bluuebunny/crossref_metadata_2025_split huggingface dataset:
P11.81.B PRELIMINARY RESULTS FROM A RETROSPECTIVE STUDY OF AWAKE CRANIOTOMIES WITH INTRAOPERATIVE MAPPING IN YOUNG ADULTS WITH GLIOMA
Authors: Kønig A B , Engelmann C M , Skjøth-Rasmussen J 
Published: September 2023

Abstract

BACKGROUND
Awake craniotomy with intraoperative mapping (ACWM) has been proven beneficial in achieving maximal resection of gliomas in eloquent brain areas while preserving neurological function, thus maintaining onco-functional balance. The present study aimed to describe the intraoperative symptoms not related to resection induced deficits in young adult glioma patients during ACWM.

METHODS
A retrospective, descriptive study of young adults (18-39 years of age) with glioma operated with ACWM in Copenhagen between 2016 and 2022. Patients were identified using the hospital operation booking system cross-referenced with the patient coding system. All data was available in and extracted from the Epic Systems healthcare software used at the hospital.

RESULTS
So far 37 patients with glioma (median age 31 years, range 21-39 years; 51% females; 78% high-grade gliomas) have been included, constituting 46 planned ACWMs. Most patients (95%) reported some level of intraoperative pain and/or headache with 27% receiving supplemental local anesthetics and 63% receiving supplemental fentanyl or fentanyl analogues during the awake phase. The median for the immediate postoperative Numeric Pain Rating Scale was 1, range 0-7. Intraoperative non-localization specific symptoms included shivering (41%), fatigue (22%), nausea/vomiting (17%), emotionally overwhelm (15%), anxiety (5%) and postoperative vasovagal syncope (5%). Focal seizures were reported in 24% of patients while 1 patient was untimely converted to general anesthesia due to non-convulsive status epilepticus. Operations were terminated due to completed macro-radical resection (32%), reaching the functional limit of resection (63%) and severe fatigue (5%).

CONCLUSION
Our results represent the practice of a single institution and comply well with previous literature in terms of symptomatic complications not related to resection induced deficits. These symptoms are predominantly simple to manage without the need for untimely termination of surgery. Awake craniotomy with mapping is deemed well-tolerated by young adults and is considered beneficial in optimizing the onco-functional balance of selected glioma patients.
P12.11.B THE BIOLOGICAL CHARACTERISTICS OF HUMAN GLIOBLASTOMA ASSOCIATED MESENCHYMAL STEM CELLS
Authors: Yu Y , Wang J , Chen Z 
Published: September 2023

Abstract

BACKGROUND
Mesenchymal stem cells (MSCs) have been identified existing in the tumor microenvironment (TME) as one of the important stromal cells and can be isolated from various tissues. Recently, it has been reported that tumor-associated MSCs (TA-MSCs) are involved in tumorigenesis. Experimental studies revealed MSCs in glioblastoma progress with numerous controversies. The aim of this study was to determine the characteristics and clarify functions of MSCs in the glioblastoma microenvironment.

MATERIAL AND METHODS
Herein, 32 surgical specimens from patients with high-grade glioma were collected for primary culture of glioma mesenchymal stem cells (GMSCs). After being cultured for 3 passages, the surface antigens of GMSCs were identified by flow cytometry and the trilineage differentiation ability was determined in vitro. The related gene expression on RNA and protein levels was detected by PCR and flow cytometry. Proliferation, cell cycle, migration and invasion assays were used to make sure the characteristics of GMSCs. In addition, the effects of GMSCs on glioma cells were detected both in vitro and in vivo.

RESULTS
We observed that GMSCs showed a typical spindle-like shape and multipotency in vitro, similar to MSCs derived from bone marrow (BMSCs). GMSCs were strongly positive for the mesenchymal markers, especially CD90(Thy-1), while the expression amount for CD44, SOX2 and Nucleostemin were consistent among BMSCs, glioma cell line and primary tumor cells. Additionally, the results of proliferation, migration and invasion assays indicated GMSCs was a group of normal stem cells. We also demonstrated that GMSCs could promote GBM malignant progression by enhancing the migrative ability of tumor cells.

CONCLUSION
We successfully isolated and identified GMSCs from glioblastoma primary culture. The results verified the characteristics of GMSCs were similar to BMSCs, but different from glioma cells. Taken together, MSCs exist in the glioblastoma tumor microenvironment and they may play a crucial role in tumor initiation and invasive growth, which might serve as a potential target for cancer therapy.
P13.08.A JAKOB V. E. GERSTL, MBBS
Authors: Gerstl J V E , von Grothusen C A G , Kilgallon J L , Lindberg R , Onnela J , Smith T R 
Published: September 2023

Abstract

BACKGROUND
Pituitary adenomas are benign neoplasms which can have a profound impact on quality of life. In-situ assessments of patient quality of life with pituitary adenomas and recovery from surgery are limited; existing patient reported outcome measures are, moreover, biased by patient recollection. Smartphone-based digital phenotyping may provide a means of monitoring patient recovery and quality of life at a more granular and accurate level.

MATERIALS AND METHODS
Patients with pituitary adenomas were enrolled during preoperative clinic visits. Included patients installed the Beiwe application, which passively collected GPS data during patient follow-up. Dates of significant clinical events were recorded to assess how they affected mobility. Using a LOESS regression line, aggregate trends amongst patients who underwent transsphenoidal resection were established and compared to baseline values from preoperative patients awaiting surgery and non-operative controls.

RESULTS
As part of a still ongoing study, 35 Patients with pituitary adenomas were enrolled between October 2022 and February 2023. Of these, 13 underwent transsphenoidal resection, the remaining 22 patients were either waiting for surgery and/or served as non-operative controls. Patients undergoing transsphenoidal resection of pituitary adenomas spent more time at home, spent less time walking, walked fewer steps and traveled shorter distances away from home compared following surgery compared to baseline preoperative data and non-operative controls.

CONCLUSION
The authors were able to generate initial digital phenotypes for a cohort of pituitary patients based on passively collected smartphone GPS data; the authors also hope that these initial data may help in the establishment of an in-situ tool to monitor recovery following surgery for pituitary adenoma. It is the authors’ contention that such preoperative mobility metrics may be further utilized to predict postoperative outcomes following surgery which has been demonstrated in the general surgery setting. In the case of pituitary disease, these include postoperative CSF leak, infection, dysnatremia and hospital length of stay.
P13.10.A PREDICTING SURVIVAL OF GLIOBLASTOMAAFTER RADIOTHERAPY USING DEEP LEARNING AND NEUROIMAGING IN A MULTI-CENTRE COHORT
Authors: Chelliah A , Wood D A , Canas L S , Shuaib H , Linares C , Bassiouny A , Luis A , Young T , Roman A , Dragos C , MacDonald M , Lau Y H , Currie S , Fatania K , Frood R , Mathew R , Brock J , Chandy E , Tenant S , Rowland-Hill C , Williams M , Wang Q , Beaumont E , Lam T , Welsh L , Foweraker K , Lewis J , Thust S , Wastling S , Glendenning J , Brazil L , Swampillai A , Ourselin S , Modat M , Booth T C 
Published: September 2023

Abstract

BACKGROUND
Glioblastoma is an aggressive brain tumour routinely monitored with MRI. However, the potential to use imaging as a prognostic biomarker predicting survival after treatment starts is unclear. This study aims to predict survival within eight months of completing radiotherapy from MRIs using deep learning.

MATERIAL AND METHODS
The dataset consists of 206 prospective and retrospective consecutive patients with glioblastoma (WHO 2021) across 11 UK centres (short-term survival: N=64; 31.1%). Models were trained/validated on N=158 (76.7%) retrospective patients (3 centres). Two holdout sets were sampled: retrospective test set (N=19); and external, prospective test set (N=29; 8 separate centres). Dense convolutional neural networks were developed with separate branches for T1c-w and T2-w MR sequences; a third branch concatenates outputs from those branches to predict survival. Dense blocks used pretrained weights for an abnormality detection model. A semi-supervised approach was implemented; patients without known outcomes were added with pseudo-labels during training. Parameter tuning included the number of updated blocks, linear layer sizes, and weighting of pseudo-labels. Imaging models were compared to counterparts that apply non-imaging variables (demographics, MGMT status/%, treatment). Logistic regression, support vector classifier, and decision tree models were fit on non-imaging features alone with feature selection and mean/mode imputation. Combined imaging/non-imaging networks were developed that added a branch for non-imaging inputs.

RESULTS
The current best-performing imaging model used MR sequences alone (validation weighted-ROC=0.80, 95% CI=0.75-0.84; balanced accuracy=0.70, 95% CI=0.55-0.85). Among non-imaging models, the logistic regression model with feature selection performed best (validation weighted-ROC=0.59, 95% CI=0.56-0.63; balanced accuracy=0.59, 95% CI=0.56-0.63). Combined model development is ongoing.

CONCLUSION
This is the first known model applying deep learning to MRIs from multiple centres to distinguish patients with failure to respond to chemoradiotherapy, and those who survive the subsequent treatment window. Based on initial results, image-based models performed best at predicting survival. Such models could be used across centres to suggest closer monitoring and trial targeting of patients with expected short-term survival compared to treatment response.
P14.01.A LIQUID BIOPSY OF GLIOMA-RELATED GENES USING A NOVEL AMPLIFICATION TECHNIQUE
Authors: Adachi J , Suzuki T , Nishikawa R 
Published: September 2023

Abstract

BACKGROUND
In the pathological classification of brain tumors, newly revised in 2021, molecular genetic analysis of gliomas has become more important for diagnosis and understanding of the pathogenesis of gliomas. Gliomas are prone to recurrence and malignant progression, and collecting tumor tissue during every genetic analysis is highly invasive. Therefore, techniques have been developed to analyze tumor-derived circulating cell-free DNA (ccfDNA) in the cerebrospinal fluid as a substitute for tissue collection. However, the amount of ccfDNA derived from the cerebrospinal fluid is extremely small and the number of cases for whom genetic analysis is possible is currently limited. In this study, we attempted to establish a novel method for the integrated analysis of glioma-related genes by in vitro amplification of cerebrospinal fluid-derived ccfDNA from glioma patients and a highly sensitive assay. Methods : Tumor-derived ccfDNA was extracted and purified from 1 ml of cerebrospinal fluid obtained by lumbar puncture using the Maxwell RSC instrument in five glioma cases. Hot spots of mutations in IDH1 and H3F3A genes were analyzed by high resolution melting (HRM), TERT mutation by droplet digital PCR, MGMT promoter methylation by methylation-specific HRM, and chromosome 1p/19q loss by multiplex ligation-dependent probe amplification. For samples in which the amount of ccfDNA was too small to analyze, DNA was amplified approximately 500-fold by DNA polymerase using the GenomiPhi kit and analyzed by the same assay method. Results and

CONCLUSION
s : Although two of the five cases required amplification with the GenomiPhi kit, it was possible to analyze all cases for glioma-related genes as described above. Although the amount of ccfDNA obtained from low-grade gliomas and gliomas that are not in contact with the ventricles or subarachnoid space is small, this amplification method may increase the possibility of liquid biopsy using cerebrospinal fluid in gliomas.
P14.04.B CIRCULATING TUMOR CELLS AS A NON-INVASIVE GLIOBLASTOMA DIAGNOSTIC AND PROGNOSTIC TOOL
Authors: Lessi F , Morelli M , Franceschi S , Aretini P , Ferri G , Menicagli M , Pasqualetti F , Gambacciani C , Pieri F , Grimod G , Di Stefano A , Santonocito O S , Mazzanti C M 
Published: September 2023

Abstract

BACKGROUND
Circulating tumor cells (CTCs) detection in the blood of glioblastoma (GBM) patients can facilitate the assessment of tumoral information without the need for invasive approaches. Our aim is to use GBM CTCs to obtain knowledge about the tumor and improve the current GBM diagnosis and prognosis.

MATERIAL AND METHODS
We collected primary, matched recurrent GBM and healthy controls blood samples. CTCs were enriched from whole blood controls with Parsortix Cell Separation System and analysed on DEPArray system. CTCs were recognized by immunofluorescence with GFAP.The CTCs have been counted for all the samples. Copy Number Aberrations (CNAs) analysis was performed on CTCs. To compare CTCs genetic background with the same patient’s primary and recurrence tissues, whole exome sequencing (WES) was realized on tumor tissues. Recurrence of GBM was diagnosed according to the RANO criteria +/-path proven second surgery +/- FET PET imaging proven. We assessed tumor volume of contrast enhanced (CE) (as a surrogate marker of BBB damage) and nCE at the time of the CTCs collection by seminautomatic segmentation on ITKsnap software.

RESULTS
We found CTCs in GBM patients newly diagnosed at the time of first surgery (86%) but also at recurrence (100 %). Cell counting demonstrated in both primary and recurrent GBM patients’ blood a statistically significantly higher number of CTCs compared to healthy controls (average of cells number 15.8 vs 2.3). Interestingly, recurrent GBM patients showed more CTCs than primary GBM patients (average 9 vs 22.7). CNAs analysis confirmed the tumor status of the selected CTCs. Some of GBM classical mutations (in HTERT promoter, BRAF, PTEN, PI3KCA and EGFR genes) have been searched both in the tumor tissues and in the CTCs. HTERT was found mutated in CTCs of one patient’s tumor carrying mutant HTERT and wild type IDH1/2. We also included three IDH1 mutant glioma patients and one BRAFV600E mutant GBM patient in order to track these in CTCs. We did not find BRAF mutations in CTCs isolated from one recurrent BRAFV600E GBM patient with a very low allele frequency in the recurrent tumor (&lt;1%).

CONCLUSION
We found CTCs in GBM patients newly diagnosed and at recurrence. Several factors may affect CTCs release such as tumor volume, CE and the CTCs genetic

BACKGROUND
, which seems to be heterogeneous. CTCs detection by our methodology could be helpful in the clinical setting for diagnostic, prognostic and theranostic purposes and for patients monitoring. Prospective study is ongoing in order to assess CTCs variations on and after therapy. This study, first investigated the genetic heterogeneity of CTCs released in the blood flow from the parental tumor.
P14.07.B CELL-FREE DNA IN LONGITUDINALLY-ACQUIRED CEREBROSPINAL FLUID FOR DISEASE MONITORING
Authors: Riviere-Cazaux C , Mo W , Dong X , Luo S , Wang A , Du P , Ghadimi K , Warrington A , Burns T 
Published: September 2023

Abstract

BACKGROUND
Few methods exist via which to assess treatment response with high fidelity in gliomas. Cell-free DNA (cfDNA) is of growing interest as a liquid biomarker in plasma and CSF and has been used in other cancer types to optimize therapeutic regimens for individual patients. While CSF has previously been used as a source of cfDNA for gliomas, it remains unknown how cfDNA abundance and sequencing change throughout treatment and inevitable recurrence. To that end, we leveraged our growing biobank of longitudinal CSF specimens, acquired via CSF access devices, to determine the potential utility of CSF cfDNA as a monitoring tool for treatment response in patients with gliomas.

MATERIAL AND METHODS
Longitudinal CSF specimens were acquired via Ommaya reservoirs (NCT04692337) or ventriculoperitoneal shunts (NCT04692324) in patients with brain tumors, including gliomas. cfDNA was extracted from 1-5 mL of CSF based on available sample volumes and quantified via Qubit. Next-Generation sequencing (PredicineCARE) or low-pass whole genome sequencing (LPWGS) was performed by Predicine, Inc based on the amount of cfDNA available.

RESULTS
CSF acquired prior to versus after resection demonstrated an increase in quantified cfDNA (2.97x, range: 1.58-5.26x), consistent with the impact of increased parenchymal disruption and closer contact with CSF. Thereafter, CSF cfDNA continued to decrease throughout chemoradiation and adjuvant treatment and increased at recurrence, including in patients co-enrolled in immunotherapy trials for IL-7 agonists and pembrolizumab. Interestingly, copy number burden (CNB) increased by the time of recurrence in three patients with known disease progression, and continued to decrease throughout immunotherapy treatment in one patient despite concerns of pseudoprogression. In one patient with a hypermutated glioblastoma, CSF cfDNA revealed over 59 genomic alterations, including MAP2K1, KIT, and PDGFRA, and over 100 more variants of unknown significance, each of which had been detected in sequencing of the tissue acquired at resection and subsequently decreased with chemoradiation. In another patient with a known progressing EGFR-amplified GBM, over 200 new variants were identified by the patient’s final sample and EGFR copy number increased from 2 to over 30.

CONCLUSION
Analysis of cfDNA over a patient’s disease course, including resection and treatment with standard-of-care and experimental therapies, may be of use for disease monitoring and treatment response. Further work is needed to evaluate these findings in a larger cohort of patients and to determine the sensitivity of changes in mutations, CNB, and cfDNA quantity for glioma disease burden.
P14.12.A PLASMA CFDNA LIQUID BIOPSY IN THE FOLLOW-UP OF HIGH-GRADE GLIOMAS
Authors: Pieri V , Berzero G , Paterra R , D'Alessandris Q , Sferruzza G , Pompeo E , Roncelli F , Nocera G , Bailo M , Barzaghi L , Castellano A , Falini A , Mortini P , Galli R , Finocchiaro G , Filippi M 
Published: September 2023

Abstract

BACKGROUND
As highlighted by the 2021 WHO classification of brain tumors, molecular characterization of gliomas is now critical to complement histopathological evaluation. However, intratumor heterogeneity may lead to surgical specimens not being fully representative of the whole tumor. Moreover, given the invasiveness of surgery, tissue analyses are not repeatable over time, thus limiting the possibility to monitor the response to therapies. In this context, we investigated the potential value of plasmatic cell-free DNA (PcfDNA) as a non-invasive ‘liquid biopsy’ marker of disease evolution.

MATERIAL AND METHODS
Patients’ blood was collected at 4 time points (TP), in parallel to clinical follow-up. A reproducible pipeline was optimized for blood withdrawal, centrifugation, plasma storage, cfDNA extraction from plasma by QIAamp MinElute ccfDNA Midi Kit (Quiagen) and cfDNA fluorometric quantification by Qubit (Thermo Fisher Scientific). MRI volumes were segmented in T1+contrast and T2-FLAIR sequences.

RESULTS
Fifty-four high-grade glioma patients and 14 healthy controls were enrolled. Blood samples were collected from all 54 patients at radiological diagnosis before surgery (TP0), from 33 patients after surgery (TP1), from 21 patients after radio-chemotherapy(TP2), from 10 patients at the first radiological progression (TP3). At T0, a significantly higher concentration of PcfDNA was detected in patients than in controls. IDH-wild-type gliomas showed a trend toward higher PcfDNA when compared with IDH-mutant gliomas. Digital-droplet PCR, performed at T0on PcfDNA of 4 patients with IDH-mutations in tumor tissues, identified the same IDH1-R132H mutation in all cases. When PcfDNA at TP0 was compared to that at TP1 of the same patient (n=33), there was a significant reduction of plasmatic cfDNA after surgery, mirroring the extensive tumor-resection shown by MRI. Finally, PcfDNA was evaluated in 10 patients until their radiological progression. Interestingly, PcfDNA levels not only followed the same trend of the volumes of T2-FLAIR hyperintensities and T1 contrast-enhancements, but were also mirrored by the evolution of KPS and NANO scores.

CONCLUSION
Preliminary results suggest that PcfDNA content may be an informative tool to complement MRI during the follow-up of high-grade gliomas.
P15.01.A FET PET SENSITIVITY IN PRIMARY BRAIN TUMORS ACCORDING TO CNS WHO 2021: VALUE AND PITFALLS IN PRESURGICAL IMPLEMENTATION
Authors: Oster C , Blau T , Keyvani K , Schmidt T , Lazaridis L , Sure U , Kleinschnitz C , Scheffler B , Herrmann K , Barbato F , Kebir S , Glas M 
Published: September 2023

Abstract

BACKGROUND
FET PET imaging has emerged as a valuable tool in the characterization of unclear brain lesions that cannot be clearly diagnosed with conventional diagnostic

METHODS
.In 2021,the Central Nervous System(CNS) World Health Organization(WHO) introduced significant changes in the classification of CNS tumors.Notably,under the new classification,certain cases of glioma may be reclassified as glioblastoma.Unfortunately,a subset of gliomas,as defined by the 2016 WHO classification,may exhibit no detectable FET uptake and lack contrast enhancement on MRI,which can lead to underestimation of such tumors and potentially result in inappropriate treatment decisions.

MATERIAL AND METHODS
In this study,we conducted a retrospective analysis of all patients who underwent FET PET imaging of the brain between 2017 and 2021,prior to their first surgical brain intervention.We obtained the results from presurgical MRI scans and categorized the lesions based on whether they exhibited contrast media enhancement or not,in addition to the postsurgical histopathologic diagnosis.Our analysis focused on identifying the number of cases in which the diagnosis of malignancy was underestimated in the context of the WHO 2016 classification.To further investigate these cases,we conducted NGS and 850k-analysis to reclassify the results in accordance with the new classification.Finally,we assessed the number of cases that were underestimated using the new classification criteria.

RESULTS
After enrolling 85 patients,our study found that according to the 2016 classification,preoperative imaging underestimated malignancy in 14 cases (16%) where histopathological analysis revealed high-grade malignant brain tumors.In 32 cases (27%), the preoperative imaging correctly suggested a malignant tumor,which was later confirmed by histopathological analysis after surgery.Additionally,22 cases were suggested to be low grade or benign,which was confirmed by postsurgical tissue analysis. Further analysis revealed that some patients diagnosed with low-grade glioma according to the WHO 2016 classification actually had molecular glioblastomas after reclassification.The final results of this reclassification after the CNS WHO 2021 will be presented at the annual meeting.

CONCLUSION
The findings of this study suggest that presurgical brain imaging,as per the WHO 2016 classification,may underestimate the malignancy of unclear brain lesions in up to 16% of cases.Our initial analysis also indicates that this underestimation may be more prevalent when using the new WHO CNS classification from 2021.Therefore,caution is advised when recommending non-surgical follow-ups in such cases, as it may lead to incorrect treatment decisions and worse patient outcomes.