Approach

The treatment of gliomas depends on the tumor type, grade, location, and molecular profile.[20][21][22][24][27][39][40]

If the tumor is deemed accessible, maximal safe surgical resection is performed independent of histology, and samples are sent for histologic confirmation and analysis of molecular markers before initiating further management. Circumscribed astrocytomas (pilocytic/pilomyxoid astrocytoma, subependymal giant cell astrocytoma, and pleomorphic xanthoastrocytoma) may be cured by surgery alone.[24]

If the tumor cannot be safely resected, a biopsy is indicated to enable diagnosis and appropriate management.

Emergency management

If a diagnosis of glioma is suspected based on clinical and radiographic findings, the patient should initially be referred to neurosurgery for resection or biopsy. Certain presentations require emergency treatment.

Seizures[27][41][42]

  • 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.[41]  

Vasogenic edema and intracranial hypertension[27][42][43]

  • 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

Maximal safe resection is the mainstay of treatment. If this is achieved, cure can be obtained and surveillance is recommended.[21][24] For a surgically inaccessible lesion in asymptomatic patients, monitoring with brain magnetic resonance imaging (MRI) at least every 6 months is recommended.[21] For symptomatic patients in whom resection is precluded by location, treatment modalities include chemotherapy, targeted therapies, and radiation therapy. Guidelines favor chemotherapy or targeted therapies, if suitable options are available, in order to minimize the long-term effects of radiation.[21][24]

Pilocytic/pilomyxoid astrocytoma, World Health Organization (WHO) grade 1

Maximal safe resection is carried out if possible. If the lesion is inaccessible and the patient is asymptomatic, observation is recommended. In the brainstem, particularly at the tectal plate of the midbrain, obstructive hydrocephalus can be addressed with a cerebrospinal fluid diversion procedure. If there is progression, or symptoms other than cerebrospinal fluid obstruction develop, treatments such as targeted systemic therapy (e.g., BRAF and/or mitogen-activated protein kinase kinase [MEK] inhibitors if targetable alterations are present) and radiation therapy are appropriate.[21][24]

Subependymal giant cell astrocytoma, WHO grade 1

Subependymal giant cell astrocytomas are only found in patients with tuberous sclerosis complex. If the patient is asymptomatic, observation is advised.[6][21] Subependymal giant cell astrocytomas are typically surgically accessible. mTOR (mammalian target of rapamycin) 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.

Pleomorphic xanthoastrocytoma, WHO grade 2

These tumors are almost always accessible. For tumors with a high mitotic rate, or if initial resection was subtotal, the recommended treatment is targeted therapy, radiation therapy, or radiosurgery.[21][24]​ 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]

Circumscribed gliomas: recurrent

If there is recurrence following initial therapy, maximal safe resection should be repeated if feasible. If complete resection is not possible, radiation therapy is considered standard treatment.[24] Radiosurgery may be considered if tumor size and location are appropriate.[24] Targeted therapies (e.g., BRAF and/or MEK inhibitors) can be considered if targetable mutations have been identified in tissue from initial resection.[24] 

Diffuse infiltrating gliomas: newly diagnosed

Tumor types are diffuse astrocytoma, isocitrate dehydrogenase (IDH)-mutant (grades 2-4), oligodendroglioma, IDH-mutant, 1p/19q co-deleted, and glioblastoma, IDH-wildtype (grade 4).[1] Treatment depends on tumor type and grade.[20][21][22][27][44]

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.[45] Several surgical adjuncts may be used to maximize resection while minimizing risk of postoperative disability.[20][21][22][46]

If safe resection is not possible (e.g., due to tumor location or if the patient is not a candidate for surgery due to comorbidities), a stereotactic biopsy should be performed.[22]

Chemotherapy should be offered as indicated. When available, 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.[21][22][27]​​ See Emerging treatments.

Grade 2 tumors

After surgery, further treatment may be deferred in some low-risk patients (i.e., younger than 40 years with complete tumor 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), and all patients in whom surgery is not feasible, standard care is a combination of radiation therapy and chemotherapy.[21][48][49]​ It is important that the long-term adverse effects of radiation therapy (e.g., on neurocognition) and chemotherapy are taken into account.[7][48][50][51]

The recommended chemotherapy regimen is PCV (procarbazine, lomustine, and 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]

Grade 3 and 4 tumors

In addition to surgery (or without surgery if the tumor is inaccessible), standard of care involves radiation therapy and chemotherapy.[20][21][22][27][40][48]

  • For diffuse astrocytoma, IDH-mutant, grade 3, the recommended treatment following maximal safe resection is radiation followed by 12 cycles of adjuvant temozolomide.[53]

  • For oligodendroglioma, IDH-mutant, 1p/19q codeleted, grade 3, radiation followed by PCV chemotherapy is recommended. Temozolomide is an alternative.[40]

  • 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.[40]

Older patients and/or those with a poor performance status may be offered hypofractionated radiation therapy (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 tumors are thought to derive greater benefit from treatment with temozolomide.[20][21][22]​ 

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

If gross total resection is possible and the surgical cavity is not in contact with the ventricular system, there is the option of placing biodegradable carmustine wafers at the time of surgery. However, evidence for effectiveness is equivocal, it is very hard to assess progression on imaging, and patients with carmustine wafers are often ineligible for clinical trials at progression.[21][22][56]​ 

Diffuse midline glioma, H3 K27M-altered

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.

When clinical trials or investigational therapies are not available, treatment is with radiation therapy and chemotherapy, as for other grade 4 gliomas.[21][22][38][40]

Diffuse infiltrating gliomas: progressive disease

With radiographic evidence of disease progression, standard therapies should be considered, including repeat maximal safe resection if possible, for tumor debulking and characterizing new genomic drivers of progression in the tumor.[57][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 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][40][50][60][61]

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 (CCNU) and temozolomide. Platinum-based regimens are not recommended.[21][22][27][60]​​[62][63]

Targeted therapies (e.g., BRAF/MEK inhibitors) can be considered if targetable alterations are identified after molecular characterization of tumor 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][60]​​​​​​[63][64]

Advanced care planning and palliative care

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][65]

Discussions about advance care planning with the patient and their family should start soon after diagnosis, before the patient loses cognitive capacity. Early neuropalliative care consultation is recommended in order to maximize symptom management.[27][65]

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