hearing loss related cisplatin-based therapy in childhood cancer patients.
Authors: Grosnik Amy , Graham Richard T , Pillay-Smiley Natasha , de Blank Peter , Hummel Trent , Mochizuki Aaron , Raskin Scott , Windmill Ian 
Published: June 2022

Abstract
BACKGROUND: Most children who require cisplatin chemotherapy incur hearing loss. The basal end of the cochlea, corresponding to high frequency sound perception, is typically affected first, with progression along the basilar membrane and to lower frequencies over time. Typical audiologic protocols for children are often restricted to the speech frequencies (500-4000Hz). However, reliable responses to higher frequencies can be obtained using specialized electrophysiologic measures or adapted behavioral test procedures, which may lead to earlier identification of hearing loss during ototoxicity monitoring. METHODS: Auditory Brainstem Response (ABR) and behavioral threshold assessments were completed for patients during cisplatin treatment at Cincinnati Children’s Hospital between 2017 and 2021. High frequency ABR protocols were established to include 6000 and 8000 Hz and behavioral testing protocols were expanded to include frequencies 8000 through 16000 Hz. Hearing loss was defined as &gt;20 dB eHL at any frequency. The typical and high frequency protocols were compared to determine if higher frequency measurement provides a more sensitive means to detect the onset of hearing loss. RESULTS: One-hundred and fifty-three patients receiving cisplatin were assessed audiometrically. For patients who required ABR evaluations, 38% were identified with hearing loss when using the typical test protocol, where 79% of the patients were identified with hearing loss when using the high frequency protocol. For patients who were able to complete behavioral audiometric evaluations, 42% were identified with hearing loss with the typical protocol while 84% were identified with the high frequency protocol. CONCLUSIONS: The addition of higher frequencies to audiologic evaluation protocols for both ABR and behavioral audiometry significantly increases sensitivity to detect hearing loss during ototoxicity monitoring of cisplatin treatment and is a feasible strategy in pediatric cancer patients. Audiologically, the increased sensitivity to detect hearing loss may lead to earlier intervention regarding hearing and communication for the patient/family.