bluuebunny/crossref_metadata_2025_split huggingface dataset:
P20.16.A PEDIATRIC CENTRAL NERVOUS SYSTEM TUMOR WITH CIC-LEUTX FUSION: A DIAGNOSTIC CHALLENGE
Authors: Hu W , Hou Y 
Published: October 2024

Abstract

BACKGROUND
The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5) recognized CIC-rearranged sarcoma as a distinct mesenchymal, non-meningothelial tumors, designated as CNS WHO grade 4. This entity is characterized by CIC fusion with various partners, notably NUMT1 or DUX4, serving as its key molecular feature and essential diagnostic criterion. However, due to their rarity, the genetic background, etiology and clinical implications of CIC-fused CNS tumors still remains elusive. In a recent study by Philipp Sievers et al., a set of CIC-fused pediatric high-grade neuroepithelial tumors exhibit a distinct DNA methylation profile (CIC-HGNET), differing from CIC-rearranged sarcomas and suggesting an intermediate malignancy grade.Does all the central nervous system CIC tumors are CIC sarcomas or CIC-HGNETs? In this multi-center study, we assembled a series of CIC-rearranged CNS tumors, specifically those with rare fusion partners. Our aim is to broaden the understanding and diversity of CIC-fused CNS tumors, and to discuss whether CNS tumors with CIC fusions merit classification as a unified entity.

MATERIAL AND METHODS
Using histological evaluation, immunohistochemistry, next generation sequencing and DNA methylation cluster analysis.

RESULTS
The final cohort included 13 CNS CIC-cases and 6 peripheral CIC sarcoma cases. We find that not all intracranial CIC tumors are CIC sarcomas. Unlike peripheral CIC sarcomas (common features are WT1 positive and GFAP/Olig2 negative with relatively abundant reticular fibers), pure intracranial CIC-LEUTX fusion tumors with some GFAP/Olig2/Syn expression, WT1 negative, and no reticular fibers are still neuroepithelial tumor, not sarcoma. CIC-HGNET does exist. However, CIC-HGNETs can’t include all the intracranial CIC tumors. There were still some cases that methylation failed to cluster, indicating new subtypes in CIC tumors (One case of PXA morphology clustered in GG and one case of embryonal tumor morphology clustered in independent group with near LGG-MYB and ependymoma-ZFTA). Although they are not CIC-HGNET, they also belong to CIC-NET, not sarcoma. This point requires special attention, because the two types of tumors have different treatments and different prognosis. The prognosis of neuroepithelial tumors with CIC-LEUTX fusion are much better than CIC sarcomas!

CONCLUSION
Pediatric central nervous system tumor with CIC fusion have heterogeneity. It manifests varied methylation signature and clinical characteristics. Whatever, there are two types in CNS tumor with CIC fusion. One is CIC sarcoma and the other is CIC-NET (including new type of CIC-HGNET).
P20.21.A SPINAL CORD ASTROBLASTOMA WITH EWSR1-BEND2 FUSION IN FEMALE PATIENTS: A REPORT OF FOUR CASES FROM CHINA AND A COMPREHENSIVE LITERATURE REVIEW
Authors: Fu L , Hu W , Xi S 
Published: October 2024

Abstract

BACKGROUND
Astroblastoma is an extremely rare central nervous system (CNS) tumor characterized by astroblastic pseudorosettes and vascular hyalinization. Despite these histologic hallmarks, its morphology can vary, occasionally resembling other CNS tumors like ependymoma. A novel tumor entity, astroblastoma, meningioma 1 (MN1)-altered, has been identified, featuring MN1 gene rearrangements typically involving BEN-domain containing 2 (BEND2) as a fusion partner. Most astroblastomas arise in the cerebral hemisphere.

MATERIAL AND METHODS
We present four cases of female patients with astroblastoma, focusing on their uncommon spinal cord location and the unique molecular feature of EWSR1-BEND2 fusion. All cases underwent next-generation sequencing (NGS), RNA sequencing (RNA-seq), and fluorescence in situ hybridization (FISH). Additionally, two cases underwent DNA methylation profiling.

RESULTS
These tumors displayed growth patterns akin to traditional intracranial astroblastomas, with three cases demonstrating high-grade histology, including elevated mitotic activity and necrosis. Interestingly, some cases exhibited positive staining for pan-cytokeratin (CK) and hormone receptors. Three out of the four patients experienced recurrence, underscoring the aggressive nature of this disease.

CONCLUSION
We suggest recognizing a new molecular subgroup of spinal astroblastoma and recommend testing newly diagnosed infratentorial astroblastomas for EWSR1-BEND2 fusion.
P22.01.A “IT FEELS LIKE I’M GRIEVING FOR SOMEONE THAT IS STILL ALIVE”: A QUALITATIVE STUDY OF THE EXPERIENCES OF NEURO-ONCOLOGY CAREGIVERS
Authors: Zanotto A , Goodall K , Ellison M , McVittie C 
Published: October 2024

Abstract

BACKGROUND
Informal caregiving of someone with a primary brain tumor is highly distressing and associated with an increased risk of depressive symptoms, anxiety, and caregiver burden. A brain tumor diagnosis poses unique symptoms and challenges, including an uncertain prognosis and related existential concerns, as well as neurological symptoms such as cognitive deficits or personality changes. Due to these characteristics and related care demands, family caregivers experience a different set of challenges compared to other types of cancer. The purpose of this qualitative study was to understand in-depth the experiences of informal caregivers’ coping, support needs, and changes in relationships while caring for a loved one with a brain tumor.

METHODS
In-depth interviews were conducted with 10 informal caregivers (3 spouses/partners, 4 parents, 2 children, and 1 sibling) of people with low- or high-grade tumor. The mean age of participants was 42 years (range 19-68 years), and 90% of participants were female (n = 9). Interviews were transcribed verbatim and analyzed using interpretative phenomenological analysis (IPA).

RESULTS
Participants experienced grief and feeling unappreciated, and were advocating for the person diagnosed. Caregivers described grieving for the loss of their loved one as they were before the diagnosis, but also for the loss of their previous lifestyle and the loss of a future together as they imagined it to be. There was a sense of uniqueness in caring for someone with a brain tumor. Participants felt unappreciated by society, particularly when comparing their current role to their professional identities. They were involved in the care decisions, researching treatment and support availability, and advocating for the needs of the person diagnosed.

CONCLUSION
The current findings highlight the importance of involving informal caregivers of persons with a brain tumor in the treatment process. It is crucial that their role is acknowledged and appreciated during interactions with healthcare professionals. Implications for communication with clinicians will be discussed.
P22.08.B INDICES OF SOCIOECONOMIC STATUS AND NEURO-ONCOLOGY CAREGIVERS’ RISK FOR IMMUNE DYFUNCTION
Authors: Sherwood P , Ho R , Ren D , Deng Z , Donovan H 
Published: October 2024

Abstract

BACKGROUND
In neuro-oncology, family income has been shown to impact both family caregiver and patient outcomes. In addition, subgroups of neuro-oncology caregivers have been shown to be at risk for immune dysfunction due to the stress of providing care. How socioeconomic status, particularly measures of socioeconomic status beyond simply income, plays a role in risk for altered cytokine levels is unexplored. The purpose of this analysis was to determine the effect of neighborhood level indices of socioeconomic status on Interleukin (IL)6, Il1ra, and C-reactive protein (CRP) levels in neuro-oncology family caregivers.

MATERIAL AND METHODS
Data were collected from 120 family caregivers of persons with a primary malignant brain tumor (NIH NR013170; only baseline data used for analysis). High sensitivity CRP, IL6, and IL1ra were assessed from five milliliters of blood obtained by standard venipuncture technique using sodium heparin tubes. Standardized neighborhood deprivation and social vulnerability levels were obtained using metrics from the United States Census Bureau which includes variables such as neighborhood unemployment, public transportation, education, health insurance coverage and family poverty levels. Final analyses were performed using multivariate linear regression adjusting for potential covariates.

RESULTS
Greater neighborhood deprivation was associated with higher CRP (p=0.05) and potentially (p=0.08) IL6 levels in family caregivers. Higher levels of social vulnerability (p=0.05) were also associated with higher CRP levels. All models adjusted for gender, age, race/ethnicity, any change in health over the two months prior to data collection, smoking, caffeine use, recent cold or fever, and number of comorbid conditions.

CONCLUSION
Recognizing the impact of characteristics placing neuro-oncology caregivers at risk for compromised immunity can inform health strategies and targeted interventions. Using indices of environmental vulnerability broader than simply income holds promise for targeting individuals for whom reduction of inflammation should be a primary target in order to improve quality of life and overall health outcomes.
P22.11.A POOR SELF-REPORTED PHYSICAL FUNCTIONING IN GLIOMA PATIENTS ACROSS THE DISEASE TRAJECTORY
Authors: Blom M E C , Gorter M , Belgers V , Röttgering J G , de Witt Hamer P C , van Lingen M R , Knoop H , Klein M , Douw L 
Published: October 2024

Abstract

BACKGROUND
Few studies have investigated physical functioning at multiple moments in the disease trajectory of glioma patients, nor have the correlates of physical functioning been determined. We therefore analyzed physical functioning in a large sample of glioma patients both at time of diagnosis and after primary treatment.

MATERIAL AND METHODS
In this retrospective study (patients were diagnosed between 2007-2023), the self-reported physical functioning subscale of the 36-Item Short Form Health Survey (SF-36) was used. Each patient was matched with two general population controls based on age, sex, and educational level. First, we compared physical functioning at time of diagnosis and after treatment with matched controls. Next, we determined correlates of patients’ physical functioning at both time points, namely age, sex, educational level, tumor histology, location, lateralization and grade, type of treatment, presence of epilepsy, usage of dexamethasone, Karnofsky Performance Status (KPS) and the National Institutes of Health Stroke Scale (NIHSS). Finally, in patients with assessments both at diagnosis and after treatment, we determined change in physical functioning over time.

RESULTS
We included 260 glioma patients at time of diagnosis and 109 glioma patients after treatment. Compared to controls, physical functioning of patients was significantly lower at the time of diagnosis (p = 0.022) and after treatment (p = 0.002). At both time points, poorer physical functioning was associated with having a tumor grade III, and KPS lower than 80. Moreover, at diagnosis only, poorer physical functioning correlated with lower educational level and right-sided tumor lateralization. Within the 77 glioma patients with data available at both time points, there was a large individual variability in change over time (28% increased; 40% decreased), but there was no significant change at the group level (p = 0.300).

CONCLUSION
Physical functioning is poor in glioma patients, regardless of phase of the disease. The main correlates of poor physical functioning are tumor and patient characteristics, such as KPS, tumor grade, educational level, tumor lateralization. Interestingly, neurological deficits were not related to physical functioning. Interventions aimed at improving physical functioning in glioma patients should be explored.
P23.05.B LOCKED-IN SYNDROME: A CHALLENGING COMPLICATION FOR SURGERY OF FORAMEN MAGNUM MENINGIOMAS: A SYSTEMATIC REVIEW AND ILLUSTRATIVE CASE
Authors: Torio J R , Meceda E , Concepcion C , Sylva J 
Published: October 2024

Abstract

BACKGROUND
Locked-in syndrome (LiS) as a complication from foramen magnum meningiomas (FMM) surgery is rare but impactful. Its exact occurrence rate isn’t well-documented due to its scarcity, often emerging from surgical maneuvers near the brainstem.

MATERIAL AND METHODS
We present a case of a 63-year-old female who was admitted for 5-month history of progressive bilateral lower extremity weakness who underwent a left suboccipital craniectomy, C1 laminectomy under neuronavigation and intra-operative neuromonitoring for MEP and SEP. We did a systematic search using MeSH keywords “Foramen Magnum Meningioma”, “Surgical Outcomes”, “Surgical Complications” and “Locked-In Syndrome” on November 26 2023, across multiple databases: PubMed, Google Scholar and Cochrane Library, wherein nine studies were included in the final qualitative analysis.

RESULTS
Majority of the surgically managed cases had FMM located anterolaterally with a median size of 2.06 -6.7cm. 32 cases had tumors encasing the vertebral artery. Morbidity rate was 38.6%, with most of the complications involved neurologic deficits secondary to the proximity of lesions to the brainstem and lower cranial nerves and hydrocephalus. No literature was able to report incidence of locked-in syndrome.

CONCLUSION
Incidence of LiS as a complication of FMM surgery is low but can have significant implications. Although vascular related etiology portends higher mortality as compared to non-vascular causes, role of prompt stroke treatments such as EVT can increase chance of better recovery. Outcomes tend to be challenging with limited prospects for complete recovery.
P25.04.B TEN YEARS EXPERIENCE OF THE “BRAIN TUMOR CENTER” OF ALMADA
Authors: Casimiro C D , Silva M , Monteiro J , Viegas C , Cunha e Sá M 
Published: October 2024

Abstract

BACKGROUND
The growing scientific knowledge on brain tumors and the progressive complexity of therapeutic options requires a multidisciplinary approach in a specialized environment. Brain tumor centers (BTC) are crucial in various aspects of assistance given to patients. Since 2013 our BTC assists in the diagnosis, treatment and monitoring of neuro-oncological patients in a multidisciplinary setting involving neurosurgery, neuro-oncology, medical oncology, radiotherapy, neuroradiology, pathology, rehabilitation, neuropsychology, palliative care, nursing and social care.

METHODS
Review of the data-set and activities of our BTC since its foundation.

RESULTS
Our BTC maintained an initial yearly growth and admitted 2055 patients during this period (~206 yearly). Patients were referred via primary care, regional hospitals or by admission for urgent care. The average time between proposal and surgery was ~16 days, with ~23 days until pathology results. Primary tumors of the central nervous system (CNS), namely glial tumors, were most frequent (54% of patients in 2023), followed by metastatic disease (36%, notably from lung origin). During this period, 17% of the diagnosis were made by biopsy and 6% of tumors were resected during awake surgery. Follow-up was carried out in accordance with evidence based international clinical guidelines, within the framework of a multidisciplinary neuro-oncology discussion where cases are presented, and exams and treatments are reviewed. Around ~11 patients were discussed per meeting, with ~24 meetings yearly. Overall, chemotherapy was proposed to 30% of patients, radiotherapy to 26% and radiosurgery to 8,5%.

DISCUSSION
Our BTC was founded to solve shortcomings identified in the treatment of patients and to create an organizational structure to optimizes their care. The multidisciplinary meetings have a distinct importance allowing the individual analysis of each case. Data recording contributes to epidemiological registries and must embrace the continuous neuro-oncology updates. Our data reinforces the need to guarantee fluid coordination and continuity of care, avoiding duplication of services, delays and waste of resources. The role of a nurse-coordinator is essential for the monitoring, coordination and follow-up of patients. The importance of efficient administrative work also cannot be understated. Besides wanting to receive the best treatment, patients wish to be cared for with dignity and respect and have their opinion taken into account. A guidance manual is being updated with the main aspects surrounding clinical care.

CONCLUSIONS
The last 10 years of an organized BTC made possible to gather relevant clinical information and to improve on the multidisciplinary care given to our neuro-oncological patients.
P26.04.A CASEIN KINASE 2 INHIBITOR, CX-4945, INDUCES APOPTOSIS AND RESTORES BLOOD BRAIN BARRIER HOMEOSTASIS IN A PRECLINICAL MODEL OF GLIOBLASTOMA
Authors: Caffo M , Casili G , Filippone A , Bova V , Mannino D , Salako A , Scuderi S , Bulzomì M , Campolo M , Esposito E 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma multiforme (GBM) is the most common primary malignant tumor of the central nervous system (CNS). Casein kinase 2 (CK2), a serine/threonine kinase, has been reported to have a dual action, regulating cellular processes and acting as an oncogenic promoter of tumor development. Here, we aimed to study the effect of CK2 inhibition by CX-4945 in U87 and hCMEC/D3 cells.

MATERIAL AND METHODS
U87 cells were treated with CX-4945 (5, 10 and 15 μM) for 24 hrs, while the hCMEC/D3 cell line were first stimulated with lipopolysacharide (LPS) and then treated with CX-4945 (5, 10 and 15 μM). Cytotoxicity tests, Western blot analysis and Immunofluorescence were performed to study the involvement of the different pathways.

RESULTS
We found that CX-4945 suppressed proliferation, reduced the inflammatory pathway and angiogenesis, oxidative stress, attenuated the activation of neurotrophic factors (NFs), while enhancing the apoptosis pathway. Furthermore, it promoted the restoration tight junctions.

CONCLUSION
These new insights into CK2 molecular signaling in GBM and blood brain barrier (BBB) demonstrate that CX-4945 may represent a promising approach for future GBM therapy, not only in the tumor microenvironment but also at the BBB.
P26.05.B DOSE-DEPENDENT DISTRIBUTION OF METHOTREXATE IN THE JUVENILE PIG BRAIN FOLLOWING INTRAVENOUS HIGH-DOSE METHOTREXATE INFUSION
Authors: Rasmussen T , Guscott M , Bascal Z , Ward S , Howard S , Buddington R K , Palmfeldt J , Mikkelsen T S 
Published: October 2024

Abstract

BACKGROUND
High-dose methotrexate (HD-MTX) is an essential element in the treatment of numerous cancers, including pediatric acute lymphoblastic leukemia with central nervous system involvement, and malignant brain tumors. However, our understanding of MTX distribution and elimination within the brain is incomplete. This limits the development of optimal dosing strategies. Additionally, while HD-MTX is effective, it is also known to cause acute central nervous system (CNS) toxicity in some patients. The exact mechanisms behind this toxicity are still unknown but is assumed by many to be linked to MTX mediated changes in brain metabolism. This calls for further investigation into MTX distribution and elimination within the brain, alongside a deeper understanding of MTX-induced changes in brain metabolism.

MATERIAL AND METHODS
This study assessed MTX levels in the brain of healthy, anesthetized juvenile pigs following a four-hour intravenous infusion of either standard 5 g/m2 HD-MTX or an increased dose of 20 g/m2 very high-dose MTX (VHD-MTX). A microdialysis probe was inserted into the cerebral frontal lobe to assess extracellular fluid MTX concentration. Blood plasma and urine samples were also collected. MTX concentrations were measured across samples using a highly sensitive liquid chromatography-mass spectrometry (LC-MS).

RESULTS
Serial samples of microdialysate, plasma, and urine were successfully collected from sedated pigs and MTX was detectable across all samples. The median MTX exposure represented as area under the drug concentration curve (AUC) in plasma and microdialysate was increased 3.6-fold and 3.1-fold respectively at the end of the four-hour infusion of VHD-MTX compared to HD-MTX. This increase was 4.9-fold and 3.1-fold after an additional four hours of observation post MTX-infusion (p &lt; 0.05, n=12).

CONCLUSION
This study is part of a larger investigation exploring the use of VHD-MTX in treating CNS cancers. The results demonstrate a dose dependent increase in MTX exposure in extracellular fluid of the cerebral frontal lobe as demonstrated by microdialysis. Further studies using this model will investigate the effects of combining VHD-MTX with strategies to manage systemic toxicity. Additionally, we will employ explorative LC-MS metabolomics to assess changes in the metabolomic profile in CNS samples to address possible changes that could explain the phenomenon of CNS toxicity.
P26.09.A METFORMIN REPURPOSING FOR GLIOBLASTOMA TREATMENT
Authors: Barciszewska A , Belter A , Barciszewski J F , Gawrońska I , Giel-Pietraszuk M , Naskręt-Barciszewska M Z 
Published: October 2024

Abstract

BACKGROUND
Being the most common and aggressive malignant primary brain tumor in adults, glioblastoma (GBM) is, simultaneously, the best-studied central nervous system neoplasm with the continuous development of new treatments, including targeted therapies and immunotherapy, to improve outcomes for GBM patients. However, even with such a big effort, GBMs are still challenging to manage, with poor prognosis. Recurrence is certain, and the average survival time is relatively short. In the search for effective therapies, the focus switches now to existing drugs with the aim of repurposing. One of the possible candidates is the first-line drug for type 2 diabetes - metformin (MTF). It acts mainly through decreasing liver glucose production and improving insulin sensitivity. However, the exact mechanism of MTF’s action is not fully understood. Its positive influence is observed in many aspects of cardiovascular disease, gut microbiota modulation, hormonal balance, cancer prevention and treatment, as well as longevity and aging. These multiple effects highlight the potential of MTF as a versatile medication beyond its traditional use in diabetes. They also drive attention to possible underlying molecular processes responsible for such a broad action. The only phenomenon that can explain such a complex influence on diverse biological processes is epigenetics. One of the main epigenetic processes is DNA methylation, which directly influences gene expression. 5-methylcytosine (m5C) in DNA is the best-characterized epigenetic mark. Our project aimed to evaluate the total DNA methylation level after MTF administration on the GBM cell lines.

MATERIAL AND METHODS
Using the nucleotide post-labeling method, we analyzed the total amount of m5C in DNA of GBM (T98G, U138), and normal (HaCaT) cell lines treated with MTF.

RESULTS
No significant changes in total DNA methylation were observed in non-cancer cell lines (HaCaT) treated with MTF, due to small toxicity confirmed also with global DNA guanosine oxidation (8-oxo-dG). On the opposite, DNA hypomethylation was observed for GBM cell lines (T98G and U138) with increasing MTF concentration and incubation time. We also analyzed the combined effects of MTF with temozolomide (TMZ), the first-line chemotherapeutic for GBM. MTF potentiated the demethylating effect of TMZ. The concomitant application of both drugs induced DNA oxidation.

CONCLUSION
Total DNA methylation changes in GBM cell lines under MTF treatment suggest the new mechanism of that drug action and promote clinical implications for adjusting MTF and TMZ therapy in GBM patients. Our results show the potential and possible obstacles of the combined therapy of TMZ with MTF. Combined therapy with both drugs leads to total DNA hypomethylation. Therefore it is necessary to adjust MTF administration during TMZ therapy.

FUNDING
M.Z.N.-B. is supported by the OPUS 19 (2020/37/B/NZ5/03249)