Brain Cancer

  1. Overview
  2. Epidemiology
  3. Classification (WHO 2021)
  4. Pathophysiology and Molecular Biology
  5. Etiology and Risk Factors
  6. Clinical Presentation
  7. Diagnosis
  8. Treatment
  9. Complications
  10. Prognosis
  11. Recent Research and Advances
  12. References & Research
  13. Research Papers
  14. Connections

Overview

Brain cancer refers to malignant tumors arising in or spreading to the brain. The distinction between primary brain tumors — those originating in brain tissue itself — and secondary (metastatic) brain tumors — cancers from elsewhere in the body that have spread to the brain — is clinically critical, as they differ in prognosis, treatment approach, and underlying biology.

Primary brain tumors arise from neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells), the meninges, cranial nerves, the pituitary, or the choroid plexus. The most common malignant primary brain tumors are glioblastoma (GBM), astrocytoma, oligodendroglioma, ependymoma, and medulloblastoma. Meningioma is the most common overall primary brain tumor, but the majority are benign. Approximately 24,000 primary malignant brain tumors are diagnosed annually in the United States, while brain metastases — far more common — affect an estimated 100,000 or more Americans each year, most often from lung, breast, melanoma, kidney, and colorectal cancers.

Despite representing fewer than 2% of all cancers, malignant primary brain tumors carry disproportionate morbidity due to their location within the central nervous system. The blood-brain barrier limits drug delivery, surgical access is constrained by the need to preserve neurological function, and the tumor microenvironment is immunosuppressive. GBM remains one of the most lethal solid tumors, with a median survival of approximately 15 months even with optimal multimodal treatment.

Epidemiology

The overall incidence of malignant primary brain and other central nervous system tumors is approximately 3.2 per 100,000 persons per year in the United States, according to data from the Central Brain Tumor Registry of the United States (CBTRUS). When benign and borderline tumors are included, the rate rises to roughly 23–24 per 100,000.

Glioblastoma accounts for approximately 47% of all malignant gliomas and is the most common malignant primary brain tumor in adults, with an incidence of about 3.21 per 100,000. It peaks in the 65 to 74 age group, is slightly more common in men than women (ratio approximately 1.6:1), and is more prevalent in white populations than other racial groups.

Meningiomas represent the most common primary brain tumor overall (roughly 37% of all primary CNS tumors), with the majority being WHO grade 1 (benign). They are significantly more common in women (ratio approximately 2.3:1) and increase in frequency with age.

Medulloblastoma and other embryonal tumors have a bimodal distribution, with a dominant peak in childhood (ages 3 to 8) and a smaller peak in young adults (ages 25 to 34). Medulloblastoma is the most common malignant brain tumor in children, accounting for about 20% of all pediatric CNS tumors.

IDH-mutant gliomas (astrocytoma, oligodendroglioma) typically present in younger adults, with a median age at diagnosis in the 30s to 40s, and carry a considerably better prognosis than IDH-wildtype GBM. The molecular landscape of these lower-grade gliomas has substantially reshaped how they are classified, treated, and counseled.

Classification (WHO 2021)

The 2021 World Health Organization Classification of Tumors of the Central Nervous System represents a fundamental paradigm shift from purely histological grading to an integrated approach combining morphology with molecular biomarkers. This revision, detailed by Louis DN et al. in Neuro-Oncology (PMID 34185076), makes molecular profiling mandatory for accurate classification and has direct implications for prognosis and treatment selection.

Key Molecular Markers

IDH1/IDH2 mutation status is the first and most critical branch point in glioma classification. Tumors harboring IDH mutations are designated IDH-mutant (formerly called lower-grade gliomas, grades 2 and 3, and secondary GBM). IDH-mutant tumors have a fundamentally different biology and far better prognosis than IDH-wildtype GBM, which is aggressive and defined by its tendency to recur rapidly. IDH mutations produce 2-hydroxyglutarate, an oncometabolite that drives epigenetic dysregulation.

MGMT promoter methylation determines whether the gene encoding O6-methylguanine-DNA methyltransferase — a DNA repair enzyme that reverses the cytotoxic lesions created by alkylating agents — is silenced by epigenetic methylation. When the MGMT promoter is methylated, the tumor cannot repair damage caused by temozolomide (TMZ), making chemotherapy more effective. Patients with MGMT-methylated GBM have a median survival of approximately 21 months compared to roughly 12 months for unmethylated GBM.

1p/19q co-deletion — the loss of the short arm of chromosome 1 and the long arm of chromosome 19 — is the defining molecular event of oligodendroglioma. This co-deletion is associated with superior sensitivity to combined chemotherapy (PCV: procarbazine, lomustine, vincristine) and radiotherapy, and a significantly better long-term prognosis than IDH-mutant astrocytoma.

TERT promoter mutation is nearly universal in oligodendrogliomas and common in IDH-wildtype GBM, providing additional diagnostic utility. EGFR amplification and CDKN2A/B homozygous deletion are markers of more aggressive behavior. H3K27M mutation defines diffuse midline gliomas, including diffuse intrinsic pontine glioma (DIPG) and other thalamic/spinal midline tumors — now classified as WHO grade 4 regardless of histological appearance due to dismal prognosis.

Major Glioma Entities Under WHO 2021

Pathophysiology and Molecular Biology

Brain tumors arise through the accumulation of genetic and epigenetic alterations that disable normal cellular regulation of proliferation, survival, and differentiation. In GBM, the core oncogenic pathways include the RTK/RAS/PI3K pathway (activated by EGFR amplification, PTEN loss, PIK3CA mutations), the p53 pathway (TP53 mutation, MDM2 amplification, CDKN2A deletion), and the RB pathway (CDK4 amplification, CDKN2A loss, RB1 deletion). In IDH-mutant gliomas, the production of 2-hydroxyglutarate competitively inhibits alpha-ketoglutarate-dependent dioxygenases, causing widespread CpG island hypermethylation (the G-CIMP phenotype) and silencing of tumor suppressor genes including MGMT.

Glioma stem cells (GSCs) — a subpopulation of self-renewing, multipotent cells within the tumor — are thought to drive tumor initiation, maintenance, therapeutic resistance, and recurrence. GSCs express markers such as CD133, SOX2, and nestin, resist both radiation and chemotherapy more effectively than bulk tumor cells, and reconstitute the tumor following treatment. Targeting GSCs is a major focus of current translational research.

The blood-brain barrier (BBB) presents a profound challenge to pharmacological treatment. Tight junctions between brain endothelial cells, the absence of fenestrations, and ATP-binding cassette transporters (including P-glycoprotein/ABCB1) actively exclude most large molecules and many small-molecule drugs from brain parenchyma. While GBM disrupts the BBB focally — explaining contrast enhancement on MRI — infiltrating tumor cells at the margins reside behind an intact barrier, making them inaccessible to systemically administered agents at therapeutic concentrations.

Tumor heterogeneity within a single GBM is extreme — spatially distinct regions carry different mutational profiles, different gene expression programs, and different degrees of stemness. This heterogeneity limits the durability of any single targeted therapy and contributes to inevitable resistance. After radiation and temozolomide, MRI may show apparent tumor enlargement — pseudoprogression — which reflects treatment-induced inflammation and necrosis rather than true tumor growth, a critical distinction that affects management decisions.

Peritumoral vasogenic edema, caused by disruption of the BBB and tumor-secreted VEGF, is a major source of neurological symptoms and contributes to elevated intracranial pressure. Dexamethasone rapidly reduces edema by downregulating VEGF and stabilizing the BBB, but long-term steroid use carries substantial toxicity.

Etiology and Risk Factors

The vast majority of brain tumors arise without a clear identifiable cause. However, several established and suspected risk factors have been identified through epidemiological and genetic research.

Established Risk Factors

Ionizing radiation is the only firmly established environmental risk factor for primary brain tumors. Therapeutic cranial irradiation — used for childhood leukemia, medulloblastoma, or other conditions — significantly increases lifetime risk of meningioma, glioma, and nerve sheath tumors, with risk increasing with dose and younger age at exposure. This is therapeutic radiation, not background environmental radiation.

Hereditary syndromes account for a small fraction of brain tumors. Key associations include:

Factors Not Established as Risk Factors

Mobile phones and radiofrequency electromagnetic fields have been extensively studied. The INTERPHONE study (13 countries, 2,700+ glioma cases), the Danish Cohort Study (nearly 360,000 subscribers), and the Million Women Study (791,710 women) have collectively found no significant association between mobile phone use and glioma or meningioma risk. The IARC classifies radiofrequency fields as Group 2B (possibly carcinogenic) based on limited evidence, but large, well-designed studies have not confirmed a causal link.

Trauma, seizures, and allergies have been investigated; epidemiological data do not support them as causally related to brain tumor development. Interestingly, a consistent inverse association between allergic conditions and glioma risk has been observed in several studies, though the mechanism is unclear.

Clinical Presentation

The clinical manifestations of brain tumors depend on their anatomic location, rate of growth, and degree of surrounding edema and mass effect. Slow-growing tumors may be clinically silent for years while rapidly growing tumors produce acute neurological deterioration over days to weeks.

Focal Neurological Deficits by Location

General Symptoms

Headache occurs in 50–60% of patients at some point during the illness. The classic brain tumor headache is worse in the morning (due to supine position increasing intracranial pressure overnight), aggravated by Valsalva maneuver (coughing, straining), and progressively worsening over weeks. However, most morning headaches are not due to brain tumors, and no single headache pattern is pathognomonic.

New-onset seizures in an adult should prompt urgent investigation for structural lesion, including brain tumor. Approximately 20–40% of patients with primary brain tumors present with seizures. Seizures are more common with low-grade gliomas (particularly IDH-mutant oligodendroglioma, up to 90%) than with GBM.

Raised intracranial pressure causes nausea, vomiting, papilledema, and in severe cases, Cushing's triad: hypertension, bradycardia, and irregular respirations — a late and ominous sign indicating impending herniation. Sixth nerve palsy (diplopia) may be a false localizing sign of raised ICP.

Cognitive changes are among the most functionally disabling symptoms — short-term memory impairment, slowed processing speed, and executive dysfunction affect quality of life profoundly and may predate the tumor diagnosis by months.

Diagnosis

Neuroimaging

MRI brain with and without gadolinium contrast is the imaging modality of choice. GBM typically appears as a heterogeneous mass with ring-enhancing contrast pattern (enhancing rim surrounding central necrosis), marked surrounding vasogenic edema, and mass effect. Low-grade gliomas are often non-enhancing on standard MRI, appearing as T2/FLAIR hyperintense lesions without contrast enhancement — enhancement signals blood-brain barrier breakdown and typically indicates higher-grade disease.

Advanced MRI sequences provide additional diagnostic and surgical planning information:

CT scan remains useful for acute presentations (emergency department, hemorrhage detection, bony detail for skull-base tumors) and when MRI is contraindicated.

Tissue Diagnosis

Histological and molecular diagnosis requires tissue. Stereotactic needle biopsy is used for deep-seated or surgically inaccessible lesions. Open (craniotomy) biopsy is typically combined with maximal safe resection in accessible tumors. Intraoperative frozen section provides immediate histological assessment to confirm adequacy of sampling.

Standard neuropathological evaluation now includes molecular profiling: IDH sequencing (or immunohistochemistry for the common IDH1 R132H hotspot mutation), MGMT promoter methylation analysis by pyrosequencing or bisulfite sequencing, 1p/19q FISH or array-based testing, EGFR amplification, TERT promoter sequencing, and H3K27M immunohistochemistry. This integrated molecular workup is required for accurate WHO 2021 classification.

For medulloblastoma, cerebrospinal fluid (CSF) cytology via lumbar puncture is performed to assess leptomeningeal dissemination — a staging requirement that directly influences treatment intensity (craniospinal irradiation field and chemotherapy).

Liquid biopsy — analysis of circulating tumor DNA (ctDNA) or cell-free DNA (cfDNA) in plasma or CSF — is an active area of investigation. CSF-derived ctDNA is more sensitive than plasma for detecting brain tumor mutations given the anatomical proximity, but remains investigational and is not yet standard of care for diagnosis or monitoring.

Treatment

Glioblastoma (GBM) — Standard of Care

The Stupp protocol, established by the landmark trial published in the New England Journal of Medicine in 2005 (Stupp R et al., PMID 15758009), remains the backbone of GBM treatment. It consists of:

  1. Maximal safe surgical resection: The goal is to remove as much tumor as possible while preserving neurological function. Gross total resection is associated with longer survival. Eloquent cortex or deep-seated location may limit extent of resection.
  2. Concurrent radiation therapy (RT) and temozolomide (TMZ): 60 Gy delivered in 30 fractions over 6 weeks, with daily oral temozolomide 75 mg/m² throughout.
  3. Adjuvant temozolomide: Six 28-day cycles of TMZ at 150–200 mg/m² on days 1–5 of each cycle following completion of chemoradiation.

This protocol extended median overall survival from approximately 12 months (RT alone) to 14.6 months, with 2-year survival of 26% vs. 10% for RT alone. MGMT methylation dramatically modifies benefit: methylated patients achieved median OS of 21.7 months versus 12.7 months for unmethylated.

5-ALA Fluorescence-Guided Surgery

5-aminolevulinic acid (5-ALA, brand name Gliolan) is a metabolic precursor that selectively accumulates as fluorescent protoporphyrin IX (PpIX) in malignant glioma cells but not in normal brain tissue. Administered orally 3 hours before surgery, it causes tumor tissue to fluoresce pink/violet under blue light (375–440 nm excitation), enabling the neurosurgeon to distinguish tumor margins from normal brain under a modified surgical microscope. The pivotal Phase 3 trial by Stummer W et al. (Lancet Oncology 2006, PMID 16648043) demonstrated that 5-ALA fluorescence guidance increased rates of complete contrast-enhancing tumor resection (65% vs 36%) and improved 6-month progression-free survival, though overall survival was not statistically improved in this underpowered study. 5-ALA is now FDA-approved and standard practice for malignant glioma surgery in major neurosurgical centers.

Tumor Treating Fields (TTFields, Optune)

Tumor treating fields are alternating electric fields delivered non-invasively via adhesive transducer arrays worn on the shaved scalp. At frequencies of 100–300 kHz, they interfere with mitotic spindle formation and cytokinesis, selectively disrupting rapidly dividing cells without meaningful effect on post-mitotic neurons. The EF-14 trial (Stupp R et al., JAMA 2015, PMID 26670971) randomized 695 newly diagnosed GBM patients after completing chemoradiation to TTFields plus adjuvant TMZ versus TMZ alone. TTFields improved median progression-free survival from 4.0 to 6.7 months and median overall survival from 16.0 to 20.9 months (an improvement of approximately 5 months). Compliance correlated with benefit. TTFields received FDA approval for newly diagnosed GBM in 2015 and for recurrent GBM in 2011. Skin irritation under the transducers is the primary side effect.

Bevacizumab (Anti-VEGF Therapy)

Bevacizumab (Avastin), a monoclonal antibody targeting VEGF-A, reduces tumor vasogenicity and edema, allowing steroid reduction. For recurrent GBM, it is FDA-approved based on response rates and improved progression-free survival. However, the two large randomized trials in newly diagnosed GBM — AVAglio (Chinot OL et al., NEJM 2014, PMID 24552318) and RTOG 0825 — demonstrated improved PFS but no improvement in overall survival, and AVAglio noted worse quality of life in some cognitive domains in the bevacizumab arm. Its role is therefore primarily palliative — relieving edema, permitting steroid taper — rather than curative.

IDH Inhibitors for IDH-Mutant Gliomas

Vorasidenib, an oral dual IDH1/IDH2 inhibitor that penetrates the blood-brain barrier, was evaluated in the INDIGO trial (Tesileanu CMS et al., NEJM 2023, PMID 37272516). In patients with IDH-mutant grade 2 glioma who had undergone surgery but not yet received adjuvant radiation or chemotherapy, vorasidenib significantly improved median PFS compared to placebo (17.0 months vs 7.3 months; hazard ratio 0.39). This represented a practice-changing result, offering an oral targeted therapy that delays the need for more toxic treatments in low-grade glioma. Vorasidenib received FDA approval for IDH-mutant low-grade glioma in 2024.

Lomustine (CCNU) and Alkylating Agents

For recurrent GBM, lomustine (CCNU) alone or in combination is a standard second-line option. The BELOB trial suggested lomustine-bevacizumab activity; the subsequent EORTC 26101 trial (Wick W et al., NEJM 2017, PMID 29141164) compared lomustine plus bevacizumab versus lomustine alone in recurrent GBM and found no OS benefit for the combination despite a PFS advantage.

Medulloblastoma

Treatment is risk-stratified based on molecular subgroup, age, extent of resection, and M-stage (degree of leptomeningeal dissemination):

Meningioma

Management options include active surveillance (small, incidentally discovered, asymptomatic tumors in elderly patients), surgical resection (Simpson grade I–III correlates with recurrence risk), and stereotactic radiosurgery (SRS/Gamma Knife) for tumors less than 3 cm or surgically inaccessible recurrent lesions. Conventional fractionated radiotherapy is used for larger tumors or after incomplete resection of atypical (grade 2) meningiomas. Systemic therapy has limited efficacy for refractory meningioma; octreotide, hydroxyurea, and bevacizumab have shown modest activity. FAK inhibitors and SMO inhibitors targeting specific molecular subtypes are under investigation.

Complications

Cerebral edema is the most immediate life-threatening complication. Vasogenic edema from BBB disruption responds to dexamethasone, typically 4 mg every 6 hours, with dose titrated to clinical effect. Long-term steroid use causes hyperglycemia (managed with insulin if needed), myopathy, gastrointestinal bleeding (particularly with concurrent NSAIDs), opportunistic infections (Pneumocystis jirovecii prophylaxis with TMP-SMX is indicated for patients on prolonged steroids), and neuropsychiatric effects.

Seizures occur in 20–40% of brain tumor patients. Prophylactic antiepileptic drugs (AEDs) are not recommended in seizure-naive patients (no level I evidence of benefit; enzyme-inducing AEDs increase chemotherapy metabolism). Levetiracetam (Keppra) is the preferred AED when seizures occur, due to minimal drug interactions and lack of enzyme induction. Valproate has data suggesting possible survival benefit in GBM patients on temozolomide (inhibits HDAC), but this is not practice-changing.

Venous thromboembolism (VTE) — deep vein thrombosis and pulmonary embolism — affects 20–30% of malignant brain tumor patients, one of the highest rates of any cancer. Risk factors include prolonged immobility, paresis, and pro-thrombotic factors secreted by the tumor (tissue factor, VEGF). Prophylactic low-molecular-weight heparin is considered safe and appropriate in most patients despite intracranial disease; concerns about intratumoral hemorrhage are generally manageable with proper patient selection.

Cognitive effects of radiation include subacute encephalopathy (somnolence syndrome, weeks to months post-RT), and late delayed radiation injury manifesting as white matter T2 hyperintensity, radiation necrosis, and progressive cognitive decline particularly affecting memory, attention, and processing speed. Hippocampal-sparing RT and memantine have shown modest protective effects in randomized trials.

Temozolomide toxicity includes myelosuppression (nadir at days 21–28 of each cycle), nausea/vomiting, fatigue, and rare but serious aplastic anemia. Blood count monitoring is required. Myelosuppression may necessitate dose reduction or treatment delays.

Prognosis

Prognosis in brain tumors varies enormously by tumor type, molecular subtype, age, and performance status.

Glioblastoma (IDH-wildtype) carries the worst prognosis of the common primary brain tumors. With Stupp protocol, median overall survival is approximately 14.6–15 months, and 5-year survival remains below 5–10%. Favorable prognostic factors include younger age, better performance status, gross total resection, and MGMT methylation. Despite decades of clinical trials involving hundreds of experimental agents, no therapy has substantially improved on the Stupp protocol in unselected patients.

IDH-mutant astrocytoma has considerably better prognosis. Grade 2 tumors have median survival of 8–15 years; grade 3 tumors 3–7 years; grade 4 (formerly "secondary GBM") approximately 3–5 years — all markedly better than IDH-wildtype GBM.

Oligodendroglioma (IDH-mutant, 1p/19q co-deleted) has the best prognosis among gliomas, with median survival of 10–15 or more years for grade 2 and 6–10 years for grade 3, particularly with combined PCV chemotherapy and radiotherapy (demonstrated in RTOG 9402 and EORTC 26951 trials, with benefit persisting at 10+ year follow-up).

Meningioma (WHO grade 1): 10-year recurrence rates of 7–25% after gross total resection; excellent long-term survival. Grade 2 (atypical): higher recurrence rates (~40% at 10 years), more aggressive behavior. Grade 3 (anaplastic): poor prognosis, median survival 2–3 years.

Medulloblastoma: Standard-risk pediatric patients achieve 5-year overall survival of 80–90%. WNT-activated subgroup exceeds 90%. High-risk patients and those with disseminated disease have survival of approximately 50–70%. Adult medulloblastoma carries modestly inferior prognosis to pediatric disease.

The MGMT methylation survival impact within GBM is the single most powerful biomarker — the approximately 9-month median OS difference between methylated and unmethylated populations (21.7 vs 12.7 months in the Stupp/Hegi analysis) is larger than the benefit conferred by temozolomide itself in unmethylated tumors.

Recent Research and Advances

Vorasidenib and IDH inhibition represent the clearest recent therapeutic advance in glioma. The INDIGO trial result in 2023 established a new standard-of-care option for residual or recurrent IDH-mutant grade 2 glioma and catalyzed a wave of trials testing IDH inhibitors earlier in the disease course and in combination with RT/chemotherapy.

CAR-T cell therapy for GBM is in early clinical development. Targets include EGFRvIII (a GBM-specific EGFR deletion variant), GD2, IL13Rα2, and EGFRvIII combined with IL13Rα2. Initial results have shown tumor responses but limited durability, partly due to target antigen heterogeneity and the immunosuppressive tumor microenvironment. Regional intracranial delivery of CAR-T cells (via intraventricular or intratumoral infusion) is being explored to achieve higher local concentrations.

Oncolytic viruses — genetically engineered viruses that selectively replicate in and lyse tumor cells — have advanced to Phase 2 trials. DNX-2401 (tasadenoturev), an oncolytic adenovirus, demonstrated a subset of durable responses in recurrent GBM (approximately 12% at 3 years in a Phase 2 study). DNX-2401 in combination with pembrolizumab (anti-PD-1) is under investigation.

Dendritic cell vaccines aim to prime the immune system against tumor-specific antigens. The DCVax-L trial — an autologous tumor lysate-pulsed dendritic cell vaccine for newly diagnosed GBM — published results in 2022 showing a median OS of 19.3 months in intent-to-treat patients with a long-tail survival pattern, with approximately 13% of vaccinated patients surviving at 5 years. While intriguing, the trial's unusual design (crossover at recurrence) made interpretation complex; it did not establish a clear survival benefit over placebo in a conventional randomized comparison.

Convection-enhanced delivery (CED) bypasses the blood-brain barrier by directly infusing therapeutic agents under positive pressure through catheters stereotactically placed into the tumor or surrounding brain. This approach delivers drugs, oncolytic viruses, and immunotoxins directly to tumor tissue at concentrations orders of magnitude higher than systemic administration would achieve. Phase 1–2 trials of CED-delivered agents (including IL13Rα2-targeted immunotoxins and LOVA CAR-T cells) are ongoing.

Liquid biopsy for brain tumors — detection of tumor-derived cell-free DNA, circulating tumor cells, extracellular vesicles, and microRNAs in plasma or CSF — is advancing. CSF ctDNA can detect IDH, TERT, and EGFR mutations with high specificity and may enable tumor monitoring without repeated biopsies. Challenges include low concentration of brain-derived nucleic acids in plasma and technical sensitivity limitations.

DIPG and H3K27M-targeted therapies: Diffuse intrinsic pontine glioma remains essentially untreatable with current modalities (median survival 9–11 months). H3K27M-targeted approaches including EZH2 inhibitors, HDAC inhibitors, and ONC201 (a DRD2/DRD3 antagonist with activity against H3K27M-mutant DMG) are in clinical trials, with ONC201 showing early signals of activity in H3K27M-mutant diffuse midline gliomas.

Targeted therapy for meningioma is an emerging area — approximately 5% of meningiomas harbor SMO mutations (SHH pathway), and vismodegib has shown modest activity. AKT inhibitors (for NF2-loss meningiomas with PI3K/AKT pathway activation) and FAK inhibitors are in early trials.

References & Research

  1. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–996. PMID: 15758009. DOI: 10.1056/NEJMoa043330
  2. Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997–1003. PMID: 15758010. DOI: 10.1056/NEJMoa043331
  3. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro-Oncology. 2021;23(8):1231–1251. PMID: 34185076. DOI: 10.1093/neuonc/noab106
  4. Stummer W, Pichlmeier U, Meinel T, et al. Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7(5):392–401. PMID: 16648043. DOI: 10.1016/S1470-2045(06)70665-9
  5. Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial (EF-14). JAMA. 2015;314(23):2535–2543. PMID: 26670971. DOI: 10.1001/jama.2015.16669
  6. Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma (AVAglio). N Engl J Med. 2014;370(8):709–722. PMID: 24552318. DOI: 10.1056/NEJMoa1308345
  7. Wick W, Gorlia T, Bendszus M, et al. Lomustine and bevacizumab in progressive glioblastoma. N Engl J Med. 2017;377(20):1954–1963. PMID: 29141164. DOI: 10.1056/NEJMoa1707358
  8. Cairncross G, Wang M, Shaw E, et al. Phase III trial of chemoradiotherapy for anaplastic oligodendroglioma: long-term results of RTOG 9402. J Clin Oncol. 2013;31(3):337–343. PMID: 23269987. DOI: 10.1200/JCO.2012.43.2674
  9. Tesileanu CMS, Dirven L, Wijnenga MMJ, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma (INDIGO trial). N Engl J Med. 2023;389(7):589–601. PMID: 37272516. DOI: 10.1056/NEJMoa2304194
  10. Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310(17):1842–1850. PMID: 24193082. DOI: 10.1001/jama.2013.280319
  11. Liau LM, Ashkan K, Tran DD, et al. First results on survival from a large Phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma (DCVax-L). J Neurooncol. 2018;139(3):637–644. PMID: 30069956. DOI: 10.1007/s11060-018-2975-2
  12. Tan AC, Ashley DM, López GY, et al. Management of glioblastoma: state of the art and future directions. CA Cancer J Clin. 2020;70(4):299–312. PMID: 32478924. DOI: 10.3322/caac.21613

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Research Papers

Explore peer-reviewed literature on PubMed:

  1. Glioblastoma treatment (temozolomide + radiotherapy)
  2. Brain tumor WHO 2021 classification (molecular)
  3. MGMT promoter methylation in glioma
  4. Tumor treating fields (TTFields) in glioblastoma
  5. IDH mutation in low-grade glioma (vorasidenib)
  6. Meningioma treatment (surgery and radiosurgery)
  7. Medulloblastoma pediatric molecular subgroups
  8. Brain cancer immunotherapy (CAR-T, checkpoint inhibitors)
  9. 5-ALA fluorescence-guided surgery in glioma
  10. Blood-brain barrier and drug delivery in GBM
  11. Brain metastases treatment (stereotactic radiosurgery)
  12. Glioma stem cells (resistance and recurrence)

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Connections

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