bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIOM-64. TARGETING IDENTIFICATION OF HOST-BRAIN CANCER SYSTEMIC CYTOKINE SIGNALLING FOR EARLY DETECTION AND TUMOUR SUB-TYPING
Authors: Brennan Paul , Baker Matt 
Published: November 2022

Abstract

Background
The host-tumour interaction is fundamental to brain tumour biology, orchestration of which is mediated in part by cytokines. We reasoned that detection of a tumour-specific cytokine profile in patient serum could contribute to early diagnosis strategies, and permit prediction of tumour subtypes before histological diagnosis.

METHOD
Patient serum blood samples (300ul) were collected prospectively from patients with radiological evidence of a new brain tumour diagnosis pre-treatment, and from symptom-matched patients without radiological evidence of a tumour (controls). Our in-house cytokine assay incorporates antibodies captured onto a nitrocellulose slide. 64 capture antibodies are printed per slide, with 4 replicates per antibody. Fluorescence is measured from a biotin secondary antibody, the signal compared to a standard curve, and the averaged relative intensity across 4 replicates determined. We used a hierarchical clustering strategy to examine the relative expression of all 64 biomarkers for each patient class, and for cancer versus non-cancer. We refined this to identify the most discriminatory biomarkers. We made a univariate examination of the association of each antibody with brain tumour type.

RESULTS
Cytokine profiles were collected from 83 patients (42 glioblastoma, 8 meningioma, 12 metastatic cancer, 6 grade III gliomas, 3 grade II gliomas, 2 other brain tumours, 10 non-cancer patients). The top 4 biomarkers with greatest separation for brain cancer versus non-cancer were osteopontin, MMP3, MMP9 and TIMP-1. A principal component analysis demonstrated clear separation between clusters for these biomarkers. Univariate analysis evidenced discrimination of tumour subtypes, for example MMP9 and oligodendrogliomas.

CONCLUSION
Cytokine signals can be identified in small volumes of patient serum and used to identify brain cancer ‘risk.’ This could support prioritization for brain imaging, and prediction of tumour subtype to guide pre-operative management decision-making. Combination with other liquid biopsy strategies such as serum spectroscopy may improve spectroscopy test performance and utility.
BIOM-65. SAFE MAXIMAL RESECTION OF IDH-WILDTYPE GLIOBLASTOMA WITH TUMOR-FREE MOLECULAR MARGIN RESULTS IN PROLONGED PROGRESSION-FREE SURVIVAL
Authors: Shankar Ganesh , Massaad Elie , Bradley Joseph , Lennerz Jochen , Dietrich Jorg , Choi Bryan , Nahed Brian , Curry William , Batchelor Tracy , Carter Bob , Cahill Daniel 
Published: November 2022

Abstract
Purpose Although maximal resection of wild-type GBM tumors is associated with longer survival, the association of genomic alterations with the ability to resect disease has not been elucidated. This study aimed to determine whether certain molecular alterations are less amenable to surgical resection and whether achieving a surgical margin devoid of tumor cell burden provides a clinical benefit. Methods Molecular profiling of 148 consecutive tumor samples from newly diagnosed patients with IDH-WT GBM SNaPshot genotyping, and methylation-specific PCR for MGMT promoter methylation. The association of alterations with residual volume and progression-free survival was evaluated in regression analyses. We prospectively investigated the impact of TERTp status at the surgical margin on progression-free survival (PFS) in 47 patients. PFS and overall survival (OS) were evaluated with the log-rank test and Cox regression models.Results Overall, 148 patients (91 men [61.5%], median age, 62.5 years [range 56–70 years] had maximally safe surgery. The median follow-up duration was 18 months (IQR, 4-32 months). The rate of PFS was significantly lower in MGMT promoter unmethylated IDH-WT GBM amenable to resection with residual volume &gt;4.9cc (hazard ratio [HR], 2.35; 95% CI, 1.44-3.84; P=.005). Gene amplification (PDGFRA, KIT, KDR) on 4q12 and TP53 and RB1 mutations were associated with greater RV. Prospective trial revealed median PFS for tumors with TERTp mutations in the surgical margin was 10.1 months while tumors with undetectable TERTp mutations in the margin did not progress (median follow-up 8.1 months, IQR 1.6-14.6). Surgical tumor margins devoid of TERTp mutations were associated with significantly different probability of PFS (0.23; 95%CI 0.15-0.43; P&lt; 0.01)Conclusion In conclusion, 4q12 amplification (KDR/PDGFRA/KIT) and tumor suppressor gene alterations (RB1, TP53) were associated with greater residual volume. Tumor-free margins defined spatially by intraoperative navigation as assessed by quantifying TERTp mutation allelic fraction was correlated with prolonged PFS.
BIOS-04. CONTACT: CLINICAL OUTCOME ASSESSMENTS TRENDS IN BRAIN CANCER TRIALS
Authors: Kim Yeonju , Armstrong Terri , Gilbert Mark , Celiku Orieta 
Published: November 2022

Abstract

BACKGROUND
Clinical outcome assessments (COAs) are a key component of patient-centered assessment of net clinical benefit in trials. In neuro-oncology, unique symptoms, treatment-related toxicities, and overall poor prognosis further necessitate a focus on symptom management and quality of life. We conducted a computational survey of trends of COA use in past and ongoing neuro-oncology trials.

METHODS
Neuro-oncology trials on ClinicalTrials.gov were identified using primary malignant CNS tumor terms. Instrument names from PROQOLID (n= 2695) were used to determine COA use. Regression and interrupted time-series analyses assessed chronological and design-related trends.

RESULTS
Among 3584 adult neuro-oncology studies, 20% reported using a specific COA instrument: 21% among (n= 3038) interventional and 16% among (n= 524) observational trials. Among interventional studies, most trials used one instrument (91%) as a secondary outcome (81%). 269 unique COAs were reported overall, most frequently patient-reported (72%) and clinician-reported outcomes (44%) indicated for general neoplasms (59%), all conditions (30%), and brain tumors (21%). Most commonly used instruments among treatment-focused trials (n= 523 reporting COAs) included Performance Status (KPS 18%, ECOG 9%), EORTC QLQ-C30 and QLQ-BN20 (9%), and MMSE (7%). Among supportive care studies (n= 47), HADS (13%), FACT-Br (11%), and KPS (11%) were most frequent. COAs use was more likely in phase 3 versus early phase 1 and phase 1 (OR= 0.12 [(95% CI:) 0.02-0.42]; OR= 0.22 [0.09-0.52]) but not versus phase 2 (OR= 0.60 [0.26-1.36]), and was more likely in supportive care trials (versus diagnostics and prevention: OR= 0.10 [0.01-0.65]; OR= 0.05 [0.00-0.79]). The rate of COA use increased linearly over time (1998-2020; β= 1.1 [0.8–1.4]), with no significant changes surrounding individual regulatory events.

CONCLUSION
A growing proportion of neuro-oncology trials specified COA use, reflecting positive changes toward patient-centered drug evaluation. Further investigation of COA use by phase and trial focus may inform future trial design.
BIOS-05. SANGER SEQUENCING AND COPY-NUMBER ALTERATION ANALYSIS WITH MLPA CAN CLINICALLY CLASSIFY IDH-WILD-TYPE LOWER-GRADE ASTROCYTOMA
Authors: Arakawa Yoshiki , Makino Yasuhide , Yoshioka Ema , Shofuda Tomoko , Kawauchi Takeshi , Terada Yukinori , Tanji Masahiro , Kanematsu Daisuke , Mineharu Yohei , Miyamoto Susumu , Kanemura Yonehiro 
Published: November 2022

Abstract
The IDH-wild-type lower-grade astrocytomas are a heterogeneous entity. According to 2021 WHO classification, IDH-wild-type astrocytomas with any of the following factors show poor prognosis: combination of chromosome 7 gain and 10 loss (+7/-10), and/or EGFR amplification, and/or TERT promoter (TERTp) mutation. Multiplex ligation-dependent probe amplification (MLPA) can detect copy number alterations with a reasonable cost. The purpose of this study was to find precise and cost-effective method for stratifying the prognosis of IDH-wild-type astrocytomas. Sanger sequencing, MLPA, and quantitative methylation-specific PCR were performed for 42 IDH-wild-type lower-grade astrocytomas surgically treated at Kyoto University Hospital, and overall survival was analyzed for 40 patients. Of the 42 IDH-wild-type astrocytomas, 21 were classified as grade 4 in 2021 WHO classification and all of them had either TERTp mutation or EGFR amplification. Kaplan-Meier analysis confirmed the prognostic significance of 2021 WHO Classification, and WHO grade was also prognostic. Cox regression hazard model identified PTEN loss and PDGFRA amplification as independent significant prognostic indicators (Risk ratio of 9.75, p&lt; 0.001 and 13.9, p=0.002). The classification recommended by 2021 WHO Classification could be completed using Sanger sequencing and MLPA. Survival analysis revealed PTEN and PDGFRA were significant prognostic factors for IDH-wild-type lower-grade astrocytomas.
CNSC-08. TUMOUR-INFILTRATED CORTEX PARTICIPATES IN LARGE-SCALE COGNITIVE CIRCUITS
Authors: Mandal Ayan , Assem Moataz , Romero-Garcia Rafael , Coelho Pedro , McDonald Alexa , Woodberry Emma , Morris Robert , Price Stephen , Duncan John , Santarius Thomas , Suckling John , Hart Michael , Erez Yaara 
Published: November 2022

Abstract
In neurosurgery, tumour-infiltrated cortex is generally assumed to be non-functional. While prior studies have suggested integration of tumour-infiltrated tissue in relatively local circuits responsible for language and motor function, it is unknown whether such tissue can participate in distributed networks important for higher-order cognitive abilities like executive function. We tested the hypothesis that diffuse low-grade gliomas integrate into large-scale cognitive circuits using intracranial electrocorticography and resting-state functional magnetic resonance imaging of four patients. To identify brain areas recruited for executive function, electrocorticography recordings were acquired from tumour-infiltrated tissue under three conditions: i) baseline (rest), ii) simple counting (1-20; “easy”), and iii) switch counting (1-a-2-b-3-c etc.; “hard”). In each patient, we observed significant task-based high gamma power modulations in tumour-infiltrated cortex in response to increasing cognitive effort (p &lt; 0.05), implying preserved functionality of neoplastic tissue for complex tasks. Additionally, tumour locations corresponding to task-responsive electrodes exhibited functional connectivity patterns that significantly co-localised with canonical brain networks implicated in higher-order cognitive processing (p &lt; 0.05). Finally, dorsal attention network connectivity in tumour-infiltrated cortex correlated with high gamma power elevations during increased cognitive demand (χ 2(1) = 5.14; p = 0.023), establishing a concordance between both techniques. Overall, this study contributes convergent evidence that tumour-infiltrated cortex can participate in large-scale neurocognitive circuits, prompting a reconsideration of traditional notions of neoplastic brain tissue.
CNSC-10. THE COMPLEX RELATIONSHIP BETWEEN NEURONAL ACTIVITY AND FUNCTIONAL NETWORK PROPERTIES IN GLIOMA PATIENTS
Authors: Zimmermann Mona , Breedt Lucas , Centeno Eduarda , Kulik Shanna , Santos Fernando , Stam Cornelis , van Lingen Marike , Hillebrand Arjan , Douw Linda 
Published: November 2022

Abstract

BACKGROUND
Glioma is associated with pathologically high peritumoral neuronal activity, which associates with faster tumor progression. Concurrently, glioma patients have local and widespread disturbances of the functional brain network as measured with magnetoencephalography (MEG), such as higher network clustering (the extent to which regions connected to a particular area are also connected to each other) and locally altered integrative connectivity (for instance assessed with a centrality measure). How local neuronal activity and nodal network properties relate to each other has yet to be investigated.

METHODS
We obtained eyes-closed resting-state MEG in 95 de novo glioma patients and 57 matched healthy controls (HCs). The offset of the power spectrum was calculated for 210 cortical atlas regions as a proxy for neuronal activity. Regional clustering coefficient (CC) and eigenvector centrality (EC) were calculated in the delta, theta and alpha bands. Offset and network values were then averaged across peritumoral regions, contralateral homologue regions and all non-peritumoral regions. Linear mixed models were used to relate nodal CC and EC to local offset in patients and HCs.

RESULTS
The peritumoral area was significantly more active than the non-peritumoral homologue in patients, and showed pathologically high activity in comparison to HCs. However, patients’ functional network was disturbed globally, showing higher clustering and lower centrality than HCs. Whereas high activity related to high centrality in HCs and patients alike, high activity seemed to relate to low clustering in non-peritumoral regions in patients, but not HCs.

CONCLUSION
We find that the relationship between neuronal activity and functional network properties is disturbed in a complex manner in glioma patients. Our results further underline the importance of investigating how local activity may impact global network topology in order to understand how neuron-glioma interactions shape brain functioning.
CNSC-15. DECIPHERING RAMAN-SPECTRAL TISSUE HETEROGENEITY IN GLIOBLASTOMA
Authors: Klein Karoline , Klamminger Gilbert Georg , Mombaerts Laurent , Jelke Finn , Mirizzi Giulia , Slimani Redouane , Husch Andreas , Mittelbronn Michel , Hertel Frank , Borgmann Felix Kleine 
Published: November 2022

Abstract
Raman Spectroscopy is able to provide a fast identification method for healthy and pathological tissues without the need for sample preparation. This makes it highly interesting for intraoperative use in identifying tumor types and borders. However, the capability of a machine-learning classifier to recognize known tissues based on Raman spectra relies on a solid ground truth that is usually provided by measuring small tissue samples first and analyzing the sample later by histopathology. This approach is limited in very closely interspersed tissues that cannot be identified macroscopically, such as glioblastoma where vital tumor tissue, necrosis and peritumoral tissue with characteristic changes to healthy brain tissue are tightly arranged. These areas have been shown to be distinct in their spectral properties, which makes tumor border identification aided by Raman Spectroscopy challenging. As infiltrative tumors leaving no tumor-cell-free brain tissue, borders need to be defined on a clinical scale, where extensive resection must be weighed against retaining functional brain tissue. For this, spectral analysis beyond tumor identification is necessary. In a computational approach we use methods of unsupervised learning and K-means Clustering to investigate heterogeneity within glioblastomas in the native state in order to reduce the complexity of this tumor type. Thereby, it was possible to extract spectra of necrotic tumor areas and to calculate a prediction probability for necrotic tissue within glioblastomas. Several clusters with spectral similarity to each other could be identified, which might represent the different areas of a glioblastoma. Two of these clusters were identified as probable grey and white matter, respectively, by comparison with autopsy tissue. In addition, this assignment independently confirmed the prediction of the classifier as non-necrotic tissue. Deciphering the spectral heterogeneity of glioblastoma in this way may be a great advantage for the surgeon to identify tumor borders and assist in resection control.
CNSC-18. HYPOXIA-INDUCED METABOLIC ADAPTATIONS THROUGH ACOX-1 IN GLIOBLASTOMA
Authors: Bhattacharya Ayon , Caflisch Laura , Balinda Henriette , Boyer Andrew , Lodi Alessia , Zhou Mei , Li Mengxing , Chiou Jennifer , Pandey Renu , Tiziani Stefano , Vadlamudi Ratna , Brenner Andrew 
Published: November 2022

Abstract

BACKGROUND
Hypoxia is a major driver of invasiveness and resistance in glioblastoma (GBM). We hypothesize that GBM adapts to chronic hypoxic conditions through utilization of peroxisomal fatty acid oxidation (FAO). We explored the contribution of acyl coenzyme A oxidase 1 (ACOX-1), a rate-limiting enzyme for peroxisomal FAO, in metabolic adaptation to hypoxia and as a potential therapeutic target.

METHODS
A primary cell line from a bevacizumab-resistant tumor (012015) was cultured under chronic hypoxia (2%O2) or normoxia (21% O2). We used UPLC-MS/MS and GC-MS to determine lipid and polar metabolites. RNA seq was performed on U251 ACOX-1 (KO) cells under normoxic and hypoxic conditions. Differential gene expression was obtained using TopHat2 (genome alignment), HTSeq, and DEseq. Gene set enrichment analysis was used to compare biological pathways between conditions. ACOX-1 was deleted using CRISPR-Cas9 and orthotopically implanted in NCr/SCID nude mice. Animals were treated with 30 mg/kg of pazopanib or vehicle daily through oral gavage.

RESULTS
In 012015 cells we observed altered carnitine metabolites, increase in specific triglycerides, and S-lactoylglutathione indicating dysfunctional mitochondrial FAO, and increase in oxidative stress between hypoxic and normoxic conditions. Also, decrease in citric acid cycle metabolites, increase in glycolytic metabolites were seen in hypoxia. Further RNA seq on U251 ACOX-1 (KO) cells showed downregulated genes such as PCK1, SCD, SREBF1, PIPOX (p&lt; 1E-8) and significant KEGG pathways such as unsaturated fatty acid (p= 0.009), peroxisome (p= 0.025) and PPAR (p= 0.016) between hypoxia and normoxia suggesting increased dependence of these cells on peroxisomal FAO. ACOX-1 (KO) mice showed increased survival when treated (p= 6.7E-04) with pazopanib.

CONCLUSION
In ACOX-1 (KO) model, we observed metabolomic reprogramming with downregulated genes, dysregulated metabolites, and pathways in peroxisomal FAO in hypoxia. These identified genes could be potential targets for therapy in combination with anti-angiogenic therapies that increase hypoxia in GBM.
SURG-36. EVALUATION OF SURGICAL RESULTS AND PREDICTIVE FACTORS OF HYDROCEPHALUS IN PEDIATRIC PATIENTS WITH POSTERIOR FOSSA TUMORS
Authors: Formentin Cleiton , Matias Leo Gordiano , de Santos Santos Lucas Souza Rodrigues , Joaquim Andrei Fernandes , Tedeschi Helder , Ghizoni Enrico 
Published: November 2022

Abstract

INTRODUCTION
Infratentorial tumors represent 45 to 60% of all brain tumors in children and are associated with hydrocephalus in 70 to 90% of cases. The aim of this study is to describe and analyze the surgical results and correlate them with the incidence of hydrocephalus, as well as identify predictive factors of hydrocephalus in pediatric patients underwent to a surgical treatment of posterior fossa tumors.

METHODS
This is a retrospective observational study, based on demographic, clinical and radiological information of pediatric patients underwent to surgical resection of posterior fossa tumors by a single group between 2011 and 2019.

RESULTS
We included 135 patients with a mean age of 7.56 years, mean follow-up of 35.7 months and overall survival of 18.8 months. Considering the histology, most tumors were pilocytic astrocytomas (34.1%), followed by medulloblastomas (27.4%) Total resection was achieved in 77.8% and tumor recurrence was observed in 16.2%. The rate of hydrocephalus was 36.3%, with most shunt procedures performed preoperatively. There was a high rate of complications associated with shunting (42.9%), mostly represented by infection (71.5%). Patients with hydrocephalus were younger (p = 0.001), showing a faster evolution between the onset of symptoms and diagnosis (p = 0.008). Tumor volume (p = 0.1) and location (p = 0.32) were not statistically significant for hydrocephalus, however, the presence of leptomeningeal disease (p = 0.001) was. The resection rate was also significant, with lesions totally resected showing the best results (p = 0.009). Regarding tumor histology, 33.3% of patients with medulloblastoma and 62.5% of patients with ependymoma were shunted.

CONCLUSION
One third of children with posterior fossa tumors will require a shunt procedure. Some factors should guide the neurosurgeon during patient counseling and surgical planning to minimize the use of permanent shunts and avoid related complications.
SURG-37. NEURO-ONCOLOGICAL AUGMENTED REALITY: A MORE INTUITIVE APPROACH TO RESECTION PLANNING
Authors: Van Gestel Frederick , Frantz Taylor , Neuville Quentin , Klein Sam , Bruneau Michaël , Jansen Bart , Scheerlinck Thierry , Vandemeulebroucke Jef , Duerinck Johnny 
Published: November 2022

Abstract

BACKGROUND
When preparing for the resection of an intracranial lesion, its borders and optimal approach are often determined using neuronavigation with a tracked pointer. This can sometimes prove challenging, especially for deep-seated lesions. Augmented reality (AR) can simplify and improve this step by directly displaying the lesion on the patient's skin.

METHODS
A proprietary inside-out infrared tracking solution was developed, allowing for heads-up displaying AR scenes on the Microsoft HoloLens II without the need for an external tracking camera or computer. We included twenty patients with an intracerebral lesion planned for resection. After semi-automatic hologram-to-patient registration, different participants marked the lesion outlines on the patient’s skin, consecutively aided by the Brainlab neuronavigation system and the HoloLens. Each registration on both systems provided a registration transform that was compared for accuracy and consistency. Participant performance was quantified in terms of duration and accuracy for both patient registration and lesion delineation, and compared to expert performance.

RESULTS
When using AR both registration and delineation were significantly faster than with conventional neuronavigation (p = 0.02 and p &lt; 0.001, respectively, and p &lt; 0.001 for the total duration), taking 79.23 ± 17.48 and 39.58 ± 39.10 seconds while neuronavigation required 96.61 ± 24.54 and 90.80 ± 44.09 seconds. AR had a registration offset of 3.3mm and 3.4°, and was more consistent compared to neuronavigation. AR facilitated more accurate and detailed lesion delineation, while neuronavigation often overestimated lesion size.

CONCLUSION
Augmented reality provides a faster and more accurate alternative for resection planning. Lesion delineation was more intuitive while retaining high accuracy. Future research should focus on further intraoperative implementations.