tbuckley/cabot-search huggingface dataset:
P19.03.A CHARACTERIZATION OF THE IMMUNE MICROENVIRONMENT IN ATYPICAL MENINGIOMAS
Authors: M Del Bene, F Agistri, M Patanè, G Carone, E D’Angeli, E Porto, A Stroppa, C Calatozzolo, F Di Meco, B Pollo
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Meningiomas are the most frequent primary intracranial tumors. The high incidence of grade 2 meningiomas (or atypical meningiomas) and their tendency to recur make them a challenge for patients and healthcare systems. Treatment is based primarily on surgical resection, which may be followed by radiotherapy and, seldom and only in extreme cases, chemotherapy. The most controversial topic regarding the treatment concerns the use of adjuvant radiotherapy. To evaluate if a better knowledge of the immune microenvironment of meningioma may help in planning treatments, we carried out a study on the tumor immune infiltrate (TII) looking for a role as a prognostic/predictive marker, suggesting tailored therapies. With this aim our study proposes the development of a panel including demographic, clinical, and pathological data, focusing on the TII, with the highest goal of adding a tool useful for guiding the indication and timing of adjuvant treatments. MATERIAL AND METHODS For this purpose, we carried out a histological review of 53 atypical meningiomas following The 2021 World Health Organization (WHO) Classification of CNS Tumors. Through an immunohistochemical analysis, with an expert pathologist, we evaluated the presence of different classes of immune infiltrates. The panel includes different immune infiltrate markers, microglia, monocytes and macrophages biomarkers and NK cells. We also evaluated the loss of H3K27-me3 as prognostic marker of aggressiveness. RESULTS 27/53 samples showed a massive presence of lymphocytic infiltrate, mostly CD3+ and CD8+ T cells, which is widespread in the tumor and not only in the interface with the healthy nervous tissue. In a large number of cases, these data were also correlated to the presence of PD1 (Programmed death-1). CD4+ T lymphocytes and CD20+ B lymphocytes in the majority of cases were poorly represented, while microglia and macrophages were widely present in tumors.Furthermore, we noticed a discrete or high presence of NK cells, widespread throughout the tumor mass. CD11b+ monocytes were mostly expressed in blood vessels, in adjacent nervous tissue (when present in the sample) and in the interface between the latter and the tumor. Suppressive myeloid immune cells CD14+ were found in most samples, with a degree of labeling ranging from weak to strong. CONCLUSION The data we obtained lead us to assume that atypical meningiomas present a “hot” tumor microenvironment characterized by a high immune infiltrate, however, the meaning and the role of this profile will be correlated with clinical data, investigating the impact on the tumor progression. Moreover, we are also looking to understand if meningiomas with abundant TII may be potentially responsive to immuno-oncological therapies.
P19.01.A A SYSTEMATIC REVIEW OF THE NEUROSURGICAL MANAGEMENT OUTCOMES OF POSTERIOR PETROUS MENINGIOMAS
Authors: W Awuah, S Ali, J Tan, F Adebusoye, M Shah, A Boye, V Sanker, P Tenkorang, S Chidi-Ikeji, M Frimpong, T Abdul Rahman, O Attalah
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Posterior petrous meningiomas (PPMs) present challenges in neurosurgical practice due to their proximity to critical neurovascular structures. Surgical management necessitates consideration of tumour characteristics and adjacent structures to optimise outcomes and minimise complications. Despite advancements in techniques and imaging, determining the optimal surgical approach and outcomes for PPMs remains an area of ongoing investigation. Understanding surgical outcomes and factors influencing postoperative recovery is crucial for informing clinical decisions and enhancing patient care. MATERIALS AND METHODS Databases such as PubMed/Medline, Web of Science (WOS) and Cochrane Library were systematically searched from their inception to April 2024. Among the retrieved articles were 10 retrospective studies, 2 case series, and 9 case reports encompassing a cohort of 622 patients who had undergone various procedures for PPMs. A meticulous quantitative analysis was conducted on the individual patient data extracted from these sources, allowing for a comprehensive examination of the aggregated findings. Additionally, a qualitative analysis was performed on available individual patient data, utilising the Chi-Squared Test methodology to explore potential associations between preoperative symptoms, surgical approach, and postoperative outcomes. In this analysis, a significant threshold of p &amp;lt; 0.05 was employed to determine noteworthy correlations. RESULTS Our search revealed studies with 622 individuals (468 females and 154 males), with a mean age of 54.92 years. Quantitative analysis revealed some degree of hearing loss as the predominant symptom (32%). For treatment, the retrosigmoid approach was most common (63%), followed by the translabyrinthine approach (16%). Resections were mostly total, with the most common postoperative complications being neurological deficits of the 8th cranial nerve (21%). Postoperative facial nerve function was fully preserved in 71.5% of patients, and 36.5% retained unimpaired hearing. Qualitative analysis indicated significant associations between postoperative hearing status, surgical approach (p = 0.001), and neurological deficits (p = 0.003). CONCLUSION Preliminary evidence from this systematic review suggests that the surgical approach matters when it comes to avoiding sequelae arising from surgical treatment of PPM. Specifically, the widened retrolabyrinthine approach shows promise in reducing neurological deficits, while the retrosigmoid approach appears favourable for preserving postoperative auditory function. However, given the limited scope of the current literature, further research is warranted to corroborate these findings and enhance our understanding of optimal surgical strategies for PPM management.
P19.04.B CHROMOGRANIN A IN HUMAN MENINGIOMAS
Authors: S E Tollefsen, O Solheim, P Mjønes, S H Torp
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Meningiomas are the most common intracranial tumor. The neoplasms are usually benign and slow-growing, but the recurrence rates are substantial. There is currently no established pharmaceutical treatment for patients suffering from meningioma, marking the need for a further understanding of tumor biology and investigation of treatment options. Somatostatin receptors are well-known to be present in human meningiomas and somatostatin analogs are investigated as a potential targeted treatment. The presence of somatostatin receptors may suggest a possible expression of other neuroendocrine proteins in human meningiomas. The neuroendocrine glycoprotein chromogranin A is a precursor for several biologically active peptides and contributes to the intracellular formation of secretory granules. Chromogranin A is a well-established neuroendocrine differentiation marker. To our knowledge the immunohistochemical expression of chromogranin A in human meningiomas is not previously investigated. The aim of this study was to investigate neuroendocrine differentiation in human meningiomas by using chromogranin A as an immunohistochemical marker. MATERIAL AND METHODS The immunohistochemical expression of chromogranin A were measured in tissue specimens from 162 patients operated for primary World Health Organization 2016 classification grade 1 or 2 meningioma in the period of 1991 to 2000 at St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. Sections were incubated for 40 minutes in room temperature with a monoclonal chromogranin A antibody (clone DAK-A3, dilution 1:100). RESULTS None of the 162 tissue specimens of meningioma were immunoreactive for chromogranin A. CONCLUSION Chromogranin A was not immunohistochemically expressed in our series of 162 meningioma specimens, thus not supporting neuroendocrine differentiation in human meningiomas. However, as other neuroendocrine peptides (such as somatostatin receptors) are previously detected in meningiomas, further investigations are needed to conclude on the matter of neuroendocrine differentiation in meningiomas.
P19.02.B CHALLENGES AND OUTCOME OF THE RESECTION OF A LEFT PETROCLIVAL MENINGIOMA IN A LOW INCOME COUNTRY
Authors: J Ssembatya, E Tan, B Taremwa
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Petroclival meningiomas pose a surgical challenge due to their complex regional anatomy, with proximity to vital neurovascular structures and involvement of deep, narrow surgical corridors. Until 1970, they were generally considered unresectable due to high operative morbidity. However since the introduction of advanced microscopic surgery with neuronavigation and intraoperative neurophysiological monitoring, surgical outcomes have improved. Sadly, this technology is not available in most low income countries. We report a case of successful resection of a left petroclival meningioma in Mbarara Regional Referral Hospital in Uganda, despite the lack of advanced technology. CASE REPORT A 36 year old female presented with a 1 year history of intermittent vomiting and convulsions, worsening over 2 weeks. Neurological examination was normal except a Grade 2 left facial palsy. CT head was performed locally but a 7 hour journey was required for MRI brain; this confirmed a left petroclival meningioma. She returned for tumour resection 2 weeks later due to theatre capacity; neuronavigation, auditory brainstem response testing, sensory/motor evoked potentials and cranial nerve monitoring were not available. A left frontal EVD was initially inserted to control intracranial pressure, before placement in a right park bench position and head secured in a Mayfield clamp. Left retrosigmoid approach was used, with the meningioma visible on reflection of the dura. Under basic microscopic vision, gross total resection was performed with Simpson Grade 2 outcome. The EVD was replaced with an Ommaya reservoir. Postoperative CT head showed no tumour residual, with resolution of the facial palsy and all symptoms. Complications included CSF leak from the nose and Ommaya site, which resolved with conservative management, and DVT treated with anticoagulation. She was discharged at 3 weeks, is fully functioning and working in the community, with Modified Rankin Score 1. Neuropathology results reported meningothelial meningioma WHO Grade 1. CONCLUSION Lack of advanced technology in low income countries results in more difficulty locating lesions, increased risk of injury to neurovascular structures and longer operative time. Reduced availability of MRI delays diagnosis, whilst the low resourced hospital wards, together with reliance on patients’ families to fund medication and investigations, results in a challenging perioperative period. Despite this, we report the successful gross total resection of a petroclival meningioma in Uganda. We rely on an in depth understanding of skull base neuroanatomy, three dimensional mental imagery, detailed clinical examination and thorough review of preoperative imaging. We aspire to adopt more advanced technology and collaborate with higher income countries, but hope this case will inspire other low income countries who face similar challenges.
P27.04.A CLINICAL EXPERIENCES AND LEARNING CURVES FROM ROBOT-ASSISTED NEUROSURGICAL BIOPSIES WITH STEALTH AUTOGUIDEΤΜ
Authors: J Ljungqvist, H Barchéus, F Abbas, A Ozanne, D Nilsson, A Corell
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Biopsies of intracranial lesions is a cornerstone in the diagnosis of unresectable tumors to guide neurooncological treatment; however, the procedure is also associated with risks. The results from the cranial robot guidance system Stealth AutoguideΤΜ were studied after introduction at a neurosurgical department. Primary aims include the presentation of clinical and radiological data, accuracy of radiological diagnosis, learning curves of the new technology, diagnostic yield, and precision. The secondary aim was to study complications. METHODS Retrospective data inclusion was performed on patients ≥18 years undergoing biopsy with Stealth AutoguideΤΜ due to suspected brain tumor in the first three years after introduction of the technique. Data regarding clinical characteristics, intraoperative variables, pathological diagnosis, and complications were recorded. Analyses of learning curves were performed. RESULTS A total of 79 procedures were performed on 78 patients with a mean age of 62 years (SD 12.7, range 23-82), 30.8% were female. Tumors were often multifocal (63.3%) and supratentorial (89.9%). The diagnostic yield was 87.3%. The first-hand radiological diagnosis was correct in 62.0%. A slight decrease in operation time was observed, although not significant. The surgeon contributed to 12% of the variability. CONCLUSION Robot-assisted biopsies with Stealth AutoguideΤΜ seem to be comparable, with regards to complications, to frame-based and other frame-less neurosurgical biopsies. Learning curves demonstrated no statistical differences in time of surgery and only 12% surgeon related variation (i.e. variation caused by change of performing surgeon), suggesting a successful implementation of this technical adjunct.
P19.07.A INCREASED LOCAL TUMOR CONTROL AFTER POSTOPERATIVE RADIOTHERAPY IN RECURRENT MOLECULARLY HIGH-RISK WHO GRADE 1 MENINGIOMAS
Authors: M Y Deng, S N Maas, J Debus, F Sahm, L König
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Despite an overall favorable prognosis, early recurrences occur in a significant proportion of WHO grade 1 meningiomas following surgical resection. Given a wide variety of institutional preferences, individualized patient circumstances, and a lack of level 1 evidence, there are no standardized guidelines for the treatment of recurrent WHO grade 1 meningiomas, in particular to the requisiteness of radiotherapy and its timing. Our study assessed the local tumor control after postoperative radiotherapy in recurrent molecularly high-risk WHO grade 1 meningiomas. MATERIAL AND METHODS Patients with primary WHO grade 1 meningioma and DNA methylation profiles (n=224) were retrospectively screened for recurrences (n=31). The local 3-year progression-free survival (PFS) after primary resection, as well as recurrence resection, was determined using Kaplan-Meier analysis. Integrated risk scores were calculated for primary and recurrent WHO grade 1 meningiomas. RESULTS Primary WHO grade 1 meningiomas were completely resected (GTR) in 81.3% (182/224). The 3-year PFS was 95.4% for molecularly prognostically favorable (IntS-low) versus 71.1% for prognostically unfavorable (Int-S-int/high) primary WHO grade 1 meningiomas. None of the patients received postop-RT after primary resection. After recurrence resection (n=31, Int-S-low: 14/31, Int-S-int/high: 17/31), 85% of subtotally resected meningioma recurrences received postop-RT. Notably, the local 3-year PFS for clinically-molecularly prognostically unfavorable recurrences (STR, Int-S-int/high) after postop-RT was 85.9%. CONCLUSION Postop-RT in molecularly prognostically unfavorable, recurrent WHO grade 1 meningiomas after STR may lead to improved local tumor control. Future matched-pair analyses with patients with recurrent WHO grade 1 meningiomas are warranted to further illustrate the benefit of postop-RT after recurrence resection.
P27.05.B DECODING GLIOBLASTOMA SURVIVAL: UNRAVELING THE PROGNOSTIC POTENTIAL OF OLFACTORY FUNCTION IN A PROSPECTIVE OBSERVATIONAL STUDY
Authors: C Oster, A Matyar, T Hummel, E Hattingen, T Schmidt, M Jokisch, D Jokisch, Y Ahmadipour, U Sure, M Stuschke, T Tertel, B Giebel, C Kleinschnitz, B Scheffler, C Deuschl, S Kebir, M Glas
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Olfactory impairment is a common neurologic deficit among glioblastoma patients. We have previously shown that glioblastoma patients with reduced smell sensitivity had lower overall survival rates compared to those with normal olfactory function. A notable limitation in that study was the unequal distribution of prognostic factors between the two groups, and the absence of continuous olfactory assessments during treatment to investigate if therapy-associated neurotoxicity could be a contributing factor to diminished olfactory acuity. In this trial olfactory function will be evaluated in glioblastoma patients as a prognostic marker with regard to overall survival, neurocognition and quality of life. METHODS This prospective, multicenter study is set to recruit 64 glioblastoma patients alongside 64 healthy controls. Stratification of participants is based on prognostically relevant variables such as resection status, MGMT promoter methylation status, radiographic involvement of olfactory brain areas, olfactory function, age, and Karnofsky performance status scale. We utilize Sniffin´ Sticks to evaluate olfactory function through identification and threshold tests, and this assessment is carried out longitudinally throughout the therapy starting from tumor diagnosis. Infiltration of the olfactory nerves or olfactory brain are scrutinized using a high-resolution coronal T2-weighted sequence which is added to a dedicated brain tumor protocol. MRI images are independently reviewed by two board-certified radiologists from distinct institutions, who are blinded to the patients’ olfactory function status. Furthermore, quality of life data, neuropsychological testing, and psychosomatic screening are performed at specific intervals throughout the study. Also, we examine next-generation sequencing results to investigate potential genetic associations with hyposmia in glioblastoma patients. RESULTS The first participant was enrolled in May 2023. Currently, 16 patients and three controls are already enrolled (April 2024). Plans are underway to open a second study site in 2024, with the aim to complete recruitment by December 2025. Follow-up assessments will continue until December 2027. We anticipate that the final results of the study will be available in 2028. CONCLUSIONS In the process, this study is the first prospective study which investigates the olfactory function systematically as prognostic factor in glioblastoma patients.
P27.10.B FACTORS INFLUENCING TIMELY DIAGNOSIS IN NEUROLYMPHOMATOSIS
Authors: S Doubrovinskaia, A Egert, P Karschnia, G Scheffler, A Huttner, R Fulbright, J M Baehring, L D Kaulen
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Neurolymphomatosis refers to infiltration of the peripheral nervous system (PNS) by non-Hodgkin lymphoma (NHL). Diagnostic intervals in NL and factors facilitating or delaying diagnosis have not been thoroughly evaluated. We therefore aimed to analyze diagnostic intervals in a large cohort from a tertiary referral center. MATERIAL AND METHODS The quality control database at Yale Cancer Center, Section of Neuro-Oncology, was searched for neurolymphomatosis cases diagnosed between 2001-2021. Univariate analyses were performed to identify parameters influencing diagnostic intervals. RESULTS We identified 22 neurolymphomatosis cases including 7 without previous NHL (primary NL) and 15 with PNS relapse of NHL (secondary NL), which occurred after a median of 16 months (range: 4-144). Patients typically presented with painful polyneuropathy (73%), that was asymmetrical and rapidly progressive. Diagnosis was based on PNS biopsy (50%) or integration of neuroimaging findings (50%) with NHL history and diagnostic cerebrospinal fluid examinations. NL was diagnosed a median of 3 months (range: 1-12) after symptom onset. Secondary NL (median 2 vs 6 months; p =0.02), presentation with rapidly-progressive asymmetrical neuropathy (median 2 vs 6 months; p &amp;lt; 0.001), upfront evaluation with either MRI or FDG-PET (median 2 vs 5 months; p = 0.04), and absence of nerve root lesions (median 1.5 vs 4 months; p = 0.04) were associated with earlier diagnosis after symptom onset. CONCLUSION Diagnostic delays in NL are common, particularly in patients with primary disease, atypical clinical presentation, upfront assessment with conventional CT, and nerve root lesions. Findings may guide prompt initiation of appropriate diagnostic work-up in NL.
P27.06.B EFFECT OF CHOLINE ALPHOSCERATE ON THE SURVIVAL OF GLIOBLASTOMA PATIENTS
Authors: Y KIM
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Cognitive impairment often occurs in glioblastoma (GBM) patients due to the tumor itself and treatment side effects. Choline alphoscerate (L-alpha-glycerylphosphorylcholine, GPC) is frequently used to compensate for cognitive impairment in GBM patients. This study was conducted to determine whether GPC affects the overall survival (OS) and progression-free survival (PFS) of GBM patients. MATERIAL AND METHODS From 2011 to 2020, 187 isocitrate dehydrongenase (IDH)-wild-type GBM patients were analyzed. The patients were classified based on whether GPC was continuously used for at least 3 or 12 months (mos) after GBM diagnosis. RESULTS Although GPC usage (≥3 mos) did not make significant differences in survival extension, median OS in the long-term GPC group (≥12 mos) was longer with statistical significance, compared to the control group (&amp;lt;12 mos) (38.3 vs. 24.0 mos, p = 0.004). In addition to younger age, supratentorial location, complete resection, and MGMT promoter methylation, long-term use of GPC (≥12 mos) was significantly associated with longer OS in multivariate analysis (p = 0.019, hazard ratio [HR] 0.532, 95% confidence interval [CI] 0.314-0.900). CONCLUSION Despite the limitations of this study, long-term GPC use was possibly associated with prolonged survival in GBM patients. Multi-center prospective randomized studies with a large number of patients are needed to validate these findings.