bluuebunny/crossref_metadata_2025_split huggingface dataset:
PL02.4.A SHARED DECISION-MAKING IN NEUROSURGICAL CONSULTATIONS WITH NEWLY DIAGNOSED BRAIN TUMOR PATIENTS: A THEMATIC ANALYSIS OF PATIENT INVOLVEMENT
Authors: Bras I J M , Sitskoorn M M , Joosen M C W , Vugt I J M , Hoogendoorn A P Y , Rutten G J M , Gehring K 
Published: September 2023

Abstract

BACKGROUND
In shared decision-making (SDM) the patient serves as the expert on his or her own life and the health care professional serves as the medical expert. However, many SDM instruments that employ observer coding schemes primarily focus on information provision, and less on patient involvement. The items that are included on patient involvement are as follows: 1) introducing SDM to the patient, 2) providing personalized information and 3) discussing patient’s views, values and situation. These items may mark the presence of patient involvement and will be taken as a starting-point for this study, yet they do not provide information on how these items are discussed as part of the SDM process. The aim of this study is to illustrate the involvement of newly diagnosed brain tumor patients in SDM by analysing the decision-making process during neurosurgical consultations and identifying sub-themes related to patient involvement.

MATERIAL AND METHODS
This study employed a codebook thematic analysis to identify the sub-themes concerning aspects of patient involvement in the neurosurgical decision-making process. The first consultation between newly diagnosed glioma or meningioma patients and their neurosurgeons were audio-recorded, transcribed and coded. The study followed a recursive design continuing with analysis until data saturation was reached.

RESULTS
Saturation was reached after analysing 11 consultations. We identified 13 sub-themes within the three main themes, and we will support our findings with direct quotes from the consultations during the conference presentation. Theme 1 was comprised of the sub-themes inviting the patients to participate, presenting treatment options, inquiring about symptoms and daily life, asking patients about treatment preference and room for questions. Questions about patients’ personal circumstances are often asked near the end of a consultation, when the decision regarding treatment has already been made. Theme 2 was comprised of the sub-themes personalizing information, personalizing aspects of treatment and personalizing treatment recommendations. There are examples of neurosurgeons integrating information provided by the patient to personalize the decision-making process. Theme 3 was comprised of the sub-themes interference of disease, daily life, family and requested information. These sub-themes show what patients (spontaneously) share about their lives.

CONCLUSION
We illustrated how brain tumor patients contribute to the SDM process, what information patients and their decision-partners provide and how this information is integrated in the decision-making process during neurosurgical consultations. Our findings may provide handholds to further improve patient involvement and personalization of the decision-making process.
KS02.5.A OVERALL SURVIVAL ASSOCIATED WITH FIRST-LINE PCV OR TEMOZOLOMIDE IN COMBINATION WITH RADIOTHERAPY IN PATIENTS WITH IDH-MUTANT, 1P/19Q CODELETED, GRADE 3 OLIGODENDROGLIOMA: ANALYSIS FROM THE POLA COHORT
Authors: Kacimi S E O , Dehais C , Carpentier C , Chinot O , Bronnimann C , Vauleon E , Djelad A , Moyal E C , Campone M , Ducloie M , Noel G , Cuzzubbo S , Thaillandier L , Ramirez C , Colin C , Appay R , Tabouret E , Nichelli L , Mathon B , Thomas A , Tran S , Bielle F , Alentor A , Labreche K , Idbaih A , Figarella-Branger D , Ducray F , Touat M 
Published: September 2023

Abstract

BACKGROUND
Patients with IDH-mutant, 1p/19q codeleted, grade 3 oligodendroglioma (Olig-3) derive benefit from the addition of alkylating agent chemotherapy to radiotherapy. However, to date, the choice between Procarbazine, Lomustine, and Vincristine (PCV) or Temozolomide (TMZ) as an optimal chemotherapy regimen for these patients remains unclear due to the lack of randomized clinical trial data comparing the two regimens.

MATERIAL AND METHODS
The objective was to assess the survival outcomes associated with first-line radiotherapy and PCV compared to radiotherapy and TMZ in patients with IDH-mutant, 1p/19q codeleted Olig-3 (WHO 2021). We included patients with histologically-proven IDH-mutant, 1p/19q codeleted Olig-3 from a large prospective French network cohort (POLA). The overall survival (OS) from surgery date was computed using Kaplan-Meier methods and Cox proportional hazards regression model.

RESULTS
A total of 306 patients with IDH-mutant, 1p/19q codeleted Olig-3 treated with radiotherapy and chemotherapy between 2008 and 2022 were included. In all, 67.6% of patients (n=207, median age at diagnosis 49.3y [IQR: 40.4-58.7]) were treated with PCV and 32.4% with TMZ (n=99, 50.3y [IQR: 43.8-61.2]) as first-line chemotherapy. Baseline characteristics were comparable between patients from both groups. The median follow-up duration was 78.4 months (IQR: 44.4-103.0). Median OS was not reached (95% CI: NR-NR) and 140 months (95% CI: 110-NR) in the PCV and TMZ groups, respectively (log rank test for OS, P=0.0023). On univariate analysis, there was a significant difference in both 5-year (PCV: 89%, 95% CI: 85-94 vs TMZ: 75%, 95% CI: 67-84; P = 0.0014) and 10-year OS (PCV: 73%, 95% CI: 62-85 vs TMZ: 60%, 95%CI: 49-73; P = 0.003) in favor of PCV. In the adjusted analysis for age, extent of resection, gender and Karnofsky performance scale (n=288), a significant OS difference between TMZ and PCV was found in the Cox proportional hazards regression model (TMZ vs. PCV HR 2.01, 95% CI: 1.16-3.50, P=0.013).

CONCLUSION
In the POLA cohort, among patients with IDH-mutant, 1p/19q codeleted Olig-3 receiving first-line radiotherapy combined with chemotherapy, treatment with PCV was associated with better survival compared to TMZ in both univariate and adjusted analyses. The small sample size and event rate especially in TMZ group warrants further validation. However, these results provide preliminary data on survival outcomes associated with first-line chemotherapy with PCV or TMZ in patients with IDH-mutant, 1p/19q codeleted Olig-3.
JS08.4.A LINEAR GRADING COEFFICIENT REVEALS EMBRYONIC DEVELOPMENT GENE SIGNATURE AS TREATMENT-INDEPENDENT PROGNOSTIC FACTOR IN IDH-MUTANT ASTROCYTOMA
Authors: Ghisai S A , Hoogstrate Y , Tesileanu C M S , van Hijfte L , de Heer I , Vallentgoed W R , van den Bent M J , French P J 
Published: September 2023

Abstract

BACKGROUND
Diffuse gliomas are classified into grade II/III and grade IV IDH-mutant (IDHmt) astrocytoma based on histology and homozygous deletion of the CDKN2AB locus, according to the 2021 WHO classification. There is considerable variation in prognosis within these classification groups and we therefore sought to identify features that might aid further tumor grading.

MATERIAL AND METHODS
RNA sequencing was performed on IDHmt astrocytomas included in the CATNON trial and overlaid with previously generated genome-wide methylation data. This dataset was extended by multi-omics data from the TCGA and GLASS-NL studies, where the latter was used for validation. For all datasets, only IDHmt astrocytomas were selected. We defined a linear grading coefficient (LGC) based on calibrated DNA methylation-based probability scores and performed differential gene expression (DGE) regression analysis on the LGC. Statistical analyses were intersected across the CATNON and TCGA cohorts ("discovery set") and validated on the primary-recurrent GLASS-NL dataset. Single-nucleus RNA-sequencing (snRNAseq) data of high-grade IDHmt astrocytomas was used to explore the source of expression signals.

RESULTS
DGE regression analysis revealed that higher-grade IDHmt tumors (high LGC) exhibited mRNA upregulation of key embryonic developmental transcription factors (HOXA/C/D, NKX, PAX, and TBX). Although the vast majority of CpG sites in LGC high tumors were hypomethylated, homeobox genes were strongly hypermethylated in our discovery set. All HOX gene clusters showed gene-ordered (differential) expression where e.g. HOXD10&gt;D9&gt;D8&gt;D4&gt;D1 and HOXA3&gt;A7&gt;A9&gt;A13 suggesting derepression of enhancer sequences up/downstream of the gene cluster. Our expression-based gene signature was positively correlated with, but not limited to, the G-CIMP-low subtype and homozygous CDKN2AB deletion. More than half of the genes from the HOX gene family were part of our signature. Our embryonic development signature was prognostic (log-rank test) on both the discovery (CATNON: p &lt; 0.0005, TCGA: p &lt; 0.0005) and validation set (GLASS-NL: p &lt; 0.005). As our signature was developed on molecular data from the first resection its prognostic value is treatment-independent. SnRNAseq on high-grade IDHmt astrocytomas indicated expression of embryonic development genes from tumor cells, which was not restricted to cells from the stemness program.

CONCLUSION
Our study highlights upregulation of embryonic development genes as potential molecular mechanism associated with the malignant progression of IDH-mutant astrocytomas.
OS01.5.A THE USE OF MULTIOMICS IN THE IDENTIFICATION AND CHARACTERISATION OF TERTIARY LYMPHOID STRUCTURES IN GLIAL TUMORS
Authors: Lun J H , Singh A , Cakmak P , Köhler M , Schupp J , Macas J , Plate K H , Reiss Y , Imkeller K 
Published: September 2023

Abstract

BACKGROUND
Tertiary Lymphoid Structures (TLSs) are organized immune cell aggregates present in non-lymphoid tissues for the initiation and maintenance of local and systemic anti-tumor immune response. The presence of TLS has been associated with better prognosis and clinical outcome in several cancer types, including lung and melanoma. However, the formation of TLS and its potential role in intra-tumoral immune response remains unclear. TLS are particularly interesting in gliomas as tumor-infiltrating lymphocytes is inefficient possibly due to the immunosuppressive microenvironment and the presence of the blood brain barrier. This study aims to identify and characterize the presence of TLS in glioma patients, to understand its role in generating a local immune response against tumors and identify potential biomarkers. We characterized TLS in glioma by immunohistochemistry, RNA sequencing from TLS positive tumors and used spatial transcriptomics to map TLS gene expression within the tumors.

MATERIAL AND METHODS
Of the 1274 adult patients with diffuse glioma, resected between 2015 and 2021, a total of 663 FFPE-tissue samples were available for B cell infiltration IHC-screening. Subsequently, the TLS+ samples were characterized using spatial transcriptomics and Opal-TSA mIHC, a spatial proteomic method that enables a simultaneous detection of 6 antigens in FFPE tumor tissues. A selection of TLS+ and matched TLS- tumors were subjected to bulk-tissue whole RNA sequencing. Downstream analysis such as cell-type specific transcriptional deconvolution and differential gene expression were performed. Furthermore, a multimodal analysis of TLS in glioma was conducted by combining the genomic, transcriptomic, spatial proteomics and clinical data.

RESULTS
B cell accumulations were observed in 13.1% of all gliomas. Small CD20 B cells accumulation, named perivascular immune cells (PVIC), and TLS were observed in 10.7% and 2.4%, respectively. We investigated the overall survival of patients in the TLS+, TLS- and PVIC groups. So far, no significant differences were observed. The transcriptomic analyses of TLS+ with TLS- tumors revealed an upregulation of genes related to innate and adaptive immune responses, complement cascade and the extracellular matrix. Genes associated with neural differentiation were expressed higher in TLS- compared to TLS+ tumors. Moreover, our multimodal analysis revealed the presence of distinct classes of TLS in glioma which differed in their cellular and molecular compositions.

CONCLUSION
Using a multimodal analysis, this study identified B cell accumulation and TLS in glioma patients. In contrast to other cancer types, the presence of TLS in glioma did not correlate with a higher overall survival. However, the role of TLS in glioma and their prognostic and therapeutic relevance remains under investigation with further analyses currently underway.
OS02.5.A DEVELOPMENT OF A PATIENT DECISION AID FOR PATIENTS WITH RECURRENT HIGH-GRADE GLIOMA - A CO-CREATION PROCESS
Authors: Sørensen von Essen H , Rom Poulsen F , Hedegaard Dahlrot R , Piil K , Dahl Steffensen K 
Published: September 2023

Abstract

BACKGROUND
Patients with high-grade gliomas (HGG) face a difficult decision when the tumor recurs. There are no curable treatments, and all palliative treatment options include risks of complications and adverse effects. In this situation, support is needed for patients to navigate between these trade-offs and make preference-sensitive decisions. Shared decision making (SDM) is an approach where a decision is made in collaboration between a clinician and a patient by combining the clinician’s scientific evidence and knowledge with the patient’s subjective values and preferences. SDM aims to make quality decisions congruent with the individual patient’s informed preferences and to support patients in the decisional process. Patient decision aids (PtDA’s) have proven to be an efficient tool for facilitating SDM. However, there are no PtDA’s available for patients with recurrent HGG. This study aimed to develop a PtDA in a co-creation process with patients with recurrent HGG and family caregivers

MATERIAL AND METHODS
Based on the International Patient Decision Aids Standards, our team developed a PtDA through an iterative process of drafting and re-drafting. Patients and family caregivers were involved throughout the process as active team members. The PtDA was alpha-tested using structured interviews and the Preparation for Decision Making Scale questionnaire to assess the understandability, acceptability, and perceived usefulness of the PtDA. Data were analyzed using descriptive statistics and a directed content-analysis approach.

RESULTS
The final draft of the PtDA contained six treatment and care options, including the option of doing nothing. A balanced presentation of benefits and disadvantages was described for each option. In the alpha test, 31 patients with HGG, family caregivers, and clinicians assessed the final draft of the PtDA and found it to be understandable and acceptable. Patients and family caregivers perceived the PtDA to have a higher level of usefulness in supporting and preparing for decision making than did the clinicians (p=0.05). Ten of 11 clinicians were willing to use the PtDA in future consultations.

CONCLUSION
The PtDA was assessed to be understandable and acceptable by patients, family caregivers, and clinicians. It was perceived to support and prepare patients with recurrent HGG for decision making, and the clinicians were willing to use it in consultations. The involvement of patients and family caregivers as team members added value to the development process and the PtDA. However, the most applicable model of patient involvement in neurooncological research must be further explored to identify the benefits and limitations of approaches.
OS05.6.A TELEMEDICINE IN NEURO-ONCOLOGY - AN EVALUATION OF REMOTE CONSULTATIONS DURING THE COVID-19 PANDEMIC
Authors: Feldheim J , Schmidt T , Oster C , Feldheim J , Sure U , Kleinschnitz C , Lazaridis L , Kebir S , Glas M 
Published: September 2023

Abstract

BACKGROUND
To minimize the risk of infections during the Covid-19 pandemic, remote video consultations (VC) experienced an upswing in most medical fields. However, despite its multiple benefits, telemedicine in neuro-oncology comprises unique challenges and opportunities: Comprehensive neurological examinations that might not translate sufficiently to VC are very relevant for neuro-oncological patients. Also, communication in neuro-oncology can be highly emotional and challenging on a personal level, and VC have been accused of creating emotional distance between the patients and doctors. So far, evidence-based insights to evaluate and potentially customize current concepts of VC in neuro-oncology are scarce.

MATERIAL AND METHODS
We analyzed &gt;3.700 neuro-oncological consultations conducted at our institution between the 1st of April 2020 and the 30th of June 2021, of which &gt;300 were conducted as VC by patients' preference. Then we collected patients' basic demographic and clinical data and compared how the collective of patients that chose to participate in VC distinguished from those who did not. Also, we examined the reasons, suitable/less suitable encounters, VC's benefits and disadvantages and future opportunities by conducting an anonymized survey in the VC collective.

RESULTS
The ratio of VC participation correlated with the incidence of SARS-CoV-2 infections (r=0.5, p=0.03). Patients that participated in VC had worse clinical conditions and higher grades of malignancy, were more often diagnosed with glioblastoma, and had a longer travel distance (all p&lt;0.01). VC were considered a fully adequate alternative to face-to-face consultations for almost all encounters that patients chose to participate in (&gt;70%), except initial consultations. Most participants preferred to alternate between both modalities rather than participate in one alone but preferred VC over telephone consultation. Patients stated that VC made them feel safer. Participants also expressed interest in implementing other telemedicine modalities (e.g. apps) into neuro-oncology.

CONCLUSION
VC are a promising addition to patient care in neuro-oncology. However, patients and encounters should be selected individually. Patient subgroups that might be especially suitable for VC are patients with long travel distances seeking an expert opinion, patients in poor clinical condition, glioblastoma patients and patients requiring frequent consultations in person. A strength of face-to-face consultations is the more intense personal contact, whereas VC convince with a lower expense. VC made patients feel safer, and participants expressed their interest in expanding the offer of telemedicine in neuro-oncology further.
OS06.6.A FLAIR-SIGNAL INTENSITY CHANGE AS A PREDICTOR OF PROGRESSIVE GLIOBLASTOMA IN THE EORTC CENTRIC AND CORE STUDIES
Authors: Flies C M , Friedrich M , Lohmann P , van Garderen K , Smits M , Tonn J C , Weller M , Gatson N N , Galldiks N , Snijders T J 
Published: September 2023

Abstract

BACKGROUND
In patients with glioblastoma, radiological recurrence of enhancing tissue after chemoradiotherapy can originate from progressive disease (PD) or pseudoprogression/treatment-associated changes. In earlier studies, a change of the FLAIR-signal intensity (SI) predicted PD with 18-84% sensitivity and 71-100% specificity, both with quantitative resection cavity to ventricle SI ratio of 7.3. We assessed the rate of FLAIR-signal intensity change in patients with O6-methylguanine DNA methyltransferase (MGMT) promoter-methylated or -unmethylated glioblastoma from the randomised CENTRIC and CORE studies (NCT00689221, NCT00813943). These patients were treated with chemoradiotherapy or chemoradiotherapy with cilengitide, an integrin inhibitor.

METHODS
Patients from both studies with a gross total resection and ≥3 follow-up MRIs were included. The outcome was determined by the modified RANO criteria of 2017. Two researchers evaluated the FLAIR-SI of the resection cavity. A positive SI change was scored qualitatively in case of a visually brighter signal intensity than on the previous MRI. Quantitative analysis was based on a ratio of SI in the resection cavity compared to SI of the ventricles.

RESULTS
Follow-up was available for 307 patients. Median time from RT to (preliminary) progressive disease was 6.2 months for MGMT promoter-methylated (interquartile range, (iqr)=2.5-14.7) and 6.0 for MGMT promoter-unmethylated glioblastoma (iqr=2.7-8.9). Of the 307 patients, 142 patients showed stable disease, response, or treatment-associated changes and 165 (preliminary) PD at the end of follow-up. A qualitative FLAIR-SI change was found in 61 patients (19.9%) and 44 of these developed (preliminary) PD, with a positive predictive value of 72.1% (95%-CI 59.2-82.9%); positive predictive value was 88.9% for MGMT promoter-unmethylated and 67.4% for MGMT promoter-methylated glioblastoma. We found an overall sensitivity of the FLAIR-SI-change for PD of 26.7% (95%-CI 20.1-34.1%), with ranges of 22.9 to 39.2% depending on MGMT promoter methylation status and treatment allocation; specificity ranged from 88 to 91.3%, with an overall specificity of 88.0% (95%-CI 81.5-92.9%). Median time from first FLAIR-SI to progression was 0 months (iqr=0-2.7) with a range of 0 to 13, and from the brightest signal was 0 months (iqr=0-1.0). The average signal intensity ratio was 10.2 at the time of the brightest signal; further quantitative analyses will be presented.

CONCLUSION
We confirmed the positive predictive value of a change in FLAIR-signal intensity of the resection cavity for concurrent or subsequent progressive disease in resected glioblastoma. Patients with such a change of the signal intensity should be worked up further on (e.g. PET imaging, biopsy, any clinical change) or else undergo another MRI closely.
OS09.1.AIN VIVOTWO-PHOTON TUMOR IMAGING IN AN ORTHOTOPIC MEDULLOBLASTOMA MOUSE MODEL
Authors: Teske N , Kutlu N N , Herold J J , Dengler L , Eberle C , Nikolaishvili E , Karschnia P , Blobner J , Müller K , Langer S , Buschinger V , Warmuth L , Busch D H , Buchholz V R , Thon N , Tonn J , Feuchtinger T , von Baumgarten L 
Published: September 2023

Abstract

BACKGROUND
Medulloblastoma represents the most common primary brain malignancy in pediatric patients and is associated with neuro-cognitive impairment and frequent relapses after aggressive multimodal therapy. Adoptive immunotherapies such as CAR T-cell therapy are currently being investigated, showing promising results in preclinical models but lacking efficacy in first-in-human trials. Refined in vivo models to investigate reasons for treatment failures are therefore urgently needed.

METHODS
We developed a xenogeneic orthotopic medulloblastoma (MB) model in mice by combining a chronic cerebellar window with repetitive intravital two-photon laser scanning microscopy. Red tdTomato-fluorescent DAOY (SHH MB) tumor cells expressing EphA2 were implanted intracranially into the cerebellum of immunodeficient mice (n = 7), and tumor cell formation was followed by in vivo-microscopy. Intravenous fluorescein isothiocyanate (FITC)-dextran was used for intravascular plasma staining. EphA-directed CAR T-cells were injected into the adjacent brain parenchyma.

RESULTS
Chronic cranial window implantation was well tolerated and allowed repetitive visualization of the mouse cerebellum. After intracranial tumor cell implantation, continuous tumor growth could be evaluated with epifluorescence as well as 2-photon laser scanning microscopy. Tumor formation was identified as early as day 5 in every mouse and could continuously be followed up to 35 days until mice succumbed due to tumor burden. Window quality and fluorescence intensity remained high until the end of the experiments. Studies on GFP-expressing CAR T-cell injection directed against EphA2 are currently ongoing.

CONCLUSIONS
We herein establish a robust orthotopic medulloblastoma mouse model that allows repetitive in vivo tracking of fluorescence-expressing tumor cells, CAR T-cells and blood vessels over weeks. Such models may be used to study medulloblastoma tumor growth under the influence of different immunotherapies and reveal interactions between tumor cells and CAR T-cell therapies on a single-cell level.