Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

elevated intracranial pressure or vasogenic oedema

1st line – dexamethasone ± mannitol

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INITIAL
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elevated intracranial pressure or vasogenic oedema
1st line – 

dexamethasone ± mannitol

If a patient has imaging evidence of vasogenic oedema leading to neurological 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 papilloedema.

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.

Primary options

dexamethasone sodium phosphate: children: 1-2 mg/kg intravenously initially, followed by 1 to 1.5 mg/kg every 4-6 hours until symptoms subside, then gradually taper dose (switch to oral dose when possible), maximum 16 mg/day; adults: 10 mg intravenously initially, followed by 4 mg every 6 hours until symptoms subside, then gradually taper dose (switch to oral dose when possible)

OR

dexamethasone sodium phosphate: children: 1-2 mg/kg intravenously initially, followed by 1 to 1.5 mg/kg every 4-6 hours until symptoms subside, then gradually taper dose (switch to oral dose when possible), maximum 16 mg/day; adults: 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: children and adults: 0.25 g/kg intravenously initially, may repeat every 6-8 hours as needed

Consider – temporary hyperventilation

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INITIAL
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elevated intracranial pressure or vasogenic oedema
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comatose and intubated
Consider – 

temporary hyperventilation

Additional treatment recommended for SOME patients in selected patient group

If a patient with severe intracranial hypertension is comatose and intubated, temporary hyperventilation may be necessary.

Plus – anticonvulsant

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INITIAL
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elevated intracranial pressure or vasogenic oedema
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with seizures
Plus – 

anticonvulsant

Treatment recommended for ALL patients in selected patient group

Patients presenting with tumour-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.[41]

Primary options

levetiracetam: children and adults: consult specialist for guidance on dose

OR

lacosamide: children and adults: consult specialist for guidance on dose

OR

lamotrigine: children and adults: consult specialist for guidance on dose

ACUTE

circumscribed glioma: pilocytic/pilomyxoid astrocytoma (World Health Organization [WHO] grade 1)

1st line – maximal safe resection

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ACUTE
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circumscribed glioma: pilocytic/pilomyxoid astrocytoma (World Health Organization [WHO] grade 1)
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accessible
1st line – 

maximal safe resection

Maximal safe resection is the mainstay of treatment. If this is achieved, cure can be obtained and surveillance is recommended.[21][24]​​​

Consider – systemic therapy and/or radiotherapy

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ACUTE
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circumscribed glioma: pilocytic/pilomyxoid astrocytoma (World Health Organization [WHO] grade 1)
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accessible
Consider – 

systemic therapy and/or radiotherapy

Additional treatment recommended for SOME patients in selected patient group

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 radiotherapy. Recent guidelines favour chemotherapy or targeted therapies, if suitable options are available, in order to minimise the long-term effects of radiation.[21][24][28]​​​ See local specialist protocol for choice of regimen and dosing guidelines.

1st line – observation

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ACUTE
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circumscribed glioma: pilocytic/pilomyxoid astrocytoma (World Health Organization [WHO] grade 1)
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inaccessible without symptoms
1st line – 

observation

If the lesion is inaccessible and the patient is asymptomatic, observation with brain magnetic resonance imaging at least every 6 months is recommended.[21][24]​​​​ 

1st line – systemic therapy and/or radiotherapy ± CSF diversion procedure

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ACUTE
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circumscribed glioma: pilocytic/pilomyxoid astrocytoma (World Health Organization [WHO] grade 1)
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inaccessible with symptoms
1st line – 

systemic therapy and/or radiotherapy ± CSF diversion procedure

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 radiotherapy. Recent guidelines favour chemotherapy or targeted therapies, if suitable options are available, in order to minimise the long-term effects of radiation.[21][24][28]​​ See local specialist protocol for choice of regimen and dosing guidelines.

circumscribed glioma: subependymal giant cell astrocytoma (WHO grade 1)

1st line – observation

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ACUTE
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circumscribed glioma: subependymal giant cell astrocytoma (WHO grade 1)
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without symptoms
1st line – 

observation

Subependymal giant cell astrocytomas (SEGAs) are only found in patients with tuberous sclerosis complex. If the patient is asymptomatic, observation is advised.[6][21]

See Tuberous sclerosis complex.

1st line – maximal safe resection and/or mTOR inhibitor

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ACUTE
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circumscribed glioma: subependymal giant cell astrocytoma (WHO grade 1)
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with symptoms
1st line – 

maximal safe resection and/or mTOR inhibitor

Subependymal giant cell astrocytomas (SEGAs) are typically surgically accessible. Mammalian target of rapamycin (mTOR) inhibitors such everolimus and sirolimus may be used to induce tumour 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)

1st line – maximal safe resection or observation

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ACUTE
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circumscribed glioma: pleomorphic xanthoastrocytoma (WHO grade 2)
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without symptoms
1st line – 

maximal safe resection or observation

These tumours are almost always accessible. If the patient is asymptomatic, possible options include maximal safe resection or close observation.

If maximal safe resection is achieved, cure can be obtained and surveillance is recommended.[21][24]​​​​

1st line – maximal safe resection

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ACUTE
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circumscribed glioma: pleomorphic xanthoastrocytoma (WHO grade 2)
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with symptoms
1st line – 

maximal safe resection

These tumours are almost always accessible. Maximal safe resection is the mainstay of treatment. If this is achieved, cure can be obtained and surveillance is recommended.[21][24]​​​​

Consider – intraoperative electrocorticography

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ACUTE
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circumscribed glioma: pleomorphic xanthoastrocytoma (WHO grade 2)
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with symptoms
Consider – 

intraoperative electrocorticography

Additional treatment recommended for SOME patients in selected patient group

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]

Consider – targeted therapy or radiotherapy or radiosurgery

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ACUTE
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circumscribed glioma: pleomorphic xanthoastrocytoma (WHO grade 2)
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with symptoms
Consider – 

targeted therapy or radiotherapy or radiosurgery

Additional treatment recommended for SOME patients in selected patient group

If resection is partial in symptomatic patients, additional treatment modalities include targeted therapies, radiotherapy, or radiosurgery. Recent guidelines favour targeted therapies, if suitable options are available, in order to minimise the long-term effects of radiation.[21][24][28]​​​ See local specialist protocol for choice of regimen and dosing guidelines.

diffuse infiltrating glioma: grade 2

1st line – maximal safe resection

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ACUTE
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diffuse infiltrating glioma: grade 2
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accessible
1st line – 

maximal safe resection

Maximal safe resection is the primary treatment if the tumour is surgically accessible. However, preventing new permanent neurological 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.[45]​ Several surgical adjuncts may be used to maximise resection while minimising risk of postoperative disability.[20][21][22]​​​​​​​​[28][46]

If the patient is not a candidate for surgery due to comorbidities, a stereotactic biopsy should be performed.[22]

Consider – radiotherapy + chemotherapy

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ACUTE
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diffuse infiltrating glioma: grade 2
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accessible
Consider – 

radiotherapy + chemotherapy

Additional treatment recommended for SOME patients in selected patient group

After surgery, further treatment may be deferred in some low-risk patients (i.e., younger than 40 years with complete tumour resection as indicated by T2-fluid-attenuated inversion recovery [FLAIR] hyperintense signal) until there are signs of disease progression.[21][22][40][47][48]

For high-risk patients after surgery (i.e., ages 40 years or older, or subtotal resection), standard care is a combination of radiotherapy and chemotherapy.[21][48][49]​​ It is important that the long-term adverse effects of radiotherapy (e.g., on neurocognition) and chemotherapy are taken into account.[7][48][50][51]​​

The recommended chemotherapy regimen is PCV (procarbazine, lomustine, vincristine).[21][22][40][52]​​ Temozolomide may be used as an alternative, given data on effectiveness in high-grade gliomas and a better side-effect profile.[7] See local specialist protocol for dosing guidelines.

When available, clinical trials or investigational therapies may be considered as the initial therapeutic option, as none of the available therapies are curative.[21][22][27]​​​​​ See Emerging treatments.

1st line – stereotactic biopsy + radiotherapy + chemotherapy

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ACUTE
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diffuse infiltrating glioma: grade 2
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inaccessible
1st line – 

stereotactic biopsy + radiotherapy + chemotherapy

If safe resection is not possible due to tumour location, a stereotactic biopsy should be performed.[22]

In patients in whom surgery is not feasible, standard care is a combination of radiotherapy and chemotherapy.[21][48][49]​​​ It is important that the long-term adverse effects of radiotherapy (e.g., on neurocognition) and chemotherapy are taken into account.[7][48][50][51]​​

The recommended chemotherapy regimen is PCV (procarbazine, lomustine, vincristine).[21][22][40][52]​​​ Temozolomide may be used as an alternative, given data on effectiveness in high-grade gliomas and a better side-effect profile.[7] See local specialist protocol for dosing guidelines.

When available, clinical trials or investigational therapies may be considered as the initial therapeutic option, as none of the available therapies are curative.[21][22][27]​​ See Emerging treatments.

diffuse infiltrating glioma: grades 3 and 4

1st line – maximal safe resection

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ACUTE
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diffuse infiltrating glioma: grades 3 and 4
|
accessible
1st line – 

maximal safe resection

Maximal safe resection is the primary treatment if the tumour is surgically accessible. However, preventing new permanent neurological 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.[45]​ Several surgical adjuncts may be used to maximise resection while minimising risk of postoperative disability.[20][21][22]​​​​​​​​​​[28][46]

If the patient is not a candidate for surgery due to comorbidities, a stereotactic biopsy should be performed.[22]

Plus – radiotherapy + chemotherapy

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ACUTE
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diffuse infiltrating glioma: grades 3 and 4
|
accessible
Plus – 

radiotherapy + chemotherapy

Treatment recommended for ALL patients in selected patient group

In addition to surgery, standard of care involves radiotherapy and chemotherapy.[20][21]​​​​​[22][27][28][40][48]​​​​​​​

When available, clinical trials or investigational therapies should be considered as the initial therapeutic option, as none of the available therapies are curative.[21][22][27]​​ See Emerging treatments.

Diffuse astrocytoma, isocitrate dehydrogenase (IDH)-mutant, grade 3: recommended treatment following maximal safe resection is radiation followed by 12 cycles of adjuvant temozolomide.[53]​ 

Oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 3: radiation followed by PCV (procarbazine, lomustine, vincristine) chemotherapy is recommended. Temozolomide is an alternative.[40]

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.[40]

Older patients and/or those with a poor performance status may be offered hypofractionated radiotherapy (alone or with temozolomide), temozolomide alone, or best supportive care.[20][21][40][54]​​​​

In patients with IDH-wildtype glioblastoma, MGMT promoter methylation status is a predictive biomarker of benefit from alkylating chemotherapy: patients with MGMT promoter methylated tumours are thought to derive greater benefit from treatment with temozolomide.[20][21][22]​​​​​ 

See local specialist protocol for choice of regimen and dosing guidelines.

Consider – alternating electric field therapy

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ACUTE
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diffuse infiltrating glioma: grades 3 and 4
|
accessible
Consider – 

alternating electric field therapy

Additional treatment recommended for SOME patients in selected patient group

Alternating electric field therapy may be considered in the adjuvant chemotherapy phase of treatment for grade 4 tumours.[21][40][55]

Plus – palliative care

Back
ACUTE
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diffuse infiltrating glioma: grades 3 and 4
|
accessible
Plus – 

palliative care

Treatment recommended for ALL patients in selected patient group

Early neuropalliative care consultation is recommended in order to maximise symptom management.[27][66]

For patients with poor prognosis and those who do not want to undergo further treatment, active palliative care may be the most suitable approach.[20][28][66]​​

1st line – stereotactic biopsy + radiotherapy + chemotherapy

Back
ACUTE
|
diffuse infiltrating glioma: grades 3 and 4
|
inaccessible
1st line – 

stereotactic biopsy + radiotherapy + chemotherapy

If safe resection is not possible due to tumour location, a stereotactic biopsy should be performed.[22]

Standard of care involves radiotherapy and chemotherapy.[20][21][22][27][28][40][48]​​

When available, clinical trials or investigational therapies may be considered as the initial therapeutic option, as none of the available therapies are curative.[21][22][27]​​ See Emerging treatments.

Diffuse astrocytoma, isocitrate dehydrogenase (IDH)-mutant, grade 3: recommended treatment is radiation followed by 12 cycles of adjuvant temozolomide.[53]

Oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 3: radiation followed by PCV (procarbazine, lomustine, vincristine) chemotherapy is recommended. Temozolomide is an alternative.[40]

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.[40]

Older patients and/or those with a poor performance status may be offered hypofractionated radiotherapy (alone or with temozolomide), temozolomide alone, or best supportive care.[20][21][40][54]

In patients with IDH-wildtype glioblastoma, MGMT promoter methylation status is a predictive biomarker of benefit from alkylating chemotherapy: patients with MGMT promoter methylated tumours are thought to derive greater benefit from treatment with temozolomide.[20][21][22]​​ 

See local specialist protocol for choice of regimen and dosing guidelines.

Consider – alternating electric field therapy

Back
ACUTE
|
diffuse infiltrating glioma: grades 3 and 4
|
inaccessible
Consider – 

alternating electric field therapy

Additional treatment recommended for SOME patients in selected patient group

Alternating electric field therapy may be considered in the adjuvant chemotherapy phase of treatment for grade 4 tumours.[21][40][55]

Plus – palliative care

Back
ACUTE
|
diffuse infiltrating glioma: grades 3 and 4
|
inaccessible
Plus – 

palliative care

Treatment recommended for ALL patients in selected patient group

Early neuropalliative care consultation is recommended in order to maximise symptom management.[27][66]

For patients with poor prognosis and those who do not want to undergo further treatment, active palliative care may be the most suitable approach.[20][28][66]​​

diffuse midline glioma, H3 K27M-altered

1st line – stereotactic biopsy + radiotherapy + chemotherapy

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ACUTE
|
diffuse midline glioma, H3 K27M-altered
1st line – 

stereotactic biopsy + radiotherapy + chemotherapy

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 tumour 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.

When clinical trials or investigational therapies are not available, treatment is with radiotherapy and chemotherapy, as for other grade 4 gliomas.[22][57][40]​​​ 

See local specialist protocol for choice of regimen and dosing guidelines.

Plus – palliative care

Back
ACUTE
|
diffuse midline glioma, H3 K27M-altered
Plus – 

palliative care

Treatment recommended for ALL patients in selected patient group

Early neuropalliative care consultation is recommended in order to maximise symptom management.[27][66]

For patients with poor prognosis and those who do not want to undergo further treatment, active palliative care may be the most suitable approach.[20][28][66]​​

ONGOING

recurrent circumscribed glioma

1st line – repeat maximal safe resection if possible

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ONGOING
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recurrent circumscribed glioma
1st line – 

repeat maximal safe resection if possible

If there is recurrence following initial therapy, maximal safe resection should be repeated if feasible.[24]

2nd line – radiotherapy or radiosurgery

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ONGOING
|
recurrent circumscribed glioma
2nd line – 

radiotherapy or radiosurgery

If complete resection is not possible, radiotherapy is considered standard treatment.[24] Radiosurgery may be considered if tumour size and location are appropriate.[24]

Consider – targeted therapy

Back
ONGOING
|
recurrent circumscribed glioma
Consider – 

targeted therapy

Additional treatment recommended for SOME patients in selected patient group

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

1st line – repeat maximal safe resection + repeat radiotherapy and/or rechallenge with chemotherapy

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ONGOING
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progressive diffuse infiltrating glioma
1st line – 

repeat maximal safe resection + repeat radiotherapy and/or rechallenge with chemotherapy

If feasible, repeat maximal safe resection is used for tumour debulking and characterising new genomic drivers of progression in the tumour.[58][59]​​​

When available, clinical trials or investigational therapies should be considered as first-line treatment.[21][40]​ ​See Emerging treatments.

If no clinical trials or investigational therapies are available, repeat radiotherapy may be considered, depending on time since previous treatment and tumour location, but neurocognitive adverse effects and risks of radionecrosis must be taken into account.[20][21][22][27][40][50][61]​​​​[62]

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 tumour, performance status, and patient preference. Options include nitrosourea-based regimens and temozolomide. Platinum-based regimens are not recommended.[21][22][27][61]​​​[63][64]

Targeted therapies (e.g., BRAF/MEK inhibitors) can be considered if targetable alterations are identified after molecular characterisation of tumour samples.[21][22][27]

The monoclonal antibody bevacizumab may be considered for treatment of recurrent glioma, although evidence of effectiveness is limited.[21][22][27][40][61]​​[64][65]

See local specialist protocol for choice of regimen and dosing guidelines.

Plus – palliative care

Back
ONGOING
|
progressive diffuse infiltrating glioma
Plus – 

palliative care

Treatment recommended for ALL patients in selected patient group

Early neuropalliative care consultation is recommended in order to maximise symptom management.[27][66]

For patients with poor prognosis and those who do not want to undergo further treatment, active palliative care may be the most suitable approach.[20][28][66]​​

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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