EANO guideline on molecular testing of meningiomas for targeted therapy selection.

Meningiomas are the most common primary intracranial tumors of adults. For meningiomas that progress or recur despite surgical resection and radiotherapy, additional treatment options are limited due to lack of proven efficacy. Meningiomas show recurring molecular aberrations, which may serve as predictive markers for systemic pharmacotherapies with targeted drugs or immunotherapy, radiotherapy or radioligand therapy.

ESTRO-EANO guideline on target delineation and radiotherapy for IDH-mutant WHO CNS grade 2 and 3 diffuse glioma.

Purpose: This guideline will discuss radiotherapeutic management of IDH-mutant grade 2 and grade 3 diffuse glioma, using the latest 2021 WHO (5th) classification of brain tumours focusing on: imaging modalities, tumour volume delineation, irradiation dose and fractionation.

Methods: The ESTRO Guidelines Committee, CNS subgroup, nominated 15 European experts who identified questions for this guideline. Four working groups were established addressing specific questions concerning imaging, target volume delineation, radiation techniques and fractionation.

Multiomic and clinical analysis of multiply recurrent meningiomas reveals risk factors, underlying biology, and insights into evolution.

An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex ( = 0.

Central nervous system tumors in adolescents and young adults: A Society for Neuro-Oncology consensus review on diagnosis, management, and future directions.

Adolescents and young adults (AYAs; ages 15-39 years) are a vulnerable population facing challenges in oncological care, including access to specialized care, transition of care, unique tumor biology, and poor representation in clinical trials. Brain tumors are the second most common tumor type in AYA, with malignant brain tumors being the most common cause of cancer-related death. The 2021 WHO Classification for central nervous system (CNS) Tumors highlights the importance of integrated molecular characterization with histologic diagnosis in several tumors relevant to the AYA population.

Epigenetic therapy potentiates transposable element transcription to create tumor-enriched antigens in glioblastoma cells.

Inhibiting epigenetic modulators can transcriptionally reactivate transposable elements (TEs). These TE transcripts often generate unique peptides that can serve as immunogenic antigens for immunotherapy. Here, we ask whether TEs activated by epigenetic therapy could appreciably increase the antigen repertoire in glioblastoma, an aggressive brain cancer with low mutation and neoantigen burden.

SNO-EANO-EURACAN consensus on management of pineal parenchymal tumors.

Pineal parenchymal tumors are rare neoplasms for which evidence-based treatment recommendations are lacking. These tumors vary in biology, clinical characteristics, and prognosis, requiring treatment that ranges from surgical resection alone to intensive multimodal antineoplastic therapy. Recently, international collaborative studies have shed light on the genomic landscape of these tumors, leading to refinement in molecular-based disease classification in the 5th edition of the World Health Organization (WHO) classification of tumors of the central nervous system.

Tumor-informed deep sequencing of ctDNA detects minimal residual disease and predicts relapse in osteosarcoma.

Background: Current surveillance modalities of osteosarcoma relapse exhibit limited sensitivity and specificity. Although circulating tumor DNA (ctDNA) has been established as a biomarker of minimal residual disease (MRD) in many solid tumors, a sensitive ctDNA detection technique has not been thoroughly explored for longitudinal MRD detection in osteosarcoma.

Methods: From August 2019 to June 2023, 59 patients diagnosed with osteosarcoma at the First Affiliated Hospital of Sun Yat-sen University were evaluated in this study.

Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma.

Purpose: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines.

Multimodal neuro-nanotechnology: Challenging the existing paradigm in glioblastoma therapy.

Integrating multimodal neuro- and nanotechnology-enabled precision immunotherapies with extant systemic immunotherapies may finally provide a significant breakthrough for combatting glioblastoma (GBM). The potency of this approach lies in its ability to train the immune system to efficiently identify and eradicate cancer cells, thereby creating anti-tumor immune memory while minimizing multi-mechanistic immune suppression. A critical aspect of these therapies is the controlled, spatiotemporal delivery of structurally defined nanotherapeutics into the GBM tumor microenvironment (TME).

Association of county-level socioeconomic status with meningioma incidence and outcomes.

Background: Prior literature suggests that individual socioeconomic status (SES) may influence incidence, treatments, and survival of brain tumor cases. We aim to conduct the first national study to evaluate the association between US county-level SES and incidence, treatment, and survival in meningioma.

Methods: The Central Brain Tumor Registry of the United States analytic dataset, which combines data from CDC's National Program of Cancer Registries (NPCR) and National Cancer Institute's Surveillance, Epidemiology, and End Results Program, was used to identify meningioma cases from 2006 to 2019.

Bevacizumab Alone and in Combination With Irinotecan in Recurrent Glioblastoma.

Purpose: We evaluated the efficacy of bevacizumab, alone and in combination with irinotecan, in patients with recurrent glioblastoma in a phase II, multicenter, open-label, noncomparative trial.

Patients And Methods: One hundred sixty-seven patients were randomly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m or 125 mg/m (with or without concomitant enzyme-inducing antiepileptic drugs, respectively) once every 2 weeks. Primary end points were 6-month progression-free survival and objective response rate, as determined by independent radiology review.

Engineering a tunable micropattern-array assay to sort single extracellular vesicles and particles to detect RNA and protein in situ.

The molecular heterogeneity of extracellular vesicles (EVs) and the co-isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single-EV and particle (siEVP) protein and RNA assay ( PRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The PRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ.

Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer's disease.

Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4.

Age-associated disparity in phagocytic clearance affects the efficacy of cancer nanotherapeutics.

Nanomedicines have been approved to treat multiple human diseases. However, clinical adoption of nanoformulated agents is often hindered by concerns about hepatic uptake and clearance, a process that is not fully understood. Here we show that the antitumour efficacy of cancer nanomedicine exhibits an age-associated disparity.

Queries Raised During Oncology Business Pipeline Meetings at the European Medicines Agency: A 5-Year Retrospective Analysis.

The European Medicines Agency (EMA) offers guidance and support to pharmaceutical companies through bilateral discussions called business pipeline meetings (BPMs). An analysis of BPMs in oncology over a 5-year period was conducted to identify common topics and recurring queries. The documents of all BPMs available at the EMA regarding the field of oncology from January 1, 2018, to Decemer 31, 2022, were reviewed.

Molecular diagnostic tools for the World Health Organization (WHO) 2021 classification of gliomas, glioneuronal and neuronal tumors; an EANO guideline.

In the 5th edition of the WHO CNS tumor classification (CNS5, 2021), multiple molecular characteristics became essential diagnostic criteria for many additional CNS tumor types. For those tumors, an integrated, "histomolecular" diagnosis is required. A variety of approaches exists for determining the status of the underlying molecular markers.

Diffusion basis spectrum imaging as an adjunct to conventional MRI leads to earlier diagnosis of high-grade glioma tumor progression versus treatment effect.

Background: Following chemoradiotherapy for high-grade glioma (HGG), it is often challenging to distinguish treatment changes from true tumor progression using conventional MRI. The diffusion basis spectrum imaging (DBSI) hindered fraction is associated with tissue edema or necrosis, which are common treatment-related changes. We hypothesized that DBSI hindered fraction may augment conventional imaging for earlier diagnosis of progression versus treatment effect.

The function of histone methylation and acetylation regulators in GBM pathophysiology.

Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM.

TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma.

Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ-induced immunoactivation, proinflammatory polarization, and tumoricidal capacity.

Redox Homeostasis and Beyond: The Role of Wild-Type Isocitrate Dehydrogenases for the Pathogenesis of Glioblastoma.

Glioblastoma is an aggressive and devastating brain tumor characterized by a dismal prognosis and resistance to therapeutic intervention. To support catabolic processes critical for unabated cellular growth and defend against harmful reactive oxygen species, glioblastoma tumors upregulate the expression of wild-type isocitrate dehydrogenases (IDHs). IDH enzymes catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG), NAD(P)H, and CO.

Corrigendum: Identification and management of aggressive meningiomas.

[This corrects the article DOI: 10.3389/fonc.2022.