High-grade Gliomas Research Articles

A patient with heterochronous double primary tumor of basal ganglia germ cell tumors followed by diffuse hemispheric glioma: a case report.

Basal ganglia germ cell tumor (BGGCT) is a rare central nervous system (CNS) tumor. Diffuse hemispheric gliomas, H3 G34-mutant (DHGs) is an invasive glioma involving the cerebral hemispheres. The diagnosis of DHGs depends on the integration of histopathology and molecular pathology. We reported a patient with an initial diagnosis of BGGCT that was sensitive to subsequent chemoradiotherapy. Unfortunately, a second high-grade glioma was found on magnetic resonance imaging (MRI) six years later. Subsequently, the tumor was completely removed after surgery and the following histopathology plus next generation sequencing (NGS) testing confirmed the diagnosis of DHGs. Interestingly, we found a germline likely pathogenic variant in FANCA. After surgery, the patient received Stupp regimen. The patient had a relapse 13months after the Stupp regimen and was doing well after surgery. This is the first report of a patient with heterochronous double primary tumor of BGGCT followed by DHGs.

Predictive and Explainable Artificial Intelligence for Neuroimaging Applications

Background: The aim of this review is to highlight the new advance of predictive and explainable artificial intelligence for neuroimaging applications. Methods: Data came from 30 original studies in PubMed with the following search terms: “neuroimaging” (title) together with “machine learning” (title) or ”deep learning” (title). The 30 original studies were eligible according to the following criteria: the participants with the dependent variable of brain image or associated disease; the interventions/comparisons of artificial intelligence; the outcomes of accuracy, the area under the curve (AUC), and/or variable importance; the publication year of 2019 or later; and the publication language of English. Results: The performance outcomes reported were within 58–96 for accuracy (%), 66–97 for sensitivity (%), 76–98 for specificity (%), and 70–98 for the AUC (%). The support vector machine and the convolutional neural network registered the best performance (AUC 98%) for the classifications of low- vs. high-grade glioma and brain conditions, respectively. Likewise, the random forest delivered the best performance (root mean square error 1) for the regression of brain conditions. The following factors were discovered to be major predictors of brain image or associated disease: (demographic) age, education, sex; (health-related) alpha desynchronization, Alzheimer’s disease stage, CD4, depression, distress, mild behavioral impairment, RNA sequencing; (neuroimaging) abnormal amyloid-β, amplitude of low-frequency fluctuation, cortical thickness, functional connectivity, fractal dimension measure, gray matter volume, left amygdala activity, left hippocampal volume, plasma neurofilament light, right cerebellum, regional homogeneity, right middle occipital gyrus, surface area, sub-cortical volume. Conclusion: Predictive and explainable artificial intelligence provide an effective, non-invasive decision support system for neuroimaging applications.

Out-of-pocket costs for patients diagnosed with high-grade glioma and their carers

Abstract Background This study aimed to describe the out-of-pocket costs incurred by patients diagnosed with high-grade glioma and their carers in the standard care arm of the Care-IS trial in the six to eight months following their diagnosis. Methods Carers completed monthly cost surveys detailing the out-of-pocket costs incurred by patients and carers over a six-month period. Seventy carers reported out-of-pocket costs at baseline (within two months following patient diagnosis), and a maximum of 50% of participants reported costs in any subsequent month. Costs were adjusted to 2023 AUD and reported as medians with interquartile range. Demographic factors were assessed to determine if any were significantly associated with being in the first or fourth quartile of total out-of-pocket costs at baseline. Results Median monthly costs for patient-carer dyads were highest at baseline ($535(IQR:$170-$930)), and two months post-recruitment ($314 (IQR:$150-$772)). The largest contributors to patient-carer costs were patient health service use and patient medications. Patient and carer health service use and medication costs varied over time. The median health service use and medication out-of-pocket costs for patients and carers were mostly below $100 per month, however, there was large variance in the upper 75th percentile for these cost categories. No factors were significantly associated with higher baseline out-of-pocket costs. Conclusion A HGG diagnosis has a significant and sustained financial impact on people who are diagnosed and their carers. Patients experience significant additional costs relating to their diagnosis and travel to receive care, and their carers also continue to experience sustained costs whilst managing the additional tasks associated with informal caregiving.

Unite and Conquer: Association of Two G-Quadruplex Aptamers Provides Antiproliferative and Antimigration Activity for Cells from High-Grade Glioma Patients

Background: High-grade gliomas remain a virtually incurable form of brain cancer. Current therapies are unable to completely eradicate the tumor, and the tumor cells that survive chemotherapy or radiation therapy often become more aggressive and resistant to further treatment, leading to inevitable relapses. While the antiproliferative effects of new therapeutic molecules are typically the primary focus of research, less attention is given to their influence on tumor cell migratory activity, which can play a significant role in recurrence. A potential solution may lie in the synergistic effects of multiple drugs on the tumor. Objectives: In this study, we investigated the effect of combined exposure to bi-(AID-1-T), an anti-proliferative aptamer, and its analog bi-(AID-1-C), on the migratory activity of human GBM cells. Results: We examined the effects of various sequences of adding bi-(AID-1-T) and bi-(AID-1-C) on five human GBM cell cultures. Our findings indicate that certain sequences significantly reduced the ability of tumor cells to migrate and proliferate. Additionally, the expression of Nestin, PARP1, L1CAM, Caveolin-1, and c-Myc was downregulated in human GBM cells that survived exposure, suggesting that the treatment had a persistent antitumor effect on these cells.

Targeting the RAS/MAPK pathway in children with glioma.

Pediatric gliomas are the most common brain tumor in children, encompassing both low-grade glioma (pLGG) and high-grade glioma (pHGG). Alterations in the RAS/MAPK pathway are the driver event in the majority of pLGG and account for a subset of pHGG. Identification of these alterations has resulted in the transition to targeted therapy as a treatment option. In pLGG, multiple trials have demonstrated superior outcomes using targeted therapy compared to traditional chemotherapy regimens. This has transformed care for these patients over the past decade with targeted therapy moving into front-line treatment regimens in certain scenarios. Despite these advances, novel targeted therapy approaches continue to present unique challenges to patient care, including optimal duration of therapy, distinct toxicity profiles and the unknown potential impact on the natural history of disease. While targeted therapy has revolutionized treatment of pLGG, additional questions remain in regard to pHGG including the role of targeted therapy in combination with other treatments, such as chemotherapy/radiation, and mechanisms of resistance. These developments are promising treatment options for pediatrics gliomas, enabling a move towards precision medicine. Herein, we review the role of RAS/MAPK targeted therapy for treatment of pediatric glioma along with the current controversies and outstanding questions.

Commentary: Use of a Single-Fiber Optical Probe for the Detection of Tumor Fluorescence in High-Grade Glioma.

Commentary: Use of a Single-Fiber Optical Probe for the Detection of Tumor Fluorescence in High-Grade Glioma.

A novel scoring system proposal to guide surgical treatment indications for high grade gliomas in elderly patients: DAK-75.

High-grade gliomas are the most prevalent neurooncological desease in adults, their incidence increases with age, peaking in the seventh decade. This paper aims to address how to select patients for surgical resection by identifying pre-surgical predictors of 12-month mortality in newly diagnosed HGG patients aged ≥ 75years. A prognostic score will be proposed to guide surgical decisions based on expected survival. Retrospective observational single-center cohort study was carried out at the "Città della Salute e della Scienza-Molinette" University Hospital in Turin, Italy. All consecutive patients aged ≥ 75years newly diagnosed with HGG were included, regardless of whether they underwent surgical resection. Clinical, radiological, histological and molecular data were collected.Variables potentially available at the time of diagnosis were considered to develop a multivariable logistic regression predictive model, with 12-months overall survival as the dependent variable. 102 patients aged 75years or older received a new diagnosis of high-grade glioma, of whom 68 underwent surgical resection. Patients undergoing surgery were slightly younger (76.9 vs 79.0years, p = 0.007) and had better performance status (median KPS 80 vs 70). Most tumors undergoing surgery were localized in cortical or subcortical non-motor areas (p < 0.001) and less frequently deep-seated (p = 0.023) or multifocal (p < 0.001). A predictive model, the DAK-75 score, was developed: the AUROC of the final model was 0.822 (95% CI 0.741-0.902). The score includes clinical presentation, tumor location, and KPS, ranging from 0 to 20, categorizing risk scores into low-risk and high-risk groups (< or > 8). Higher scores corresponded to fewer surgical patients and higher one-year mortality rates (92.2% vs 47.1%, p < 0.001). DAK-75 score may represent a valuable tool in the decision-making process for neurosurgical intervention in elderly patients diagnosed with HGG. Further studies are needed to externally and prospectively validate the scoring system.

Spatial transcriptomics analysis identifies therapeutic targets in diffuse high-grade gliomas

IntroductionDiffuse high-grade gliomas are the most common malignant adult neuroepithelial tumors in humans and a leading cause of cancer-related death worldwide. The advancement of high throughput transcriptome sequencing technology enables rapid and comprehensive acquisition of transcriptome data from target cells or tissues. This technology aids researchers in understanding and identifying critical therapeutic targets for the prognosis and treatment of diffuse high-grade glioma.MethodsSpatial transcriptomics was conducted on two cases of isocitrate dehydrogenase (IDH) wild-type diffuse high-grade glioma (Glio-IDH-wt) and two cases of IDH-mutant diffuse high-grade glioma (Glio-IDH-mut). Gene set enrichment analysis and clustering analysis were employed to pinpoint differentially expressed genes (DEGs) involved in the progression of diffuse high-grade gliomas. The spatial distribution of DEGs in the spatially defined regions of human glioma tissues was overlaid in the t-distributed stochastic neighbor embedding (t-SNE) plots.ResultsWe identified a total of 10,693 DEGs, with 5,677 upregulated and 5,016 downregulated, in spatially defined regions of diffuse high-grade gliomas. Specifically, SPP1, IGFBP2, CALD1, and TMSB4X exhibited high expression in carcinoma regions of both Glio-IDH-wt and Glio-IDH-mut, and 3 upregulated DEGs (SMOC1, APOE, and HIPK2) and 4 upregulated DEGs (PPP1CB, UBA52, S100A6, and CTSB) were only identified in tumor regions of Glio-IDH-wt and Glio-IDH-mut, respectively. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses revealed that upregulated DEGs were closely related to PI3K/Akt signaling pathway, virus infection, and cytokine-cytokine receptor interaction. Importantly, the expression of these DEGs was validated using GEPIA databases. Furthermore, the study identified spatial expression patterns of key regulatory genes, including those involved in protein post-translational modification and RNA binding protein-encoding genes, with spatially defined regions of diffuse high-grade glioma.DiscussionSpatial transcriptome analysis is one of the breakthroughs in the field of medical biotechnology as this can map the analytes such as RNA information in their physical location in tissue sections. Our findings illuminate previously unexplored spatial expression profiles of key biomarkers in diffuse high-grade glioma, offering novel insight for the development of therapeutic strategies in glioma.

Response assessment in pediatric neurooncology (RAPNO) criteria revisited: a practical navigation guide for neuroradiologists.

The Response Assessment in Pediatric Neuro-Oncology (RAPNO) Working Group is an international, collaborative network of experts dedicated to pediatric central nervous system (CNS) tumors that was created in 2011. Since then, six RAPNO articles with imaging guidelines for response assessment in diverse pediatric tumor subgroups have been published, namely: 1) medulloblastomas and leptomeningeal seeding tumors (2018), 2) pediatric high-grade gliomas (2020), 3) pediatric low-grade gliomas (2020), 4) diffuse intrinsic pontine gliomas (2020), 5) pediatric intracranial ependymomas (2022) and 6) pediatric craniopharyngiomas (2023). The purpose of this article is to review all current available RAPNO criteria using a systematized and comparative approach centered on the role of neuroradiologists and supported by neuroimaging examples. Special emphasis will be placed on clarification of core concepts as well as practical adoption aspects of the RAPNO guidelines, namely how and when to image the brain and/or the spine; how to interpret the imaging findings; which other clinical, therapeutic and laboratory variables to consider; and finally how to apply the information to attribute the final appropriate response assessment classification.

Correlation of Pre-Operative Myo-Inositol/Creatine Ratio with Histopathological Grade of Glioma

Background: Introduction: Gliomas are the most frequent primary intracerebral tumors in adults &amp; constitute 35–50% of all intracranial neoplasms. In determining a treatment plan, tumor grade is a key consideration for minimizing the risk of unnecessary morbidity and mortality. Objective: To evaluate Correlation of pre-operative Myo-inositol/Creatine ratio with histopathological grade of glioma. Materials and method: This was a cross sectional experimental study. Total 33 patients consistent with selection criteria were enrolled in this study. Myo-inositol/ Creatine ratio was obtained from MRS. Histopathological grade of glioma was obtained from biopsy (hematoxylin and eosin stain or HE stain) report. The obtained results were then grouped categorically. Result: Out of 33 patients, 22 were male and 11 were female. According to histopathology, 14 gliomas were confirmed as high grade and 19 gliomas were confirmed as low grade. Spearman Rank Correlation Test showed a moderate negative association between Myo-inositol/Creatine ratio with glioma grading with coefficient value of r = -0.611 with a statistically significant p-value (p&lt;0.001). We were able to differentiate between low grade (II) and high grade (III + IV) gliomas using the Myoinositol/ Creatine ratio. The levels of MI/Cr were higher (e”0.48) in patients with lowgrade glioma, and lower (&lt;0.48) in patients high grade glioma Conclusion: This study has shown a significant correlation between pre-operative Myo-inositol/Creatine ratio with histopathological grade of glioma. It may help neurosurgeons in taking clinical decisions about patient management and counselling. Bang. J Neurosurgery 2024; 13(2): 57-63

CAA-ri Masquerading as a High-Grade Glioma: A Case Report

CAA-ri Masquerading as a High-Grade Glioma: A Case Report

Oxime Linked Doxorubicin Glycoconjugates Improve the Specific Targeting of Glioblastoma in High-Grade Glioma Therapy

Oxime Linked Doxorubicin Glycoconjugates Improve the Specific Targeting of Glioblastoma in High-Grade Glioma Therapy

Neurosurgical application of olaparib from a thermo-responsive paste potentiates DNA damage to prolong survival in malignant glioma.

There is increased pan-cancer specific interest in repurposing the poly adenosine diphosphate-ribose polymerase-1 (PARP-1) inhibitor, olaparib, for newly diagnosed or recurrent isocitrate dehydrogenase wild type glioblastoma. We explore whether intra-cavity delivery of olaparib confers a survival benefit in a pre-clinical high-grade glioma model. Primary tumor RNA sequencing data was used to determine PARP-1 as a target in the glioblastoma infiltrative margin. We assessed radiosensitization conferred by olaparib alone and concomitant to genotoxic insults in vitro using clonal growth assays, cell cycle analysis and immunocytochemistry, and in vivo upon post-surgical delivery from a temperature-sensitive polymeric paste. RNA-sequencing confirmed PARP-1 as a viable therapy target in glioblastoma infiltrative disease. Acute exposure of glioma cells to olaparib impaired proliferation and induced late-stage apoptosis associated with DNA damage in vitro, potentiated by radiation. Using high-grade glioma orthotopic allografts, a long-term overall survival benefit was observed upon interstitial olaparib delivery concomitant with radiotherapy, compared to systemic olaparib and standard glioblastoma treatment. Combined delivery of olaparib with either temozolomide or etoposide increased long-term survival, suggestive of olaparib functioning as DNA damage sensitizer. Collectively, our data support a rationale for localized olaparib delivery concomitant with the current clinical regimen for malignant glioma treatment.

Tectal glioma: clinical, radiological, and pathological features, and the importance of molecular analysis.

Tectal glioma (TG) is a rare lower grade glioma (LrGG) that occurs in the tectum, mainly affecting children. TG shares pathological similarities with pilocytic astrocytoma (PA), but recent genetic analyses have revealed distinct features, such as alterations in KRAS and BRAF. We conducted a retrospective review of cases clinically diagnosed as TG and treated at our institute between January 2005 and March 2023. Six cases were identified and the median age was 30.5years. Four patients underwent biopsy and two patients underwent tumor resection. Histological diagnoses included three cases of PA, one case of astrocytoma, and two cases of high-grade glioma. The integrated diagnosis, according to the fifth edition of the World Health Organization Classification of Tumours of the central nervous system, included two cases of PA and one case each of diffuse high-grade glioma; diffuse midline glioma H3 K27-altered; glioblastoma; and circumscribed astrocytic glioma. Among the three patients who underwent molecular evaluation, two had KRAS mutation and one had H3-3A K27M mutation. Our results demonstrate the diverse histological and molecular characteristics of TG distinct from other LrGGs. Given the heterogeneous pathological background and the risk of pathological progression in TG, we emphasize the importance of comprehensive diagnosis, including molecular evaluation.

Radiological Hypertrophic Olivary Degeneration Following Posterior Fossa Tumor Surgery

Hypertrophic olivary degeneration is a rare form of transsynaptic degeneration, caused by injury to the Dentato-rubro-olivary pathway (DROP). Radiologically this manifests as T2 hyperintensity, with or without enlargement of the inferior olivary nucleus (ION). The purpose of the study was to evaluate the incidence, associated imaging characteristics, potential etiologies, latency period, and temporal progression of HOD in patients undergoing surgical resection of posterior fossa tumors (PFTs). A retrospective analysis of patients with PFTs and post-surgical MRI scans was conducted. HOD was diagnosed based on ION signal abnormalities and size changes. Demographics, tumor characteristics, time to HOD onset, involved DROP components, and clinical symptoms were recorded. HOD was seen in 40 (6.2%) patients following PFT surgery. 26 patients were aged 17 or less while the rest were older than 17 years. Medulloblastoma was the most frequently diagnosed tumor type (n=25), followed by pilocytic astrocytoma (n=8), ependymoma (n=6), and high grade glioma (n=1). No statistical association was found between the development of HOD and tumor grade (p=0.882). Ataxia was the most commonly reported clinical symptom (n=15). The time elapsed between surgery and the diagnosis of HOD varied, with median intervals of 1 month, 5 months, and 37 months for different stages. Dentate nucleus was the most commonly affected component of the DROP (n=36). HOD is a frequently overlooked postoperative complication following PFT resection. Increased recognition of HOD by neuroradiologists is essential for timely diagnosis and avoidance of unnecessary diagnostic procedures.

A New Tool for Extracting Static and Dynamic Parameters from [18F]F-DOPA PET/CT in Pediatric Gliomas

Background/Objectives: PET imaging with [18F]F-DOPA has demonstrated high potential for the evaluation and management of pediatric brain gliomas. Manual extraction of PET parameters is time-consuming, lacks reproducibility, and varies with operator experience. Methods: In this study, we tested whether a semi-automated image processing framework could overcome these limitations. Pediatric patients with available static and/or dynamic [18F]F-DOPA PET studies were evaluated retrospectively. We developed a Python software to automate clinical index calculations, including preprocessing to delineate tumor volumes from structural MRI, accounting for lesions with low [18F]F-DOPA uptake. A total of 73 subjects with treatment-naïve low- and high-grade gliomas, who underwent brain MRI within two weeks of [18F]F-DOPA PET, were included and analyzed. Static analysis was conducted on all subjects, while dynamic analysis was performed on 32 patients. Results: For 68 subjects, the Intraclass Correlation Coefficient for T/S between manual and ground truth segmentation was 0.91. Using our tool, ICC improved to 0.94. Our method demonstrated good reproducibility in extracting static tumor-to-striatum ratio (p = 0.357); however, significant differences were observed in tumor slope (p &lt; 0.05). No significant differences were found in time-to-peak (p = 0.167) and striatum slope (p = 0.36). Conclusions: Our framework aids in analyzing [18F]F-DOPA PET images of pediatric brain tumors by automating clinical score extraction, simplifying segmentation and Time Activity Curve extraction, reducing user variability, and enhancing reproducibility.

Novel paediatric case of a spinal high-grade astrocytoma with piloid features in a patient with Noonan Syndrome

Noonan Syndrome (NS) is associated with an increased risk of low-grade central nervous system tumours in children but only very rarely associated with high-grade gliomas. Here we describe the first reported case of a spinal high-grade astrocytoma with piloid features (HGAP) in a child with NS. This case was a diagnostic and treatment dilemma, prior to whole-genome germline and tumour sequencing, tumour transcriptome sequencing and DNA methylation analysis. The methylation profile matched strongly with HGAP and sequencing identified somatic FGFR1 and NF1 variants and a PTPN11 germline pathogenic variant. Therapeutic targets were identified but also alterations novel to HGAP such as differential expression of VEGFA and PD-L1. The germline PTPN11 finding has not been previously described in individuals with HGAP. This case underscores the power of precision medicine from a diagnostic, therapeutic and clinical management perspective, and describes an association between HGAP and NS which has not previously been reported.

PRMT5 maintains tumor stem cells to promote pediatric high-grade glioma tumorigenesis.

Pediatric high-grade gliomas (PHGG) are aggressive, undifferentiated CNS tumors with poor outcomes, for which no standard-of-care drug therapy currently exists. Through a knockdown screen for epigenetic regulators, we identified PRMT5 as essential for PHGG cell growth. We hypothesized that, similar to its effect in normal cells, PRMT5 promotes self-renewal of stem-like PHGG tumor initiating cells (TICs) essential for tumor growth. We conducted in vitro analyses, including limiting dilution studies of self-renewal, to determine the phenotypic effects of PRMT5 KD. We performed ChIP-Seq to identify PRMT5-mediated epigenetic changes and performed gene set enrichment analysis to identify pathways that PRMT5 regulates. Using an orthotopic xenograft model of PHGG, we tracked survival and histological characteristics resulting from PRMT5 KD or administration of a PRMT5 inhibitor ± radiation therapy (RT). In vitro, PRMT5 KD slowed cell cycle progression, tumor growth and self-renewal, and altered chromatin occupancy at genes associated with differentiation, tumor formation and growth. In vivo, PRMT5 KD increased survival and reduced tumor aggressiveness; however, pharmacological inhibition of PRMT5 with or without RT did not improve survival. PRMT5 KD epigenetically reduced TIC self-renewal, leading to increased survival in preclinical models. Pharmacological inhibition of PRMT5 enzymatic activity may have failed in vivo due to insufficient reduction of PRMT5 activity by chemical inhibition, or this failure may suggest that non-enzymatic activities of PRMT5 are more relevant. Implications: PRMT5 maintains and promotes the growth of stemlike cells that initiate and drive tumorigenesis in pediatric high grade glioma.

P10.24.B PREDICTION OF PCFDNA LEVELS, PROGRESSION-FREE SURVIVAL, AND OVERALL SURVIVAL THROUGH MACHINE-LEARNING MODELS BASED ON MRI-DERIVED RADIOMIC FEATURES IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA

Abstract BACKGROUND Circulating cell-free DNA (ccfDNA) is a promising tool for monitoring patients with high-grade gliomas (HGGs) in addition to follow-up with conventional (cMRI) and advanced MRI (aMRI), which harbors an enormous amount of quantitative subvisual data that can be used to build models predicting disease behavior. Examining the relationship between ccfDNA levels and quantitative features extracted from cMRI and aMRI gives further insight into this novel biomarker, aiming to combine the biological value of ccfDNA and the spatial resolution of image biomarkers to improve HGGs monitoring. MATERIAL AND METHODS Features were extracted from each T1 post-contrast and FLAIR images by using the FLAIR hyperintensity and enhancement automatic segmentation tool (Pyradiomics software, v2.2.0). The radiomic dataset underwent Z-score normalization, feature reduction, and feature selection. Highly correlated features were excluded using a threshold of 0.9 person-correlation-coefficient. The ‘F_regression’ function was used to select the most important features concerning the ccfDNA concentration, Overall survival (OS), and progression-free survival (PFS). This dataset was used as input for four machine learning models: Linear Regression (LR), Support Vector Regression (SVR), Random Forest (RF), and least absolute shrinkage and selection operator (LASSO). Hyperparameter tuning was performed at the first training iteration of each model using a 4-fold cross-validation GridSearchCV and model-specific parameters. The train-test strategy involved randomizing datasets into 80% training and 20% testing subsets across 100 iterations, ensuring robustness and reducing biases. RMSE values of each run were averaged based on sample test frequencies. Root means square error (RMSE) was used to assess the model’s performance. RESULTS 405 features were successfully extracted from T1 post-contrast and FLAIR images from both tumoral masks. A total of 287 were found to be highly correlated and, therefore, removed from the dataset. The ‘F_regression’ with a 90-percentile threshold separates 12 features divided into 3 shapes features relative to FLAIR segmentation, 6 features relative to the T1 post-contrast image, and 3 features for the FLAIR image. The SVR achieves the best RMSE performances when compared to other models when predicting the ccfDNA concentration, reaching an RMSE of 8.58. An analogous strategy was used for the models built to predict PFS and OS reaching an RMSE of 5.89 and 6.77, respectively. CONCLUSION Machine-learning models based on radiomic features combined with clinical variables are valuable tools for predicting OS and PFS in HGGs’ patients. The radiomic signature provides additional information compared to the tumoral volume to forecast ccfDNA levels. Combining both techniques could provide more precise assessment of disease status.

P18.39.A SEIZURE PROPHYLAXIS IN GLIOMA SURGERY (SPRING): A MULTI-CENTRE, UNBLINDED, RANDOMISED TRIAL

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.