bluuebunny/crossref_metadata_2025_split huggingface dataset:
KS03.7.A INDEPENDENT PROGNOSTIC ROLE OF METHYLATION CLASS IN ATYPICAL AND MALIGNANT MENINGIOMA UNDERGOING ADJUVANT HIGH-DOSE RADIOTHERAPY: COMPREHENSIVE MOLECULAR ANALYSIS OF EORTC TRIAL 22042-26042
Authors: Maas S L N , Sievers P , Weber D , Weller M , van den Bent M J , Mair M J , Kros J M , Caparrotti F , Salvador V , Peerdeman S M , Casas J , Gorlia T , Sahm F , Preusser M 
Published: September 2023

Abstract

BACKGROUND
In EORTC trial 22042-2604 WHO grade 2 and 3 meningioma patients underwent adjuvant high dose radiotherapy. The current study investigated clinicopathological correlations and the prognostic impact of genetic and epigenetic molecular factors in EORTC 22042-26042 trial patients.

METHODS
For patients that gave consent for additional molecular analysis of the resected tumor specimens (53 of 78 enrolled patients), Illumina Infinium Methylation EPIC BeadChip DNA methylation arrays and next generation sequencing (NGS) panels were performed to investigate the meningioma methylation class, and the presence of mutations in AKT1, TRAF7, BAP1, NF2 and the TERT-promotor as well as loss of chromosomes 1p and 22q and/or homozygous loss of CDKN2A/B. The cohort included 50 atypical and 3 malignant meningiomas per local assessment according to WHO classification at the time of patient enrollment. Factors significant at 10% significance in the univariate and interaction factor analyses were included in multivariate analyses with stepwise selection at the same significance.

RESULTS
The Cox multivariate analyses identified meningioma methylation class as a significant independent prognostic factor for progression-free survival (PFS) and overall survival (OS) measured from patient registration in the trial, respectively Chromosome 1p loss was significantly associated with PFS but not with OS. Age was significantly associated with OS but not with PFS. Due to small number of cases and/or events the prognostic value of homozygous deletion of CDKN2A/B (n=2) and TERT-promotor mutation (n=2) could not be adequately studied.

CONCLUSIONS
In this cohort of WHO grade 2 and 3 meningioma undergoing high-dose adjuvant radiotherapy, meningioma methylation class was identified as an independent prognostic factor for PFS and OS. Chromosome 1p loss was associated with reduced PFS but not OS. Larger cohorts are required to validate our findings.
JS01.3.A EPIGENETICALLY DEFINED ANGIOCENTRIC GLIOMAS MAY LACK ANGIOCENTRIC GROWTH AND INSTEAD SHOW A VARIETY OF GROWTH PATTERNS
Authors: Stegat L , Rohwer J L , Stichel D , Schrimpf D , Coras R , Pagès M , Tauziède-Espariat A , Varlet P , Hans V H , Meyer J , Schittenhelm J , Staszewski O , Cheesman E , Glatzel M , Schmid S , Wesseling P , Korshunov A , Sexton-Oates A , Schüller U , Kõrgvee L , Mueller S , Olar A , Snuderl M , Schweizer L , Aronica E , Sahm F , von Deimling A , Blumcke I , Jones D T W , Capper D , Wefers A K 
Published: September 2023

Abstract

BACKGROUND
Angiocentric glioma mainly occurs in children and young adults. It is associated with a good prognosis (CNS WHO grade 1). Molecularly, most angiocentric gliomas have a MYB-QKI fusion. Histologically, angiocentric gliomas were initially defined by angiocentric growth of the tumor cells. However, we noticed that epigenetically defined angiocentric gliomas often get different diagnoses based on their histology as they may lack this angiocentric growth pattern. We therefore wanted to further analyze epigenetically defined angiocentric gliomas and evaluate how reliable these gliomas are histologically diagnosed based on the criteria defined by the WHO.

MATERIAL AND METHODS
We collected 48 epigenetically defined angiocentric gliomas (37 supratentorial, 11 infratentorial) from 46 patients with sufficient tissue for histological and molecular analyses (DNA methylation analyses; RNA sequencing of a subset). The classification was done using unsupervised hierarchical cluster analyses from DNA methylation data and the brain tumor classifiers v11b4 and v12.5 (www.molecularneuropathology.org).

RESULTS
Angiocentric gliomas were epigenetically distinct from other gliomas including the diffuse astrocytomas, MYB- or MYBL1-altered. A MYB-QKI fusion was detected in 69% (n = 18/26) of angiocentric gliomas, confirming the diagnosis. Other fusions detected were fusions of MYB with intergenic sites, mainly close to QKI (19%; n = 5/26), and MYBL1-QKI (8%; n = 2/26). Histological workup revealed that 75% of the cases included in this study showed the typical angiocentric growth pattern. However, in many of these tumors this was not very pronounced. Many angiocentric gliomas displayed an unspecific growth pattern or resembled pilocytic astrocytoma or ependymoma. Hence, about 59% of angiocentric gliomas were initially misdiagnosed without molecular analyses (supratentorial 50%, infratentorial 100%). We obtained similar results expanding the cohort with further epigenetically defined angiocentric gliomas for which no tissue for a histological re-evaluation was available (total 68 cases; 50 supratentorial, 12 infratentorial; 65 patients). In this expanded cohort, 54% of cases were initially misdiagnosed (45% of supratentorial and 100% of infratentorial cases).

CONCLUSION
In summary, we show that angiocentric glioma often does not show the typical angiocentric growth pattern, resulting in different diagnoses in more than 50% of the cases without molecular analyses. Thus, DNA methylation analyses are needed for a reliable diagnosis of this tumor type.
JS05.6.A CONTINUOUS DYNAMIC MAPPING OF LANGUAGE FUNCTION AND COGNITIVE CONTROL AND SPATIAL CORRELATION TO WHITE MATTER TRACTS USING INTRAOPERATIVE MRI TRACTOGRAPHY
Authors: Mughal A A , Holthe Ø Ø , Olsen K , Nævra M , Løvland G , Vatnehol S , Undseth R , Espinoza A , Etholm L , Vik-Mo E O 
Published: September 2023

Abstract

BACKGROUND
Subcortical mapping of white matter tracts (WMTs) subserving complex processes as movement, language and cognition is critical in glioma surgery. Continuous dynamic mapping (CDM) is an indispensable tool for mapping of the corticospinal tract (CST). There is, however, no widespread method for CDM of more advanced brain functions.

MATERIAL AND METHODS
Patients undergoing awake craniotomy for diffuse gliomas at the Oslo University Hospital with the use of neuronavigation, diffusion tensor imaging (DTI) and CDM coupled with structured evaluation as well as intraoperative magnetic resonance imaging (iMRI) were included in a retrospective analysis. Subcortical CDM was conducted when resection became close to the arcuate fasciculus (AF) and the frontal aslant tract (FAT) with clinical testing using language paradigms and Stroop task. The current was delivered through a monopolar suction probe applying a modified Taniguchi technique with short train of pulses. The spatial relationship between the stimulation response and the examined tracts was determined by measuring the shortest distance between the resection cavity and the relevant white matter tracts (WMTs) using iMRI DTI.

RESULTS
Twenty IDH-mutant and eight IDH wild type gliomas operated 2021-2023 were included in the analysis. Subcortical CDM of the AF and the FAT proved to be amenable as both language function and the ability to perform Stroop test were affected when the stimulation site gradually became close (&lt; 1 cm) to the examined tracts. Positive stimulation response was verified by repeat challenge. The stimulation intensity was thereafter reduced in a stepwise fashion when there was a consistent hesitation in the patient’s response. Resection was continued until the tumor border was reached and not beyond the threshold of 3mA. The threshold of stimulation intensity correlated to the minimal distance from the resection cavity to the delineated WMTs. We did not observe any seizure activity induced by CDM.

CONCLUSION
We have experienced subcortical CDM to be a safe and reliable method, where distance to identified WMT appear to be correlated to the applied stimulation intensity.
OS03.6.A UNSUPERVISED CLUSTERING OF MORPHOLOGY PATTERNS ON WHOLE SLIDE IMAGES GUIDE PROGNOSTIC STRATIFICATION OF GLIOBLASTOMA PATIENTS
Authors: Baheti B , Innani S , Nasrallah M P , Bakas S 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma is the most common malignant adult brain tumor with a poor prognosis and heterogeneous morphology. Stratifying glioblastoma patients according to overall survival (OS) from H&E-stained histopathology whole slide images (WSI) using advanced computational methods is a challenging task with direct clinical implications. We hypothesize that quantifying morphology patterns present in WSI can yield biomarkers of prognostic relevance contributing to optimizing clinical decision-making.

MATERIAL AND METHODS
This work is based on 188 glioblastoma (IDH-wt, grade 4) cases identified in the TCGA-GBM and TCGA-LGG, based on the 2021 WHO classification criteria. One Diagnostic WSI from each patient at 10X magnification was selected (ntraining/nhold-out-test =152 /36) and labeled as short (&lt;9 months, n=94) or long (&gt;13 months, n=94) survivors. The WSI is split into non-overlapping 256x256 patches, and extensive patch-level WSI curation is conducted to discard artifactual content, i.e., glass reflections, pen markings, black lines on the slide, and tissue tearing. Each patch is described by a feature vector of 512 dimensions using a pre-trained VGG16. Principal component analysis reduced the dimensionality of these vectors to 236 such that 85% variance is retained. Unsupervised k-means clustering revealed distinct groups of morphology patterns, where the number of clusters is automatically determined based on the rand index and silhouette coefficient. The proportions of these patterns describe the tumor’s spatial heterogeneity and are used to distinguish between short and long survivors using a random forest classifier.

RESULTS
We identified seven clusters of distinct morphology patterns, including 3 categories of tumor cellularity (low/intermediate/high), necrosis/macrophages, and other prognostically-relevant characteristics. The patient-level short vs long survivor prediction is driven by the proportion of these patterns present in WSI achieving classification accuracy, sensitivity and specificity of 83.83%, 94.44%, and 72.72% respectively on the hold-out test set. The high sensitivity signifies the algorithm’s ability to accurately predict the short survivors which is important in treatment planning and patient management.

CONCLUSION
The interpretability analysis of various morphologic patterns in distinct histologic sub-regions of glioblastoma may uncover correlations with short and long survivors, providing a deeper understanding of the complex relationship between histologic features and clinical outcomes and shedding light on the heterogeneity of glioblastoma. This association could offer additional prognostic information to clinical neuropathologists during microscopic assessment, leading to more refined prognostication and potentially impacting clinical decision-making for improved patient outcomes.
OS03.7.A AUTOFLUORESCENCE BASED RECOGNITION OF BRAIN TUMORS WITH A CONVOLUTIONAL NEURAL NETWORK
Authors: Richter S , Dremel J , Wang T , Eyüpoglu I , Czarske J , Kirsche K , Kuschmierz R , Polanski W , Uckermann O 
Published: September 2023

Abstract

BACKGROUND
The delineation of malignant brain tumors from surrounding tissue is crucial for maximal safe resection. Existing tools for intraoperative tumor visualization lack the possibility of real-time tissue classification. We therefore built a coherent fiber bundle (CFB) endoscope for autofluorescence imaging and trained a convolutional neural network (CNN) to distinguish tumor tissue (T) and non-tumor tissue (nT) in an ex vivo proof of concept study.

MATERIAL AND METHODS
The T-cohort included frozen tissue sections of 35 glioblastoma and 30 brain metastasis patients (10 breast cancer, 10 melanoma, 10 lung cancer). The nT-cohort comprised frozen tissue sections of hippocampi and temporal lobes from 23 patients undergoing surgery for epilepsy treatment. For image acquisition, a laser with excitation wavelength of 473 nm was coupled into a CFB and tissue autofluorescence between 500-550 nm was collected using a bandpass filter. The acquisition time of the camera was set to 700 ms. A CNN (VGG-19) was trained to differentiate the labels T from nT wherein the ground truth was defined by histopathological diagnosis. Training, validation and test sets were randomly generated across all patients in 66.6% / 16.6% / 16.6% proportion. Set generation was repeated 5 times and reported results for the independent test sets are mean values of all iterations.

RESULTS
In total, 3259 CFB images were acquired (T:2408, nT:851), with usually 40 CFB images per sample. Removal of CFB background was not improving classification accuracy and thus, was not performed. The classification accuracy of the CNN with a threshold probability of 0.5 for T-label assignment was 0.986 (sensitivity: 0.988, specificity: 0.982) for analysis of images and 0.98 (sensitivity: 0.971, specificity: 1) when calculating the result for each patient. To simulate clinical application where correct identification of healthy tissue is essential, we created a specificity-tuned CNN with adjusted threshold probability of 0.9 for T-label assignment. This led to a decreased accuracy of 0.945 but increased specificity on the image evaluation approach to 1 (sensitivity: 0.92).

CONCLUSION
Autofluorescence imaging through a CFB is capable of ex vivo recognition of brain tumor tissue with a CNN. The simplicity of the setup and minimal need for data pre-processing allows for intraoperative implementation and potentially enables real-time in vivo brain tumor delineation. To realize intraoperative transition, analysis of ex vivo bulk tissue will be upcoming to capture the signal complexity caused by tissue depth.
OS05.7.A MICROLENS: EXPLORING THE GAP BETWEEN PATIENT AND CAREGIVER NEEDS, AND TECHNICAL DEVELOPMENTS IN AI-ENABLED MEDICAL IMAGE INTERPRETATION
Authors: Pakzad-Shahabi L , Mauricaite R , Karamchandani U , Williams M 
Published: September 2023

Abstract

BACKGROUND
MicroLens aims to co-develop tools and functionality to enable patients & caregivers to view and understand their own brain tumour images, using an explicit design-led approach. Over 7 months we used meetings, written reports and online questionnaires to capture the views of 20 staff, patient and caregiver participants requirements for an AI-enhanced online medical image viewing tool. We have described our initial approach and results (1), but here we focus on how patient and caregiver needs differ from technological approaches described in the medical imaging literature.

MATERIAL AND METHODS
As part of the MicroLens project, we used thematic analysis to extract key patient, caregiver and staff concerns and needs. We then compared this with technical themes of the medical imaging technical literature, drawn from conference proceedings (MICCAI).

RESULTS
The desired level of technical performance was relatively low: patients and caregivers would mostly be happy with labelling of common simple structures and sides, rather than detailed annotation. Other desirable functionality was around sharing imaging with family members and better understanding of imaging. In contrast, the technical literature had a focus on tumour segmentation, classification and prediction of outcomes - none of which appeared in patients' desiderata.

CONCLUSION
Patients, caregivers and staff want very different functionality than the work being conducted in the technical literature. The reasons for this are interesting, and multi-factorial, but reinforce the need for patient-led development. We are currently implementing a prototype and our software developers are designing and developing five of the key tools that emerged from MicroLens project, based on a combination of our findings and theoretical approaches such as the NASSS framework (2).
(1) https://blogs.imperial.ac.uk/componc/2022/10/04/introducing-microlens-using-a-design-approach-to-understand-what-brain-tumour-patients-want-from-their-images/
(2)Greenhalgh T, et al A New Framework for Theorizing and Evaluating Nonadoption, Abandonment, and Challenges to the Scale-Up, Spread, and Sustainability of Health and Care Technologies J Med Internet Res 2017;19(11):e367
OS07.5.A GLIOBLASTOMA VESSEL CO-OPTION AND TRANSITION TO A RESISTANT CELL STATE ARE INDUCED BY CHEMORADIATION
Authors: Pichol-Thievend C , Anezo O , Pettiwala A M , Bourmeau G , Montagne R , Lyne A , Guichet P , Deshors P , Ballestín A , Blanchard B , Reveilles J , Ravi V M , Joseph K , Heiland D H , Julien B , Leboucher S , Besse L , Legoix P , Dingli F , Liva S , Furumaya C , Kovandzic Marcos L , Masliantsev K , Daubon T , Schnell O , Beck J , Servant N , Karayan-Tapon L , Cavalli F M G , Seano G 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma (GB) is one of the deadliest types of human cancer. Despite a very aggressive treatment regime, including resection of the tumor, radiation, and chemotherapy, the recurrence rate is more than 90%. Recurrence is mostly caused by the regrowth of highly invasive and resistant cells that have spread from the tumor bulk and are not removed by resection. To develop an effective therapeutic approach, we need to better understand the underlying molecular and cellular mechanisms of GB chemoradiation resistance and tumor spreading.

MATERIAL AND METHODS
To dynamically follow the changes occurring in GB post-therapy and investigate its relationship with vascular microenvironment, we employed multiple bulk and single-cell RNA-Seq analyses, phosphoproteome, in vitro and in vivo real-time imaging, organotypic cultures and functional assays, digital pathology, and spatial transcriptomics on patient material or preclinical models of GB.

RESULTS
We demonstrated that chemoradiation and the brain vasculature induce a transition to a functional cell state, which we named VC-Resist. This cell state is midway through the transcriptomic axis between proneural and mesenchymal GB cells and is closer to the AC/MES-like state. Better cell survival, G2M-arrest, activation of senescence/stemness pathways make this GB cell state more resistant to therapy. Notably, these persister GB cells are highly vessel co-opting, allowing homing to the perivascular niche, which, in turn, increases their transition to this cell state and resistance to therapy. Molecularly, the transition to the VC-Resist cell state is driven by FGF-FGFR1 signaling, which leads to the activation of DNA damage repair and YAP1 pathways.

CONCLUSION
These findings demonstrate that the perivascular niche and GB cell plasticity jointly generate a vicious loop that leads to resistance to therapy and brain infiltration during GB recurrence.

SUPPORT
This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 (Grant Agreement No. 805225), the INSERM-CNRS ATIP-Avenir grant, the NanoTheRad grant from Paris-Saclay University, Fondation ARC pour la recherche sur le cancer, Campus France and Canceropole Ile-de-France (2022-1-EMERG-06-ICR-1).
OS09.7.A THE ROLE OF MICROSURGERY IN THE FIRST LINE TREATMENT OF VESTIBULAR SCHWANNOMA: IT IS ALL ABOUT THE ODDS
Authors: Naros G , Wang S , Machetanz K , Weinbrenner E , Tatagiba M 
Published: September 2023

Abstract

BACKGROUND
Given the risk for a deterioration of facial function (FDR), first-line (1stline) microsurgery (MS) is discouraged in vestibular schwannoma (VS). In contrast, 1stline radiosurgery (SRS) preserves facial function but has a higher recurrence rate (RR). As salvage VS surgery is very challenging, it could be reasonable to accept a slightly increased FDR of 1stline MS in favor of the lower RR. The aim of the present study was to determine the FDR and RR values of salvage surgery and to calculate the break-even point of MS in the 1stline VS treatment.

MATERIAL AND METHODS
This retrospective study analyzed all patients with unilateral VS undergoing microsurgery between 03/2008 and 10/2021 (n=1470). We identified patient with 2ndline MS after previous MS (MS-MS) or radiosurgery (SRS-MS) as well as patients with 3rdline MS (MS-SRS-MS). After reviewing patients’ clinical and imaging data, we determined FDR and RR for each cohort. This data was compared to a 1stline MS cohort (CTRL) with a follow-up of at least 10 years (n=572). A mathematical prediction model (MPM) was applied to calculate the odds ratio (OR) of different treatment strategies (i.e., MS-MS, SRS-MS, MS-SRS-MS) depending on different FDR and RR values.

RESULTS
We identified 48 patients with 2ndline and 11 patients with 3rdline MS after failed MS/SRS. Time to recurrence in relation to the initial treatment was shortest in SRS-MS (35±34 mo) compared to MS-MS (128±179 mo) and MS-SRS-MS (38±17 mo). These patients had a significant worse preoperative facial function than CTRL patients. Extent-of-resection (EOR) was diminished in 2ndline (79% and 75%) compared to 1stline MS (97%). Both the FDR and RR were significantly increased in MS-MS (FDR:17%, RR:14%) and SRS-MS (FDR:45%, RR:5%) compared to CTRL (FDR:12%, RR:4%). Notably, MS-SRS-MS was associated with the highest FDR (60%) while having the lowest GTR rate (54%). MPM indicated that FDR&lt;15% and RR&lt;5% justify a 1stline MS. In the present cohort, these criteria were met for Koos 1-3 tumors (FDR:0-7%, RR:0-3%).

CONCLUSION
Recurrent VS surgeries fare much worse considering FDR, EOR and RR than first-line surgeries. Hence, reducing the RR of the first-line VS treatment is required. In smaller VS, the surgical oncofunctional outcome can reach the break-even point favoring microsurgery over radiosurgery as first-line treatment option. However, in situations with high FDR (e.g., large or cystic VS) a more conservative surgical approach might be beneficial.