bluuebunny/crossref_metadata_2025_split huggingface dataset:
P09.04.B PNES IN BRAIN TUMOR PATIENTS : AN UNEXPECTED CHALLENGE
Authors: Loebenstein R , Eltity M , Magiel E , Haisraely O , Noga A , Jan E , Boxer M , Taliansky A 
Published: September 2023

Abstract

BACKGROUND
Epileptic seizures (ES) are common in brain tumor patients. The phenomenon of psychogenic non-epileptic seizures (PNES) amongst those patients has not been well described. PNES Phenomenology could be similar to ES, however, epileptogenic activity on electro-encephalogram (EEG) is absent. The diagnosis of PNES can be challenging in brain tumor patients since both types of seizures can present with similar symptoms and might occur together. Risk factors for the development of PNES include a history of negative events in childhood, exposure to trauma, history of psychiatric illness and chronic pain, and substance abuse. Diagnosing PNES is important for delivering the appropriate treatment, and preventing the toxic influence of unneeded treatment and procedures.

MATERIAL AND METHODS
The Electronic files of patients with ES and PNES were evaluated, in A retrospective analysis from the database of the Neuro-Oncology unit at Sheba Medical-Center.

RESULTS
4 patients with brain tumor related epilepsy and PNES were identified: a female 22 years old with right frontal IDH1 mutated non 1p/19q deleted glioma WHO2, a 44 years old male with right frontal IDH1 mutated 1p/19q deleted glioma WHO2, a 48 years old female with left temporo-insular IDH1 mutated non 1p/19q deleted glioma WHO2 and a 65 years old female with multiple radiation induced meningiomas. Seizures semiology were compatible with the lesions. The first two patients had recent stress factors, and the last two suffered severe diagnosis-related anxiety. All patients presented initially with ES and developed PNES subsequently. They were treated with 2-4 Anti-Epileptic drugs(AED’s). They were referred to EEG video monitoring due to worsening seizures frequency despite increasing the AED’s and no evidence of tumor progression at that time. All patients had clinical seizures which did not have any epileptiform activity correlation on Video-EEG. Hence, PNES was diagnosed. Three patients underwent psychological treatment and two patients received medical therapy for underlying psychological factors contributing to PNES. Seizure frequency and number of AED's decreased in all patients.

CONCLUSION
In patients with brain tumors the diagnosis of PNES can be challenging but should be considered in patients with increased seizures frequency regardless of stable imaging and absence of any other provocative factors. Video EEG is pivotal for PNES diagnosis. Psychological consulting and treatment are recommended in PNES cases. Correct diagnosis and treatment will contribute to the patient's quality of life.
P09.05.A IMPACT OF A 16-WEEK SUPERVISED EXERCISE INTERVENTION ON CANCER-RELATED FATIGUE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA UNDERGOING ADJUVANT CHEMOTHERAPY
Authors: Jost J , Kloss M S , Brandt R , Völker K , Stummer W , Wiewrodt R G , Wiewrodt D 
Published: September 2023

Abstract

BACKGROUND
Cancer-related fatigue (CRF) is considered one of the most prevalent symptoms in brain tumor patients undergoing concurrent chemoradiation (approx. 80 % of those affected). Several studies have identified beneficial effects of physical activity on reducing CRF. However, few studies have examined the reduction of CRF by exercise in glioma patients. Here we present prospective data showing the effect of an intensive 16-week supervised exercise intervention on CRF in neuro-oncological patients.

MATERIAL AND METHODS
Between July 2020 and April 2023, patients with newly diagnosed glioblastoma and after surgery and concomitant radiochemotherapy have been recruited for this single-arm trial in progress. Participants have received a 16-week supervised training intervention on a 1:1-basis consisting of two intensive 50-minute sessions per week (bicycle ergometry at an average of 75 % of maximum heart rate and progressive whole-body resistance training). CRF has been assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). We calculated change scores (scores: 0-100; 100=max. fatigue) from baseline, after 8 weeks, and post-intervention (week 16).

RESULTS
So far, 26 glioblastoma patients (13 women) aged 35-84 years (mean 59 years) participated in the exercise intervention. All patients received adjuvant chemotherapy (50 % Stupp, 42 % CeTeG, 8 % other). Paired t-test indicated a statistically significant reduction in CRF from baseline to post-intervention (p=.030; 95 % CI: -0.5 - 24.2). Mean scores reduced from 40.4 to 36.2 (week 8) to 26.9 (week 16). However, the decrease between week 0 and week 8 was not yet significant (p=.281; 95 % CI: -7.6 - 13.6).

CONCLUSION
The present trial shows that a 16-week supervised exercise program can reduce CRF in glioblastoma patients despite adjuvant chemotherapy. Thus, and consistent with studies of exercise interventions in patients of other tumor types, glioblastoma patients have the opportunity to actively contribute to the reduction of tumor- and therapy-induced side effects through intensive physical training.
P09.12.B EFFECT OF TRADITIONAL CHINESE MEDICINE (TCM) AND WESTERN NATUROPATHY ON PATIENTS WITH GLIOBLASTOMA
Authors: Goldbrunner R , Roth-Goldbrunner S , Timmer M , Nettekoven C , Kochs S 
Published: September 2023

Abstract

BACKGROUND
IDH wildtype Glioblastoma (GBM) is an aggressive brain tumor with dismal prognosis. Current efforts focus on integration of supportive therapies like psychooncology and palliative care in routine care. Traditional Chinese Medicine (TCM) and western naturopathy are integrative modalities that have been studied recently for managing various symptoms and diseases. Aim of this study was to assess effects of TCM and western naturopathy on symptom burden relief and survival of glioblastoma patients.

METHODS
In this retrospective study we performed a matched pair analysis comparing 21 GBM patients with a combined treatment comprising standard radio chemotherapy plus TCM and western naturopathy (TCM group) with matched control patients receiving standard radiochemotherapy alone (control group). Matching was done according to age, gender, IDH status, MGMT methylation status and KPS. Statistical analysis was performed using GraphPad Prism 9.

RESULTS
The patient in the TCM group felt better regarding their general condition and had less symptom burden. Moreover, progression free survival (PFS) was significantly longer in the TCM group (17.4 +/- 12.2 months) compared to the control group (12.6 +/- 6.9 months; p &lt; 0.01). Overall survival increased from 20.5 +/- 8.5 (control group) to 25.0 +/- 14.5 months (TCM group, n.s.).

CONCLUSION
Glioblastoma patients seem to benefit significantly from additional integrative medicine including TCM and western naturopathy , both, in terms of symptom relieve and regarding progression free survival. However, a prospective randomized trial with a larger patient cohort would be necessary in order to confirm this effect.
P10.04.B LONGITUDINAL [18F ]FET-PET-BASED IMAGING AND PROFILING OF PDGFB-DRIVEN EXPERIMENTAL GLIOMA USING THE RCAS-TVA SYSTEM
Authors: Becker H , Castaneda-Vega S , Patzwaldt K , Przystal J M , Walter B , Michelotti F C , Canjuga D , Tatagiba M , Pichler B , Beck S C , Holland E C , la Fougère C , Tabatabai G 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma are aggressive and incurable primary tumors of the central nervous system. As patients present with already established tumors, longitudinal imaging by MRI and [18F]FET-PET in human glioblastoma for characterizing temporal and spatial metabolic alterations is only possible to characterize alterations during therapy, but not during tumor evolution. In this regard, genetically engineered preclinical models are very relevant. The replication-competent avian sarcoma-leukosis virus (RCAS)/tumor virus receptor-A (tva) system provides a high grade of spatial and temporal control of somatic gene delivery in vivo. In this study, we used longitudinal MRI and [18F]FET-PET to characterize the evolution and growth of platelet-derived growth factor B (PDGFB)-driven glioma model using the RCAS-tva system.

MATERIAL AND METHODS
DF-1 cells transfected with PDGFB were implanted into adult 129S.Tg(NES-TVA)-Cdkn2a−/− mice intracranially. Mice received MRI twice and [18F]FET-PET measurements once per week. Longitudinal growth pattern and [18F]FET-PET uptake were assessed and analyzed. We measured symptom-free survival and performed immunohistochemistry on collected tumor tissue samples.

RESULTS
We observed robust tumor formation with highly reproducible symptom-free survival times of treatment-naïve experimental animals. Contrast-enhanced MRI volumetry revealed exponential growth dynamics starting around day 25 after DF-1 inoculation. Here, the PDGFB-driven gliomas present an escalating [18F]FET-PET uptake as well as increasing BBB permeability over time. These imaging features match the clinical scenario, which underlines the translational relevance of this model. Histology corroborated the imaging findings and an immunogenic glioma-associated microenvironment.

CONCLUSION
These data provide further valuable insights into this RCAS/tva-based PDGFB-driven murine glioma model and advocates for an imaging-stratified design of preclinical therapeutic interventions.
P10.11.A CHARACTERISTICS OF DIFFUSE MIDLINE GLIOMA WITH H3 K27M MUTATION IN ADULTS
Authors: Tanaka K , Nagashima H , Yamanishi S , Itoh T , Sasayama T 
Published: September 2023

Abstract

BACKGROUND
H3 K27M-mutant diffuse midline gliomas (DMG) occur primarily in children but can also be encountered in adults. Adult H3 K27M-mutant DMG is a still challenging disease with no effective medical therapies.

MATERIAL AND METHODS
We retrospectively analyzed the characteristics and prognostic factors of 49 adult patients with intracranial midline gliomas treated in Kobe University Hospital from 2006 to 2022.

RESULTS
The median age at diagnosis in midline gliomas was 50.8 years (range: 17-83 y). All tumors were located in thalamus n=25, brainstem n=10, cerebellum n=14. Isocitrate dehydrogenase 1 (IDH1) and H3 K27M mutation was recognized in 6 and 16 patients, respectively, which was mutually exclusive. In all midline gliomas, the identification of H3 K27M mutation was significantly a poor prognosis factor (median 18.5 months vs 34.2 months, p=0.041). Among IDH1 wild-type midline gliomas, however, H3 K27M-mutant DMG had no worse overall survival (median 18.8 months vs 22.2 months, p=0.805).

CONCLUSION
H3 K27M-mutant DMG is considered as a distinct WHO Grade 4 regardless of histological features, but the biological properties of H3 K27M mutation is not yet defined in IDH1 wild-type midline gliomas in adults.
P10.27.A THE INFLUENCE OF DEXAMETHASONE ON TOTAL DNA METHYLATION LEVEL IN GLIOBLASTOMA CELL LINES
Authors: Barciszewska A , Belter A , Giel-Pietraszuk M , Gawrońska I , Naskręt-Barciszewska M 
Published: September 2023

Abstract

BACKGROUND
Dexamethasone (DEX) is a first-line antiedematic drug for glioblastoma (GBM) patients. There is also some evidence it also inhibits GBM cell proliferation and migration, thus impacting patients’ outcomes. However, other studies show that the use of DEX is associated with poor treatment outcomes in GBM patients. The exact mechanism of DEX action is unclear, and no definitive conclusion has yet been reached on its benefits in neurooncological treatment. Temozolomide (TMZ) is a first-line chemotherapeutic in GBM. Epigenetics offers a connection between genetic and environmental factors that influence the development of the disease. The best-characterized epigenetic mark is 5-methylcytosine (m5C) in DNA. The aim of that project is to show the effects of DEX administration on the total DNA methylation level.

MATERIAL AND METHODS
Using the nucleotide post-labeling method, we analyzed the total amount of m5C in DNA of GBM (T98G, U118, U138), cancer (HeLa) and normal (HaCaT) cell lines treated with DEX, and a combination of DEX and with TMZ.

RESULTS
We adjusted the DEX doses to the ones achieved in the central nervous system during treatment. We observed dose-dependent increase in total DNA methylation in all cell lines. However, the exposition of GBM cells to the combination of DEX and TMZ caused an adverse synergistic effect resulting in DNA demethylation in high doses of both drugs. In lower concentrations of both drugs DEX kept the increased DNA methylation and attenuated the demethylating effect of TMZ.

CONCLUSION
Total DNA methylation changes in glioma cell lines under DEX treatment suggest the new mechanism of that drug action and promote clinical implications for adjusting DEX and TMZ therapy in GBM patients. Our results show the potential and possible obstacles of the combined therapy of TMZ with DEX. Our experiments show that combined therapy with both drugs leads to total DNA hypomethylation in high doses of both drugs. Therefore the conclusion would be to adjust DEX administration during TMZ chemotherapy.
P10.33.A TARGETED INHIBITION OF THREE MAJOR PROLIFERATION PATHWAYS IN GLIOBLASTOMA INDUCES SENESCENCE THROUGH A MITOCHONDRIA-DEPENDENT MECHANISM
Authors: Baltira C , Mayayo-Peralta I , Guillén-Navarro M , Thijssen B , Alkan F , Pello K , Fedorushkova D M , Their A , Silva J , Jochems F , Bleijerveld O , Janssen H , Faller W J , Bernards R , de Gooijer M C , van Tellingen O 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma (GBM) is a fatal brain tumor with a great unmet need for better therapies. Research on the genomic landscape of GBM has revealed that three major proliferation pathways — the PI3K-mTOR-AKT, the MAPK, and the CDK4/6-RB pathways — are overactive in the majority of GBM patients. Based on that knowledge we have developed a multi-target combination therapy (MTCT) by employing inhibitors of these three pathways. When these inhibitors are used in combination, lower, clinically more relevant concentrations of each drug are sufficient for target inhibition and proliferation arrest than with single agents.Excitingly, we find that MTCT not only shuts down proliferation but also causes permanent growth inhibition by the induction of senescence and the secretion of a senescence-associated secretory phenotype (SASP).

MATERIAL AND METHODS
Senescence is identified in a multimodal way, including morphological characterization, SASP production, beta-galactosidase activity, and colony outgrowth potential. RNAseq together with (phospho)proteomics are also applied to investigate the molecular mechanism in combination with techniques such as DNA damage assays, flow cytometry, western blot, metabolic assays, and fluorescence microscopy.

RESULTS
MTCT-senescent cells have increased mitochondrial reactive oxygen species (mtROS). However, they do not acquire nuclear DNA damage but only local mitochondrial DNA damage. Addition of antioxidants that deplete mtROS resulted in senescence rescue both in terms of morphology and proliferation arrest. MTCT-senescent cells display an enhancement in total mitochondrial mass, mitochondrial DNA copy numbers, and the transcription of mitochondrial proteins. Despite this enhancement, the basal respiration rate of these cells is comparable to untreated cells, indicating an impaired maximal respiration capacity in MTCT-senescent cells. Concordantly, these cells display striking disturbances of their mitochondrial network.Intriguingly, depletion of functional mitochondria prevents the induction of mtROS and senescence by MTCT but not by classical senescence inducers such as ionizing radiation or high concentrations of CDK4/6 inhibitors.

CONCLUSION
MTCT induces senescence in GBM cells through a unique nuclear DNA damage-independent mechanism for which the mitochondria are essential.
P11.04.B ASSESSMENT OF TUMOR ELOQUENCE IN GLIOMA RESECTIONS: A SYSTEMATIC REVIEW
Authors: Rammeloo E , Schouten J W , Krikour K , Bos E M , Berger M S , Gerritsen J K W , Vincent A J P E 
Published: September 2023

Abstract

BACKGROUND
Tumor location and eloquence are two crucial factors when deciding on the optimal surgical strategy in glioma management. Consensus is currently lacking on the assessment and definition of eloquent areas. This systematic review aims to evaluate the existing definitions and assessment methods of eloquent areas used in current clinical practice.

MATERIAL AND METHODS
A computer-aided search of Embase, Medline (OvidSP), and Google Scholar was performed to identify relevant studies. This review includes articles describing preoperative definitions of eloquence in the study’s Methods section. These definitions were compared and categorized by anatomical structure. Additionally, various techniques to preoperatively assess tumor eloquence were extracted, along with their benefits, drawbacks and ease of use.

RESULTS
This review covers 98 articles including 12,714 participants. Evaluation of these studies indicated considerable variability in defining eloquence. Categorization of these definitions yielded a list of 32 brain regions that were considered eloquent. The most commonly used methods to preoperatively determine tumor eloquence were anatomical classification systems and structural MRI, followed by DTI-FT, functional MRI and nTMS.

CONCLUSION
None of the definitions or techniques to define eloquence described in the articles are entirely satisfactory as an objective, quantifiable, preoperative factor in glioma treatment and surgical decision-making. Therefore, we propose the development of a new, easily applicable and interpretable anatomical preoperative grading system to assess tumor eloquence. This may aid neurosurgeons in their perioperative decision-making to improve surgical outcomes on an individual patient level and to facilitate the execution and interpretation of multicenter studies.
P11.11.A VOLUMETRIC AND SPATIAL ANALYSES OF TREATMENT-RELATED INJURY IN GLIOMA
Authors: van der Boog A T J , David S , Vreeman M , Steennis A A M , Cialdella F , Dankbaar J , Snijders T J , Verhoeff J J C , Robe P A 
Published: September 2023

Abstract

BACKGROUND
As diffuse glioma cannot yet be cured, benefits of therapeutic strategies should be carefully balanced against their burden. Postoperative ischemia is a relatively common adverse event of surgery, which can lead to serious neurological deficits. Radiation therapy (RT) can cause post-RT lesions, which may cause clinical symptoms and can create a therapeutic impasse since they mimic tumor progression. We aimed to explore the spatial and volumetric tumor and treatment characteristics in relation to development of treatment-related effects in glioma. Materials and

METHODS
We retrospectively included 144 WHO grade II-IV supratentorial glioma cases, which were resected from 2012 till 2014 and had early postoperative MRI with diffusion-weighted imaging (DWI). Tumors were delineated on preoperative contrast-enhanced T1 MRI for high grade gliomas and FLAIR for low grade gliomas. Postoperative ischemia was defined as new, confluent diffusion restriction on postoperative DWI. Post-RT injury was investigated in patients who received RT after first surgery and had at least 6 months of follow-up (FU), and was defined as new or increasing contrast-enhancement that subsequently stabilized or decreased during FU. After manual delineation and non-linear registration to MNI stereotaxic space, all lesions were investigated with regard to size and location of pre-operative tumor, resection cavity, residual tumor and extent of resection (EOR). Voxel-based analysis (VBA) was performed with family-wise error correction for multiple comparisons.

RESULTS
Postoperative ischemia occurred in 93 of 144 cases and was associated with a larger EOR (P=0.02). Ischemic volume was correlated with a larger preoperative tumor volume (P=0.009) and resection volume (P=0.001). Post-RT injury was found in 25 of 67 analyzed cases and was associated with a larger residual tumor volume (P=0.021) and a smaller EOR (P=0.005). VBA showed an association of the occurrence of post-RT lesions with a cluster of preoperative tumor voxels in the left temporal lobe and clusters of residual tumor voxels in the left temporal and right frontal region. No association in volume or location was found between postoperative ischemia and post-RT lesions.

CONCLUSION
Adverse events of glioma treatment may be influenced by tumor and treatment volumes. In our population, a larger EOR was associated with the occurrence of postoperative ischemia, and larger tumor and resection volumes were correlated with the volume of ischemia. Additionally, the occurrence of post-RT injury was associated with a larger residual tumor and a smaller EOR, as well as a left temporal preoperative tumor location and a right frontal or left temporal residual tumor location. A thorough examination of spatial and volumetric characteristics of the tumor, treatment and subsequent complications can help elucidate the etiology and guide treatment decisions.
P11.21.A LONG-TERM SURVIVAL WITH IDH WILDTYPE GLIOBLASTOMA: FIRST RESULTS FROM THE ETERNITY BRAIN TUMOR FUNDERS’ COLLABORATIVE CONSORTIUM (EORTC 1419)
Authors: Weller M , Felsberg J , Gramatzki D , Le Rhun E , Clarke J , Soffietti R , Wick W , Chinot O , Ducray F , Roth P , McDonald K , Hau P , Hottinger A F , Reijneveld J , Schnell O , Marosi C , Glantz M , Darlix A , Lombardi G , Krex D , Glas M , Reardon D A , van den Bent M J , Lefranc F , Herrlinger U , Razis E , Carpentier A F , Phillips S , Rudà R , Wick A , Tabouret E , Meyronet D , Maurage C , Rushing E , Rapkins R 
Published: September 2023

Abstract

BACKGROUND
Median survival with glioblastoma remains in the range of 12 months on population levels. Only few patients survive for more than 5 years. Patient and disease features associated with long-term survival remain poorly defined.

METHODS
European Organization for Research and Treatment of Cancer (EORTC) 1419 (ETERNITY) is a registry study supported by the Brain Tumor Funders Collaborative in the US and by the EORTC Brain Tumor Group. Patients with glioblastoma surviving at least 5 years from diagnosis were identified at 24 sites in Europe, US, and Australia. In patients with isocitrate dehydrogenase (IDH) wildtype tumors, prognostic factors were analyzed using the Kaplan-Meier method and the Cox proportional hazards model. A population-based reference cohort was obtained from the Cantonal cancer registry Zurich.

RESULTS
At the database lock of July 2020, 280 patients with histologically centrally confirmed glioblastoma (189 IDH wildtype, 80 IDH mutant, 11 incompletely characterized) had been registered. In the IDH wildtype population, median age was 56 years (range 24-78 years), 96 patients (50.8%) were female, 139 patients (74.3%) had tumors with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Median overall survival was 9.9 years (95% CI 7.9-11.9). Patients without recurrence experienced longer median survival (not reached) than patients with one or more recurrences (8.92 years) (p&lt;0.001) and had a high rate (48.8%) of MGMT promoter unmethylated tumors.

CONCLUSION
s Freedom from progression is a powerful predictor of overall survival in long-term survivors with glioblastoma. Patients without relapse often have MGMT promoter-unmethylated glioblastoma and may represent a distinct subtype of glioblastoma.