bluuebunny/crossref_metadata_2025_split huggingface dataset:
P18.29.A METHYLATION PATTERN OF ANDROGEN RECEPTOR REGULATORS IN ADULT-TYPE DIFFUSE GLIOMAS
Authors: Gatto L , Asioli S , Morandi L , Di Nunno V , Tosoni A , Bartolini S , Griva L , Melotti S , Foschini M , Franceschi E 
Published: October 2024

Abstract

BACKGROUND
Androgen receptor (AR) is a ligand-mediated transcription factor that belongs to the superfamily of steroid receptors. AR is overexpressed in several solid tumors and is a potential therapeutic target. The AR gene is located on X chromosome at Xq11-12. In addition to AR, a group of genes involved in the regulation of AR function and expression are located on X chromosome: FLNA, UXT genes and the MAGE family genes, (MAGEA1, MAGEA2, MAGEA3, MAGEA9, MAGEA11, MAGEC1, MAGEC2). Our study aims to characterize AR in adult-type diffuse gliomas, evaluating the AR status and the methylation pattern of AR regulatory genes.

MATERIAL AND METHODS
In this retrospective analysis we included patients diagnosed with adult-type diffuse gliomas grade 2 or 3 or 4 according to WHO 2021 classification, treated at our institution. Immunohistochemistry (IHC) and gene methylation analysis were performed to evaluate AR expression and its regulatory status.

RESULTS
We included samples from 50 patients (M:F=26:24). Immunohistochemical AR positivity was predominant in males (p= 0.04) and in patients with glioblastoma IDH-wild type compared to lower grade adult-type diffuse gliomas (p= 0.04). AR positivity was more frequent in astrocytomas IDH-mutant compared to oligodendrogliomas IDH-mutant and 1p19q codeleted (p= 0.02). Moreover, AR expression was more frequent in MGMT unmethylated gliomas compared to MGMT methylated tumors (p=0.02). AR was found hypomethylated in cases with immunohistochemical positivity AR (Kruskal Wallis&lt;0.05). UXT, MAGEA1and MAGEA1-11 were hypermethylated in AR positive gliomas (Kruskal Wallis&lt;0.05). AR hypomethylation was deeper in GB (Kruskal Wallis&lt;0.05).

CONCLUSION
AR overexpression seems to be predominant in male patients with high-grade unmethylated adult-type diffuse gliomas. The AR gene promoter is hypomethylated in AR positive adult-type diffuse gliomas. Methylation pattern of AR regulatory genes located on X chromosome regulate AR expression. These data suggest that AR signaling may be promising for potential treatment using antiandrogen therapies.
P18.38.A ROLE OF CARBOHYDRATE-BINDING PROTEINS IN CONTROLLING GLIOBLASTOMA STEM CELL FATE AND TUMORIGENESIS
Authors: Sliusar M , Chaillot L , Burban A , Sharanek A , Bikfalvi A 
Published: October 2024

Abstract

BACKGROUND
Carbohydrate-binding proteins, galectins (GAL, LGALS), is a family of proteins that specifically bind β-galactoside sugars. Some members of the GAL family have been shown to be associated with tumor development, including glioblastoma (GB). However, their precise role is poorly investigated.

MATERIAL AND METHODS
Publicly available data sets were analyzed with SUMO software. scRNA-seq data analysis was conducted with the R toolkit Seurat and SingleR package. For in vitro experiments, patient-derived glioblastoma stem cells (GSCs) BTSC73 and BTSC12 were used as cellular models. Differentiation was induced by culturing GSCs on laminin-coated plates in media supplemented with 10% FBS. Hypoxia-response was studied at 1% O2. For depletion experiments siRNA silencing was used as well as CRISPR-Cas9. Proliferation was assessed by EDU staining. Cell death was assessed using Annexin/PI double staining assay.

RESULTS
We first conducted an in silico analysis for LGALS1, -3, -8, and -9 expression in GB. We found that specific combinations of these Galectins are associated with a poor prognosis. In GB patients. When scRNASeq data were analyzed, Galactins are distributed heterogeneously in different cell types in the tumor. For example, Gal3 is expressed in tumor cells, macrophages, and T-cells. We then conducted in vitro experiments to assess the role of Gal3 and Gal9. Depletion of LGALS3 in BTSC73 led to a decrease in cell number related to an effect on proliferation but not apoptosis. In addition, LGALS3 depletion in GSCs reduced stemness markers such as Sox2 and Nestin. We also investigated LGALS3 and LGALS9 expression during differentiation and found their expression increased which was also the case under hypoxia.

CONCLUSION
This indicates that Gals and especially Gal3 and Gal9 are involved in GB development including, proliferation stemness and differentiation.
P18.41.A SINGLE CENTRE EXPERIENCE OF BENEFIT OF CHEMOTHERAPY WITH 40GY/15# RADIOTHERAPY IN PATIENTS WITH GLIOBLASTOMA MULTIFORME (GBM)
Authors: Streatfield K , Davies A , Glendenning J , Forner S L 
Published: October 2024

Abstract

BACKGROUND
GBM patients are associated with a poor prognosis. Hypofractionated radiotherapy (RT) - 40Gy/15# - is standard in the older population (&gt;70), lower performance status and in extensive disease. This regimen provides a median overall survival (mOS) of 8 months and progression free survival (PFS) of 3.9 months (1). The addition of Temozolomide increases outcomes (mOS 9.3 months, PFS 5.3 months). Methylated MGMT status further improves mOS to 13.5 months (2). This review analyses outcomes of patients treated with this regimen at the Kent Oncology Centre (KOC).

MATERIAL AND METHODS
A retrospective review of GBM patients at the regional KOC treated with the 40Gy/15# regimen between 2018 and 2022. Demographics, histology, treatment and survival data were gathered through electronic records. Statistical information was gathered using Python and the Lifelines survival analysis library.

RESULTS
Data was collected for 82 GBM patients with a 33-80 age range. Of the cohort, 39 patients (48%) were female and 43 were male (52%). Type of surgery was divided into biopsy (46%) and debulking (50%), with the remaining not applicable. Within the cohort, 27 patients received temozolomide with RT, with an average of 5 adjuvant cycles received; the remaining receiving RT alone (55). 28 patients were MGMT methylated, 48 unmethylated, with the remaining unknown. mOS for the total population was 8 months. In MGMT methylated patients, OS increased to 13 months. In the sub group of unmethylated patients OS increased to 10 months with the addition of temozolomide, compared to 7 months for radiotherapy alone. PFS was measured as the time between the date of action sheet and date of first progression. For the whole cohort this was 4 months, however this increased to 5 months for the methylated cohort. The addition of temozolomide for unmethylated patients showed no improvement for PFS.

CONCLUSION
Local results support previously published trial data, validating the use of chemotherapy for GBM patients, regardless of MGMT status, with additional overall survival benefit. However, unmethylated patients saw no additional PFS benefit from temozolomide.
P18.47.A THE PROGNOSTIC IMPACT OF CDKN2A/B HETEROZYGOUS DELETIONS IN IDH-MUTANT GLIOMA
Authors: Ippen F M , Hielscher T , Göbel K , Friedel D , Reuss D , von Deimling A , Wick W , Sahm F , Suwala A 
Published: October 2024

Abstract

BACKGROUND
Homozygous deletions of CDKN2A/B confer unfavorable prognosis in IDH-mutant gliomas and are a criterion for CNS WHO grade 4 in IDH-mutant astrocytomas, but the role of heterozygous CDKN2A/B deletions remains less well understood. The aim of this study was to assess the prognostic impact of CDKN2A/B heterozygous deletions in IDH-mutant low-grade astrocytoma and oligodendroglioma.

MATERIAL AND METHODS
Tissue samples diagnosed as astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3 were collected from the archive of the Institute of Neuropathology in Heidelberg. DNA methylation analysis was performed on formalin-fixed paraffin-embedded (FFPE) samples. Evaluation of the CDKN2A/B locus was performed by visual inspection of copy-number plots derived from methylation-array data for each case. Heterozygous and homozygous losses were assessed in relation to whole chromosomal or larger segmental losses and gains in the chromosomal profile. Survival was assessed using the Kaplan-Meier method.

RESULTS
A total of 334 low-grade glioma cases were identified. Those cases included 173 astrocytomas and 161 oligodendrogliomas. Heterozygous deletions in CDKN2A/B (37/173 in astrocytomas, 15/161 in oligodendrogliomas) did not confer worse survival outcomes compared to CDKN2A/B wildtype cases in neither low grade astrocytoma (p= 0.2458) nor oligodendroglioma (p= 0.2779), regardless of CNS WHO grade, which was further demonstrated on a subgroup of astrocytoma, IDH mutant CNS WHO 4 cases (p= 0.1143).

CONCLUSION
Our study suggests that heterozygous CDKN2A/B deletions do not confer worse survival rates with respect to OS and PFS in astrocytoma, IDH-mutant and oligodendroglioma, IDH-mutant, 1p/19q co-deleted CNS WHO grade 2 and 3.
P18.52.B UNVEILING THE IMPACT OF CANCER-IGG ON GLIOMA: INSIGHTS FROM BIOLOGICAL BEHAVIOR AND TUMOR MICROENVIRONMENT
Authors: Han X , Li H , Su L , Tian L , Wang W , Xiao Z , Guo H , Li X , Fan T , Zhou H , Xue X 
Published: October 2024

Abstract

BACKGROUND
Gliomas are the most common malignant brain tumor in the central nervous system, with high invasiveness and heterogeneity. In recent years, cancer derived immunoglobulin G (Cancer-IgG) has been drawing attention of researchers. Cancer-IgG was identified in tumors and could promote tumorigenesis and progression.

MATERIAL AND METHODS
In this study, we explored the expression pattern of Cancer-IgG using available datasets and validated with our own patient samples. A serious of loss- and gain-of function assays were performed to investigate the role of Cancer-IgG. Possible mechanisms were unveiled by co-immunoprecipitation and RNA sequencing.

RESULTS
Our result demonstrated that Cancer-IgG expresses in glioma. And the expression pattern is associated with poor prognosis and malignant molecular characterization. Functional assays confirmed that Cancer-IgG could promote glioma cells proliferation, migration, invasion and resistant to apoptosis. The cGMP/PKG/VASP pathway could be the underlying mechanisms by which Cancer-IgG has an effect. Evidence from co-culture assay suggest that Cancer-IgG could induce macrophages M2 polarization.

CONCLUSION
Collectively, Cancer-IgG could be identified in glioma cells and it could facilitate the malignant biological phenotype in vivo and in vitro. In glioma microenvironment, Cancer-IgG could induce M2 macrophages polarization.
P19.06.B EXPLORING FIBROBLAST ACTIVATING PROTEIN (FAP) EXPRESSION AS THERANOSTIC TARGET IN HIGH-GRADE MENINGIOMA
Authors: Mair M J , Hartenbach S , Tomasich E , Maas S L N , Bosch S A , Widhalm G , Eckert F , Sahm F , Hainfellner J A , Hartenbach M , Berghoff A S , Preusser M , Albert N L 
Published: October 2024

Abstract

BACKGROUND
The therapeutic management of higher-grade meningiomas is challenging given their high recurrence rates and limited treatment options after exhaustion of local modalities. Radioligand therapies such as [177Lu]Lu-DOTATATE targeting somatostatin receptors (SSTR) have shown promising results in small clinical trials and retrospective case series. Further studies on theranostic approaches targeting fibroblast activating protein (FAP) are ongoing in a variety of extracranial solid tumors.

MATERIAL AND METHODS
Formalin-fixed, paraffin-embedded tumor samples of atypical (WHO grade 2) and anaplastic (WHO grade 3) meningioma were immunohistochemically stained for FAP and SSTR2a. Antibodies used were monoclonal rabbit anti-FAP (clone JA56-11, Thermo Fisher Scientific) and monoclonal rabbit anti-SSTR2a (clone EP149, Cell Marque). Panel sequencing for frequently altered genes in meningioma (NF2, TRAF7, KLF4, SMO, AKT1, TERT-promotor, ARID, SUFU, PIK3CA) was performed using Illumina NextSeq, and DNA methylation analysis was done using Illumina 850k chips.

RESULTS
In total, samples of 58 patients were used for analysis, of whom 35/58 (60.3%) were female and median age was 60 years (range: 19-83). Included specimen were from first resection in 39 cases (67.2%). Original histological diagnoses were atypical meningioma in 30/58 (51.7%), chordoid meningioma in 9/58 (15.5%), anaplastic meningioma in 18/58 (31.0%) and rhabdoid meningioma in 1/58 (1.7%). Reclassification according to WHO 2021 identified CNS WHO grade 2 in 39/58 (67.2%), CNS WHO grade 3 in 18/58 (31.0%) and CNS WHO grade 1 in 1/58 (1.7%) patients. FAP expression was observed in 15/58 (25.9%) included samples, most markedly at tumor borders and in stroma-rich areas. Of these, 12 (80.0%) also showed membranous staining for SSTR2a, of whom 6 showed strong, 3 medium and 3 weak positivity. FAP expression was associated with malignant biological behavior, as 12/18 (66.7%) of CNS WHO grade 3 tumors (compared to 3/39, 7.7% of CNS WHO 2, p &lt; 0.001) and 4/5 (80.0%) samples with homozygous deletion in CDKN2A/B were FAP-positive (p = 0.013). In addition, FAP expression was more frequently observed in patients with NF2 mutations (10/25, 40.0%) than in those with wild-type NF2 (5/33, 15.2%, p = 0.032). FAP-positive samples were numerically more common among tumors of malignant (4/8, 50.0%) than intermediate (int-A/int-B: 7/27, 25.9%) or benign (ben-1/2/3: 4/23, 17.4%, p = 0.069) methylation classes.

CONCLUSION
FAP is expressed in a subset of higher-grade meningioma samples, and further investigation of FAP-targeted radioligands is warranted. Given that SSTR2a and FAP are frequently co-expressed, potential synergistic effects of combination treatments can be investigated.
P19.11.B PRELIMINARY DATA FROM THE REGION ÖREBRO COUNTY MENINGIOMA PROJECT
Authors: Löfgren D , Olivecrona M 
Published: October 2024

Abstract

BACKGROUND
Meningioma is typically benign and is occasionally detected during examinations due to other reasons (e.g. suspected stroke, trauma). Reported incidence figures usually come from various registers, and most reported prevalence figures are estimations derived from incidence figures and survival data. The Region Örebro County meningioma project aims to gain a better understanding of the incidence and prevalence of meningioma in the population. With these preliminary data, we seek to ascertain the practical feasibility of our proposed search method.

MATERIAL AND METHODS
In the Swedish county of Örebro with 302,252 inhabitants (2019), all radiology departments are within the public healthcare system. The electronic radiology archive (ERA) includes all patients who have undergone any type of radiological examination in the region since its introduction in 1996. To determine the number of individuals with meningioma in the region and when they were diagnosed, we conducted free-text searches for the word “meningioma” with various spelling variations in ERA and included all patients where the word appears in ERA referrals or responses. Subsequently, using data from the region’s electronic medical records (EMR), we excluded all patients not residing within the region. We then manually reviewed these patients’ referrals, written reports and radiology examinations, to determine whether they have meningioma, the date of diagnosis, whether it was an incidental finding, and presence of multiple meningioma.

RESULTS
We identified 3,428 patients, of which 3,064 have been included in this study (being residents of the region). In a preliminary review, we have been able to identify 1,663 (55 %) patients with likely meningioma. Of the 1,663 patients, 5 % had a diagnosis date before the introduction of ERA. The median age was 73 (IQR 61-82) years. There were 24 % males and 76 % females. Multiple meningioma were found in 9 % of the patients. In the preliminary review 64 % were incidental findings, while 21 % and 15 % were classified as non-incidental and indeterminate, respectively.

CONCLUSION
Performing free-text ERA/EMR searches is a potential avenue to achieve better coverage when investigating incidence and prevalence of a disease such as meningioma in a public healthcare setting. In our initial review, it is evident that the method identifies and can retrieve meningioma patients from the ERA. Gender distribution, median age and multiple meningioma numbers are comparable to other reported meningioma populations. Based on our experience with this dataset, it is not advisable to rely solely on simple automated searches. Projects akin to this would likely be well suited for future automated image analysis (volumetric measurement, meningioma identification, etc.).
P19.13.A RESULTS FROM THE COSMIC PROJECT: CORE OUTCOME SETS FOR MENINGIOMA IN CLINICAL EFFECTIVENESS STUDIES
Authors: Jenkinson M D , Millward C P , Islim A I , Keshwara S M , Srikandarajah N , Brodbelt A R , Marson A G , Williamson P R 
Published: October 2024

Abstract

BACKGROUND
The minimum outcomes that should be measured and reported in all clinical trials for a specific health condition or health area can be defined by a Core Outcome Sets. The aim was to develop core outcome sets for cranial meningioma; for clinical trials (COSMIC: Intervention) and observational studies (COSMIC: Observation).

MATERIAL AND METHODS
An international study advisory group was formed with representation from charities (IBTA, TBTC, brainstust), neuro-oncology organisations (BNOS, EANO, EORTC, ICOM, RANO-PRO, SNO) and neurosurgery societies (SBNS, BIMS). Systematic literature reviews and trial registry searches were performed to identify outcomes reported in published and ongoing 1) meningioma clinical trials, and 2) studies of incidental/untreated meningioma. Outcomes were deduplicated and categorised. Individuals from stakeholder groups (including meningioma patients and carers, healthcare professionals, researchers) were invited to participate in 2-round, international, modified eDelphi surveys. The final core outcome sets were ratified through online consensus meetings.

RESULTS
The COSMIC: Intervention systematic review identified 660 verbatim outcomes, rationalized into 24 Delphi survey items. Following the consensus meeting, 15 outcomes were included in the final set. For COSMIC: Observation, 267 verbatim outcomes were identified and rationalized into 17 Delphi survey items. 16 outcomes were included in the final set. Eight core outcomes common to both COSMIC: Intervention and COSMIC: Observation COS: tumour growth, physical, emotional, and neurocognitive functioning, overall quality of life, progression-free survival, meningioma specific mortality and overall survival. Role and social functioning were core outcomes in COSMIC Observation but not COSMIC intervention.

CONCLUSION
COSMIC has defined the core outcome sets for use in future meningioma clinical trials and studies. Role and social functioning were important to incidental meningioma patients and likely reflects the anxiety and uncertainty around clinical treatment. The international stakeholder community will adopt and use these core outcome sets in future trials.
P20.02.B ANAPLASTIC ASTROCYTOMA AS A SECOND PRIMARY BRAIN MALIGNANCY IN PATIENT WITH NON-HODGKIN LYMPHOMA
Authors: Ardhini R 
Published: October 2024

Abstract

BACKGROUND
Malignant lymphoma survivor can develop second primary malignancies, but have been rarely reported to occur in central nervous system. Risk factor increasing second primary tumor is not well determined, possibly due to lymphoma subtype, patients demographic, previous chemotherapy or radiation therapy. We report a very rare case of anaplastic astrocytoma in patient with remission of non-Hodgkin’s lymphoma (NHL).

CASE PRESENTATION
43-year-old man presented with progressive weakness on the left extremity for the past two months followed by progressive headache and left pacial palsy. Patient had a history of diffuse large B-cell lymphoma (DLBCL) in the lower leg in the previous 5 years and had received systemic chemotherapy. He was on regular follow-up without any evidence of relapsing disease. Brain MRI showed heterogenous intraaxial lesion in the right periventricular white matter of frontal lobe with large peritumoral edema suggestive secondary central nervous system lymphoma. There were no evidence of reccurence disease in the lower leg or other active disease, and no blast cells were found in CSF examination. Craniotomy was performed and histopathological examination revealed Anaplastic astrocytoma, NOS, WHO grade III (based on the WHO 2016 classification). Then the patient received concomittant chemoradiation and adjuvant Temozolomide.

CONCLUSION
Second primary brain malignancy is extremely rare in patient with treated diffuse large B-cell lymphoma. Surgical management and pathological examination must be performed to obtain a definite diagnosis, and to rule out secondary central nervous system lymphoma.
P20.03.B ASSESSING QUALITY OF LIFE IN SCHWANNOMATOSIS: A SYSTEMATIC REVIEW
Authors: Lawson McLean A , Rosahl S , Lawson McLean A , Freier A , Löschner D , Kamp M , Neumeister A , Senft C , Demetriades A 
Published: October 2024

Abstract

BACKGROUND
The term schwannomatosis refers to rare genetic disorders associated with the development of multiple tumours within the central and/or peripheral nervous system. Recent advancements in our molecular understanding of these disorders have led to a redefined conceptual framework within the field. This revised framework groups nf2-related schwannomatosis with other forms of schwannomatosis resulting from various causative pathogenic variants, highlighting their distinct nature compared to neurofibromatosis 1.

MATERIAL AND METHODS
A comprehensive search of electronic databases, including PubMed, MEDLINE, and Scopus, was performed in August 2023. The search methodology entailed variations of keywords such as “neurofibromatosis 2,” “schwannomatosis,” “quality of life,” and “patient-reported outcomes.” Inclusion criteria encompassed studies evaluating QoL in schwannomatosis patients, utilising validated QoL appraisal tools or patient-reported outcome metrics. Case studies and reviews were excluded.

RESULTS
Initial searches yielded 224 articles after removal of duplicates. Following screening, 37 articles met inclusion criteria. These studies employed diverse assessment instruments, including the SF-36 (n=7), PHQ-9 (n=8), GAD-7 (n=5), and the disease-specific questionnaire NFTI-QOL (n=13). Interestingly, patients with nf2-related schwannomatosis overall had worse physical and emotional well-being than the general population, while non-nf2-schwannomatosis patients mainly reported worse pain than the general population.

CONCLUSION
This systematic review provides a comprehensive synopsis of QoL literature pertinent to patients with schwannomatosis. The findings underscore the imperative of a holistic patient-care paradigm, addressing not only tumour management but also the augmentation of overall well-being and QoL among affected individuals.