bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCOG-28. SERUM PROTEIN BIOMARKERS LINKED TO NEURODEGENERATIVE PROCESSES ARE ELEVATED IN GLIOMA PATIENTS AND ASSOCIATED WITH SEVERITY OF NEUROLOGIC SYMPTOMS
Authors: Hsieh Emory , Mendoza Tito , Raval Dhaivat , Kauss McKenzie C , Slattery Kaitlynn , Wright Michelle L , Davis Tara S , Choi Ann , Reinhart Kimberly , Miller Hope , Vera Elizabeth , Penas-Prado Marta , Gilbert Mark R , Armstrong Terri S , Guedes Vivian A 
Published: November 2024

Abstract

BACKGROUND
Glioma patients frequently report neurologic symptoms, adding to the complexity of cancer management and negatively impacting quality of life. However, mechanisms associated with the development of neurologic symptoms in glioma patients remain unclear. Pathological changes in the brain of glioma patients might result in elevated peripheral blood levels of proteins previously linked to central nervous system (CNS) damage and neurodegeneration, including neurofilament light chain (NfL), tau, and glial fibrillary acidic protein (GFAP). Here, we tested the hypothesis that the circulating levels of these proteins in blood are elevated in glioma patients and associated with the severity of neurologic symptoms.

METHODS
Patients (n=73) were enrolled in a natural history study (NCT02851706, PI T. Armstrong). Healthy subjects (n=39) were recruited by the National Institutes of Health Clinical Center Blood Bank. Neurologic symptom severity and walking interference were assessed using MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT). Serum proteins were analyzed using ultrasensitive assays (Meso Scale Discovery).

RESULTS
Participants were predominantly white (patients 74%, healthy subjects 67%) and male (patients 58%, healthy subjects 54%). The median age was 44 (range=24,74) for patients and 49 (range=19,78) for healthy volunteers. No significant differences in age, sex, or race were observed between patients and healthy subjects. Serum levels of NfL (p&lt;0.0001), GFAP (p&lt;0.0001), and tau (p&lt;0.0001) were higher in glioma patients when compared to healthy subjects. Patients with walking interference had higher levels of GFAP (p=0.003), NfL (p=0.003), and tau (p=0.004), and those who reported numbness had higher levels of GFAP (p=0.012).

CONCLUSIONS
These findings suggest that serum levels of protein markers of neurodegeneration are elevated in glioma patients and associated with the presence of neurologic symptoms. Blood-based biomarkers have the potential to shed light on the mechanisms underlying symptoms and offer a non-invasive alternative for monitoring CNS damage that impact patient outcomes.
NCOG-31. NEUROCOGNITIVE OUTCOME FOLLOWING AWAKE CRANIOTOMY FOR INSULAR GLIOMA RESECTION: IMPACT OF SURGICAL APPROACH AND TUMOR CLASSIFICATION
Authors: Noll Kyle , Bander Evan D , de Almeida Romulo A Andrade , Seaman Scott , Banu Matei , Clark Victoria E , Suki Dima , Wefel Jeffrey S , Bradshaw Mariana , Ferguson Sherise , Weinberg Jeffrey S , Prabhu Sujit S , Lang Frederick F 
Published: November 2024

Abstract

BACKGROUND
Insular glioma resection harbors similar risk of neurocognitive function (NCF) decline as other tumor locations. However, differences in outcomes according to transsylvian versus transcortical surgical approach and tumor classification remain unknown.

METHODS
53 patients with newly diagnosed insular glioma (47% high-grade; 23% GBM; 75% left hemisphere) underwent awake craniotomy for resection (transsylvian, 64%; transcortical, 36%). Patients completed neuropsychological testing preoperatively and &lt;2 months postoperatively (M interval=23.7 days). Tumor location was described with Berger-Sinai zones collapsed into anterior (I and/or IV), posterior (II and/or III), superior (I and/or II), and inferior (III and/or IV) groups. Tumor extension was characterized with the Pitskhelauri system into insula only, insula with extension (lobar or medial), and predominantly (&gt;50%) extra-insular groups. Result: Decline (z-score change&lt;-1.0) on at least 1 test occurred in 85% of patients with largest effect (partial η2) in memory (.29–.44) and verbal fluency (.39). There was no interaction with approach on any NCF change score, though transcortical was associated with more frequent fluency decline (61% vs. 26%, p=.014). Left hemisphere tumor was associated with poorer outcome on 6/12 tests (all p&lt;.01). Predominantly extra-insular tumors showed greater reductions in fluency (M=-1.21, SD=0.90) than insula only tumors (M=-0.10, SD=0.76; p=0.024). Number of Berger-Sanai quadrants involved was inversely associated with change in executive functioning (r=-0.34, p=.018). Poorer executive function outcome was also found in anterior (M=-0.61, SD=1.41) versus posterior tumors (M=0.86, SD=1.51; p=.014), and recognition memory outcome worse for inferior (M=-2.44, SD=1.81) than superior lesions (M=-0.31, SD=1.47; p=.021).

CONCLUSIONS
NCF decline is common in the early term following resection of insular glioma. While risk of verbal fluency decline may be greater for transcortical surgeries, outcomes were largely similar across approaches. In addition to hemisphere, tumor extension and insular zone localization may inform domain-specific risk of NCF decline following resection.
NCOG-32. RELATIONSHIPS BETWEEN INTRAOPERATIVE TASK-BASED GAMMA BAND ELECTROCORTICOGRAMS, DIRECT ELECTRICAL STIMULATION, AND COGNITIVE-LINGUISTIC OUTCOME FOLLOWING AWAKE BRAIN TUMOR RESECTION
Authors: Noll Kyle , Tasnim Israt , Asman Priscella , Swamy Chandra , Connelly Katherine , Muir Matthew , Hall Matthew , Pellizzer Guiseppe , Ince Nuri , Prabhu Sujit 
Published: November 2024

Abstract

BACKGROUND
As an adjunct to direct electrical stimulation (DES), intraoperative electrocorticography (ECoG) can aid detection of language-eloquent cortex. However, it is unclear how surgical impact upon mapping findings relates to cognitive-linguistic outcomes.

METHODS
Ten patients underwent awake craniotomy for tumor resection with ECoG and DES language mapping. Mapping utilized iPad stimulus presentation coupled to an electrode array capable of both recording ECoG activity and delivering DES. Time-frequency gamma band activations were visualized (Early, Long, Late, Double Peak) for 3 naming paradigms (Object, Action, Auditory). DES was also conducted for each task. Mapping results were overlayed on postoperative MRI to examine proximity to parenchymal trauma (cavity, sulcal displacement). Patients completed cognitive-linguistic testing [WAB-R (N=3) or Neuropsychological Assessment (N=7)] prior to surgery and &lt;2 months postoperatively. Patients with persisting aphasia at 6-month follow-up were also identified.

RESULTS
Postoperative language decline was found in 50% of patients, with 30% showing worsening (&gt;1SD) in Naming and Phonemic Fluency, and 60% in Semantic Fluency. Surgery impacted ECoG features in 60% of patients and DES arrest sites in 30%. A trend was observed where Early and Late Object naming ECoG features were associated with Semantic Fluency decline [rpb(5)=-.69, p=.067]. Arrest during Auditory naming DES &lt;1 cm of surgical effect was associated with decline in Abstraction [rpb(5)=-.83, p=.042; FET, p=.029] and Semantic Fluency [rpb(5)=-.87, p=.012; FET, p=.024]. Excluding the 3 transsulcal surgeries, arrest during Auditory naming DES &lt;1 cm of resection was associated with general language decline [FET, p=.047]. All 3 patients with persisting aphasia had Auditory naming arrest &lt;1 cm of resection and 2/3 patients had Object naming ECoG features resected.

CONCLUSIONS
While preliminary, results suggest that surgical proximity to ECoG and DES mapping results may inform risk of surgically-acquired cognitive-linguistic decline. Findings support the potential of multimethod-multitask intraoperative language mapping.
NCOG-36. CLINICAL AND DEMOGRAPHIC CHARACTERISTICS PREDICT POSTOPERATIVE BEHAVIORAL DYSFUNCTION FOLLOWING HIGH-GRADE (WHO 2-4) GLIOMA RESECTION
Authors: Ambati Vardhaan , Kaur Jasleen , Hervey-Jumper Shawn 
Published: November 2024

Abstract

BACKGROUND
Gliomas have the highest incidence (85%) of cancer-related cognitive and behavioral impairments. Few studies have explored preoperative clinical and demographic drivers/predictors of postoperative behavioral impairment.

METHODS
We analyzed prospectively collected data from patients 1) who underwent glioma (WHO 2-4) resection and 2) who had postoperative Flanker testing, an assessment of inhibitory control and selective attention (NIH Toolbox Cognition Battery). Patients whose age-adjusted Flanker score (last follow-up) was less than the cohort mean were classified as having “poor” outcomes. Univariate analysis, multivariate logistic, and LASSO regressions were performed to identify drivers of poor outcomes.

RESULTS
In total, 43 patients (mean age at diagnosis 45.9 [range 18-77] years, 35% female) met inclusion criteria. The average age-adjusted Flanker score was 83.3±13.6; twenty (46.5%) patients had below-average scores. On univariate analysis, there were no significant differences in demographic factors (age, sex, education, employment) and tumor characteristics (grade, location). Multivariate logistic regression identified having high school versus higher degree (OR:1.6x10^4, p=0.017), WHO Grade 4 versus Grade 2 (OR:2.36, p=0.026), and parietal lesion (OR:1.6x10^3, p=0.034) as risk factors, while increased age (OR per 1-year increase:0.71, p=0.009) and dominant language hemisphere lesion (OR 0.002, p=0.048) were protective against poor behavioral outcome. LASSO regression (efficiently narrows down predictors) identified higher WHO grade (4 vs. 2), lower education (high school vs. higher), and insular and parietal lesions as predictive of poor outcomes. Increased age at diagnosis, frontal lobe lesions, and lesions on the dominant language hemisphere were protective.

CONCLUSION
Lower education status, higher WHO grade, and insular and parietal lesions are risk factors for poor behavioral outcomes postoperatively following glioma resection. In contrast, increased age, frontal lobe lesions, and dominant language hemisphere lesions were positive prognostic factors. Neuro-oncologists may use these findings to preoperatively counsel patients and tailor care plans with necessary postoperative support.
NCOG-43. THE APPLICATION OF INDUCTION CHEMOTHERAPY COMBINED WITH RADIOTHERAPY IN YOUNG ADULTS WITH CNS GERM CELL TUMORS
Authors: Liu Hao , Nahm Josh , Ware Cornelius , Hsu Sigmund , Amsbaugh Mark , Blanco Angel , Zhu Jay-jiguang 
Published: November 2024

Abstract

BACKGROUND
Central nervous system (CNS) germ cell tumors are rare brain neoplasms, accounting for approximately 0.3-0.5% of all CNS tumors. A combination of radiotherapy and chemotherapy is the standard of care (SOC) in pediatric patients. However, there is no SOC for young adult or adult patients. This study evaluates a regimen of induction chemotherapy followed by radiation in treating young adults with CNS germ cell tumors.

METHOD
Nine young adult patients diagnosed with pure CNS germinomas were identified in our institution. They underwent a treatment regimen of induction chemotherapies that were planned for four cycles and consisted of bleomycin (three doses per cycle), cisplatin (five doses per cycle) and etoposide (five doses per cycle) followed with whole brain and/or ventricular radiotherapy. The patients’ overall survival (OS), neurological function (including cognition), and adverse events (AE) were analyzed.

RESULT
Among the nine patients (seven males and two females), the median age is 20 years (range: 17-33 years). They received bleomycin, cisplatin and etoposide (median: two cycles, range: 1-4), and subsequent radiotherapy with plans based on tumor location by radiation oncologists, with a median radiotherapy dose of 45 Gy (range: 36-50.4). Seven patients had a complete response after chemotherapy. The median OS is 53 months (range: 39-121). There is no identifiable cognitive impairment by neurological exam. All patients experienced at least one, reversible, grade 3 AE of myelosuppression. All patients return to their normal baseline including employment. Results of neuropsychological evaluation and all AEs will be presented at the conference.

CONCLUSION
Induction chemotherapy followed by radiotherapy is potentially safe and effective with manageable and reversible side effects from chemotherapy without cognitive and functional impairment in the nine young adult patients with CNS germ cell tumors. A prospective study of this approach in a clinical trial setting is warranted.
NCOG-44. EXPLORING THE IMPACT OF PRE-OPERATIVE MAJOR DEPRESSIVE DISORDER ON POSTOPERATIVE OUTCOMES IN PATIENTS UNDERGOING SURGICAL EXCISION OF MENINGIOMAS
Authors: Sallese Greta , Kandhadai Anuttham , Brindley Paul 
Published: November 2024

Abstract

INTRODUCTION
Meningiomas are prevalent brain tumors that can cause significant morbidity for patients. Major depressive disorder (MDD), especially in the setting of other medical conditions, is associated with poor prognoses and increased mortality. This study aims to investigate whether pre-operative MDD is a risk factor for postoperative mortality and cognitive impairment in patients with meningiomas undergoing surgical excision.

METHODS
A retrospective cohort study was conducted using the TriNetX database including adults undergoing craniotomy for meningioma excision, one group comprising patients with pre-operative MDD and the other without. Propensity-score matching was performed to control for age, sex, race, ethnicity, history of cognitive impairment, neurodegenerative diseases, other psychiatric disorders, and socioeconomic barriers to care. Primary outcomes were postoperative mortality, depressive episodes, and cognitive impairment measured within 5 years postoperatively.

RESULTS
After matching, the study included 289 patients per cohort. Postoperative mortality rates for patients with pre-operative MDD compared to those without were similar (11.42% vs 9.69%, RR: 1.179, 95% CI: 0.732-1.898). Patients with MDD had a significantly higher prevalence of postoperative depressive episodes compared to those without MDD (64.71% vs 38.06%, RR: 1.7, 95% CI: 1.434-2.015). There were no statistically significant differences between the two groups in the prevalence of attention and concentration deficits (5.88% vs 4.15%, RR: 1.417, 95% CI: 0.689-2.913), cognitive communication deficits (8.99% vs 6.57%, RR: 1.368, 95% CI: 0.775-2.416), or executive function deficits (3.46% vs 3.46%, RR: 1, 95% CI: 0.423-2.366).

CONCLUSION
This study suggests no significant relationship between pre-operative MDD and post-operative mortality and cognitive deficits in patients undergoing meningioma resection. However, the risk of experiencing a depressive episode within 5 years post-operation is very high, especially in those with pre-operative MDD. Therefore, preoperative psychiatric evaluation and postoperative monitoring in patients with meningiomas and MDD are crucial. Further research is warranted to elucidate underlying mechanisms and relationships.
NCOG-47. DEFINING PERIOPERATIVE RISK FACTORS IN STEREOTACTIC BRAIN BIOPSIES AMONG DIFFERENT HISTOLOGIC DIAGNOSES
Authors: Tripathy Arushi , Harake Edward , Saleh Sara , Al-Holou Wajd 
Published: November 2024

Abstract

INTRODUCTION
Stereotactic brain biopsies (SBB) are critical for diagnosing neoplastic central nervous system pathologies including gliomas, metastatic carcinomas (cA), and lymphomas. While SBB-related complications have been cited in the literature, we sought to characterize the perioperative risk factors/outcomes.

METHODS
We conducted a retrospective review of 615 patients who underwent a SBB at the same tertiary academic hospital between 2000-2020. Logistic regression was conducted across all recorded variables to assess the relative impact on intra/postoperative complications, and Kaplan-Meier curves were calculated to assess probability of 1-year hospice enrollment.

RESULTS
Of the 615 patients, the average (+/- SD) age was 56+/- 19 years with 286 (46.5%) female patients and the following histological groups: glioma (n=422), lymphoma (n=74), and metastatic cA (n=22). Complications included intraoperative bleeding (7.1%), general postoperative hemorrhage (34%), symptomatic postoperative hemorrhage (3.3%), and discharge-to-hospice (6.8%). General hemorrhage and discharge-to-hospice were most common in glioma (p &lt; 0.001) and lymphoma patients (p=0.003), respectively. Independent risk factors for general hemorrhage included medical history (mental status deficits, glioma, GBM; p= 0-0.02) and biopsy characteristics (parietal lobe, subcortical, eloquent, M8 hole, multiple depths; p= 0-0.05). Preoperative systematic workups and history of lymphoma were independently associated with lower hemorrhage risk (p= &lt;0.001). Risk factors for hospice discharge included preoperative deficits (gait, speech, and mental status; p=0.001-0.05) and postoperative complications (prolonged ICU, UTI, pneumonia; p&lt;0.001). Of the 15 cases of symptomatic hemorrhage, there was a significantly greater representation of glioma patients (p&lt;0.001) with 67% GBM patients and 50% with multiple-depth biopsies. These patients had similar probability of 1-year hospice enrollment compared to non-hemorrhagic patients (p= 0.92).

DISCUSSION
While complication rates were relatively similar among different histological categories, perioperative risk factors broadly differed based on the type of complication. Understanding perioperative risk factors in SBB may help inform surgical decision making and prognostication.
NCOG-49. EFFICACY OF POSTOPERATIVE RADIOTHERAPY AFTER GROSS TOTAL RESECTION FOR INTRACRANIAL SOLITARY FIBROUS TUMORS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Min Kwon Sae , Na Min Kyun 
Published: November 2024

Abstract

BACKGROUND
The efficacy of postoperative radiotherapy (PORT) after gross total resection (GTR) for intracranial solitary fibrous tumors (SFT) remains unclear as previous studies yielded inconsistent results. Therefore, this study aimed to clarify this uncertainty using a comprehensive meta-analysis. By evaluating and synthesizing data from relevant studies, we sought to investigate the role of PORT, as compared with surgery alone, in survival outcomes after GTR of intracranial SFT.

METHODS
We conducted a systematic literature search, adhering to PRISMA guidelines, using Medline, Embase, and the Cochrane Library to identify relevant literature. The outcomes of interest included progression-free survival (PFS), overall survival (OS), and metastasis-free survival (MFS) at 3, 5, and 10 years, respectively. Differences between the two cohorts (GTR+PORT vs. GTR only) were estimated by calculating the hazard ratios. Results. Twelve studies, including data from 419 patients (PORT, n = 225 vs. surgery only, n = 194), were selected for meta-analysis. Pooled hazard ratios revealed that the PORT cohort showed sustained superiority in both PFS and OS over the surgery-only cohort after GTR of the tumor. These results were consistent with those of a subgroup analysis that focused on grade 2 and 3 intracranial SFT. However, no significant improvement was observed in MFS with PORT addition. Conclusion. The present study underscores the importance of PORT in enhancing the PFS and OS of patients with intracranial SFT after GTR. These findings suggest that PORT should be considered an effective treatment strategy for all patients with intracranial SFT, irrespective of the extent of resection.
EXTH-01. EFFICACY OF PERAMPANEL AGAINST GLIOBLASTOMA CELLS
Authors: Yamamuro Shun , Nishide Takuma , Nara Kaoru , Aida Yumi , Yazawa Genki , Ohyama Kentaro , Ozawa Yoshinari , Yoshimura Sodai , Sano Emiko , Yoshino Atsuo 
Published: November 2024

Abstract
We investigated the antitumor effect of perampanel, which is the AMPA-type glutamate receptor antagonist widely used as an antiepileptic drug in Japan, on glioblastoma cells both in vitro and vivo. Commercially available glioblastoma cell lines (A-172, AM-38, T98G, U-138MG, U-251MG and YH-13) and newly established glioblastoma cell line 0125-DGC were used in the experiments. First, the antitumor effect of perampanel was evaluated by cell counting assay. The number of surviving cells after administrating drugs (perampanel, carbamazepine, sodium valproate, levetiracetam, and temozolomide) was counted. The cell proliferation inhibitory effect was observed in all cell lines after administration of perampanel and temozolomide. The antitumor effect was greater when perampanel and temozolomide were used together than when they were used alone. Next, we investigated the mechanism of the antitumor effect of perampanel on glioblastoma cells using FACS, western blotting, RT-PCR, and transwell assay. The expression levels of apoptosis-related proteins and mRNAs on glioblastoma cells were increased after administration of perampanel. Furthermore, perampanel demonstrated the inhibitory effect on the migration of glioblastoma cells. Finally, we evaluated the antitumor effect of perampanel in vivo. U-87MG cells were transplanted into the brains of immunodeficient mice, and these mice were treated by perampanel and/or temozolomide. The transplanted mice were divided into an untreated control group, a perampanel treatment group, a temozolomide treatment group, and a combination treatment group. As a result, survival times were significantly prolonged in all treatment groups compared to the untreated control group. Notably, survival times in the combination therapy group was significantly longer than in the monotherapy group. These results revealed that perampanel exhibits antitumor effects on glioblastoma cells by inducing apoptosis and suppressing cell migration ability. Furthermore, perampanel may enhance the antitumor effect of temozolomide for glioblastoma when it used as combination therapy.
EXTH-06. DEVELOPMENT OF ANTISENSE OLIGONUCLEOTIDE THERAPY AGAINST ZFTA-RELA EPENDYMOMA
Authors: Laboe Nicholas , Gee David , Bertrand Kelsey , Agnihotri Sameer , Mack Stephen 
Published: November 2024

Abstract

Treatment for ependymoma (EPN), the third most common pediatric brain tumor, has not changed in the last 30 years, consisting of surgery and radiotherapy. When EPNs relapse, there are very limited therapeutic options, thus highlighting a dire need for more effective treatment for these tumors. Over 95% of supratentorial EPN are driven by ZFTA fusion oncoproteins, the most common variant being ZFTA-RELA. ZFTA fusion oncoproteins (FO) alone are sufficient to drive tumors in murine models. We hypothesize that: these tumors continue to depend on ZFTA-RELA expression, and that the FO represents a lead target for therapeutic development.

RESULTS
To assess this dependency, we utilized CRISPR-Cas9 mediated knockout (KO) of ZFTA-RELA oncoproteins from a series of patient derived cell lines as compared to control cells. We found that ZFTA FO driven patient models were dependent upon ZFTA FO expression, and KO led to impaired cellular proliferation. To determine whether a reduction in FO protein levels would also be sufficient to reduce tumor growth, we screened a series of antisense oligonucleotides (ASOs) for ZFTA FO knockdown efficiency in patient-derived cell lines. We quantified knockdown efficiency by western blot and selected the top-performing ASOs targeting a functionally important zinc finger domain of ZFTA. Top-performing ASOs reduced tumor cell proliferation in single dose experiments by 50%, while a non-targeting ASO treated population was unaffected. Repeated ASO doses over 96 hours saw a 75% reduction compared to a 10% reduction in the non-targeting group.

CONCLUSION
Our findings suggest that ZFTA-RELA drives tumor initiation and continued maintenance and proliferation of EPN. Tumor proliferation can be slowed by reducing FO levels below a required threshold. ASO therapy, potentially in combination with translation inhibitors, is one promising route for targeted treatments in this aggressive EPN subtype and could be expanded against other EPN driver proteins such as EZHIP.