High-grade Astrocytomas Research Articles

SURG-52. LEPTOMENINGEAL DISSEMINATION AFTER GAMMATILE AND LITT IN HIGH GRADE ASTROCYTOMA PATIENTS

Abstract PURPOSE To present a case series of leptomeningeal dissemination after localized treatment with GammaTile or laser interstitial thermal therapy (LITT) in patients with high grade astrocytoma. BACKGROUND Leptomeningeal dissemination occurs primarily in glioblastoma patients with prolonged survival and those who undergo aggressive treatment courses. Targeted therapies such as GammaTile (which contains cesium-131 radiation-emitting seeds) or LITT may provide localized disease control following recurrence and serve as an immediate treatment modality for patients with recurrent disease in the weeks leading up to radiotherapy or systemic treatment. METHODS We retrospectively reviewed all consecutive patients with high grade astrocytoma treated with GammaTile or LITT who were found to have leptomeningeal dissemination of disease. Histological diagnosis, NGS and immunohistochemistry of tumor tissue were performed at both original diagnosis and at time of GammaTile placement or LITT procedure. Leptomeningeal dissemination was diagnosed through MRI findings on brain and spine. Cases were analyzed for time to development of leptomeningeal dissemination, median overall survival, survival from time of leptomeningeal dissemination diagnosis, time of dissemination to second radiation therapy. Tumor location, MGMT status and other molecular markers were also reviewed. RESULTS Out of 90 high grade astrocytoma patients treated with gamma tile radiation, 4 progressed to exhibit disseminated disease. There were 2 female patients, mean age was 50 years. Location of tumor was in the left temporal lobe in 3 patients and right temporal in 1. They were all IDH wild type. Two were MGMT methylated, two were non methylated. The median time from initial glioma diagnosis to LMD was 221 months (range 11-152) and overall survival after disseminated disease diagnosis was 7.5 weeks (range 3–13). CONCLUSION Leptomeningeal dissemination is a devastating complication of aggressive gliomas. Currently, there is no standard treatment for disseminated disease in high grade astrocytoma patients. Systemic therapy is needed following localized therapies to control disease. Further research into new therapies is needed to allow for better outcomes.

BIOM-32. GENOMIC DETERMINANTS OF DIFFUSELY INFILTRATIVE GLIOMATOSIS CEREBRI PATTERN

Abstract Gliomatosis cerebri (GC), though no longer a distinct pathological entity in WHO 2021, is a unique and aggressive phenotype of diffuse gliomas with extensive and widespread infiltration. GC can present as primary de novo or secondary after treatment. We aimed to study the genomic determinants of GC. We identified 72 GC cases from 2013-2023 at MD Anderson Cancer Center. Cases were confirmed by detailed radiographic review. This included 57 glioblastoma (79%), 13 IDH mutant astrocytoma (18%), 1 IDH mutant oligodendroglioma (1.4%), and 1 high-grade astrocytoma with piloid features (1.4%). 53/72 (73.6%) were primary and 19/72 (26.4%) were secondary GC. We used 40 patients without the GC pattern as controls. Among glioblastoma GC cases and in comparison with controls, mutations in PTEN and EGFR were significantly associated with the GC pattern: 18/57 (32%) vs 3/38 (7.9%), p-value=0.01 and 23/57 (40%) vs 6/38 (16%), p-value=0.013, respectively. This held true in primary but not secondary GC. Out of 20 most commonly mutated genes in GC, mutations in EGFR, TERT, and MDM4 were associated with worse PFS: p-value=0.004, p-value=0.007, p-value=0.013, respectively and mutations in TERT and MDM4, but not EGFR, were associated with worse OS: p-value=0.003, p-value=0.015, respectively. Secondary GC was associated with IDH mutation compared to control non-GC cases: 8/19 (42%) vs 2/40 (5%), p-value=0.001. As expected, IDH mutation was associated with improved PFS, p-value<0.001 and OS, p-value=0.003 in GC. No genes were significantly associated with laterality of GC. We found novel associations between PTEN and EGFR mutations and the GC phenotype and IDH mutation with the occurrence of secondary GC after treatment. While MDM4 is not associated with outcomes in gliomas, we show that MDM4 mutation is associated with poor survival in GC. These findings shed light into molecular basis of GC and need to be further validated in larger studies.

PATH-14. UTILITY OF DNA METHYLATION ANALYSIS IN HISTOLOGICALLY-CONFIRMED PA PATIENTS WITH POOR PROGNOSIS

Abstract INTRODUCTION Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, some PA patients experience unfavorable outcomes; advanced age was known as an independent poor prognostic factor. This study retrospectively reviewed PA patients and conducted molecular analyses for elderly patients. METHODS We analyzed data from 29 histologically confirmed PA patients treated at a single center from 2002 to 2021 and conducted integrated molecular analyses including DNA methylation profiling for elderly PA patients. RESULTS The median age at diagnosis was 14 years (range 3-82 years), with 4 patients (14%) being elderly (patients≥60years old). Elderly patients had significantly worse progression-free survival and overall survival. DNA methylation analysis was performed on 2 of the 4 elderly patients. Despite histological diagnoses of PA, methylation profiling classified one case as high-grade astrocytoma with piloid features (methylation class scores below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score over 0.5 in both v11b4 and v12.5), using classifiers from the German Cancer Research Center and t-SNE analysis. CONCLUSION Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.

CSIG-29. BRAF INHIBITOR THERAPY IN BRAF-MUTATED PRIMARY BRAIN TUMORS: A SINGLE-CENTER EXPERIENCE

Abstract BACKGROUND BRAF pathway alterations are frequent in glial/neuroepithelial tumors. BRAF-targeted therapy with BRAF inhibitors (BRAFi) and/or MEK inhibitors (MEKi) has proven efficacy in clinical trials, though mainly enrolling pediatric patients. We sought to investigate real-world data for adult patients with BRAF-pathway mutant glial/neuroepithelial neoplasms treated with BRAFi/MEKi. METHODS Adults with BRAF-pathway mutated glial/neuroepithelial neoplasms treated with BRAFi/MEKi were retrospectively reviewed. RESULTS Five patients (n=4 female, median age at diagnosis 36) were identified (tumor types: glioblastoma n=1, high-grade astrocytoma with epithelioid features n=1, low-grade neuroepithelial tumor n=1, pilocytic astrocytoma n=1, pleomorphic xanthoastrocytoma n=1). Four had BRAF V600E and one had NF1 p.S2687Cfs*5 mutant tumors. Prior to targeted therapy initiation, patients underwent a median 2.4 treatments including surgery (n=4), radiation therapy (n=4), chemotherapy (temozolomide n=4; carboplatin/vincristine n=1). BRAF-targeted therapies included dabrafenib/trametinib (n=4), binimetinib/encorafenib (n=2), binimetinib (n=2). One NF1-mutant glioblastoma received binimetinib followed by binimetinib/bevacizumab. Median BRAFi/MEKi treatment was 15.2 months (range: 6-36 months). Toxicities included leukopenia (n=3), peripheral edema (n=1), reduced ejection fraction (n=1), skin rash (n=5), transaminitis (n=1) with all patients requiring dose reductions and 3 cases requiring discontinuation. Among patients where BRAFi/MEKi was discontinued due to toxicity, 2 received other treatments at progression, then switched to a different BRAFi/MEKi combination, which they tolerated (duration 6-10months). Best radiographic response was partial response, noted in 3 patients treated with dabrafenib/trametinib. Four patients remain alive and continue BRAFi/MEKi. CONCLUSIONS In this cohort of heavily-pretreated patients with glial/neuroepithelial neoplasms, BRAF-targeted therapy was associated with durable responses. Interestingly, two patients who were unable to tolerate one combination of BRAFi/MEKi were able to tolerate a different combination with sustained response. Our findings support ongoing use of BRAF targeted therapy for CNS tumors. Optimal timing and duration of treatment requires further prospective evaluation in adult patients.

BIOM-02. A HIGH-GRADE GLIOMA, NOT ELSEWHERE CLASSIFIED IN AN OLDER ADULT WITH DISCORDANT GENETIC AND EPIGENETIC ANALYSES

Abstract World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) uses integrated diagnoses, which incorporates both histologic and molecular features of the neoplasms. With each new iteration, there is refinement and expansion of the diagnostic categories. DNA methylation profiling is a powerful technique to diagnose existing CNS tumors and define new tumor types. However, challenging diagnostic cases that do not conform to the updated WHO classification remain. We present a case of a 72-year-old male with a high grade glioma (HGG) suggestive of high grade astrocytoma with piloid features (HGAP), but it did not “match” to HGAP on DNA methylation profiling, which is essential diagnostic criterion for HGAP. This resulted in an HGG, not elsewhere classified (NEC) diagnosis. This lack of classification posed additional challenges for treatment decision-making.

CTIM-20. IDENTIFYING CANDIDATE ANTIGEN TARGETS FOR PEDIATRIC BRAIN TUMOR IMMUNOTHERAPIES THROUGH COMPREHENSIVE IMMUNOGENOMIC ANALYSIS

Abstract BACKGROUND Identifying tumor rejection antigens continues to be a significant challenge in the development of effective immunotherapies and their application to pediatric brain tumors. METHODS To identify candidate antigen targets for Medulloblastoma (primary MB, n=170; recurrent MB, n=21), Diffuse Intrinsic Pontine Glioma (DIPG, n=10), and Pediatric High-Grade Astrocytoma (HGA, n=12) for adoptive cellular therapy, we conducted a comprehensive immunogenomic analysis of the transcription profiles of the most aggressive pediatric brain tumors and performed in silico antigen prediction across a wide range of antigen classes. IMPORTANCE OF THE STUDY Pediatric brain tumors are heterogeneous diseases, and current standard treatments do not adequately address this variability. Newer and safer patient-specific treatment approaches are needed for high-risk patients who do not respond to standard therapies. Cellular immunotherapy could be crucial for improving survival and reducing morbidity. For an effective immune response against these brain tumors, appropriate tumor antigens must be targeted. While subgroup-specific genetic mutations in medulloblastoma patients have been reported, the immunogenicity of these genetic alterations remains unknown. Using a custom antigen prediction pipeline, we identified potential tumor rejection antigens with significant implications for the development of cellular therapies for MB, DIPG, and HGA. RESULTS Antigen prediction analysis revealed that most patients express few candidate neoantigen targets that pass all filtering criteria. Overall, the proportion of predicted tumor-associated antigens (TAAs) was higher than that of neoantigens and gene fusions for all molecular subtypes, except for SHH, which exhibited a higher neoantigen burden. Notably, cancer-testis antigens and previously unrecognized neurodevelopmental antigens were found to be expressed in most patients across all medulloblastoma subgroups. Although the absolute immune cell content is predicted to be low, immune gene-signature analysis revealed subgroup-specific differences.

High-grade astrocytoma with piloid features in the conus medullaris: a rare presentation of a new World Health Organization diagnosis. Illustrative case.

Neuroepithelial tumors with histological features of pilocytic astrocytoma (PA), increased mitotic activity with high-grade features of microvascular proliferation, and palisading necrosis have often been designated as anaplastic PAs. High-grade astrocytoma with piloid features (HGAP) was recently classified as its own entity by the World Health Organization (WHO) in 2021, after being grouped under anaplastic PA. This rare tumor typically arises in the cerebellum. The authors present the case of a patient with HGAP in the conus medullaris, a rare occurrence, with only 17 reported HGAP cases in other parts of the spinal cord. An 83-year-old female patient presented with progressive lower-extremity weakness over 2 weeks. Subsequent imaging revealed an intramedullary spinal cord mass near the conus. Histopathological analysis confirmed a neuroepithelial tumor. Chromosomal microarray revealed the diagnosis of HGAP, an exceedingly unusual tumor to be found near the conus. The tumor characteristics showed uniformly low cellularity and low proliferation of medium-sized ovoid cells with elongated nuclei, embedded in a loose pilocytic matrix. This report presents the case of a patient with HGAP in the conus medullaris, a new WHO diagnosis that needs to be included in the differential diagnosis for conus masses. https://thejns.org/doi/10.3171/CASE24390.

Correlation of degree and pattern of contrast enhancement on Magnetic Resonance Imaging with histopathological grade of intracranial astrocytoma

Background/Objective: Astrocytomas, a type of glioma, require accurate grading to guide treatment. This study evaluates the correlation between MRI contrast enhancement and histopathological grades of astrocytomas. Methods: A cross-sectional study of 37 patients with biopsy-confirmed astrocytomas was conducted. Non-probability or purposive sampling was carried out. MRI scans assessed contrast enhancement characteristics, and tumors were classified radiologically and histopathologically. Results: The age range of the patients was 11 to 74 years and mean age was 40.25±16.04 years. The male to female ratio was 4:1. Headache was the most common presenting symptoms (95%). Most of the tumors were located at the cerebral hemispheres (78%). None or slight contrast enhancement was found in 17 (46%) and the pattern of contrast enhancement was heterogeneous in 24 (65%) patients. Maximum 20 (54%) patients had high grade astrocytoma. In the present study, 85% high grade astrocytoma showed moderate to marked whereas 82.4% low grade astrocytoma showed none or slight contrast enhancement. Sensitivity & specificity of contrast enhanced MRI was 82.4% and 85% respectively. The overall accuracy was 83.78%. Conclusion: MRI is a reliable non-invasive tool for grading astrocytomas, with strong correlation between contrast enhancement and tumor grade, supporting its use in clinical decision-making. J Shaheed Suhrawardy Med Coll 2023; 15(1): 13-19

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.

Spinal diffuse midline glioma: An unusual case presentation

Primary spinal cord neoplasms are rare, accounting for 1% of paediatric central nervous system tumours. The majority of which are low-grade gliomas (LGG). A teenage male presented with rapidly progressive lower limb paralysis. He subsequently underwent a near-total resection of an intramedullary thoracic tumour. Although the initial histopathology report suggested a LGG, closer review of the morphology and immunohistochemical staining revealed a diffusely infiltrating high-grade astrocytoma. Methylation profiling later confirmed a H3K27M-mutated spinal DMG. He underwent spinal radiation to the tumour bed soon after surgery but succumbed to his disease 8 days after completing radiation, and 3 months after presentation.Conclusion: Spinal DMGs are rare, can lead to diagnostic challenges and have a poor prognosis.

Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case.

High-grade astrocytoma with piloid features (HGAP) is a novel condition introduced in the 2021 World Health Organization classification. Given that it has been recently classified, reports clarifying its clinical features or diagnostic criteria are lacking, especially in cases of atypical presentation. Herein, the authors present a rare case of HGAP with repeated symptomatic hemorrhages. A woman in her 20s presented with an acute headache and vertigo. Computed tomography and magnetic resonance imaging revealed a 2.5 × 2.8 × 2.3-cm hemorrhagic cerebellar mass with calcifications. After moderate improvement of her symptoms, she developed recurrent hemorrhage, and the tumor size increased (3.0 × 3.6 × 4.0 cm) 18 days later, necessitating resection. Pathological and molecular analyses confirmed the diagnosis of HGAP with an FGFR1-TACC1 fusion, MTAP/CDKN2A/B deletion, and SETD2 rearrangement. Radiologically, the presence of calcification and cystic components and the absence of perilesional edema were atypical features of previously reported HGAP. Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.

The Role of Radiotherapy, Chemotherapy, and Targeted Therapies in Adult Intramedullary Spinal Cord Tumors.

Intramedullary primary spinal cord tumors are rare in adults and their classification has recently evolved. Their treatment most frequently relies on maximal safe surgical resection. Herein, we review, in light of the WHO 2021 classification of central nervous system tumors, the knowledge regarding the role of radiotherapy and systemic treatments in spinal ependymomas, spinal astrocytomas (pilocytic astrocytoma, diffuse astrocytoma, spinal glioblastoma IDH wildtype, diffuse midline glioma H3-K27M altered, and high-grade astrocytoma with piloid features), neuro-glial tumors (ganglioglioma and diffuse leptomeningeal glioneuronal tumor), and hemangioblastomas. In spinal ependymomas, radiotherapy is recommended for incompletely resected grade 2 tumors, grade 3 tumors, and recurrent tumors not amenable to re-surgery. Chemotherapy is used in recurrent cases. In spinal astrocytomas, radiotherapy is recommended for incompletely resected grade 2 astrocytomas and grade 3 or 4 tumors as well as recurrent tumors. Chemotherapy is indicated for newly diagnosed high-grade astrocytomas and recurrent cases. In hemangioblastomas not amenable to surgery, radiotherapy is an effective alternative option. Targeted therapies are playing an increasingly important role in the management of some intramedullary primary spinal cord tumor subtypes. BRAF and/or MEK inhibitors have demonstrated efficacy in pilocytic astrocytomas and glioneuronal tumors, belzutifan in von Hippel-Lindau-related hemangioblastomas, and promising results have been reported with ONC201 in diffuse midline glioma H3-K27M altered.

Fractional tumor burden maps increase the confidence of reading brain MR perfusion

Rationale and objectivesVarious methods exist to perform and post-process perfusion weighted MR imaging in the post-treatment imaging of glioma patients to differentiate tumor progression from tumor-related abnormalities. One of these post-processing methods produces ‘fractional tumor burden’ maps. This multi-reader study investigated the clinical feasibility of fractional tumor burden maps on real world data from radiological follow-up of high-grade astrocytoma patients. MethodsFive readers with background in radiology and varying levels of experience were tasked with assessing 30 astrocytoma and glioblastoma patients during one reader session. First, they were provided with a dataset of conventional MRI sequences, including perfusion MRI with regional cerebral blood volume maps. Then the dataset was expanded with a corresponding fractional tumor burden maps. Diagnostic accuracy, duration of post-processing, duration of the assessment of the fractional tumor burden maps, the diagnostic confidence reported by the readers and their diagnoses were recorded. Final diagnosis was determined by clinical and radiological follow-up and/or histopathological data used as gold standard. ResultsA mean sensitivity of 83.3 % and mean specificity of 55.1 % was obtained without the use of fractional tumor burden maps, whereas their additional of fractional tumor burden maps resulted in a mean sensitivity and specificity of 79.5 % and 54.2 %, respectively. Diagnostic accuracies with and without fractional tumor burden maps were not significantly different (Z = 0.76, p = 0.450). The median time spent post-processing was 313 s, while the median duration of the assessment of the FTB maps was 19 s. Interestingly, reader confidence increased significantly after adding the fractional tumor burden-maps to the assessment (Z = 454, p < 0.01). ConclusionsWhile the use of fractional tumor burden maps does not carry additional value in the radiological follow-up of post-operative high-grade astrocytoma and glioblastoma patients, it does give readers more confidence in their diagnosis.

Unraveling morphology, methylation profiling, and diagnostic challenges in BRAF-Mutant pediatric glial and glioneuronal tumors.

To elucidate the relationship between DNA methylation profiling (DMP) and pathological diagnosis (PD) in pediatric glial and glioneuronal tumors with B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations, addressing their diagnostic challenges. This retrospective study, conducted in Saudi Arabia, analyzed 47 cases from the Children's Brain Tumor Network online database using scanned images, next-generation sequencing data, and methylation profiles processed using the Heidelberg methylation brain tumor classifiers v12.5 and v12.8. The data was last access on 10 November 2023. The highest prevalence of BRAF mutations was observed in pilocytic astrocytoma and ganglioglioma. The DMP was consistent with PD in 23 cases, but discrepancies emerged in others, including diagnostic changes in diffuse leptomeningeal glioneuronal tumor and polymorphous low-grade neuroepithelial tumor of the young. A key inconsistency appeared between a pilocytic astrocytoma MC and a glioneuronal tumor PD. Two high-grade astrocytomas were misclassified as pleomorphic xanthoastrocytomas. Additionally, low variant allelic frequency in gangliogliomas likely contributed to misclassifications as control in 5 cases. This study emphasized the importance of integrating DMP with PD in diagnosing pediatric glial and glioneuronal tumors with BRAF mutations. Although DMP offers significant diagnostic insights, its limitations, particularly in cases with low tumor content, necessitate cautious interpretation, as well as its use as a complementary diagnostic tool, rather than a definitive method.

NFS-08. CLINICAL AND MOLECULAR FEATURES OF HIGH-GRADE GLIOMA IN CHILDREN AND ADULTS WITH NEUROFIBROMATOSIS TYPE 1: A PRELIMINARY ANALYSIS

Abstract BACKGROUND Individuals with neurofibromatosis type 1 (NF1) are at increased risk for developing high-grade glioma (HGG) relative to the general population. Despite the elevated incidence in NF1, adequately powered studies of HGG have not been performed to date, limiting understanding of the clinical course, prevalent treatment approaches, recurrent molecular features, and outcomes. METHODS Patients with NF1 and pathologic or molecularly confirmed high grade glioma and high-grade astrocytoma with piloid features at Children’s Hospital of Philadelphia, University of California San Francisco, Washington University, and Cincinnati Children’s Hospital Medical Center diagnosed between 2005 to 2021 were included. Retrospective clinical, molecular, treatment, and imaging data were collated and analyzed. RESULTS Thirty-four patients met eligibility criteria, 13 (38%) were female. The median age at diagnosis was 22.7 years; 10 were pediatric (children &amp;lt;18 years of age). The most common diagnoses included high-grade astrocytoma (7), anaplastic astrocytoma (8), glioblastoma multiforme (5), and high-grade astrocytoma with piloid features (5). Fifteen (44%) of tumors underwent biopsy only and 4 (12%) were gross totally resected. Nine tumors (26%) were considered to have transformed from a pre-existing low-grade lesion. In the 22 cases with molecular testing, the most prevalent genetic variants involved the NF1, CDKN2A/B, ATRX, TP53, and SUZ12 genes. Frontline treatment approach varied; however, 26 individuals (76%) received radiation as part of their initial therapy. Overall survival at 2 years was 52% (95% CI 33-67) across all ages and 70% (95% CI 33-89) in children. There was no significant difference in overall survival at 2 years by extent of tumor resection at diagnosis. CONCLUSIONS High grade glioma in individuals with NF1 demonstrate a high prevalence of alterations in the CDKN2A/B and ATRX genes, with a poor overall survival despite radiation-inclusive treatment regimens. Collection of additional patient data from collaborating institutions is ongoing to support further analyses.

IMG-28. AUTOMATIC BRAIN TUMOR VOLUMETRIC ANALYSIS IN MAGNETIC RESONANCE IMAGING GENERALIZABLE TO PEDIATRIC NEURO-ONCOLOGY

Abstract BACKGROUND The prognosis of brain tumors is variable in clinical practice if it only relies on human interpretation of magnetic resonance imaging (MRI). The automatic segmentation of brain tumors in MRI enables quantitative analysis in support of clinical trials and personalized patient care. We developed benchmarked deep learning-based tools that are generalizable to the volumetric quantification of various tumor types across diverse populations. METHODS We participated in the well-established international brain tumor segmentation challenge (BraTS 2023) and benchmarking competition. The challenge made available 4,500 multi-national brain tumor cases with multi-sequence MRIs, including pediatric high-grade gliomas (PED), i.e., high-grade astrocytoma and diffuse midline glioma, and adult gliomas, brain metastases (MET) and intracranial meningiomas (MEN). Each case comprises four MRI volumes: T1, contrast-enhanced T1, T2, and T2-FLAIR. Manual segmentations were provided to establish ground truth for enhancing tumor (ET), tumor core (TC), and whole tumor (WT). Our framework used a model ensemble strategy based on two state-of-the-art deep learning models: a convolutional neural network (nnU-Net) and a vision transformer (Swin UNETR) and was tested for broader applicability across multiple tumor types. The framework was trained on 99, 1,000, and 165 cases and validated on 45, 141, and 31 unseen cases for PED, MEN, and MET, respectively. Automatic segmentations were evaluated by lesion-wise volume overlap (Dice similarity score, DSC) and Hausdorff distance (HD). RESULTS In the evaluation on independent unseen test datasets, our automatic tool was ranked first for PED, third for MEN, and fourth for MET volumetric analysis. Our method resulted in PED lesion-wise DSC of 0.733, 0.782, 0.817 and HD (mm) of 75.93, 25.54, 24.18 for ET, TC, and WT, respectively. CONCLUSIONS These brain tumor volumetric analysis tools are readily available to be efficiently tested on diverse datasets. Automatic MRI analysis provides consistent quantitative data for multi-institutional protocols and clinical trials.

EPID-09. CONGENITAL CENTRAL NERVOUS SYSTEM NEOPLASMS: A RETROSPECTIVE REVIEW FROM THEMARGARET HACKETT FAMILY PROGRAM CONSORTIUM

Abstract INTRODUCTION Congenital intracranial neoplasms are a heterogeneous group of lesions that account for &amp;lt;2% of pediatric CNS tumors. Current understanding of histopathologic and survival outcomes in this population is limited. METHODS Pediatric patients (&amp;lt;3-years) with congenital neoplasms were retrospectively evaluated across five institutions. Demographic, prenatal care, clinical presentation, histopathologic characteristics, operative and adjuvant therapies, and survival outcomes were collected. RESULTS 323 patients met inclusion. The mean age at diagnosis was 1.5-years. Six patients were conceived through IVF. Eleven families reported abnormal prenatal ultrasounds, although only six were diagnosed prenatally. The most common histopathologies included low-grade astrocytoma (30.6%), ependymoma (15.8%), ATRT (11.5%), medulloblastoma (8.0%), and high-grade astrocytoma (2.8%). 48.9% of patients had low-grade neoplasms, and a third of patients (33.1%) had high-grade tumors. Patients commonly presented with hydrocephalus (59.1%), emesis (34.7%), ocular abnormalities (20.4%), macrocrania (18.0%), lethargy (14.6%), developmental delays (12.7%), and irritability (11.8%). All patients received surgical resection: 55.4% received gross-total (GTR) and 20.4% received subtotal resection. Concurrent treatment with adjuvant therapies occurred in a subset of patients, with 52.9% of patients receiving chemotherapy, 27.2% undergoing radiation, and 6.2% participating in a clinical trial. Patients with low-grade tumors had a rate of 88% progression-free (PFS) at 1-year, 74% PFS at 3-years, and 64% PFS at 5-years post-operative. Patients with high-grade neoplasms had worse PFS, with estimates at 59%, 40%, and 37% at 1-, 3-, and 5-years, respectively. There was statistically significant differences in PFS between patients with high- and low-grade neoplasms (p&amp;lt;0.0001). CONCLUSIONS This series consisted of very young pediatric patients across five participating institutions with diverse histopathologies that vary in frequency relative to the entire pediatric population. Lesions were rarely detected prenatally, despite their young age at diagnosis. GTR occurred in half of patients and subsequent management with adjuvant therapies was common in both sub-totally resected low-grade lesions and high-grade tumors.

Single center experience of IDH inhibitors in high-grade gliomas.

e14036 Background: IDH inhibitors have shown to improve progression free survival in low grade gliomas. Antitumor effect in high-grade gliomas is not well known, with conflicting views regarding the role of IDH mutations in high-grade gliomas and the potential for resistance to DNA-damage-inducing therapies. We present the outcomes of high-grade gliomas that were treated in our institution with IDH inhibitors. Methods: We performed a retrospective review of patients with gliomas treated with FDA approved IDH inhibitors (ivosidenib and enasidenib) in the past 5 years at our institution (January 1st 2019- January 1st 2024). Our search identified 32 patients of which 11 were identified as high-grade gliomas (both oligodendrogliomas and astrocytomas). Institutional Review Board PA17-0222 was used for this study. Results: Eleven high grade, IDH-mutant glioma patients treated with IDH inhibitors were identified with a median age at diagnosis of 31 years; 63.6% of these patients were men. Over 63% of patients were categorized as WHO grade 3 and 36.4% as grade 4 tumors. Over 63% of patients were astrocytoma (4 out of 7 patients with WHO grade 4 astrocytoma) while the rest were oligodendrogliomas. All patients underwent initial resection and had received radiation plus at least one prior line of systemic therapy prior to starting an IDH inhibitor. Over 72% were started on IDH-inhibitor therapy after 3 or more recurrences; previous lines of systemic therapy included temozolomide, bevacizumab, and lomustine. Five patients were treated with more than 1 cycle of IDH inhibitor, 2 patients with 8 cycles, and 1 patient with 18 cycles. Of the 11 treated patients, four had progression while on an IDH inhibitor, of which one patient died. IDH inhibitors were discontinued in two patients (due to headaches and abnormal liver enzymes). Median survival and progression free survival after IDH inhibitors were not reached. Conclusions: IDH inhibitors were started on patients with high-grade astrocytoma and oligodendroglioma after multiple recurrences and after receiving DNA-damage-inducing therapies. Prolonged responses were observed in 3 patients (one oligodendroglioma and two WHO grade 3 astrocytomas). Further investigation is needed to establish the role for IDH inhibitors in the treatment of high-grade gliomas.

HIF-1α and VEGF Expression in Adult-type Diffuse High-Grade Astrocytoma

HIF-1α and VEGF Expression in Adult-type Diffuse High-Grade Astrocytoma

High-grade astrocytoma with piloid features: case report

High-grade astrocytoma with piloid features: case report