Highlights & Basics
- Gliomas may be described as circumscribed or diffuse.
- Circumscribed gliomas (e.g., pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, pilocytic/pilomyxoid astrocytoma) have well-defined margins, and are generally benign. Maximal safe resection is the mainstay of treatment.
- Diffuse astrocytomas (grade 2-4) represent a spectrum of the same highly infiltrative disease, with lower grades inevitably progressing to higher-grade lesions. They can be characterized on the basis of the isocitrate dehydrogenase (IDH) and histone 3 (H3) mutation status.
- IDH-wildtype diffuse glioma (glioblastoma) is an aggressive primary brain tumor that presents in patients in the sixth or seventh decade of life.
- IDH-mutant gliomas (including oligodendroglioma, IDH-mutant, 1p/19q codeleted, grades 2-3; and astrocytoma, IDH-mutant, grades 2-4) tend to occur in young or middle-age patients.
- H3 mutant gliomas (including diffuse midline glioma, H3 K27M altered; and diffuse hemispheric glioma, H3 G34-mutant) are aggressive (grade 4) brain tumors occurring in children, adolescents, and young adults.
- There are no known predisposing factors for gliomas except for rare familial syndromes and prior cranial radiation therapy.
- Treatments vary depending on tumor grade and molecular characteristics. Initial treatment typically includes maximal safe surgical resection, with the aim of gross total resection if possible. Adjuvant radiation therapy and chemotherapy is indicated for most diffuse gliomas, with regimens varying based on molecular pathology, extent of resection, and other patient-specific factors. For diffuse infiltrating gliomas, clinical trials or investigational therapies should be considered as the initial therapeutic option, as none of the available therapies are curative and prognosis is poor.
Quick Reference
History & Exam
Key Factors
Other Factors
altered mental status
headache
nausea and/or vomiting
gait abnormality
ataxia
weakness
seizures
visual disturbances
speech deficit
aphasia/dysphasia
sensory deficit
motor weakness
visual change
cranial nerve palsy
papilledema
personality change/emotional lability
Diagnostics Tests
1st Tests to Order
MRI head
ophthalmologic evaluation; visual field testing
CT head
brain MR spectroscopy
brain perfusion MRI
histopathology
molecular analyses
Other Tests to consider
pituitary hormones tests
diffusion tensor imaging (DTI)
Emerging Tests
2-hydroxyglutarate-targeted magnetic resonance spectroscopy
Treatment Options
presumptive
elevated intracranial pressure or vasogenic edema
elevated intracranial pressure or vasogenic edema
comatose and intubated
with seizures
acute
circumscribed glioma: pilocytic/pilomyxoid astrocytoma (World Health Organization [WHO] grade 1)
accessible
inaccessible without symptoms
inaccessible with symptoms
Definition
Classifications
World Health Organization (WHO) classification
- Adult-type diffuse gliomas
- Astrocytoma, isocitrate dehydrogenase (IDH)-mutant (CNS WHO grades 2, 3, or 4)
- Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted (CNS WHO grades 2 or 3)
- Glioblastoma, IDH-wildtype (CNS WHO grade 4)
- Pediatric-type diffuse low-grade gliomas
- Diffuse astrocytoma, MYB- or MYBL1-altered
- Angiocentric glioma
- Polymorphous low-grade neuroepithelial tumor of the young
- Diffuse low-grade glioma, MAPK pathway-altered
- Pediatric-type diffuse high-grade gliomas
- Diffuse midline glioma, H3 K27-altered
- Diffuse hemispheric glioma, H3 G34-mutant
- Diffuse pediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
- Infant-type hemispheric glioma
- Circumscribed astrocytic gliomas
- Pilocytic astrocytoma
- High-grade astrocytoma with piloid features
- Pleomorphic xanthoastrocytoma
- Subependymal giant cell astrocytoma
- Chordoid glioma
- Astroblastoma, MN1-altered
Tumor location
- The majority of gliomas are supratentorial, with the exception of diffuse midline gliomas, H3 K27M-altered, and pilocytic astrocytomas, which tend to involve the brainstem/posterior fossa.[2]
- The frontal lobe is the most frequent location for gliomas of all grades, followed by the temporal lobe, and less frequently the parietal and occipital lobes.[3]
- Intramedullary tumors account for less than 10% of tumors, with astrocytomas and ependymomas accounting for approximately 40% and 60% of these, respectively.[3]
Vignette
Common Vignette 1
Common Vignette 2
Epidemiology
Etiology
Pathophysiology
Images
Simplified classification of diffuse gliomas based on the 2021 WHO classification of CNS tumors. *Astrocytoma, IDH-mutant, can be diagnosed as grade 2, 3, or 4 based on histopathologic grading criteria and cyclin-dependent kinase inhibitor 2A/cyclin-dependent kinase inhibitor 2B (CDKN2A/B) status. ***Oligodendroglioma, IDH-mutant with codeletion of the short arm of chromosome 1 and the long arm of chromosome 19 (1p19q), can be diagnosed as grade 2 or 3 based on histopathologic features
T2-weighted MRI without (A) and with (B) contrast demonstrating a pontine glioma
MRI: T2 and T1 post-contrast, demonstrating a tectal glioma (grade 2)
MRI demonstrating a right temporal glioblastoma (grade 4)
MRI demonstrating a right frontal grade 2 diffuse astrocytoma
MRI demonstrating a cerebellar pilocytic astrocytoma (grade 1)
Important molecular tests to establish the diagnosis and prognosis of glioblastoma
Diagnostic Approach
Neurologic deficits according to location
- Personality change
- Cognitive decline
- Emotional lability
- Nonfluent aphasia (if dominant inferior frontal gyrus involved)
- Motor weakness (precentral gyrus)
- Visual field deficits
- Fluent aphasia (if dominant lobe involved)
- Sensory deficits
- Dominant side inferior parietal lobule: expressive aphasia
- Superior: Gerstmann syndrome (acalculia, finger agnosia, left-right confusion, alexia without agraphia)
- Nondominant side: neglect, anosognosia
- Visual field deficits
- Contralateral homonymous hemianopsia
- Vermis: truncal ataxia
- Hemisphere: ipsilateral dysmetria, nystagmus
- Cranial nerve (CN) palsies
- CN III, IV, VI: diplopia
- CN V: facial sensory disturbances
- CN VII: facial palsy
- CN VIII: hearing or balance problems
- CN IX: sensory problems in throat, swallowing problems
- CN X: voice change (i.e., hoarseness), swallowing problems
- CN XI: weakness of sternocleidomastoid or trapezium muscles
- CN XII: deviation of the tongue
- Nystagmus
- Cerebellar signs
- Long tract signs
- Visual field deficits
- Excess or deficiency in pituitary hormones
- Hypothalamic syndrome
- Motor (ipsilateral weakness, hyperreflexia, clonus, spasticity)
- Sensory (ipsilateral light touch, proprioceptive, vibration deficits/contralateral pain and temperature deficits)
- Autonomic changes
- Cord syndromes (central, Brown-Sequard, posterior, anterior)
- Dorsal pain
- Radicular pain
- Sphincter disturbances
- One review reported that 75% to 80% of patients with low-grade gliomas have seizures, compared with 29% to 60% of patients with glioblastoma.[25]
Intracranial hypertension and vasogenic edema
Laboratory evaluation
Magnetic resonance imaging
- N-acetylaspartate: highest peak in the normal brain, neuronal marker.
- Choline: marker of cell membrane turnover; increases in this peak are associated with malignancy.
- Lactate: marker of hypoxia; increases in this peak are associated with malignancy.
Computed tomography
Ophthalmologic evaluation
Histopathologic investigations
Molecular analyses
Risk Factors
History & Exam
Tests
Differential Diagnosis
Brain metastasis
Differentiating Signs/Symptoms
- May or may not have systemic disease and/or known history of cancer.
- Systemic symptoms may include cachexia, respiratory problems, hemoptysis, chest pain, and bone pain.
Differentiating Tests
- MRI: typically, more localized lesions that may be multiple, and with proportionally more vasogenic edema.
- Chest-abdominal CT scan, bone scan, PET scan provide evidence of systemic disease.
- Histology provides a definitive diagnosis.
Brain abscess
Differentiating Signs/Symptoms
- May or may not have systemic symptoms such as fever, cachexia, and chills.
- Risk factors differ and may include pulmonary abnormalities, congenital cyanotic heart disease, bacterial endocarditis, and penetrating head injury.
Differentiating Tests
- MRI demonstrates a thinner capsule toward the ventricle, with restricted diffusion of pus and elevated lactate level; may show multiple lesions.
- Blood tests suggestive of infection: for example, elevated WBC count, elevated erythrocyte sedimentation rate, and elevated C-reactive protein, with sensitivity 90% and specificity 77%.[35]
- Biopsy or aspiration provides the definite diagnosis, demonstrating pus (inflammatory cells), no tumor cells, and a positive culture of bacterial agent or fungus.
Multiple sclerosis
Differentiating Signs/Symptoms
- Typically, presents in women aged 20-40 years with acute neurologic symptoms that wax and wane (dissemination in space and time): for example, optic neuritis, transverse myelitis (spinal cord symptoms), and focal neurologic symptoms.
- Although rare, glioma may occur in patients with multiple sclerosis.[36]
Differentiating Tests
- MRI shows multiple lesions in the periventricular white matter; may or may not enhance.
- Cerebrospinal fluid shows oligoclonal bands.
- Histology provides the definitive diagnosis, demonstrating demyelinating lesions, inflammatory cells, and absence of tumor cells, but usually is not necessary.
Differentiating Signs/Symptoms
- Known brain tumor treated with radiation therapy in the past.
- May present with progressive neurologic symptoms or no symptoms at all.
Differentiating Tests
- PET scan is cold. MR perfusion with decreased cerebral blood volume (relative CBV).
- Histology provides definitive diagnosis (no tumor cells and extensive necrosis).
Acute stroke
Differentiating Signs/Symptoms
- Acute onset of neurologic symptoms.
- Often in older patients with cardiovascular risk factors.
- Rarely present with seizures (3% to 5% only).
Differentiating Tests
- MRI shows typical vasculature distribution and restricted diffusion.
- Of note, subacute strokes may exhibit contrast enhancement.
Encephalitis
Differentiating Signs/Symptoms
- Systemic symptoms present (fever and cachexia).
Differentiating Tests
- Cerebrospinal fluid shows leukocytosis, herpes simplex virus antibodies, and/or red blood cells.
- Electroencephalogram is characteristic with periodic lateralizing epileptiform discharges.
- CT or MRI shows edematous temporal lobes and hemorrhagic transformation.
- Brain biopsy is definitive with virus isolation.
Treatment Approach
Emergency management
- Patients presenting with tumor-related epilepsy should be treated with an anticonvulsant drug.
- Levetiracetam, lacosamide, and lamotrigine are preferred to older anticonvulsants (e.g., phenytoin, phenobarbital, valproic acid) because they are better tolerated and have less potential for drug-drug interactions.
- Patients presenting without seizures should not be prescribed an anticonvulsant to reduce the risk of seizures.
- Prophylactic anticonvulsant treatment may be used perioperatively, but evidence for effectiveness is limited.[40]
- If a patient has imaging evidence of vasogenic edema leading to neurologic deficits, dexamethasone is recommended.
- Presenting symptoms indicative of intracranial hypertension might include drowsiness, headache, nausea, vomiting, and double vision, or in more severe cases, sixth (VI) nerve palsy and papilledema.
- For symptoms suggestive of severe intracranial hypertension, intravenous mannitol should be added to high doses of intravenous dexamethasone.
- If a patient with severe intracranial hypertension is comatose and intubated, temporary hyperventilation may be necessary.
- An emergency neurosurgery consultation for possible decompression surgery is recommended for these patients.
Circumscribed gliomas: newly diagnosed
Circumscribed gliomas: recurrent
Diffuse infiltrating gliomas: newly diagnosed
- For diffuse astrocytoma, IDH-mutant, grade 3, the recommended treatment following maximal safe resection is radiation followed by 12 cycles of adjuvant temozolomide.[52]
- For oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 3, radiation followed by PCV chemotherapy is recommended. Temozolomide is an alternative.[39]
- For diffuse astrocytoma, IDH-mutant, grade 4, and glioblastoma, IDH-wildtype, grade 4, the recommended treatment is radiation with concurrent temozolomide followed by 6 cycles of adjuvant temozolomide.[39]
Diffuse infiltrating gliomas: progressive disease
Treatment Options
elevated intracranial pressure or vasogenic edema
dexamethasone ± mannitol
Primary Options
- dexamethasone sodium phosphate
10 mg intravenously initially, followed by 4 mg every 6 hours until symptoms subside, then gradually taper dose (switch to oral dose when possible)
- dexamethasone sodium phosphate
- dexamethasone sodium phosphate
10 mg intravenously initially, followed by 4 mg every 6 hours until symptoms subside, then gradually taper dose (switch to oral dose when possible)
and
- mannitol
0.25 to 2 g/kg intravenously initially, may repeat every 6-8 hours as needed
- dexamethasone sodium phosphate
Comments
- If a patient has imaging evidence of vasogenic edema leading to neurologic deficits, dexamethasone is recommended. Presenting symptoms indicative of intracranial hypertension might include drowsiness, headache, nausea, vomiting, and double vision, or in more severe cases, sixth (VI) nerve palsy and papilledema.
- For symptoms suggestive of severe intracranial hypertension, intravenous mannitol should be added to high doses of intravenous dexamethasone. Monitor serum osmolarity, fluid and electrolytes, renal function, cardiac function, and pulmonary function during and after mannitol infusion.
- An emergency neurosurgery consultation for possible decompression surgery is recommended for these patients.
comatose and intubated
temporary hyperventilation
Comments
- If a patient with severe intracranial hypertension is comatose and intubated, temporary hyperventilation may be necessary.
with seizures
anticonvulsant
Primary Options
- levetiracetam
consult specialist for guidance on dose
- levetiracetam
- lacosamide
consult specialist for guidance on dose
- lacosamide
- lamotrigine
consult specialist for guidance on dose
- lamotrigine
Comments
- Patients presenting with tumor-related epilepsy should be treated with an anticonvulsant. Levetiracetam, lacosamide, and lamotrigine are preferred to older anticonvulsants (e.g., phenytoin, phenobarbital, valproic acid) because they are better tolerated and have less potential for drug-drug interactions.
- Patients presenting without seizures should not be prescribed an anticonvulsant to reduce the risk of seizures.
- Prophylactic anticonvulsant treatment may be used perioperatively, but evidence for effectiveness is limited.[40]
circumscribed glioma: pilocytic/pilomyxoid astrocytoma (World Health Organization [WHO] grade 1)
accessible
systemic therapy and/or radiation therapy
Comments
- If resection is partial in symptomatic patients, additional treatment modalities include chemotherapy, targeted therapies (BRAF and/or mitogen-activated protein kinase kinase [MEK] inhibitors if targetable alterations are present), and radiation therapy. Recent guidelines favor chemotherapy or targeted therapies, if suitable options are available, in order to minimize the long-term effects of radiation.[21] [24] See local specialist protocol for choice of regimen and dosing guidelines.
inaccessible without symptoms
inaccessible with symptoms
systemic therapy and/or radiation therapy ± CSF diversion procedure
Comments
- In the brainstem, particularly at the tectal plate of the midbrain, obstructive hydrocephalus can be addressed with a cerebrospinal fluid (CSF) diversion procedure.
- For symptomatic patients in whom resection is precluded by location, treatment modalities include chemotherapy, targeted therapies (e.g., BRAF and/or mitogen-activated protein kinase kinase [MEK] inhibitors if targetable alterations are present), and radiation therapy. Recent guidelines favor chemotherapy or targeted therapies, if suitable options are available, in order to minimize the long-term effects of radiation.[21] [24] See local specialist protocol for choice of regimen and dosing guidelines.
circumscribed glioma: subependymal giant cell astrocytoma (WHO grade 1)
without symptoms
with symptoms
maximal safe resection and/or mTOR inhibitor
Comments
- Subependymal giant cell astrocytomas (SEGAs) are typically surgically accessible. Mammalian target of rapamycin (mTOR) inhibitors such everolimus and sirolimus may be used to induce tumor remission or size reduction before resection, or as first-line treatment if surgical resection is not possible or if patients prefer medical treatment.[21]
- See Tuberous sclerosis complex .
circumscribed glioma: pleomorphic xanthoastrocytoma (WHO grade 2)
without symptoms
with symptoms
intraoperative electrocorticography
Comments
- If a patient presents with intractable epilepsy due to epileptogenic foci, intraoperative electrocorticography may be used to guide complete resection of the epileptogenic area.[25]
targeted therapy or radiation therapy or radiosurgery
Comments
- If resection is partial in symptomatic patients, additional treatment modalities include targeted therapies, radiation therapy, or radiosurgery. Recent guidelines favor targeted therapies, if suitable options are available, in order to minimize the long-term effects of radiation.[21] [24] See local specialist protocol for choice of regimen and dosing guidelines.
diffuse infiltrating glioma: grade 2
accessible
maximal safe resection
Comments
- Maximal safe resection is the primary treatment if the tumor is surgically accessible. However, preventing new permanent neurologic deficits that might affect the patient's independence, reduce their quality of life, or increase the risk of complications that might compromise further therapy is more important than the extent of resection.[44] Several surgical adjuncts may be used to maximize resection while minimizing risk of postoperative disability.[20] [21] [22] [45]
- If the patient is not a candidate for surgery due to comorbidities, a stereotactic biopsy should be performed.[22]
radiation therapy + chemotherapy
Comments
- For high-risk patients after surgery (i.e., ages 40 years or older, or subtotal resection), standard care is a combination of radiation therapy and chemotherapy.[21] [47] [48] It is important that the long-term adverse effects of radiation therapy (e.g., on neurocognition) and chemotherapy are taken into account.[7] [47] [49] [50]
inaccessible
stereotactic biopsy + radiation therapy + chemotherapy
Comments
- If safe resection is not possible due to tumor location, a stereotactic biopsy should be performed.[22]
diffuse infiltrating glioma: grades 3 and 4
accessible
maximal safe resection
Comments
- Maximal safe resection is the primary treatment if the tumor is surgically accessible. However, preventing new permanent neurologic deficits that might affect the patient's independence, reduce their quality of life, or increase the risk of complications that might compromise further therapy is more important than the extent of resection.[44] Several surgical adjuncts may be used to maximize resection while minimizing risk of postoperative disability.[20] [21] [22] [45]
- If the patient is not a candidate for surgery due to comorbidities, a stereotactic biopsy should be performed.[22]
radiation therapy + chemotherapy
Comments
- Diffuse astrocytoma, isocitrate dehydrogenase (IDH)-mutant, grade 3: recommended treatment following maximal safe resection is radiation followed by 12 cycles of adjuvant temozolomide.[52]
- Oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 3: radiation followed by PCV (procarbazine, lomustine, vincristine) chemotherapy is recommended. Temozolomide is an alternative.[39]
- Diffuse astrocytoma, IDH-mutant, grade 4; and glioblastoma, IDH-wildtype, grade 4: recommended treatment is radiation with concurrent temozolomide followed by 6 cycles of adjuvant temozolomide.[39]
- See local specialist protocol for choice of regimen and dosing guidelines.
inaccessible
stereotactic biopsy + radiation therapy + chemotherapy
Comments
- If safe resection is not possible due to tumor location, a stereotactic biopsy should be performed.[22]
- Diffuse astrocytoma, isocitrate dehydrogenase (IDH)-mutant, grade 3: recommended treatment is radiation followed by 12 cycles of adjuvant temozolomide.[52]
- Oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 3: radiation followed by PCV (procarbazine, lomustine, vincristine) chemotherapy is recommended. Temozolomide is an alternative.[39]
- Diffuse astrocytoma, IDH-mutant, grade 4; and glioblastoma, IDH-wildtype, grade 4: recommended treatment is radiation with concurrent temozolomide followed by 6 cycles of adjuvant temozolomide.[39]
- See local specialist protocol for choice of regimen and dosing guidelines.
diffuse midline glioma, H3 K27M-altered
stereotactic biopsy + radiation therapy + chemotherapy
Comments
- A diffuse midline glioma, H3 K27M-altered, grade 4 (formerly called a diffuse intrinsic pontine glioma) is a rare type of astrocytoma found primarily in children that has a high recurrence rate because of its invasiveness of adjacent brain tissue. The tumor is always inaccessible, so resection is not possible, but biopsy should be pursued to confirm the diagnosis.
- Clinical trials or investigational therapies should be considered as a first-line therapy, given the aggressive nature of the disease and its very poor prognosis. See Emerging treatments .
- See local specialist protocol for choice of regimen and dosing guidelines.
recurrent circumscribed glioma
repeat maximal safe resection if possible
Comments
- If there is recurrence following initial therapy, maximal safe resection should be repeated if feasible.[24]
targeted therapy
Comments
- Targeted therapies (e.g., BRAF and/or mitogen-activated protein kinase kinase [MEK] inhibitors) can be considered if targetable mutations have been identified in tissue from initial resection.[24] See local specialist protocol for choice of regimen and dosing guidelines.
progressive diffuse infiltrating glioma
repeat maximal safe resection + repeat radiation therapy and/or rechallenge with chemotherapy
Comments
- If no clinical trials or investigational therapies are available, repeat radiation therapy may be considered, depending on time since previous treatment and tumor location, but neurocognitive adverse effects and risks of radionecrosis must be taken into account.[20] [21] [22] [27] [39] [49] [59] [60]
- There is no good evidence to recommend any particular chemotherapy regimen over another at the time of disease progression, and clinicians should take into account factors such as time since last treatment, molecular features of the tumor, performance status, and patient preference. Options include nitrosourea-based regimens and temozolomide. Platinum-based regimens are not recommended.[21] [22] [27] [59][61] [62]
- See local specialist protocol for choice of regimen and dosing guidelines.
Emerging Tx
Isocitrate dehydrogenase inhibitors
Other targeted molecular therapies
Therapies targeting DNA damage response pathways
Immunotherapies
Other therapies
Follow-Up Overview
Prognosis
Circumscribed astrocytic gliomas
Diffuse infiltrating gliomas
- Oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 2: >14 years
- Oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 3: 10-14 years
- Diffuse astrocytoma, IDH-mutant, grade 2: >10 years
- Diffuse astrocytoma, IDH-mutant, grade 3: 5-10 years
- Diffuse astrocytoma, IDH-mutant, grade 4: approximately 3 years
- Glioblastoma, IDH-wildtype, MGMT promoter methylated : 22-24 months
- Glioblastoma, IDH-wildtype, MGMT promoter unmethylated: 15-18 months
- Diffuse midline glioma, H3 K27M-altered: 10-16 months.
Monitoring
- For grade 1 tumors: 6 months to 1 year follow-up clinically and radiographically
- For grade 2 tumors: 3-4 months follow-up
- For grade 3 and 4 tumors: 2-3 months follow-up.
Complications
Citations
Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-51.[Abstract][Full Text]
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: central nervous system cancers [internet publication].[Full Text]
Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021 Mar;18(3):170-86.[Abstract][Full Text]
Mohile NA, Messersmith H, Gatson NT, et al. Therapy for diffuse astrocytic and oligodendroglial tumors in adults: ASCO-SNO guideline. J Clin Oncol. 2022 Feb 1;40(4):403-26.[Abstract][Full Text]
Liau LM. Guidelines for newly diagnosed glioblastoma. J Neurooncol. 2008 Sept;89(3).[Full Text]
Buckner JC, Shaw EG, Pugh SL, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med. 2016 Apr 7;374(14):1344-55.[Abstract][Full Text]
American Association of Neurological Surgeons; Congress of Neurological Surgeons. Updated AANS/CNS guidelines for progressive glioblastoma patients. Jun 2022 [internet publication].[Full Text]
1. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO classification of tumors of the central nervous system: a summary. Neuro Oncol. 2021 Aug 2;23(8):1231-51.[Abstract][Full Text]
2. Burkhard C, Di Patre PL, Schuler D, et al. A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma. J Neurosurg. 2003 Jun;98(6):1170-4.[Abstract]
3. Ostrom QT, Price M, Neff C, et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2015-2019. Neuro Oncol. 2022 Oct 5;24(5 suppl):v1-95.[Abstract][Full Text]
4. Thakkar JP, Dolecek TA, Horbinski C, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):1985-96.[Abstract][Full Text]
5. Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007 Feb;44(2):81-8.[Abstract][Full Text]
6. Northrup H, Aronow ME, Bebin EM, et al. Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol. 2021 Oct;123:50-66.[Abstract][Full Text]
7. Miller JJ, Gonzalez Castro LN, McBrayer S, et al. Isocitrate dehydrogenase (IDH) mutant gliomas: a Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncol. 2023 Jan 5;25(1):4-25.[Abstract][Full Text]
8. World Health Organization. Central nervous system tumours: WHO classification of tumours. 5th ed. vol 6. Lyon, France: IARD Press; 2021.
9. Paulino AC, Mai WY, Chintagumpala M, et al. Radiation-induced malignant gliomas: is there a role for reirradiation? Int J Radiat Oncol Biol Phys. 2008 Aug 1;71(5):1381-7.[Abstract]
10. Gurney JG, Kadan-Lottick N. Brain and other central nervous system tumors: rates, trends and epidemiology. Curr Opin Oncol. 2001 May;13(3):160-6.[Abstract]
11. Braganza MZ, Kitahara CM, Berrington de González A, et al. Ionizing radiation and the risk of brain and central nervous system tumors: a systematic review. Neuro Oncol. 2012 Nov;14(11):1316-24.[Abstract][Full Text]
12. Campian J, Gutmann DH. CNS tumors in neurofibromatosis. J Clin Oncol. 2017 Jul 20;35(21):2378-85.[Abstract][Full Text]
13. Roth J, Roach ES, Bartels U, et al. Subependymal giant cell astrocytoma: diagnosis, screening, and treatment - recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012. Pediatr Neurol. 2013 Dec;49(6):439-44.[Abstract][Full Text]
14. Rocca V, Blandino G, D'Antona L, et al. Li-Fraumeni syndrome: mutation of TP53 is a biomarker of hereditary predisposition to tumor: new insights and advances in the treatment. Cancers (Basel). 2022 Jul 27;14(15):3664.[Abstract][Full Text]
15. Hamilton SR, Liu B, Parsons RE, et al. The molecular basis of Turcot's syndrome. N Engl J Med. 1995 Mar 30;332(13):839-47.[Abstract][Full Text]
16. Schüz J, Pirie K, Reeves GK, et al. Cellular telephone use and the risk of brain tumors: update of the UK million women study. J Natl Cancer Inst. 2022 May 9;114(5):704-11.[Abstract][Full Text]
17. Ostrom QT, Bauchet L, Davis FG, et al. The epidemiology of glioma in adults: a "state of the science" review. Neuro Oncol. 2014 Jul;16(7):896-913.[Abstract][Full Text]
18. Turner MC. Epidemiology: allergy history, IgE, and cancer. Cancer Immunol Immunother. 2012 Sep;61(9):1493-510.[Abstract]
19. Wrensch M, Minn Y, Chew T, et al. Epidemiology of primary brain tumors: current concepts and review of the literature. Neuro Oncol. 2002 Oct;4(4):278-99.[Abstract][Full Text]
20. McKinnon C, Nandhabalan M, Murray SA, et al. Glioblastoma: clinical presentation, diagnosis, and management. BMJ. 2021 Jul 14;374:n1560.[Abstract]
21. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: central nervous system cancers [internet publication].[Full Text]
22. Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021 Mar;18(3):170-86.[Abstract][Full Text]
23. Gritsch S, Batchelor TT, Gonzalez Castro LN. Diagnostic, therapeutic, and prognostic implications of the 2021 World Health Organization classification of tumors of the central nervous system. Cancer. 2022 Jan 1;128(1):47-58.[Abstract][Full Text]
24. Rudà R, Capper D, Waldman AD, et al. EANO - EURACAN - SNO guidelines on circumscribed astrocytic gliomas, glioneuronal, and neuronal tumors. Neuro Oncol. 2022 Dec 1;24(12):2015-34.[Abstract][Full Text]
25. Gonzalez Castro LN, Milligan TA. Seizures in patients with cancer. Cancer. 2020 Apr 1;126(7):1379-89.[Abstract][Full Text]
26. Johnson DR, Glenn CA, Javan R, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of imaging in the management of progressive glioblastoma in adults. J Neurooncol. 2022 Jun;158(2):139-65.[Abstract]
27. Wen PY, Weller M, Lee EQ, et al. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions. Neuro Oncol. 2020 Aug 17;22(8):1073-113.[Abstract][Full Text]
28. McAleenan A, Jones HE, Kernohan A, et al. Diagnostic test accuracy and cost-effectiveness of tests for codeletion of chromosomal arms 1p and 19q in people with glioma. Cochrane Database Syst Rev. 2022 Mar 2;3(3):CD013387.[Abstract][Full Text]
29. Snyder H, Robinson K, Shah D, et al. Signs and symptoms of patients with brain tumors presenting to the emergency department. J Emerg Med. 1993 May-Jun;11(3):253-8.[Abstract]
30. Alentorn A, Hoang-Xuan K, Mikkelsen T. Presenting signs and symptoms in brain tumors. Handb Clin Neurol. 2016;134:19-26.[Abstract]
31. DeAngelis LM. Brain tumors. N Engl J Med. 2001 Jan 11;344(2):114-23.[Abstract]
32. Whittle IR, Pringle AM, Taylor R. Effects of resective surgery for left-sided intracranial tumors on language function: a prospective study. Lancet. 1998 Apr 4;351(9108):1014-8.[Abstract]
33. Wu JS, Zhou LF, Tang WJ, et al. Clinical evaluation and follow-up outcome of diffusion tensor imaging-based functional neuronavigation: a prospective, controlled study in patients with gliomas involving pyramidal tracts. Neurosurgery. 2007 Nov;61(5):935-48.[Abstract]
34. Kickingereder P, Andronesi OC. Radiomics, metabolic, and molecular MRI for brain tumors. Semin Neurol. 2018 Feb;38(1):32-40.[Abstract]
35. Grimstad IA, Hirschberg H, Rootwelt K. 99m Tc-hexamethyl propyleneamine oxime leukocyte scintigraphy and C-reactive protein levels in the differential diagnosis of brain abscess. J Neurosurg. 1992 Nov;77(5):732-6.[Abstract]
36. Berkman JM, Nakhate V, Gonzalez Castro LN. Glioblastoma in patients with multiple sclerosis. Neurohospitalist. 2022 Oct;12(4):607-16.[Abstract]
37. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: pediatric central nervous system cancers [internet publication].[Full Text]
38. Stupp R, Brada M, van den Bent MJ, et al. High-grade glioma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep;25(suppl 3):iii93-101.[Abstract]
39. Mohile NA, Messersmith H, Gatson NT, et al. Therapy for diffuse astrocytic and oligodendroglial tumors in adults: ASCO-SNO guideline. J Clin Oncol. 2022 Feb 1;40(4):403-26.[Abstract][Full Text]
40. Walbert T, Harrison RA, Schiff D, et al. SNO and EANO practice guideline update: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Neuro Oncol. 2021 Nov 2;23(11):1835-44.[Abstract][Full Text]
41. Roth P, Pace A, Le Rhun E, et al. Neurological and vascular complications of primary and secondary brain tumours: EANO-ESMO clinical practice guidelines for prophylaxis, diagnosis, treatment and follow-up. Ann Oncol. 2021 Feb;32(2):171-82.[Abstract][Full Text]
42. Youssef G, Wen PY. Medical and neurological management of brain tumor complications. Curr Neurol Neurosci Rep. 2021 Sep 20;21(10):53.[Abstract]
43. Liau LM. Guidelines for newly diagnosed glioblastoma. J Neurooncol. 2008 Sept;89(3).[Full Text]
44. Zhang L, Li D, Xiao D, et al. Improving brain health by identifying structure-function relations in patients with neurosurgical disorders. BMJ. 2020 Oct 9;371:m3690.[Abstract][Full Text]
45. Fountain DM, Bryant A, Barone DG, et al. Intraoperative imaging technology to maximise extent of resection for glioma: a network meta-analysis. Cochrane Database Syst Rev. 2021 Jan 4;1(1):CD013630.[Abstract][Full Text]
46. Dhawan S, Patil CG, Chen C, et al. Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas. Cochrane Database Syst Rev. 2020 Jan 20;1(1):CD009229.[Abstract][Full Text]
47. Halasz LM, Attia A, Bradfield L, et al. Radiation therapy for IDH-mutant grade 2 and grade 3 diffuse glioma: an ASTRO clinical practice guideline. Pract Radiat Oncol. 2022 Sep-Oct;12(5):370-86.[Abstract][Full Text]
48. Bell EH, Zhang P, Shaw EG, et al. Comprehensive genomic analysis in NRG oncology/RTOG 9802: a phase III trial of radiation versus radiation plus procarbazine, lomustine (CCNU), and vincristine in high-risk low-grade glioma. J Clin Oncol. 2020 Oct 10;38(29):3407-17.[Abstract][Full Text]
49. Lawrie TA, Gillespie D, Dowswell T, et al. Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma. Cochrane Database Syst Rev. 2019 Aug 5;8(8):CD013047.[Abstract][Full Text]
50. Yu Y, Villanueva-Meyer J, Grimmer MR, et al. Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas. Neuro Oncol. 2021 Nov 2;23(11):1872-84.[Abstract][Full Text]
51. Buckner JC, Shaw EG, Pugh SL, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med. 2016 Apr 7;374(14):1344-55.[Abstract][Full Text]
52. van den Bent MJ, Tesileanu CMS, Wick W, et al. Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2021 Jun;22(6):813-23.[Abstract][Full Text]
53. Khan L, Soliman H, Sahgal A, et al. External beam radiation dose escalation for high grade glioma. Cochrane Database Syst Rev. 2020 May 21;5(5):CD011475.[Abstract][Full Text]
54. 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. JAMA. 2017 Dec 19;318(23):2306-16.[Abstract][Full Text]
55. Hart MG, Grant R, Garside R, et al. Chemotherapy wafers for high grade glioma. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007294.[Abstract][Full Text]
56. Patrick HH, Sherman JH, Elder JB, et al. Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of cytoreductive surgery in the management of progressive glioblastoma in adults. J Neurooncol. 2022 Jun;158(2):167-77.[Abstract]
57. American Association of Neurological Surgeons; Congress of Neurological Surgeons. Updated AANS/CNS guidelines for progressive glioblastoma patients. Jun 2022 [internet publication].[Full Text]
58. Goodman AL, Velázquez Vega JE, Glenn C, et al. Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of neuropathology in the management of progressive glioblastoma in adults. J Neurooncol. 2022 Jun;158(2):179-224.[Abstract]
59. McBain C, Lawrie TA, Rogozińska E, et al. Treatment options for progression or recurrence of glioblastoma: a network meta-analysis. Cochrane Database Syst Rev. 2021 May 4;5(1):CD013579.[Abstract][Full Text]
60. Ziu M, Goyal S, Olson JJ. Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of radiation therapy in the management of progressive and recurrent glioblastoma in adults. J Neurooncol. 2022 Jun;158(2):255-64.[Abstract]
61. Germano IM, Ziu M, Wen P, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults. J Neurooncol. 2022 Jun;158(2):225-53.[Abstract]
62. Wang H, Guo J, Wang T, et al. Efficacy and safety of bevacizumab in the treatment of adult gliomas: a systematic review and meta-analysis. BMJ Open. 2021 Dec 2;11(12):e048975.[Abstract][Full Text]
63. Winograd E, Germano I, Wen P, et al. Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma. J Neurooncol. 2022 Jun;158(2):265-321.[Abstract][Full Text]
64. Taylor LP, Besbris JM, Graf WD, et al. Clinical guidance in neuropalliative care: an AAN position statement. Neurology. 2022 Mar 8;98(10):409-16.[Abstract][Full Text]
65. Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al. Vorasidenib in IDH1- or IDH2-mutant low-grade glioma. N Engl J Med. 2023 Aug 17;389(7):589-601.[Abstract]
66. Lombardi G, De Salvo GL, Brandes AA, et al. Regorafenib compared with lomustine in patients with relapsed glioblastoma (REGOMA): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol. 2019 Jan;20(1):110-9.[Abstract]
67. Juric V, Murphy B. Cyclin-dependent kinase inhibitors in brain cancer: current state and future directions. Cancer Drug Resist. 2020;3(1):48-62.[Abstract][Full Text]
68. Bota DA, Mason W, Kesari S, et al. Marizomib alone or in combination with bevacizumab in patients with recurrent glioblastoma: phase I/II clinical trial data. Neurooncol Adv. 2021 Jan-Dec;3(1):vdab142.[Abstract][Full Text]
69. ClinicalTrials.gov. Stage 1: marizomib + bevacizumab in WHO Gr IV GBM; Stage 2: marizomib alone; Stage 3: combination of marizomib and bevacizumab. Jun 2022 [internet publication].[Full Text]
70. Sim HW, Galanis E, Khasraw M. PARP inhibitors in glioma: a review of therapeutic opportunities. Cancers (Basel). 2022 Feb 16;14(4):1003.[Abstract][Full Text]
71. Reardon DA, Brandes AA, Omuro A, et al. Effect of nivolumab vs bevacizumab in patients with recurrent glioblastoma: the CheckMate 143 phase 3 randomized clinical trial. JAMA Oncol. 2020 Jul 1;6(7):1003-10.[Abstract][Full Text]
72. Lee A, Arasaratnam M, Chan DLH, et al. Anti-epidermal growth factor receptor therapy for glioblastoma in adults. Cochrane Database Syst Rev. 2020 May 12;5(5):CD013238.[Abstract][Full Text]
73. Youssef G, Dietrich J. Ipilimumab: an investigational immunotherapy for glioblastoma. Expert Opin Investig Drugs. 2020 Nov;29(11):1187-93.[Abstract]
74. Cloughesy TF, Petrecca K, Walbert T, et al. Effect of vocimagene amiretrorepvec in combination with flucytosine vs standard of care on survival following tumor resection in patients with recurrent high-grade glioma: a randomized clinical trial. JAMA Oncol. 2020 Dec 1;6(12):1939-46.[Abstract][Full Text]
75. Liau LM, Ashkan K, Brem S, et al. Association of autologous tumor lysate-loaded dendritic cell vaccination with extension of survival among patients with newly diagnosed and recurrent glioblastoma: a phase 3 prospective externally controlled cohort trial. JAMA Oncol. 2023 Jan 1;9(1):112-21.[Abstract][Full Text]
76. Platten M, Bunse L, Wick A, et al. A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature. 2021 Apr;592(7854):463-8.[Abstract][Full Text]
77. Maggs L, Cattaneo G, Dal AE, et al. CAR T cell-based immunotherapy for the treatment of glioblastoma. Front Neurosci. 2021 May 25;15:662064.[Abstract][Full Text]
78. Majzner RG, Ramakrishna S, Yeom KW, et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature. 2022 Mar;603(7903):934-41.[Abstract][Full Text]
79. Kristeleit R, Evans J, Molife LR, et al. Phase 1/2a trial of intravenous BAL101553, a novel controller of the spindle assembly checkpoint, in advanced solid tumours. Br J Cancer. 2020 Oct;123(9):1360-9.[Abstract][Full Text]
80. Ha W, Sevim-Nalkiran H, Zaman AM, et al. Ibudilast sensitizes glioblastoma to temozolomide by targeting macrophage migration Inhibitory Factor (MIF). Sci Rep. 2019 Feb 27;9(1):2905.[Abstract][Full Text]
81. Dhillon S. Decitabine/cedazuridine: first approval. Drugs. 2020 Sep;80(13):1373-8.[Abstract][Full Text]
82. Dhillon S. Correction to: Decitabine/cedazuridine: first approval. Drugs. 2021 Jan;81(1):179.[Abstract][Full Text]
83. Pace A, Dirven L, Koekkoek JAF, et al. European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma. Lancet Oncol. 2017 Jun;18(6):e330-40.[Abstract]
84. Johnson DR, Brown PD, Galanis E, et al. Pilocytic astrocytoma survival in adults: analysis of the surveillance, epidemiology, and end results program of the National Cancer Institute. J Neurooncol. 2012 May;108(1):187-93.[Abstract]
85. Tabash MA. Characteristics, survival and incidence rates and trends of pilocytic astrocytoma in children in the United States; SEER-based analysis. J Neurol Sci. 2019 May 15;400:148-52.[Abstract]
86. von Deimling A, Ono T, Shirahata M, et al. Grading of diffuse astrocytic gliomas: a review of studies before and after the advent of IDH testing. Semin Neurol. 2018 Feb;38(1):19-23.[Abstract]
87. Hamilton MG, Hull RD, Pineo GH. Venous thromboembolism in neurosurgery and neurology patients: a review. Neurosurgery. 1994 Feb;34(2):280-96.[Abstract]
88. Beevers Z, Hussain S, Boele FW, et al. Pharmacological treatment of depression in people with a primary brain tumour. Cochrane Database Syst Rev. 2020 Jul 17;7(7):CD006932.[Abstract][Full Text]
89. Kirkman MA, Day J, Gehring K, et al. Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation. Cochrane Database Syst Rev. 2022 Nov 25;11(11):CD011335.[Abstract][Full Text]
Key Articles
Referenced Articles
Guidelines
Diagnostic
Summary
Includes recommendations on the diagnosis of pediatric diffuse high-grade gliomas.Published by
National Comprehensive Cancer Network
Published
2023
Summary
Includes information on the diagnosis of astrocytic brain tumors.Published by
National Comprehensive Cancer Network
Published
2023
Summary
Evidence-based guideline including recommendations on the diagnosis of circumscribed astrocytic gliomas in adults.Published by
European Association of Neuro-Oncology; EURACAN; Society for Neuro-Oncology
Published
2022
Summary
Evidence-based guideline including recommendations on the diagnosis of diffuse gliomas in adults.Published by
European Association of Neuro-Oncology
Published
2021
Treatment
Summary
Provides a comprehensive overview of the management of pediatric diffuse high-grade gliomas.Published by
National Comprehensive Cancer Network
Published
2023
Summary
Provides a comprehensive overview of the management of adult glioma.Published by
National Comprehensive Cancer Network
Published
2023
Summary
Evidence- and consensus-based recommendations on the treatment of diffuse astrocytic and oligodendroglial tumors in adults.Published by
American Society of Clinical Oncology; Society for Neuro-Oncology
Published
2022
Summary
Guidelines for the management of recurrent glioblastoma.Published by
American Association of Neurological Surgeons; Congress of Neurological Surgeons
Published
2022
Summary
Evidence-based recommendations for management of isocitrate dehydrogenase (IDH)-mutant grade 2 and grade 3 diffuse glioma in adults.Published by
American Society for Radiation Oncology
Published
2022
Summary
Guidance on neuropalliative care focusing on specific needs of patients with neurologic illness and their families, with the aim of helping patients to have the best quality of life for as long as possible.Published by
American Academy of Neurology
Published
2022
Summary
Evidence-based guideline including recommendations on management of circumscribed astrocytic gliomas in adults.Published by
European Association of Neuro-Oncology; EURACAN; Society for Neuro-Oncology
Published
2022
Summary
Evidence-based guideline on the use of anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.Published by
Society for Neuro-Oncology; European Association of Neuro-Oncology
Published
2021
Summary
Evidence-based guideline including recommendations on treatment and follow-up for adult patients with diffuse gliomas.Published by
European Association of Neuro-Oncology
Published
2021
Summary
Evidence-based guideline on the use of anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.Published by
European Association of Neuro-Oncology; European Society for Medical Oncology
Published
2020
Summary
Recommendations for the palliative care of adult patients with glioma, with the aim of reducing symptom burden and improving quality of life of patients and caregivers.Published by
European Association for Neuro-Oncology
Published
2017
Credits
Patient Instructions
- Tailor communication of the diagnosis to the needs of the patient and their family.
- Provide information on both the survival benefits of treatments and the potential impact of adverse effects of treatments on quality of life.[20]
- Start discussions about advance care planning with the patient and family/caregivers as early as possible, before the patient loses cognitive capacity. This must be done in a sensitive manner.[64]
- Provide support and information (e.g., regarding coping with potential behavioral and communication problems in the future) to the patient's family and other caregivers.[64]
- Advise patients to contact their specialist if they have any change in clinical/neurologic status, such as appearance of headache or any new focal neurologic symptoms.
- Advise patients on chemotherapy to consult a healthcare professional if they have any fever, symptoms of infection, or bleeding tendency.