Malignant Primary Brain Tumor Research Articles

Cannabis and Craniotomy for Glioblastoma: Impact on Complications and Health Care Utilization

Despite advances in treatment of glioblastomas (GBMs), the median survival remains 14-16 months. In the United States, 52.5 million people ≥12 years of age used cannabis in 2021. We aim to elucidate differences in complications after craniotomy for resection of GBM between users and nonusers of cannabis. Merative MarketScan Research Data (2008-2019) (includes >265 million patients) were used to extract adults (≥18 years of age) with GBM diagnosis (International Classification of Diseases-9 code 191.x and International Classification of Diseases-10 code C71.x) who had a craniotomy (Current Procedure Terminology code 61510) from inpatient admission data. The inverse probability treatment weighted analysis balanced the groups of cannabis abuse disorder (CAD) and no CAD in terms of age, gender, insurance coverage, comorbidities, and prior 12-month opioid dependence. Individuals with CAD were younger (median, 37 vs. 51 years; P < 0.0001). There was a lower percentage of women (19% vs. 45%; P < 0.0001). In the CAD group, opioid abuse pattern for ≥12 months was higher (16% vs. 5%; P=0.001) and the rate of complications was higher (32% vs. 15%; P= 0.001) during index hospital stay. At 6 months postdischarge, neurologic complications were higher among the CAD group (27% vs. 8%; P < 0.001). At 1 year postdischarge, patients with CAD sought feweroutpatient services (P= 0.012). More neurologic complications were seen in the CAD group (31% vs. 12%; P< 0.001). This retrospective population-based study sounds a higher rate of neurologic complications among patients using cannabis who also had a newly diagnosed GBM. This suggests the lack of a protective effect from use of cannabis in patients with primary malignant brain tumors.

A novel TAp73-inhibitory compound counteracts stemness features of glioblastoma stem cells.

Glioblastoma (GB) is the most common and fatal type of primary malignant brain tumor for which effective therapeutics are still lacking. GB stem cells, with tumor-initiating and self-renewal capacity, are mostly responsible for GB malignancy, representing a crucial target for therapies. The TP73 gene, which is highly expressed in GB, gives rise to the TAp73 isoform, a pleiotropic protein that regulates neural stem cell biology; however, its role in cancer has been highly controversial. We inactivated TP73 in human GB stem cells and revealed that TAp73 is required for their stemness potential, acting as a regulator of the transcriptional stemness signatures, highlighting TAp73 as a possible therapeutic target. As proof of concept, we identified a novel natural compound with TAp73-inhibitory capacity, which was highly effective against GB stem cells. The treatment reduced GB stem cell-invasion capacity and stem features, at least in part by TAp73 repression. Our data are consistent with a novel paradigm in which hijacking of p73-regulated neurodevelopmental programs, including neural stemness, might sustain tumor progression, pointing out TAp73 as a therapeutic strategy for GB.

AB045. E2F6 promotes temozolomide resistance in glioblastoma by enrichment in CARD6 and POSTN promoter region.

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor. Temozolomide (TMZ) is the most used first-line chemotherapeutic agent for GBM after surgery, but acquired resistance to TMZ frequently leads to treatment failure and is a major challenge in the clinical treatment of GBM. Increasing evidence suggests that E2F transcription factor 6 (E2F6) is associated with a variety of tumor malignant biological behaviors and drug resistance, but its biological function and underlying molecular mechanisms in GBM are unknown. The study investigated the levels of E2F6 in both TMZ-sensitive and TMZ-resistant GBM cells and tissues using Western blotting and immunofluorescence assays. In vitro experiments were conducted to explore the impact of E2F6 on TMZ resistance and glioma stem cell stemness. These experiments included Western blotting, colony formation assay, flow cytometry assay, and TdT-mediated dUTP nick-end labeling (TUNEL) assay. Bioinformatic analyses were conducted to investigate the mechanism behind the high expression of E2F6 in TMZ-resistant cells and its correlation with caspase recruitment domain 6 (CARD6) and disulfide-linked cell adhesion protein (POSTN). The study employed bioinformatic analyses, messenger RNA (mRNA) sequencing, chromatin immunoprecipitation sequencing assay, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. To examine the function of E2F6, an intracranial xenograft tumor mouse model was used for in vivo experiments. It was found that CARD6 and POSTN were significantly associated with TMZ resistance and survival of GBM patients. E2F6 was up-regulated in TMZ-resistant cells and tissues. Knockdown of E2F6 down-regulated the expression of CARD6, promoted TMZ-induced apoptosis, and enhanced chemo-sensitivity, whereas its overexpression significantly increased TMZ resistance in vitro and in vivo. In addition, E2F6 can promote TMZ resistance through stem-like properties acquisition. We identified a signaling pathway related to E2F6 and POSTN, which maintains the self-renewal of GBM stem cells (GSCs). E2F6 concentrates in the promoter region of POSTN, thereby regulating the expression of GSCs-related genes cluster of differentiation 133 (CD133), Nestin, and sex-determining region Y-box 2 (SOX2), which may be involved in tumor metabolism and drug resistance processes. Down-regulation of E2F6 down-regulated the expression of POSTN and inhibited tumor growth in nude mice. These results suggest that the E2F6-CARD6/POSTN signaling axis regulates the malignant biological behaviors of GBM and TMZ resistance. These findings are expected to provide promising therapeutic targets for CARD6 overcoming GBM TMZ resistance.

Development of a biocompatible 3D hydrogel scaffold using continuous liquid interface production for the delivery of cell therapies to treat recurrent glioblastoma.

Glioblastoma (GBM) is the most common primary malignant brain tumor diagnosed in adults, carrying with it an extremely poor prognosis and limited options for effective treatment. Various cell therapies have emerged as promising candidates for GBM treatment but fail in the clinic due to poor tumor trafficking, poor transplantation efficiency, and high systemic toxicity. In this study, we design, characterize, and test a 3D-printed cell delivery platform that can enhance the survival of therapeutic cells implanted in the GBM resection cavity. Using continuous liquid interface production (CLIP) to generate a biocompatible 3D hydrogel, we demonstrate that we can effectively seed neural stem cells (NSCs) onto the surface of the hydrogel, and that the cells can proliferate to high densities when cultured for 14 days in vitro. We show that NSCs seeded on CLIP scaffolds persist longer than freely injected cells in vivo, proliferating to 20% higher than their original density in 6 days after implantation. Finally, we demonstrate that therapeutic fibroblasts seeded on CLIP more effectively suppress tumor growth and extend survival in a mouse model of LN229 GBM resection compared to the scaffold or therapeutic cells alone. These promising results demonstrate the potential to leverage CLIP to design hydrogels with various features to control the delivery of different types of cell therapies. Future work will include a more thorough evaluation of the immunological response to the material and improvement of the printing resolution for biocompatible aqueous resins.

Microfluidic-Derived Docosahexaenoic Acid Liposomes for Targeting Glioblastoma and Its Inflammatory Microenvironment.

Glioblastoma (GBM) is the most common malignant primary brain tumor, characterized by limited treatment options and a poor prognosis. Its aggressiveness is attributed not only to the uncontrolled proliferation and invasion of tumor cells but also to the complex interplay between these cells and the surrounding microenvironment. Within the tumor microenvironment, an intricate network of immune cells, stromal cells, and various signaling molecules creates a pro-inflammatory milieu that supports tumor growth and progression. Docosahexaenoic acid (DHA), an essential ω3 polyunsaturated fatty acid for brain function, is associated with anti-inflammatory and anticarcinogenic properties. Therefore, in this work, DHA liposomes were synthesized using a microfluidic platform to target and reduce the inflammatory environment of GBM. The liposomes were rapidly taken up by macrophages in a time-dependent manner without causing cytotoxicity. Moreover, DHA liposomes successfully downregulated the expression of inflammatory-associated genes (IL-6; IL-1β; TNFα; NF-κB, and STAT-1) and the secretion of key cytokines (IL-6 and TNFα) in stimulated macrophages and GBM cells. Conversely, no significant differences were observed in the expression of IL-10, an anti-inflammatory gene expressed in alternatively activated macrophages. Additionally, DHA liposomes were found to be more efficient in regulating the inflammatory profile of these cells compared with a free formulation of DHA. The nanomedicine platform established in this work opens new opportunities for developing liposomes incorporating DHA to target GBM and its inflammatory milieu.

Rehabilitation utilization in malignant primary brain tumors compared to stroke and traumatic brain injury: Analysis using a large claim database

Abstract Background There is concern regarding the underutilization of rehabilitation services for the malignant primary brain tumor (MPBT) population following hospitalization. Our aim is to assess physical therapy (PT), occupational therapy (OT), and speech-language pathology (SLP) use after a MPBT diagnosis, evaluate the trend from 2001-2018, and compare to traumatic brain injury (TBI) and stroke. Methods Adult cases of MPBT, TBI, and stroke were extracted from MarketScan database. Inpatient and outpatient data were screened for inpatient rehabilitation use at the time of diagnosis and post-discharge outpatient PT, OT, and SLP over 12 months. Generalized linear regressions were used for analysis. Results Cohort was composed of 3,381 MPBT, 205,366 stroke, and 24,825 TBI patients. After diagnosis, 1% of MPBTs were discharged to skilled nursing facilities (SNF) and 3% to inpatient rehabilitation facilities (IRF). Rehabilitation use at 12 months was 19% PT, 8% OT, and 6% SLP. These percentages were lower than stroke and TBI; stroke: 8% SNF, 8% IRF, 22% PT, 10% OT, and 8% SLP; TBI: 7% SNF, 7% IRF, 22% PT, 8% OT, and 6% SLP. Outpatient therapies increased from 2001 to 2018, with PT use consistently higher than OT and SLP. MPBT had the greatest increases in OT (7.95 times) and PT (3.89 times) compared to stroke and TBI, while stroke had the greatest increase in SLP (.98 times). Conclusion MPBT patients had the highest increase of OT and PT utilization when compared to stroke and TBI. However, there remains a utilization gap which demonstrates the need for improvement.

“Not me!” a qualitative, vignette-based study of nurses’ and physicians’ reactions to spiritual distress on neuro-oncological units

PurposePeople with primary malignant brain tumors experience serious health-related suffering caused by limited prognosis and high symptom burden. Consequently, neuro-oncological healthcare workers can be affected emotionally in a negative way. The aim of this study was to analyze the attitudes and behavior of nurses and physicians when confronted with spiritual distress in these patients.MethodsNeurospirit-DE is a qualitative vignette–based, multicenter, cross-sectional online survey that was conducted in Bavaria, Germany. Reflexive thematic analysis was used for data analysis.ResultsA total of 143 nurses and physicians working in neurological and neurosurgical wards in 46 hospitals participated in the survey. The participants questioned if the ability to provide spiritual care can be learned or is a natural skill. Spiritual care as a responsibility of the whole team was highlighted, and the staff reflected on the appropriate way of involving spiritual care experts. The main limitations to spiritual care were a lack of time and not viewing spiritual engagement as part of the professional role. Some were able to personally benefit from spiritual conversations with patients, but many participants criticized the perceived emotional burden while expressing the imminent need for specific training and team reflection.ConclusionsMost neuro-oncological nurses and physicians perceive spiritual care as part of their duty and know how to alleviate the patient’s spiritual distress. Nonetheless, validation of spiritual assessment tools for neuro-oncology and standardized documentation of patients’ distress, shared interprofessional training, and reflection on the professional and personal challenges faced when confronted with spiritual care in neuro-oncology require further improvement and training.

Metal-Doping Strategy for Carbon-Based Sonosensitizer in Sonodynamic Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and known for its challenging prognosis. Sonodynamic therapy (SDT) is an innovative therapeutic approach that shows promise in tumor elimination by activating sonosensitizers with low-intensity ultrasound. In this study, a novel sonosensitizer is synthesized using Cu-doped carbon dots (Cu-CDs) for the sonodynamic treatment of GBM. Doping with copper transforms the carbon dots into a p-n type semiconductor having a bandgap of 1.58eV, a prolonged lifespan of 10.7 µs, and an improved electron- and hole-separation efficiency. The sonodynamic effect is efficiency enhanced. Western blot analysis reveals that the Cu-CDs induces a biological response leading to cell death, termed as cuproptosis. Specifically, Cu-CDs upregulate dihydrosulfanyl transacetylase expression, thereby establishing a synergistic therapeutic effect against tumor cell death when combined with SDT. Furthermore, Cu-CDs exhibit excellent permeability through the blood-brain barrier and potent anti-tumor activity. Importantly, the Cu-CDs effectively impede the growth of glioblastoma tumors and prolong the survival of mice bearing these tumors. This study provides support for the application of carbon-based nanomaterials as sonosensitizers in tumor therapy.

Neuroinflammation in Glioblastoma: Progress and Perspectives.

Glioblastoma is the most common and malignant primary brain tumor, with high morbidity and mortality. Despite an aggressive, multimodal treatment regimen, including surgical resection followed by chemotherapy and radiotherapy, the prognosis of glioblastoma patients remains poor. One formidable challenge to advancing glioblastoma therapy is the complexity of the tumor microenvironment. The tumor microenvironment of glioblastoma is a highly dynamic and heterogeneous system that consists of not only cancerous cells but also various resident or infiltrating inflammatory cells. These inflammatory cells not only provide a unique tumor environment for glioblastoma cells to develop and grow but also play important roles in regulating tumor aggressiveness and treatment resistance. Targeting the tumor microenvironment, especially neuroinflammation, has increasingly been recognized as a novel therapeutic approach in glioblastoma. In this review, we discuss the components of the tumor microenvironment in glioblastoma, focusing on neuroinflammation. We discuss the interactions between different tumor microenvironment components as well as their functions in regulating glioblastoma pathogenesis and progression. We will also discuss the anti-tumor microenvironment interventions that can be employed as potential therapeutic targets.

Tumor biomechanics as a novel imaging biomarker to assess response to immunotherapy in a murine glioma model

Glioblastoma is the most common and aggressive primary malignant brain tumor with poor prognosis. Novel immunotherapeutic approaches are currently under investigation. Even though magnetic resonance imaging (MRI) is the most important imaging tool for treatment monitoring, response assessment is often hampered by therapy-related tissue changes. As tumor and therapy-associated tissue reactions differ structurally, we hypothesize that biomechanics could be a pertinent imaging proxy for differentiation. Longitudinal MRI and magnetic resonance elastography (MRE) were performed to monitor response to immunotherapy with a toll-like receptor 7/8 agonist in orthotopic syngeneic experimental glioma. Imaging results were correlated to histology and light sheet microscopy data. Here, we identify MRE as a promising non-invasive imaging method for immunotherapy-monitoring by quantifying changes in response-related tumor mechanics. Specifically, we show that a relative softening of treated compared to untreated tumors is linked to the inflammatory processes following therapy-induced re-education of tumor-associated myeloid cells. Mechanistically, combined effects of myeloid influx and inflammation including extracellular matrix degradation following immunotherapy form the basis of treated tumors being softer than untreated glioma. This is a very early indicator of therapy response outperforming established imaging metrics such as tumor volume. The overall anti-tumor inflammatory processes likely have similar effects on human brain tissue biomechanics, making MRE a promising tool for gauging response to immunotherapy in glioma patients early, thereby strongly impacting patient pathway.

Epidemiology of malignant gliomas in Iran: first report of Iranian National Population-based Cancer Registry, 2009-2017.

Malignant gliomas constitute the most common type of primary malignant brain tumors. Most previous studies have evaluated the epidemiology of malignant gliomas in developed countries. Hence, there is a lack of evidence in this regard from developing countries. This study is the first epidemiological report on the status of malignant glioma in Iran between 2009 and 2017. Data from the Iranian National Population-based Cancer Registry (covering 98% of the Iranian population) on CNS tumors recorded from 2009 to 2017 were used for analysis. Age-adjusted incidence rates were calculated by sex, tumor histology, tumor site, and year of diagnosis. Trend analysis of incidence rates was also performed. Survival data were recorded and the Cox proportional hazards model was used to evaluate underlying risk factors. A total of 8484 patients were diagnosed with malignant glioma between 2009 and 2017 in Iran. The overall age-adjusted incidence rate of malignant gliomas over the 9-year period was 1.71 per 100,000 persons. The most common histology of malignant gliomas was glioblastoma (81.4%). A significant increase in the incidence of malignant gliomas was found between 2009 and 2012. The median overall survival was 13.0 (95% CI 12.6-13.5) months over the study period. Older age groups, higher tumor grade, male sex, the first half of the study period, and receiving no treatment were significantly associated with worse prognoses. This study is the latest epidemiological report on the status of malignant gliomas in Iran. Although the overall incidence rate was lower than the rates in developed countries, several findings were consistent with those in prior reports.

In Silico Research in Glioma Vaccine Discovery from Isocitrate Dehydrogenase Type 1 (R132H) Epitopes

Glioma is a primary malignant brain tumor, which is often detected using the mutation of isocitrate dehydrogenase type 1 (IDH1) at the R132H position. Several studies have also reported the use of mutated IDH1 (R132H) specific immunogenic epitopes as vaccines against this tumor. Therefore, this study aimed to determine the high-affinity epitopes of IDH1 (R132H) as a plausible candidate of preventive and curative glioma vaccines and to predict the stability of epitope-receptor complex through molecular dynamics simulation. The binding affinity of epitopes for preventing and treating glioma were predicted by docking epitope to major histocompatibility complexes class II (MHC II) and ephrin type-A receptor 3 (EphA3), respectively, using Dock version 6.7. This study used the rigid body docking method, where the samples were treated in their compact state. The highest binding affinity for MHC II was exhibited by epitope 42, as indicated by a grid score of -62.73 kcal/mol. Meanwhile, epitope 54, with a grid score of -55.56 kcal/mol, had the highest binding affinity for the EphA3 receptor. The results showed that the protein conformation in the 42-MHC II epitope complex changed significantly in molecular dynamics simulations using GROMACS version 5.0.6 at 300 K for 25 ns with RMSD &gt; 3 Å, while epitope 54-EphA3 complex was stable from the beginning up to 15.29 ns. Based on these findings, the best candidates for prophylactic and curative glioma vaccination were epitope 42 and 54, respectively.

Ophiobolin A derivatives with enhanced activities under tumor-relevant acidic conditions

Glioblastoma (GBM) is the most common form of malignant primary brain tumor and is one of the most lethal cancers. The difficulty in treating GBM stems from its highly developed mechanisms of drug resistance. Our research team has recently identified the fungal secondary metabolite ophiobolin A (OpA) as an agent with significant activity against drug-resistant GBM cells. However, the OpA’s mode of action is likely based on covalent modification of its intracellular target(s) and thus possible off-target reactivity needs to be addressed. This work involves the investigation of an acid-sensitive OpA analogue approach that exploits the elevated acidity of the GBM microenvironment to enhance the selectivity for tumor targeting. This project identified analogues that showed selectivity at killing GBM cells grown in cultures at reduced pH compared to those maintained under normal neutral conditions. These studies are expected to facilitate the development of OpA as an anti-GBM agent by investigating its potential use in an acid-sensitive analogue form with enhanced selectivity for tumor targeting.

Pro-Oxidant Auranofin and Glutathione-Depleting Combination Unveils Synergistic Lethality in Glioblastoma Cells with Aberrant Epidermal Growth Factor Receptor Expression.

Glioblastoma (GBM) is the most prevalent and advanced malignant primary brain tumor in adults. GBM frequently harbors epidermal growth factor receptor (EGFR) wild-type (EGFRwt) gene amplification and/or EGFRvIII activating mutation. EGFR-driven GBM relies on the thioredoxin (Trx) and/or glutathione (GSH) antioxidant systems to withstand the excessive production of reactive oxygen species (ROS). The impact of EGFRwt or EGFRvIII overexpression on the response to a Trx/GSH co-targeting strategy is unknown. In this study, we investigated Trx/GSH co-targeting in the context of EGFR overexpression in GBM. Auranofin is a thioredoxin reductase (TrxR) inhibitor, FDA-approved for rheumatoid arthritis. L-buthionine-sulfoximine (L-BSO) inhibits GSH synthesis by targeting the glutamate-cysteine ligase catalytic (GCLC) enzyme subunit. We analyzed the mechanisms of cytotoxicity of auranofin and the interaction between auranofin and L-BSO in U87MG, U87/EGFRwt, and U87/EGFRvIII GBM isogenic GBM cell lines. ROS-dependent effects were assessed using the antioxidant N-acetylsteine. We show that auranofin decreased TrxR1 activity and increased ROS. Auranofin decreased cell vitality and colony formation and increased protein polyubiquitination through ROS-dependent mechanisms, suggesting the role of ROS in auranofin-induced cytotoxicity in the three cell lines. ROS-dependent PARP-1 cleavage was associated with EGFRvIII downregulation in U87/EGFRvIII cells. Remarkably, the auranofin and L-BSO combination induced the significant depletion of intracellular GSH and synergistic cytotoxicity regardless of EGFR overexpression. Nevertheless, molecular mechanisms associated with cytotoxicity were modulated to a different extent among the three cell lines. U87/EGFRvIII exhibited the most prominent ROS increase, P-AKT(Ser-473), and AKT decrease along with drastic EGFRvIII downregulation. U87/EGFRwt and U87/EGFRvIII displayed lower basal intracellular GSH levels and synergistic ROS-dependent DNA damage compared to U87MG cells. Our study provides evidence for ROS-dependent synergistic cytotoxicity of auranofin and L-BSO combination in GBM in vitro. Unraveling the sensitivity of EGFR-overexpressing cells to auranofin alone, and synergistic auranofin and L-BSO combination, supports the rationale to repurpose this promising pro-oxidant treatment strategy in GBM.

Network-Based Transcriptome Analysis Reveals FAM3C as a Novel Potential Biomarker for Glioblastoma.

Glioblastoma (GBM) is the most common form of malignant primary brain tumor with a high mortality rate. The aim of the present study was to investigate the clinical significance of Family with Sequence Similarity 3, Member C, FAM3C, in GBM using bioinformatic-integrated analysis. First, we performed the transcriptomic integration analysis to assess the expression profile of FAM3C in GBM using several data sets (RNA-sequencingand scRNA-sequencing), which were obtained from TCGA and GEO databases. By using theSTRING platform, we investigated FAM3C-coregulated genes to construct the protein-protein interaction network. Next,Metascape, Enrichr, and CIBERSORT databases were used. We found FAM3C high expression in GBM with poor survival rates. Further, we observed, via FAM3C coexpression network analysis, that FAM3C plays key roles in several hallmarks of cancer. Surprisingly, we also highlighted five FAM3C‑coregulated genes overexpressed in GBM. Specifically, we demonstrated the association between the high expression of FAM3C and the abundance of the different immune cells, which may markedly worsen GBM prognosis. For the first time, our findings suggest that FAM3C not only can be a new emerging biomarker with promising therapeutic values to GBM patientsbut also gavea new insight into a potential resource for future GBM studies.

Challenges and opportunities in newly diagnosed glioblastoma in the United Kingdom: A Delphi panel

Abstract Background Glioblastoma is the deadliest primary malignant brain tumor in adults with limited treatment options and an average survival time of 12–18 months in the United Kingdom. In addition, glioblastoma has a highly detrimental impact on physical, cognitive, and emotional well-being, leaving substantial unmet needs for patients and caregivers. This study aimed to identify unmet needs in people with newly diagnosed glioblastoma and opportunities to mitigate them. Methods Utilizing Delphi methodology, an initial roundtable discussion with patient advocacy experts from 5 brain tumor organizations in the United Kingdom informed the development of 2 rounds of surveys across 9 domains (diagnosis, treatment, integrated care, support beyond treatment, quality of life, access to new treatments, access to trials, measures to ease the burden, and impact of COVID-19). Consensus was predefined as ≥70% agreement. Results A total of 17 Delphi panelists (glioblastoma patients, caregivers, and patient representatives) completed the first round of questionnaires and 26 completed the second. Consensus was reached on 16/21 questions (76.2%) and 7/9 domains. Panelists reached a consensus on key questions including the high frequency of diagnosis via emergency departments, the lack of effective personalized treatments and holistic care, the high caregiver burden, the lack of awareness and availability of access to clinical trials, and the negative impact of COVID-19 on glioblastoma care. Conclusions Significant unmet needs exist for newly diagnosed glioblastoma patients in the United Kingdom, highlighting the demand for increased research funding, comprehensive patient care, caregiver support, enhanced awareness and access to clinical trials, and new treatments.

Identifying research priorities and essential elements of palliative care services for people facing malignant brain tumors: A participatory co-design approach.

Primary malignant brain tumors (ie, brain cancer) impact the quality of life (QoL) for patients and care partners in disease-specific ways involving cognition and communication. Palliative care (PC) addresses patient/care partner QoL, but it is not known how PC may address the unique needs of brain cancer patients. The purpose of this project was to identify brain cancer PC research priorities using participatory co-design methods. Participatory co-design included the formation of a longitudinal, collaborative advisory group, engagement frameworks, design-thinking processes, and social media-based engagement over a 1-year period. Community-identified brain cancer QoL needs and research priorities were mapped to proposed "essential elements" of brain cancer PC services. We engaged an estimated 500 patients, care partners, healthcare professionals, and others with an interest in QoL and PC services for people with malignant brain tumors. Research priorities included testing the early introduction of PC services designed to address the unique QoL needs of brain cancer patients and care partners. Essential elements of brain cancer PC include: (1) addressing brain cancer patients' unique range of QoL needs and concerns, which change over time, (2) tailoring existing services and approaches to patient needs and concerns, (3) enhancing the involvement of interprofessional care team members, and (4) optimizing timing for PC services. This was the first participatory research effort exploring brain cancer patient and care partner QoL needs and PC services. The brain tumor community calls for research testing PC service models for patients that incorporate the "essential elements" of palliative care.

A novel methylation signature predicts extreme long-term survival in glioblastoma

PurposeGlioblastoma (GBM) is the most common malignant primary brain tumor with a dismal prognosis of less than 2 years under maximal therapy. Despite the poor prognosis, small fractions of GBM patients seem to have a markedly longer survival than the vast majority of patients. Recently discovered intertumoral heterogeneity is thought to be responsible for this peculiarity, although the exact underlying mechanisms remain largely unknown. Here, we investigated the epigenetic contribution to survival.MethodsGBM treatment-naïve samples from 53 patients, consisting of 12 extremely long-term survivors (eLTS) patients and 41 median-term survivors (MTS) patients, were collected for DNA methylation analysis. 865 859 CpG sites were examined and processed for detection of differentially methylated CpG positions (DMP) and regions (DMR) between both survival groups. Gene Ontology (GO) and pathway functional annotations were used to identify associated biological processes. Verification of these findings was done using The Cancer Genome Atlas (TCGA) database.ResultsWe identified 67 DMPs and 5 DMRs that were associated with genes and pathways - namely reduced interferon beta signaling, in MAPK signaling and in NTRK signaling - which play a role in survival in GBM.ConclusionIn conclusion, baseline DNA methylation differences already present in treatment-naïve GBM samples are part of genes and pathways that play a role in the survival of these tumor types and therefore may explain part of the intrinsic heterogeneity that determines prognosis in GBM patients.

An Update on the Clinical Status, Challenges, and Future Directions of Oncolytic Virotherapy for Malignant Gliomas.

Malignant gliomas are common central nervous system tumors that pose a significant clinical challenge due to the lack of effective treatments. Glioblastoma (GBM), a grade 4 malignant glioma, is the most prevalent primary malignant brain tumor and is associated with poor prognosis. Current clinical trials are exploring various strategies to combat GBM, with oncolytic viruses (OVs) appearing particularly promising. In addition to ongoing and recently completed clinical trials, one OV (Teserpaturev, Delytact®) received provisional approval for GBM treatment in Japan. OVs are designed to selectively target and eliminate cancer cells while promoting changes in the tumor microenvironment that can trigger and support long-lasting anti-tumor immunity. OVs offer the potential to remodel the tumor microenvironment and reverse systemic immune exhaustion. Additionally, an increasing number of OVs are armed with immunomodulatory payloads or combined with immunotherapy approaches in an effort to promote anti-tumor responses in a tumor-targeted manner. Recently completed oncolytic virotherapy trials can guide the way for future treatment individualization through patient preselection, enhancing the likelihood of achieving the highest possible clinical success. These trials also offer valuable insight into the numerous challenges inherent in malignant glioma treatment, some of which OVs can help overcome.

EPID-01. ESTIMATING THE BURDEN DUE TO BRAIN AND OTHER CNS TUMORS IN ADOLESCENTS IN THE UNITED STATES

Abstract BACKGROUND Brain and other central nervous system (CNS) tumors in adolescents have unique biological and behavioral distinctions from both children and adults. As a result, they pose challenges to treatment and reporting. Here, we describe the epidemiology of brain and other CNS tumors in adolescents (ages 15-19 years) in the United States, including mortality, survival, and prevalence. METHODS The Central Brain Tumor Registry of the United States (CBTRUS) data (containing data from the CDC’s National Program of Cancer Registries (NPCR) and NCI’s Surveillance, Epidemiology and End Results (SEER) data) were used to calculate average annual age-specific incidence rates (AASIR) per 100,000 population overall and by sex and race/ethnicity. Average annual age-specific mortality rates (AASMR) per 100,000 population for deaths resulting from all primary malignant brain and other CNS tumors were calculated using mortality data from NCHS. NPCR survival data were used to calculate relative survival (RS). Estimated prevalence counts as of December 31, 2024 were estimated using incidence from CBTRUS and SEER, and survival from SEER. RESULTS AASIR for all brain and other CNS tumors among adolescents was 7.51/100,000. Tumors of the sellar region had the highest incidence (AASIR=2.74/100,000). Overall, incidence was higher for females and non-Hispanic White persons. Overall AASMR was 0.56/100,000. Total five-year RS was 92.0%. Tumors of the pituitary had the highest RS (five-years=99.9%) and glioblastoma had the lowest (five-years=16.4%). As expected, prevalence was highest for tumors of the sellar region (3,720 cases). CONCLUSION Incidence, prevalence, and survival patterns for brain and other CNS tumors vary between adolescents, adults, and children. An accurate statistical assessment of these tumors in adolescents is required to understand risk and impact on this unique population, and to serve as a reference for afflicted individuals, for researchers investigating new therapies, and for the clinicians who treat them.