tbuckley/cabot-search huggingface dataset:
P23.02.A BPPV IS A SIGNIFICANT CAUSE OF DIZZINESS IN VESTIBULAR SCHWANNOMA TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: J Jethwa, L Williams, S Davenport, A Adonis
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Vestibular schwannoma (VS), a vestibulocochlear nerve tumour, causes disequilibrium (sensory disorientation) and imbalance. The Royal Marsden Hospital (RMH) treats VS with stereotactic radiosurgery (SRS). Those with vestibular symptoms are referred for vestibular rehabilitation, where co-existing Benign Paroxysmal Positional Vertigo (BPPV) has been found on numerous occasions. BPPV causes vertigo on head movements due to dislodged crystals in the vestibular apparatus. UK incidence is 0.04%, with causative factors being head injury, increased age, and inner-ear inflammation such as infection. Cardinal signs are history of vertigo on head movements, and vertigo and nystagmus on Dix-Hallpike testing. BPPV is treated by the Eply manoeuvre. No evidence exists of significant post-SRS BPPV in VS, but does in nasopharyngeal cancer receiving similar SRS to VS. PURPOSE To investigate incidence of post-SRS BPPV in VS. METHODS A case-note audit of VS referred for rehabilitation from 2017-2022, identifying subjective BPPV symptoms, vertigo and nystagmus on Dix-Hallpike testing, and BPPV treatment outcome. RESULTS 24.6% (n=16) of VS patients referred to physiotherapy with dizziness had co-existing BPPV post-SRS. This was significant (p= &amp;lt; 0.001) compared to UK incidence. Diagnosis was confirmed by resolution of vertigo following treatment in all cases. However, disequilibrium associated with VS remained in all. In 68.7%, nystagmus was significantly absent (p=0.002) on BPPV testing compared to post-SRS nasopharyngeal cancer population. There was no significant difference in age between those with and without BPPV. The time from SRS to BPPV was 2-43 weeks (mean=12). DISCUSSION This is the first study finding significant incidence of BPPV in VS post-SRS. Remaining disequilibrium following successful BPPV treatment confirmed dual causes of dizziness. The causative factor is likely inflammation caused by SRS as there was no age difference, no head injury or inner-ear infection, and all cases occurred post-SRS. As BPPV occurred over a wide time following SRS, degradation of crystals may be attributable to acute inflammation and/or delayed inflammation from radiation necrosis. Lack of nystagmus in BPPV with VS may cause misdiagnosis, affecting clinical management. A theory for absent nystagmus is: nystagmus is a result of vestibular imbalance. However, VS causes slowly progressing vestibular imbalance allowing the central nervous system time to compensate, resulting in lack of nystagmus. CONCLUSION BPPV should be considered a side-effect of SRS in VS. Nystagmus should not be a diagnostic essential to avoid misdiagnosis and ensure correct management. More robust research is necessary to substantiate findings.
P20.14.A METASTATIC EPITHELIOD SOLITARY FIBROUS TUMOR
Authors: R Wang, S Pejhan, L Ang, J Megyesi
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Epitheliod solitary fibrous tumor is a rare central nervous system tumor that can rarely metastasize. An unusual case is illustrated. MATERIAL AND METHODS A 76 year old man underwent resection of a lower cervical spinal cord (C5-C7) tumor that was called hemangiopericytoma at time of resection. He was treated with radiotherapy. Twenty-four years later he presented with headache and gait ataxia and neuroimaging revealed a 4th ventricular tumor. He underwent surgical resection via a suboccipital craniectomy. RESULTS Pathology showed a hypercellular tumor composed of epitheliod cells with eosinophilic cytoplasm and moderately pleomorphic enlarged oval nuclei containing finely dispersed chromatin and prominent eosinophilic nucleoli in some nuclei. The tumor cells were arranged in nests and sheets separated by thin walled branching to thick walled hyalinized vessels with frequent areas of hemorrhage. Tumor cells showed high mitotic activity (about 8 mitoses/mm squared). The majority of tumor cells were positive for CK7, synaptophysin, E-cadherin, and rarely for CK20 and D2-40. Tumor cells were negative for EMA, transthyretin, myogenin, desmin, progesterone receptor, NeuN, Olig-2, TTF-1, GATA3, PAX8, OCT3/4, SALL4, CD117, S100 and GFAP. Vasculature was highlighted by PAS, reticulin, CD31, ERG, and CD34. INI-1 was intact in the nuclei. Final diagnosis was epitheliod solitary fibrous tumor, at least CNS WHO grade 2. This was consistent with the pathology from 24 years prior. CONCLUSION Solitary fibrous tumor is known for recurrence and metastasis a long time after initial diagnosis. However, this case highlights the delayed metastatic spread of a relatively rare subtype of solitary fibrous tumor (epitheliod) to a rare location (intraventricular, specifically the 4th ventricle). The literature will be reviewed.
P16.12.A PROPERLY TIMED AND EFFECTIVE HYDROCEPHALUS INTERVENTION ENHANCES EFFICACY IN PINEAL TUMOR MANAGEMENT
Authors: A M Nyalali, F Li, K Zhang, A Leonard
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Pineal region tumors continue to pose challenges in their management because of their histological heterogeneity, complex anatomical location, age of presentation, and presentation with obstructive hydrocephalus. Hydrocephalus creates a paradox of management whereby both medical and surgical approaches, their timing, and outcomes are interdependent with that of hydrocephalus. We aimed to determine the more effective intervention approaches for the interdependent management of pineal tumors and the associated hydrocephalus. MATERIAL AND METHODS We conducted a retrospective cohort study involving 154 patients diagnosed with pineal region tumors between January 2015 and January 2021 with a minimum follow-up of one year. RESULTS About seventy percent (111) of patients with pineal tumors had obstructive hydrocephalus that accounted mostly for the presenting clinical symptoms (76.9 %, p=0.0001). 102 patients were intervened for hydrocephalus with about half (54) also undergoing tumor resection meanwhile the other half received chemotherapy and or radiotherapy as definitive treatments for pineal tumors. Hydrocephalus intervention was performed as primary intervention by external ventricular drainage (15), endoscopic third ventriculostomy (32), ventriculoperitoneal shunt (34), and direct tumor resection (21). Tumor resection as a secondary intervention was performed in 33 patients. Within one year, 14% of patients treated for hydrocephalus had persistent or recurrent hydrocephalus which largely occurred in patients who also had tumor removal (p=0.0001). There was a significant difference among hydrocephalus intervention approaches regarding mean surgical interventions under general anesthesia (p=0.006) and hydrocephalus-related invasive procedures such as subdural lumber puncture and drainage (p=0.016). Among the 154 patients with pineal tumors, 122 (79.2%) required intervention whereby 60 patients (49.2%) underwent tumor resection with or without adjuvant chemoradiotherapy while 62 received definitive chemotherapy and or radiotherapy. Interestingly, the extent of tumor resection was negatively affected by the interval between hydrocephalus intervention and tumor resection (p=0.009). CONCLUSION Ventriculoperitoneal shunting, endoscopic third ventriculostomy, and direct tumor resection remain the mainstay intervention options for pineal tumor-associated hydrocephalus. Although direct tumor removal has dual therapeutic potential by resolving hydrocephalus and tumor removal, the procedure itself increases the risk of hydrocephalus persistence or recurrence thus calling for diligently effective planning for hydrocephalus intervention parallel to the medical or surgical alternatives.
P26.01.B A PHARMACOLOGICAL SURVEY ACROSS GLIOMA STEM CELL PHENOTYPES REVEAL NOVEL GLIOBLASTOMA DRUG-TARGETS, DRUG REPURPOSING OPPORTUNITIES AND FUTURE DRUG COMBINATION STRATEGIES
Authors: R J R ELLIOTT, M Furqan, P Nagle, A Munro, C Drake, J C Dawson, V Brunton, M Frame, N O Carragher
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Owing to the lack of therapeutic advancement in the treatment of glioblastoma (GBM) over the past two decades, Cancer Research UK has designated malignant brain tumours a ‘strategic priority⋯ as a cancer of unmet need’. The inter- and intra-molecular heterogeneity of glioblastoma presents significant obstacles to effective clinical progression of novel treatments. Phenotypic drug screening is ideally suited to heterogeneous diseases, where targeting specific oncogenic drivers (such as EGFR) are broadly ineffective. Phenotypic hits can then be used to systematically identify synergistic combinations which overcome variable therapeutic response observed across multi-cell panels. Synergistic drug combinations between approved drugs (or drug candidates in early clinical trials) provides a repurposing context that could accelerate the bench to bedside model. Our preliminary objective was to incorporate a panel of patient derived GBM stem cell lines into an unbiased ‘cell painting’ assay to quantify multiple GBM stem cell phenotypes and create an updated pharmacological survey by screening these cell lines across several drug libraries containing commercially available, FDA approved and/or Phase I/II/III compounds. MATERIAL AND METHODS We profiled patient derived GBM stem cells against several thousand annotated compounds covering multiple doses, using our established image-based high throughput screening protocols. Multiplexed ‘cell painting’ dyes were used to quantify in detail the cellular response to each drug via CellProfiler image analysis software. Data processing, QC, dimensionality reduction and hit thresholding was carried out primarily using Stratominer-HCA platform. Putative hits based on phenotypic distance and potency were selected for validation and further characterisation. RESULTS Predominant drug sensitivities include the highly potent but expected pan-cytotoxic effects of compounds that target microtubules, the proteasome, topoisomerases, DNA/RNA synthesis and histone deacetylases. Beyond these, approximately 50 compounds have been selected for further studies including mechanism-of-action and pathway profiling, dose-ratio matrix combination testing in 2D and 3D GBM models, neuronal cytotoxicity and in vivo proof-of-concept studies via intracranial implantation. CONCLUSION Our preliminary results serve as a foundation for a systematic approach to identify novel drug combinations including combinations that could be used concurrently with standard treatment protocols for GBM.
P22.08.B INDICES OF SOCIOECONOMIC STATUS AND NEURO-ONCOLOGY CAREGIVERS’ RISK FOR IMMUNE DYFUNCTION
Authors: P Sherwood, R Ho, D Ren, Z Deng, H Donovan
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND In neuro-oncology, family income has been shown to impact both family caregiver and patient outcomes. In addition, subgroups of neuro-oncology caregivers have been shown to be at risk for immune dysfunction due to the stress of providing care. How socioeconomic status, particularly measures of socioeconomic status beyond simply income, plays a role in risk for altered cytokine levels is unexplored. The purpose of this analysis was to determine the effect of neighborhood level indices of socioeconomic status on Interleukin (IL)6, Il1ra, and C-reactive protein (CRP) levels in neuro-oncology family caregivers. MATERIAL AND METHODS Data were collected from 120 family caregivers of persons with a primary malignant brain tumor (NIH NR013170; only baseline data used for analysis). High sensitivity CRP, IL6, and IL1ra were assessed from five milliliters of blood obtained by standard venipuncture technique using sodium heparin tubes. Standardized neighborhood deprivation and social vulnerability levels were obtained using metrics from the United States Census Bureau which includes variables such as neighborhood unemployment, public transportation, education, health insurance coverage and family poverty levels. Final analyses were performed using multivariate linear regression adjusting for potential covariates. RESULTS Greater neighborhood deprivation was associated with higher CRP (p=0.05) and potentially (p=0.08) IL6 levels in family caregivers. Higher levels of social vulnerability (p=0.05) were also associated with higher CRP levels. All models adjusted for gender, age, race/ethnicity, any change in health over the two months prior to data collection, smoking, caffeine use, recent cold or fever, and number of comorbid conditions. CONCLUSION Recognizing the impact of characteristics placing neuro-oncology caregivers at risk for compromised immunity can inform health strategies and targeted interventions. Using indices of environmental vulnerability broader than simply income holds promise for targeting individuals for whom reduction of inflammation should be a primary target in order to improve quality of life and overall health outcomes.
P18.33.A PROGNOSTIC FACTORS OF MALIGNANT TRANSFORMATION IN LOW GRADE GLIOMA: A RETROSPECTIVE STUDY
Authors: A Joanta-Gomez, J Furnari, R Chang, M Diaz, K Bagri-Manjrekar, C Ng, F Iwamoto
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Malignant transformation (MT) of low-grade gliomas (LGGs) represents a critical event in disease progression, requiring early identification of at-risk patients and the development of preventive strategies. This retrospective cohort study aimed to assess clinical, molecular, and radiological markers predictive of MT in LGG patients. MATERIAL AND METHODS Institutional database medical records of adult LGG patients (n=175) diagnosed between 1994-2018 were analyzed. MT was defined as histological confirmation of grade 3-4 after the 1st recurrence or new/increased post-progression enhancement (PPE) consistent with MT by multidisciplinary consensus. Patients were categorized into groups based on MT pattern: group 2-2 (no MT), group 2-3 (MT to grade 3), and group 2-4 (MT to grade 4). Risk factors from the EORTC adapted prognostic index were assessed and logistic regression examined their association with MT. Survival was evaluated using Kaplan-Meier analysis, and PPE’s predictive value for MT was calculated. RESULTS Among 55 patients with recurrent LGG, MT occurred in 35 (63.64%), primarily in males (57.20%) with a median age of 39.75 years. Astrocytoma (68.57%) and oligodendroglioma (31.43%) were common initial diagnoses. Majority of the MT patients (62.86%) were allocated to group 2-3. Multivariate analysis revealed 1p19q codeletion negative (OR=3.75, p&amp;lt;0.05), high-risk status (OR=3.71, p&amp;lt;0.05), and resection extent/biopsy (OR=2.38, p&amp;lt;0.05) as prognostic factors for MT. Survival analysis demonstrated longer post-recurrence survival in group 2-2 versus 2-3 and 2-4 (log rank p&amp;lt;0.05). A similar trend was observed in 1p19q codeletion positive versus negative and low-risk versus high-risk groups. PPE exhibited 72% sensitivity, 75% specificity, 83% positive predictivity, and 60% negative predictivity for MT. CONCLUSION MT in LGG patients was associated with unfavorable molecular characteristics (1p19q codeletion negative) and high-risk status. Further research is warranted to elucidate preventive strategies against MT occurrence.
P18.30.B MYCN AMPLIFICATION PREDICTED A WORSE PROGNOSIS IN PATIENTS WITH LOWER-GRADE IDH-MUTANT GLIOMAS AND WAS RELATED TO THE EPITHELIOID HISTOLOGICAL FEATURES
Authors: S Xi, X Xie, Y Qin, J Lu
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND In the newest WHO criteria, molecular alterations are increasingly incorporated into the diagnosis and grading of gliomas. MYCN amplification is reported to be significantly associated with poor prognosis in many tumors. However, the prognostic significance of MYCN amplification in IDH mutant gliomas has not yet been well established. This study was performed to explore the role of MYCN gene amplification in the tumor grade and prognosis of IDH-mutant gliomas. MATERIAL AND METHODS We evaluated the clinical and pathological features of 190 patients with IDH-mutant gliomas. MYCN amplification was detected by fluorescence in situ hybridization (FISH) using a MYCN probe. Overall survival (OS) was calculated via Kaplan‒Meier analysis and multivariable Cox proportional hazards regression models were used to analyze independent prognostic factors. The morphological features of the patients with MYCN amplification were reviewed and analyzed. RESULTS MYCN amplification was detected in 28/190 (14.7%) IDH-mutant glioma patients and was significantly related to a high tumor grade and high Ki-67 index (P&amp;lt;0.05). MYCN amplification was significantly correlated with overall survival in IDH-mutant glioma patients (112.13 ± 6.58 vs. 91.14 ± 14.96 months, p=0.001) and in lower-grade patients (grades 2 and 3) (122.12 ± 6.81 vs. 47.76 ± 6.58 months, p&amp;lt;0.001). Due to the limitations of the current grading system, we refined the grading system by upgrading the lower-grade IDH-mutant astrocytomas with MYCN amplification to high grade and found that the novel MYCN grading system was significantly related to the prognosis of IDH-mutant astrocytoma patients (112.84 ± 10.40 and 77.65 ± 11.15 months, p&amp;lt;0.001). One-half of the patients (14/28) with MYCN amplification exhibited epithelioid histological features, which included abundant eosinophilic cytoplasm and a dislocated nucleus. CONCLUSION MYCN amplification should be considered a prognostic factor in IDH-mutant gliomas, especially in lower-grade gliomas. Patients with MYCN amplification often exhibit epithelioid histological features.
P25.05.A THE IMPACT OF THE COVID-19 PANDEMIC ON NEURO-ONCOLOGY: REPORT FROM THE DUTCH BRAIN TUMOUR REGISTRY
Authors: V K Y Ho, J A F Koekkoek, M Wagemakers, F Y F de Vos, R J A Nabuurs, G Wester, E M Bongers, C O Nogarede, A M E Walenkamp, V van Dis, S L N Maas, P C de Witt Hamer, A Compter, T Seute
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The COVID-19 pandemic affected all healthcare domains, including neuro-oncology. This study investigated the effects of the COVID-19 pandemic on the diagnosis, treatment and outcomes of adult patients with a glioma or meningioma in the Netherlands. MATERIAL AND METHODS Patients diagnosed in 2020 were divided into 5 periods, based on the severity of the COVID-19 pandemic in the Netherlands, and compared to patients diagnosed in the same period in the years 2017-2019. RESULTS The number of meningioma diagnoses decreased during the first 3 periods of the COVID-19 pandemic, and patients diagnosed in 2020 differed in their socioeconomic status from those diagnosed in 2017-2019. Glioma patients diagnosed in 2020 more often received adjuvant chemotherapy. Those aged 70+ years were more often treated with chemoradiotherapy instead of radiotherapy following neurosurgery. Both glioma and meningioma patients diagnosed in 2020 experienced a somewhat longer time to neurosurgery, with a median difference of 2 (95%-confidence interval [CI]: 1-3) and 4 days (95%CI: 0-8), respectively, while their time to initial adjuvant therapy was shortened, with a median difference of -1 (95%CI: -2-0) and -2 days (95%CI: -22-20), respectively. No difference was detected in patients’ overall survival. CONCLUSION The COVID-19 pandemic mostly impacted meningioma incidence during the first four months of 2020. With relatively limited adjustments, the neuro-oncology field was able to cope with the challenges posed by the pandemic.
P17.02.B BMSCOPE: A SCOPING REVIEW TO CHART THE EVOLVING CLINICAL STUDY LANDSCAPE IN BRAIN AND LEPTOMENINGEAL METASTASIS
Authors: R Heywood, V Cheng, R Zakaria, R Burger, K Zucker, S Kannan, M Putra, A Fitzpatrick, G Doherty, P Sanghera, M Jenkinson, C Palmieri
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Recent studies have challenged the notion that patients with brain metastasis (BM) or leptomeningeal metastasis (LM) should be excluded from systemic therapy clinical trials. This scoping study summarises BM/LM clinical studies published globally between 2010 and 2023. MATERIAL AND METHODS Eleven electronic databases were searched on 21 June 2021, with an updated search on 21 February 2023. Clinical studies were included if they involved the investigation of a therapeutic intervention in patients with BM and/or LM, and a reported patient outcome. Study-level data was extracted by study authors, including study type, date of publication, country of data collection, number of BM/LM patients in study, primary tumour type and type of therapeutic intervention RESULTS 48222 studies were identified from the electronic search and 4921 unique studies were eligible for analysis, with increasing numbers of studies (and international collaborations) through the study period. 627 of these publications were clinical trials. Over the study period there was a shift towards later stage clinical trials, predominantly trials of systemic therapy that included BM/LM patients. Despite this, only 29.2% reported intracranial-specific outcomes. CONCLUSION In this comprehensive analysis of the BM/LM literature, we chart the evolving landscape of studies involving this previously clinically excluded population. Given the increasing clinical research activity, particularly late-stage systemic therapy trials, it is imperative that consideration is given to the intracranial activity of new investigational agents. Wider adoption of standardised reporting of intracranial-specific endpoints will facilitate evaluation of intracranial efficacy
P17.01.A ANAMNESTIC RADIOLOGICAL METASTASES OUTCOME SURGICAL SCORE (ARMO-S). A PURPOSE OF A PREDICTIVE SCORING SYSTEM FOR SURGICAL BRAIN METASTASES
Authors: D Armocida, T Ius, F Cofano, F Tartara, M Salvati, A Frati, D Garbossa
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Several risk stratification scores have been suggested to aid prognostication and guide treatment strategies for brain metastases (BMs). However, the current scores do not focus on the specific neurosurgical population, therefore not predicting short-term mortality and postoperative performance status. MATERIAL AND METHODS This retrospective observational study of 362 consecutive patients treated with surgery for BMs aims to identify the factors associated with post-surgical outcomes and propose a surgery-specific prognostic score for patients with BMs candidate for open surgery. RESULTS Factors significantly associated with OS and performance status in multivariate analysis were age, KPS, surgical site, synchronous debut of BM, number, tumor volume, seizure, extra-cranial metastases, and deep-seated location. The variables were incorporated into the Anamnestic Radiological Metastases Outcome Surgical score (ARMO-S). The values range between 0 and 10. Patients were divided into two groups (low-risk and high-risk) based on each significant subgroup’s median survival and performance status with an optimal cutoff value determined as 4. The two groups have significant differences in OS (9.6 versus 14 months, p = 0.0048) postoperative KPS (90 versus 70, p=0.012) and KPS at last follow-up evaluation (75 versus 30, p&amp;lt;0.001) CONCLUSION ARMO-S is a simple and comprehensive score for BM patients selected for neurosurgery, as it incorporates the main factors of the most important prognostic scores, implementing them with more surgery-specific predictive elements such as tumor location and volume, presence of seizures at onset, and involvement of eloquent brain areas.