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Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions
Open accessAbstract
Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
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“For this patient population, there is currently no efficacious treatment option available [4].”
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“The current standard of care for GBM includes surgical resection and post-surgery radiotherapy with or without temozolomide (TMZ) chemotherapy [4, 5].”
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“Despite standard of care treatment, GBM recurrence is inevitable and there is no agreed salvage therapy post-recurrence [4, 5].”
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“This can be approached in two ways: (1) MRI can be performed in the context of autopsies105,107–109, giving the opportunity to correlate MRI and histological parameters on a single-cell level with high-resolution microscopy parameters, and (2) in the context of a standardized supramarginal resection (for example, ante…”
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Self-citationTowards controlled drug delivery in brain tumors with microbubble-enhanced focused ultrasound
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“93 As a next step, the relevance of treatment related diagnostics should be proven and care providers should reimburse also deducted therapies.”
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“Patients were selected based on the following criteria: (1) first radiographic recurrence of a previously resected IDH wild-type glioblastoma per WHO 2021 classification,10 (2) information on treatment and outcome following first recurrence available for review, and (3) pre-and post-operative magnetic resonance imagin…”
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“Glioblastomas, the most common type of primary brain tumor, are particularly aggressive with a median overall survival (OS) of 15 to 18 months after standard care (3).”
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Self-citationTargeting immunoliposomes to EGFR-positive glioblastoma
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Updates in IDH-Wildtype Glioblastoma
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“Factors usually associated with longer survival include young age, good Karnofsky performance status (KPS) at diagnosis, and O 6 -methylguanine DNA methyltransferase ( MGMT) promoter methylation [1,2,7,8].”
Self-citationTawil, N., Bassawon, R., Meehan, B., Nehme, A., Montermini, L., Gayden, T., Jay, N. D., Spinelli, C., Chennakrishnaiah, S., Choi, D., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020002998 · Cited by 82
Self-citationDistinct metabolic hallmarks of WHO classified adult glioma subtypes
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“26 This finding indicates that the 45-year-old glioblastoma age group might carry less aggressive tumors more similar to lower grade astrocytoma, which is in line with our metabolomic characterization.”
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“[38].”
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“Brain tumors continue to exhibit a poor prognosis, with less than 20% of patients surviving beyond 5 years post-diagnosis [1].”
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“A comprehensive review focused on the current management of IDH-wt GBM with consideration also given to future directions has recently been published.(49)”
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A Phase II Study of the Efficacy and Safety of Oral Selinexor in Recurrent Glioblastoma
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“Glioblastoma (GBM) is the most common primary brain tumor in adults (1), with a poor prognosis (2).”
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“The standard therapy for GBM is maximal safe resection followed by adjuvant radiation and oral temolozomide (TMZ), which extends patients’ life expectancy only by 16 to 18 months [1].”
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Self-citationFunctional Contribution and Clinical Implication of Cancer-Associated Fibroblasts in Glioblastoma
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Principles in the Management of Glioblastoma
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EMP3 mediates glioblastoma‐associated macrophage infiltration to drive T cell exclusion
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“While immunotherapy-based approaches have been widely attempted, most clinical trials involving these modalities have failed to report significant outcomes [26, 27].”
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“The current standard of care for patients with GBM includes maximal surgical resection followed by radiotherapy and/or chemotherapy, which offers minimal clinical bene fi ts [1,2].”
BackgroundMethodPathogenetic Features and Current Management of Glioblastoma
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“cell cycle arrest and apoptosis [156] and include drugs such as palbociclib, ribociclib or abemaciclib that are FDA approved for other cancer types and are currently being clinically evaluated in GBM (Table 2) [157,158].”
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“Despite a multimodal treatment scheme comprised of neurosurgical intervention and concurrent chemoradiotherapy with temozolomide, recurrence within 1 year occurs in most patients (2, 3).”
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Spatial architecture of high-grade glioma reveals tumor heterogeneity within distinct domains
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“8,9 Thus, patients still receive radiation and alkylating chemotherapy 4,5,10,11 using regimens unchallenged for the past 25 years, highlighting a need for improved stratification and treatment options.”
Clinical research framework proposal for ketogenic metabolic therapy in glioblastoma
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“Time interval between end of radiation and postradiation MRI, days, median (range) 28 (3-47)”
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“Thepatient characteristics areprovidedinSupplementaryTable 3.”
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The Role of Hypoxia and SRC Tyrosine Kinase in Glioblastoma Invasiveness and Radioresistance
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“, temozolomide), and radiotherapy [1].”
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Immunotherapy in Glioblastoma: Current Approaches and Future Perspectives
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“According to Central Brain Tumor Registry of the United States (CBTRUS), incidence is 3.23 per one hundred thousand with an average of 12,011 cases diagnosed per year between 2013 and 2017 [2].”
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Self-citationIn vitro biomimetic models for glioblastoma-a promising tool for drug response studies
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“8 Gy per fraction is the standard of care for adult grade 2 and 3 gliomas, followed by procarbazine, lomustine, vincristine (PCV chemotherapy), or temozolomide chemotherapy [2].”
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Self-citationGCN2 kinase activation by ATP-competitive kinase inhibitors
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Self-citationCranioencephalic functional lymphoid units in glioblastoma
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“As our understanding of immunosurveillance in the brain continues to evolve, we can learn much from its disruption during malignant disease, for example, from glioblastoma, the most malignant adult brain cancer, that remains uniformly lethal with a median survival of less than 2 years 8 .”
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Metadata
- Authors
- Wen, P. Y., Weller, M., Lee, E. Q., Alexander, B. M., Barnholtz-Sloan, J. S., Barthel, F. P., Batchelor, T. T., Bindra, R. S., Chang, S. M., Chiocca, E. A., Cloughesy, T. F., DeGroot, J. F., Galanis, E., Gilbert, M. R., Hegi, M. E., Horbinski, C., Huang, R. Y., Lassman, A. B., Le Rhun, E., Lim, M., Mehta, M. P., Mellinghoff, I. K., Minniti, G., Nathanson, D., Platten, M., Preusser, M., Roth, P., Sanson, M., Schiff, D., Short, S. C., Taphoorn, M. J. B., Tonn, J.-C., Tsang, J., Verhaak, R. G. W., von Deimling, A., Wick, W., Zadeh, G., Reardon, D. A., Aldape, K. D., & van den Bent, M. J.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Zurich (CH)
- Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio, USA
- The Jackson Laboratory for Genomic Medicine (US)
- Yale University (US)
- University of California, San Francisco (US)
- University of California, Los Angeles (US)
- The University of Texas MD Anderson Cancer Center (US)
- Mayo Clinic (US)
- National Institutes of Health (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Northwestern University (US)
- NewYork–Presbyterian Hospital (US)
- University of Lille, Inserm, Neuro-oncology, General and Stereotaxic Neurosurgery service, University Hospital of Lille, Lille, France; Breast Cancer Department, Oscar Lambret Center, Lille, France and Department of Neurology & Brain Tumor Center, University Hospital and University of Zurich, Zurich, Switzerland
- Johns Hopkins University (US)
- Miami Cancer Institute, Miami, Florida, USA
- Memorial Sloan Kettering Cancer Center (US)
- University of Siena (IT)
- Heidelberg University (DE)
- Medical University of Vienna (AT)
- Centre National de la Recherche Scientifique (FR)
- University of Virginia (US)
- University of Leeds (GB)
- Leiden University Medical Center (NL)
- LMU Klinikum (DE)
- Neuropathology and Clinical Cooperation Unit Neuropathology, University Heidelberg and German Cancer Center, Heidelberg, Germany
- Princess Margaret Cancer Centre (CA)
- National Cancer Institute (US)
- Department of Neurology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
- Corresponding author
- Wen, Patrick Y
- Weller, Michael
- ORCID
- Wen, Patrick Y
- Weller, Michael
- Lee, Eudocia Quant
- Alexander, Brian M
- Barthel, Floris P
- Batchelor, Tracy T
- Bindra, Ranjit S
- Chang, Susan M
- Chiocca, E Antonio
- Cloughesy, Timothy F
- Galanis, Evanthia
- Gilbert, Mark R
- Hegi, Monika E
- Horbinski, Craig
- Huang, Raymond Y
- Lassman, Andrew B
- Lim, Michael
- Mehta, Minesh P
- Mellinghoff, Ingo K
- Minniti, Giuseppe
- Nathanson, David
- Platten, Michael
- Preusser, Matthias
- Roth, Patrick
- Sanson, Marc
- Schiff, David
- Short, Susan C
- Taphoorn, Martin J B
- Tonn, Joerg-Christian
- Tsang, Jonathan
- Verhaak, Roel G W
- Wick, Wolfgang
- Zadeh, Gelareh
- Reardon, David A
- Aldape, Kenneth D
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-04-24
- Volume
- 22
- Issue
- 8
- Pages
- 1073-1113
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- PMC
- PMC7594557
- OpenAlex
- W3020099303
- Cited by
- 1,168
- References
- 334
- Citations by year
- 2026: 166 · 2025: 215 · 2024: 242 · 2023: 204 · 2022: 194 · 2021: 118 · 2020: 28
- FWCI
- 71.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Neuro-Oncology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- IRIS (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- HAL (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- LillOA (Université de Lille (University Of Lille)) (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Funders
- University of Leeds
- National Institutes of Health (UL1TR001863)
- National Cancer Institute (P01CA069246, P30CA008748, P50CA211015, P30CA016672, P01CA163205)
- National Institute of Neurological Disorders and Stroke (R35NS105109)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Keywords
- glioblastoma, IDH-wildtype glioblastoma, adult brain tumors, molecular pathogenesis, targeted therapy, DNA damage response, metabolic therapy, immunotherapy, viral therapy, treatment management
- MeSH terms
- Brain Neoplasms, Glioblastoma, Humans, Isocitrate Dehydrogenase, Randomized Controlled Trials as Topic, Clinical Trials, Phase III as Topic, Chemoradiotherapy
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