BACKGROUND: High-grade gliomas (HGG) are the most aggressive primary brain tumors with poor prognoses despite conventional treatments. Immunotherapy has emerged as a promising avenue due to its potential to elicit a targeted immune response against tumor cells.
OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of various immunotherapeutic strategies, including immune checkpoint inhibitors (ICI), virotherapy, and dendritic cell vaccines (DCV) in treating HGG.
METHODS: Following the PRISMA framework, we searched PubMed, Cochrane, and Embase for studies reporting outcomes of HGG patients treated with immunotherapy. Key metrics included overall survival, progression-free survival, and treatment-related adverse events.
RESULTS: We reviewed 47 studies, analyzing data from 3674 HGG patients treated with immunotherapy. The mean overall survival for patients treated with ICI was 11.05 months, with virotherapy at 11.79 months and notably longer for DCV at 24.11 months. The mean progression-free survival (PFS) for ICIs was 3.65 months. Virotherapy demonstrated a PFS favoring the control group, indicating minimal impact, while DCV showed substantial PFS improvement with a median of 0.43 times lower hazard compared to controls (95% CI: 29-64%). Adverse events were primarily Grade 1 or 2 for ICI, included a Grade 5 event for virotherapy, and were predominantly Grade 1 or 2 for DCV, indicating a favorable safety profile.
CONCLUSIONS: Immunotherapy holds potential as an effective treatment for HGG, especially DCV. However, results vary significantly with the type of therapy and individual patient profiles. Further randomized controlled trials are necessary to establish robust clinical guidelines and optimize treatment protocols.

Glioblastoma remains a devastating disease with a bleak prognosis despite continued research and numerous clinical trials. Convection-enhanced delivery offers researchers and clinicians a platform to bypass the blood-brain barrier and administer drugs directly to the brain parenchyma. While not without significant technological challenges, convection-enhanced delivery theoretically allows for a wide range of therapeutic agents to be delivered to the tumoral space while preventing systemic toxicities. This article provides a comprehensive review of the antitumor agents studied in clinical trials of convection-enhanced delivery to treat adult high-grade gliomas. Agents are grouped by classes, and preclinical evidence for these agents is summarized, as is a brief description of their mechanism of action. The strengths and weaknesses of each clinical trial are also outlined. By doing so, the difficulty of untangling the efficacy of a drug from the technological challenges of convection-enhanced delivery is highlighted. Finally, this article provides a focused review of some therapeutics that might stand to benefit from future clinical trials for glioblastoma using convection-enhanced delivery.

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and trial data from 201 interventional trials completed between 2010 and 2023, encompassing 18,563 participants. Although we found that all trials reported participant age and sex, only 52% of trials reported participant demographics, resulting in 51% of total participant demographics being unreported. The majority of studies did not report ethnicity, with approximately 60% of participants unreported. Additionally, males were significantly underrepresented in trials, comprising 60% of participants despite representing 75% of glioblastoma patients. Improved demographic reporting has been observed since 2011; however, it is inconsistent. Furthermore, we cataloged the geographic diversity of trials across the United States and found significant coverage deserts in relatively rural, but highly affected, areas such as Montana and Maine. We found a wider distribution of trials in both urban and wealthier regions, which indicates extensive coverage gaps and decreased access to participation for patients of a lower socioeconomic status.

Glioma, a predominant type of brain tumor, can be fatal. This necessitates an early diagnosis and effective treatment strategies. Current diagnosis is based on biopsy, prompting the need for non invasive neuroimaging alternatives. Diffusion tensor imaging (DTI) is a promising method for studying the pathophysiological impact of tumors on white matter (WM) tissue. Single-shell DTI studies in brain glioma patients have not accounted for free water (FW) contamination due to tumors. This study aimed to (a) assess the efficacy of a two-compartment DTI model that accounts for FW contamination and (b) identify DTI-based biomarkers to classify low-grade glioma (LGG) and high-grade glioma (HGG) patients. DTI data from 86 patients (LGG n = 39, HGG n = 47) were obtained using a routine clinical imaging protocol. DTI metrics of tumorous regions and normal-appearing white matter (NAWM) were evaluated. Advanced stacked-based ensemble learning was employed to classify LGG and HGG patients using both single- and two-compartment DTI model measures. The DTI metrics of the two-compartment model outperformed those of the standard single-compartment DTI model in terms of sensitivity, specificity, and area under the curve of receiver operating characteristic (AUC-ROC) score in classifying LGG and HGG patients. Four features (out of 16 features), namely fractional anisotropy (FA) of the edema and core region and FA and mean diffusivity of the NAWM region, showed superior performance (sensitivity = 92%, specificity = 90%, and AUC-ROC = 90%) in classifying LGG and HGG. This demonstrates that both tumorous and NAWM regions may be differentially affected in LGG and HGG patients. Our results demonstrate the significance of using a two-compartment DTI model that accounts for FW contamination by improving diagnostic accuracy. This improvement may eventually aid in planning treatment strategies for glioma patients.

High-grade gliomas (HGGs) are the most aggressive of brain tumors and are one of the most common primary intracranial malignancies. The poor prognosis after aggressive treatment of HGGs makes these gliomas a challenge to treat with curative intent. Proton radiation therapy is a recent radiation modality that is being explored for the treatment of HGGs. Proton radiation therapy provides improved sparing of critical normal structures while giving an ablative dose of radiation to the tumor, which can be performed more accurately than photon beam radiation therapy. We report a case of a diffuse HGG treated with proton radiotherapy and chemotherapy after previously being treated with photon irradiation. A complete radiographic response was seen on MRI imaging after proton irradiation.

UNASSIGNED: Glioma resection aims for maximal tumor removal while preserving neurological function. Neuronavigation systems (NS), with intraoperative imaging, have revolutionized this process through precise tumor localization and detailed anatomical navigation.
UNASSIGNED: To assess the efficacy and breadth of neuronavigation and intraoperative imaging in glioma resections, identify operational challenges, and provide educational insights to medical students and non-neurosurgeons regarding their practical applications.
UNASSIGNED: This systematic review analyzed studies from 2012 to 2023 on glioma patients undergoing surgical resection with neuronavigation, sourced from MEDLINE (PubMed), Embase, and Web of Science. A database-specific search strategy was employed, with independent reviewers screening for eligibility using Rayyan and extracting data using the Joanna Briggs Institute (JBI) tool.
UNASSIGNED: The integration of neuronavigation systems with intraoperative imaging modalities such as iMRI, iUS, and 5-ALA significantly enhances gross total resection (GTR) rates and extent of resection (EOR). While advanced technology improves surgical outcomes, it does not universally reduce operative times, and its impact on long-term survival varies. Combinations like NS + iMRI and NS + 5-ALA + iMRI achieve higher GTR rates compared to NS alone, indicating that advanced imaging adjuncts enhance tumor resection accuracy and success. The results underscore the multifaceted nature of successful surgical outcomes.
UNASSIGNED: Integrating intraoperative imaging with neuronavigation improves glioma resection. Ongoing research is vital to refine technology, enhance accuracy, reduce costs, and improve training, considering various factors impacting patient survival.

Bevacizumab, temozolomide (TMZ), and radiotherapy are three therapeutic methods, but the combination of them as a new approach for the treatment of newly diagnosed high-grade gliomas (HGGs) is still under investigation. Therefore, this study aims to evaluate the safety, efficacy, and clinical utility of this treatment approach for patients with glioblastoma (GBM). PubMed/Medline, Scopus, Embase, and Web of Science were systematically reviewed from inception to 24 August 2023. Relevant studies evaluating the therapeutic effect of adding Bevacizumab to TMZ-based chemotherapy and radiation therapy were enrolled. All statistical analysis was performed using the \"meta\" package of R. A total of 21 studies were included in this study. Our meta-analysis found that adding bevacizumab to standard therapy improved progression-free survival (PFS) in patients with newly diagnosed GBM. The pooled 6-month PFS rate was significantly higher with bevacizumab (79% vs. 56%, odds ratio 3.17). Overall survival (OS) showed modest improvements, with 2-year OS rates of 39% vs. 20% favoring bevacizumab. Radiological response rates varied, with a pooled overall response rate of 44% for bevacizumab-treated patients. The complete response rate was 16%, partial response 32%, and progressive disease 25%. Adverse events occurred in 62% of bevacizumab-treated patients. Common complications included fatigue, thrombocytopenia, and thromboembolic events. When added to standard therapy, bevacizumab demonstrates modest improvements in PFS and OS for newly diagnosedGBM. While it shows promise in short-term outcomes and radiological responses, long-term survival benefits remain limited. The risk of adverse events, particularly CNS hemorrhage, necessitates careful patient selection. These findings suggest that bevacizumab may have a role in treating high-grade gliomas, but its use should be individualized based on patient characteristics and risk-benefit assessment.

Primary diffuse central nervous system large B-cell lymphoma (CNS-pDLBCL) and high-grade glioma (HGG) often present similarly, clinically and on imaging, making differentiation challenging. This similarity can complicate pathologists\' diagnostic efforts, yet accurately distinguishing between these conditions is crucial for guiding treatment decisions. This study leverages a deep learning model to classify brain tumor pathology images, addressing the common issue of limited medical imaging data. Instead of training a convolutional neural network (CNN) from scratch, we employ a pre-trained network for extracting deep features, which are then used by a support vector machine (SVM) for classification. Our evaluation shows that the Resnet50 (TL + SVM) model achieves a 97.4% accuracy, based on tenfold cross-validation on the test set. These results highlight the synergy between deep learning and traditional diagnostics, potentially setting a new standard for accuracy and efficiency in the pathological diagnosis of brain tumors.

UNASSIGNED: Simultaneous involvement of multiple distinct brain regions occurs in 2-5% of all high-grade gliomas (HGG) and is associated with poor prognosis. Whereas radiotherapy (RT) is an important and well-established treatment for high-grade glioma, the role of dose-escalated radiotherapy has yet to be established. In this case series, we report upon the dosimetry, adverse effects, and response in patients with multiple un-methylated high-grade gliomas receiving dose-escalated radiation.
UNASSIGNED: We reviewed charts of patients with multifocal high grade glioma treated at our institution since January 2022. All patients had stereotactic biopsies after an magnetic resonance imaging (MRI) contrast-enhanced with T1, T2, FLAIR sequences and were discussed in a multidisciplinary oncology team. MGMT-positive patients received either TMZ alone or RT with TMZ and were excluded from this analysis. Un-methylated patients received dose-escalated RT without temezolamide (TMZ). Following computed tomography (CT) and MR simulation, the gros tumor volume (GTV) was delineated and prescribed 52.5 Gy in 15 fractions within the standard 40.05 Gy planning treatment volume (PTV). Treatment planning was volumetric modulated arc therapy.
UNASSIGNED: A total of 20 patients with multiple un-methylated MGMT glioblastoma multiforme were treated with dose-escalated radiation therapy between January 2022 and June 2023. All patients completed dose escalated radiotherapy without acute adverse effects. Progression-free survival at six months was 85%, as defined by the RANO criteria.
UNASSIGNED: In this case series, we showed that un-methylated multiple high-grade glioma could be safely treated with dose escalation. Results of progression-free survival should be validated in a larger prospective clinical trial.

BACKGROUND: Intraoperative photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) is a widely adopted technique to enhance the extent of resection during high-grade glioma (HGG) surgery. Recent updates to the package insert for 5-ALA in Japan now allow its use in combination with drugs that may induce photosensitivity, such as talaporfin sodium (TS). TS is employed in intraoperative photodynamic therapy (PDT) and has been shown to improve overall survival. The combination of 5-ALA with TS is expected to offer further benefits. However, the safety of this combination had not been established. This study reports on the safety of 5-ALA-PDD with TS-PDT in the treatment of recurrent HGG.
METHODS: 7 patients with recurrent HGG underwent tumor resection using a combination of 5-ALA-PDD and TS-PDT. The incidence of photosensitivity as an adverse effect associated with 5-ALA and TS was evaluated as described in the package insert. Adverse events were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
RESULTS: Tumor-specific fluorescence intensity was strong in 4 cases and weak in 3. Photosensitivity occurred in only 1 patient (14.3%). Three patients exhibited CTCAE grade 1 or 2 abnormal liver function, and 1 patient experienced CTCAE grade 1 γ-GTP elevation. All abnormalities improved during follow-up.
CONCLUSIONS: The combined use of 5-ALA-PDD and TS-PDT for HGG surgery did not increase the risk of serious adverse events in our study. Further investigations with a larger number of cases are needed for a more accurate assessment of its safety and efficacy.