Measuring the diagnostic management and follow-up imaging for glioma patients across Belgian hospitals between 2016 and 2019.

Objectives: This study aimed to assess the diagnostic management and follow-up imaging for glioma patients across Belgian hospitals by calculating process indicators.

Methods: Patients with newly diagnosed glioma in Belgium (2016-2019) were selected from the Belgian Cancer Registry. The National Social Security Number served as unique patient identifier, linking the Registry to vital status and reimbursement data.

Mitotic count is prognostic in IDH mutant astrocytoma without homozygous deletion of CDKN2A/B. Results of consensus panel review of EORTC trial 26053 (CATNON) and EORTC trial 22033-26033.

Background: Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameters still contribute to prognostic information on top of the molecular classification, remains unanswered.

Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial.

Background: Patients with recurrent glioblastoma (rGB) have a poor prognosis with a median overall survival (OS) of 30-39 weeks in prospective clinical trials. Intravenous administration of programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors has low activity in patients with rGB. In this phase I clinical trial, intracerebral (IC) administration of ipilimumab (IPI) and nivolumab (NIVO) in combination with intravenous administration of NIVO was investigated.

Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx).

Background: No treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.

Methods: Adult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids.

Neuroanatomical Reconstruction of the Canine Visual Pathway Using Diffusion Tensor Imaging.

The first anatomical atlas of diffusion tensor imaging (DTI) of white matter pathways in the canine brain was published in 2013; however, the anatomical orientation of the entire visual pathway in the canine brain, from the retina to the cortex, has not yet been studied using DTI. In the present study, 3T DTI magnetic resonance (MR) images of three dogs euthanized for reasons other than neurological disorders were obtained. The process of obtaining combined fractional anisotropy and directional maps was initiated within 1 h of death.

Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours.

The aim of this study is to assess differences in patient characteristics, tumour characteristics and hormone levels between acromegalic patients with and without hyperprolactinemia. 44 patients of the University Hospital of Brussels, Belgium with acromegaly who were diagnosed between January 2007 and July 2018 were included in this study. Nineteen patients were classified in the hyperprolactinemia group and 25 patients were classified in the normoprolactinemia group.

Focal radiation necrosis of the brain in patients with melanoma brain metastases treated with pembrolizumab.

Introduction: Up to 60% of patients with metastatic melanoma develop melanoma brain metastasis (MBM) during the course of their disease. Surgery, radiosurgery (SRS), stereotactic radiotherapy (SRT), and whole-brain radiation therapy (WBRT) or combinations of these are commonly used local treatment modalities. Inhibitory monoclonal antibodies against the CTLA-4 and PD-1 immune checkpoint receptors significantly improved the survival of metastatic melanoma patients, including patients with MBM.

Both invasiveness and proliferation criteria predict recurrence of non-functioning pituitary macroadenomas after surgery: a retrospective analysis of a monocentric cohort of 120 patients.

Introduction: Additional robust criteria to predict early postoperative recurrence of non-functioning pituitary macroadenomas (NFMAs) are needed. Recently, a new classification of pituitary tumors has been proposed, which is based on both radiological and histological criteria and allows the grading into 5 groups of different potential aggressiveness. The aim of this study was to use this classification to further characterize predictive factors of recurrence in an independent series of NFMA.

Randomized phase II trial comparing axitinib with the combination of axitinib and lomustine in patients with recurrent glioblastoma.

Axitinib is a small molecule tyrosine kinase inhibitor with high affinity and specificity for the family of vascular endothelial growth factor receptors. It has previously demonstrated anti-tumor activity in a small cohort of patients with recurrent glioblastoma (rGB). We conducted a non-comparative randomized phase II clinical trial investigating axitinib monotherapy versus axitinib plus lomustine (LOM) in patients with rGB.

Slc7a11 (xCT) protein expression is not altered in the depressed brain and system xc- deficiency does not affect depression-associated behaviour in the corticosterone mouse model.

The cystine/glutamate antiporter (system xc-) is believed to contribute to nonvesicular glutamate release from glial cells in various brain areas. Although recent investigations implicate system xc- in mood disorders, unambiguous evidence has not yet been established. Therefore, we evaluated the possible role of system xc- in the depressive state.

Pancreas and gallbladder agenesis in a newborn with semilobar holoprosencephaly, a case report.

Background: Pancreatic agenesis is an extremely rare cause of neonatal diabetes mellitus and has enabled the discovery of several key transcription factors essential for normal pancreas and beta cell development.

Case Presentation: We report a case of a Caucasian female with complete pancreatic agenesis occurring together with semilobar holoprosencephaly (HPE), a more common brain developmental disorder. Clinical findings were later confirmed by autopsy, which also identified agenesis of the gallbladder.

TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1.

Bone Marrow Metastases from a 1p/19q Co-deleted Oligodendroglioma - A Case Report.

Background: Metastasis of oligodendroglioma outside of the central nervous system (CNS) is a very rare event.

Case: We describe in detail the clinical story of a 50-year-old woman diagnosed with profound pancytopenia and signs of extramedullary hematopoiesis caused by diffuse bone marrow replacement by a metastatic oligodendroglioma.

Results: Upon development of pancytopenia, a diagnostic bone marrow examination revealed the presence of metastatic oligodendroglial cells.

Randomized phase II study of axitinib versus physicians best alternative choice of therapy in patients with recurrent glioblastoma.

We conducted a randomized, non-comparative, multi center, phase II clinical trial in order to investigate the efficacy of axitinib, an oral small molecule tyrosine kinase inhibitor with high affinity and specificity for the vascular endothelial growth factor receptors, in patients with recurrent glioblastoma following prior treatment with radiation and temozolomide. Forty-four patients were randomly assigned to receive treatment with axitinib (5 mg BID starting dose; N = 22) or "physicians best alternative choice of therapy" that consisted of bevacizumab (N = 20) or lomustine (N = 2). Six-month progression-free survival served as the primary endpoint.

Sunitinib Malate plus Lomustine for Patients with Temozolomide-refractory Recurrent Anaplastic or Low-grade Glioma.

Tyrosine kinase signaling through the vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor- α (PDGFR-α) and KIT cell surface receptors mediates neo-angiogenesis and contributes to cancer cell survival in recurrent anaplastic and low-grade glioma. Thirteen patients with temozolomide-refractory recurrent anaplastic or low-grade glioma were treated with sunitinib malate, a small-molecule tyrosine kinase inhibitor of the VEGFR, PDGFR, and KIT receptors, in combination with lomustine. The most frequent grade 3 and 4 adverse events were fatigue, thrombocytopenia, neutropenia and lymphopenia.

Nasal heterotopia versus pilocytic astrocytoma: A narrow border.

Failure of the anterior neuropore can lead to three main types of anomalies: nasal dermal sinus, encephalocele and nasal glioma or heterotopia. In this report, we describe a case of intracranial and extracranial glial heterotopia that probably resulted from a common failure of anterior neuropore development. We describe the prenatal radiological assessment based on ultrasound and MRI results, and consider their limitation for early fetal diagnosis.

Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials.

Purpose: With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values.

Methods: The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis.

Two siblings with homozygous pathogenic splice-site variant in mitochondrial asparaginyl-tRNA synthetase (NARS2).

A homozygous missense mutation (c.822G>C) was found in the gene encoding the mitochondrial asparaginyl-tRNA synthetase (NARS2) in two siblings born to consanguineous parents. These siblings presented with different phenotypes: one had mild intellectual disability and epilepsy in childhood, whereas the other had severe myopathy.

Symptomatic Histologically Proven Necrosis of Brain following Stereotactic Radiation and Ipilimumab in Six Lesions in Four Melanoma Patients.

Four cases previously treated with ipilimumab with a total of six histologically confirmed symptomatic lesions of RNB without any sign of active tumour following stereotactic irradiation of MBM are reported. These lesions were all originally thought to be disease recurrence. In two cases, ipilimumab was given prior to SRT; in the other two ipilimumab was given after SRT.