Adult Gliomas Research Articles

Association of immunoglobulin E levels with glioma risk and survival.

Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n = 1319) and cancer-free controls (n = 1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. Elevated total IgE was associated with reduced risk of IDH-wildtype (RR = 0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR = 0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR = 0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR = 0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001). Elevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.

A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design.

Mutations in the Isocitrate Dehydrogenase (IDH) genes, IDH1 or IDH2, define a group of adult diffuse gliomas associated with a younger age at diagnosis and better prognosis than IDH wild-type glioblastoma. Within IDH mutant gliomas, a small fraction of astrocytic tumors present with grade 4 histologic features and poor prognosis. In molecular studies, homozygous deletion of CDKN2A/B is independently predictive of poor prognosis and short survival. As a consequence, 2021 WHO classification now also recognizes this molecular feature, CDKN2A/B deletion, as sufficient for classifying an astrocytoma as IDH-mutant, WHO Grade 4, regardless of histological grading. Here, we investigate outcomes of patients with WHO Grade 4 IDH-mutant astrocytoma both with and without CDKN2A/B deletion, to compare these groups and evaluate clinical and radiographic factors that contribute to survival. We retrospectively identified 79 patients with IDH-mutant astrocytoma with CDKN2A/B deletion detected at initial diagnosis across five international institutions as well as a comparison group of 51 patients with IDH-mutant, astrocytoma, histologically Grade 4 without detectable CDKN2A/B deletion. We assembled clinical and radiographic features for all patients. We find that CDKN2A/B deletion was associated with significantly worse overall survival (OS; p = 0.0004) and progression-free survival (PFS; p = 0.0026), with median OS of 5.0 years and PFS of 3.0 years, compared to 10.1 and 5.0 years for tumors with a grade 4 designation based only on histologic criteria. Multivariate analysis confirmed CDKN2A/B deletion as a strong negative prognosticator for both OS (HR = 3.51, p < 0.0001) and PFS (HR = 2.35, p = 0.00095). In addition, in tumors with CDKN2A/B deletion, preoperative contrast enhancement is a significant predictor of worse OS (HR 2.19, 95% CI 1.22-3.93, p = 0.0090) and PFS (HR = 1.74, 95% CI = 1.02-2.97, p = 0.0420). These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.

Mechanical properties of pediatric low-grade gliomas in children with and without neurofibromatosis type 1.

Prognoses for pediatric brain tumors are suboptimal, as even in low-grade tumors, management techniques can lead to damage in the developing brain. Therefore, advanced neuroimaging methods are critical for developing optimal management plans and improving patient care. Magnetic resonance elastography (MRE) has allowed for the characterization of adult gliomas by their mechanical properties, which are uniquely sensitive to the complex interplay of cellularity, vasculature, and interstitium. However, pediatric tumors differ in behavior and cytoarchitecture, and their mechanical properties have never been assessed. Here, we conduct the first study of pediatric brain tumor mechanical properties by using MRE to measure tissue stiffness and damping ratio in low grade gliomas (LGGs). We additionally measure the mechanical properties of non-neoplastic focal abnormal signal intensities (FASIs) in children with neurofibromatosis type 1 (NF1). 23 patients age 4-17 years who had MR imaging results consistent with a primary LGG or with NF1 were included in this study. We found that pediatric gliomas are on an average 10.9% softer (p = 0.010) with a 17.3% lower (p = 0.009) viscosity than reference tissue. Softness of tumors appeared consistent across tumor subtypes and unrelated to tumor size or contrast-enhancement. In NF1 we found that, unlike gliomas, FASIs are stiffer, though not significantly, than reference tissue by an average of 10.4% and have a 16.7% lower damping ratio. Measuring tumor mechanical properties patterning and heterogeneity has potential to aid in prediction of biological behavior and inform management strategies for pediatric patients.

P10.06.A AGENT-BASED MODELING FOR PATIENT-CENTERED CLINICAL DECISION SUPPORT IN NEURO-ONCOLOGY

Abstract BACKGROUND Complex clinical decision-making in neuro-oncology is a multifaceted process involving numerous specialties influenced by various objective factors and patient preferences. Modeling these multidisciplinary neuro-oncology discussions presents significant challenges, particularly given the multimodal nature of the data. Recent advancements in large language models (LLMs) have enabled the development of LLM “agents”. These agents pave the way for multi-agent systems capable of simulating interacting components, thus capturing the nuances of interdisciplinary clinical discussions. MATERIAL AND METHODS Utilizing GPT-4, we developed conversational agents with an agent-based modeling (ABM) approach; each agent was assigned a specific specialty. We simulated their interactions in various clinical decision-making scenarios. Lastly, we simulated 30 patient-agents and included them in the ABM system. We applied this ABM approach to a dataset of 16 clinical vignettes extracted from the UCSF Clinical Data Warehouse of primary adult glioma patients who underwent tumor board (TB) reviews. The TB decision was used as ground truth for quantitative evaluation. Seven independent clinicians evaluated the final decisions. RESULTS Our quantitative assessment showed that, when blinded to whether ABM or TB generated responses, evaluators preferred ABM recommendations 47.8% of the time, followed by TB recommendations (38%). The highest recommendation concordance was between TB and ABM (50.6%). The ABM was deemed clinically accurate in 76.8% of cases and provided clinically appropriate reasoning in 73.2%. Our qualitative assessment showed that including the patient agent significantly influenced the course of discussions, notably when the patient agents participated in the system by stating their healthcare goals. The most recommended individual treatment was standard-of-care chemotherapy, followed by targeted therapies, clinical trials, immunotherapy, and palliative care. The least frequently recommended management options were radiation, surgery, consultation with other specialties, and devices. CONCLUSION This study underscores the potential of ABM in neuro-oncology, particularly in simulating complex, real-world scenarios. ABM not only empowers patients but also offers clinicians a novel tool for understanding and navigating the multifaceted landscape of patient preferences and treatment options. It provides a platform for clinicians to visualize the potential impacts of various decisions, enhancing their ability to provide personalized, effective care. We envision future work where ABM systems are patient-centric, enabling patients to explore the potential impacts of their individual characteristics on clinical management options.

DIFFERENTIAL CELL SURFACE PROTEOMICS OF FLOTILLIN-1, HMGB1 AND AMINOPEPTIDASE N IN H3 MUTATED PAEDIATRIC HIGH-GRADE GLIOMAS

Abstract AIMS High-grade gliomas (HGG) are central nervous system tumour in children, where treatment options remain elusive, leaving children with a dismal prognosis. Histone H3.3 mutations, K27M and G34V/R have been identified as the two most common recurrent somatic mutations in paediatric HGG (pHGG). These mutations are present in 50% of pHGG compared to only 1% in adult gliomas. Our previous proteomic research on cell membrane protein through protein MS data analyses have identified different signatures of differentially expressed cell membrane proteins in H3-G34R/V mutated pHGG cells, in comparison to H3 wild type tumour cells in culture. Among these proteins we have identified flotillin-1, HMGB1 (High mobility group box 1) and aminopeptidase N. Flotillin-1 is associated with numerous malignancies and HMGB1 also functions as an oncogene and aminopeptidase N is a cell surface metalloprotease involved in tumour progression. Our aim is to study the expression and localisation of these cell surface proteins in H3 mutated and wild type tumour cells, to validate them as targets for developing novel therapeutics. METHOD Expression and localisation of flotillin-1, HMGB1 and aminopeptidase N in H3.3 mutated pHGG cell lines in comparison to H3 wildtype glioma and control cells was analysed, using different protein expression assays including immunofluorescence microscopy and western blotting. RESULTS Results showed statistically significant differential protein expression and localisation of these proteins. Flotillin-1 had increased cell membrane localization in H3 mutated cells. HMGB1 expression was increased, while aminopeptidase N expression was decreased in the H3 mutated cells in comparison to wildtype pHGG. CONCLUSION This new knowledge of the cell membrane proteomics of H3 mutated pHGG may help us utilise Flotillin- 1,HMGB1 and aminopeptidase N, as potential therapeutic targets for these unique H3 mutated children’s brain tumours.

M6A RNA METHYLATION AS A THERAPEUTIC TARGET IN HIGH GRADE GLIOMA

Abstract AIMS High grade glioma (HGG) is a devastating brain cancer that has poor prognostic outcomes. Very recently, the field of epitranscriptome has emerged as a novel druggable target for multiple diseases, including cancers. In the present study, we sought to investigate the functional importance of N6-methyladenosine (m6A) RNA methylation in the pathogenesis and drug resistance of paediatric and adult high grade glioma. METHOD To identify the expression of key m6A effectors, RT-qPCR and immunofluorescence were undertaken in patient derived HGG cell lines, primary low passage HGG cells and human tissues. The expression of these effectors was modified using siRNA-mediated knockdown and small molecules to identify their effects on key transcription factors. The consequences of modification on the ability of the cells to form neurospheres and invade was also assessed. Developing chemotherapy-resistant cell lines is undertaking to assess the effect of m6A RNA levels on the ability of HGG cells to adapt to environmental changes. Measuring the level of m6A-modified transcripts were achieved by developing LC-MS/MS and MeRIP (methylated RNA immunoprecipitation) qPCR techniques. RESULTS We found that key m6A effectors such as methyltransferase like 3 (METTL3), Wilms tumor 1-associating protein (WTAP) and fat mass and obesity-associated (FTO) are expressed at significantly higher level in paediatric and adult HGG models than in control at both gene and protein levels. Furthermore, these effectors regulate the expression of key transcription factors in self-renewal, cell cycle regulation and tumorigenesis. siRNA-mediated depletion of m6A effectors and inhibition of METTL3 using small molecules such as STM2457 and STM3006 reduce the capacity of cells to form neurospheres and invade as well as improving the sensitivity of HGG cells to chemotherapeutic agents. CONCLUSION Our findings suggest that m6A effectors are potential pro-oncogenic factors that, if druggable, will represent an advanced avenue in HGG therapy.

IN VIVO APPLICATION OF LOCAL DRUG DELIVERY SYSTEMS AGAINST MEDULLOBLASTOMA GROUP 3 AND ATYPICAL/TERATOID/RHABOID TUMOURS

Abstract AIMS Local drug delivery systems (LDDSs) applied during neurosurgery offer a means of overcoming poor blood brain barrier (BBB) permeability and have been extensively investigated for the treatment of adult gliomas, but to the best of our knowledge, not for the treatment of paediatric cerebellar tumours. Here we report the applicability of an LDDS against medulloblastoma group 3 (MB3) and atypical teratoid/rhaboid tumours (AT/RT), both of which are associated with poor prognoses. METHOD We prepared and characterised an injectable and biodegradable poly(ethyleneglycol)-poly(caprolactone)- poly(ethyleneglycol) (PECE) hydrogel, which has been investigated with an array of therapeutic agents against numerous cancer types. Here, we loaded the PECE hydrogel with chemotherapeutics previously identified as being effective against primary MB3 and AT/RT in vitro, but which do not cross the BBB in vivo, namely CHIR99021, ribavirin and PG545. Biocompatibility and cytotoxicity of drug loaded hydrogels was assessed in vitro. LDDSs safety and efficacy was evaluated using patient derived MB3 and AT/RT intracranial xenograft surgical resection models. RESULTS The hydrogel was both biocompatible and effected cytotoxicity following drug release. In vivo efficacy experiments against MB3 indicated a comparable median survival in treatment arms receiving radiotherapy or CHIR99021 and PG545 loaded LDDS. However, combined radiotherapy and LDDS conferred a significant survival enhancement, including long-term survivors. Against AT/RT, the median survival of arms receiving radiotherapy was comparable to that of the CHIR99021 and ribavirin loaded LDDS, with long-term survivors observed only in the latter arm. CONCLUSION The application of LDDSs against cerebellar brain tumours offers a promising novel therapeutic alternative. For MB3, the combination of radiotherapy and a LDDS significantly enhances survival compared to radiotherapy alone. For AT/RT, the comparable survival of the LDDS and radiotherapy alone is encouraging and indicates the possibility of circumventing radiation-induced adverse effects for young children impacted by this disease.

HAS THE INITIATION OF A FORMAL PATHWAY FOR TUMOUR TISSUE COLLECTION IN NEURO ONCOLOGY PATIENTS LED TO AN INCREASE IN PATIENT’S HAVING WHOLE GENOME SEQUENCING (WGS), AND HOW WILL THIS IMPACT ONCOLOGY MANAGEMENT IN THE FUTURE?

Abstract AIMS To change the standard of care for collection of glial tumour tissue at a London teaching hospital. This would enable WGS on the tumour tissue, and give patients access to further clinical trials. METHOD The previous standard of care was for brain tumour pathology samples to be stored in paraffin. This was not suitable for WGS or for many clinical trials; the tumour samples needed to be sent to the lab as fresh tissue. The introduction of a genomics clinical nurse specialist meant that relationships were built between the surgical team, pathology teams and ward teams. There was a teaching by one of the neurosurgical team to the theatre staff. Genomics CNS led training for the nursing team. Adults started having WGS in May 2023 but many patient’s still had tissue incorrectly stored and could not have the sequencing performed. There was an introduction of a formal pathway in theatre created by one of the neurosurgeons in Dec 2023. RESULTS From May 2023 - November 2023, 58% adult glioma patients had WGS. Since December 2023 - current (March 2023) and the introduction of the formal pathways, 71% had WGS. CONCLUSION A formal pathway has now changed the standard of care for collecting tissue. There is still not 100% compliance, and this remains multifactorial. However the introduction of a formal pathway has now increased the percentage of eligible patients receiving WGS. This positive outcome has now led to discussions about freezing the fresh glioma tissue to allow glioma patient’s wider access to clinical trials which they would previously not have had access to.

Functional germline variants in DNA damage repair pathways are associated with altered survival in adults with glioma treated with temozolomide.

Temozolomide (TMZ) treatment has demonstrated, but variable, impact on glioma prognosis. This study examines associations of survival with DNA repair gene germline polymorphisms among glioma patients who did and did not have TMZ treatment. Identifying genetic markers which sensitize tumor cells to TMZ could personalize therapy and improve outcomes. We evaluated TMZ-related survival associations of pathogenic germline SNPs and genetically predicted transcript levels within 34 DNA repair genes among 1504 glioma patients from the UCSF Adult Glioma Study and Mayo Clinic whose diagnoses spanned pre- and post-TMZ eras within the major known glioma prognostic molecular subtypes. Among those who received TMZ, 5 SNPs were associated with overall survival, but not in those who did not receive TMZ. Only rs2308321-G, in MGMT , was associated with decreased survival (HR=1.21, p=0.019) for all glioma subtypes. Rs73191162-T (near UNG ), rs13076508-C (near PARP3 ), rs7840433-A (near NEIL2 ), and rs3130618-A (near MSH5 ) were only associated with survival and TMZ treatment for certain subtypes, suggesting subtype-specific germline chemo-sensitization. Genetically predicted elevated compared to normal brain expression of PNKP was associated with dramatically worse survival for TMZ-treated patients with IDH -mutant and 1p/19q non-codeleted gliomas (p=0.015). Similarly, NEIL2 and TDG expressions were associated with altered TMZ-related survival only among certain subtypes. Functional germline alterations within DNA repair genes were associated with TMZ sensitivity, measured by overall survival, among adults with glioma, these variants should be evaluated in prospective analyses and functional studies. We observed SNPs associated with glioma survival, specific to cases receiving TMZ An MGMT variant may reduce glioma survival indirectly through myelosuppression Decreased genetic PNKP expression in the brain may sensitize cells to TMZ. The introduction of temozolomide (TMZ) as a part of standard-of-care in the treatment of gliomas marked the last notable increase in patient survival. However, the effectiveness of TMZ is not universal, and can result in serious complications. The mechanism of action behind the drug is the introduction of damaging methyl groups across the tumor genome and leveraging of DNA damage repair (DDR) mechanisms to signal programmed cell death. Previous literature has identified that defects in DDR mechanisms can alter TMZ sensitivity. Using a unique dataset that spans the pre- and post-TMZ eras, we demonstrate that germline variation in DDR-related genes may have significant impact on overall survival for patients treated with TMZ, with no effects observed in the pre-TMZ era. This suggests that germline variants in these DDR genes could be used to personalize TMZ therapy to improve patient survival.

A clinically feasible algorithm for the parallel detection of glioma-associated copy number variation markers based on shallow whole genome sequencing.

Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm-level (1p/19q codeletion, +7/-10 signature) and gene-level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost-effectiveness and versatility. However, the parallel detection of glioma-associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model-based approach to classify the CNV status of glioma-associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model-based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma-associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm-level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For EGFR gene amplification and CDKN2A/B homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma-associated markers in parallel.

Sex differences in the molecular profile of adult diffuse glioma are shaped by IDH status and tumor microenvironment.

Sex differences in adult diffuse glioma (ADG) are well-established clinically, yet the underlying molecular mechanisms remain inadequately understood. Here, we aim to reveal molecular features and cellular compositions unique to each sex in ADG to comprehend the role of sex in disease etiology. We quantified sex differences in transcriptome of ADG using multiple independent glioma patient datasets. Next, we delved into the single-cell landscape to examine sex differences in gene expression and cellular composition. To explore how sex influences disease progression, we analyzed paired samples from primary and recurrent ADG cases, aiming to identify sex-specific differences in molecular and cellular features. Our analysis revealed that mutations in isocitrate dehydrogenase (IDH) genes and the tumor microenvironment emerged as primary influencers of sex-differential molecular enrichments. In IDHwt tumors, genes in neuronal signaling pathway are found to be enriched in male tumors, while genes in hypoxia and inflammatory response pathways are enriched in female tumors. This pattern was reversed in IDHmut gliomas. We hypothesized that these distinctions could be attributed to heterogeneous cellular composition between sexes. Using single-cell data, we observed distinctive patterns of sex differences in cell states, cell composition and cell-cell interaction in IDHwt and IDHmut tumors separately. Further, by comparing molecular changes in paired primary and recurrent ADG samples, we identified sex-specific differences in molecular characteristics and cellular compositions of recurrent tumors. Our results provide a comprehensive multi-level characterization of sex differences in ADG, such findings provide novel insights into glioma disease progression in each sex.

Patterns of intersectional tumor volumes in T2-weighted MRI and [18F]FET PET in adult glioma: a prospective, observational study

Brain tumor volumes as assessed by magnetic resonance imaging (MRI) do not always spatially overlap with biological tumor volumes (BTV) measured by [18F]Fluoroethyltyrosine positron emission tomography ([18F]FET PET). We prospectively investigated volumetric patterns based on the extent of tumor volume overlap between the two modalities. Eighty-six patients with newly diagnosed glioma who had undergone MRI and [18F]FET PET between 2007 and 2009 were included in this prospective study and (re-)classified according to CNS WHO 2021 (Classification of Tumors of the Central Nervous System by the World Health Organization). Four different patterns of volume overlap were defined mathematically according to the extent of overlap between MRI-based T2 tumor volume (non-enhancing tumor volume, nCEV) and BTVs. Progression-free (PFS) and overall survival (OS) were determined. Seventy patients were diagnosed with isocitrate dehydrogenase wildtype (IDHwt) glioblastoma and 16 with IDH-mutant glioma, respectively. The most common pattern was characterized by a larger non-contrast-enhancing tumor volume (nCEV) that enclosed all or most of the BTV and was observed in 46 patients (54%) (pattern 1). This pattern was more frequent in IDH-mutant gliomas than in IDH-wildtype glioblastoma (81% versus 47%, p = 0.02). In multivariate analyses, pattern 1 was associated with prolonged PFS (HR 0.59; 95 CI 0.34-1.0; p = 0.05), but not OS (HR 0.66; 95 CI 0.4–1.08; p = 0.1). For OS, presence of an IDH mutation (p = 0.05) and lower age (p = 0.03) were associated with prolonged OS. The spatial relation between nCEV and BTV varies within and between glioma entities. Most frequently, a larger nCEV encases the BTV. Some patients show spatially dissociated nCEVs and BTVs. Not accounting for this phenomenon in surgery or radiotherapy planning might lead to undertreatment.

Unique properties of clinical manifestation and magnetic resonance imaging for differential diagnosis of optic nerve hemangioblastoma.

To investigate the unique properties of clinical manifestation and radiological imaging for differential diagnosis of optic nerve hemangioblastoma (ONH) from adult optic nerve glioma (ONG) prior to surgical resection. ONH and adult ONG patients were recruited from 2012 to 2022. A total of seven ONH patients (8 eyes) and 23 adult ONG patients (24 eyes) were assessed. The median onset age of ONH patients was older than that of adult ONG patients (p = 0.007). There were 42.9% (3/7) of ONH patients closely associated with the diagnosis of Von Hippel-Lindau (VHL) syndrome. Notably in Magnetic Resonance Imaging (MRI), the retrobulbar hemangioblastomas in all ONH patients were primarily intraorbital (100%, 8/8), canalicular (87.5%, 7/8), and anterior intracranial (12.5%, 1/8), especially concentrated in the orbital apex, with little posterior optic pathway involvement. Nearly all affected parts of optic nerve in the ONH group (75.0%, 6/8) presented with circumscribed cystic-solid components, characterized by cystic lesions (peritumoral oedema) anteriorly and solid tumours posteriorly, with significant heterogeneous enhancement. Adult ONG lesions prior to extend from the anterior portion to the whole length of the optic nerve, with relatively innocent enlargement in the postcontrast study. Optic nerve tumours in those with older ages at diagnosis (>30 years) or those diagnosed with VHL syndrome are more likely to be indicative of ONH. In the absence of associated VHL syndrome, a distinguishing MRI feature is the concentration of tumours in the orbital apex, characterized by circumscribed cystic-solid components and heterogeneous enhancement of the solid portion.

Multimodal magnetic resonance imaging (MRI) of juvenile and adult diffuse hemispheric gliomas with H3 G34-mutation: a case description.

Multimodal magnetic resonance imaging (MRI) of juvenile and adult diffuse hemispheric gliomas with H3 G34-mutation: a case description.

Study protocol for a multicentre randomised controlled trial evaluating the efficacy of an online yoga intervention in high-grade glioma patients and their caregivers: the YINOTA-O-trial

IntroductionHigh-grade glioma patients and their caregivers often suffer from distress and a lower quality of life. Results from studies with patients with mixed cancer entities suggest that yoga can be...

Transcriptomic and proteomic spatial profiling of pediatric and adult diffuse midline glioma H3 K27-Altered.

Diffuse midline glioma, H3 K27-altered (DMG) are highly aggressive malignancies of the central nervous system (CNS) that primarily affect the pediatric population. Large scale spatial transcriptomic studies have implicated that tumor microenvironmental landscape plays an important role in determining the phenotypic differences in tumor presentation and clinical course, however, data connecting overall transcriptomic changes to the protein level is lacking. The NanoString GeoMx™Digital Spatial Profiler platform was used to determine the spatial transcriptomic and proteomic landscape in a cohort of both pediatric and adult H3 K27-altered DMG biopsy samples. Three fluorescently labeled antibodies targeting immune cells (CD45), epithelial cells (PanCK), tumor cells (H3 K27M) and a nucleic acid stain (SYTO-13) were used to establish regions of interest (ROI) for genomic and proteomic analysis. We found genetic alterations within the tumor which can be delineated across patient age and spatial location. We show that the H3 K27M mutation itself has a profound impact on tumor cells transcriptomics and interestingly we found limited fidelity between overall transcriptome and proteome. Our data also validate a previously described genomic signature at the proteomic level and reveal a special shift in the signature based on the local TME composition.

Erratum to: Glioma resource outreach with support: A program to identify and initiate supportive care interventions for unmet needs among adult lower-grade glioma patients

Erratum to: Glioma resource outreach with support: A program to identify and initiate supportive care interventions for unmet needs among adult lower-grade glioma patients

From Voxel to Gene: A Scoping Review on MRI Radiogenomics' Artificial Intelligence Predictions in Adult Gliomas and Glioblastomas-The Promise of Virtual Biopsy?

Gliomas, including the most severe form known as glioblastomas, are primary brain tumors arising from glial cells, with significant impact on adults, particularly men aged 45 to 70. Recent advancements in the WHO (World Health Organization) classification now correlate genetic markers with glioma phenotypes, enhancing diagnostic precision and therapeutic strategies. This scoping review aims to evaluate the current state of deep learning (DL) applications in the genetic characterization of adult gliomas, addressing the potential of these technologies for a reliable virtual biopsy. We reviewed 17 studies, analyzing the evolution of DL algorithms from fully convolutional networks to more advanced architectures (ResNet and DenseNet). The methods involved various validation techniques, including k-fold cross-validation and external dataset validation. Our findings highlight significant variability in reported performance, largely due to small, homogeneous datasets and inconsistent validation methods. Despite promising results, particularly in predicting individual genetic traits, the lack of robust external validation limits the generalizability of these models. Future efforts should focus on developing larger, more diverse datasets and integrating multidisciplinary collaboration to enhance model reliability. This review underscores the potential of DL in advancing glioma characterization, paving the way for more precise, non-invasive diagnostic tools. The development of a robust algorithm capable of predicting the somatic genetics of gliomas or glioblastomas could accelerate the diagnostic process and inform therapeutic decisions more quickly, while maintaining the same level of accuracy as the traditional diagnostic pathway, which involves invasive tumor biopsies.

Association of immunoglobulin E levels with glioma risk and survival.

Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the association between IgE and glioma prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, and IgE class modulate the association of serum IgE levels with glioma risk and survival. We conducted a case-control study using participants from the University of California, San Francisco Adult Glioma Study (1997-2010). Serum IgE levels for total, respiratory and food allergy were measured in adults diagnosed with glioma (n=1319) and cancer-free controls (n=1139) matched based on age, sex, and race and ethnicity. Logistic regression was adjusted for patient demographics to assess the association between IgE levels and glioma risk. Multivariable Cox regression adjusted for patient-specific and tumor-specific factors compared survival between the elevated and normal IgE groups. All statistical tests were 2-sided. Elevated total IgE was associated with reduced risk of IDH-wildtype (RR=0.78, 95% CI: 0.71-0.86) and IDH-mutant glioma (RR=0.73, 95% CI: 0.63-0.85). In multivariable Cox regression, positive respiratory IgE was associated with improved survival for IDH-wildtype glioma (RR=0.79, 95% CI: 0.67-0.93). The reduction in mortality risk was significant in females only (RR=0.75, 95% CI: 0.57-0.98) with an improvement in median survival of 6.9 months (P<.001). Elevated serum IgE was associated with improved prognosis for IDH-wildtype glioma, with a more pronounced protective effect in females than males, which has implications for the future study of IgE-based immunotherapies for glioma.

Observations from the first 100 cases of intraoperative MRI – experiences, trends and short-term outcomes

BackgroundWe sought to analyze, in well-defined clinical setting, the first 100 patients treated at the intraoperative MRI (iMRI) hybrid surgical theatre at our facility in a population-based setting to evaluate which pathologies are best approached with iMRI assisted surgeries, as this is not yet clearly defined.MethodsPatients undergoing surgery in the 3T iMRI hybrid surgical theatre at our neurosurgical department between December 2017 to May 2021 were included after informed consent. Demographic, clinical, surgical, histological, radiological and outcome parameters, as well as variables related to iMRI, were retrospectively collected and analyzed. Patients were subdivided into adult and pediatric cohorts.ResultsVarious neurosurgical procedures were performed; resection of tumors and epileptic foci, endoscopic skull base procedures including pituitary lesions, deep brain stimulation (DBS) and laser interstitial thermal therapy (LITT). In total, 41 patients were pediatric. An iMRI scan was carried out in 96% of cases and led to continuation of surgery in 50% of cases, mainly due to visualized remaining pathological tissue (95.2%). Median time to iMRI from intubation was 280 min and median total duration of surgery was 445 min. The majority of patients experienced no postoperative complications (70%), 13 patients suffered permanent postoperative deficits, predominantly visual.ConclusionHerein, we demonstrate the first 100 patients undergoing neurosurgery aided by iMRI at our facility since introduction. Indications for surgery differed between pediatric and adult patients. The iMRI was utilized for tumor surgeries, particularly adult low-grade gliomas and pediatric tumors, as well as for epilepsy surgery and DBS. In this heterogenous population, iMRI led to continuation of surgery in 50%. To establish the benefit in maximizing the extent of resection in these brain pathologies future studies are recommended.Clinical trial numberNot applicable.