bluuebunny/crossref_metadata_2025_split huggingface dataset:
P18.39.A SEIZURE PROPHYLAXIS IN GLIOMA SURGERY (SPRING): A MULTI-CENTRE, UNBLINDED, RANDOMISED TRIAL
Authors: Jenkinson M D , Bulbeck H , Rooney A , Thompson G , Burns J , Robinson T , Vale L , Erridge S , Watts C , Grant R ,   SPRING trial investigators
Published: October 2024

Abstract

BACKGROUND
50-80% of all glioma patients will suffer from seizures during their lifetime. Over half of these patients will have drug resistant seizures. Seizure risk is increased peri-operatively, at tumour progression, and shortly before death. Current guidelines do not support routine use of prophylactic peri-operative anti-epileptic drugs (AED) in seizure naïve patients; despite this, levetiracetam is frequently prescribed for this indication. The aim of this trial was to determine the clinical and cost effectiveness of prophylactic levetiracetam in seizure naïve patients undergoing surgery for a glioma at reducing the risk of seizures.

MATERIAL AND METHODS
Seizure naïve patients with newly diagnosed glioma undergoing surgery (biopsy or resection) were randomised (1:1) to receive 12 months prophylactic levetiracetam or no prophylaxis at 14 neurosurgery and neuro-oncology units in the UK. Participants received standard of care neurosurgery and neuro-oncology treatment and were followed until death or for a maximum of one year. The primary outcome was one year risk of first seizure analyzed using a logistic regression model and intention to treat analysis. Outcomes were analyzed by intention-to-treat. The target accrual was 804 participants. This trial was registered with ISRCTN 49474281.

RESULTS
Between Oct 10, 2019 and Aug 30, 2022, we randomised 96 patients, from 24 to 79 years of age, to levetiracetam (n=49) or no prophylaxis (n=47). Due to slow accrual during the Covid-19 pandemic the trial closed early. In the levetiracetam group there were 43 high grade glioma (HGG) and 6 low grade glioma (LGG), and in the no prophylaxis group there were 43 HGG and 4 LGG. Seventeen (35%) of 49 patients randomised to levetiracetam had a seizure, compared to 15 (32%) of 47 patients randomised to no prophylaxis (OR 1.25, 95%CI 0.49-3.21, p=0.64). Median time to first seizure was 4.8 months in the levetiracetam group and 3.0 months in the no prophylaxis group. In the levetiracetam group 20 (41%) of 49 patients died within 12 months (median overall survival 6.8 months; range 0.2-11.9), and in the no prophylaxis group 15 (32%) of 47 patients died within 12 months (median 4.7 months; range 0.1-12.0). There were no serious adverse events or suspected unexpected serious adverse events related to levetiracetam.

CONCLUSION
Due to poor accrual caused by the Covid-19 pandemic the SPRING trial closed early and is therefore underpowered. Based on the limited data there was no difference in the 12 month seizure risk in the prophylaxis and no prophylaxis patients undergoing surgery for newly diagnosed glioma. The role of prophylactic anti-epileptic drugs remains undefined.
P18.40.B SET UP AND RECRUITMENT TO A RANDOMISED CONTROLLED TRIAL OF MEDICINAL CANNABINOIDS IN RECURRENT GLIOBLASTOMA - THE ARISTOCRAT TRIAL
Authors: Savage J , Mant R , Kirkham A , Buckle P , Banks E , Meade S , Boele F , Williams M , Collinson F , Billingham C , Short S C 
Published: October 2024

Abstract

BACKGROUND
ARISTOCRAT is a unique, randomised, double-blind, placebo-controlled phase II trial of cannabinoids (nabixomols) alongside temozolomide in patients with MGMT-methylated recurrent GBM.

MATERIAL AND METHODS
This UK based trial was funded through a crowdfunding campaign run by The Brain Tumour Charity in 2020 and a multi-disciplinary team of co-applicants including PPI representatives designed the protocol, which randomises patients with first recurrence of IDH wild-type GBM patients in a 2:1 ratio between nabiximols or matched placebo with standard dose temozolomide. Unique aspects include self-titration of nabiximols based on individual tolerance, and fully blinded randomisation with matched placebo. The primary outcome measure is overall survival time with key secondary outcomes including survival at 6, 12 and 24 months, progression-free survival time, health-related QoL and adverse events. The trial initially aimed to recruit a total of 234 patients over 18 months. Intermediate assessment of feasibility to confirm safety, compliance and achievability of recruitment was planned after 40 patients are randomised.

RESULTS
The trial opened in February 2023 and has promoted a high level of patient and public interest, including national press coverage. Despite this, recruitment has been slower than anticipated due to factors including slow site activation complicated by the blinding of a controlled drug, and low numbers of patients screened. We have not identified specific issues in our screening data but did, on request of local PIs broaden inclusion criteria to include patients who received short course (40Gy in 15 fractions) radiotherapy first line. To further address this we have highlighted the use of genomics data from Tessa Jowell BRAIN MATRIX, to identify eligible patients at first diagnosis who can then be flagged for study consideration at relapse. We have also initiated a unique collaboration to use real-world data [the GlioCova data set] to re-test our estimates for potential patient recruitment in the UK, which may suggest specific remedies to ensure the study can deliver definitive data in a realistic time frame.

CONCLUSION
ARISTOCRAT will provide unique, robust clinical data on the role of nabiximols (combined with temozolomide) in improving overall survival and the impact on QoL for patients with recurrent GBM and is the first of its kind in cancer patients. Challenges to set up and recruitment are being addressed using national support through the BRAIN MATRIX genomics platform and real-world modelling approaches.
P18.42.B TAU AND AMYLOID BETA PATHOLOGY IN IDH-MUTANT GLIOMA
Authors: Greutter L , Klotz S , Schnitzenlehner L , Kiesel B , Miller-Michlits Y , Makoli J , Krause E , Widhalm G , Baumann B , Woehrer A 
Published: October 2024

Abstract

BACKGROUND
With an aging population the incidence of brain tumors and neurodegenerative diseases is increasing. Although biological associations between glioma and Alzheimer’s disease (AD) have been suggested, the frequency of comorbidity is insufficiently defined. We here screen tumor-adjacent cortex of a representative cohort of patients with low grade glioma for AD neuropathological changes (ADNC) specifically for phosphorylated tau (pTau) and amyloid beta (Abeta) deposition, microglial activation, amyloid precursor protein (APP) expression, diffuse axonal injury, and cortical tumor cell infiltration.

MATERIAL AND METHODS
A total of 85 patients with astrocytoma, IDH mutant, CNS-WHO grade 2-3, (N=37, median age: 39) and oligodendroglioma, IDH mutant and 1p-19q co-deleted, CNS-WHO grades 2-3 (N=48 median age: 50) were included. 2µm sections were immunohistochemically stained for the markers b-A4, t-AT8, NeuN, APP and Iba1. Whole slide quantification was performed using Matlab and QuPath codes. For a subset of 15 patients, longitudinal samples were available for analysis of post-treatment effects.

RESULTS
The median cell density in the tumor-adjacent cortex was 1355/mm2 for astrocytoma and 1392/mm2 for oligodendroglioma, which was significantly higher than in non-tumor infiltrated cortex (median: 1030 cells/mm², p-value&lt;0.0001). A total of 32 patients (38%) showed Abeta (14%, n=12/85) and/or pTau pathology (36%, n=31/85) in the tumor-adjacent cortex. No difference between astrocytoma and oligodendroglioma was reported. ADNC was mostly frequently observed in older patients but was also present in young individuals (median: 34 years, range: 17 to 77 years). pTau was significantly positively correlated with tumor cell infiltration (Kendall´s tau=0.13, p=0.002). Both Abeta and pTau deposits were frequently observed in the frontal cortex (30%, N=18/60). The tumor infiltration into the cortical regions was associated with neuronal loss (Kendall´s tau=-0.29, p&lt;0.0001). Microglial activation depended on the degree of tumor infiltration (R=0.29), followed by increasing patient age (R=0.12). Diffuse axonal injury was associated with ADNC (Chi²=19.6, p&lt;0.05). APP expression of tumor cells was highest in patients of old age (R=0.35). Longitudinal samples showed stable ANDC pathology in 15/15 subjects.

CONCLUSION
Our preliminary findings suggest presence of ADNC in roughly a third of patients with low-grade glioma, which increases with tumor cell infiltration into the cortex, microglial activation and patient age. Notably, isolated pTau pathology was more pronounced than Abeta pathology suggesting the acquisition of a secondary tauopathy.
P19.08.B MENINGIOMA: A CHALLENGE FOR RADIOLIGAND THERAPY. THE INITIAL EXPERIENCE OF TWO EUROPEAN CENTRES
Authors: Asadurova S , Flaus A , García-Burillo A , Lorenzo-Bosquet C , Lachachi B , Al Mansour L , Gonzalez M , Vieito M , Gamez-Cenzano C 
Published: October 2024

Abstract

BACKGROUND
Evaluation of the treatment with [177Lu}Lu-DOTA-TATE in patients with recurrent meningioma.

MATERIAL AND METHODS
International bicenter retrospective study including 6 patients with recurrent meningiomas treated with [177Lu}Lu-DOTA-TATE between 12/02/2019 and 11/03/2022. Prior to the treatment, the expression of somatostatin receptors has been confirmed by [68Ga]Ga-DOTA-TOC PET/CT. Patients received between two and four cycles of 7400 MBq of [177Lu}Lu-DOTA-TATE. To mitigate potential complications, 50% (3/6) received corticosteroids. We calculated the progression-free survival (PFS), the progression-free survival at 6 months (PFS-6) and the overall survival at 12 months (OS-12). As a secondary objective we assessed the somatostatin receptor expressing tumor volume (SSTR-TV), the total lesion somatostatin receptor expression (TL-SSTR), the SUVmax of the tumor, the pituitary gland and the liver on the [68Ga]Ga-DOTA-TOC PET/CT using Syngo.via software.

RESULTS
The mean age is 61±11.5 years, men:women 1:1. All patients were diagnosed with WHO grade II meningioma, 83% (5/6) with multifocal involvement, 83% (5/6) with intracranial location and 17% (1/6) had a spinal meningioma. One patient had the NF2 mutation. All patients have previously been treated with surgery and radiotherapy as first line treatment, achieving total resection (Simpson grade II) in 50%. 33.3% (2/6) of the patients received [177Lu}Lu-DOTA-TATE as a first line treatment post-recurrence, 33.3% (2/6) as a second line after proton therapy or [177Lu}Lu-DOTA-TATE (retreatment) and 33% (2/6) as a fourth line after somatostatin analogues, mTOR and angiogenesis inhibitors or others. The treatment has been well tolerated, showing asthenia in 50% (3/6), alopecia in 33% (2/6) and mild haematological toxicity in 50% (3/6) of the patients, two of them with multiple previous lines of systemic therapy. The PFS is 14.5 months, PFS-6 was achieved by 83%, and OS-12 is 100%. The patient with the lowest lesion SUVmax (5.2) and the lowest TL-SSTR (23.6 SUV-lbm x cm3) had the shortest PFS (6 months) and the patient with the highest SSTR-TV (68.2 cm3) and TL-SSTR (4206.78 SUV-lbm x cm3) had PFS of 7 months, significantly less than the cohort average. The best responder (17 months) had a small SSTR-TV (12 cm3) with a high TL-SSTR (165 SUV-lbm x cm3).

CONCLUSION
The treatment with [177Lu]Lu-DOTA-TATE in recurrent meningiomas is safe, well tolerated and demonstrates comparable PFS, PFS-6 and OS-12 with other systemic therapies. The total tumor burden (SSTR-TV) and the total lesion somatostatin receptor expression (TL-SSTR) might have an important role in patient selection and therapeutic outcome prediction.
P19.10.A POST-OPERATIVE HYPOFRACTIONATED RADIOSURGERY FOR INTERMEDIATE RISK MENINGIOMA
Authors: Ghosh D , Conger R , Choudhury A , Nguyen M P , Sethi I , Viner J , Oberheim Bush N , Morshed R A , Goldschmidt E , Braunstein S E , Raleigh D R , Chen W C 
Published: October 2024

Abstract

BACKGROUND
Conventional post-operative radiotherapy (RT) after resection of intermediate risk meningioma requires daily outpatient treatment for 6 weeks or more, which impose logistic and financial burdens on patients and the healthcare system. Although shortened course hypofractionated radiosurgery (hypoSRS) over 3 to 5 days has been applied for intact WHO grade 1 or imaging-defined meningiomas, no studies report on post-operative hypoSRS targeting the resection cavity after gross total resection (GTR) of intermediate risk meningiomas. To address this limitation in treatment for patients with the most common primary intracranial tumor, this retrospective case series investigated preliminary safety and efficacy data for patients undergoing hypoSRS after GTR of intermediate risk meningiomas.

MATERIAL AND METHODS
Seven patients (median age 62.2, interquartile range [IQR] 53.9-71.2, 57.1% female) who underwent GTR of intermediate risk meningioma, defined as primary WHO grade 2 (5 of 7, 71.4%), recurrent WHO grade 1 (1 of 7, 14.3%), or WHO grade 1 with a high risk molecular feature (1 of 7, 14.3%, BAP1 deletion), followed by post-operative hypoSRS, were identified. Meningiomas had a median of 4 mitoses/10 hpf (IQR 3-5) and MIB1 labeling index of 6.5% (IQR 4-8.5%) and were located at the convexity (4 of 7, 57.1%) or parasagittal regions (2 of 7, 28.6%). An institutional targeted DNA sequencing panel was performed on 4 of 7 meningiomas (57.1%). Of these, 3 were intermediate molecular risk (integrated grade 2) and 1 was high molecular risk (integrated grade 3). The hypoSRS target was comprised of at-risk dura and the resection bed without any expansion into brain parenchyma.

RESULTS
Patients were treated with a median dose of 30Gy in 5 daily fractions (range 25-30Gy, prescribed to a median 87% [IQR 68-89%] isodose line) to a median target volume of 13.6cc (range 7.4-49.9). Four patients were treated with linear accelerator based hypoSRS and 3 with frameless Gamma Knife Icon. Median volume of brain receiving at least 24Gy (V24Gy) was 7.8cc (IQR 3.0-18.0). At a median of 2.4 years of follow up (IQR 1.0-3.7), there were no recurrences, no occurrences of radionecrosis, and no CTCAEv5 G3+ toxicities.

CONCLUSION
As an alternative to 6 weeks of conventional post-operative RT, this case series suggests that hypoSRS is a safe and convenient treatment for patients with favorable anatomy after resection of intermediate risk meningioma. Larger studies with longer follow up are needed, and a future prospective trial of this approach is planned.
P19.12.A QUANTIFICATION OF DIVERSE IMMUNE CELL SUBSETS IN PRIMARY MENINGIOMAS
Authors: Giuliani Canizales N , Lotsch C , Warta R , Jassowicz L , von Deimling A , Sahm F , Unterberg A , Herold-Mende C 
Published: October 2024

Abstract

BACKGROUND
Meningiomas (MGM) often exhibit clinically aggressive progression, although being primarily benign. Immunotherapy could be an alternative treatment, but knowledge regarding meningioma immunobiology remains limited. This study delved into less explored subtypes, such as B cells, NK cells, and granulocytes, to analyze their associations with disease progression and cell-cell relations.

MATERIAL AND METHODS
A cohort comprising 100 primary MGM cases was used, including all WHO grades (°1, °2, and °3), and DNA methylation classes (MCs; benign, intermediate, and malignant). To quantify infiltration of T cells, B cells, NK cells, neutrophils, and eosinophils, tumor tissue cryo-sections were obtained from the institutional biobank. Immunofluorescence stainings were performed on tumor cryo-sections and digitized as high-resolution multiple image alignments for semi-automated cell counting. The infiltration rates were then correlated with clinical data, including clinical grading, age, sex, progression-free survival (PFS) and overall survival.

RESULTS
Each subtype´s median cell infiltration varied, with T cells (0.64%) having the highest, followed by neutrophils (0.079%), B cells (0.003%), NK cells (0.006%), and eosinophils (0.0018%). B cell infiltration correlated with increasing T cells, as did eosinophils with neutrophils. WHO°1 cases exhibited higher NK cell and eosinophil infiltration compared to other WHO grades. High NK cell infiltration was characteristic of the benign MC. Neutrophils and NK cells infiltrated more in the younger sub-population (&lt;61yo). Overall, patients with higher PFS tended to have higher infiltration of T cells, NK cells, and eosinophils, but lower B cells and neutrophils. Aggregates of T cells and B cells were found in 10% of cases, which also showed high infiltration rates of all cell types and higher PFS.

CONCLUSION
This study provides infiltration rates of rarer immune cell subtypes and their variation with clinical grading, age, and sex, as well as their relevance for MGM progression.
P20.01.B A MONO-INSTITUTIONAL RETROSPECTIVE ANALYSIS OF MENINGEAL SOLITARY FIBROUS TUMOR/ HEMANGIOPERICYTOMA: CLASSIFICATION AND GRADING SCHEMES CORRELATION WITH OUTCOME
Authors: Redaelli V , Patanè M , Pinzi V , Del Bene M , Gaviani P , Botturi A , Simonetti G , Calatozzolo C , Silvani A , Pollo B , Marucci G 
Published: October 2024

Abstract

BACKGROUND
The aim of the present study was to enrol a large mono-institutional cohort of patients affected by meningeal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC), collecting all available clinical features and information about treatments and outcomes, in order to: - classify this population according to the 2021 WHO CNS Classification and comparing that with the previous 2016 WHO Classification; - better characterize and analyse the prognostic significance of clinical and pathological variables; - identify patients with high risk of recurrence and metastases, to improve the management of these neoplasms, with benefits also for health service

MATERIAL AND METHODS
This retrospective study included 77 patients with histopathologically proven SFT/HPC. Reclassification according to the 2021 and 2016 WHO guidelines was done. Progression-free survival (PFS) and Overall Survival (OS) were evaluated for all patients.

RESULTS
The median follow-up period was 105 months. The median PFS and OS were 106 and 154 months, respectively. Correlating OS of patients to WHO grading we observed that all Grade 1 patients according to the 2016 WHO Classification are all still alive, while only 57% of patients with Grade 1 according to the 2021 WHO Classification are alive. At the same time, only 18% of patients with Grade 1 according to the 2016 WHO Classification relapsed, while 50% of patients with Grade 1 according to the 2021 WHO Classification relapsed. These differences resulted statistically significant (p&lt;0.05). Regarding Grades 2 and 3 cases, the differences between the WHO Classifications did not reach the level of significance.

CONCLUSION
In conclusion, the 2016 WHO Classification of SFT/HPC demonstrated a greater ability to discriminate aggressive from more indolent cases, in comparison to the 2021 WHO Classification.
P20.07.A CLINICAL OUTCOMES OF LOW-GRADE INTRACRANIAL GANGLIOGLIOMA IN ADULT POPULATION
Authors: Kulkarni J , Hutton D , Syed K , Cearns M D , Mills S J , Jenkinson M D 
Published: October 2024

Abstract

BACKGROUND
Gangliogliomas are rare, primary tumors of the central nervous system that occur more commonly in the paediatric and young adult demographic. While they are generally low-grade and have a favorable prognosis, tumor recurrence and progression to malignancy may occur. The aim of this study was to investigate risk factors for recurrence and the outcomes of intracranial ganglioglioma in the adult population.

MATERIAL AND METHODS
Thirteen adult patients with WHO grade 1 and 2 ganglioglioma were identified retrospectively from patient database at a tertiary neurosurgical center between 2010 and 2022. Patient characteristics, MRI features, tumor location, clinical and seizure outcomes were obtained. Surgical treatment strategies were categorized into subtotal (STR) or gross total resection (GTR).

RESULTS
Median patient age was of 29.0 years with 84.6% (n=11) temporal lobe tumors and the most common presentation (69.2%) being seizures. STR and GTR were achieved in five and nine patients, respectively. Adjuvant radiotherapy was not administered to any patient. Only one patient with STR had a recurrence at 65 months during the median follow up period of 6.5 years. Two patients had persisting seizures at last outpatient follow-up. There were no deaths.

CONCLUSION
Adult intracranial gangliogliomas WHO grade 1 or 2 have an extremely favorable prognosis with a recurrence rate of less than 10%. In cases where GTR is achieved, long term MRI surveillance is not required. Patients can be safely discharged after annual MRI for 3 years post surgical treatment. In patients where STR is achieved, annual MRI surveillance is required although the recurrence and progression rates remain low.
P20.20.B SINGLE-CENTER EXPERIENCE IN THE MANAGEMENT OF ADULT MEDULLOBLASTOMAS: A RETROSPECTIVE ANALYSIS
Authors: Kamer S , Karaman E , Acar M , Anacak Y 
Published: October 2024

Abstract

BACKGROUND
Medulloblastoma is a type of brain tumor that is less common in adults than in children. The standard treatment involves surgically removing as much of it as possible, followed by radiation therapy and chemotherapy. However, because this type of tumor is rare in adults, there is limited information available about its clinical characteristics and prognostic factors. This study aims to investigate the clinical features and treatment outcomes of adult patients who received postoperative radiotherapy for medulloblastoma at a single tertiary center.

MATERIAL AND METHODS
Patients aged 18 or above with a pathologic confirmation of medulloblastoma diagnosis who received postoperative craniospinal irradiation (CSI) at our institution between 2000-2021, was included in the study. Radiotherapy was administered with 3D conformal technique initially to whole cranium and spinal axis to 36Gy, followed by 18Gy boost to posterior fossa or tumor bed with 1.8Gy per fraction. Clinical characteristics, prognostic factors and survival outcomes were obtained from follow-up visits and electronic health records.

RESULTS
31 cases (median age:28 (19-44)) were analyzed, of which 54.8% were male. The pathologic diagnoses comprised of 51.6% for desmoplastic/nodular histology, 41.6% classical histology and 6.4% anaplastic histology. 25 cases were at non-metastatic stage according to Chang Classification. Total tumor resection (residual disease &lt;1.5cm2) was achieved in 83.9% cases. Twenty-one cases (67.7%) were categorized as standard risk, while ten were classified as high-risk group. Median treatment time was 47 days (38-71) and time between surgery and radiotherapy was 44 days (14-110). Median follow-up time was 91 months. Overall, 70.4% of patients were alive and no evidence of disease while 8 of patients were deceased. Six deaths were due to disease progression, one to traumatic intracranial hemorrhage, and the cause of death for one patient could not be obtained. 5 and 10-year overall survival was found to be 89.4% and 71.9%, respectively. Sex, histopathologic subtype, risk group were not found to be statistically significant prognostic factors, whereas a prolonged duration between surgery and radiotherapy (&gt; 6 weeks) correlated adversely with prognosis (p: 0.025). Relapse-free survival was estimated to be 71.8% and 68.2% for 5- and 10-years, respectively. Nine recurrences occurred, all being in primary site with two also recurred in spinal axis. Seven cases received surgery, five received chemotherapy and five cases received radiotherapy as a salvage treatment. Five of nine patients were deceased due to disease progression after salvage treatment.

CONCLUSION
Adult patients with medulloblastoma have a better prognosis compared to pediatric patients. Craniospinal irradiation is a crucial part of local treatment. Extended follow-up is needed to monitor for recurrence and toxicity.