Added prognostic value of DCE blood volume imaging in patients with suspected recurrent or residual glioblastoma-A hybrid [F]FET PET/MRI study.

Background: Magnetic resonance imaging (MRI) cerebral blood volume (CBV) measurements improve the diagnosis of recurrent gliomas. The study investigated the prognostic value of dynamic contrast-enhanced (DCE) CBV imaging in treated IDH wildtype glioblastoma when added to MRI or amino acid positron emission tomography (PET).

Methods: Hybrid [F]FET PET/MRI with 2CXM (2-compartment exchange model) DCE from 86 adult patients with suspected recurrent or residual glioblastoma were retrospectively analyzed.

Magnetic resonance imaging and o-(2-[F]fluoroethyl)-l-tyrosine positron emission tomography for early response assessment of nivolumab and bevacizumab in patients with recurrent high-grade astrocytic glioma.

Background: In the present study, early response assessment by o-(2-[F]fluoroethyl)-l-tyrosine (FET) positron emission tomography (PET) and contrast-enhanced magnetic resonance imaging (MRI) were investigated in a phase II open-label single-center study of nivolumab plus bevacizumab for recurrent high-grade astrocytic glioma.

Methods: Twenty patients with nonresectable first recurrence of high-grade astrocytic glioma after EORTC/NCIC protocol underwent [F]FET PET/MRI at baseline and after 2 cycles of treatment. Whole brain values of contrast-enhancing volume on MRI (CEV), of the mean (TBR) and maximal tumor-to-background ratio (TBR), and of metabolically active volume (MTV) on [F]FET PET were obtained.

Degradation fragments of Tau and type IV collagen as serum biomarkers in patients with recurrent glioblastoma treated with nivolumab and bevacizumab.

Purpose: There is an unmet need for new treatment options and biomarkers for patients with glioblastoma (GBM). Here we investigated three non-invasive biomarkers: type VI collagen degraded by granzyme B (C4G) and matrix metalloproteases (C4M), respectively, and ADAM10-degraded Tau (Tau-A).

Methods: Biomarker levels in pre- and on-treatment serum samples from patients with recurrent GBM (n = 39) treated with nivolumab and bevacizumab (NCT03890952) were compared to healthy levels (n = 22) and associated with overall survival (OS) outcome (median cutpoint).

Repurposing the Public BraTS Dataset for Postoperative Brain Tumour Treatment Response Monitoring.

The Brain Tumor Segmentation (BraTS) Challenge has been a main driver of the development of deep learning (DL) algorithms and provides by far the largest publicly available expert-annotated brain tumour dataset but contains solely preoperative examinations. The aim of our study was to facilitate the use of the BraTS dataset for training DL brain tumour segmentation algorithms for a postoperative setting. To this end, we introduced an automatic conversion of the three-label BraTS annotation protocol to a two-label annotation protocol suitable for postoperative brain tumour segmentation.

A prospective clinical study of the influence of oral protein intake on [F]FET-PET uptake and test-retest repeatability in glioma.

Background: O-(2-[F]fluoroethyl)-L-tyrosine positron emission tomography ([F]FET PET) scanning is used in routine clinical management and evaluation of gliomas with a recommended 4 h prior fasting. Knowledge of test-retest variation of [F]FET PET imaging uptake metrics and the impact of accidental protein intake can be critical for interpretation. The aim of this study was to investigate the repeatability of [F]FET-PET metrics and to assess the impact of protein-intake prior to [F]FET PET scanning of gliomas.

Nivolumab Reaches Brain Lesions in Patients with Recurrent Glioblastoma and Induces T-cell Activity and Upregulation of Checkpoint Pathways.

Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis. Although immunotherapy is being explored as a potential treatment option for patients with GBM, it is unclear whether systemic immunotherapy can reach and modify the tumor microenvironment in the brain. We evaluated immune characteristics in patients receiving the anti-PD-1 immune checkpoint inhibitor nivolumab 1 week prior to surgery, compared with control patients receiving salvage resection without prior nivolumab treatment.

Prognostic relevance of radiological findings on early postoperative MRI for 187 consecutive glioblastoma patients receiving standard therapy.

Several prognostic factors are known to influence survival for patients treated with IDH-wildtype glioblastoma, but unknown factors may remain. We aimed to investigate the prognostic implications of early postoperative MRI findings. A total of 187 glioblastoma patients treated with standard therapy were consecutively included.

Immunotherapy drives mesenchymal tumor cell state shift and TME immune response in glioblastoma patients.

Background: Glioblastoma is a highly aggressive type of brain tumor for which there is no curative treatment available. Immunotherapies have shown limited responses in unselected patients, and there is an urgent need to identify mechanisms of treatment resistance to design novel therapy strategies.

Methods: Here we investigated the phenotypic and transcriptional dynamics at single-cell resolution during nivolumab immune checkpoint treatment of glioblastoma patients.

A systematic review of targeted therapy for vestibular schwannoma in patients with related schwannomatosis.

Background: One of the hallmarks of related Schwannomatosis -related SWN) is bilateral vestibular schwannomas (VS) that can cause progressive hearing impairment in patients. This systematic review was performed to investigate the efficacy and toxicity of tested targeted agents.

Methods: The systematic search was conducted on PubMed and EMBASE Ovid databases from inception to October 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Evaluation of the HD-GLIO Deep Learning Algorithm for Brain Tumour Segmentation on Postoperative MRI.

In the context of brain tumour response assessment, deep learning-based three-dimensional (3D) tumour segmentation has shown potential to enter the routine radiological workflow. The purpose of the present study was to perform an external evaluation of a state-of-the-art deep learning 3D brain tumour segmentation algorithm (HD-GLIO) on an independent cohort of consecutive, post-operative patients. For 66 consecutive magnetic resonance imaging examinations, we compared delineations of contrast-enhancing (CE) tumour lesions and non-enhancing T2/FLAIR hyperintense abnormality (NE) lesions by the HD-GLIO algorithm and radiologists using Dice similarity coefficients (Dice).

Predicting survival of glioblastoma from automatic whole-brain and tumor segmentation of MR images.

Survival prediction models can potentially be used to guide treatment of glioblastoma patients. However, currently available MR imaging biomarkers holding prognostic information are often challenging to interpret, have difficulties generalizing across data acquisitions, or are only applicable to pre-operative MR data. In this paper we aim to address these issues by introducing novel imaging features that can be automatically computed from MR images and fed into machine learning models to predict patient survival.

Implementing targeted therapies in the treatment of glioblastoma: Previous shortcomings, future promises, and a multimodal strategy recommendation.

The introduction of targeted therapies to the field of oncology has prolonged the survival of several tumor types. Despite extensive research and numerous trials, similar outcomes have unfortunately not been realized for glioblastoma. For more than 15 years, the standard treatment of glioblastoma has been unchanged.

Diagnostic yield of simultaneous dynamic contrast-enhanced magnetic resonance perfusion measurements and [F]FET PET in patients with suspected recurrent anaplastic astrocytoma and glioblastoma.

Purpose: Both amino acid positron emission tomography (PET) and magnetic resonance imaging (MRI) blood volume (BV) measurements are used in suspected recurrent high-grade gliomas. We compared the separate and combined diagnostic yield of simultaneously acquired dynamic contrast-enhanced (DCE) perfusion MRI and O-(2-[F]-fluoroethyl)-L-tyrosine ([F]FET) PET in patients with anaplastic astrocytoma and glioblastoma following standard therapy.

Methods: A total of 76 lesions in 60 hybrid [F]FET PET/MRI scans with DCE MRI from patients with suspected recurrence of anaplastic astrocytoma and glioblastoma were included retrospectively.

Plasma IL-8 and ICOSLG as prognostic biomarkers in glioblastoma.

Background: CNS immune privilege has been challenged in recent years. Glioblastoma (GBM) immune dysfunction includes complex interactions with the immune system outside the CNS. The aim of this study was to determine diagnostic and prognostic potential of immune-related proteins in plasma in GBM and interrogate biomarker presence in the brain tumor microenvironment (TME).

Perspective: targeting VEGF-A and YKL-40 in glioblastoma - matter matters.

Glioblastomas (GBM) are heterogeneous highly vascular brain tumors exploiting the unique microenvironment in the brain to resist treatment and anti-tumor responses. Anti-angiogenic agents, immunotherapy, and targeted therapy have been studied extensively in GBM patients over a number of decades with minimal success. Despite maximal efforts, prognosis remains dismal with an overall survival of approximately 15 months.

A Prognostic Model for Glioblastoma Patients Treated With Standard Therapy Based on a Prospective Cohort of Consecutive Non-Selected Patients From a Single Institution.

Background: Glioblastoma patients administered standard therapies, comprising maximal surgical resection, radiation therapy with concomitant and adjuvant temozolomide, have a variable prognosis with a median overall survival of 15-16 months and a 2-year overall survival of 30%. The aim of this study was to develop a prognostic nomogram for overall survival for glioblastoma patients treated with standard therapy outside clinical trials.

Methods: The study included 680 consecutive, non-selected glioblastoma patients administered standard therapy as primary treatment between the years 2005 and 2016 at Rigshospitalet, Copenhagen, Denmark.

Genomic profiling of newly diagnosed glioblastoma patients and its potential for clinical utility - a prospective, translational study.

Glioblastoma (GBM) is an incurable brain tumor for which new treatment strategies are urgently needed. Next-generation sequencing of GBM has most often been performed retrospectively and on archival tissue from both diagnostic and relapse surgeries with limited knowledge of clinical information, including treatment given. We sought to investigate the genomic composition prospectively in treatment-naïve patients, searched for possible targetable aberrations, and investigated for prognostic and/or predictive factors.

Systemic Immune Modulation in Gliomas: Prognostic Value of Plasma IL-6, YKL-40, and Genetic Variation in YKL-40.

Complex local and systemic immune dysfunction in glioblastoma (GBM) may affect survival. Interleukin (IL)-6 and YKL-40 are pleiotropic biomarkers present in the tumor microenvironment and involved in immune regulation. We therefore analyzed plasma IL-6, YKL-40, and genetic variation in YKL-40 and explored their ability to distinguish between glioma subtypes and predict survival in GBM.

Angiotensinogen promoter methylation predicts bevacizumab treatment response of patients with recurrent glioblastoma.

Patients with recurrent glioblastoma achieving response to bevacizumab combined with chemotherapy have clinical improvement and prolonged survival. High gene expression of angiotensinogen (AGT) is associated with a poor bevacizumab response. Because AGT expression is epigenetically regulated, we aimed to investigate whether AGT promoter methylation in tumor tissue predicts response to bevacizumab combination therapy in patients with recurrent glioblastoma.

Clinical Characteristics of Gliosarcoma and Outcomes From Standardized Treatment Relative to Conventional Glioblastoma.

Gliosarcoma (GS) is a rare histopathologic variant of glioblastoma (GBM) characterized by a biphasic growth pattern consisting of both glial and sarcomatous components. Reports regarding its relative prognosis compared to conventional GBM are conflicting and although GS is treated as conventional GBM, supporting evidence is lacking. The aim of this study was to characterize demographic trends, clinical outcomes and prognostic variables of GS patients receiving standardized therapy and compare these to conventional GBM.

ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide.

Standard treatment for glioblastoma (GBM) patients is surgery and radiochemotherapy (RCT) with temozolomide (TMZ). TMZ is a substrate for ABCB1, a transmembrane drug transporter. It has been suggested that survival for GBM patients receiving TMZ is influenced by different single-nucleotide variants (SNV) of ABCB1.

Cell-free DNA in newly diagnosed patients with glioblastoma - a clinical prospective feasibility study.

Glioblastoma (GB) is an incurable brain cancer with limited treatment options. The aim was to test the feasibility of using cell-free DNA (cfDNA) to support evaluation of treatment response, pseudo-progression and whether progression could be found before clinical and/or radiologic progression. CfDNA fluctuated during treatment with the highest levels before diagnostic surgery and at progression.

Health-related quality of life and caregiver perspectives in glioblastoma survivors: a mixed-methods study.

Background: The purpose of antineoplastic treatment of high-grade glioma (HGG) is to achieve progression-free survival with delayed neurological and cognitive deterioration. Health-related quality of life (HRQOL) has become increasingly important next to more traditional outcome measures such as progression-free survival. However, the clinical outcome of long-term, HGG survivors and their caregivers' quality of life is poorly understood.