Neuro-oncology

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Glioblastomas (GBMs) display striking dysregulation of metabolism to promote tumor growth. Glioblastoma stem cells (GSCs) adapt to regions of heterogeneous nutrient availability, yet display dependency on de novo cholesterol biosynthesis. The transcription factor Sterol Regulatory Element-Binding Protein 2 (SREBP2) regulates cholesterol biosynthesis enzymes and uptake receptor. Here, we investigate adaptive behavior of GSCs under different cholesterol supplies. METHODS: In silico analysis of patient tumors demonstrated enrichment of cholesterol synthesis associated with decreased angiogenesis...

BACKGROUND: Accurate identification of brain tumour molecular subgroups is increasingly important. We aimed to establish the most accurate and reproducible ependymoma subgroup biomarker detection techniques, across 147 cases from International Society of Pediatric Oncology (SIOP) Ependymoma II trial participants, enrolled in the pan-European "Biomarkers of Ependymoma in Children and Adolescents (BIOMECA)" study. METHODS: Across six European BIOMECA laboratories we evaluated epigenetic profiling (DNA methylation array); immunohistochemistry (IHC) for nuclear p65-RELA, H3K27me3, and Tenascin-C; copy number analysis via FISH and MLPA (1q, CDKN2A), and MIP and DNA methylation array (genome-wide copy number evaluation); analysis of ZFTA- and YAP1-fusions by RT-PCR and sequencing, Nanostring and break-apart FISH...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUND: Plexiform neurofibromas can transform into atypical neurofibromas (ANF) and then further progress to aggressive malignant peripheral nerve sheath tumors (MPNST). ANF have been described to harbor distinct histological features and frequent loss of CDKN2A/B. However, histological evaluation may be rater-dependent, and detailed knowledge about the molecular mechanisms of malignant transformation is scarce. In general, malignant transformation can be accompanied by significant epigenetic changes, and global DNA methylation profiling is able to differentiate relevant tumor subgroups...

BACKGROUND: Malignant gliomas commandeer dense inflammatory infiltrates with glioma-associated macrophages and microglia (GAMM) promoting immune suppression, -evasion, and tumor progression. Like all cells in the mononuclear phagocytic system, GAMM constitutively express the poliovirus receptor, CD155. Besides myeloid cells, CD155 is widely upregulated in the neoplastic compartment of malignant gliomas. Intratumor treatment with the highly attenuated rhino:poliovirus chimera, PVSRIPO, yielded long-term survival with durable radiographic responses in patients with recurrent glioblastoma (Desjardins et al...

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Central nervous system (CNS) tumor patients commonly undergo multimodality treatment in the course of their disease. Adverse effects and complications from these interventions have not been systematically studied, but pose significant challenges in clinical practice and impact function and quality of life, especially in the management of long-term brain tumor survivors. Here the European Association of Neuro-Oncology (EANO) has developed recommendations to prevent, diagnose and manage adverse effects and complications in the adult primary brain CNS tumor (except lymphomas) patient population with a specific focus on surgery, radiotherapy and pharmacotherapy...

BACKGROUND: People with NF1 have an increased prevalence of CNS malignancy. However, little is known about the clinical course or pathologic features of NF1-associated gliomas in adults, limiting clinical care and research. METHODS: Adults (≥18 years) with NF1 and histologically confirmed non-optic pathway gliomas (non-OPGs) at Johns Hopkins Hospital, Memorial Sloan Kettering Cancer Center, and Washington University presenting between 1990-2020 were identified...

BACKGROUND: High-grade gliomas (HGG) are aggressive brain tumors associated with short median patient survival and limited response to therapies, driving the need to develop tools to improve patient outcomes. Patient-derived xenograft (PDX) models, such as mouse PDX, have emerged as potential Avatar platforms for personalized oncology approaches, but the difficulty for some human grafts to grow successfully and the long time required for mice to develop tumors preclude their use for HGG...

BACKGROUND: While recent sequencing studies have revealed that 10% of childhood gliomas are caused by rare germline mutations, the role of common variants is undetermined and no genome-wide significant risk loci for pediatric CNS tumors have been identified to date. METHODS: Meta-analysis of three population-based genome-wide association studies (GWASs) comprising 4,069 children with glioma and 8,778 controls of multiple genetic ancestries. Replication was performed in a separate case-control cohort...

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PURPOSE: Cognitive functioning is increasingly assessed as a secondary outcome in neuro-oncological trials. However, which cognitive domains or tests to assess, remains debatable. In this meta-analysis, we aimed to elucidate the longer-term test-specific cognitive outcomes in adult glioma patients. METHODS: A systematic search yielded 7098 articles for screening. To investigate cognitive changes in glioma patients and differences between patients and controls ≥one-year follow-up, random-effects meta-analyses were conducted per cognitive test, separately for studies with a longitudinal and cross-sectional design...

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BACKGROUND: Therapeutic options are limited in pediatric CNS malignancies. CheckMate 908 (NCT03130959) is an open-label, sequential-arm, phase 1b/2 study investigating nivolumab (NIVO) and NIVO+ipilimumab (IPI) in pediatric patients with high-grade CNS malignancies. METHODS: Patients (N=166) in 5 cohorts received NIVO 3 mg/kg every 2 weeks (Q2W) or NIVO 3 mg/kg+IPI 1 mg/kg every 3 weeks (4 doses) followed by NIVO 3 mg/kg Q2W. Primary endpoints included overall survival (OS; newly diagnosed diffuse intrinsic pontine glioma [DIPG]) and progression-free survival (PFS; other recurrent/progressive or relapsed/resistant CNS cohorts)...