bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCOG-22. SEIZURE OUTCOME ACROSS DISEASE TRAJECTORY IN IDH-MUTANT GRADE 2 GLIOMAS: WHICH IS THE IMPACT OF STANDARD ANTINEOPLASTIC TREATMENTS?
Authors: Bruno Francesco , Pellerino Alessia , Nibali Marco Conti , Pronello Edoardo , Bertero Luca , Garbossa Diego , Bello Lorenzo , Rudà Roberta 
Published: November 2023

Abstract

INTRODUCTION
Most patients with IDH-mutant grade 2 gliomas suffer from seizures. Recently, the INDIGO trial showed that vorasidenib prolonged progression-free-survival (PFS) and time-to-next-intervention in IDH-mutant grade 2 gliomas after surgery. We investigated which factors influence seizure-control in patients with the same characteristics of those of INDIGO. Patients and

METHODS
We retrospectively collected data of non-enhancing IDH-mutant grade 2 glioma patients (as per WHO-2021) who presented with seizures, and evaluated seizure-freedom at 2 months after surgery, 6 months from starting either observation or adjuvant treatments, at recurrence, and 6 months after treatment of recurrence.

RESULTS
Ninety-five patients were included. Oligodendrogliomas IDH-mutant/1p19q-codeleted grade 2 were 69 (72.6%), astrocytomas IDH-mutant grade 2 were 26 (27.4%). Thirty-five (36.8%) received gross-total resection (GTR). After surgery, 49 (51.6%) achieved seizure-freedom, more frequently after GTR vs non-GTR (57.9% vs 35.1%, p=0.048). Sixty-eight (71.6%) low-risk patients underwent observation, while 27 (28.4%) high-risk patients received adjuvant radiotherapy (RT) and/or chemotherapy (CT). Among the latter, 17/27 (63.0%) had persistent seizures before treatment initiation and, after 6 months, all of them displayed seizure-reduction, with 2/17 (7.4%) seizure-free. In a multivariable analysis on PFS, ≥ 50% seizure-reduction (vs &lt; 50%) after 6 months of adjuvant treatment reduced the risk of progression (HR 0.048, 0.004-0.585, p=0.017). Eighty-six (90.5%) patients recurred, and 51/86 (59.3%) displayed seizures. After 6 months of treatment of recurrence, 50/51 (98.0%) achieved seizure-reduction, with 10/51 (19.6%) seizure-free. In a multivariable analysis, either CT or RT increased the probability of seizure-freedom at 6 months after recurrence (HR 5.316, 1.582-17.869, p=0.007).

CONCLUSION
We defined the entity of seizure-control after standard treatments throughout the disease course. Two findings are noteworthy: the prognostic importance of seizure-reduction after adjuvant treatments; the possibility to achieve seizure-control also with treatment of recurrence. This study could serve as a benchmark for future evaluation of seizure-control with IDH inhibitors.
NCOG-24. RISK-ADAPTED TREATMENT STRATEGIES WITH PRE-IRRADIATION CHEMOTHERAPY IN PEDIATRIC MEDULLOBLASTOMA: OUTCOMES FROM THE POLISH PEDIATRIC NEURO-ONCOLOGY GROUP
Authors: Cochrane Anne , Perek-Polnik Marta , Wang Jinli , Chojnacka M , Drogosiewicz M , Filipek I , Swieszkowska E , Tarasinska M , Kowalczyk P , Abdelbaki Mohamed S , Dembowska-Bagińska Bożenna 
Published: November 2023

Abstract
Craniospinal irradiation (CSI) has been a major component of the standard of care treatment backbone of childhood medulloblastoma. However, chemotherapy regimens have varied based on protocol, patient age, and molecular subtyping. In one of the largest studies to date, we analyze treatment outcomes in children with newly-diagnosed medulloblastoma treated with pre-irradiation chemotherapy followed by risk-adapted radiotherapy and maintenance chemotherapy. A total of 153 patients from the Polish Pediatric Neuro-oncology Group were included in the analysis. Median age at diagnosis was 8.0 years. Sixty-seven patients were classified as standard risk and 86 as high risk. Overall survival (OS) and event-free survival (EFS) for standard-risk patients at 5 years (± standard error) were 87 ± 4.3% and 84 ± 4.6% respectively, while 5-year OS and EFS for high-risk patients were 81 ± 4.3% and 79 ± 4.5% respectively. This study demonstrates promising survival outcomes in patients treated with pre-irradiation chemotherapy followed by risk-adapted CSI and adjuvant chemotherapy. Such an approach may be useful in cases where initiation of radiotherapy may need to be delayed, a common occurrence in many institutions globally.
NCOG-27. LONG-TERM OUTCOMES OF GAMMA KNIFE RADIOSURGERY FOR GROWING MENINGIOMA
Authors: Kim Yeong Jin 
Published: November 2023

Abstract
Gamma knife radiosurgery (GKRS) has become an effective treatment modality for intracranial meningioma. However, the role of GKRS in managing growing meinigoma during follow-up remains uncertain. This study aims to investigate the long-term outcome after GKRS treatment on meningioma for growing meningioma at follow-up. A retrospective analysis was conducted on patients who underwent GKRS as primary treatment for growing meingiomas between 2004 and 2021. Growing meningioma was defined as a &gt;10% increase in volume compared to the previous imaging. Fifty-nine patients who received GKRS as initial treatment were included in this study with minimum follow-up period of 12 months. Patient clinical-radiological data, tumor characteristics and procedural details were analyzed. Tumor progression and regression were defined as a &gt;10% increase or decrease in volume, respectively, compared to pre-GKRS image. Tumor volumes within ±10% of pre-GKRS volume were considered stable. At a median follow-up of 41 months (range 15-197 months), tumor volume was unchanged in 16 patients (27.1%), decreased in 41 patients (69.5%), and increased in 2 patients (3.4%). In multivariate analysis, growth rate was significantly associated with tumor progression (hazard ratio [HR]=2.059, 95% confidence interval [CI]=1.028-4.123, p=0.042). Eleven patients (18.6%) experienced new or worsening symptoms. In multivariate analysis, factors predicting new or worsening neurological function were preexisting symptoms (HR=7.159, 95% CI=1.468-34.911, p=0.015) and tumor calcification (HR=11.921, 95% CI=2.400-59.202), p=0.002), and pre-existing peritumoral edema (HR=9.751, 95% CI=1.666-57.058, p=0.012). GKRS demonstrates a high tumor control rate as well as an acceptable complication rate in growing meningioma. Effective tumor control is more likely in patients with slow-growing tumor.
NCOG-28. RECURRENCE OF PLEOMORPHIC XANTHOASTROCYTOMA PRESENTING WITH DIFFUSE LEPTOMENINGEAL SPREAD
Authors: White Jessica , Grigsby-Rocca Giovanna , Bermudez Camilo , Neth Bryan , Uhm Joon , Mustafa Rafid 
Published: November 2023

Abstract
Pleomorphic xanthoastrocytomas (PXAs) are rare primary brain tumors that mainly affect children and young adults. We report a case of recurrent PXA in an adult and review the literature. To our knowledge, this is the first adult report highlighting clinical, CSF, and imaging findings of recurrent PXA with leptomeningeal spread. A 60-year-old woman presented with a 2-month history of fluctuating mental status, aphasia, low-back pain, progressive paraparesis, and urinary retention. She was previously diagnosed with a left temporal PXA 17 years prior and underwent gross total resection with no evidence of tumor recurrence for the next several years. Approximately 10 months prior to her current presentation, she was found to have radiographic recurrence of the left temporal PXA. She underwent gross total resection, with final pathology revealing anaplastic transformation, WHO grade 3, BRAF V600E mutation positive. She next underwent photon radiotherapy, and chemotherapy with temozolomide. She had good clinical and radiographic response to treatment for 8 months prior to developing her current symptomatology. MRI of the brain and spine showed local recurrence with new diffuse contrast enhancement of the spinal cord and nerve roots. Cerebrospinal fluid (CSF) analysis showed a total nucleated cell count of 10/mcL, protein &gt;1250 mg/dL, glucose &lt; 20 mg/dL, and xanthochromia. CSF cytology was positive for malignant cells consistent with PXA. Although PXA is often associated with a favorable prognosis, recurrence with anaplastic transformation can be associated with dissemination throughout the nervous system and worse outcomes. Despite the rarity of such cases, clinicians should remain vigilant, especially when anaplastic transformation occurs. Early detection of leptomeningeal involvement through thorough CSF analysis and appropriate imaging can facilitate prompt intervention and potentially improve patient outcomes.
NCOG-31. TUMOR TREATING FIELDS: REAL-WORLD SURVIVAL AND QUALITY OF LIFE OUTCOMES ON THE XCELSIOR PLATFORM
Authors: Palmer Joshua , de Rivera Fernando Nino , Awawda Alaa , Williams Sebastian , Irizarry Sabrina , Cole Zachariah , Chavez Gordon 
Published: November 2023

Abstract

OBJECTIVE
xCures operates a direct-to-patient, real-world evidence platform according to the nationwide observational research protocol XCELSIOR (NCT03793088), which aggregates medical data in an FDA-compliant electronic database. We used this platform to analyze advanced registry survival and Quality of Life (QoL) outcomes associated with the use of Tumor Treating Fields (TTFields) for treatment of high grade central nervous system (CNS) tumors.

METHODS
XCELSIOR participants with high grade CNS tumors were invited weekly to complete the EuroQol 5-Dimension (EQ-5D-5L) QoL questionnaire over the course of one year. A EuroQol-endorsed model was used to estimate health state utilities from patients’ EQ-5D responses. The participating patients’ clinical data was accessed from the XCELSIOR platform to enable study of clinical factors and survival outcomes.

RESULTS
225 patients with high grade CNS tumors in total completed at least one EQ-5D questionnaire. 88 patients (39%) had ever used TTFields and 58 of these patients (26%) were currently using TTFields. Patients currently using TTFields had significantly higher average health state utility estimates compared to non-users (p=.00183), with a mean improvement in utility of .14 (SE=.04), indicating significantly higher overall QoL in TTFields users. Mortality events were recorded for 40 participating patients, 14 (35%) of which had used TTFields. From these 40 events the mean/median overall survival (OS) for patients who had used TTFields was 23.39/20.15 months vs 15.77/12.72 months for patients who had not used TTFields, showing significantly higher average OS in patients who had used TTFields (p=.04139).

CONCLUSION
The XCELSIOR platform has enabled the study of real-world clinical and QoL outcomes for patients with CNS tumors. The results show that use of TTFields is associated with improved survival as well as improved overall Quality of Life for patients in a real-world setting, corroborating results seen in trial settings as well as results seen in other real-world studies.
NCOG-32. THE SPECIFIC PSYCHOSOCIAL BURDEN OF CAREGIVERS OF ADULT NEURO-ONCOLOGICAL PATIENTS - A PROSPECTIVE STUDY
Authors: Spieker Mareike , Rapp Marion , Goebel Simone , Karger André , Rieger David , Grosse Lucia , Bombach Paula , Kurz Sylvia , Hippler Melina , Tatagiba Marcos , Sabel Michael , Tabatabai Ghazaleh , Renovanz Mirjam 
Published: November 2023

Abstract

OBJECTIVE
The diagnosis of a brain tumor represents high burden for the patients’ caregivers (CG). Psychosocial screening tools adapted to the burden profile of CG are urgently required but do not exist. The aim was to develop a problem list for neuro-oncological CGs’ unmet needs for an application in combination to the Distress Thermometer scale.

METHODS
CG were prospectively assessed regarding changes in everyday life, relationship, social life, emotional, physical problems, and support needs, either via questionnaire (Center A) or by a qualitative interview (center B). A qualitative content analysis was performed by an inductive/deductive approach using MAXQDA® software.

RESULTS
A total of 50 caregivers were assessed (25 in center A via questionnaire, 25 in center B via interviews) during outpatient visits. Most frequently reported need was the need for psychological support (29/50, 58%). This was true after initial diagnosis (26/50, 52%) as well as in case of clinical deterioration of their loved-one (30/50, 60%). The results leaded to problem categories, congruent to the NCCN distress thermometer categories for cancer patients (practical, social, emotional, physical, and spiritual/existential problems). We detected new topics including “constraints/organization of (medical) appointments” (25/50, 50%) or “constant availability required for partner” (21/50, 42%). Also, 70% (35/50) put their own interests last or adapted their leisure activities. In the qualitative interviews (Center B), further items were identified, e.g., “dealing with psychological problems of the patient” (3/25, 12%), “different coping strategies among patient/caregiver” (4/25, 16%). We defined additional problem categories specifically adapted to CG of neurooncological patients, e.g., “problems due to neurocognitive/neuropsychological symptoms of the loved-one” and “problems with role as a caregiver”.

CONCLUSION
The interviews reflected the unmet needs of brain tumor caregivers. Our problem list developed for CG of neurooncological patients might allow for the targeted assessment and optimization of care.
NCOG-34. BRAIN PET IMAGING OF PAIRED HELICAL FILAMENT TAU IN OLDER ADULTS WITH CANCER: PILOT STUDY TO IDENTIFY MECHANISMS OF COGNITIVE IMPAIRMENT AFTER CANCER THERAPY
Authors: Parsons Michael , Von Imhof Liesel , Eckbo Ryan , Katsumi Yuta , Touroutoglou Alexandra , Arrillaga-Romany Isabel , Dickerson Bradford , Dietrich Jorg 
Published: November 2023

Abstract

BACKGROUND
Cancer-related cognitive impairment (CRCI) occurs in up to 75% of patients treated with chemotherapy for systemic cancer, and older patients treated for CNS cancer receiving brain radiation therapy (RT) and chemotherapy are particularly at risk. The mechanisms of injury and CRCI remain unknown. In neurodegenerative disorders, deposition of paired helical filament tau (PHFTau) is correlated with nature and extent of cognitive symptoms. The role of PHFTau in CRCI has not been elucidated. We conducted a pilot study to determine whether CRCI is associated with PHFTau.

METHODS
Patients (age &gt;60) diagnosed with mild cognitive impairment (MCI) or dementia after chemotherapy and/or brain RT underwent Tau PET imaging using [F18]Flourtaucipir. Cortical [F18]Flourtaucipir binding was quantified by standard uptake value ratio (SUVR) in 68 regions of interest (ROIs) and compared to a control group (n=22). SUVR in each ROI for each subject was considered significantly elevated when it was &gt;2SD above the control group (p&lt; 0.05). Neuropsychological test scores were correlated with PHFTau distribution.

RESULTS
Five patients with MCI/Dementia following cancer therapy participated. Two patients with prior chemo-RT for CNS cancer and prominent executive dysfunction had no significant F[18]T807 uptake. However, three patients treated with systemic chemotherapy for non-CNS cancer and neuropsychological profiles dominated by episodic memory impairment showed F[18]T807 uptake in patterns typical of AD dementia in temporal, parietal and cingulate ROI’s (n=2), or uptake in the entorhinal and inferior temporal ROIs (n=1).

DISCUSSION
In this pilot study, [F18]Flourtaucipir imaging of patients with cancer and MCI/Dementia showed that executive dysfunction after RT was not associated with abnormal PHFTau whereas amnestic declines after chemotherapy were associated with PHFTau in medial temporal lobes and beyond. Given the cross-sectional study, timing of tau accumulation in relation to cancer/treatment is unknown. Prospective studies are needed to understand the relevance of PHFTau in CRCI.
EXTH-03. A VEGF+ SUBPOPULATION OF SCHWANN CELLS DRIVES VESTIBULAR SCHWANNOMA TUMORIGENESIS
Authors: Asuzu David , Stoica Stefan , Laraba Liyam , Arhin Martin , Gandhi Jasleen , Mullaney Dustin , Mandal Debjani , Parkinson David , Chittiboina Prashant 
Published: November 2023

Abstract

INTRODUCTION
Up to 95% of vestibular schwannomas (VS) are sporadic, however their molecular underpinnings remain obscure.

OBJECTIVE
To perform transcriptomic profiling of VS and investigate novel tumorigenic mechanisms.

METHODS
We analyzed 19 VS samples (7 sporadic, 12 NF2), and performed single-cell RNA sequencing (scRNAseq, n = 4) or single-nucleus (snRNAseq, n = 15), assays for transposase-accessible chromatin (snATACseq, n = 15) and bulk DNA methylation (n = 14). CellChat was used to predict cell-cell interactions. We characterized transcription factor binding using ChIPseq. We validated our key findings at the mRNA and protein levels using RNAscope (n = 5) and multiplex immunocytochemistry (mIHC; n = 5). Mechanistic studies were conducted using NF2-null Periostin-Cre+ mice versus their Cre- control littermates.

RESULTS
We profiled the VS transcriptome and identified markers for Schwann cells, macrophages, T cells and endothelial cells. We identified eight Schwann cell subclusters which were enriched for known markers for myelinating, immature, repair and non-myelinating subtypes. We also unexpectedly identified a subset of VS Schwann cells with high expression of VEFGA, and these cells were enriched for signaling via laminin, NCAM, NRXN and NEGR pathways. Using RNAscope and mIHC, we verified VEGFA expression in S100B+ Schwann cells. snRNAseq and snATACseq demonstrated increased TEAD1 expression in Schwann cells, as well as increased chromatin accessibility for TEAD family transcription factor motifs. We used ChIPseq to confirm increased TEAD1 binding at the promoters of 714 genes including VEGFA. NF2-null Periostin-Cre+ mice developed spontaneous schwannomas within their dorsal root ganglia which showed increased vegfa expression, and this was partly reversible using a novel pharmacological TEAD inhibitor in-vivo.

CONCLUSIONS
We performed detailed epigenetic and transcriptomic profiling of sporadic and NF2-associated VS and uncovered TEAD1-mediated overexpression of VEGFA in a subset of VS Schwann cells. TEAD inhibition may constitute a novel therapeutic target for VS.
EXTH-06. GLIOBLASTOMA PATIENT SPECIFIC TRANSCRIPTOME REMODELING IN RESPONSE TO MDM2 ANTAGONIST TREATMENT OF WILD-TYPE P53 CANCER STEM CELLS IS ASSOCIATED WITH SENSITIVITY AND STRATEGIES FOR COMBINATION THERAPY
Authors: Meng Yuling , Mughal Nouman , Datta Indrani , Nuga Oluwademilade , Irtenkauf Susan , Hasselbach Laura , Quenneville Kristyn , Brown Stephen , deCarvalho Ana 
Published: November 2023

Abstract
Over 70% of glioblastomas are p53 wild-type and these patients could benefit from p53 reactivation treatment. Here we determined the sensitivity of a glioblastoma patient-derived cancer stem cells (CSCs) panel to three MDM2 antagonists (MDM2a) to test to what extent transcriptional reprogramming is affected by genomic background and correlates to response to acute treatment with MDM2 antagonists. IC50 concentrations and area above the curve (AAC) were measured from dose response curves obtained from 4 and 7-day treatment. The inhibitors were specific to wt-p53 CSCs, but these presented a wide range of sensitivity. Seven wt-p53 CSCs were treated RG7112 IC50 concentrations or DMSO control for 24h (n=4). RNA was isolated for Illumina Truseq stranded mRNA libraries sequenced at 30M depth. Quantified raw counts were processed using NOISeq R package to determine differentially expressed genes (DEG) between control and treated samples. In addition to the expected high representation of upregulated p53 targets in all cell lines, we observed significan cell specific transcriptome alterations, including enrichment of survival pathways, such as mTOR, ERK and NFkB in the less sensitive CSC lines, which did not readily correlate with the individual genomic landscapes. E2F targets, G2-M cell cycle check point and DNA-repair pathways were highly enriched in the downregulated genes. Combination of MDM2a with radiation treatment (RT) was synergistic to a subset of CSCs. As validation we found that MDM2a treatment was effective in sensitizing a resistant orthotopic mouse glioblastoma PDX to fractionated RT, with maximum efficacy when treatment started 24h prior to RT vs simultaneously (Log-rank Mantel-Cox test: p=0.0006 vs 0.0277). The integration of the treatment-mediated transcriptional patterns with differential sensibility to MDM2 antagonists and genomic landscape of the CSC panel provides a platform to identify targets for combination therapies, which is the most promising clinical application of the reactivation of wt-p53 in GBMs.
EXTH-07. NEOADJUVANT PD1 BLOCKADE ALTERS THE TUMOR MICROENVIRONMENT POST-SURGERY IN A PRECLINICAL MODEL OF RECURRENT GLIOBLASTOMA
Authors: Hoang-Minh Lan , Mitchell Duane , Klippel Kelena , Yang Changlin , Trivedi Vrunda , Doonan Bently , Von Roemeling Christina , Yegorov Oleg , Sriharan Akshayaa , Francis Connor , Shin David , Karachi Aida , Sarkisian Matthew 
Published: November 2023

Abstract

SIGNIFICANCE
Clinical trials investigating neoadjuvant immunotherapy in recurrent glioblastoma patients have shown promising results. In this study, we aimed to assess the impact of neoadjuvant PD1 blockade on the tumor microenvironment after surgery using a relevant murine model of recurrent glioblastoma.

OBJECTIVE
Our objective was to investigate the effects of neoadjuvant PD1 inhibition on mouse survival and analyze the transcriptome and spatial genomic changes within the intratumoral immune populations following surgery. We compared these changes with those observed in adjuvant anti-PD1 treatment.

RESULTS
Through our established murine resection model of recurrent KR158 glioblastoma, we demonstrated that neoadjuvant PD1 inhibition prior to tumor debulking significantly improved mouse survival compared to adjuvant treatment. Transcriptome and spatial genomic analyses revealed notable alterations in immune exhaustion and activation pathway genes after neoadjuvant anti-PD1 treatment, distinguishing it from adjuvant anti-PD1 treatment. RNA and protein analyses indicated upregulation of various pathways, including PI3K/AKT, NOTCH, NK cell, MAPK, NF-kB, type II interferon, and TNF, in the neoadjuvant treatment group compared to the adjuvant anti-PD1 treatment group. Single-cell RNA sequencing analyses further revealed an increased proportion of CD8 T, NKT, and NK cells, accompanied by a decreased percentage of CD4 T cells in the neoadjuvant group. Importantly, we observed a significant enhancement in the interaction strength between CD8 T cells and all other immune cells in the neoadjuvant group compared to the adjuvant treatment group.

CONCLUSIONS
Our findings demonstrate distinct differences in immune cell populations and gene expression profiles between neoadjuvant and adjuvant anti-PD1 therapies in our murine recurrent glioblastoma resection model. These insights provide valuable understanding of the potential mechanisms underlying the divergent efficacy of neoadjuvant and adjuvant anti-PD1 therapies.