bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.59.B HIGH GRADE GLIOMAS IN PATIENTS WITH HISTORY OF EXTRACRANIAL CANCERS, A RETROSPECTIVE MULTICENTRIC STUDY
Authors: Kalita O , Kazda T , Reguli S , Jancalek R , Fadrus P , Slachta M , Pospisil P , Krska L , Vrbkova J , Cvek J , Dolezel M , Smrcka M , Lipina R , Hrabalek L 
Published: September 2023

Abstract

BACKGROUND
Metastases are most frequent brain cancer, involving 50-60% of all intracranial neoplasm. Dominated origins are lung, breast, colorectal cancers. A progress in diagnostic and treatment strategies significantly improved the life expectancy of patients with extracranial cancers. Patients with neurological symptoms should be recommended to the brain MRI. Rarely silent primary brain cancers are revealed. Metastases are considered as a first option, but brain lesions with contrast enhancement could be misdiagnosed. We more and more often meet with high grade glioma (HGG) in patients experienced with other primary cancer. Aim of our study is evaluated an incidence of concurrent cancers, relations between former cancer staging and malignant primary brain tumor evaluation, and also appreciation of treatment efficiency.

MATERIAL AND METHODS
Data of all glioma patients treated at the three Czech neuro-oncology centers are collected regularly and prospectively during routine maintenance of a database. This work focuses on adult patients with concurrent history both of extracranial cancers and HGGs who underwent resection and oncotherapy between January 2008 and December 2020. Information on the patients’ clinical condition (Karnofsky score (KS)) was collected along with imaging and histological data on each patient’s tumor and details of their cytogenic alterations. Also regarding former extracranial cancers they have been followed up by oncologic center. We excluded the patients with prostate cancer.

RESULTS
The analysis included 48 patients aged between 44 and 79 years. The median age was 65.3 years. The group contained more women (35/48) than men (13/48). Thirty one patients had a history of breast carcinoma, nine of renal carcinomas and eight of colorectal carcinomas. Following the diagnosis of carcinoma, forty four patients received oncotherapy and four had no adjuvant therapy. Surgery of brain tumors has always revealed HGGs, IDH wild-type. Following the diagnosis HGG thirty patients underwent chemoradiotherapy, thirteen had palliative radiotherapy and five had no oncotherapy. The average time from the diagnosis of extracranial cancer to that of GBM was 4 years. The OS was 11.4 months (range 3-29 months). All the patients succumbed to GBM progression.

CONCLUSION
Limited number of these patients has been selected. Prognosis was depended on staging of extracranial cancer and performance status. If these patients would be able to pass standard oncologic treatment of primary HGG, they did not find survival distinctions to compare with no extracranial cancer history patients. For right treatment strategy it is mandatory to eliminate misdiagnose of brain metastases and primary malignant brain tumors. This research was funded and supported by Ministry of Health of the Czech Republic (grant NU21-03-00195, NU20-03-00148)
P11.62.A GENDER-RELATED DIFFERENCES IN PATIENTS CHARACTERISTICS, AND TREATMENT OUTCOME IN A COMPARATIVE STUDY OF MICROSURGERY AND RADIOSURGERY OF VESTIBULAR SCHWANNOMA
Authors: Wang S , Machetanz K , van Eck A , Horstmann G , Tatagiba M , Naros G 
Published: September 2023

Abstract

BACKGROUND
Gender-related differences in patients with sporadic, unilateral vestibular schwannoma (VS) are poorly investigated so far. In studies focusing on natural history, tumor growth was described to be indifferent in either sex. However, it remains unclear whether patient’s sex affects the treatment response to stereotactic radiosurgery (SRS) or microsurgical resection (SURGERY). This study elucidates sex-related differences in VS care.

MATERIAL AND METHODS
This is a retrospective multi-center cohort study. Data was retrospectively collected from two large centers involved in the treatment of vestibular schwannomas for patients between 2005 und 2011 to enable long-term follow-up (FU). Tumor size was classified by Koos Classification. Previously treated VS and patients with Neurofibromatosis were excluded. Clinical state was reported by House and Brackmann (H&B) and Gardner-Robertson (G&R) scale (with H&B&lt;3 and G&R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. Data on VS-associated symptoms like trigeminal affection, tinnitus, and vertigo/imbalance were also collected.

RESULTS
The study population included N=901 patients, who were treated in both centers. N=502 (56%) VS patients were female and N=399 (44%) were male. At time of treatment, women (56 years SD±13.50) were significantly older in age then men (53 years SD±13.80) (p=0.001). Tumor size, cystic morphology, intracanalicular extension, provided care (SRS, SURGERY), treatment related complications, and extent of surgical resection were insignificant in both gender-groups. The incidence of relevant preoperative vertigo was higher in women (67%) then in men (55%) (p=0.002). Pre- and postoperative facial function, hearing loss, and trigeminal symptoms were similar in both groups. Overall incidence of recurrence was insignificant (p=0.106). However, the in subgroups, tumor control with SRS was significantly worse in women compared to men (p=0.035).

CONCLUSION
Provided Care, functional outcome and peri-interventional morbidity were the same in either sex. Relevant vertigo was significantly more often present in women. The incidence of recurrence is higher in women with VS, when treated with SRS compared to men, although tumor characteristics were similar. Additional research is needed to elucidate gender-related difference in tumor biology affecting the response to VS treatment.
P11.63.B VALIDATING THE NEUROLOGIC ASSESSMENT IN NEURO-ONCOLOGY (NANO) SCALE IN CLINICAL PRACTICE: A MULTI-CENTER PROSPECTIVE STUDY IN PATIENTS WITH GLIOBLASTOMA
Authors: Lim Fat M , Fox R , Allen M , Roberto K , Machado M , Chen H , Melhem J , Gonzalez Castro L , Youssef G , Chukwueke U , McFaline-Figueroa J , Lee E , Wen P , Perry J , Reardon D , Nayak L 
Published: September 2023

Abstract

BACKGROUND
The neurologic assessment in neuro-oncology (NANO) scale was developed as a standardized metric to objectively measure neurologic function in patients with brain tumors and complement radiographic assessment in defining overall outcomes. The scale has been incorporated in clinical trials, however, real-world use of the NANO scale to drive clinical decision-making and the predictive value of the NANO scale to determine overall survival remains unclear in glioblastoma.

MATERIAL AND METHODS
We report on an ongoing multi-center study of prospective NANO score collection to evaluate neurologic function in patients with glioblastoma, seen at Dana-Farber Cancer Institute (DFCI) and Sunnybrook Health Sciences Center (SHSC). Patient demographics, tumor histology, molecular status, treatment history, and progression dates are being captured. NANO score, Karnofsky performance status (KPS) and corticosteroid dose are collected at prespecified time points (prior to start of therapy, and during each subsequent MRI visit). Changes in the NANO score will be correlated to overall survival and subgroup analyses will be performed for specific domains of the NANO scale. Statistical analyses including descriptive data analysis and generalized linear models will be performed using R (version 3.4.3).

RESULTS
Since June 2020, 145 patients have been enrolled in this study across the two sites including 90 (62%) with ≥2 follow-up visits. 129 patients had baseline post-operative NANOs captured, with 45 (35%) patients having no deficits in any NANO domain at baseline. All patients with intact baseline NANO had a KPS of 80 or above. Adaptation to a virtual platform for NANO (vNANO) allowed for improved recruitment and follow-up of patients. Validation of vNANO is being performed in a subset of this population. Our interim analysis will be presented at the 2023 EANO meeting.

CONCLUSION
Evaluation of neurologic function by NANO is feasible in both an in-person and virtual framework in a prospective multi-center study in patients with glioblastoma. NANO is able to objectively track neurologic function throughout disease course in glioblastoma. Integration of vNANO may allow for reduced clinical visits and improve access to specialized care for patients in geographically remote locations.
P11.66.A COMBINATION OF TROFOSFAMIDE AND ETOPOSIDE IN RECURRENT GLIOBLASTOMA
Authors: Schmidt T , Agkatsev S , Feldheim J , Oster C , Blau T , Sure U , Keyvani K , Kleinschnitz C , Stuschke M , Herrmann K , Deuschl C , Scheffler B , Kebir S , Glas M , Lazaridis L 
Published: September 2023

Abstract

BACKGROUND
Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients.

MATERIAL AND METHODS
We collected clinicopathological data from adult recurrent glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators’ discretion balanced for tumor entity and canonical prognostic factors served as control.

RESULTS
A total of n=22 recurrent glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 versus 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, p=0.0274) and median overall survival (9.0 versus 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, p=0.0003) were significantly prolonged compared to the control cohort (n=17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n=16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n=15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n=11/15, 73%).

CONCLUSION
This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients and may be associated with prolonged survival in recurrent glioblastoma. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective controlled trial.
P11.75.B PSEUDOPROGRESSION IN A REAL-WORLD GLIOBLASTOMA COHORT: INCIDENCE, MANAGEMENT, PROGNOSTIC IMPACT, AND ASSOCIATED FACTORS
Authors: Blakstad H , Mendoza Mireles E E , Heggebø L C , Magelssen H , Sprauten M , Johannesen T B , Vik-Mo E , Leske H , Niehusmann P , Skogen K , Helseth E , Emblem K E , Brandal P 
Published: September 2023

Abstract

BACKGROUND
Radiotherapy remains a cornerstone in glioblastoma (GBM) management. A continued and unmet need in neuro-oncology is efficient non-invasive methods to differentiate post-radiation magnetic resonance imaging (MRI) changes from progressive disease (PD) in GBM patients. The clinical challenge is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed incidence, management, prognostic impact, and associated factors with PsP in a real-world GBM patient cohort.

MATERIAL AND METHODS
Adult (≥18 years) GBM patients diagnosed in the South-Eastern Health Region of Norway from 2015 to 2018, had received radiotherapy, and follow-up MRIs were included. Patient, tumor, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at three and six months post-radiation using response assessment in neuro-oncology criteria.

RESULTS
PsP incidences at three and six months post-radiation were 20% and 8%, respectively. In adjusted analyses, methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter and absence of neurological deterioration were associated with PsP at both three (p&lt;0.001 and p=0.04, respectively) and six months (p=0.003 and p=0.04, respectively) post-radiation. Patients with PsP at MRI three months post-radiation had a median OS of 24.8 months compared to 11.4 months for patients with PD and 18.7 months in patients with stable disease (SD); the difference was significant only when comparing patients with PsP and PD (p&lt;0.001). There was no survival benefit of treatment change for patients retrospectively evaluated as PD three months post-radiation (p=0.8). Median OS for patients in the PsP group was 31.8 months and thus longer than in the PD group (13.1 months) and the SD group (24.1 months). The difference was only significant when comparing patients with PsP and PD (p&lt;0.001).

CONCLUSION
PsP incidence in this retrospective material was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that the absence of neurological deterioration significantly correlated to PsP. Continuation of temozolomide courses did not compromise survival for patients with PD at three months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings.
Funding: European Union's Horizon 2020 Programme European Research Council Grant 758657-ImPRESS.
P11.76.A SPECTRUM OF TP53 SOMATIC MUTATIONS IN A PROSPECTIVE STUDY OF PATIENTS WITH GLIOMA
Authors: Cabezas-Camarero S , Pérez-Alfayate R , García-Barberán V , Gandía M , García-Feijóo P , López-Cade I , Sotelo M J , Cerón M , Casado-Fariñas I , Pérez-Segura P 
Published: September 2023

Abstract

BACKGROUND
TP53 mutations occur frequently in gliomas, being most common in IDH-wild-type (WT) glioblastomas (GB) and in IDH-mutant (MUT) oligodendrogliomas (OD). Our aim was to describe the mutation spectrum of TP53 somatic mutations in patients (pts) with glioma.

MATERIAL AND METHODS
This was a prospective multicenter study of patients with glioma diagnosed at four different institutions in Spain. Next-generation sequencing (NGS) of formalin-fixed paraffin-embedded (FFPE) or fresh tumor samples were used for sequencing the TP53 gene in an Illumina Miseq instrument (Illumina, Inc.). Only TP53 pathogenic mutations were considered as valid and are reported here.

RESULTS
Between February 2017 and March 2020, 61 glioma patients (pts) were enrolled among which 17 different pathogenic mutations in TP53 were detected. Mutant allele frequency (MAF) was &gt; 4% in all cases. TP53 pathogenic mutations occurred at the following loci: L145P, R158H, R175H, H193R, G199V, R202C, R213X, H214R, Y234C, R248Q, I255S, E271Vfs*36, R273C, P278T, G278T, G279E, R280K. Additional clinical characteristics and survival results will be presented at the meeting.

CONCLUSION
TP53 occur frequently in glioma but widely distributed across the whole exome. The contribution of each specific pathogenic TP53 mutation in gliomas should be further studied.
P12.08.A CELL-EXTRINSIC D-2-HYDROXYGLUTARATE PROMOTES HYPERMETHYLATION AT LINEAGE-SPECIFIC REGULATORY REGIONS TO PREVENT MICROGLIAL ACTIVATION IN IDH-MUTANT GLIOMAS
Authors: Laurenge A , Pugliese P , Richard Q , Picca A , Jouannet S , Labreche K , Bielle F , Iavarone A , Ceccarelli M , Mallat M , Sanson M , Castro-Vega L 
Published: September 2023

Abstract

BACKGROUND
Tumor-associated macrophages and microglia (TAMs) are highly abundant myeloid cells in diffuse gliomas. Their composition and transcriptional programs differ according to the IDH mutation status of glioma cells. The underlying mechanisms remain until now little known.

MATERIAL AND METHODS
We compared bulk DNA methylome (Methylation EPIC array) and transcriptome of TAMs (CD11b+ purified by magnetic-activated cell sorting) from 25 IDH-mutant and 11 IDH-wildtype gliomas. The contamination of the CD11b+ fraction by tumor cells was determined by the detection of IDH and/or TERT mutations using droplet digital PCR. Only samples with a purity of at least 95% were used for analyses. To determine experimentally direct effects of D-2-hydroxyglutarate (D-2-HG), which is the oncometabolite produced and realeased into the microenvironment by IDH-mutated glioma cells, we used primary cultures of human microglial cells obtained from glioma surgery or epilepsy surgery. We exposed microglia or not to (D-2-HG) during 14 days, and analyzed their DNA methylome and transcriptome.

RESULTS
TAMs from IDH-mutant gliomas compared with TAMs from IDH-wildtype gliomas exhibit decreased expression of pro-inflammatory pathways (mainly IFN-γ, IFN-α, and TNF-α signaling) and genes related to G2-M checkpoint, glycolysis and Epithelial-Mesenchymal Transition (EMT). We uncovered that TAMs from IDH-mutant gliomas exhibit significant hypermethylation at promoters and enhancers linked to decreased expression of genes involved in inflammatory responses. Notably, these hypermethylated regions were enriched for binding motifs of transcription factors controlling an environment-dependent transcriptional network in microglial cells (such as PU.1, AP-1, C/EBP and RUNX). These findings were confirmed by comparing methylome data of TAMs from IDH-mutant gliomas and methylome of microglia from normal brains available in the literature. A 14 days exposition to D-2-HG of human microglial cells in vitro partially recapitulates the observed methylation changes. Transcriptome analyses of these cells show that this oncometabolite dampens the IFN-α/γ pathways and attenuates the response to LPS while inducing a metabolic shift toward oxidative phosphorylation.

CONCLUSION
Our findings establish a link between an extrinsic cell-effect of D-2-HG and the hypermethylation of DNA of microglial cells at regulatory regions in IDH-mutant gliomas. Our observations support the concept that oncometabolites may disrupt directly the function of immune cells of the tumor microenvironment.
P12.10.A VASCULOGENIC MIMICRY OCCURS IN PRIMARY AND RECURRENT GLIOBLASTOMA AND IS NOT ASSOCIATED WITH PSMA EXPRESSION
Authors: Tooney P , Maddison K , Faulkner S , Bowden N , Graves M , Fay M 
Published: September 2023

Abstract

BACKGROUND
Glioblastomas are highly vascular tumours that overexpress vascular endothelial growth factor (VEGF), however the anti-VEGF antibody bevacizumab has not demonstrated significant overall survival benefit for patients. Vasculogenic mimicry (VM), the ability of tumour cells to form functional microvasculature lacking an endothelial lining, may compensate for insufficient or inhibited angiogenesis. VM has been reported in primary glioblastoma tissue, but not investigated at progression in recurrent tumours. Prostate specific membrane antigen (PSMA) is expressed in abnormal vessels within primary glioblastoma tumours. We aimed to determine whether VM occurs in primary and recurrent glioblastoma tumours and whether VM vessels also express PSMA.

MATERIAL AND METHODS
Thirty-five matched pairs of primary and recurrent formalin-fixed paraffin-embedded glioblastoma tissue were immunohistochemically labelled for the endothelial cell marker CD34 and PSMA, and counterstained with periodic acid-Schiff (PAS). Vascular structures were categorised as endothelial vessels (CD34+/PAS+) or VM (CD34-/PAS+). Vessels were counted in ten regions within each tumour and a vessel density/mm2 for each vessel category was determined.

RESULTS
Data are expressed as median values. Endothelial vessels accounted for most blood vessels observed. There was a significant decrease in endothelial vessel density in recurrent (41.34 vessels/mm2) compared to primary (86.98 vessels/mm2) glioblastomas (p &lt;0.001). VM was observed in 15/35 primary tumours (42.86%) and 10/35 recurrent tumours (28.57%). VM accounted for only a small proportion of the overall vasculature and VM density was not different between the primary and recurrent groups (p = 0.266). Kaplan-Meier analyses with log rank tests indicated that VM-tumours had longer median OS time than VM+ tumours, regardless of whether VM status was determined based on the primary or recurrent tumour. However, there was no significant difference in survival distribution between VM+ and VM-tumours (primary χ2(1) = 0.381, p = 0.537; recurrent χ2(1) = 3.552, p = 0.059). PSMA is expressed in endothelia lined vessels based on serial section labelling for PSMA and CD34. PSMA expression significantly decreased in recurrent (median H-score = 0.22) compared to primary (median H-score = 0.44) tumours (one-tailed p = 0.031; n = 32) mirroring the CD34+ vessel density.

CONCLUSION
VM contributes to a relatively small proportion of the overall vasculature in glioblastoma tumours and was not associated with OS nor the expression of PMSA. Since VM- tumours had longer OS than VM+ tumours, assessment of VM in recurrent tumours in a larger cohort may determine if there is a clinical significance for VM in recurrent glioblastoma.
P13.12.A SUBTYPES AND SURVIVAL ANALYSIS ANALYSIS OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA WITH RADIOMICS FEATURES
Authors: BARILLOT N , HERNANDEZ I , KIRASIC E , HOUILLIER C , MOKHTARI K , HOANG-XUAN K , ALENTORN A 
Published: September 2023

Abstract

BACKGROUND
Primary Central Nervous System Lymphoma (PCNSL) is a rare and heterogeneous disease with dismal prognosis. Recently, four molecular clusters with clinical relevance have been identified with different potential therapeutic targets in each group. Nevertheless, multi-omics data collection and analysis are expensive and not adapted for clinical practice. Therefore, the identification of surrogate markers to identify PCNSL subtypes from routine data is required, like using hematoxylin and eosin slides from brain biopsies.

MATERIAL AND METHODS
We used a cohort of 108 patients and we selected the 5000 nuclei for each patient among roughly 1,5M nuclei. Once hematoxylin and eosin slides have been digitized, tessellated, normalized and the nuclei have been segmented and filtered with the computation of a solidity score, the PyRadiomics package provides us with more than 800 features for each nuclei. Firstly, we were interested in survival analysis. In a second time, we also used these features for training classification models. We used a partial least squared Cox model, which is a classic Cox model applied to latent components constructed by using linear combinations of the original variables.

RESULTS
Results for our first cohort are promising (C-index of 0.87, std 0.01), with a significant increase compared to the clinical features model (C-index of 0.68, std 0.03). We are now challenging these results with three other cohorts of brain and systemic lymphoma.

CONCLUSION
This study paves the way for a stratification of the clinical evolution based on the machine learning analysis of digital pathology in PCNSL that could be easily translated to a broad range of diseases or other brain tumors.