bluuebunny/crossref_metadata_2025_split huggingface dataset:
P20.24.A THE WIDE HISTOLOGICAL SPECTRUM OF ZFTA FUSED WITHOUT RELA FUSION SUPRATENTORIAL EPENDYMOMAS: FROM SARCOMA-LIKE TO EMBRYONAL TUMOR-LIKE
Authors: Xi S , Chen Z 
Published: October 2024

Abstract

BACKGROUND
According to the 5th World Health Organization (WHO) classification of the central nervous system, supratentorial-ependymomas (ST-EPN) RELA-fusion positive was replaced by ST-EPN, ZFTA-fusion positive. This modification reinforces the importance of the ZFTA gene in ST-EPN. The significant histopathological heterogeneity in supratentorial ZFTA fused without RELA fusion ependymomas (not RELA, ZFTA fused EPN) has raised concern recently, which included varied histological patterns.

MATERIAL AND METHODS
To expand the histological spectrum of not RELA, ZFTA fused EPN, we reported four cases of not RELA, ZFTA fused ST-EPN, and described the histological features of this uncommon entity.

RESULTS
In our cohort, one case showed small round cells with chondromyxoid or fibrous stromal components forming a sarcoma-like pattern. The second case presented a lobular or sheet-like pattern infiltrating with trapped glia. The tumor cells carried reticular cytoplasm, prominent cell membranes, and irregular wrinkle nuclei. They were strongly positive for cytokeratin, which resembled metastatic cancer. The third case showed an embryonal tumor-like pattern with relatively circumscribed but infiltrated cells, hypercellularity and necrosis were seen. Focal differentiation to neurocytes and ganglion cells could be observed. The tumor cells are partially positive for Neu-N. The last case presented the embryonal tumor-like pattern with highly cellular unstructured primitive areas and high-grade classic EPN histology like the rosettes and fibrillar areas with few nuclei. The first case carried ZFTA-MAML2 fusion, and three instances carried ZFTA-NOCA2 fusion. Three cases underwent DNA methylation profiling and were classified as EPN satellite clusters. The clinicopathological features and molecular alterations are summarized, one of the patients died during the follow-up.

CONCLUSION
Compared to the ST-EPN, RELA-fusion positive, not RELA, ZFTA fused ST-EPN often presented uncommon histological features, the adult cases often present morphology resembling sarcoma or metastatic cancer, and the pediatric cases present embryonal tumor-like histology. The subtype may carry a worse outcome.
P21.01.A CEREBELLOPONTINE ANGLE EPIDERMOID CYST WITH MALIGNANT TRANSFORMATION TO SQUAMOUS CELL CARCINOMA: UNUSUAL COMPLICATION OF A BENIGN INTRACRANIAL TUMOR
Authors: Garcilazo-Reyes Y J , Navarro-Fernández J O , Magos-Rodríguez D , Arias-Ruiz L F , Pérez-Díaz M L , Gómez-Apo E , Hernández-Montes de Oca R , Gutiérrez-Aceves G A 
Published: October 2024

Abstract

BACKGROUND
Intracranial epidermoid cysts (EC) account for approximately 0.2%-1.8% of all intracranial tumors. Extremely rare, these benign lesions may undergo malignant transformation into squamous cell carcinoma (SCC). The time frame for transformation can vary greatly, and the ideal management approach remains uncertain.

MATERIAL AND METHODS
55-year-old female patient with history of migraines was diagnosed with an incidental cystic lesion suggestive of EC in right cerebellopontine angle (CPA) since the age of 30. She experienced a sudden onset in March 2023 of auditory decline in her right ear, tinnitus, vertigo, headache, dysgeusia, and gait disturbance. Examination revealed involvement of the VIII right cranial nerve with sensorineural hearing loss and complete right facial nerve palsy. She underwent surgery in June 2023 where the cyst was resected however, the capsule of the tumor was strongly adhered to the brainstem, unable to be removed. It showed positive immunohistochemistry for p63, p40, CK5/6, CK7, D2-40, S100, PD-L1, Ki67 was positive in 20% of neoplastic cells, brachyury was negative, consistent with EC with malignant transformation to SCC. She developed few days after the surgery, dysarthria, diplopia, IV and VI right nerve palsies and right dysmetria. Neuroaxis contrast-enhanced MRI was performed with no evidence of lesion otherwise. Brainstem auditory evoked potentials, blink reflex test and facial nerve conduction tests were completed and abnormal due to axonal right facial nerve neuropathy with side-to-side ≥ 90% difference and profound right hearing loss.

RESULTS
The one-month follow-up brain MRI showed the right CPA lesion with heterogeneous enhancement with increase in diameter and involvement of the auditory canal. 18FDG) PET/CT demonstrated focal hypermetabolism (SUVmax 10.3) in the right CPA indicative of progression. She underwent radiosurgery with a total dose of 30 Gy in 5 sessions (October 2023). The follow-up 18FDG PET/CT (April 19, 2024) showed no distant sites associated with abnormal hypermetabolism but persistent focal hypermetabolism that decreased compared to previous exam (SUVmax 7.2). The patient is currently 11 months apart from her diagnosis without new neurological findings. Chemotherapy or checkpoint inhibitors have not been used yet.

CONCLUSION
We report a case of intracranial SCC derived from an EC, the occurrence this malignant transformation is uncommon and typically indicates a poor prognosis. Small series and case reports are to date available in the literature. After surgery, radiotherapy or radiosurgery should be considered, close follow-up is recommended, chemotherapy or immunotherapy can be used but its effectiveness remains unclear.
P22.10.B LOW-GRADE GLIOMA PATIENTS WITHOUT PROBLEMS IN DAILY FUNCTIONING: A SILENT MINORITY
Authors: Siebenga F F , van der Weide H L , Gelmers F , Rakers S E , Kramer M C A , van der Hoorn A , Enting R E , Bosma I , Groen R J , Jeltema H , Wagemakers M , Spikman J M , Buunk A M 
Published: October 2024

Abstract

BACKGROUND
Low-grade gliomas (LGG) represent a heterogeneous group of primary brain tumors. Although all patients with LGG face similar challenges in coping with an incurable disease, interestingly, a subset of patients reports no (significant) problems in daily functioning and appear to resume their activities without changes. It is crucial to identify the group of patients that seem to cope so well, in order to find possible indications to help patients who do experience problems in daily functioning. Therefore, the present study aims to characterize the LGG patient group without problems in daily functioning.

MATERIAL AND METHODS
144 patients with LGG were included post-surgery and before adjuvant therapy. Patients were divided into two groups: patients with and without problems in daily functioning, based on the Patient Competency Rating Scale (PCRS). Demographic variables, disease characteristics (tumor location, tumor volume), anxiety, depression (HADS), coping (UCL) and general cognition (neuropsychological tests) were analysed to identify characteristics specific to the patient group without problems in daily functioning.

RESULTS
Of the entire LGG cohort (mean age= 43 ± 12), 26.4% of the patients no (significant) problems in daily functioning. No significant differences were found for demographics (gender, age and educational level), disease characteristics and general cognition between patients with and without problems in daily functioning (p&gt;0.05). However, patients without problems had significantly lower scores for anxiety (p&lt;.01), depression (p&lt;.01), avoidant (p=&lt;.01) and passive coping (p&lt;.001), compared to patients with problems in daily functioning.

CONCLUSION
More than a quarter of the patients with LGG experience no (significant) problems in daily functioning, after surgery and before adjuvant therapy. Notably, this subset of patients did not differ from patients with problems in daily functioning considering demographics, disease characteristics and cognitive functioning. However, the cohort of patients with no problems in daily functioning report lower levels of anxiety and depression, and use a more effective coping style, compared to patients who do experience problems in daily functioning. Therefore, it seems to be crucial addressing coping strategies, serving as a potential to help patients who do experience problems in daily functioning. Future research should focus on whether the patient group without problems in daily functioning continues to report zero complaints after adjuvant therapy, i.e. examining if an initial problem-free status serves as a protective factor during and after treatment.
P24.03.B PATIENT AND CAREGIVER VIEWS ON AN INNOVATIVE SURGICALLY IMPLANTABLE MEDICAL DEVICE TO DELIVER ELECTRIC FIELD THERAPY IN GLIOBLASTOMA
Authors: Purdy R , Thomson A , Bulbeck H , Munir N , Venters D , Koh K , Akhtar Q , Bullock C , Price S , Fu R 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is the most common primary brain cancer in adults and carries a poor prognosis, with just 3% of those diagnosed surviving to 5 years. The standard of care (SOC) for glioblastoma has remained the same for the last 20 years: debulking brain surgery, chemotherapy, and radiotherapy. Electric field therapy (EFT), or Tumour Treating Fields (TTFields), is a promising novel treatment option for glioblastoma but there is just one commercially available device, applied to the head externally. It is currently unavailable to GBM patients in the UK through the National Health Service (NHS). QV Bioelectronics is developing an implantable medical device to deliver EFT, called GRACE, and has recently undertaken several patient and public involvement (PPI) studies alongside charity and clinical partners to understand the views of patients and caregivers on glioblastoma treatment and emerging EFT research.

MATERIAL AND METHODS
19 patients living with high grade glioma, of which glioblastoma is a subtype, and 6 caregivers were recruited to the PPI sessions. Four live workshops were conducted virtually in focus groups, each session lasting between 60 and 120 minutes. During the workshops, information was presented to participants with regular intervals for open-ended discussion. Material explored as part of the workshops included current treatment options for GBM, the design of GRACE, its eligibility criteria, and clinical trial design. A survey comprising 10 questions was also sent to a sample of participants prior to the workshops to understand views independent of technology developed by QV Bioelectronics.

RESULTS
The questionnaire was sent to 17 participants prior to the workshops, of whom 14 (82%) responded (8 patients and 6 caregivers). 100% strongly agreed that better treatment options for glioblastoma were needed, and only 21% were aware of TTFields as an approved therapy. 93% would consider an implanted medical device to deliver EFT as part of their or their close person’s treatment plan. During the workshops, the main concern expressed by participants was the impact of current treatment options on activities of daily living (ADLs) and quality of life. Participants felt that GRACE and its components were appropriate and would not hinder ADLs or negatively impact quality of life, and provided advice on patient-facing material. Participants expressed support for clinical trials and associated dissemination methods.

CONCLUSION
UK patients living with high grade glioma and their caregivers clearly outlined the current treatment gap in glioblastoma and the opportunities for improved therapy options.
P26.11.B PIWIL2 AS A POTENTIAL REGULATOR OF STEM-CELL PHENOTYPE IN GLIOBLASTOMA
Authors: Garcia-Borja E , Mateu R , Siegl F , Šána J , Šedo A , Bušek P 
Published: October 2024

Abstract

BACKGROUND
PIWI proteins are highly conserved RNA-binding proteins that constitute a germline-specific subfamily of Argonaute proteins. They bind to short non-coding RNAs known as piRNAs forming a piRISC (piRNA-induced silencing complex). The PIWI/piRNA complexes are pivotal in repressing transposable elements and regulating gene expression in stem cells. Recent findings reveal their implication in the progression of several cancer types, including glioblastoma (GBM). This study analyzed the expression profiles of the four human PIWI proteins (PIWIL1, PIWIL2, PIWIL3 and PIWIL4) in gliomas and in glioblastoma stem-like cells (GSCs), a critical subpopulation of malignant cells involved in GBM progression, treatment resistance, and recurrence.

MATERIAL AND METHODS
A panel of 160 GBMs (grade 4, IDHwt), 20 low-grade gliomas (grade 2 astrocytomas and oligodendrogliomas), and 12 non-tumorous brain tissues (pharmacoresistant epilepsy) was selected to examine the expression of PIWIL1-4 by qRT-PCR. 24 paired GSC and non-GSC cultures were derived from freshly resected human GBMs to analyze the expression of PIWIL1-4 by RT-qPCR.

RESULTS
PIWIL3 expression was not detected in an initial screening of 30 GBM tissues, leading to its exclusion from further analyses. PIWIL1 was detected in only half of the 160 GBM tissues, exhibiting very low expression. In contrast, PIWIL2 and PIWIL4 were present in the majority of tissues, with their expression being lower in GBMs compared to low-grade gliomas and non-tumorous brain tissues. In agreement with our results in tissues, PIWIL1 and PIWIL3 were either undetectable or expressed at very low levels in GSCs and non-GSCs. PIWIL4 was detected in both cell subpopulations displaying similar expression in GSCs and non-GSCs. In contrast, PIWIL2 expression was significantly higher in GSCs compared to non-GSCs and declined in GSCs upon serum-induced differentiation. Moreover, only PIWIL4 and PIWIL2, were detected in GSC-derived orthotopic tumors in immunodeficient mice.

CONCLUSION
Our findings challenge the previously reported upregulation of PIWIL1 in GBMs and its presumed relevance in GSCs. Instead, our data indicate potential contribution of PIWIL2 in maintaining the stem cell characteristics of glioma cells. Experiments aimed at silencing PIWIL2 with siRNAs in GSCs are currently ongoing. This work was supported by the Ministry of Health of the Czech Republic (NV19-03-00501), the National Institute for Cancer Research (Programme EXCELES, LX22NPO5102), the European Union - Next Generation EU, EATRIS-CZ (LM2023053), and Charles University Cooperatio Program, research area”Oncology and Haematology”.
P26.12.A REPURPOSING ITRACONAZOLE AND PYRIMETHAMINE WITH TEMOZOLOMIDE AS A COMBINATORIAL TREATMENT FOR GLIOBLASTOMA
Authors: Lootens T , Vandersteene J , Pinson H , Boterberg T , Vermeirssen V , De Wever O , De Smet F , Raedt R 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GB) is marked by a poor median overall survival of 14-16 months despite surgery, radiotherapy and chemotherapy, highlighting the need for improving treatment. Drug repurposing offers the advantage of using commercially available compounds with known safety profiles, while simultaneously addressing the need for more effective and cost-efficient cancer treatments. However, preclinical or clinical evidence of efficacy is often lacking or merely anecdotal. In this in vitro study, we evaluated the therapeutic potential of combining repurposed agents itraconazole (ITR) and pyrimethamine (PYR) with low-dose temozolomide (TMZ) using primary GB patient-derived stem cell lines (PDSCLs).

MATERIAL AND METHODS
CellTiter-Glo cell viability assays were used to assess the effects of single and combination drug treatments in PDSCLs from both primary and recurrent GB. Staining with propidium iodide followed by flow cytometry was performed to investigate changes in cell cycle stages. Western blot and qPCR analysis to confirm the mode of action are ongoing.

RESULTS
Both ITR and PYR, at concentrations within the clinical plasma range, caused marked reductions in cell viability after 120h in a heterogeneous population of eight PDSCLs. Variable response rates were observed between cell lines with lowest IC50 values of 0.5 µM and 2.2 µM for ITR and PYR, respectively. Synergy analysis revealed mainly additive effects between the two drugs (Bliss scores of -4.93, 0.15, 1.79, 1.86, 4.19 and 7.67 in six PDSCLs). These effects were accompanied by an increased fraction of cells in the G1 phase after combinatorial treatment with ITR and PYR. Lastly, combining TMZ with this repurposed combination led to a significant decrease in cell viability across five PDSCLs after nine days of treatment, compared to TMZ monotherapy.

CONCLUSION
Our data shows that combining ITR and PYR with TMZ induces strong anti-cancer effects in PDSCLs, highlighting its potential as a combinatorial treatment for glioblastoma. In vivo validation and mode of action studies are currently ongoing. [This work was funded by a fellowship grant from “Fonds voor Wetenschappelijk Onderzoek” (FWO), grant number 1SH3H24N, and a project grant from the “Cancer Research Institute Ghent” (CRIG).]
P27.03.B BIOPSY VERSUS RESECTION IN GLIOBLASTOMA TREATMENT: A PROPENSITY SCORE-MATCHED ANALYSIS OF A RETROSPECTIVE COHORT
Authors: de Haan Y , Moussa A , Gerritsen J K W , Schnitzler S J P , Dirven C M F , Vincent A J P E 
Published: October 2024

Abstract

BACKGROUND
Overall survival (OS) of glioblastoma patients remains poor, even with surgical treatment and adjuvant therapy. Gross-total resection is preferred whenever possible; when this cannot be achieved due to e.g. age or critical tumour localization, biopsy is often performed. To date, no objective guidelines are available to determine what type of surgery is most appropriate for glioblastoma patients. The choice between resection or biopsy remains a comparative assessment between maximizing survival and preventing postoperative neurological deficits. We aimed to identify which treatment strategy benefits specific subgroups of glioblastoma patients with regards to OS and maintaining neurological function.

MATERIAL AND METHODS
This retrospective cohort consists of patients recruited in a tertiary hospital in The Netherlands. Eligible patients were 18 years or older and had undergone either biopsy or resection. Secondary glioblastomas or patients with a Karnofsky Performance Status (KPS) of 50 or lower were excluded. Nearest-neighbor propensity score matching was utilized to create comparable biopsy versus resection cohorts based on sex, age, hemisphere, location, ASA score, year of presentation, pre-operative NIHSS, pre-operative KPS, tumour volume, tumour crossing of the midline and undergoing of adjuvant treatment. Survival outcomes were analyzed using the log-rank test, while NIHSS deterioration (increase of at least 1 point) was assessed using a Chi-squared test.

RESULTS
Between January 1st 2018 and December 31st 2022, 317 patients were recruited, with 98 undergoing biopsy and 219 undergoing resection. Matching resulted in equal cohorts of 86 patients each. The median OS of the unmatched cohort was 9.4 months. However, in the matched cohort, median OS significantly favored resection over biopsy, with 8.8 months versus 3.2 months respectively (p=.004). Regarding NIHSS deterioration at 6 weeks postoperative, we found a possible favoring of resection with 38.5% deterioration in the biopsy group (n=20 of 52 who had follow-up data) and 25.9% in the resection group (n=21 of 81 who had follow-up data). Non-significance of this finding (p=.182) might possibly be due to unequal missingness in follow-up data. We are currently expanding our recruitment to include patients from 2010 onwards to allow for predictive regression analysis and subgroup analysis with regards to age, pre-operative NIHSS score, pre-operative KPS score, midline location and multifocality.

CONCLUSION
Analysis of this matched cohort of glioblastoma patients undergoing biopsy and resection, favors resection with regards to both OS and preserving neurological functioning. Subgroup analysis will follow to better inform physicians and patients in their clinical decision-making.
P27.13.B INSIGHTS INTO PARANEOPLASTIC NEUROLOGICAL SYNDROMES IN THE ERA OF MODERN ONCOLOGICAL TREATMENTS
Authors: Taliansky A , Zohar D N 
Published: October 2024

Abstract

BACKGROUND
The paraneoplastic neurological syndromes (PNS) are an uncommon phenomenon with diverse clinical manifestations. The diagnosis of PNS is often challenging because of the broad range of clinical manifestations and the difficulties in the detection of antibodies (AB) that are confirmatory for the diagnosis. Recently published Updated Diagnostic Criteria for PNS improved the efficacy and accuracy of clinical practice but leaves a “gray zone”. The utilization of immunotherapy is rapidly expanding, but the safety and the efficacy of the immunotherapy in PNS patients are unclear as well. Managing PNS is challenging, as there is no consensus on the type of immunomodulatory therapy and the indications for advanced treatment lines.

MATERIAL AND METHODS
We retrospectively evaluated the data about the case of PNS treated in the neurology department and Neuro-oncology unit at Sheba MC Israel.

RESULTS
68 years old male was hospitalized at July 2022 with C7-T3 myelopathy syndrome. The evaluation was negative excluding protein 75 mg/dl and mild pleocytosis, but negative cytology. There was clinical improvement after Methylprednisolon treatment. At March 2023 the patient admitted with acute onset of Lt. hemiparesis and Lt. hemihypoesthesia that developed three weeks after COVID-19 infection. PNS panels of high-risk and low-risk AB in serum and CSF were negative. The Brain MRI showed Rt. thalamic and internal capsule lesion that was hyperintense in FLAIR sequence and homogeneously enhanced by contrast in T1 sequence. The lesion was diagnosed as TUMEFACTIVE demyelinating lesion. Transient clinical and radiological response on steroids treatment was reached. The systemic evaluation revealed the Rt. axillary mass that was diagnosed as BRAF V600E mutated melanoma and case was diagnose as probable PNS. The treatment by BRAF and MEK inhibitors was started and sustained clinical and radiological neurological improvement and oncological complete response were reached.

CONCLUSION
Many questions arise while making therapeutic decisions that relate to PNS. One of those is the question of if cancer therapy alone is sufficient and if it is possible to skip the advanced immunomodulatory treatment lines, because immunosuppression constitutes an aggravating prognostic factor for oncological outcome. New targeted oncological therapies have a short time to response which makes this therapeutic approach possible and our case illustrates the concept.