Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study.

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

Early region-specific impact of adjuvant radiation therapy on cognition and quality of life in adult patients with primary brain tumors.

Purpose: While treatments for primary brain tumors increase survival, they have cognitive sequelae. Neurocognition's anatomical distribution makes it susceptible to brain damage. This study aims to evaluate the contribution of radiotherapy on short-term cognitive impairment.

Exploring management and outcomes of elderly patients with glioblastoma using data from two randomised trials (GEINO1401/EX-TEM).

Purpose: The impact of age on optimal management of glioblastoma remains unclear. A recent combined analysis of two randomised trials, GEINO14-01 and EX-TEM, found no benefit from extending post-radiation temozolomide in newly diagnosed glioblastoma. Here, we explore the impact of age.

State of the neoadjuvant therapy for glioblastoma multiforme-Where do we stand?

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults. Despite several investigations in this field, maximal safe resection followed by chemoradiotherapy and adjuvant temozolomide with or without tumor-treating fields remains the standard of care with poor survival outcomes. Many endeavors have failed to make a dramatic change in the outcomes of GBM patients.

Marizomib for patients with newly diagnosed glioblastoma: A randomized phase 3 trial.

Background: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT), and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood-brain barrier.

The C250T Mutation of Might Grant a Better Prognosis to Glioblastoma by Exerting Less Biological Effect on Telomeres and Chromosomes Than the C228T Mutation.

Unlabelled: The aim of this study was to determine how mutations impact glioblastoma prognosis.

Materials And Methods: mutations were assessed in a retrospective cohort of 258 uniformly treated glioblastoma patients. RNA-sequencing and whole exome sequencing results were available in a subset of patients.

Unlocking Bevacizumab's Potential: rCBV as a Predictive Biomarker for Enhanced Survival in Glioblastoma IDH-Wildtype Patients.

Background: Aberrant vascular architecture and angiogenesis are hallmarks of glioblastoma IDH-wildtype, suggesting that these tumors are suitable for antiangiogenic therapy. Bevacizumab was FDA-approved in 2009 following promising results in two clinical trials. However, its use for recurrent glioblastomas remains a subject of debate, as it does not universally improve patient survival.

A combined analysis of two prospective randomised studies exploring the impact of extended post-radiation temozolomide on survival outcomes in newly diagnosed glioblastoma.

Purpose: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data.

Association of partial T2-FLAIR mismatch sign and isocitrate dehydrogenase mutation in WHO grade 4 gliomas: results from the ReSPOND consortium.

Purpose: While the T2-FLAIR mismatch sign is highly specific for isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted astrocytomas among lower-grade gliomas, its utility in WHO grade 4 gliomas is not well-studied. We derived the partial T2-FLAIR mismatch sign as an imaging biomarker for IDH mutation in WHO grade 4 gliomas.

Methods: Preoperative MRI scans of adult WHO grade 4 glioma patients (n = 2165) from the multi-institutional ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium were analyzed.

Gal-1 Expression Analysis in the GLIOCAT Multicenter Study: Role as a Prognostic Factor and an Immune-Suppressive Biomarker.

Glioblastoma (GBM) is the most frequent primary malignant brain tumor and has a dismal prognosis. Unfortunately, despite the recent revolution of immune checkpoint inhibitors in many solid tumors, these have not shown a benefit in overall survival in GBM patients. Therefore, new potential treatment targets as well as diagnostic, prognostic, and/or predictive biomarkers are needed to improve outcomes in this population.

Recurrent Glioblastoma: Ongoing Clinical Challenges and Future Prospects.

Virtually all glioblastomas treated in the first-line setting will recur in a short period of time, and the search for alternative effective treatments has so far been unsuccessful. Various obstacles remain unresolved, and no effective salvage therapy for recurrent glioblastoma can be envisaged in the short term. One of the main impediments to progress is the low incidence of the disease itself in comparison with other pathologies, which will be made even lower by the recent WHO classification of gliomas, which includes molecular alterations.

In silico validation of RNA-Seq results can identify gene fusions with oncogenic potential in glioblastoma.

RNA-Sequencing (RNA-Seq) can identify gene fusions in tumors, but not all these fusions have functional consequences. Using multiple data bases, we have performed an in silico analysis of fusions detected by RNA-Seq in tumor samples from 139 newly diagnosed glioblastoma patients to identify in-frame fusions with predictable oncogenic potential. Among 61 samples with fusions, there were 103 different fusions, involving 167 different genes, including 20 known oncogenes or tumor suppressor genes (TSGs), 16 associated with cancer but not oncogenes or TSGs, and 32 not associated with cancer but previously shown to be involved in fusions in gliomas.

Preoperative Diagnosis and Molecular Characterization of Gliomas With Liquid Biopsy and Radiogenomics.

Gliomas are a heterogenous group of central nervous system tumors with different outcomes and different therapeutic needs. Glioblastoma, the most common subtype in adults, has a very poor prognosis and disabling consequences. The World Health Organization (WHO) classification specifies that the typing and grading of gliomas should include molecular markers.

Glioblastoma: Relationship between Metabolism and Immunosuppressive Microenvironment.

Glioblastoma (GBM) is the most aggressive brain tumor in adults and is characterized by an immunosuppressive microenvironment. Different factors shaping this tumor microenvironment (TME) regulate tumor initiation, progression, and treatment response. Genetic alterations and metabolism pathways are two main elements that influence tumor immune cells and TME.

Hypoxia: The Cornerstone of Glioblastoma.

Glioblastoma is the most aggressive form of brain tumor in adults and is characterized by the presence of hypervascularization and necrosis, both caused by a hypoxic microenvironment. In this review, we highlight that hypoxia-induced factor 1 (HIF-1), the main factor activated by hypoxia, is an important driver of tumor progression in GB patients. HIF-1α is a transcription factor regulated by the presence or absence of O.

Lack of Benefit of Extending Temozolomide Treatment in Patients with High Vascular Glioblastoma with Methylated .

In this study, we evaluated the benefit on survival of the combination of methylation of O6-methylguanine-DNA methyltransferase () promotor gene and moderate vascularity in glioblastoma using a retrospective dataset of 123 patients from a multicenter cohort. MRI processing and calculation of relative cerebral blood volume (rCBV), used to define moderate- and high-vascular groups, were performed with the automatic ONCOhabitats method. We assessed the previously proposed rCBV threshold (10.

Trabectedin for recurrent WHO grade 2 or 3 meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG).

Background: No systemic treatment has been established for meningioma progressing after local therapies.

Methods: This randomized, multicenter, open-label, phase II study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.