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Tractography fluorescence and confocal endomicroscopy are complementary technologies to targeted tumor resection, and it is certain that as our technology for fluorescent probes continues to evolve, the confocal microscope will continue to be refined. Recent work suggests that intraoperative high-resolution augmented reality endomicroscopy, a real-time alternative to invasive biopsy and histopathology, has the potential to better quantify tumor burden at the final stages of surgery and ultimately to improve patient outcomes when combined with wide-field imaging approaches. Additional studies are needed to further elucidate the clinical benefits of these new technologies for brain tumor patients.

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Introduction: Infrared thermography (IT) is a non-invasive real-time imaging technique with potential application in different areas of neurosurgery. Despite technological advances in the field, intraoperative IT (IIT) has been an underestimated tool with scarce reports on its usefulness during intracranial tumor resection. We aimed to evaluate the usefulness of high-resolution IIT with static and dynamic thermographic maps for transdural lesion localization, and diagnosis, to assess the extent of resection, and the occurrence of perioperative acute ischemia. Methods: In a prospective study, 15 patients affected by intracranial tumors (six gliomas, four meningiomas, and five brain metastases) were examined with a high-resolution thermographic camera after craniotomy, after dural opening, and at the end of tumor resection. Results: Tumors were transdurally located with 93.3% sensitivity and 100% specificity (p < 0.00001), as well as cortical arteries and veins. Gliomas were consistently hypothermic, while metastases and meningiomas exhibited highly variable thermographic maps on static (p = 0.055) and dynamic (p = 0.015) imaging. Residual tumors revealed non-specific static but characteristic dynamic thermographic maps. Ischemic injuries were significantly hypothermic (p < 0.001). Conclusions: High-resolution IIT is a non-invasive alternative intraoperative imaging method for lesion localization, diagnosis, assessing the extent of tumor resection, and identifying acute ischemia changes with static and dynamic thermographic maps.

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Introduction: Data on medulloblastoma outcomes and experiences in low- and middle-income countries, especially in Latin America, is limited. This study examines challenges in Mexico's healthcare system, focusing on assessing outcomes for children with medulloblastoma in a tertiary care setting. Methods: A retrospective analysis was conducted, involving 284 patients treated at 21 pediatric oncology centers in Mexico. Results: High-risk patients exhibited markedly lower event-free survival than standard-risk patients (43.5% vs. 78.3%, p<0.001). Influential factors on survival included anaplastic subtype (HR 2.4, p=0.003), metastatic disease (HR 1.9, p=0.001); residual tumor >1.5cm², and lower radiotherapy doses significantly impacted event-free survival (EFS) and overall survival (OS). Platinum-based chemotherapy showed better results compared to the ICE protocol in terms of OS and EFS, which was associated with higher toxicity. Patients under 3 years old displayed notably lower OS and EFS compared to older children (36.1% vs. 55.9%, p=0.01).

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Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABAA receptors. The GABRA5 gene, which encodes the α5 subunit of the GABAA receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABAA receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABAA receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABAA receptor subunit genes. OS was calculated using the Kaplan-Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABAA receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABAA receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABAA receptors as a therapeutic target in glioma.

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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.

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BACKGROUND: Brain tumors represent the most common cause of cancer-related death in children. Few studies concerning the palliative phase in children with brain tumors are available. OBJECTIVES: (i) To describe the palliative phase in children with brain tumors; (ii) to determine whether the use of palliative sedation (PS) depends on the place of death, the age of the patient, or if they received specific palliative care (PC). METHODS: Retrospective multicenter study between 2010 and 2021, including children from one month to 18 years, who had died of a brain tumor. RESULTS: 228 patients (59.2% male) from 10 Spanish institutions were included. Median age at diagnosis was 5 years (IQR 2-9) and median age at death was 7 years (IQR 4-11). The most frequent tumors were medulloblastoma (25.4%) and diffuse intrinsic pontine glioma (DIPG) (24.1%). Median number of antineoplastic regimens were 2 (range 0-5 regimens). During palliative phase, 52.2% of the patients were attended by PC teams, while 47.8% were cared exclusively by pediatric oncology teams. Most common concerns included motor deficit (93.4%) and asthenia (87.5%) and communication disorders (89.8%). Most frequently prescribed supportive drugs were antiemetics (83.6%), opioids (81.6%), and dexamethasone (78.5%). PS was administered to 48.7% patients. Most of them died in the hospital (85.6%), while patients who died at home required PS less frequently (14.4%) (p = .01). CONCLUSION: Children dying from CNS tumors have specific needs during palliative phase. The optimal indication of PS depended on the center experience although, in our series, it was also influenced by the place of death.

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Neuropilins are transmembrane glycoproteins that regulate developmental processes in the nervous system and other tissues. Overexpression of neuropilin-1 (NRP1) occurs in many solid tumor types and, in several instances, may predict patient outcome in terms of overall survival. Experimental inhibition of NRP1 activity can display antitumor effects in different cancer models. Here, we review NRP1 expression and function in adult and pediatric brain cancers, particularly glioblastomas (GBMs) and medulloblastomas, and present analyses of NRP1 transcript levels and their association with patient survival in GBMs. The case of NRP1 highlights the potential of regulators of neurodevelopment as biomarkers and therapeutic targets in brain cancer.

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OBJECTIVE: This study aimed to identify if there are ethnic differences in the age and sex distribution of gliomas in the Latino adult population. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Databases used were MEDLINE, LILACS, Web of Science, and Scopus. Studies were included if they reported the age and/or sex distribution of gliomas in Latin adults, published in English or Spanish from January 1st, 1985, to December 1st, 2022. The quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale and the NIH Quality Assessment Tool. RESULTS: From 1096 articles, fifteen studies with information on 6,815 patients were selected for the systematic review, and thirteen were selected for the meta-analysis. The mean ages of diagnosis of glioma and glioblastoma were 50.9, 95\%\ CI [47.8-53.9] years and 53.33 years, 95 \% CI [51-55.6], respectively. The male-to-female incidence rate ratio of gliomas was 1.39. CONCLUSION: Our study found mean ages of glioma and glioblastoma were 6 and 10 years lower than those reported in the CBTRUS. Our study suggests disparities in the age and sex distribution of gliomas in Latin America compared to other regions. PROSPERO REGISTRATION NUMBER: CRD42021274423.

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Medulloblastoma (MB) is a heterogeneous group of malignant pediatric brain tumors, divided into molecular groups with distinct biological features and prognoses. Currently available therapy often results in poor long-term quality of life for patients, which will be afflicted by neurological, neuropsychiatric, and emotional sequelae. Identifying novel therapeutic agents capable of targeting the tumors without jeopardizing patients' quality of life is imperative. Rosmarinic acid (RA) is a plant-derived compound whose action against a series of diseases including cancer has been investigated, with no side effects reported so far. Previous studies have not examined whether RA has effects in MB. Here, we show RA is cytotoxic against human Daoy (IC50 = 168 µM) and D283 (IC50 = 334 µM) MB cells. Exposure to RA for 48 h reduced histone deacetylase 1 (HDAC1) expression while increasing H3K9 hyperacetylation, reduced epidermal growth factor (EGFR) expression, and inhibited EGFR downstream targets extracellular-regulated kinase (ERK)1/2 and AKT in Daoy cells. These modifications were accompanied by increased expression of CDKN1A/p21, reduced expression of SOX2, and a decrease in proliferative rate. Treatment with RA also reduced cancer stem cell markers expression and neurosphere size. Taken together, our findings indicate that RA can reduce cell proliferation and stemness and induce cell cycle arrest in MB cells. Mechanisms mediating these effects may include targeting HDAC1, EGFR, and ERK signaling, and promoting p21 expression, possibly through an increase in H3K9ac and AKT deactivation. RA should be further investigated as a potential anticancer agent in experimental MB.

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BACKGROUND: Radiomics refers to the acquisition of traces of quantitative features that are usually non-perceptible to human vision and are obtained from different imaging techniques and subsequently transformed into high-dimensional data. Diffuse midline gliomas (DMG) represent approximately 20% of pediatric CNS tumors, with a median survival of less than one year after diagnosis. We aimed to identify which radiomics can discriminate DMG tumor regions (viable tumor and peritumoral edema) from equivalent midline normal tissue (EMNT) in patients with the positive H3.F3K27M mutation, which is associated with a worse prognosis. PATIENTS AND METHODS: This was a retrospective study. From a database of 126 DMG patients (children, adolescents, and young adults), only 12 had H3.3K27M mutation and available brain magnetic resonance DICOM file. The MRI T1 post-gadolinium and T2 sequences were uploaded to LIFEx software to post-process and extract radiomic features. Statistical analysis included normal distribution tests and the Mann-Whitney U test performed using IBM SPSS® (Version 27.0.0.1, International Business Machines Corp., Armonk, NY, USA), considering a significant statistical p-value ≤ 0.05. RESULTS: EMNT vs. Tumor: From the T1 sequence 10 radiomics were identified, and 14 radiomics from the T2 sequence, but only one radiomic identified viable tumors in both sequences (p < 0.05) (DISCRETIZED_Q1). Peritumoral edema vs. EMNT: From the T1 sequence, five radiomics were identified, and four radiomics from the T2 sequence. However, four radiomics could discriminate peritumoral edema in both sequences (p < 0.05) (CONVENTIONAL_Kurtosis, CONVENTIONAL_ExcessKurtosis, DISCRETIZED_Kurtosis, and DISCRETIZED_ExcessKurtosis). There were no radiomics useful for distinguishing tumor tissue from peritumoral edema in both sequences. CONCLUSIONS: Less than 5% of the radiomic characteristics identified tumor regions of medical-clinical interest in T1 and T2 sequences of conventional magnetic resonance imaging. The first-order and second-order radiomic features suggest support to investigators and clinicians for careful evaluation for diagnosis, patient classification, and multimodality cancer treatment planning.