Somatostatin analogues in treatment-refractory meningioma: a systematic review with meta-analysis of individual patient data.

Treatment-refractory meningiomas have a dismal prognosis and limited treatment options. Meningiomas express high-densities of somatostatin receptors (SSTR), thus potentially susceptible to antitumorigenic effects of somatostatin analogues (SSA). Evidence for SSA in meningiomas is scarce, and it is unclear if published literature would either (1) support wider use of SSA, if (2) more evidence is desirable, or if (3) available evidence is sufficient to discard SSA.

Implementation of TERT promoter mutations improve prognostication of the WHO classification in meningioma.

TERT promoter mutations have been associated with increased risk of recurrence in meningioma cohorts, thus a potential biomarker for aggressive phenotypes. A main purpose of refining tumour classification is better predictions on the patient level. We compiled data from previous published cohorts to investigate patient-level predictions of recurrence based on TERTp-mut status.

Brain tumor biomarkers for research, clinics, and registries - The 2021 Brain Tumor Epidemiology Consortium meeting report.

The Brain Tumor Epidemiology Consortium (BTEC) is an international consortium that fosters interdisciplinary collaborations focusing on research related to the etiology, outcomes, and prevention of brain tumors. The 21 annual BTEC meeting with the theme "" was held virtually from June 22 to 24, 2021. Scientists from North America and Europe, representing a broad range of brain tumor research interests, presented recent research and progress in the field.

Pathologic Characteristics of Pregnancy-Related Meningiomas.

Meningiomas are the most common intracranial tumor. During pregnancy, explosive growth of a known meningioma occasionally occurs, but the underlying reasons remain unknown. Prolactin has been suggested as a possible key contributor to pregnancy-related meningioma growth.

The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output.

Eukaryotic initiation factor 4A-III (eIF4A3), a core helicase component of the exon junction complex, is essential for splicing, mRNA trafficking, and nonsense-mediated decay processes emerging as targets in cancer therapy. Here, we unravel eIF4A3's tumor-promoting function by demonstrating its role in ribosome biogenesis (RiBi) and p53 (de)regulation. Mechanistically, eIF4A3 resides in nucleoli within the small subunit processome and regulates rRNA processing via R-loop clearance.

Diagnostic accuracy and clinical impact of [18F]FET PET in childhood CNS tumors.

Background: Central nervous system (CNS) tumors cause the highest death rates among childhood cancers, and survivors frequently have severe late effects. Magnetic resonance imaging (MRI) is the imaging modality of choice, but its specificity can be challenged by treatment-induced signal changes. In adults, O-(2-[18F]fluoroethyl)-l-tyrosine ([18F]FET) PET can assist in interpreting MRI findings.

Regional Differences in Neuroinflammation-Associated Gene Expression in the Brain of Sporadic Creutzfeldt-Jakob Disease Patients.

Neuroinflammation is an essential part of neurodegeneration. Yet, the current understanding of neuroinflammation-associated molecular events in distinct brain regions of prion disease patients is insufficient to lay the ground for effective treatment strategies targeting this complex neuropathological process. To address this problem, we analyzed the expression of 800 neuroinflammation-associated genes to create a profile of biological processes taking place in the frontal cortex and cerebellum of patients who suffered from sporadic Creutzfeldt-Jakob disease.

Expression of the stem cell marker CD133 in malignant meningioma.

The stem cell marker CD133 has been sporadically investigated in meningioma, but because of the rarity of malignant meningioma (WHO grade III), only 7 malignant meningioma specimens have been included in previous studies. We investigated CD133 expression using the AC133 antibody clone in a consecutive cohort of 38 malignant meningiomas. Our results showed few, small CD133-positive hot spots with a pattern dominated by membranous staining and capping of the proteins without any nuclear CD133 staining in 30 of the 38 tumors.

Distinct circular RNA expression profiles in pediatric ependymomas.

Pediatric ependymomas frequently develop in the cerebellum and are currently treated using non-specific therapies, in part, because few somatically mutated driver genes are present, and the underlying pathobiology is poorly described. Circular RNAs (circRNAs) constitute as a large class of primarily non-coding RNAs with important roles in tumorigenesis, but they have not been described in pediatric ependymomas. To advance our molecular understanding of ependymomas, we performed Next Generation Sequencing of rRNA-depleted total RNA of 10 primary ependymoma and three control samples.

Mitotic and Proliferative Indices in WHO Grade III Meningioma.

Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI.

Somatostatin Receptor-Targeted Radiopeptide Therapy in Treatment-Refractory Meningioma: Individual Patient Data Meta-analysis.

Somatostatin receptor (SSTR)-targeted peptide receptor radionuclide therapy (PRRT) represents a promising approach for treatment-refractory meningiomas. We performed an individual patient data meta-analysis, including all published data on meningioma patients treated with SSTR-targeted PRRT. The main outcomes were toxicity, response to treatment, progression-free survival (PFS), and overall survival (OS).

TERT promoter mutations in primary and secondary WHO grade III meningioma.

Purpose: TERT promoter mutation (TERTp ) has a strong association to recurrence and has been suggested to act as a driver mutation for malignant transformation of WHO grade I and II meningiomas. TERTp has been investigated in selected high-grade meningioma samples. The existence of TERTp across recurrent tumors in a population-based cohort needs to be investigated in order to identify when TERTp emerges across recurrent samples and to validate prognostic impact among WHO grade III tumors.

Pearls and Pitfalls in Interpretation of 68Ga-DOTATOC PET Imaging.

DOTA-D-Phe-Tyr-octreotide labeled with Ga (Ga-DOTATOC) is the commonly used PET tracer for imaging meningioma because of its high affinity to somatostatin receptor subtype 2 (SSTR2) and an established imaging modality for planning radiation and radionuclide therapy. However, SSTR2 is not an exclusive marker for meningioma, and not all meningiomas express high levels of SSTR2. The SSTR2 expression has been reported in other intracranial tumors, for example, glioma, pituitary adenoma, medullablastoma, primitive neuroectodermal tumors, and hemangioblastoma leading to a significant risk of misinterpretation of PET/CT findings.

[Overlooked deadly infection with Coccidioides immitis].

Coccidioides immitis is a dimorphic fungus endemic to the southwestern North America and Central America. Infection is acquired through inhalation of soil containing spores. This case report describes a case of C.

Pharmacokinetic analysis of [Ga]Ga-DOTA-TOC PET in meningiomas for assessment of in vivo somatostatin receptor subtype 2.

Purpose: DOTA-D-Phe-Tyr-octreotide with gallium-68 ([Ga]Ga-DOTA-TOC) is one of the PET tracers that forms the basis for peptide receptor radionuclide therapy based on somatostatin receptor subtype 2 (SSTR2) expression in meningiomas. Yet, the quantitative relationship between [Ga]Ga-DOTA-TOC accumulation and SSTR2 is unknown. We conducted a correlative analysis of a range of [Ga]Ga-DOTA-TOC PET metric(s) as imaging surrogate(s) of the receptor binding in meningiomas by correlating the PET results with SSTR2 expression from surgical specimens.

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.

Poor prognosis associated with TERT gene alterations in meningioma is independent of the WHO classification: an individual patient data meta-analysis.

Background: gene alterations (-alt) have been linked to increased risk of recurrence in meningiomas, whereas the association to mortality largely remain incompletely investigated. As incongruence between clinical course and WHO grade exists, reliable biomarkers have been sought.

Methods: We applied the Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data Statement.

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.

Recurrent glioblastoma versus late posttreatment changes: diagnostic accuracy of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET).

Background: Diagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non-standard-of-care therapies, and PET scans performed at different time points post radiotherapy. We investigated the diagnostic accuracy of a 20-minute 18F-FET PET scan in MRI-suspected recurrent glioblastoma 6 months after standard radiotherapy and its ability to prognosticate overall survival (OS).

Methods: In total, 146 glioblastoma patients with 168 18F-FET PET scans were reviewed retrospectively.

Multiple Extracranial Metastases from Primary Gliosarcoma in a Patient with Two Previous Different Primary Cancers.

Gliosarcoma (GS) constitutes a minor fraction of primary glioblastoma (GBM), which is the most frequent malignant brain tumor in adults. Despite the fact that malignant gliomas are highly invasive, extracranial metastases are very rarely seen, and the mechanisms behind extracranial dissemination are still unclarified. We report a case of a 55-year-old male with a prior history of two distinct primary cancer types who, as a third independent type, developed GS with penetrating tumor growth to the skull and subcutaneous soft tissue via explosive spreading through a titanium net as well as extracranial metastases to the lumbar spine, paravertebral musculature, and most likely the right lung.

Molecular Characterization of the Danish Prion Diseases Cohort With Special Emphasis on Rare and Unique Cases.

The purpose of this study was to perform an updated reclassification of all definite prion disease cases with available fresh-frozen samples referred to the Danish Reference Center over the past 40 years, putting a special emphasis on the molecular characterization of novel disease subtypes. Investigation of the Danish prion diseases cohort revealed rare sporadic Creutzfeldt-Jakob disease cases with mixed subtypes and subtypes with previously uncharacterized white matter plaques, a new case of sporadic fatal insomnia, and 3 novel mutations, including 2 large octapeptide repeat insertions, and a point mutation in the prion protein gene. The evaluation of methionine and valine distribution at codon 129 among the prion disease patients in the cohort revealed the increased prevalence of methionine homozygotes compared to the general population.

A Novel Eight Octapeptide Repeat Insertion in PRNP Causing Prion Disease in a Danish Family.

Octapeptide repeat insertions (OPRI) found in the prion protein gene (PRNP) constitute a subgroup of pathogenic mutations linked to inherited prion diseases, a hallmark of which is a misfolded prion protein. The number of repeats in OPRI has been associated with different disease phenotypes. However, due to the rarity of the cases and heterogenous disease manifestations, the recognition and classification of these variants has been difficult.