bims-malgli 2024-10-13 papers

bims-malgli

Biomed News

on Biology of malignant gliomas

Issue of 2024‒10‒13
eleven papers selected by
Oltea Sampetrean, Keio University

Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres.
EZH2 functional dichotomy in reactive oxygen species-stratified glioblastoma.
Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer.
Contemporary strategies in glioblastoma therapy: Recent developments and innovations.
Metabolomic characterization of human glioblastomas and patient plasma: a pilot study.
MALT1 protease inhibition restrains glioblastoma progression by reversing tumor-associated macrophage-dependent immunosuppression.
Cholinergic Neuronal Activity Promotes Diffuse Midline Glioma Growth through Muscarinic Signaling.
Metabolic remodeling in glioblastoma: a longitudinal multi-omics study.
Impact of genomic background and developmental state on signaling pathways and response to therapy in glioblastoma patient-derived cells.
Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma.
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021.

Neuro Oncol. 2024 Oct 11. pii: noae211. [Epub ahead of print]

Synergistic combination of perphenazine and temozolomide suppresses patient-derived glioblastoma tumorspheres.

Jun Pyo Hong, Ran Joo Choi, Jin-Kyoung Shim, Kibyeong Kim, Ryong Nam Kim, Hye Joung Cho, Seo Jin Kim, Sohyun Kim, Nam Hwa Kim, Hun Ho Park, Ju Hyung Moon, Eui Hyun Kim, Wan-Yee Teo, Seungsoo Chung, Jong Hee Chang, Seok-Gu Kang.

  BACKGROUND: Glioblastoma (GBM), a primary malignant brain tumor, has a poor prognosis, even with standard treatments such as radiotherapy and chemotherapy. In this study, we explored the anticancer effects of the synergistic combination of perphenazine (PER), a dopamine receptor D2/3 (DRD2/3) antagonist, and temozolomide (TMZ), a standard treatment for GBM, in patient-derived human GBM tumorspheres (TSs).METHODS: The biological effects of the combination of PER and TMZ in GBM TSs were assessed by measuring cell viability, ATP, stemness, invasiveness, and apoptosis. Changes in protein and mRNA expression were analyzed using western blotting and RNA sequencing. Co-administration of PER and TMZ was evaluated in vivo using a mouse orthotopic xenograft model.
RESULTS: The Severance dataset showed that DRD2 and DRD3 expression was higher in tumor tissues than in the tumor-free cortex of patients with GBM. DRD2/3 knockout by CRISPR/Cas9 in patient-derived human GBM TSs inhibited cell growth and ATP production. The combined treatment with PER and TMZ resulted in superior effects on cell viability and ATP assays compared to those in single treatment groups. Flow cytometry, western blotting, and RNA sequencing confirmed elevated apoptosis in GBM TSs following combination treatment. Additionally, the combination of PER and TMZ downregulated the expression of protein and mRNA associated with stemness and invasiveness. In vivo evaluation showed that combining PER and TMZ extended the survival period of the mouse orthotopic xenograft model.
CONCLUSIONS: The synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM.

Keywords:  DRD2/3; glioblastoma; perphenazine; temozolomide; tumorsphere

DOI:  https://doi.org/10.1093/neuonc/noae211
Neuro Oncol. 2024 Oct 07. pii: noae206. [Epub ahead of print]

EZH2 functional dichotomy in reactive oxygen species-stratified glioblastoma.

Lynnette Wei Hsien Koh, Qing You Pang, Wisna Novera, See Wee Lim, Yuk Kien Chong, Jinyue Liu, Samantha Ya Lyn Ang, Ron Weng Yee Loh, Huilin Shao, Jianhong Ching, Yulan Wang, Stephen Yip, Patrick Tan, Shang Li, David Chyi Yeu Low, Anne Phelan, Gabriel Rosser, Nguan Soon Tan, Carol Tang, Beng Ti Ang.

  BACKGROUND: EZH2, well-known for its canonical methyltransferase activity in transcriptional repression in many cancers including glioblastoma (GBM), has an understudied non-canonical function critical for sustained tumor growth. Recent GBM consortial efforts reveal complex molecular heterogeneity for which therapeutic vulnerabilities correlated with subtype stratification remain relatively unexplored. Current enzymatic EZH2 inhibitors (EZH2inh) targeting its canonical SET domain show limited efficacy and lack durable response, suggesting that underlying differences in the non-canonical pathway may yield new knowledge. Here, we unveiled dual roles of the EZH2 CXC domain in therapeutically-distinct, reactive oxygen species (ROS)-stratified tumors.METHODS: We analyzed differentially expressed genes between ROS classes by examining cis-regulatory elements as well as clustering of activities and pathways to identify EZH2 as the key mediator in ROS-stratified cohorts. Pull-down assays and CRISPR knockout of EZH2 domains were used to dissect the distinct functions of EZH2 in ROS-stratified GBM cells. The efficacy of NF-κB-inducing kinase inhibitor (NIKinh) and standard-of-care temozolomide was evaluated using orthotopic patient-derived GBM xenografts.
RESULTS: In ROS(+) tumors, CXC-mediated co-interaction with RelB drives constitutive activation of non-canonical NF-κB2 signaling, sustaining the ROS(+) chemoresistant phenotype. In contrast, in ROS(-) subtypes, PRC2 methyltransferase activity represses canonical NF-κB. Addressing the lack of EZH2inh targeting its non-methyltransferase roles, we utilized a brain-penetrant NIKinh that disrupts EZH2-RelB binding, consequently prolonging survival in orthotopic ROS(+)-implanted mice.
CONCLUSION: Our findings highlight the functional dichotomy of the EZH2 CXC domain in governing ROS-stratified therapeutic resistance, thereby advocating for the development of therapeutic approaches targeting its non-canonical activities and underscoring the significance of patient stratification methodologies.

Keywords:  EZH2; Precision medicine; brain cancer; glioblastoma; patient stratification

DOI:  https://doi.org/10.1093/neuonc/noae206
Cancer Discov. 2024 Oct 07.

Glioblastoma-cortical organoids recapitulate cell state heterogeneity and intercellular transfer.

Vamsi Mangena, Rony Chanoch-Myers, Rafaela Sartore, Bruna Paulsen, Simon Gritsch, Hannah Weisman, Toshiro Hara, Xandra O Breakefield, Koen Breyne, Aviv Regev, Kwanghun Chung, Paola Arlotta, Itay Tirosh, Mario L Suva.

Glioblastoma is characterized by heterogeneous malignant cells that are functionally integrated within the neuroglial microenvironment. Here, we model this ecosystem by growing glioblastoma into long-term cultured human cortical organoids that contain the major neuroglial cell types found in the cerebral cortex. Single-cell RNA-seq analysis suggests that, compared to matched gliomasphere models, glioblastoma cortical organoids (GCO) more faithfully recapitulate the diversity and expression programs of malignant cell states found in patient tumors. Additionally, we observe widespread transfer of glioblastoma transcripts and GFP proteins to non-malignant cells in the organoids. Mechanistically, this transfer involves extracellular vesicles and is biased towards defined glioblastoma cell states and astroglia cell types. These results extend previous glioblastoma-organoid modeling efforts and suggest widespread intercellular transfer in the glioblastoma neuroglial microenvironment.

DOI: https://doi.org/10.1158/2159-8290.CD-23-1336
Neuroscience. 2024 Oct 03. pii: S0306-4522(24)00474-3. [Epub ahead of print]560 211-237

Contemporary strategies in glioblastoma therapy: Recent developments and innovations.

Mariya Khan, Modassir Nasim, Mohammadamin Feizy, Rabea Parveen, Azka Gull, Saba Khan, Javed Ali.

  Glioblastoma multiforme (GBM) represents one of the most prevailing and aggressive primary brain tumors among adults. Despite advances in therapeutic approaches, the complex microenvironment of GBM poses significant challenges in its optimal therapy, which are attributed to immune evasion, tumor repopulation by stem cells, and limited drug penetration across the blood-brain barrier (BBB). Nanotechnology has emerged as a promising avenue for GBM treatment, offering biosafety, sustained drug release, enhanced solubility, and improved BBB penetrability. In this review, a comprehensive overview of recent advancements in nanocarrier-based drug delivery systems for GBM therapy is emphasized. The conventional and novel treatment modalities for GBM and the potential of nanocarriers to overcome existing limitations are comprehensively covered. Furthermore, the updates in the clinical landscape of GBM therapeutics are presented in addition to the current status of drugs and patents in the same context. Through a critical evaluation of existing literature, the therapeutic prospect and limitations of nanocarrier-based drug delivery strategies are highlighted offering insights into future research directions and clinical translation.

Keywords:  And nanotechnology-based carriers; Chemotherapy; Classification; Conventional treatment; Drug delivery; Glioblastoma multiforme (GBM); Novel treatment

DOI:  https://doi.org/10.1016/j.neuroscience.2024.09.022
F1000Res. 2024 ;13 98

Metabolomic characterization of human glioblastomas and patient plasma: a pilot study.

Yin Allison Liu, Orwa Aboud, Lina A Dahabiyeh, Orin Bloch, Oliver Fiehn.

  Background: Glioblastoma (GBM) is a clinically challenging primary brain tumor with poor survival outcome despite surgical resection and intensive chemoradiation. The metabolic heterogeneity of GBM can become biomarkers for treatment response, resistance, and outcome prediction. The aim of the study is to investigate metabolic distinctions between primary and recurrent GBM tissue and patient plasma to establish feasibility for metabolic profiling.Methods: A single-center cohort study analyzed tissue and blood samples from 15 patients with GBM using untargeted metabolomic/lipidomic assays. Metabolomic, lipidomic, and biogenic amine analyses were conducted on GBM tissue and patient plasma at diagnosis and recurrence using untargeted mass spectrometry. The study utilized a small but longitudinally collected cohort to evaluate alteration in metabolites, lipids, and biogenic amines between specimens at diagnosis and recurrence.
Results: Exploratory analysis revealed significant alteration in metabolites, lipids, and biogenic amines between diagnostic and recurrent states in both tumor and plasma specimens. Notable metabolites differed at recurrence, including N-alpha-methylhistamine, glycerol-3-phosphate, phosphocholine, and succinic acid in tissue, and indole-3-acetate, and urea in plasma. Principal component analysis revealed distinct metabolomic profiles between tumor tissue and patient plasma. Distinct metabolic profiles were observed in GBM tissue and patient plasma at recurrence, demonstrating the feasibility of using metabolomic methodologies for longitudinal studies. One patient exhibited a unique tumor resistance signature at diagnosis, possibly indicating a high-risk metabolomic phenotype.
Conclusions: In this small cohort, the findings suggest the potential of metabolomic signatures of GBM tissue and patient plasma for risk stratification, outcome prediction, and the development of novel adjuvant metabolic-targeting therapies. The findings suggest metabolic discrepancies at diagnosis and recurrence in tissue and plasma, highlighting potential implications for evaluation of clinical response. The identification of significant changes in metabolite abundance emphasizes the need for larger studies using targeted metabolomics to validate and further explore these profiles.

Keywords:  biomarker; feasibility; glioblastoma; pilot; untargeted metabolomics

DOI:  https://doi.org/10.12688/f1000research.143642.3
bioRxiv. 2024 Sep 27. pii: 2024.09.26.614808. [Epub ahead of print]

MALT1 protease inhibition restrains glioblastoma progression by reversing tumor-associated macrophage-dependent immunosuppression.

Juliana Hofstätter Azambuja, Saigopalakrishna S Yerneni, Lisa M Maurer, Hannah E Crentsil, Gabriela N Debom, Linda Klei, Mei Smyers, Chaim T Sneiderman, Kristina E Schwab, Rajesh Acharya, Yijen Lin Wu, Prasanna Ekambaram, Dong Hu, Pete J Gough, John Bertin, Ari Melnick, Gary Kohanbash, Riyue Bao, Peter C Lucas, Linda M McAllister-Lucas.

MALT1 protease is an intracellular signaling molecule that promotes tumor progression via cancer cell-intrinsic and cancer cell-extrinsic mechanisms. MALT1 has been mostly studied in lymphocytes, and little is known about its role in tumor-associated macrophages. Here, we show that MALT1 plays a key role in glioblastoma (GBM)-associated macrophages. Mechanistically, GBM tumor cells induce a MALT1-NF-κB signaling axis within macrophages, leading to macrophage migration and polarization toward an immunosuppressive phenotype. Inactivation of MALT1 protease promotes transcriptional reprogramming that reduces migration and restores a macrophage "M1-like" phenotype. Preclinical in vivo analysis shows that MALT1 inhibitor treatment results in increased immuno-reactivity of GBM-associated macrophages and reduced GBM tumor growth. Further, the addition of MALT1 inhibitor to temozolomide reduces immunosuppression in the tumor microenvironment, which may enhance the efficacy of this standard-of-care chemotherapeutic. Together, our findings suggest that MALT1 protease inhibition represents a promising macrophage-targeted immunotherapeutic strategy for the treatment of GBM.Graphical abstract:

DOI: https://doi.org/10.1101/2024.09.26.614808
bioRxiv. 2024 Sep 24. pii: 2024.09.21.614235. [Epub ahead of print]

Cholinergic Neuronal Activity Promotes Diffuse Midline Glioma Growth through Muscarinic Signaling.

Richard Drexler, Antonia Drinnenberg, Avishai Gavish, Belgin Yalcin, Kiarash Shamardani, Abigail Rogers, Rebecca Mancusi, Kathryn R Taylor, Yoon Seok Kim, Pamelyn J Woo, Alexandre Ravel, Eva Tatlock, Charu Ramakrishnan, Alberto E Ayala-Sarmiento, David Rincon Fernandez Pacheco, La'Akea Siverts, Tanya L Daigle, Bosiljka Tasic, Hongkui Zeng, Joshua J Breunig, Karl Deisseroth, Michelle Monje.

Neuronal activity promotes the proliferation of healthy oligodendrocyte precursor cells (OPC) and their malignant counterparts, gliomas. Many gliomas arise from and closely resemble oligodendroglial lineage precursors, including diffuse midline glioma (DMG), a cancer affecting midline structures such as the thalamus, brainstem and spinal cord. In DMG, glutamatergic and GABAergic neuronal activity promotes progression through both paracrine signaling and through bona-fide neuron-to-glioma synapses. However, the putative roles of other neuronal subpopulations - especially neuromodulatory neurons located in the brainstem that project to long-range target sites in midline anatomical locations where DMGs arise - remain largely unexplored. Here, we demonstrate that the activity of cholinergic midbrain neurons modulates both healthy OPC and malignant DMG proliferation in a circuit-specific manner at sites of long-range cholinergic projections. Optogenetic stimulation of the cholinergic pedunculopontine nucleus (PPN) promotes glioma growth in pons, while stimulation of the laterodorsal tegmentum nucleus (LDT) facilitates proliferation in thalamus, consistent with the predominant projection patterns of each cholinergic midbrain nucleus. Reciprocal signaling was evident, as increased activity of cholinergic neurons in the PPN and LDT was observed in pontine DMG-bearing mice. In co-culture, hiPSC-derived cholinergic neurons form neuron-to-glioma networks with DMG cells and robustly promote proliferation. Single-cell RNA sequencing analyses revealed prominent expression of the muscarinic receptor genes CHRM1 and CHRM3 in primary patient DMG samples, particularly enriched in the OPC-like tumor subpopulation. Acetylcholine, the neurotransmitter cholinergic neurons release, exerts a direct effect on DMG tumor cells, promoting increased proliferation and invasion through muscarinic receptors. Pharmacological blockade of M1 and M3 acetylcholine receptors abolished the activity-regulated increase in DMG proliferation in cholinergic neuron-glioma co-culture and in vivo . Taken together, these findings demonstrate that midbrain cholinergic neuron long-range projections to midline structures promote activity-dependent DMG growth through M1 and M3 cholinergic receptors, mirroring a parallel proliferative effect on healthy OPCs.HIGHLIGHTS: Activity of midbrain cholinergic neuron long-range projections increases proliferation of both healthy oligodendrocyte precursor cells (OPC) and malignant diffuse midline glioma (DMG) cells.Optogenetic stimulation of cholinergic midbrain nuclei promotes growth in thalamic and pontine glioma in a circuit-dependent manner.Reciprocally, DMG cells increase cholinergic neuronal activity in cholinergic midbrain nuclei.The muscarinic receptors CHRM1 and CHRM3 are identified as therapeutic targets in DMG.

DOI: https://doi.org/10.1101/2024.09.21.614235
Acta Neuropathol Commun. 2024 Oct 12. 12(1): 162

Metabolic remodeling in glioblastoma: a longitudinal multi-omics study.

Maxime Fontanilles, Jean-David Heisbourg, Arthur Daban, Frederic Di Fiore, Louis-Ferdinand Pépin, Florent Marguet, Olivier Langlois, Cristina Alexandru, Isabelle Tennevet, Franklin Ducatez, Carine Pilon, Thomas Plichet, Déborah Mokbel, Céline Lesueur, Soumeya Bekri, Abdellah Tebani.

  Monitoring tumor evolution and predicting survival using non-invasive liquid biopsy is an unmet need for glioblastoma patients. The era of proteomics and metabolomics blood analyzes, may help in this context. A case-control study was conducted. Patients were included in the GLIOPLAK trial (ClinicalTrials.gov Identifier: NCT02617745), a prospective bicentric study conducted between November 2015 and December 2022. Patients underwent biopsy alone and received radiotherapy and temozolomide. Blood samples were collected at three different time points: before and after concomitant radiochemotherapy, and at the time of tumor progression. Plasma samples from patients and controls were analyzed using metabolomics and proteomics, generating 371 omics features. Descriptive, differential, and predictive analyses were performed to assess the relationship between plasma omics feature levels and patient outcome. Diagnostic performance and longitudinal variations were also analyzed. The study included 67 subjects (34 patients and 33 controls). A significant differential expression of metabolites and proteins between patients and controls was observed. Predictive models using omics features showed high accuracy in distinguishing patients from controls. Longitudinal analysis revealed temporal variations in a few omics features including CD22, CXCL13, EGF, IL6, GZMH, KLK4, and TNFRSP6B. Survival analysis identified 77 omics features significantly associated with OS, with ERBB2 and ITGAV consistently linked to OS at all timepoints. Pathway analysis revealed dynamic oncogenic pathways involved in glioblastoma progression. This study provides insights into the potential of plasma omics features as biomarkers for glioblastoma diagnosis, progression and overall survival. Clinical implication should now be explored in dedicated prospective trials.

Keywords:  Glioblastoma; Liquid biopsy; Mass spectrometry; Metabolomic; Proteomic

DOI:  https://doi.org/10.1186/s40478-024-01861-5
bioRxiv. 2024 Sep 23. pii: 2024.03.14.585115. [Epub ahead of print]

Impact of genomic background and developmental state on signaling pathways and response to therapy in glioblastoma patient-derived cells.

Artem Berezovsky, Oluwademilade Nuga, Indrani Datta, Kimberly Bergman, Thais Sabedot, Katherine Gurdziel, Susan Irtenkauf, Laura Hasselbach, Yuling Meng, Claudius Mueller, Emanuel F Petricoin, Stephen Brown, Neeraja Purandare, Sidhesh Aras, Tom Mikkelsen, Laila Poisson, Houtan Noushmehr, Douglas Ruden, Ana C deCarvalho.

Glioblastoma (GBM) tumors represents diverse genomic epigenomic, and transcriptional landscapes, with significant intratumoral heterogeneity that challenges standard of care treatments involving radiation (RT) and the DNA-alkylating agent temozolomide (TMZ). In this study, we employed targeted proteomics to assess the response of a genomically-diverse panel of GBM patient-derived cancer stem cells (CSCs) to astrocytic differentiation, growth factor withdrawal and traditional high fetal bovine serum culture. Our findings revealed a complex crosstalk and co-activation of key oncogenic signaling in CSCs and diverse patterns of response to these external stimuli. Using RNA sequencing and DNA methylation, we observed common adaptations in response to astrocytic differentiation of CSCs across genomically distinct models, including BMP-Smad pathway activation, reduced cholesterol biosynthesis, and upregulation of extracellular matrix components. Notably, we observed that these differentiated CSC progenies retained a subset of stemness genes and the activation of cell survival pathways. We also examined the impact of differentiation state and genomic background on GBM cell sensitivity and transcriptional response to TMZ and RT. Differentiation of CSCs increased resistance to TMZ but not to RT. While transcriptional responses to these treatments were predominantly regulated by p53 in wild-type p53 GBM cells, its transcriptional activity was modulated by the differentiation status and treatment modality. Both mutant and wild-type p53 models exhibited significant activation of a DNA-damage associated interferon response in CSCs and differentiated cells, suggesting this pathway may play a wider role in GBM response to TMZ and RT. Our integrative analysis of the impact of GBM cell developmental states, in the context of genomic and molecular diversity of patient-derived models, provides valuable insights for pre-clinical studies aimed at optimizing treatment strategies.

DOI: https://doi.org/10.1101/2024.03.14.585115
Genome Biol. 2024 Oct 10. 25(1): 264

Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma.

Varsha Thoppey Manoharan, Aly Abdelkareem, Gurveer Gill, Samuel Brown, Aaron Gillmor, Courtney Hall, Heewon Seo, Kiran Narta, Sean Grewal, Ngoc Ha Dang, Bo Young Ahn, Kata Osz, Xueqing Lun, Laura Mah, Franz Zemp, Douglas Mahoney, Donna L Senger, Jennifer A Chan, A Sorana Morrissy.

BACKGROUND: Diffuse invasion of glioblastoma cells through normal brain tissue is a key contributor to tumor aggressiveness, resistance to conventional therapies, and dismal prognosis in patients. A deeper understanding of how components of the tumor microenvironment (TME) contribute to overall tumor organization and to programs of invasion may reveal opportunities for improved therapeutic strategies.RESULTS: Towards this goal, we apply a novel computational workflow to a spatiotemporally profiled GBM xenograft cohort, leveraging the ability to distinguish human tumor from mouse TME to overcome previous limitations in the analysis of diffuse invasion. Our analytic approach, based on unsupervised deconvolution, performs reference-free discovery of cell types and cell activities within the complete GBM ecosystem. We present a comprehensive catalogue of 15 tumor cell programs set within the spatiotemporal context of 90 mouse brain and TME cell types, cell activities, and anatomic structures. Distinct tumor programs related to invasion align with routes of perivascular, white matter, and parenchymal invasion. Furthermore, sub-modules of genes serving as program network hubs are highly prognostic in GBM patients.
CONCLUSION: The compendium of programs presented here provides a basis for rational targeting of tumor and/or TME components. We anticipate that our approach will facilitate an ecosystem-level understanding of the immediate and long-term consequences of such perturbations, including the identification of compensatory programs that will inform improved combinatorial therapies.

DOI: https://doi.org/10.1186/s13059-024-03407-3
Neuro Oncol. 2024 Oct 06. 26(Supplement_6): vi1-vi85

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2017-2021.

Mackenzie Price, Christine Ballard, Julia Benedetti, Corey Neff, Gino Cioffi, Kristin A Waite, Carol Kruchko, Jill S Barnholtz-Sloan, Quinn T Ostrom.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. Between 2017 and 2021, the average annual age-adjusted incidence rate (AAAIR) of all primary malignant and non-malignant brain and other CNS tumors was 25.34 per 100,000 population (malignant AAAIR=6.89 and non-malignant AAAIR=18.46). This overall rate was higher in females compared to males (28.77 versus 21.78 per 100,000) and non-Hispanic Black persons compared to persons who were non-Hispanic White (26.60 versus 25.72 per 100,000), non-Hispanic American Indian/Alaska Native (23.48 per 100,000), non-Hispanic Asian or Pacific Islander (19.86 per 100,000), and Hispanic persons of all races (22.37 per 100,000). Gliomas accounted for 22.9% of all tumors. The most commonly occurring malignant brain and other CNS histopathology was glioblastoma (13.9% of all tumors and 51.5% of all malignant tumors), and the most common predominantly non-malignant histopathology was meningioma (41.7% of all tumors and 56.8% of all non-malignant tumors). Glioblastomas were more common in males, and meningiomas were more common in females. In children and adolescents (ages 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.02 per 100,000 population. There were 87,053 deaths attributed to malignant brain and other CNS tumors between 2017 and 2021. This represents an average annual mortality rate of 4.41 per 100,000 population and an average of 17,411 deaths per year. The five-year relative survival rate following diagnosis of a malignant brain or other CNS tumor was 35.7%. For a non-malignant brain or other CNS tumor the five-year relative survival rate was 92.0%.

DOI: https://doi.org/10.1093/neuonc/noae145