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).

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.

The Neurogenome study: Comprehensive molecular profiling to optimize treatment for Danish glioblastoma patients.

Background: Glioblastoma is an aggressive brain cancer with no possibility for cure. Treatment and survival have only improved slightly since 2005 when the current regime was implemented. The limited improvements in the treatment of glioblastoma may reflect our poor understanding of the disease.

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.

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.

Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme.

Background: Bevacizumab combined with chemotherapy has recently shown promising efficacy in recurrent high-grade glioma. Phosphatase and tensin homolog (PTEN) mutation in glioblastoma multiforme (GBM) patients causes abnormally high activity of the pathways of Phosphatidylinositide 3-kinases (PI3K), Protein Kinase B (AKT), and the mammalian target of rapamycin (mTOR) and is associated with unfavorable prognosis. Temsirolimus, an mTOR inhibitor, has been well-tolerated in monotherapy, but with limited effects.

Irinotecan and bevacizumab in recurrent glioblastoma multiforme.

Introduction: Glioblastoma multiforme (GBM) is the most common high grade primary brain tumor in adults. Despite significant advances in treatment, the prognosis remains poor. Bevacizumab (BVZ) and irinotecan (CPT-11) are currently being investigated in the treatment of GBM patients.

Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan.

Several recent studies have demonstrated a beneficial effect of anti-angiogenic treatment with the vascular endothelial growth factor-neutralizing antibody bevacizumab in recurrent high-grade glioma. In the current study, immunohistochemical evaluation of biomarkers involved in angiogenesis, hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan.

Cetuximab insufficiently inhibits glioma cell growth due to persistent EGFR downstream signaling.

Overexpression and/or amplification of the epidermal growth factor receptor (EGFR) is present in 35-45% of primary glioblastoma multiforme tumors and has been correlated with a poor prognosis. In this study, we investigated the effect of cetuximab and intracellular signaling pathways downstream of EGFR, important for cell survival and proliferation. We show insufficient EGFR downregulation and competition with endogenous EGFR ligands upon cetuximab treatment.

Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial.

The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard treatment (radiotherapy and temozolomide). Bevacizumab and irinotecan were administered IV every 2 weeks.

Bevacizumab plus irinotecan in the treatment patients with progressive recurrent malignant brain tumours.

Material And Methods: We retrospectively determined the efficacy and safety of a combination of bevacizumab and irinotecan in a consecutive series of 52 heavily pre-treated patients with recurrent high-grade brain tumours. Patients received bevacizumab (10 mg/kg) and irinotecan [340 mg/m(2) for those receiving enzyme-inducing antiepileptic drugs (EIAEDs) and 125 mg/m(2) for those not receiving EIAEDs] every 2 weeks. Fifty-two patients were included and 47 were evaluable for response.