bluuebunny/crossref_metadata_2025_split huggingface dataset:
P25.05.A THE IMPACT OF THE COVID-19 PANDEMIC ON NEURO-ONCOLOGY: REPORT FROM THE DUTCH BRAIN TUMOUR REGISTRY
Authors: Ho V K Y , Koekkoek J A F , Wagemakers M , de Vos F Y F , Nabuurs R J A , Wester G , Bongers E M , Nogarede C O , Walenkamp A M E , van Dis V , Maas S L N , de Witt Hamer P C , Compter A , Seute T 
Published: October 2024

Abstract

BACKGROUND
The COVID-19 pandemic affected all healthcare domains, including neuro-oncology. This study investigated the effects of the COVID-19 pandemic on the diagnosis, treatment and outcomes of adult patients with a glioma or meningioma in the Netherlands.

MATERIAL AND METHODS
Patients diagnosed in 2020 were divided into 5 periods, based on the severity of the COVID-19 pandemic in the Netherlands, and compared to patients diagnosed in the same period in the years 2017-2019.

RESULTS
The number of meningioma diagnoses decreased during the first 3 periods of the COVID-19 pandemic, and patients diagnosed in 2020 differed in their socioeconomic status from those diagnosed in 2017-2019. Glioma patients diagnosed in 2020 more often received adjuvant chemotherapy. Those aged 70+ years were more often treated with chemoradiotherapy instead of radiotherapy following neurosurgery. Both glioma and meningioma patients diagnosed in 2020 experienced a somewhat longer time to neurosurgery, with a median difference of 2 (95%-confidence interval [CI]: 1-3) and 4 days (95%CI: 0-8), respectively, while their time to initial adjuvant therapy was shortened, with a median difference of -1 (95%CI: -2-0) and -2 days (95%CI: -22-20), respectively. No difference was detected in patients’ overall survival.

CONCLUSION
The COVID-19 pandemic mostly impacted meningioma incidence during the first four months of 2020. With relatively limited adjustments, the neuro-oncology field was able to cope with the challenges posed by the pandemic.
P26.01.B A PHARMACOLOGICAL SURVEY ACROSS GLIOMA STEM CELL PHENOTYPES REVEAL NOVEL GLIOBLASTOMA DRUG-TARGETS, DRUG REPURPOSING OPPORTUNITIES AND FUTURE DRUG COMBINATION STRATEGIES
Authors: ELLIOTT R J R , Furqan M , Nagle P , Munro A , Drake C , Dawson J C , Brunton V , Frame M , Carragher N O 
Published: October 2024

Abstract

BACKGROUND
Owing to the lack of therapeutic advancement in the treatment of glioblastoma (GBM) over the past two decades, Cancer Research UK has designated malignant brain tumours a ‘strategic priority⋯ as a cancer of unmet need’. The inter- and intra-molecular heterogeneity of glioblastoma presents significant obstacles to effective clinical progression of novel treatments. Phenotypic drug screening is ideally suited to heterogeneous diseases, where targeting specific oncogenic drivers (such as EGFR) are broadly ineffective. Phenotypic hits can then be used to systematically identify synergistic combinations which overcome variable therapeutic response observed across multi-cell panels. Synergistic drug combinations between approved drugs (or drug candidates in early clinical trials) provides a repurposing context that could accelerate the bench to bedside model. Our preliminary objective was to incorporate a panel of patient derived GBM stem cell lines into an unbiased ‘cell painting’ assay to quantify multiple GBM stem cell phenotypes and create an updated pharmacological survey by screening these cell lines across several drug libraries containing commercially available, FDA approved and/or Phase I/II/III compounds.

MATERIAL AND METHODS
We profiled patient derived GBM stem cells against several thousand annotated compounds covering multiple doses, using our established image-based high throughput screening protocols. Multiplexed ‘cell painting’ dyes were used to quantify in detail the cellular response to each drug via CellProfiler image analysis software. Data processing, QC, dimensionality reduction and hit thresholding was carried out primarily using Stratominer-HCA platform. Putative hits based on phenotypic distance and potency were selected for validation and further characterisation.

RESULTS
Predominant drug sensitivities include the highly potent but expected pan-cytotoxic effects of compounds that target microtubules, the proteasome, topoisomerases, DNA/RNA synthesis and histone deacetylases. Beyond these, approximately 50 compounds have been selected for further studies including mechanism-of-action and pathway profiling, dose-ratio matrix combination testing in 2D and 3D GBM models, neuronal cytotoxicity and in vivo proof-of-concept studies via intracranial implantation.

CONCLUSION
Our preliminary results serve as a foundation for a systematic approach to identify novel drug combinations including combinations that could be used concurrently with standard treatment protocols for GBM.
P26.02.A AN IN VITRO MULTIDIMENSIONAL DRUG ASSESSMENT TOOL FOR PERSONALIZED PREDICTION OF DRUG RESPONSE AND RESISTANCE IN HUMAN GLIOBLASTOMA ORGANOIDS
Authors: Camenisch S , Mathews L , Hoch T , Neidert M , Zeitlberger A , Hundsberger T , Jochum W , Vélez Char N , Ayala V , Wick P 
Published: October 2024

Abstract
Glioblastoma (GBM) is a highly aggressive brain tumor treated with surgery, radiotherapy, and concomitant as well as maintenance temozolomide (TMZ). Despite treatment adherence to this so called Stupp’s regime, patient survival is typically less than 18 months, with high relapse rates. Current pre-clinical drug research is performed with cell line or patient-derived xenografts or with in vitro 2D models. These models lack inter- and intratumoral heterogeneity as well as a tumor microenvironment, thus bench to bed translational issues occur. Using patient-derived glioblastoma organoids (PDOs) the necessary cell heterogeneity can be provid-ed by growing them out of micro-dissected biopsy samples from 3 different GBM tumor sub-regions (pe-riphery, contrast-enhancing zone and tumor core). PDOs are considered in vitro models with high clinical rel-evance to evaluate the anticancer potential of novel preclinical drugs. In this project, we translated the Stupp’s regime to an in vitro multidimensional drug assessment tool using our in vitro GBM model. This tool allows us to monitor drug response over time and predict the performance of preclinical drugs with high predictability. The multidimensional drug assessment tool was initially optimized with TMZ in glioblastoma spheroids and then extended to PDOs. Our assessment included a morphological analysis, 2D & 3D confocal imaging, NGS mutational profiling, apoptotic/necrotic cell fraction assessment, cell metabolic activity assays (XTT), and su-pernatant-based cell toxicity assays (LDH). The apoptotic cell fraction was detected by looking at nuclear morphology in H&E stained tissue slices and detected using a pre-trained AI-driven image readout software. Over the duration of 14 days, GBM spheroid and organoids were treated according to the adapted in vitro Stupp’s regime and TMZ was monitored with our in vitro multidimensional drug assessment tool. Multiple concentrations and time points were evaluated to detected TMZ effect on tumor size reduction, metabolic activity, cytotoxicity, appearance of new drug-induced mutations, and extent of apoptosis and necrosis. GBM models treated with clinically relevant TMZ concentration (100 uM) were approximately 33% smaller after 10 days and metabolic activity decreased by up to 53%. Further preclinical drug candidates will be compared to TMZ performance and clinical data. To conclude, we are confident that this dynamic and multidimensional screening tool using physiologically relevant patient-derived GBM models provides high predictive power in order to assist preclinical anti-GBM drug screening and can address current translational issues persisting in drug development.
P26.07.A FGFR1 INHIBITION SENSITIZES GLIOBLASTOMA STEM CELLS TO TUMOR TREATING FIELDS
Authors: Gouaze-Andersson V , Deshors P , Cohen-Jonathan Moyal E 
Published: October 2024

Abstract

BACKGROUND
Glioblastoma (GBM) is the most lethal primary brain tumor in adult and is known to be particularly aggressive and resistant despite a treatment associating surgery and radio-chemotherapy. Over the last few decades, only few therapeutic advances have been achieved on GBM, but Tumor Treating Fields (TTFields) have recently improved outcomes of clinical trials. TTFields are a non-invasive, physical, local therapy relying on the delivery of alternating electrical fields with low intensity and intermediate frequency and are now a part of the first-line clinical treatment for GBM. Although TTFields increase patient’s survival, GBM is still an incurable disease with recurrences due to treatment resistance. Therefore, there is a need to understand mechanisms of GBM resistance to TTFields and to identify new therapeutic targets. One of the causes of resistance is the presence of Glioblastoma Stem Cells (GSC) known to be radio- and chemo-resistant and responsible for tumor regrowth. We have previously shown that tyrosine kinase receptor FGFR1 controls GBM agressiveness as well as GSC invasion and radioresistance and that its inhibition leads to radiosensitization through increasing mitotic cell death and microenvironment modulation. Because one of the main mechanisms of action of TTFields is mitotic disturbance and because TTFields act synergistically in vitro with irradiation, we hypothesize that targeting FGFR1 could sensitize GSC to TTFields.

MATERIAL AND METHODS
In this work we used a panel of primary GSC established from patient’s surgical GBM sample to test the potential role of FGFR1 in GSC response to TTFields. For this purpose, GSC were treated for 72 h with TTFields at 200 kHz which is the same frequency delivered to the patient receiving this therapy. TTFields treated GCS were also treated with siRNA targeting FGFR1 or pemigatinib, which is an inhibitor of FGFR1-3.

RESULTS
TTFields treatment increases expression and activation of FGFR1. Treatment of GSC with pemigatinib decreases FGFR1 expression and inhibits FGFR1 signaling pathway even when TTFields are applied. We demonstrated that pemigatinib, as well as FGFR1 silencing with RNA interference, sensitizes all GSC used in our experiments to TTFields by decreasing their survival. Finally, the adjunction of pemigatinib to treatment combining irradiation (IR) and TTFields also sensitizes GSC by inducing a further decrease in the repair of IR-induced DNA damages.

CONCLUSION
These results demonstrated that FGFR1 inhibition in concomittance with TTFields application as standard GBM treatment would improve patient prognosis.
P26.08.B LASER-ASSISTED FABRICATION OF AN IN VITRO 3D-ENGINEERED BLOOD-BRAIN/TUMOR BARRIER MODEL
Authors: Barin N , Balcioglu H E , Accardo A , French P 
Published: October 2024

Abstract

BACKGROUND
Efficient drug delivery to brain tumors is greatly hindered by the blood-brain barrier (BBB). Although different in vitro BBB models have been developed, they do not capture the capillary dimensions, incorporate multiple cell types, feature biomimetic flows, and/or provide sufficient 3D cell-to-cell contact. We aimed to develop a model for the blood-brain/tumor barrier (BBTB) that incorporates these characteristics simultaneously.

MATERIALS AND METHODS
3D micro-porous capillary-like structures (µPCs) that mimic the brain capillary dimensions were fabricated using two-photon polymerization (2PP), a 3D light-assisted printing technique that enables precise microscale fabrication. These structures serve as a scaffold for culturing and organizing various BBTB cell types. µPCs are fabricated at the intersection of two channels within a microfluidic slide, facilitating controlled fluid flow inside and outside the µPCs using a pressure-driven pump. Human umbilical vein endothelial cells (HUVECs) and the U87 glioblastoma cell line are utilized. Immunofluorescence staining (using CD31, tubulin, actin, and DAPI) and scanning electron microscopy are performed to assess cell colonization.

RESULTS
Initially, we cultured endothelial cells on µPCs under static conditions (i.e. without fluid flow). We optimized µPC designs by modifying channel and rod diameters, alignment, and pore sizes to improve structure stability, confocal microscopy visibility, and cell colonization. These experiments resulted in a design that achieved complete endothelial cell coverage. We also confirmed that the µPCs setup allows co-cultures of glioblastoma and endothelial cells. Next, we 3D printed the 2PP-fabricated µPCs within single-channel microfluidic slides that allowed control of internal fluid flow within the µPCs. When endothelial cells were perfused through the µPCs under biomimetic flow rates, after three days of culture, they uniformly covered the surface of µPCs. We also developed a protocol for precise printing of µPCs in 2-channel slides. The first channel enables internal fluid flow within the µPCs, where endothelial cells are cultured via physiological microfluidic flows. The second channel controls the external flow surrounding the µPCs, where astrocytes, pericytes, and glioma cells can be cultured in static conditions. We will use this setup to soon perform co-cultures of endothelial cells, gliomas and pericytes.

CONCLUSION
We designed a representative model for the BBTB capillaries, using a hybrid approach that combines 2PP and microfluidics. To ensure the BBTB model’s physiological relevance, future assessments will include cellular adherence, cellular spatial distribution, expression of integrity proteins, basal lamina formation, and vessel permeability. This work was partly funded by the Dutch Research Council via the ENW-XS grant N. OCENW.XS23.2.105.
P27.01.A ANLOTINIB COMBINED WITH RADIOTHERAPY IN THE TREATMENT OF ADULT NEWLY MALIGNANT BRAINSTEM GLIOMA PATIENTS: A MULTICENTER, PHASE II STUDY
Authors: Chen Y , Li P 
Published: October 2024

Abstract

BACKGROUND
Due to the challenging location, adult malignant brainstem glioma can not undergo aggressive surgery and is associated with a quite poor prognosis. Effective therapy regimens for this disease have not been developed. This study assessed the efficacy and safety of anlotinib, a multitarget tyrosine kinase inhibitor, combined with radiotherapy in treating this group of patients.

MATERIAL AND METHODS
This is an ongoing phase II, multicenter, single-arm trial investigating the safety, tolerability, and activity of anlotinib combined with radiotherapy in malignant brainstem glioma. Eligible participants include adults (18-70 years old) with newly diagnosed malignant (WHO III - IV) brainstem glioma based on histology or radiology who are radiotherapy (RT), chemotherapy, immunotherapy, or biotherapy naïve. Patients with Karnofsky score &lt; 40 and a life expectancy &lt; 3 months are excluded. All participants received 54-60 Gy radiotherapy (RT,1.8-2.0 Gy per fraction, five days per week). Anlotinib (10mg, orally, daily, d1-14/3 weeks) concurrently administered with radiotherapy, then consolidatedly used until disease progression or occurrence of intolerable adverse events. The primary objective includes disease control rate (DCR) and 6-month progression-free survival rate (6m-PFS). The secondary objective includes overall survival (OS), and toxicity profile (NCT04668508).

RESULTS
As of January 31, 2024, 19 participants have enrolled, all patients have completed radiotherapy. Sixteen patients who with a follow-up of 6 months or longer were included in the analysis for this report. The median age is 32 (range 18-68) years old. The median follow-up is 22.7 (range 6.0-38.3) months. Seven patients were pathologically diagnosed and nine patients were radiologically diagnosed with high-grade glioma. The DCR is 100% (Stable disease, SD: 16/16) at the end of radiotherapy and is 100% three months after radiotherapy (Partial response, PR: 2/16; SD: 14/16). The median PFS is 11.7 months, 95%CI 6.9-16.4, and the 6m-PFS and 1 year-PFS rates are 74.0% 11.2% and 36.3% 13.3%. The median OS is 18.7 months, 95%CI 10.7-34.7, the 6m-OS and 1 year-OS rates are 93.3% 6.4%and 58.3% 15.0%. No death occurred during the treatment. No ≥ grade 3 adverse events were observed up to the last follow-up (January 31, 2024) of this study.

CONCLUSION
Anlotinib combined with radiotherapy is efficacious and well-tolerated and might be a treatment option for newly diagnosed malignant brain stem glioma in adults.
P27.02.A ANTI-EPILEPTIC WITHDRAWAL IN GLIOMAS: A RETROSPECTIVE STUDY IN A SINGLE SCOTTISH TERTIARY CENTRE
Authors: Merchant F , Molinari E 
Published: October 2024

Abstract

BACKGROUND
Seizures are common in brain tumours (BTs). With no fixed guidelines to guide anti-epileptics (AEDs) discontinuation in BTs, we evaluated factors influencing the decision to discontinue AEDs and its outcome.

MATERIAL AND METHODS
Retrospective study on single regional centre for neuro-oncological service from April 2018 to April 2023. Eligible BT patients were seizure free ≥ 1 year post surgery, had histologically confirmed gliomas (WHO grade I-IV) and underwent gross total resection. We analysed separately patients who were weaned after being started on AEDs prophylactically. Primary outcomes were: (1) shared decision-making outcome and (2) seizure recurrence. Data analysed included tumour characteristics, antitumour treatments and seizure freedom.

RESULTS
Over 2020-2023, 30/240 patients (13%) met the selection criteria for AED withdrawal and 22/30 (73%) were agreeable to AEDs withdrawal. 9/22 (41%) of those who withdrew AEDs had seizure recurrence, with 6/9 (67%) having a seizure within 6 months following withdrawal. 5/9 (55%) had tumour progression within 3-6 months of having a seizure. None of those who remained on AEDs had seizure recurrence.A shorter BT related epilepsy (BTRE) duration (p&lt;0.01) and radiotherapy treatment (p&lt;0.05) resulted in decreased seizure recurrence following withdrawal. Most patients were on Levetiracetam monotherapy and our data did not allow comparison with other AEDs.

CONCLUSION
In 73% of patients, a shared decision process led to AEDs withdrawal, with 59% remaining seizure free. Lower recurrence risk was linked to shorter BTRE duration and radiotherapy. Further studies are required to better stratify patients at higher risk of seizure recurrence.
P27.06.B EFFECT OF CHOLINE ALPHOSCERATE ON THE SURVIVAL OF GLIOBLASTOMA PATIENTS
Authors: KIM Y 
Published: October 2024

Abstract

BACKGROUND
Cognitive impairment often occurs in glioblastoma (GBM) patients due to the tumor itself and treatment side effects. Choline alphoscerate (L-alpha-glycerylphosphorylcholine, GPC) is frequently used to compensate for cognitive impairment in GBM patients. This study was conducted to determine whether GPC affects the overall survival (OS) and progression-free survival (PFS) of GBM patients.

MATERIAL AND METHODS
From 2011 to 2020, 187 isocitrate dehydrongenase (IDH)-wild-type GBM patients were analyzed. The patients were classified based on whether GPC was continuously used for at least 3 or 12 months (mos) after GBM diagnosis.

RESULTS
Although GPC usage (≥3 mos) did not make significant differences in survival extension, median OS in the long-term GPC group (≥12 mos) was longer with statistical significance, compared to the control group (&lt;12 mos) (38.3 vs. 24.0 mos, p = 0.004). In addition to younger age, supratentorial location, complete resection, and MGMT promoter methylation, long-term use of GPC (≥12 mos) was significantly associated with longer OS in multivariate analysis (p = 0.019, hazard ratio [HR] 0.532, 95% confidence interval [CI] 0.314-0.900).

CONCLUSION
Despite the limitations of this study, long-term GPC use was possibly associated with prolonged survival in GBM patients. Multi-center prospective randomized studies with a large number of patients are needed to validate these findings.
P27.12.B IMPACT OF SEQUENCING TEMOZOLOMIDE TO DEFINITIVE RADIOTHERAPY IN GRADE-II GLIOMA- A CLINICAL AUDIT
Authors: Kumar N , Tiwari A , Madan R , Saroya B , Tripathi M , Chatterjee D , Ahuja C , Devi H , Singla N , Shah D , Singh A , Sahoo S , Chhabra R 
Published: October 2024

Abstract

BACKGROUND
For low-grade Gliomas (LGG), total surgery remains the cornerstone of treatment; recent studies have demonstrated a remarkable improvement in overall survival (OS) when PCV chemotherapy is added to the radiation therapy treatment regimen for patients with low-grade Gliomas. In clinical practice, multi-agent PCV chemotherapy is being replaced with the Alkylating and oral drug Temozolomide (TMZ) for its better compliance in terms of administration and side effects. Thus, we performed a clinical audit to evaluate the role of TMZ instead of PCV in treating patients with LGG.

MATERIAL AND METHODS
Objectives- 1-Τo understand the pattern of use of temozolomide along with adjuvant radiotherapy in Grade 2 Glioma and its impact on outcome. 2-Quantify the impact of concurrent and adjuvant chemotherapy on the survival of Grade II Gliomas 3-Difference in the survival of Oligodendroglioma and Astrocytoma with respect to adjuvant treatment. All patient data from 2014 to 2020 was extracted in this clinical audit. Patients with the diagnosis of Grade II oligodendroglioma and Grade II astrocytoma were recorded. Information was recorded regarding surgical details, radiotherapy, and concurrent and adjuvant therapy. The patient’s last follow-up date was recorded. These patients were divided into five groups depending on the adjuvant treatment received after surgery. Group 1: Received External Beam Radiotherapy with concurrent and adjuvant chemotherapy (XRT+CC+ACT) Group 2: Received External Beam Radiotherapy and concurrent Chemotherapy (XRT+ CCT) Group 3: Only External Beam Radiotherapy (XRT) Group 4: No Adjuvant treatment (No Treatment) Group 5: External Beam Radiotherapy followed by adjuvant chemotherapy (XRT + ACT)

RESULTS
There were 469 patients with grade 2 glioma, including both Astrocytoma (n=192) and Oligodendroglioma(n=223). There was no difference in survival between Grade 2 ODG and Astrocytoma, with mean survival of 29.33 (±28.03) months and 28.53(±28.3) months (p=0.4). In patients with Grade 2 astrocytoma, the highest estimated survival was seen in Group 5 (39.63±7.34 months) and the lowest in Group 4 (7.24±2.27 months) with significant p-value (0.0001). In Patients with Grade 2 Oligodendroglioma, the highest estimated survival was seen in Group 5 (44±6.49 months) and the lowest in Group 3 (32.98±3.49 months) with non-significant p-value (0.4).

CONCLUSION
In the lack of definitive data on the role of adjuvant treatment in grade II Glioma, our study provides convincing evidence for the use of adjuvant Temozolomide in low-grade Glioma. Our study revealed that adjuvant Chemotherapy with Temozolomide after Radiotherapy results in better overall survival