A brave new framework for glioma drug development.

Patients with brain tumours are motivated to participate in clinical trials involving repeat tissue sampling. Normalising the use of neoadjuvant and staged surgical trials necessitates collaboration among patients, regulatory agencies, and researchers. Initial and repetitive tissue sampling plays a crucial role in enhancing our understanding of resistance mechanisms and vulnerabilities in brain tumour therapy. Standardising biopsy techniques and ensuring technical uniformity across institutions are vital for effective interinstitutional collaboration. Although liquid biopsy technologies hold promise, they are not yet ready to replace tissue analysis. Clear communication about the risks and benefits of biopsies is essential, particularly regarding potential postoperative deficits. Changes in mindset and neurosurgical culture are imperative to achieve much needed breakthroughs in the development of new, effective therapies for brain tumours.

Primary brain tumours in adults.

The most frequent adult-type primary CNS tumours are diffuse gliomas, but a large variety of rarer CNS tumour types exists. The classification of these tumours is increasingly based on molecular diagnostics, which is reflected in the extensive molecular foundation of the recent WHO 2021 classification of CNS tumours. Resection as extensive as is safely possible is the cornerstone of treatment in most gliomas, and is now also recommended early in the treatment of patients with radiological evidence of histologically low-grade tumours. For the adult-type diffuse glioma, standard of care is a combination of radiotherapy and chemotherapy. Although treatment with curative intent is not available, combined modality treatment has resulted in long-term survival (>10-20 years) for some patients with isocitrate dehydrogenase (IDH) mutant tumours. Other rarer tumours require tailored approaches, best delivered in specialised centres. Targeted treatments based on molecular alterations still only play a minor role in the treatment landscape of adult-type diffuse glioma, and today are mainly limited to patients with tumours with BRAFV600E (ie, Val600Glu) mutations. Immunotherapy for CNS tumours is still in its infancy, and so far, trials with checkpoint inhibitors and vaccination studies have not shown improvement in patient outcomes in glioblastoma. Current research is focused on improving our understanding of the immunosuppressive tumour environment, the molecular heterogeneity of tumours, and the role of tumour microtube network connections between cells in the tumour microenvironment. These factors all appear to play a role in treatment resistance, and indicate that novel approaches are needed to further improve outcomes of patients with CNS tumours.

Diffuse infiltrating tumour with the molecular profile of an atypical teratoid rhabdoid tumour (AT/RT SHH-1B) in an adult patient.

We describe a 46-year-old patient with an IDH-wildtype diffusely infiltrating atypical teratoid/rhabdoid tumour (AT/RT), SHH-1B molecular subtype. The unusual histology and subsequent diagnosis in an adult patient will be discussed.

MicroRNA-575 acts as a novel oncogene via targeting multiple signaling pathways in glioblastoma.

PURPOSE: Glioblastoma (GBM) patients currently face poor survival outcomes with an average survival period of <15 months, while only 3-5% of patients survive longer than 36 months. Although the mechanisms of tumorigenesis are still being elucidated, miRNAs are promising candidates to explore as novel and prognostic biomarkers in GBM. In this study, we identified the association between miR-575 expression and overall survival (OS) of primary GBM patients and undertook functional studies to discern the contribution of miR-575 to GBM tumorigenesis. METHODS: Total RNAs were isolated from 254 FFPE GBM tumor samples and miR expression was assayed (simultaneously) using NanoString Technologies. To determine the association between miR-575 and patients' prognosis, Kaplan-Meier, univariable and multivariable Cox regression analyses were performed. Cell proliferation, colony formation, migration assays were conducted to investigate the function of miR-575 in vitro and in vivo. In silico target gene network analysis was performed to identify the putative targets of miR-575 in GBM, which were further verified by luciferase reporter assay, as well as qPCR and immunoblotting. RESULTS: Our clinical data (n = 254) show that miR-575 is associated with worse GBM OS by univariable analysis (UVA, HR = 1.27, p-value<0.001) and multivariable (MVA, HR = 1.23, p = 0.007) analysis incorporating critical clinical variables. Functional studies indicated that overexpression of miR-575 significantly increased cell proliferation and migration of GBM cells in vitro, as well as tumor growth in vivo. Subsequent in silico target gene network and mechanistic studies identified CDKN1B/p27 and PTEN, as potential targets of miR-575 in GBM. MicroRNA-575 can also regulate the activity of AKT and ERK pathways in GBM. CONCLUSION: miR-575 has prognostic value in GBM, with higher expression associating with worse OS of patients, and contributes to GBM tumorigenesis by regulating multiple signaling pathways in GBM.

Treatment of anaplastic gliomas: evidences and controversies.

PURPOSE OF REVIEW: Evolving molecular data have led to a new and advanced grading system of anaplastic glioma. In everyday practice, physicians have to translate evidence from old clinical trials into evidence meeting the reclassified tumor types. RECENT FINDINGS: New biomarkers allow the identification of anaplastic glioma with relatively poor prognosis and with prognosis similar to glioblastoma. An update with molecular analysis of the phase 3 CATNON trial demonstrates the benefit of adjuvant temozolomide (TMZ) to be dependent on the mutational status of isocitrate dehydrogenase. In the ongoing debate on the optimal chemotherapy regimen, a large retrospective study suggesting a better tumor control with vincristine (PCV) as compared to TMZ is added to the evidence. The best timing for treatment of anaplastic astrocytoma also remains a matter of controversy. A recent study shows that even in selected patients with anaplastic glioma with foci of malignant tumor following (sub)total resection, postponement of medical treatment can be considered. SUMMARY: In clinical practice, the trade-off between efficacy and (acute and long-term) toxicity of treatments needs to be re-evaluated for the newly (molecularly) defined entities. Updates from past clinical trials on anaplastic glioma with molecular analysis and subgroup analyses are needed to further guide treatment decisions.

Treatment Restrictions and the Risk of Death in Patients With Ischemic Stroke or Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Do-not-resuscitate (DNR) orders in the first 24 hours after intracerebral hemorrhage have been associated with an increased risk of early death. This relationship is less certain for ischemic stroke. We assessed the relation between treatment restrictions and mortality in patients with ischemic stroke and in patients with intracerebral hemorrhage. We focused on the timing of treatment restrictions after admission and the type of treatment restriction (DNR order versus more restrictive care). METHODS: We retrospectively assessed demographic and clinical data, timing and type of treatment restrictions, and vital status at 3 months for 622 consecutive stroke patients primarily admitted to a Dutch university hospital. We used a Cox regression model, with adjustment for age, sex, comorbidities, and stroke type and severity. RESULTS: Treatment restrictions were installed in 226 (36%) patients, more frequently after intracerebral hemorrhage (51%) than after ischemic stroke (32%). In 187 patients (83%), these were installed in the first 24 hours. Treatment restrictions installed within the first 24 hours after hospital admission and those installed later were independently associated with death at 90 days (adjusted hazard ratios, 5.41 [95% CI, 3.17-9.22] and 5.36 [95% CI, 2.20-13.05], respectively). Statistically significant associations were also found in patients with ischemic stroke and in patients with just an early DNR order. In those who died, the median time between a DNR order and death was 520 hours (interquartile range, 53-737). CONCLUSIONS: The strong relation between treatment restrictions (including DNR orders) and death and the long median time between a DNR order and death suggest that this relation may, in part, be causal, possibly due to an overall lack of aggressive care.

Development of healthy and sustainable food-based dietary guidelines for the Netherlands.

OBJECTIVE: To derive healthy and sustainable food-based dietary guidelines (FBDG) for different target groups in the Netherlands and describe the process. DESIGN: Optimised dietary patterns for children, adolescents, adults and the elderly were calculated using an optimisation model. Foods high in saturated and trans-fatty acids, salt and sugar, and low in dietary fibre, were excluded. The dietary patterns resembled the current food consumption as closely as possible, while simultaneously meeting recommendations for food groups, nutrients, maximum limits for foods with a high environmental impact, and within 85 % of the energy requirement. Recommended daily amounts of food groups were based on the optimised dietary patterns and expert judgement. SETTING: The Netherlands. PARTICIPANTS: FBDG were derived for Dutch people with different ages, genders, activity levels and food preferences. RESULTS: For most target groups the optimisation model provided dietary patterns that complied with all requirements. For some food groups, the optimised amounts varied largely between target groups. For consistent messages to consumers, the optimised dietary patterns were adjusted to uniform recommendations per target group. Recommendations were visualised in the Wheel of Five. The advice is to eat the recommended amounts of foods according to the Wheel of Five and limit consumption of other foods. CONCLUSIONS: Based on an optimisation model, scientific evidence, information on dietary patterns and expert knowledge, we derived FBDG for different target groups. The Wheel of Five is a key food-counselling model that can help Dutch consumers to make their diets healthier and more environmentally sustainable.

COOLIST (Cooling for Ischemic Stroke Trial): A Multicenter, Open, Randomized, Phase II, Clinical Trial.

BACKGROUND AND PURPOSE: Animal studies suggest that cooling improves outcome after ischemic stroke. We assessed the feasibility and safety of surface cooling to different target temperatures in awake patients with acute ischemic stroke. METHODS: A multicenter, randomized, open, phase II, clinical trial, comparing standard treatment with surface cooling to 34.0°C, 34.5°C, or 35.0°C in awake patients with acute ischemic stroke and an National Institutes of Health Stroke Scale score of ≥6, initiated within 4.5 hours after symptom onset and maintained for 24 hours. The primary outcome was feasibility, defined as the proportion of patients who had successfully completed the assigned treatment. Safety was a secondary outcome. RESULTS: Inclusion was terminated after 22 patients because of slow recruitment. Five patients were randomized to 34.0°C, 6 to 34.5°C, 5 to 35.0°C (cooling was initiated in 4), and 6 to standard care. No (0%), 1 (17%), and 3 (75%) patients, respectively, completed the assigned treatment (P=0.03). No (0%), 2 (33%), and 4 (100%) patients reached the target temperature (P=0.01). Pneumonia occurred in 8 cooled patients but not in controls (absolute risk increase, 53%; 95% confidence interval, 28-79%; P=0.002). CONCLUSIONS: In awake patients with acute ischemic stroke, surface cooling is feasible to 35.0°C, but not to 34.5°C and 34.0°C. Cooling is associated with an increased risk of pneumonia. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR2616.

Advance directives, proxy opinions, and treatment restrictions in patients with severe stroke.

BACKGROUND: Patients with severe stroke often do not have the capacity to participate in discussions on treatment restrictions because of a reduced level of consciousness, aphasia, or another cognitive disorder. We assessed the role of advance directives and proxy opinions in the decision-making process of incapacitated patients. METHODS: Sixty patients with severe functional dependence (Barthel Index ≤6) at day four after ischemic stroke or intracerebral hemorrhage were included in a prospective two-center cohort study. The decision-making process with respect to treatment restrictions was assessed by means of a semi-structured questionnaire administered to the treating physician at the day of inclusion. RESULTS: Forty-nine patients (82%) did not have the capacity to participate in the decision-making process. In eight patients, there was no discussion on treatment restrictions and full care was installed. In 41 patients, the decision whether to install treatment restrictions was discussed with proxies. One patient had a written advance directive. In the remaining 40 patients, proxies based their opinion on previously expressed wishes of the patient (18 patients) or advised in the best interest of the patient (22 patients). In 36 of 41 patients, treatment restrictions were installed after agreement between physician and proxy. At six months, 23 of 49 patients had survived. In only three of them the decision on treatment restrictions was based on previously expressed wishes. Remarkably, two of these survivors could not recall any of their alleged previously expressed wishes. CONCLUSIONS: Treatment restrictions were installed in the majority of incapacitated patients after stroke. Proxy opinions frequently served as the best way to respect the patients' autonomy, but their accuracy remains unclear.

Temporal profile of body temperature in acute ischemic stroke: relation to infarct size and outcome.

BACKGROUND: High body temperatures after ischemic stroke have been associated with larger infarct size, but the temporal profile of this relation is unknown. We assess the relation between temporal profile of body temperature and infarct size and functional outcome in patients with acute ischemic stroke. METHODS: In 419 patients with acute ischemic stroke we assessed the relation between body temperature on admission and during the first 3 days with both infarct size and functional outcome. Infarct size was measured in milliliters on CT or MRI after 3 days. Poor functional outcome was defined as a modified Rankin Scale score ≥3 at 3 months. RESULTS: Body temperature on admission was not associated with infarct size or poor outcome in adjusted analyses. By contrast, each additional 1.0 °C in body temperature on day 1 was associated with 0.31 ml larger infarct size (95% confidence interval (CI) 0.04-0.59), on day 2 with 1.13 ml larger infarct size(95% CI, 0.83-1.43), and on day 3 with 0.80 ml larger infarct size (95% CI, 0.48-1.12), in adjusted linear regression analyses. Higher peak body temperatures on days two and three were also associated with poor outcome (adjusted relative risks per additional 1.0 °C in body temperature, 1.52 (95% CI, 1.17-1.99) and 1.47 (95% CI, 1.22-1.77), respectively). CONCLUSIONS: Higher peak body temperatures during the first days after ischemic stroke, rather than on admission, are associated with larger infarct size and poor functional outcome. This suggests that prevention of high temperatures may improve outcome if continued for at least 3 days.

Therapeutic hypothermia and the risk of infection: a systematic review and meta-analysis.

OBJECTIVE: Observational studies suggest that infections are a common complication of therapeutic hypothermia. We performed a systematic review and meta-analysis of randomized trials to examine the risk of infections in patients treated with hypothermia. DATA SOURCES: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched for eligible studies up to October 1, 2012. STUDY SELECTION: We included randomized controlled clinical trials of therapeutic hypothermia induced in adults for any indication, which reported the prevalence of infection in each treatment group. DATA EXTRACTION: For each study, we collected information about the baseline characteristics of patients, cooling strategy, and infections. DATA SYNTHESIS: Twenty-three studies were identified, which included 2,820 patients, of whom 1,398 (49.6%) were randomized to hypothermia. Data from another 31 randomized trials, involving 4,004 patients, could not be included because the occurrence of infection was not reported with sufficient detail or not at all. The risk of bias in the included studies was high because information on the method of randomization and definitions of infections lacked in most cases, and assessment of infections was not blinded. In patients treated with hypothermia, the prevalence of all infections was not increased (rate ratio, 1.21 [95% CI, 0.95-1.54]), but there was an increased risk of pneumonia and sepsis (risk ratios, 1.44 [95% CI, 1.10-1.90]; 1.80 [95% CI, 1.04-3.10], respectively). CONCLUSION: The available evidence, subject to its limitations, strongly suggests an association between therapeutic hypothermia and the risk of pneumonia and sepsis, whereas no increase in the overall risk of infection was observed. All future randomized trials of hypothermia should report on this important complication.

H3 K27M-altered glioma and diffuse intrinsic pontine glioma: Semi-systematic review of treatment landscape and future directions.

H3 K27M-mutant diffuse glioma is a recently identified brain tumor associated with poor prognosis. As of 2016, it is classified by the World Health Organization as a distinct form of grade IV glioma. Despite recognition as an important prognostic and diagnostic feature in diffuse glioma, radiation remains the sole standard of care and no effective systemic therapies are available for H3K27M mutant tumors. This review will detail treatment interventions applied to diffuse midline glioma and diffuse intrinsic pontine glioma (DIPG) prior to the identification of the H3 K27M mutation, the current standard-of-care for H3 K27M-mutant diffuse glioma treatment, and ongoing clinical trials listed on www.clinicaltrials.gov evaluating novel therapeutics in this population. Current clinical trials were identified using clinicaltrials.gov, and studies qualifying for this analysis were active or ongoing interventional trials that evaluated a therapy in at least 1 treatment arm or cohort comprised exclusively of patients with DIPG and H3 K27M-mutant glioma. Forty-one studies met these criteria, including trials evaluating H3 K27M vaccination, chimeric antigen receptor T-cell therapy, and small molecule inhibitors. Ongoing evaluation of novel therapeutics is necessary to identify safe and effective interventions in this underserved patient population.

The role of molecular biomarkers in recurrent glioblastoma trials: an assessment of the current trial landscape of genome-driven oncology.

For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments.

State of the Art in Low-Grade Glioma Management: Insights From Isocitrate Dehydrogenase and Beyond.

Low-grade gliomas present a formidable challenge in neuro-oncology because of the challenges imposed by the blood-brain barrier, predilection for the young adult population, and propensity for recurrence. In the past two decades, the systematic examination of genomic alterations in adults and children with primary brain tumors has uncovered profound new insights into the pathogenesis of these tumors, resulting in more accurate tumor classification and prognostication. It also identified several common recurrent genomic alterations that now define specific brain tumor subtypes and have provided a new opportunity for molecularly targeted therapeutic intervention. Adult-type diffuse low-grade gliomas are frequently associated with mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), resulting in production of 2-hydroxyglutarate, an oncometabolite important for tumorigenesis. Recent studies of IDH inhibitors have yielded promising results in patients at early stages of disease with prolonged progression-free survival (PFS) and delayed time to radiation and chemotherapy. Pediatric-type gliomas have high rates of alterations in BRAF, including BRAF V600E point mutations or BRAF-KIAA1549 rearrangements. BRAF inhibitors, often combined with MEK inhibitors, have resulted in radiographic response and improved PFS in these patients. This article reviews emerging approaches to the treatment of low-grade gliomas, including a discussion of targeted therapies and how they integrate with the current treatment modalities of surgical resection, chemotherapy, and radiation.

Gender balance and suitable positive actions to promote gender equality among healthcare professionals in neuro-oncology: The EANO positive action initiative.

Background: The proportion of women among healthcare and biomedical research professionals in neuro-oncology is growing. With changes in cultural expectations and work-life balance considerations, more men aspire to nonfull-time jobs, yet, leadership positions remain dominated by men. Methods: The European Association of Neuro-Oncology (EANO) disparity committee carried out a digital survey to explore gender balance and actions suitable to promote gender equality. The survey was distributed among EANO members in 2021, with responses analyzed descriptively. Results: In total, 262 participants completed the survey (141 women, 53.8%; median age 43). Respondents were neurosurgeons (68, 26.0%); neurologists (67, 25.6%), medical oncologists (43, 16.4%), or other healthcare or research professionals; 208 participants (79.4%) worked full-time. Positive action to enforce the role of women in neuro-oncology was deemed necessary by 180 participants (68.7%), but only 28 participants (10.7%) agreed that women only should be promoted until gender balance is reached. A majority of respondents (162, 61.8%) felt that women with an equivalent CV should be prioritized over men to reach gender balance. If in the future the balance favored women at higher positions, 112 respondents (42.7%) agreed to apply positive action for men. The top indicators considered relevant to measure gender balance were: salary for similar positions (183/228, 80.3%), paid overtime (176/228, 77.2%), number of permanent positions (164/228, 71.9%), protected time for research (161/227, 70.9%), and training opportunities (157/227, 69.2%). Conclusions: Specific indicators may help to measure and promote gender balance and should be considered for implementation among healthcare professionals in neuro-oncology.

Updated EANO guideline on rational molecular testing of gliomas, glioneuronal, and neuronal tumors in adults for targeted therapy selection - Update 1.

The standard of care for adult patients with gliomas, glioneuronal and neuronal tumors consists of combinations of surgery, radiotherapy, and chemotherapy. For many systemic cancers, targeted treatments are a major part of the standard treatment, however, the predictive significance of most of the targets for treatment in systemic cancer are less well established in central nervous system (CNS) tumors . In 2023 the EANO Guideline Committee presented evidence based recommendations for rational testing of molecular targets for targeted treatments. From all targets reviewed, only testing for BRAF V600E mutations was of proven clinical benefit; despite regulatory approvals for tumor agnostic treatment of NTRK gene fusions and high Tumor Mutational Burden (TMB) for patients with adult brain tumors, the evidence of clinical benefit for patients was still limited . This guideline has a modular structure, allowing regular updating of individual sections and adding new ones. The present version (Update 1) presents a review of the rationale of testing for PTEN, H3F3A, MTAP, RET and IDH, and presents an update of the text on TMB high and mismatch repair deficiency. It also presents an overview of therapeutic yield of routine next generation sequencing for mutations and fusion detection. The supplement accompanying this version contains the in depth review of all targets, whereas in the main manuscript the final recommendations of the revised and new targets are presented. Updates will be made on a regular basis.

Surgical decompression for space-occupying cerebral infarction: outcomes at 3 years in the randomized HAMLET trial.

BACKGROUND AND PURPOSE: We assessed whether the effects of surgical decompression for space-occupying hemispheric infarction, observed at 1 year, are sustained at 3 years. METHODS: Patients with space-occupying hemispheric infarction, who were enrolled in the Hemicraniectomy After Middle cerebral artery infarction with Life-threatening Edema Trial within 4 days after stroke onset, were followed up at 3 years. Outcome measures included functional outcome (modified Rankin Scale), death, quality of life, and place of residence. Poor functional outcome was defined as modified Rankin Scale >3. RESULTS: Of 64 included patients, 32 were randomized to decompressive surgery and 32 to best medical treatment. Just as at 1 year, surgery had no effect on the risk of poor functional outcome at 3 years (absolute risk reduction, 1%; 95% confidence interval, -21 to 22), but it reduced case fatality (absolute risk reduction, 37%; 95% confidence interval, 14-60). Sixteen surgically treated patients and 8 controls lived at home (absolute risk reduction, 27%; 95% confidence interval, 4-50). Quality of life improved between 1 and 3 years in patients treated with surgery. CONCLUSIONS: In patients with space-occupying hemispheric infarction, the effects of decompressive surgery on case fatality and functional outcome observed at 1 year are sustained at 3 years. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN94237756.

Alternative normalization and analysis pipeline to address systematic bias in NanoString GeoMx Digital Spatial Profiling data.

Spatial transcriptomics is a novel technique that provides RNA-expression data with tissue-contextual annotations. Quality assessments of such techniques using end-user generated data are often lacking. Here, we evaluated data from the NanoString GeoMx Digital Spatial Profiling (DSP) platform and standard processing pipelines. We queried 72 ROIs from 12 glioma samples, performed replicate experiments of eight samples for validation, and evaluated five external datasets. The data consistently showed vastly different signal intensities between samples and experimental conditions that resulted in biased analysis. We evaluated the performance of alternative normalization strategies and show that quantile normalization can adequately address the technical issues related to the differences in data distributions. Compared to bulk RNA sequencing, NanoString DSP data show a limited dynamic range which underestimates differences between conditions. Weighted gene co-expression network analysis allowed extraction of gene signatures associated with tissue phenotypes from ROI annotations. Nanostring GeoMx DSP data therefore require alternative normalization methods and analysis pipelines.

The effect of dexamethasone on the microenvironment and efficacy of checkpoint inhibitors in glioblastoma: a systematic review.

Background: Checkpoint inhibitor immunotherapy has not proven clinically effective in glioblastoma. This lack of effectiveness may be partially attributable to the frequent administration of dexamethasone in glioblastoma patients. In this systematic review, we assess whether dexamethasone (1) affects the glioblastoma microenvironment and (2) interferes with checkpoint inhibitor immunotherapy efficacy in the treatment of glioblastoma. Methods: PubMed and Embase were systematically searched for eligible articles published up to September 15, 2021. Both in vitro and in vivo preclinical studies, as well as clinical studies were selected. The following information was extracted from each study: tumor model, corticosteroid treatment, and effects on individual immune components or checkpoint inhibitor immunotherapy. Results: Twenty-one preclinical studies in cellular glioma models (n = 10), animal glioma models (n = 6), and glioblastoma patient samples (n = 7), and 3 clinical studies were included. Preclinical studies show that dexamethasone decreases the presence of microglia and other macrophages as well as the number of T lymphocytes in both tumor tissue and periphery. Dexamethasone abrogates the antitumor effects of checkpoint inhibitors on T lymphocytes in preclinical studies. Although randomized studies directly addressing our research question are lacking, clinical studies suggest a negative association between corticosteroids and survival outcomes in glioblastoma patients receiving checkpoint inhibitors after adjustment for relevant prognostic factors. Conclusions: Preclinical research shows that dexamethasone inhibits the antitumor immune response in glioma, thereby promoting a protumorigenic microenvironment. The efficacy of checkpoint inhibitor immunotherapy in glioblastoma patients may therefore be negatively affected by the use of dexamethasone. Future research could investigate the potential of edema-reducing alternatives to dexamethasone.