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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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“[3] Since the definition of the current standard of care (SOC) in 2005 [4], only two trials reported some prolongation of median overall survival by optimizing diagnostic and therapeutic management [5, 6].”
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“Glioblastoma, the most common form of malignant brain tumor in adults, ranks among the deadliest of all human cancers [1–3].”
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“Despite these treatments, most patients experience tumor recurrence within a year, with no standardized treatment options available at that point [52].”
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“Glioblastoma is the most lethal brain tumor, with a median survival of approximately 15 months [1, 2].”
20 years of the Stupp protocol: confronting stagnation in glioblastoma therapy
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Glioblastoma with deep supratentorial extension is associated with a worse overall survival
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“For HGG, radiotherapy was used with different protocols of chemotherapy in accordance with the histological findings and most recent literature suggestions [6,19].”
MethodNon-animal glioblastoma models for personalized treatment
Zottel, A., Jovčevska, I., & Šamec, N. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e21070 · Cited by 8
“It is a rare cancer with an incidence of approximately 3/100 000 people in the United States [1].”
BackgroundInfluentialNovel trial designs in neuro-oncology
Song, K.-W., & Wen, P. Y. (2023) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001210 · Cited by 7
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LncRNAs unraveling their sponge role in glioblastoma and potential therapeutic applications
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An MRI Radiomics Approach to Predict the Hypercoagulable Status of Gliomas
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“Despite intensive therapeutic modalities, GBM has a nearly systematic fatal outcome marked by recurrence and a median overall survival of less than two years [1].”
BackgroundChen, J., Yang, R., Yu, H., Wu, H., Wu, N., Wang, S. H., Yin, X., Shi, X., & Wang, H. (2024) · Journal of Materials Chemistry B · doi:10.1039/d3tb02966b · Cited by 7
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Self-citationFougner, V., Urup, T. H., Poulsen, H. S., Grunnet, K., Yde, C. W., Melchior, L. C., Larsen, K. B., Højgaard, M., Spanggaard, I., Belcaid, L., et al. (2024) · Neuro-Oncology Practice · doi:10.1093/nop/npae082 · Cited by 7
Genomic Profiling in Glioma Patients to Explore Clinically Relevant Markers
Varachev, V. O., Susova, O. Y., Mitrofanov, A., Насхлеташвили, Д. Р., Krasnov, G. S., Ikonnikova, A. Y., Bezhanova, S. D., Semenova, V. V., Sevyan, N. V., Прозоренко, Е. В., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313004 · Cited by 7
Lim, S., Clarke, N. H., Maloney, S. L., Sener, U. T., Caron, S. J., Kizilbash, S. H., Campian, J. L., Neth, B. J., Carabenciov, I. D., Uhm, J. H., et al. (2025) · Journal of Neuro-Oncology · doi:10.1007/s11060-024-04916-8 · Cited by 7
Chiou, J., Impedovo, V., Huynh, Y. B., Gorgoglione, R., Penalva, L. O. F., Lodi, A., Brenner, A. J., & Tiziani, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26020474 · Cited by 9
“Despite these therapies, the 5-year relative survival rate for GBM patients in the United States has remained at only 3–6% since 2004, highlighting the limited progress in treatment efficacy since TMZ’s approval for glioblastoma in 2008 [1,5–8].”
InfluentialPerioperative clinical trials for glioma: Raising the bar
Mweempwa, A., Rosenthal, M. A., Dimou, J., Drummond, K. J., & Whittle, J. R. (2021) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2021.04.026 · Cited by 7
Predictors of Citation Rates in High-Impact Glioblastoma Clinical Trials
Jamjoom, A. M., Gahtani, A. Y., & Jamjoom, A. B. (2021) · Cureus · doi:10.7759/cureus.19229 · Cited by 7
“This probably reflects the current widely accepted standard treatment for newly diagnosed GBM, which includes surgery followed by concurrent radiotherapy with TZM and further adjuvant TZM [21,22].”
BackgroundMiR-33a targets FOSL1 and EN2 as a clinical prognostic marker for sarcopenia by glioma
Wang, W. T., Liu, W., Xu, J., & Jin, H. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.953580 · Cited by 6
“The most common treatment for glioma is surgical resection followed by radiotherapy and chemotherapy (Wen et al., 2020).”
BackgroundBrighi, C., Keall, P., Holloway, L. C., Walker, A., Whelan, B., Hamer, P. C. D. W., Verburg, N., Aly, F., Chen, C. Y.-H., Koh, E., et al. (2022) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdac134 · Cited by 7
“Compared to the standard plans, DP (1) did not affect dose delivered to organs at risk; (2) increased mean and maximum dose and improved minimum dose coverage for the target volumes; (3) reduced minimum dose within the radiotherapy treatment margins; (4) improved local tumor control probability within the target volum…”
BackgroundHernández, A., Muñoz-Mármol, A. M., Esteve‐Codina, A., Alameda, F., Carrato, C., Pineda, E., Arpí-LLucià, O., Martinez‐García, M., Mallo, M., Gut, M., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-18608-8 · Cited by 7
Comparing tumor microRNA profiles of patients with long‑ and short‑term‑surviving glioblastoma
Schneider, B., Lamp, N., Zimpfer, A., Henker, C., & Erbersdobler, A. (2022) · Molecular Medicine Reports · doi:10.3892/mmr.2022.12895 · Cited by 7
“8% (varying with age at diagnosis) (3,4) which barely improved for decades (5), and a median overall survival (OS) of about 15‐18 months after diagnosis which still remains at this low level despite several efforts (1‐4).”
BackgroundLiu, W., & Li, Z. (2022) · Journal of Clinical Ultrasound · doi:10.1002/jcu.23402 · Cited by 7
“This study included 220 patients newly and histopathologically diagnosed with grade IV GBM according to “The 2021 WHO Classification of Tumors of the Central Nervous System,22” who underwent the surgical resection at our hospital, followed by the standard radiation therapy with concurrent TMZ and 6 cycles of adjuvant…”
MethodInfluentialXu, Y., Guan, H., Yu, K., Ji, N., & Zhao, Z. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1191480 · Cited by 7
“However, there are few randomized trials to definitively prove whether radiotherapy prolongs survival time (Wen et al., 2020).”
BackgroundWu, Z., Yang, Y., & Zha, Y. (2023) · Cancers · doi:10.3390/cancers15184661 · Cited by 7
Implantable microdevices for treating brain tumors
Yearley, A. G., Patel, R. V., Blitz, S. E., Park, S., Madinger, A. M., Li, J., Johnston, B. R., Peruzzi, P. P., Lee, S., Srinivasan, S. S., et al. (2023) · Device · doi:10.1016/j.device.2023.100068 · Cited by 7
Clinical and Genomic Predictors of Adverse Events in Newly Diagnosed Glioblastoma
Lim-Fat, M. J., Iorgulescu, J. B., Rahman, R. M., Bhave, V. M., Muzikansky, A., Woodward, E. L., Whorral, S., Allen, M., Touat, M., Li, X., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-23-3018 · Cited by 7
Self-citationTargeting the RhoGEF βPIX/COOL-1 in Glioblastoma: Proof of Concept Studies
Connor, K., Murray, D. W., Jarzabek, M. A., Tran, N. L., White, K., Dicker, P., Sweeney, K. J., O’Halloran, P. J., MacCarthy, B., Shiels, L. P., et al. (2020) · Cancers · doi:10.3390/cancers12123531 · Cited by 7
“Glioblastoma (GBM), a heterogeneous and lethal brain tumour, remains an incurable malignancy, capable of rapidly developing resistance to treatment [1].”
BackgroundFunctional Contribution of Cancer-Associated Fibroblasts in GlioblastomaPreprint
Galbo, P. M., Liu, Y., Peng, M., Wei, Y., Madsen, A. T., Graff, S., Montagna, C., Segall, J. E., Sidoli, S., Zang, X., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.07.487495 · Cited by 7
Zeng, Y., Liu, N., Yang, X., Huang, C., & Liu, M. (2024) · Journal of Cancer · doi:10.7150/jca.95987 · Cited by 6
“Consistent follow-up monitoring is also essential due to the significant risk of recurrence and metastasis in gliomas [10,11].”
BackgroundIppen, F. M., Scherm, A., Keßler, T., Hau, P., Agkatsev, S., Baurecht, H., Wick, W., Knüttel, H., Leitzmann, M. F., & Seliger, C. (2024) · Cancer Medicine · doi:10.1002/cam4.7362 · Cited by 6
Self-citationDell’Albani, P., Carbone, C., Sposito, G., Spatuzza, M., Chiacchio, M. A., Grasso, R., Legnani, L., Santonocito, D., Puglia, C., Parenti, R., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25158397 · Cited by 6
Song, P., Deng, H., Liu, Y., & Zhang, M. (2024) · BMC Medical Genomics · doi:10.1186/s12920-024-01991-8 · Cited by 6
“Alternatively, WHO grade 4 glioblas-tomas (GBM) have the worst prognosis, with only 6.8% five-year overall survival (OS) rate [2, 3].”
BackgroundInfluentialYoung, J. S., Cho, N. W., Lucas, C. G., Najem, H., Mirchia, K., Chen, W., Tamaki, C. M., Congivaram, H., Seo, K., Zakimi, N., et al. (2026) · Cancer Research · doi:10.1158/0008-5472.can-25-2922 · Cited by 9
Horschitz, S., Jabali, A., Heuer, S., Zillich, E., Zillich, L., Hoffmann, D. C., Kumar, A. S., Hausmann, D., Azorín, D. D., Hai, L., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.03.055 · Cited by 10
“In order to validate the hGliCS model for drug screening tests we first treated hGliCS with classical cytostatic drugs commonly used in clinical GBM contexts [1,48,49].”
Self-citationSu, D., Hong, B., Yang, S., Zhao, J., Cui, X., Zhan, Q., Yi, K., Huang, Y., Ju, J., Yang, E., et al. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.05.012 · Cited by 6
Advancement in tumor treating fields of mechanism, clinical applications, and future directions
Zang, M., Zhu, S., & Niu, Q. (2025) · Discover Oncology · doi:10.1007/s12672-025-02861-0 · Cited by 8
“The current standard of care involves maximal surgical resection and chemoradiotherapy with TMZ [85], but the highly infiltrative nature of GBM hinders complete surgical resection [86].”
Yi, Z., Song, M. S., Liang, L., Ren, J., Tian, J., Mao, G., Mao, G., & Chen, M. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000002634 · Cited by 6
Wang, X., Yin, F., He, Y., Qiao, Y., Yan, Y., & Ma, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1621585 · Cited by 6
Li, C., Ma, W., Shen, H., Hou, Z., Chen, J., Yang, L., & Sun, W. Y. (2025) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2025.115059 · Cited by 7
Li, J., Liu, R., Xing, Y., Yin, Q., & Su, Q. (2025) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2025.111111 · Cited by 6
Pan, S., Mirchia, K., Payne, E., Liu, S. J., Al-Adli, N. N., Peeran, Z., Shukla, P. D., Young, J. S., Gupta, R. K., Wu, J., et al. (2025) · JCI Insight · doi:10.1172/jci.insight.192658 · Cited by 6
Self-citationTumor and immune cell distribution in the tumor core and outer part of glioblastoma, IDH wildtype
Pedersen, V., Knudsen, A. M., Michaelsen, S. R., Dahlrot, R. H., & Kristensen, B. W. (2025) · Journal of Neuro-Oncology · doi:10.1007/s11060-025-05232-5 · Cited by 7
“Immunotherapies have revolutionized therapy for several different cancer types [ 1–3], but glioblastoma, the most common and aggressive brain tumor in adults, has shown a minimal response [ 4, 5].”
Piotrowski, A. F., Shih, K. C., Giglio, P., Colman, H., Wen, P. Y., Campian, J. L., Butowski, N. A., Cloughesy, T. F., Zhu, Z., Gisin, V., et al. (2025) · Current Oncology · doi:10.3390/curroncol32100541 · Cited by 6
“First-line treatment of glioblastoma consists of maximal safe surgical resection, often followed by radiotherapy (RT) and chemotherapy [5–9].”
Self-citationTeske, N., Dono, A., Young, J. S., Juenger, S. T., Youssef, G., Häni, L., Sciortino, T., Bruno, F., Dietrich, J., Mau, C. Y., et al. (2025) · Neuro-Oncology · doi:10.1093/neuonc/noaf239 · Cited by 6
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“2,6 As seizure and cognitive disorder are the most common clinical presentation, GBM carries a high social and psychological burden on patients and caregivers.”
InfluentialA blueprint for local and distal invasion programs in glioblastoma
Chanoch-Myers, R., Hara, T., Greenwald, A., Hoefflin, R., Bussema, L., Weisman, H., Nieblas‐Bedolla, E., Gurramkonda, J., Bekezhankyzy, Z., Jucht, A., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-70470-8 · Cited by 7
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Gallardo‐Pérez, J. C., Trejo‐Solís, C., Robledo‐Cadena, D. X., López‐Marure, R., Agredano‐Moreno, L. T., Jiménez‐García, L. F., & Sánchez‐Lozada, L. G. (2023) · Medical Oncology · doi:10.1007/s12032-023-01969-z · Cited by 6
“In human GBM biopsies, NLK and AMFR are upregulated in hypoxic pseudopalisades cells, which is associated with poorer survival in patients with GBM [37].”
BackgroundPrognostic significance of carboxypeptidase Q and its methylation in glioblastoma
Liu, Q., Wang, R., Li, Z., Peng, Y., Qin, W., Peng, X.-M., & Liu, Z. (2023) · Translational Cancer Research · doi:10.21037/tcr-22-2562 · Cited by 6
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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