Search Results (49)

Background: The natural history of pediatric patients with metastasis of primary brain tumors within and outside the central nervous system is poorly understood, as too are possible clinical correlates with outcome. Correspondingly, the aim of this study was to interrogate a national database to characterize this diagnosis and its clinical course in pediatric patients. Methods: The U.S. National Cancer Database (NCDB) was interrogated between the years 2005–2016 for all patients aged 18 years and younger with a primary brain tumor diagnosis, as well as evidence of disease metastasis at initial diagnosis. Data were summarized and overall survival (OS) was modeled using Kaplan–Meier and Cox regression analyses. Results: Out of a total of 8615 pediatric brain tumor patients, 356 (4%) had evidence of metastasis at initial diagnosis. Compared to patients without metastasis, patients with metastasis were statistically younger, more often male, and less likely to have private health insurance (all p < 0.050). With respect to clinical characteristics, the primary tumors of patients with metastasis were statistically more likely to be located in the cerebellum; be of higher histologic grading, with a higher proportion of medulloblastoma diagnoses and lower proportion of malignant glioma and pilocytic astrocytoma diagnoses; and were more likely to be treated by subtotal surgical resection, chemotherapy and radiation therapy (all p < 0.050) when compared to patients without metastasis. Five-year OS for those with metastasis was significantly lower than those without (48% vs. 75%, p < 0.001), with the median overall survival for patients with metastasis being 53 months (95% CI 29–86). Multivariate analysis indicated that a shorter OS was independently associated with the primary diagnoses of malignant glioma (HR 27.7, p = 0.020) and Atypical Teratoid/Rhabdoid Tumor (ATRT, HR 41.1, p = 0.041) and with WHO grades 3 (HR 20.1, p = 0.012) and 4 (HR 11.5, p < 0.001). Longer OS was significantly and independently associated with surgery (HR 0.49, p < 0.001), chemotherapy (HR 0.53, p = 0.041), and radiation therapy (HR 0.57, p = 0.026). Conclusions: Although uncommon, pediatric brain tumors with evidence of metastasis at initial diagnosis will present with a distinct socioeconomic and clinical profile compared to patients without metastasis. Multiple predictors are independently associated with overall prognosis, and understanding these features should be validated in prospective efforts to identify vulnerable patients earlier in order to maximize the impact of treatment. Full article

Gliomas, ranging from low-grade pilocytic astrocytomas to highly malignant glioblastomas, are primary brain tumors that originate from neural or glial stem cells. Classified by the WHO into grades 1 to 4, these tumors exhibit varying prognoses, with oligodendrogliomas and astrocytomas having better and intermediate outcomes, respectively, while glioblastomas are associated with a poor prognosis. Despite advancements in molecular and genetic research that have improved diagnosis and the development of targeted therapies, treating high-grade gliomas remains a significant challenge due to their diffuse nature. In this context, lectins, carbohydrate-binding proteins, have shown promise as diagnostic and therapeutic agents for cancer, including gliomas. Plant lectins, particularly those from legumes, exhibit significant antiproliferative effects on glioma cells. These effects include decreased cell viability and migration, alongside the induction of autophagy and apoptosis, suggesting their potential as therapeutic agents. Although the mechanisms underlying these effects are not yet fully understood, molecular targets and pathways involved in the antiglioma activity of lectins have been identified. Key targets include matrix metalloproteinases (MMPs), epidermal growth factor receptor (EGFR), CD98 (xc^- system), AMPA receptor, and CD73. This review focuses on the antiglioma potential of legume lectins, their applications, and the main molecular targets based on their functions, structures, and associated molecular mechanisms. Full article

The frequency and duration of imaging surveillance in children and adolescents with pediatric low-grade gliomas (pLGGs) aims for the early detection of recurrence or progression. Although surveillance of pLGGs is performed routinely, it is not yet standardized. The aim of the current review is to provide a comprehensive synthesis of published studies regarding the optimal frequency, intervals, and duration of surveillance. Several key influencing factors were identified (age, the extent of resection, the tumor location, the histological type, and specific molecular characteristics). However, the lack of consistent definitions of recurrence/progression and the extent of resection meant that it was not possible to perform a meta-analysis of the data from the 18 included articles. This review highlights the need for updating the definition of these terms for uniform and global use both in routine clinical practice as well as in upcoming trials. Thus, future studies on the heterogenous group of pLGGs will allow for the better tailoring of both the frequency and duration of imaging surveillance protocols in relevant settings. Full article

Background: Hypothalamic gliomas, though rare, present significant challenges in neuro-oncology due to their critical location and high morbidity risk. Pilocytic astrocytoma is the most common subtype, requiring a delicate balance between tumor control and preservation of neurological function. This study explores radiosurgery as a viable treatment option for hypothalamic gliomas, with a focus on low-grade lesions. Methods: A comprehensive literature review was conducted using the PubMed database to compare the outcomes of surgical and non-surgical interventions for hypothalamic gliomas. The purpose of case report and clinical guidelines is to present a case report and critically compare its outcomes with the data identified in the literature. We report the case of a 25-year-old male presenting with hypernatremia, diabetes insipidus, and altered mental status. Imaging revealed a hypothalamic lesion consistent clinically with a low-grade astrocytoma. Given the tumor’s proximity to critical neurovascular structures, gamma knife radiosurgery was chosen as the intervention. Post treatment, tumor reduction and neurological improvement were observed and documented. Results: The case demonstrated a significant decrease in tumor size and resolution of neurological symptoms post radiosurgery. The management of hypothalamic gliomas remains contentious due to the complex anatomy of the hypothalamus. While surgical resection remains common, it carries a high risk of morbidity. Radiosurgery offers a minimally invasive alternative, effectively controlling tumor growth while reducing neurological risk. The favorable outcomes in our case, supported by the literature, highlight the efficacy of radiosurgery, particularly for low-grade astrocytomas. Conclusions: Gamma knife radiosurgery presents a promising alternative to conventional surgery for hypothalamic gliomas, particularly low-grade lesions such as pilocytic astrocytomas. The reduction in surgical risk and positive clinical outcomes make radiosurgery a valuable tool in the management of these challenging tumors. Full article

This case report delves into the case of a 56-year-old female patient presenting with progressive cephalalgia syndrome, nausea, vomiting, and gait disorders, diagnosed with a high-grade thalamic glioma. Glioma is the most common form of central nervous system (CNS) neoplasm that originates from glial cells. Gliomas are diffusely infiltrative tumors that affect the surrounding brain tissue. Glioblastoma is the most malignant type, while pilocytic astrocytomas are the least malignant brain tumors. In the past, these diffuse gliomas were classified into different subtypes and grades based on histopathologies such as a diffuse astrocytoma, oligodendrogliomas, or mixed gliomas/oligoastrocytomas. Currently, gliomas are classified based on molecular and genetic markers. After the gross total resection, a postoperative brain CT scan was conducted, which confirmed the quasi-complete resection of the tumor. The successful gross total resection of the tumor in this case, coupled with significant neurological improvement postoperatively, illustrates the potential benefits of aggressive surgical management for thalamic gliomas. This report advocates for further research to assess the efficacy of such interventions in malignant cases and to establish standardized treatment protocols, considering the heterogeneity in prognostic outcomes and the advancements in molecular diagnostics that offer deeper insights into glioma oncogenesis and progression. Full article

The World Health Organization’s (WHO) classification of central nervous system (CNS) tumors is continually being refined to improve the existing diagnostic criteria for high-grade gliomas (HGGs), including glioblastoma. In 2021, advances in molecular analyses and DNA methylation profiling were incorporated to expand upon the diagnostic criteria for HGG, including the introduction of high-grade astrocytoma with piloid features (HGAP), a new tumor entity for which a match to the HGAP class in DNA methylation profiling is an essential criterion. We present an equivocal case of a 72-year-old male with an HGG exhibiting features of both HGAP and glioblastoma, but which did not conform to any existing 2021 WHO classification of CNS tumor entities. This “no match” in DNA methylation profiling resulted in a final diagnosis of HGG not elsewhere classified (NEC), for which standard treatment options do not exist. Full article

Intramedullary primary spinal cord tumors are rare in adults and their classification has recently evolved. Their treatment most frequently relies on maximal safe surgical resection. Herein, we review, in light of the WHO 2021 classification of central nervous system tumors, the knowledge regarding the role of radiotherapy and systemic treatments in spinal ependymomas, spinal astrocytomas (pilocytic astrocytoma, diffuse astrocytoma, spinal glioblastoma IDH wildtype, diffuse midline glioma H3-K27M altered, and high-grade astrocytoma with piloid features), neuro-glial tumors (ganglioglioma and diffuse leptomeningeal glioneuronal tumor), and hemangioblastomas. In spinal ependymomas, radiotherapy is recommended for incompletely resected grade 2 tumors, grade 3 tumors, and recurrent tumors not amenable to re-surgery. Chemotherapy is used in recurrent cases. In spinal astrocytomas, radiotherapy is recommended for incompletely resected grade 2 astrocytomas and grade 3 or 4 tumors as well as recurrent tumors. Chemotherapy is indicated for newly diagnosed high-grade astrocytomas and recurrent cases. In hemangioblastomas not amenable to surgery, radiotherapy is an effective alternative option. Targeted therapies are playing an increasingly important role in the management of some intramedullary primary spinal cord tumor subtypes. BRAF and/or MEK inhibitors have demonstrated efficacy in pilocytic astrocytomas and glioneuronal tumors, belzutifan in von Hippel–Lindau-related hemangioblastomas, and promising results have been reported with ONC201 in diffuse midline glioma H3-K27M altered. Full article

Pediatric low-grade gliomas (PLGGs) comprise a heterogeneous set of low-grade glial and glioneuronal tumors, collectively representing the most frequent CNS tumors of childhood and adolescence. Despite excellent overall survival rates, the chronic nature of the disease bears a high risk of long-term disease- and therapy-related morbidity in affected patients. Recent in-depth molecular profiling and studies of the genetic landscape of PLGGs led to the discovery of the paramount role of frequent upregulation of RAS/MAPK and mTOR signaling in tumorigenesis and progression of these tumors. Beyond, the subsequent unveiling of RAS/MAPK-driven oncogene-induced senescence in these tumors may shape the understanding of the molecular mechanisms determining the versatile progression patterns of PLGGs, potentially providing a promising target for novel therapies. Recent in vitro and in vivo studies moreover indicate a strong dependence of PLGG formation and growth on the tumor microenvironment. In this work, we provide an overview of the current understanding of the multilayered cellular mechanisms and clinical factors determining the natural progression patterns and the characteristic biological behavior of these tumors, aiming to provide a foundation for advanced stratification for the management of these tumors within a multimodal treatment approach. Full article

Background and purpose: Differentiating pediatric posterior fossa (PF) tumors such as medulloblastoma (MB), ependymoma (EP), and pilocytic astrocytoma (PA) remains relevant, because of important treatment and prognostic implications. Diffusion kurtosis imaging (DKI) has not yet been investigated for discrimination of pediatric PF tumors. Estimating diffusion values from whole-tumor-based (VOI) segmentations may improve diffusion measurement repeatability compared to conventional region-of-interest (ROI) approaches. Our purpose was to compare repeatability between ROI and VOI DKI-derived diffusion measurements and assess DKI accuracy in discriminating among pediatric PF tumors. Materials and methods: We retrospectively analyzed 34 children (M, F, mean age 7.48 years) with PF tumors who underwent preoperative examination on a 3 Tesla magnet, including DKI. For each patient, two neuroradiologists independently segmented the whole solid tumor, the ROI of the area of maximum tumor diameter, and a small 5 mm ROI. The automated analysis pipeline included inter-observer variability, statistical, and machine learning (ML) analyses. We evaluated inter-observer variability with coefficient of variation (COV) and Bland–Altman plots. We estimated DKI metrics accuracy in discriminating among tumor histology with MANOVA analysis. In order to account for class imbalances, we applied SMOTE to balance the dataset. Finally, we performed a Random Forest (RF) machine learning classification analysis based on all DKI metrics from the SMOTE dataset by partitioning 70/30 the training and testing cohort. Results: Tumor histology included medulloblastoma (15), pilocytic astrocytoma (14), and ependymoma (5). VOI-based measurements presented lower variability than ROI-based measurements across all DKI metrics and were used for the analysis. DKI-derived metrics could accurately discriminate between tumor subtypes (Pillai’s trace: p < 0.001). SMOTE generated 11 synthetic observations (10 EP and 1 PA), resulting in a balanced dataset with 45 instances (34 original and 11 synthetic). ML analysis yielded an accuracy of 0.928, which correctly predicted all but one lesion in the testing set. Conclusions: VOI-based measurements presented improved repeatability compared to ROI-based measurements across all diffusion metrics. An ML classification algorithm resulted accurate in discriminating PF tumors on a SMOTE-generated dataset. ML techniques based on DKI-derived metrics are useful for the discrimination of pediatric PF tumors. Full article

Background: Pilocytic astrocytoma (PCA) are commonly observed as slow-growing noncancerous brain tumors in pediatric populations, but they can also occur in adults, albeit rarely. When located in diencephalic regions, particularly in the hypothalamus, they present unique diagnostic and management challenges due to their rarity and overlapping clinical and radiological features with other intracranial pathologies. This systematic review aims to provide a comprehensive understanding of hypothalamic PCA in adults, focusing on their differential diagnosis, neurological presentation, diagnostic modalities, treatment strategies. A case illustration is also described in order to better underline all the difficulties related to the diagnostic process. Material and methods: A systematic literature search was conducted in the PubMed/MEDLINE, Embase, and Scopus databases up to November 2023 to identify studies. Results: The systematic literature search identified a total of 214 articles. Following screening by title and abstract and full-text review, 12 studies were deemed eligible and are included here. Conclusions: Adult-onset PCA in diencephalic regions pose diagnostic challenges due to their rarity and overlapping features with other intracranial lesions. Advanced imaging techniques play a crucial role in diagnosis, while surgery remains the cornerstone of treatment. Multidisciplinary collaboration is essential for the optimal management and long-term follow-up of these patients. Full article

Medulloblastoma and pilocytic astrocytoma are the two most common pediatric brain tumors with overlapping imaging features. In this proof-of-concept study, we investigated using a deep learning classifier trained on a multicenter data set to differentiate these tumor types. We developed a patch-based 3D-DenseNet classifier, utilizing automated tumor segmentation. Given the heterogeneity of imaging data (and available sequences), we used all individually available preoperative imaging sequences to make the model robust to varying input. We compared the classifier to diagnostic assessments by five readers with varying experience in pediatric brain tumors. Overall, we included 195 preoperative MRIs from children with medulloblastoma (n = 69) or pilocytic astrocytoma (n = 126) across six university hospitals. In the 64-patient test set, the DenseNet classifier achieved a high AUC of 0.986, correctly predicting 62/64 (97%) diagnoses. It misclassified one case of each tumor type. Human reader accuracy ranged from 100% (expert neuroradiologist) to 80% (resident). The classifier performed significantly better than relatively inexperienced readers (p < 0.05) and was on par with pediatric neuro-oncology experts. Our proof-of-concept study demonstrates a deep learning model based on automated tumor segmentation that can reliably preoperatively differentiate between medulloblastoma and pilocytic astrocytoma, even in heterogeneous data. Full article

Gliomas have displayed significant challenges in oncology due to their high degree of invasiveness, recurrence, and resistance to treatment strategies. In this work, the key hub genes mainly associated with different grades of glioma, which were represented by pilocytic astrocytoma (PA), oligodendroglioma (OG), anaplastic astrocytoma (AA), and glioblastoma multiforme (GBM), were identified through weighted gene co-expression network analysis (WGCNA) of microarray datasets retrieved from the Gene Expression Omnibus (GEO) database. Through this, four highly correlated modules were observed to be present across the PA (GSE50161), OG (GSE4290), AA (GSE43378), and GBM (GSE36245) datasets. The functional annotation and pathway enrichment analysis done through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed that the modules and hub genes identified were mainly involved in signal transduction, transcription regulation, and protein binding, which collectively deregulate several signaling pathways, mainly PI3K/Akt and metabolic pathways. The involvement of several hub genes primarily linked to other signaling pathways, including the cAMP, MAPK/ERK, Wnt/β-catenin, and calcium signaling pathways, indicates potential interconnectivity and influence on the PI3K/Akt pathway and, subsequently, glioma severity. The Drug Repurposing Encyclopedia (DRE) was used to screen for potential drugs based on the up- and downregulated hub genes, wherein the synthetic progestin hormones norgestimate and ethisterone were the top drug candidates. This shows the potential neuroprotective effect of progesterone against glioma due to its influence on EGFR expression and other signaling pathways. Aside from these, several experimental and approved drug candidates were also identified, which include an adrenergic receptor antagonist, a PPAR-γ receptor agonist, a CDK inhibitor, a sodium channel blocker, a bradykinin receptor antagonist, and a dopamine receptor agonist, which further highlights the gene network as a potential therapeutic avenue for glioma. Full article

Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a favorable prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles (EVs), circulating in CSF, express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from PA, congenital hydrocephalus (CH, non-tumor control), or medulloblastoma (MB, unrelated tumoral control) patients. A total of 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which were expressed in the unprocessed total and in its large-EV (LEV), and small-EV (SEV) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted the inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers for discriminating among pilocytic astrocytoma and unrelated tumoral (MB) or non-tumoral conditions in all the fractions examined, and are proposed to be prospectively validated in the plasma for translational medicine applications. Full article

Gliomas comprise most cases of central nervous system (CNS) tumors. Gliomas afflict both adults and children, and glioblastoma (GBM) in adults represents the clinically most important type of malignant brain cancer, with a very poor prognosis. The cell surface glycoprotein CD114, which is encoded by the CSF3R gene, acts as the receptor for the granulocyte colony stimulating factor (GCSF), and is thus also called GCSFR or CSFR. CD114 is a marker of cancer stem cells (CSCs), and its expression has been reported in several cancer types. In addition, CD114 may represent one among various cases where brain tumors hijack molecular mechanisms involved in neuronal survival and synaptic plasticity. Here, we describe CSF3R mRNA expression in human gliomas and their association with patient prognosis as assessed by overall survival (OS). We found that the levels of CSF3R/CD114 transcripts are higher in a few different types of gliomas, namely astrocytoma, pilocytic astrocytoma, and GBM, in comparison to non-tumoral neural tissue. We also observed that higher expression of CSF3R/CD114 in gliomas is associated with poorer outcome as measured by a shorter OS. Our findings provide early evidence suggesting that CSF3R/CD114 shows a potential role as a prognosis marker of OS in patients with GBM. Full article

Various types of brain tumors occur in both children and adults. These tumors manifest with different characteristics such as malignancy, cellular lineage, location of origin, and genomic profile. Recently, immunotherapy, which manipulates immune cells in the tumor microenvironment (TME) to kill tumor cells, has attracted attention as a treatment strategy for tumors. Here, we analyzed the transcriptomic architecture of the brain tumor microenvironment to provide potential guidelines to overcome the therapeutic vulnerabilities to brain tumors. We decomposed the cellular populations of six brain tumor types (meningioma, pilocytic astrocytoma, ependymoma, medulloblastoma, glioblastoma, and lower-grade glioma) using publicly available microarray data and single-cell RNA sequencing (scRNA-seq) data. Interestingly, transcriptome-based immune cell profiling revealed that infiltrating immune cell types in the brain TME, particularly M2 macrophages, CD8+ T cells, and CD4+ T cells, could be distinguished by tumor type, malignancy, and location. scRNA-seq revealed differences in the proportions of dendritic and mural cells. Unsupervised clustering using immune-related genes divided all samples into two distinct clusters with different characteristics. In addition, immune subpopulations showed disparate reactions after anti-PD-1 therapy for glioblastoma. Our results unveiled the distinct TME across brain tumor types and provided a transcriptomic landscape. Our findings may contribute to realizing future precision medicine, providing a basic rationale for the therapeutics of brain tumors. Full article