Glioblastoma multiforme (GBM) is the most aggressive and malignant primary brain tumor, classified as grade IV by the WHO. Despite standard treatments like surgical resection, radiotherapy and chemotherapy (i.e. temozolomide), GBM's prognosis remains poor due to its heterogeneity, recurrence and the impermeability of the blood-brain barrier (BBB). The exact cause of GBM is unclear with potential factors including genetic predisposition and ionizing radiation. Innovative approaches such as nanomicelles-nanoscale, self-assembled structures made from lipids and amphiphilic polymers show promise for GBM therapy. These nanocarriers enhance drug solubility and stability, enabling targeted delivery of therapeutic agents across the BBB. This review explores the synthesis strategies, characterization and applications of nanomicelles in GBM treatment. Nanomicelles improve the delivery of both hydrophobic and hydrophilic drugs and provide non-invasive delivery options. By offering site-specific targeting, biocompatibility, and stability, nanomicelles can potentially overcome the limitations of current GBM therapies. This review highlights recent advancements in the use of nanomicelles for delivering therapeutic agents and nucleic acids addressing the critical need for advanced treatments to improve GBM patient outcomes.

Marred by a median survival of only around 12-15 months coupled with poor prognosis and effective therapeutic deprived drug armory, treatment/management of glioblastoma has proved to be a daunting task. Surgical resection, flanked by radiotherapy and chemotherapy with temozolomide, stands as the standard of care; however, this trimodal therapy often manifests limited efficacy due to the heterogeneous and highly infiltrative nature of GBM cells. In addition, the existence of the blood-brain barrier, tumor microenvironment, and the immunosuppressive nature of GBM, along with the encountered resistance of GBM cells towards conventional therapy, also hinders the therapeutic applications of chemotherapeutics in GBM. This review presents key insights into the molecular pathology of GBM, including genetic mutations, signaling pathways, and tumor microenvironment characteristics. Recent innovations such as immunotherapy, oncolytic viral therapies, vaccines, nanotechnology, electric field, and cancer neuroscience, as well as their clinical progress, have been covered. In addition, this compilation also encompasses a discussion on the role of personalized medicine in tailoring treatments based on individual tumor profiles, an approach that is gradually shifting the paradigm in GBM management. Endowed with the learnings imbibed from past failures coupled with the zeal to embrace novel/multidisciplinary approaches, researchers appear to be on the right track to pinpoint more effective and durable solutions in the context of GBM treatment.

Pleural mesothelioma is an incurable cancer with unmet diagnostic and therapeutic needs. Due to its pattern of local spread, few patients are candidates for multimodality treatment and thus most patients only receive systemic therapy. Chemotherapy (pemetrexed plus platinum) was standard of care until the recent addition of immunotherapy (nivolumab plus ipilimumab, or pembrolizumab plus chemotherapy) as further first-line option. Physicians treating pleural mesothelioma should be aware of another option with Tumor Treating Fields (TTFields) therapy, a locoregionally-applied therapy utilizing electric fields generated by a portable medical device, and delivered to the tumor by skin-placed arrays. TTFields therapy delivered to the thorax using the NovoTTF- 100L device concomitant with pemetrexed and platinum agent is approved for unresectable pleural mesothelioma in the US, and received Conformité Européenne certification in Europe, based on results from the phase 2 STELLAR study (EF- 23; NCT02397928), where TTFields-related toxicity was limited to mild-to-moderate reversible skin reactions. Overall survival in the STELLAR study with TTFields therapy was 18.2 months, with further post-hoc analysis showing extended survival in patients with epithelioid histology. Within the evolving landscape of systemic treatments, TTFields therapy represents a novel and clinically versatile therapeutic option in the battle against pleural mesothelioma without introducing additional toxicities other than mild-to-moderate skin irritation. While promising, additional research is needed to optimize clinical application of TTFields therapy in patients with pleural mesothelioma, such as identifying the molecular determinants of therapy efficacy, and further investigation into the safe and effective delivery of TTFields therapy together with systemic agents, including immunotherapies.

The immunosuppressive tumor immune microenvironment (TIME) renders glioblastoma (GBM) refractory to current chemo-immunotherapeutics. We sought to explore a novel approach for local GBM-associated TIME immunomodulation based on a synergistic combination of the repurposed chemotherapeutic drugs doxorubicin (DOX), which acts to induce immunogenic cell death (ICD) and gemcitabine (GEM), which depletes immunosuppressive myeloid-derived suppressor cells (MDSCs). We conjugated DOX and GEM to hyaluronic acid (HA) to improve efficacy, given this polymer's ability to target CD44 which are overexpressed on cancer cells. The HA-DOX and HA-GEM polymer-drug conjugates provided synergistic cytotoxic effects and maintained ICD-related properties in GBM cells compared to a combination of free drugs. HA-DOX and HA-GEM also reverted the immunosuppressive GBM-associated TIME in orthotopic GL261 tumor-bearing mice by selectively depleting MDSCs and reprogramming M2-like macrophages towards a pro-inflammatory M1-like state, resulting in controlled tumor growth. Local HA-DOX and HA-GEM delivery also increased median survival and controlled tumor growth in an immune refractory SB28-GBM orthotopic mouse GBM model. These findings highlight the potential of repurposing clinically applicable chemotherapeutics in the context of polymer-drug combination treatments for novel immunomodulation strategies in unresectable GBM, which may open new avenues for developing innovative therapies.

Brain tumors, both primary and secondary, represent a significant clinical challenge due to their high mortality and limited treatment options. Primary brain tumors, such as gliomas and meningiomas, and brain metastases from cancers such as non-small cell lung cancer and breast cancer require innovative therapeutic strategies. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR -TKIs) have emerged as a promising treatment option, particularly for tumors harboring EGFR mutations. This review examines the use of EGFR-TKIs in brain tumors, highlighting both laboratory and clinical research findings. In primary brain tumors and brain metastases, EGFR-TKIs have shown potential in controlling tumor growth and improving patient outcomes. Advanced applications, such as nano-formulated EGFR-TKIs and combination therapies with other pathway inhibitors, are being investigated to improve efficacy and overcome resistance. Challenges such as treatment-related events, resistance mechanisms and blood-brain barrier penetration remain significant hurdles. Addressing tumor heterogeneity through personalized medicine approaches is critical to optimizing EGFR-TKI therapies. This review highlights the need for continued research to refine these therapies and improve survival for patients with brain tumors.

Glioblastoma (GBM) remains a challenging cancer to treat with limited effective therapies. Standard treatments, including surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy, offer marginal survival benefits but are often limited by side effects and drug resistance. Temozolomide is the most commonly used chemotherapy; however, resistance and lack of efficacy in recurrent GBM hinder its success. Tumor treating fields (TTFields), a novel non-invasive modality that utilizes alternating electric fields, have recently emerged as a promising treatment for GBM. TTFields work by disrupting the function of the mitotic spindle and inducing apoptosis in cancer cells. They can be especially effective when combined with other therapies. TTFields enhance drug delivery when paired with chemotherapy by increasing the permeability of the blood-brain barrier and cell membranes, leading to more effective tumor inhibition. Similarly, TTFields increase cancer cell sensitivity to radiation therapy and improve the efficacy of targeted therapies, such as sorafenib and immunotherapy, particularly in extra-cranial tumors. The Optune device, the primary medical device for TTFields' delivery, offers a convenient and versatile treatment option, allowing remote care and exhibiting fewer adverse effects. This review discusses the potential of TTFields as a valuable addition to GBM treatment, particularly in combination therapies, and highlights the device's clinical applications.

Glioblastoma (GBM) involves disruptions in the blood-brain barrier (BBB) and alterations in the immune microenvironment, including the activation of glioma-associated macrophages (GAMs). Vascular endothelial growth factor inhibitors, commonly used in recurrent GBM treatment, can influence these processes. This study investigates the relationship between BBB disruption and GAM activation, focusing on plasmalemma vesicle-associated protein (PLVAP), a marker of BBB disruption, and α1-acid glycoprotein (AGP), an inflammatory protein implicated in tumor progression. PLVAP expression was analyzed by immunohistochemistry (IHC) in human GBM samples to determine correlations with tumor grade, proliferation, and GAM activation. Pre- and post-bevacizumab treatment GBM samples were compared to assess changes in BBB integrity and macrophage activity. AGP's role in GAM activation was studied through in vitro assays and glioma implantation in AGP knockout mice, with assessments of tumor growth and angiogenesis. Results showed elevated PLVAP expression in higher-grade gliomas, correlating with increased tumor proliferation and GAM activation, particularly around PLVAP-positive vessels. Bevacizumab treatment reduced PLVAP expression and macrophage activity. AGP localized to regions of BBB disruption, promoting macrophage-mediated tumor growth in vitro. AGP knockout mice demonstrated reduced angiogenesis and prolonged survival. Spatial analysis revealed increased expression of macrophage-inducing molecules near PLVAP-positive vessels. These findings suggest PLVAP as a marker of BBB disruption and glioma malignancy. AGP, associated with BBB leakage, contributes to GAM activation and tumor progression, highlighting its potential as a therapeutic target for GBM.

Astrocytoma grade 4 without isocitrate dehydrogenase (IDH)-based characterisation has been called glioblastoma (GBM) in historical cohorts. There have been significant advancements in diagnostic radiology and pathology, and in the technical aspects of surgery, radiation therapy, and temozolomide (TMZ) used for treatment of this disease. We analysed the outcomes of 267 adult astrocytoma grade 4/GBM patients, consecutively treated between December 2010 and November 2018 using modern techniques at our institute.

All patients underwent surgical resection, histopathology review, and O6-methylguanine-DNA methyltransferase (MGMT) methylation testing, volumetric modulated arc therapy (VMAT)-based radiation therapy using institute-specific target-delineation guidelines and image guidance, and TMZ according to Stupp protocol. Serial multiparametric magnetic resonance imaging-based follow-up ensured early detection of disease progression. Appropriate salvage therapy was determined based on clinicopathological attributes. Kaplan-Meier survival plots, log-rank test, and Cox regression analysis were performed on the prospectively recorded dataset to estimate survival and the factors affecting it.

At a median follow-up of 72 months, the median progression-free survival (PFS), 1-year PFS, and 2-year PFS were 10 months, 37.8%, and 17.5%, respectively. MGMT-methylation, a radiation dose ≥54 Gy, and ≥4 adjuvant TMZ cycles were associated with favourable PFS. Median overall survival (OS), 2-year OS and 5-year OS were 24 months, 48%, and 18%, respectively. MGMT-methylation and 1-year disease control were associated with favourable OS. Salvage treatment could be offered to 69.2% patients, with use of all the three treatment modalities in 12.4%. Salvage reirradiation could be used in 30.8% patients. Haematological toxicity ≥grade 2 was evident in 6% patients during concurrent radiation-TMZ phase and in 9% patients in adjuvant TMZ phase. Postradiation neurocognitive deficits were noted in 20.1% patients, with onset at a median duration of 10 months.

Modern diagnostic and therapeutic techniques affected a near-doubling of survival and acceptable late toxicity, as compared to historical data.

Tumor heterogeneity and an immunosuppressive microenvironment pose significant challenges for immunotherapy against solid tumors, particularly glioblastoma multiforme (GBM). Recent studies have highlighted the crucial role of glioma stem cells (GSCs) in tumor recurrence and therapeutic resistance. In this context, we developed a tandem chimeric antigen receptor (CAR)-T cell targeting CD44 and CD133 (PROM1), containing a truncated IL-7 receptor alpha intracellular domain (Δ7R) between the CD28 costimulatory receptor and the CD3ζ signaling chain (Tanζ-T28-Δ7R). Our target identification and validation were carried out using GSCs, samples from GBM patients, and the corresponding sequencing data. The antitumor efficacy of CAR-T cells was evaluated in patient-derived GSCs, intracranial xenograft models, patient-derived xenograft models, and glioblastoma organoids (GBOs). Single-cell RNA sequencing and mass cytometry were used to determine the immune phenotypes of CAR-T cells. We showed that locoregionally administered Tanζ-T28-Δ7R CAR-T cells induced long-term tumor regression with the desired safety outcomes. Patient-derived autologous Tanζ-T28-Δ7R CAR-T cells showed robust antitumor activity against GBOs. Our pre-clinical data has demonstrated the translational potential of Tanζ-T28-Δ7R CAR-T cell against GBM.

Tumor Treating Fields therapy (TTFields) is an FDA-approved locoregional treatment for patients with newly diagnosed glioblastoma (ndGBM). Previous trial data showed the addition of TTFields to standard TMZ-based therapy to significantly improve overall survival (OS), but real-world data is lacking, particularly with long follow-up duration. Here, we report real-world survival, patterns of progression, and patterns of use for patients for patients with ndGBM treated with or without TTFields.

Patients diagnosed with GBM and treated with standard of care therapy at the Medical College of Wisconsin between March 2015-March 2023 were included. Survival outcomes were assessed and compared across groups who received or did not receive TTFields therapy during maintenance treatment. Patients were followed through March 1, 2024.

A total of 208 patients (TTFields: n = 109; No-TTFields: n = 99) were included for analysis. Baseline characteristics were consistent across groups. Median OS and PFS were significantly improved for the TTFields group vs. No-TTFields group (median OS: 21.7 vs. 17.7 months, p = 0.029; median PFS: 12.4 vs. 9.6 months, p = 0.047). Patients treated with TTFields exhibited a higher rate of non-local progression vs. No-TTFields group. Median OS and PFS were each significantly longer for the ≥ 75% usage group compared with < 75% via matched analysis.

The results of this study reveal an association between TTFields use and long-term survival benefit, consistent with pivotal trial findings. TTFields use is associated with a higher incidence of non-local patterns of progression, and TTFields device usage ≥ 75% is associated with increased progression-free and long-term survival.

Gliomas represent a heterogeneous group of primary brain tumors with variable biological behavior. High-grade variants, notably glioblastomas, exhibit aggressive growth and a poor prognosis. Although surgical resection is central to management, it may lead to systemic and regional postoperative complications that adversely affect outcomes. While neurological complications have been extensively studied, comprehensive analyses of non-neurological sequelae remain limited. This study aimed to estimate the pooled proportion of postoperative systemic and regional complications following glioma resection and to identify factors influencing these proportions. A systematic review and meta-analysis was conducted per PRISMA guidelines. PubMed, Web of Science, and Embase were searched for English-language articles published between January 2000 and November 2024 reporting postoperative complications in glioma resection patients. Pooled proportion were calculated using a random-effects model, and meta-regression assessed the impact of covariates including patient age, gender, publication date, geographical location, and sample size. Seventy-seven studies were included. The pooled proportions for postoperative complications were as follows: venous thromboembolism, 4.92% (95% CI: 1.51-10.05%); deep vein thrombosis, 4.75% (95% CI: 2.86-7.05%); urinary tract infection, 3.77% (95% CI: 0.81-8.47%); hydrocephalus, 2.53% (95% CI: 1.37-3.97%); pulmonary infection, 2.39% (95% CI: 1.15-3.99%); cerebrospinal fluid leak, 2.22% (95% CI: 0.99-3.87%); surgical site infection, 2.21% (95% CI: 1.48-3.07%); meningitis, 1.49% (95% CI: 0.47-2.96%); pulmonary embolism, 1.33% (95% CI: 0.74-2.06%); and sepsis, 1.12% (95% CI: 0.08-3.02%). Significant heterogeneity was observed across studies, with meta-regression revealing that geographical location, publication date, and patient age were significant moderators influencing certain complication rates. This meta-analysis demonstrates that, while systemic and regional complication rates following glioma resection are relatively low, they remain clinically significant. In particular, venous thromboembolism and deep vein thrombosis are notably prevalent. Moreover, significant heterogeneity-shaped by geography, publication date, and patient age-underscores the need for tailored perioperative strategies and further research.

Few effective immune prognostic models based on the tumor immune microenvironment (TIME) for glioblastoma have been reported. Therefore, this study aimed to construct an immune prognostic model for glioblastoma by analyzing enriched biological processes and pathways in tumors.

A comprehensive single-sample gene set enrichment analysis (ssGSEA) of gene sets from the Molecular Signatures Database was performed using TCGA RNA sequencing data (141 glioblastoma cases). After evaluating gene sets associated with prognosis using univariable Cox regression, gene sets related to biological processes and tumor immunity in gliomas were extracted. Finally, the least absolute shrinkage and selection operator Cox regression refined the gene sets and a nomogram was constructed. The model was validated using CGGA (183 cases) and Aichi Cancer Center (42 cases) datasets.

The immune prognostic model consisted of three gene sets related to biological processes (sphingolipids, steroid hormones, and intermediate filaments) and one related to tumor immunity (immunosuppressive chemokine pathways involving tumor-associated microglia and macrophages). Kaplan-Meier curves for the training (TCGA) and validation (CGGA) cohorts showed significantly worse overall survival in the high-risk group compared to the low-risk group (p < 0.001 and p = 0.04, respectively). Furthermore, in silico cytometry revealed a significant increase in macrophages with immunosuppressive properties and T cells with effector functions in the high-risk group (p < 0.01) across all cohorts.

Construction of an immune prognostic model based on the TIME assessment using ssGSEA could potentially provide valuable insights into the prognosis and immune profiles of patients with glioblastoma and guide treatment strategies.

Glioblastoma, a grade IV astrocytoma, typically has a poor prognosis, with most patients succumbing within eighteen months of diagnosis and few experiencing long-term survival. Focused ultrasound, an emerging localized therapy, has shown promising results in early-phase studies for glioblastoma by improving the uptake of temozolomide and carboplatin. The blood-brain barrier is critical to homeostasis by regulating the movement of substances between the bloodstream and the central nervous system. While this barrier helps prevent infections from bloodborne pathogens, it also hinders the delivery of cancer therapies to gliomas. Combining focused ultrasound with circulating microbubbles enhances local blood-brain barrier permeability, facilitating the intratumoral uptake of systemic cancer therapies. The purpose of this study was to identify promising new therapeutics in the treatment of glioblastoma for localized drug delivery via focused ultrasound. This review provides an overview of the current standard of care for newly diagnosed and recurrent glioblastoma, identifies current therapies indicated for the treatment, discusses key aspects of microbubble resonators, describes focused ultrasound devices under evaluation in human trials, and concludes with a perspective of emerging therapeutics for future studies.

Rhenium (186Re) Obisbemeda (186RNL), chelated-186Re encapsulated in nanoliposomes and delivered to brain tumors via convection enhanced delivery (CED), was evaluated in a Phase 1 dose escalation trial (NCT01906385). The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included safety and tolerability, dose distribution, the overall response rate (ORR), disease-specific progression-free survival (PFS), and overall survival (OS). 21 patients received up to 22.3 mCi 186RNL over 6 dosing cohorts. Most adverse events (AEs) were unrelated to 186RNL and the MTD was not reached. Although not predefined outcomes, the mOS and mPFS were 11 and 4 months, respectively, and found to correlate with radiation absorbed dose to the tumor and percent tumor treated. When dichotomized by absorbed dose of 100 Gy, the mOS and mPFS were 17 months and 6 months, respectively, for >100 Gy, compared to 6 (mOS) and 2 (mPFS) months, respectively, for <100 Gy. For ORR, 57.1% exhibited stable disease (SD), 4.8% partial response, and 38.1% progressive disease. Overall, patients received radiation absorbed doses without significant toxicity higher than possible with external beam radiation therapy (EBRT) and demonstrated mOS beyond standard of care for recurrent glioblastoma (~8 months).

Gliomas, a type of malignant tumor, are marked by a short survival period and an unfavorable prognosis. Disulfide stress, which arises from an overabundance of intracellular cystine, can initiate disulfidoptosis, an emerging form of cell death. The link between gliomas and disulfidoptosis has not been extensively explored. This study breaks new ground by investigating the correlation between glioma prognosis and lncRNAs associated with disulfidoptosis, with the aim of improving glioma treatment strategies.

We analyzed 10 long non-coding RNAs (lncRNAs) co-expressed with disulfidoptosis genes, retrieved clinical information and gene expression profiles from glioma and normal groups in the TCGA database, and developed a prognostic model for lncRNAs based on this data. The receiver operating characteristic curve (ROC) was used to evaluate and validate the model's reliability. Furthermore, the Kaplan-Meier survival curve was employed to assess the disparity in overall survival (OS) among patients with varying risk scores. We also examined the tumor microenvironment (TME), immune cell infiltration, immune-related functions, tumor mutational burden (TMB), and OncoPredict in samples with differing risk scores. To confirm the expression variations of genes associated with prognostic models in cell lines, quantitative polymerase chain reaction (qPCR) was employed.

Eleven long non-coding RNAs (lncRNAs) were identified for constructing prognostic models by analyzing lncRNAs associated with disulfidoptosis genes using Cox regression and LASSO regression analyses. The study's findings indicate that these 11 key lncRNAs serve as independent predictors of overall survival (OS) in glioma patients. Moreover, the frequency with which patients of varying risk scores opt for immune checkpoint blockade (ICB) therapy and chemotherapy not only differs but also their responses to these treatments are significantly distinct, suggesting that the risk score could be a predictive factor for treatment response.

This research sheds light on the characteristics of disulfidoptosis in glioma, revealing that patterns of disulfidoptosis in patients can be effectively assessed using a risk score. Consequently, the judicious application of this prognostic model can significantly inform clinical treatment strategies and precision medicine for glioma, potentially improving patient outcomes.

Chimeric antigen receptor (CAR)-T cell therapy targeting novel glioblastoma (GBM)-specific cell surface antigens is a promising approach. However, transcriptome analyses have revealed few GBM-specific target antigens.

A library of monoclonal antibodies (mAbs) against tumor cell lines derived from patients with GBM was generated. mAbs reacting with tumor cells in resected tissues from patients with GBM but not with nonmalignant human brain cells were detected. The antigens that were recognized were identified through expression cloning. CAR-T cells derived from a candidate mAb were generated, and their functionality was tested in vitro and in vivo.

Approximately 3,200 clones were established. Among them, 5E17 reacted with tumor cells in six of seven patients with GBM, but not with nonmalignant human brain cells. Prostaglandin F2 receptor negative regulator (PTGFRN) was identified as an antigen recognized by 5E17. CAR-T cells derived from 5E17 produced cytokines and exerted cytotoxicity upon co-culture with tumor cells from patients with GBM. Furthermore, intracranial injection of 5E17-CAR-T cells demonstrated antitumor effects in an orthotopic xenograft murine model with patient-derived GBM cells.

Cell surface PTGFRN is a candidate target for intracranial CAR-T cell therapy for GBM. On-target off-tumor toxicity in alternative normal tissues needs to be carefully tested.

Elevated levels of androgens in the brain accelerate tumor progression in patients with glioblastoma (GBM). Despite current research efforts concentrating on decreasing peripheral androgens to improve GBM prognosis, results have not met expectations. Herein, we aim to elucidate the source of increased androgen levels in the brains of GBM patients and investigate whether lowering it can improve the prognosis of GBM patients. The Elisa was employed to measure androgen levels. The effects of androgens on U87 cells were evaluated using CCK-8 assays, clone formation assays, wound healing assays, and migration/invasion assays. RNA sequencing, RT-qPCR and Western blotting were performed to assess the expression levels of steroid enzymes, tumor drug resistance, Sirt1, FOXO1genes and proteins. Co-immunoprecipitation (Co-IP) assays were conducted to investigate the interactions and acetylation levels between Sirt1 and FOXO1. Lentiviral transfection was utilized to establish stable cell lines. Furthermore, an in vivo murine subcutaneous tumor model was established to further confirm the role of Sirt1 in tumor progression. We found androgen levels in the cerebrospinal fluid of GBM patients were higher than in the periphery, contrasting with healthy individuals. Additionally, the steroid enzymes in GBM cells were upregulated. Reducing peripheral androgens compensatorily enhances GBM androgen synthesis capacity (CYP17A1, CYP11A1, SRD5A2) and chemo-resistance (ABCB11, BIRC3, FGF2, NRG1), while the levels of androgens in the brain remain consistently high. The above results indicate that the increased androgens in the brain of GBM patients are self-secreted. Further investigations demonstrate that the transcription factor FOXO1 in GBM is regulated by silent information regulator 1 (Sirt1) through deacetylation, leading to enhanced androgen synthesis capacity in vivo and in vitro. Overexpressing Sirt1 significantly lowers brain androgen levels and delays tumor progression in mouse models. Compared to conventional finasteran therapy, the targeted-Sirt1 results in lower brain androgen levels and smaller tumor volumes. Our findings provide evidence that the elevated androgens in the brain of GBM patients came from tumor autocrine. Overexpression of Sirt1 reduces FOXO1 acetylation, lowers androgen synthesis enzyme levels, and effectively decreases brain androgen levels, thereby delaying tumor progression.

Glioblastoma is a highly heterogeneous brain tumor, posing challenges for precision therapies and patient stratification in clinical trials. Understanding how genetic mutations influence tumor imaging may improve patient management and treatment outcomes. This study investigates the relationship between imaging features, spatial patterns of tumor location, and genetic alterations in IDH-wildtype glioblastoma, as well as the likely sequence of mutational events.

We conducted a retrospective analysis of 357 IDH-wildtype glioblastomas with pre-operative multiparametric MRI and targeted genetic sequencing data. Radiogenomic signatures and spatial distribution maps were generated for key mutations in genes such as EGFR, PTEN, TP53, and NF1 and their corresponding pathways. Machine and deep learning models were used to identify imaging biomarkers and stratify tumors based on their genetic profiles and molecular heterogeneity.

Here, we show that glioblastoma mutations produce distinctive imaging signatures, which are more pronounced in tumors with less molecular heterogeneity. These signatures provide insights into how mutations affect tumor characteristics such as neovascularization, cell density, invasion, and vascular leakage. We also found that tumor location and spatial distribution correlate with genetic profiles, revealing associations between tumor regions and specific oncogenic drivers. Additionally, imaging features reflect the cross-sectionally inferred evolutionary trajectories of glioblastomas.

This study establishes clinically accessible imaging biomarkers that capture the molecular composition and oncogenic drivers of glioblastoma. These findings have potential implications for noninvasive tumor profiling, personalized therapies, and improved patient stratification in clinical trials.

With few viable treatment options, glioblastoma (GBM) is still one of the most aggressive and deadly types of brain cancer. Recent developments in lipidomics have demonstrated the potential of lipid metabolism as a therapeutic target in GBM. The thorough examination of lipids in biological systems, or lipidomics, is essential to comprehending the changed lipid profiles found in GBM, which are linked to the tumor's ability to grow, survive, and resist treatment. The use of lipidomics in drug delivery and discovery is examined in this study, focusing on how it may be used to find new biomarkers, create multi-target directed ligands, and improve drug delivery systems. We also cover the use of FDA-approved medications, clinical trials that use lipid-targeted medicines, and the integration of lipidomics with other omics technologies. This study emphasizes lipidomics as a possible tool in developing more effective treatment methods for GBM by exploring various lipid-centric techniques.

The malignant interaction between tumor cells and immune cells is one of the important reasons for the rapid progression and refractoriness of glioblastoma (GBM). As an essential metabolic center of M2 macrophages, the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the reduction of M2 macrophages. Nevertheless, the restriction of the blood-brain barrier (BBB) and non-specific cell targeting hinder the application of PERK inhibitors in GBM. Herein, the optimal NP-M-M2pep is developed successfully, which has shown the capacity of BBB penetration and specific targeting of M2 microglia. In addition to inhibiting the polarization of M2 microglia, the administration of iPERK@NP-M-M2pep reprogrammed M2 microglia into M1 ones in vitro via PERK/HIF-1α/glycolysis pathway. Efficient brain accumulation of nanoparticles is achieved after tail vein injection, with effective inhibition of GBM progression after one course of treatment. The glioma-associated microglia and macrophages (GAM) with M2 type are induced to M1 and the immunosuppressive TME is remodeled by upregulating immunostimulatory cells and downregulating immunosuppressive cells. In summary, the biomimetic membrane vesicles (BMVs) specifically delivered iPERK to GAMs offer an inspiring strategy to reprogram microglia polarization, re-educate immunosuppressive TME, and inhibit the progression of GBM.

Glioblastoma multiforme (GBM) is a highly malignant central nervous system tumor with a poor prognosis. Developing new therapeutic drugs is crucial. This study evaluates deoxyelephantopin (DET), a major component of *Elephantopus scaber* L., for its potential anti-GBM effects. The effects of DET on GBM cell lines were investigated using the MTT assay and Annexin-V kit to assess cell death and apoptosis. Western blot analysis examined apoptosis and cell cycle-related proteins. ELISA kits measured VEGF and TGF-β levels. In vivo, NOD SCID mice were injected with GL-261 cells and treated with DET to evaluate tumor growth and survival. DET inhibited GBM cell growth in a time- and dose-dependent manner. MTT and Annexin-V assays confirmed cell death and apoptosis. Western blot analysis showed DET downregulated Bcl-2 and increased caspase-3, Bax, and cytochrome c levels. ELISA results indicated that DET suppressed VEGF and TGF-β expression. DET treatment also decreased phosphorylation of AKT and STAT-3, CDK4, cyclin D2, MMP2, and MMP9 levels. In vivo, DET significantly inhibited tumor growth and improved survival rates in mice. DET exhibits significant in vitro and in vivo anticancer effects, making it a promising candidate for further research and potential clinical application against GBM.

Despite multimodal therapies, the treatment of glioblastoma remains challenging. In addition to the very complex mechanisms of cancer cells, including specialized phenotypes that enable them to proliferate, invade tissues, and evade immunosurveillance, they exhibit a pronounced resistance to chemo- and radiotherapy. More advanced tumors create a hypoxic environment that supports their proliferation and survival, while robust angiogenesis ensures a constant supply of nutrients. In GBM, these structures are very pronounced and contribute to the creation and maintenance of a highly immunosuppressive microenvironment that promotes tumor growth and immune escape. In addition, the high accumulation of immunosuppressive tumor-infiltrating leukocytes and other cells, the pronounced expression of immune checkpoint molecules, and the low mutational burden, i.e., the low number of neoantigens, are hallmarks of GBM and contribute to the challenge of therapeutic approaches. Here, we review a number of mechanisms that GBM exploits to support tumor growth and potential treatments. These include new chemotherapeutics, tumor treating fields, and small molecules, including compounds targeting angiogenesis or blockers of tyrosine kinases that inhibit tumor cell proliferation and survival. In addition, we focus on immunotherapies such as immune checkpoint blockade or cell therapies, in particular vaccination with dendritic cells and CAR-T cells, which can either kill GBM cells directly or bypass immunosuppression by modulating the tumor microenvironment or boosting the patient's own immune response.

Glioblastoma (GBM) is an aggressive cancer with limited treatment options. Immunotherapy targeting CD69, an early activation marker on T cells, has shown promise in preclinical models of non-CNS malignancies. This study investigates anti-CD69 therapy alone or in combination with anti-PD-1 in a preclinical GBM model.

CD69 expression in GBM patient tissues was analyzed using the TCGA database. Therapeutic efficacy of anti-CD69 was tested in a murine GBM model with different regimens. Immune cell populations in the tumor microenvironment (TME) were assessed by flow cytometry.

Increased CD69 expression was observed in GBM patients compared to normal brain tissue and was associated with worse prognosis. Anti-CD69 treatment reduced percentages of CD69+ immune cells but did not improve survival in GBM-bearing mice. Increased PD-1 expression on NK cells was observed following anti-CD69 treatment. Anti-CD69 treatment was not improved by the addition of anti-PD-1 in vivo.

This is the first study evaluating anti-CD69 therapy in a preclinical GBM model. Despite promising preclinical data in other cancers, anti-CD69 monotherapy or combination therapy with anti-PD-1 did not improve survival in this GBM model.

Patients with glioblastoma (GBM) often have inaccurate perceptions of prognosis. Strong religious beliefs have been associated with limited illness understanding (IU) in patients with advanced cancer, but IU and religiousness have not been investigated in patients with GBM. The aim of this study was to evaluate the association between religiousness and spirituality and IU in patients with GBM.

Patients enrolled in a prospective multicenter study of recurrent GBM (Coping with Glioblastoma, NCT02375841). Within one month of medical visits discussing MRI scans showing GBM progression, patients completed study surveys containing published measures of IU and religiousness. IU was compared between participants with moderate or high versus slight or no religiousness based on several patient-reported prompts using Fisher's exact tests.

Twenty-four patients completed surveys of religiousness and IU. IU was partial within our cohort. Fifteen participants (62.5%) acknowledged that their illness was terminal. Only 6 (25%) correctly acknowledged their prognosis (months). Eleven patients (46%) were moderately or very religious, while 9 (38%) were either slightly religious or not at all religious. High religiousness and spirituality were each associated with partial IU (P = .06 and P = .01, respectively). A belief that God could perform a miracle to cure them of cancer and a belief in sanctity through suffering were also each associated with partial IU.

This prospective study that suggests religiousness, including the belief in miracles and a belief in sanctification through suffering, might influence patients' IU. Further research is warranted to study this association.

High-grade gliomas are devastating cancers that remain incurable with standard surgical resection and radiochemotherapy. Although beneficial against neoplasms, radiation lowers lymphocyte counts, weakens immune activation, and recruits suppressive myeloid cells impairing immune responses. Tumor environments treated with radiation experience long-term immunosuppression, reducing immunotherapy effectiveness and contributing to recurrence. Investigating pre-radiation treatments in newly diagnosed patients could identify active agents, assess immunotherapy impact, and enable multiomic analyses without radiation-induced confounding factors. This literature review was conducted to describe the feasibility, safety, and outcomes of postsurgical, pre-radiation clinical trials for adults with newly diagnosed high-grade glioma.

A systematic review was performed of the English-language literature reporting results of clinical trials for adults with newly diagnosed high-grade glioma administered postsurgical treatment prior to radiation therapy. A search was conducted in PubMed and references cited in research and review articles were also considered.

From 1991 to 2024, 52 clinical trials were identified: 3 phase I, 38 phase II, 4 phase III, and 7 of unknown phase. Nine trials were randomized, 24 were multicenter trials, 21 investigated temozolomide-containing regimens, and 12 focused on inoperable tumors, involving a total of 2737 patients.

Pre-radiation neoadjuvant studies are feasible and may identify active drugs. This is particularly relevant in the era of personalized medicine with brain-penetrant drugs, targeted therapy, and immuno-oncology advancements. Investigating pre-radiation treatments in newly diagnosed high-grade glioma is a viable approach to rapidly identify active and inactive regimens while the immune system and tumor microenvironment remain intact.

Glioblastoma, isocitrate dehydrogenase (IDH)-wildtype (GBM), is the most malignant brain tumor in adults, with limited therapeutic intervention. Previous studies have identified a few prognostic markers for GBM, including the methylation status of O6-methylguanine-DNA methyltransferase (MGMT) promoter, TERT promoter mutation, EGFR amplification, and CDKN2A/2B deletion. However, the classification of GBM remains incomplete, necessitating a comprehensive analysis. In this study, we investigated the impact of p16INK4A expression in GBM and found that p16INK4A-high GBM exhibits distinct characteristics compared to p16INK4A-low GBM. Specifically, tumor cells with p16INK4A-high expression display a senescent phenotype and are correlated with higher intra-tumoral immune cell infiltration. Furthermore, an association was observed between elevated p16INK4A expression in GBM and extended overall survival of patients. Our in vivo and in vitro studies revealed that CCL13 is predominantly expressed by p16INK4A-high GBM cells. The released CCL13 enhances the infiltration of T cells within the tumor, potentially contributing to the improved prognosis observed in patients with high p16INK4A expression. These findings suggest that tumor cells with a senescence phenotype in GBM, through the secretion of chemokines such as CCL13, may augment immune cell infiltration and potentially enhance patient outcomes by creating a more immunologically active tumor microenvironment.

Purpose: Early treatment response assessments are crucial, and the results are known to better correlate with prognosis and survival outcomes. The present study was conducted to differentiate true progression (TP) from pseudoprogression (PsP) in long-term-surviving glioblastoma patients using our previously established multiparametric MRI-based predictive model, as well as to identify clinical factors impacting survival outcomes in these patients. Methods: We report six patients with glioblastoma that had an overall survival longer than 5 years. When tumor specimens were available from second-stage surgery, histopathological analyses were used to classify between TP (>25% characteristics of malignant neoplasms; n = 2) and PsP (<25% characteristics of malignant neoplasms; n = 2). In the absence of histopathology, modified RANO criteria were assessed to determine the presence of TP (n = 1) or PsP (n = 1). The predictive probabilities (PPs) of tumor progression were measured from contrast-enhancing regions of neoplasms using a multiparametric MRI-based prediction model. Subsequently, these PP values were used to define each lesion as TP (PP ≥ 50%) or PsP (PP < 50%). Additionally, detailed clinical information was collected. Results: Our predictive model correctly identified all patients with TP (n = 3) and PsP (n = 3) cases, reflecting a significant concordance between histopathology/modified RANO criteria and PP values. The overall survival varied from 5.1 to 12.3 years. Five of the six glioblastoma patients were MGMT promoter methylated. All patients were female, with a median age of 56 years. Moreover, all six patients had a good functional status (KPS ≥ 70), underwent near-total/complete resection, and received alternative therapies. Conclusions: Multiparametric MRI can aid in assessing treatment response in long-term-surviving glioblastoma patients.

Spectroscopic MRI (sMRI) is a quantitative imaging technique that maps infiltrated tumors in the brain without contrast injections. In a previous study (NCT03137888), sMRI-guided radiation treatment extended patient survival, showing promise for clinical translation. The spectral fitting of individual voxels in an sMRI dataset generate metabolite concentration maps that guide treatment. The established spectral analysis methods use iterative least-squares fitting (FITT) that are computationally demanding. This study compares the performance of NNFit, a neural network-based, accelerated spectral fitting model, to the established FITT for metabolite quantification and radiation treatment planning.

NNFit is a self-supervised deep learning model trained on 50 ms echo-time (TE) sMRI data to estimate metabolite levels of choline (Cho), creatine (Cr), and NAA. We trained the model on 30 GBM patients (56 scans) and tested it on 17 GBM patients (29 scans). NNFit's performance was compared to the FITT using structural similarity indices (SSIM) and the Dice coefficient.

NNFit significantly improved processing speed while maintaining strong agreement with FITT. The radiation target volumes defined by Cho/NAA ≥ 2x were visually comparable, with fewer artifacts in NNFit. Structural similarity indices (SSIM) indicated minimal bias and high consistency across methods.

This study highlights NNFit's potential for rapid, accurate, and artifact-reduced metabolic imaging, enabling faster radiotherapy planning.

Glioblastoma (GBM) is a lethal primary brain cancer with a 5.6% five-year survival rate. Tumor treating fields (TTFields) are alternating low-intensity electric fields that have demonstrated a GBM patient survival benefit. We previously reported that 0.5-24 h of TTFields exposure resulted in an increased uptake of FITC-dextran fluorescent probes (4-20 kDa) in human GBM cells. However, this approach, in which a fluorescence plate-based detector is used to evaluate cells attached to glass coverslips, cannot distinguish FITC-dextran uptake in live vs. dead cells. The goal of the study was to report the optimization and validation of two independent methods to quantify human GBM cell membrane permeabilization induced by TTFields exposure. First, we optimized flow cytometry by measuring mean fluorescence intensity at 72 h for 4 kDa (TTFields 6726 ± 958.0 vs. no-TTFields 5093 ± 239.7, p = 0.016) and 20 kDa (7087 ± 1137 vs. 5055 ± 897.8, p = 0.031) probes. Second, we measured the ratio of lactate dehydrogenase (LDH) to cell viability (measured using the CellTiter-Glo [CTG] viability assay); the LDH/CTG ratio was higher under TTFields (1.47 ± 0.15) than no-TTFields (1.08 ± 0.08) conditions, p < 0.0001. The findings using these two independent methods reproducibly demonstrated their utility for time-dependent evaluations. We also showed that these methods can be used to relate the cell membrane-permeabilizing effects of the non-ionizing radiation of TTFields to that of an established cell membrane permeabilizer, the non-ionic detergent Triton-X-100. Evaluating carboplatin ± TTFields, the LDH/CTG ratio was significantly higher in the TTFields vs. no-TTFields condition at each carboplatin concentration (0-30 µM), p = 0.014. We successfully optimized and validated two cost-effective methods to reproducibly quantify TTFields-induced human GBM cancer cell membrane permeabilization.

Glioblastoma(GBM) is a highly malignant primary central nervous system tumor that poses a significant threat to patient survival due to its treatment resistance and rapid recurrence.Current treatment options, including maximal safe surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, have limited efficacy.In recent years, the role of glycolytic metabolic reprogramming in GBM has garnered increasing attention. This review delves into the pivotal role of glycolytic metabolic reprogramming in GBM, with a particular focus on the multifaceted roles of lactate, a key metabolic product, within the tumor microenvironment (TME). Lactate has been implicated in promoting tumor cell proliferation, invasion, and immune evasion. Additionally, this review systematically analyzes potential therapeutic strategies targeting key molecules within the glycolytic pathway, such as Glucose Transporters (GLUTs), Monocarboxylate Transporters(MCTs), Hexokinase 2 (HK2), 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), Pyruvate Kinase Isozyme Type M2 (PKM2), and the Lactate Dehydrogenase A (LDHA). These studies provide a novel perspective for GBM treatment. Despite progress made in existing research, challenges remain, including drug penetration across the blood-brain barrier, side effects, and resistance. Future research will aim to address these challenges by improving drug delivery, minimizing side effects, and exploring combination therapies with radiotherapy, chemotherapy, and immunotherapy to develop more precise and effective personalized treatment strategies for GBM.

Recently, criteria based on amino acid positron emission tomography (PET) have been proposed for response assessment in diffuse gliomas (PET RANO 1.0). In this study, we compare the prevalence of measurable disease according to PET RANO 1.0 with magnetic resonance imaging (MRI)-based Response Assessment in Neuro-Oncology (RANO) criteria in glioblastoma.

We retrospectively identified patients with newly diagnosed IDH-wild-type glioblastoma who underwent [18F] Fluoroethyltyrosine (FET) PET and MRI after resection or biopsy and before radio-/radiochemotherapy. Two independent investigators analyzed measurable disease according to PET RANO 1.0 or MRI-RANO criteria. Additionally, lesion size, congruency patterns, and uptake intensity on [18F]FET PET images were assessed.

We evaluated 125 patients including 49 cases after primary resection and 76 cases after biopsy. Using PET criteria, 113 out of 125 patients (90.4%) had measurable disease, with a median PET-positive volume of 15.34 cm3 (8.83-38.03). With MRI, a significantly lower proportion of patients had measurable disease (57/125, 45.6%; P < .001) with a median sum of maximum cross-sectional diameters of 35.65 mm (26.18-45.98). None of the 12 patients without measurable disease on PET had measurable disease on MRI. Contrariwise, 56/68 patients (82.4%) without measurable disease on MRI exhibited measurable disease on PET. Clinical performance status correlated significantly with PET-positive volume and MRI-based sum of diameters (P < .0059, P < .0087, respectively).

[18F]FET PET identifies a higher number of patients with measurable disease compared to conventional MRI in newly diagnosed glioblastoma. PET-based assessment may serve as a novel baseline parameter for evaluating residual tumor burden and improving patient stratification in glioblastoma studies. Further validation in prospective trials is warranted.

Tumor Treating Fields (TTFields) has emerged as a significant adjunctive component in the treatment of high-grade gliomas following the EF-14 trial in 2017. The incorporation of TTFields, alongside cyclic temozolomide therapy, has demonstrated improved patient outcomes when the usage exceeds 18 h per day (75% usage). Post-hoc analysis of the EF-14 trial has demonstrated that therapy usage exceeding 90% is associated with an additional benefit, while rates above 50% have also proven effective in literature. Given the cost-intensive nature and mild- to- moderate constraints associated with the therapy, our objective is to generate real-world data on therapy usage through a retrospective analysis at a high-throughput academic center. Between June 2015 and February 2022, a total of 113 high-grade glioma patients received TTFields therapy. Eight patients discontinued TTFields therapy within 2 months with less than 50% usage and were excluded from further analysis. For the remaining patients, the median age was 51 years (range: 20-76 years) and the mean preoperative Karnofsky index was 80%-90%. Most of the patients (75.2%) initiated therapy concurrently with first-line treatment, of whom 27.6% started TTFields therapy concomitant to the first cycle of temozolomide. 15.2% started TTFields therapy in the second-line and 9.5% in the third-line setting. The study cohort had an average therapy duration of 9.3 months with 3.2 break days per month. The mean therapy usage was 65.5% (SD 17.6%). Usage was highest during the first 3 months, with rates of 77.7%, 72.3%, and 71.6%, and then dropped to around 60% in the following 6 months. Linear regression found no predictors of usage, such as age, timing of therapy initiation, and duration or gender. 55% of patients continued TTFields beyond the first recurrence. Interestingly, no drop in usage rates was observed before tumor recurrence was communicated. However, after diagnosis, patients exhibited a significant drop in usage to an average of 52.3%. This high-volume, real-world TTFields usage data reveal that the extent of usage falls short of the intended 75%. It highlights the importance of monitoring and promoting adherence to maximize its potential benefits in managing high-grade glioma patients. Furthermore, strategies to expedite therapy initiation and improve long-term adherence are warranted.

Glioblastomas (GBM) are malignant tumours with poor prognosis. Treatment involves chemotherapy and/or radiotherapy; however, there is currently no standard treatment for recurrence, and prognosis remains unfavourable. Inflammatory mediators and microRNAs (miRNAs) influence the aggressiveness of GBM, being involved in the communication with the cells of the tumour parenchyma, including microglia/macrophages, and maintaining an immunosuppressive microenvironment. Hence, the modulation of miRNAs and inflammatory factors may improve GBM treatments. In this study, we investigated the effects of agathisflavone, a biflavonoid purified from Cenostigma pyramidale (Tul.), on the growth and migration of GBM cells, on the expression of inflammatory cytokines and microRNAs, as well on the response of microglia. Agathisflavone (5-30 μM) induced a dose- and time-dependent reduction in the viability of both human GL-15 and rat C6 cells, as determined by the MTT test, and reduced cell migration, as determined by cell scratch assay. RT-qPCR analysis revealed that agathisflavone (5 μM) down-regulated the expression of miR-125b and miR-155 in the secretome derived from GL-15 cells, which was associated with upregulation of the mRNA expression of IL-6 and arginase-1 immunoregulatory factors. Exposure of human microglia/macrophage to the secretome from GL-15 GMB cells modulated proliferation and morphology, effects that were modulated by agathisflavone treatment. These results demonstrate the effect of flavonoids on the growth of GBM cells, which impacts cells in the microenvironment and can be considered for preclinical studies for adjuvant treatments.

Tumor-Treating Fields (TTFields) use intermediate-frequency and low-intensity electric fields to inhibit tumor cells. However, their mechanisms are still not well understood. This article reviews their key antitumor mechanisms at the cellular and molecular levels, including inhibition of proliferation, induction of death, disturbance of migration, and activation of the immune system. The multifaceted biological effects in combination with other cancer treatments are also summarized. The deep insight into their mechanism will help develop more potential antitumor treatments.

Glioblastoma multiforme (GBM) is one of the most aggressive and lethal brain tumors, characterized by rapid growth, invasiveness, and resistance to standard therapies, including surgery, chemotherapy, and radiotherapy. Despite advances in treatment, GBM remains highly resistant due to its complex molecular mechanisms, including angiogenesis, invasion, immune modulation, and lipid metabolism dysregulation. This review explores recent breakthroughs in targeted therapies, focusing on innovative drug carriers such as nanoparticles and liposomes, and their potential to overcome GBM's chemo- and radioresistant phenotypes. We also discuss the molecular pathways involved in GBM progression and the latest therapeutic strategies, including immunotherapy and precision medicine approaches, which hold promise for improving clinical outcomes. The review highlights the importance of understanding GBM's genetic and molecular heterogeneity to develop more effective, personalized treatment protocols aimed at increasing survival rates and enhancing the quality of life for GBM patients.

To investigate the relationship between the tumor microenvironment (TME), tumor-related seizures (TRS), and cerebrospinal fluid (CSF) markers that predict preoperative seizures in patients with glioblastoma.

In total, 47 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma who underwent preoperative CSF examination, 3-T magnetic resonance spectroscopy (MRS), and neurological surgery between January 2017 and December 2023 were included. We measured the concentrations of soluble CD163 (sCD163), a soluble form of the M2 macrophage marker, in the CSF, the metabolite concentration on MRS, and the number of CD163-positive M2 macrophages in the tumor tissue. Factors associated with preoperative seizures were examined.

Twelve patients (25.5%) had preoperative seizures. sCD163 levels in the CSF were positively correlated with the number of CD163-positive M2 macrophages in the tumor tissue, and both were significantly lower in the preoperative seizure group than in the non-preoperative seizure group (p = 0.0124 and p < 0.0001, respectively). MRS indicated that only glutathione (GSH) concentrations were higher in the preoperative seizure group than in the non-preoperative seizure group (2.55 mM and 1.87 mM, respectively; p = 0.0171). CD163-positive M2 macrophages were inversely correlated with GSH levels. sCD163 in the CSF had a high predictive accuracy (sensitivity, 91.7%; specificity, 54.3%; and area under the receiver operator curve, 0.745) for preoperative seizures.

The CSF level of sCD163 is useful for predicting the TME and preoperative seizures in IDH wild-type glioblastoma.