# Glioblastoma
**Glioblastoma** is a fast-growing central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord, with cells that look very different from normal cells; it is also called GBM, glioblastoma multiforme, and grade IV astrocytoma, and it usually occurs in adults, affecting the brain more often than the spinal cord.[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/glioblastoma) It is the most common and aggressive primary brain tumor in adults, comprising 16% of all CNS neoplasms, with a reported median survival of approximately 15 months under treatment.[2](https://www.sciencedirect.com/science/article/pii/S1040842821003279)
| Key fact | Detail |
|---|---|
| Definition | Fast-growing glial tumor of the brain and spinal cord; also called GBM, glioblastoma multiforme, and grade IV astrocytoma[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/glioblastoma) |
| Frequency | 16% of all CNS neoplasms; the most common and aggressive primary brain tumor in adults[2](https://www.sciencedirect.com/science/article/pii/S1040842821003279) |
| Standard of care | Surgery, radiotherapy, and temozolomide chemotherapy (Stupp protocol); median overall survival in well-selected trial patients approximately 15–18 months, 5-year survival under 10%[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7594557/) |
| Survival range | Median overall survival from 8 to 48 months depending on prognostic factors[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC10558397/) |
| Molecular subtypes | IDH-wildtype about 90% of cases (typically older patients, de novo); IDH-mutant about 10% (younger patients, prior lower-grade glioma)[5](https://www.luks.ch/sites/default/files/2017-06/WHO2016_ZNS.pdf) |
| Key biomarkers | MGMT promoter methylation is an independent prognostic factor for improved survival; IDH1/IDH2 variants are strong prognostic factors[6](https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq) |
| Radiotherapy dose | Typically up to 60 Gy delivered in 30 fractions to the radiographically defined tumor[7](https://www.sciencedirect.com/science/article/pii/S0360301626005870) |
## Classification and molecular features
Under the World Health Organization classification of CNS tumors, glioblastoma is a grade IV tumor, the grade associated with mitotic activity, necrosis, rapid progression, and poor outcomes.[6](https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq) The 2016 WHO classification divides glioblastoma into IDH-wildtype (about 90% of cases), which corresponds most frequently with primary or de novo glioblastoma and predominates in patients over 55 years of age; IDH-mutant (about 10% of cases), which corresponds closely to secondary glioblastoma arising from a prior lower-grade diffuse glioma and preferentially affects younger patients; and glioblastoma, NOS, reserved for tumors without full IDH evaluation.[5](https://www.luks.ch/sites/default/files/2017-06/WHO2016_ZNS.pdf)
Molecular markers carry prognostic weight. For patients with a new glioblastoma diagnosis, a methylated MGMT gene promoter, which codes for a [DNA repair](https://www.edgepedia.org/dna-repair) enzyme, serves on its own as a prognostic marker of better survival, and IDH1 or IDH2 variants are strong prognostic factors associated with significantly longer survival independent of grade or histological subtype.[6](https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq) Other alterations seen in IDH-wildtype tumors include TERT promoter mutations, EGFR amplification, and combined gain of chromosome 7 with loss of chromosome 10.[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC10931698/)
## Standard treatment
Treatment is multimodal: neurosurgery, radiation therapy, and chemotherapy.[9](https://www.sciencedirect.com/science/article/pii/S0035378723008950) The Stupp regimen, standard since 2005, combines surgery, radiotherapy, and temozolomide (TMZ) chemotherapy; in well-selected patients in clinical trials it yields a median overall survival of approximately 15 to 18 months, and 5-year survival is less than 10%.[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC7594557/) [Radiotherapy](https://www.edgepedia.org/radiotherapy) typically delivers up to 60 Gy in 30 fractions to the radiographically defined tumor with a wide margin covering infiltrating tumor cells in surrounding normal tissue.[7](https://www.sciencedirect.com/science/article/pii/S0360301626005870) A phase III trial (RTOG 0525) tested whether a dose-dense temozolomide schedule (days 1–21 of a 28-day cycle) improved response over the standard days 1–5 schedule.[6](https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq)
Median overall survival across trials ranges from 8 to 48 months depending on prognostic factors such as age and extent of resection.[4](https://pmc.ncbi.nlm.nih.gov/articles/PMC10558397/) Older patients are underrepresented in clinical trials, and a network meta-analysis of randomized trials in older patients found that the common regimens studied conferred similar survival benefits.[10](https://aacrjournals.org/clincancerres/article/26/11/2664/284512/Determining-the-Optimal-Adjuvant-Therapy-for)
## Why treatment fails
The blood-brain barrier (BBB) is a major limitation on drug efficacy. It permits only small (under 500 Da and 400 nm) and lipophilic molecules to passively diffuse across; other molecules cross only by transcytosis and solute-carrier mechanisms.[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC7794986/) In glioblastoma the barrier is heterogeneously disrupted to form a blood-tumor-brain barrier, but infiltrative margins frequently retain a relatively intact barrier, limiting drug penetration and immune cell trafficking precisely where residual tumor cells persist after resection.[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC7794986/) • [12](https://pmc.ncbi.nlm.nih.gov/articles/PMC13156397/) Strategies to overcome the barrier include enhancing delivery (high-dose or intra-arterial chemotherapy, with or without osmotic disruption) and improving penetration by modifying the drug or the barrier itself; early-phase trials have shown safety and signals of efficacy, but comparative trials of clinical benefit are still needed.[9](https://www.sciencedirect.com/science/article/pii/S0035378723008950)
Tumor biology adds further resistance. GBMs show extensive intra- and intertumoral heterogeneity at the genetic, epigenetic, transcriptomic, and immunologic levels, and cell populations can transition between transcriptional states, contributing to resistance and progression.[7](https://www.sciencedirect.com/science/article/pii/S0360301626005870) The tumor microenvironment, including glioma stem cells, tumor-associated macrophages, and myeloid-derived suppressor cells, supports immune evasion and therapeutic resistance.[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC7794986/)
## Recurrent disease
Even after surgery, radiotherapy, and chemotherapy the tumor almost always recurs.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC8121043/) Treatment options at recurrence are limited, and most interventions have been evaluated in single studies, including systemic chemotherapy, re-operation, re-irradiation, anti-angiogenic agents, antibody therapies, tumor-treating fields, and vaccines alone or in combination.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC8121043/) In a Cochrane network meta-analysis of first-recurrence patients who had already undergone surgery and standard chemoradiotherapy, the evaluated combination therapies showed no overall survival benefit relative to lomustine alone, and they frequently carried a greater risk of serious adverse events.[14](https://www.cochrane.org/evidence/CD013579_treatment-options-people-recurrent-and-progressive-glioblastoma) A systematic review of 48 randomized trials found outcome reporting so heterogeneous (overall survival in 46 studies, progression-free survival in 37, 6-month PFS in 30) that network meta-analysis was not feasible.[2](https://www.sciencedirect.com/science/article/pii/S1040842821003279)
A systematic evidence-based analysis of trials reported the highest central measures of median survival for bevacizumab (18.2 months), tumor treating fields (20.7 months), and vaccines (19.2 months).[15](https://pubmed.ncbi.nlm.nih.gov/32157552/) [Immunotherapy](https://www.edgepedia.org/immunotherapy) trials have shown no benefit for progression-free survival in six of the trials examined, with evidence confidence limited by unclear methods and unblinded outcome assessment.[16](https://www.cochrane.org/evidence/CD012532_what-are-benefits-and-risks-different-immunotherapy-drugs-treating-glioblastoma-cancerous-brain)
## References
1. [Definition of glioblastoma, NCI Dictionary of Cancer Terms](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/glioblastoma)
2. [The current landscape of systemic therapy for recurrent glioblastoma: A systematic review of randomized-controlled trials, Critical Reviews in Oncology/Hematology](https://www.sciencedirect.com/science/article/pii/S1040842821003279)
3. [Glioblastoma in adults: SNO and EANO consensus review on current management and future directions, Neuro-Oncology](https://pmc.ncbi.nlm.nih.gov/articles/PMC7594557/)
4. [Are we providing best-available care to newly diagnosed glioblastoma patients? Systematic review of phase III trials 2005–2022](https://pmc.ncbi.nlm.nih.gov/articles/PMC10558397/)
5. [The 2016 WHO Classification of Tumors of the Central Nervous System: a summary](https://www.luks.ch/sites/default/files/2017-06/WHO2016_ZNS.pdf)
6. [Central Nervous System Tumors Treatment (PDQ®), National Cancer Institute](https://www.cancer.gov/types/brain/hp/adult-brain-treatment-pdq)
7. [Mechanisms, Microenvironments, and Models: Understanding Therapeutic Resistance in Glioblastoma, International Journal of Radiation Oncology*Biology*Physics](https://www.sciencedirect.com/science/article/pii/S0360301626005870)
8. [Glioblastoma: An Update in Pathology, Molecular Mechanisms and Biomarkers](https://pmc.ncbi.nlm.nih.gov/articles/PMC10931698/)
9. [Overcoming the blood brain barrier in glioblastoma: Status and future perspective, Revue Neurologique](https://www.sciencedirect.com/science/article/pii/S0035378723008950)
10. [Determining the Optimal Adjuvant Therapy for Improving Survival in Elderly Patients with Glioblastoma, Clinical Cancer Research](https://aacrjournals.org/clincancerres/article/26/11/2664/284512/Determining-the-Optimal-Adjuvant-Therapy-for)
11. [Molecular Mechanisms of Treatment Resistance in Glioblastoma](https://pmc.ncbi.nlm.nih.gov/articles/PMC7794986/)
12. [Glioblastoma: epidemiology, molecular pathogenesis, diagnosis, management, and therapeutic resistance](https://pmc.ncbi.nlm.nih.gov/articles/PMC13156397/)
13. [Treatment options for progression or recurrence of glioblastoma: a network meta-analysis, Cochrane Database](https://pmc.ncbi.nlm.nih.gov/articles/PMC8121043/)
14. [Treatment options for people with recurrent and progressive glioblastoma, Cochrane evidence](https://www.cochrane.org/evidence/CD013579_treatment-options-people-recurrent-and-progressive-glioblastoma)
15. [Trends in glioblastoma: outcomes over time and type of intervention: a systematic evidence based analysis](https://pubmed.ncbi.nlm.nih.gov/32157552/)
16. [What are the benefits and risks of different immunotherapy drugs for treating glioblastoma? Cochrane evidence](https://www.cochrane.org/evidence/CD012532_what-are-benefits-and-risks-different-immunotherapy-drugs-treating-glioblastoma-cancerous-brain)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Human structure and function › Nervous and sensory systems › Neurological disorders and neural injury › Brain tumors and intracranial mass lesions › Gliomas*
*Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license