In children, high-grade gliomas (HGG) and diffuse midline gliomas (DMG) account for a high proportion of death due to cancer. Glioma stem cells (GSCs) are tumor cells in a specific state defined by a tumor-initiating capacity following serial transplantation, self-renewal, and an ability to recapitulate tumor heterogeneity. Their presence was demonstrated several decades ago in adult glioblastoma (GBM), and more recently in pediatric HGG and DMG. In adults, we and others have previously suggested that GSCs nest into the subventricular zone (SVZ), a neurogenic niche, where, among others, they find shelter from therapy. Both bench and bedside evidence strongly indicate a role for the GSCs and the SVZ in GBM progression, fostering the development of innovative targeting treatments. Such new therapeutic approaches are of particular interest in infants, in whom standard therapies are often limited due to the risk of late effects. The aim of this review is to describe current knowledge about GSCs in pediatric HGG and DMG, i.e., their characterization, the models that apply to their development and maintenance, the specific signaling pathways that may underlie their activity, and their specific interactions with neurogenic niches. Finally, we will discuss the clinical relevance of these observations and the therapeutic advantages of targeting the SVZ and/or the GSCs in infants.

Gliomas are severe brain malignancies, with glioblastoma (GBM) being the most aggressive one. Despite continuous efforts for improvement of existing therapies, overall survival remains poor. Over the last years, the implication of chemokines and their receptors in GBM development and progression has become more evident. Recently, large amounts of clinical data have been made available, prompting us to investigate chemokine receptors in GBM from a still-unexplored patient-oriented perspective. This study aims to highlight and discuss the involvement of chemokine receptors—CCR1, CCR5, CCR6, CCR10, CX3CR1, CXCR2, CXCR4, ACKR1, ACKR2, and ACKR3—most abundantly expressed in glioma patients based on the analysis of publicly available clinical datasets. Given the strong intratumoral heterogeneity characterizing gliomas and especially GBM, receptor expression was investigated by glioma molecular groups, by brain region distribution, emphasizing tissue-specific receptor functions, and by cell type enrichment. Our study constitutes a clinically relevant and patient-oriented guide that recapitulates the expression profile and the complex roles of chemokine receptors within the highly diversified glioma landscape. Additionally, it strengthens the importance of patient-derived material for development and precise amelioration of chemokine receptor-targeting therapies.

Cancer cells are continually exposed to environmental stressors forcing them to adapt their protein production to survive. The translational machinery can be recruited by malignant cells to synthesize proteins required to promote their survival, even in times of high physiological and pathological stress. This phenomenon has been described in several cancers including in gliomas. Abnormal regulation of translation has encouraged the development of new therapeutics targeting the protein synthesis pathway. This approach could be meaningful for glioma given the fact that the median survival following diagnosis of the highest grade of glioma remains short despite current therapy. The identification of new targets for the development of novel therapeutics is therefore needed in order to improve this devastating overall survival rate. This review discusses current literature on translation in gliomas with a focus on the initiation step covering both the cap-dependent and cap-independent modes of initiation. The different translation initiation protagonists will be described in normal conditions and then in gliomas. In addition, their gene expression in gliomas will systematically be examined using two freely available datasets. Finally, we will discuss different pathways regulating translation initiation and current drugs targeting the translational machinery and their potential for the treatment of gliomas.

Diffuse low-grade gliomas (LGG) commonly affect young adults and display a slow evolution, with a life expectancy that can surpass 15 years, thanks to multimodal therapeutic management. Therefore, preservation of quality of life (QoL), including sexual health, is mandatory. We systematically searched available medical databases of Pubmed, Cochrane, and Scopus for studies that reported data on sexual activity or dysfunction (SD) in LGG patients. We analyzed results to determine incidence of SD and its association with QoL in this population. Three studies focused on SD incidence in patients presenting specifically LGG, or brain tumors including LGG. They comprised 124 brain tumor patients, including 62 LGG, with SD incidence ranging from 44 to 63%. SD was reported by more than 50% of interrogated women in the three studies. Regarding QoL, two out of the three studies found significant associations between SD and alterations of QoL parameters, particularly in the field of social and functional wellbeing. Finally, we discussed those results regarding methods of evaluation, inherent biases, and therapeutic implications regarding antiseizure medications and also planning of surgery, chemo-, and radiotherapy. Our review showed that SD is highly prevalent but still poorly studied in LGG patients. As those patients are usually young and enjoy an active life, there is a need to assess more systematically the occurrence of SD in clinical routine, in order to adapt cancer treatments accordingly, to manage actively these troubles, and finally to improve patients’ QoL in the long run.

In vivo models are essential for the study of glioblastoma (GBM). Patient-Derived Orthotopic Xenograft (PDOX) using GBM cells in immunodeficient mice classically results into two main scenarios of tumor development, either intracerebral or intraventricular. In the present brief report, we have used brain clarification and lightsheet imaging to highlight the occurrence of a communicating hydrocephalus associated to the ventral leptomeningeal invasion by cancer cells, leading to a decreased survival. We believe that this uncommon event should be taken into account for interpretation of forthcoming survival manipulations in preclinical studies.

The study aimed to evaluate the patterns and quality of therapeutic care and pathological diagnosis for glioma patients by calculating process indicators across Belgian hospitals. All Belgian patients newly diagnosed with glioma between 2016 and 2019 were identified in the Belgian Cancer Registry (BCR). The National Social Security Number was used to link pathology reports and databases providing information on diagnostic and therapeutic procedures and vital status. Eighteen process indicators for therapeutic care and seven for pathological diagnosis were assessed for measurability based on administrative data availability. Measurable indicators were reviewed by a multidisciplinary expert board, and a validation study was conducted in six pilot hospitals. Associations between process indicators and outcomes were explored where possible. Nine indicators for therapeutic care and five for pathological diagnosis were measurable, though five required reformulations due to shortcomings in administrative data, mainly regarding radiotherapy dose and number of fractions. Most indicators met the predefined targets, indicating the provision of qualitative care. No low-grade gliomas received chemo- or radiotherapy without prior pathological confirmation. Concomitant chemoradiotherapy was initiated in 93.1% of surgically treated and 88.9% of biopsied glioblastoma patients (target 90%). For grade 3 astrocytoma and oligodendroglioma, the use of adjuvant chemo- and radiotherapy increased over time, meeting the 90% target by 2019. However, timely initiation of chemoradiotherapy (within 6 weeks of resection) in high-grade glioma could be improved (79.8% versus target 95%). The proportion of patients receiving chemotherapy (3.5%) or radiotherapy (2.5%) in the last 14 days of life remained below the 5% target. This research provides valuable feedback to Belgian hospitals and health care providers in neuro-oncology care programmes, opening opportunities for quality enhancement. On an international level, it underscores the significance of standardized quality assessment methods in neuro-oncology, which could serve as a foundation for future benchmark initiatives.