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      Drugs & Diseases > Oncology

      Glioblastoma Guidelines

      Updated: Mar 07, 2023
      • Author: Jeffrey N Bruce, MD; Chief Editor: Herbert H Engelhard, III, MD, PhD, FACS, FAANS  more...
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      Guidelines

      Guidelines Summary

      The National Comprehensive Cancer Network (NCCN) has released guidelines on central nervous system (CNS) cancers that include recommendations for the diagnosis and treatment of glioblastomas. The goals of surgery are to obtain a diagnosis, alleviate symptoms of increased intracranial pressure or compression, increase survival, and decrease the need for corticosteroids. Adjuvant treatment options depend on the patient’s performance status (PS; quantified with the Karnofsky Performance Scale score [KPS]), age, and MGMT promoter methylation status. [22]  

      Category 1 recommendations for first-line treatment are as follows: [22]

      • In patients 70 years or younger with good PS (KPS ≥60), regardless of the tumor's  MGMT methylation status: Fractionated standard brain radiation therapy (RT) plus concurrent and adjuvant temozolomide (TMZ) with or without alternating electric field therapy
      • In patients 70 years or younger with poor PS (KPS < 60), regardless of the tumor’s  MGMT methylation status: Hypofractionated brain RT with or without concurrent or adjuvant TMZ, or TMZ alone, or palliative care alone
      • In patients older than 70 years with good PS (KPS ≥60) and  MGMT promoter–methylated tumors: Hypofractionated brain RT plus concurrent and adjuvant TMZ or standard brain RT plus concurrent and adjuvant TMZ and alternating electric field therapy
      • In patients older than 70 years with good PS (KPS ≥60) and  MGMT unmethylated or indeterminant tumors: Standard brain RT plus concurrent and adjuvant TMZ and alternating electric field therapy
      • In patients older than 70 years with poor PS (KPS < 60), regardless of the tumor’s  MGMT methylation status: Hypofractionated brain RT alone, or TMZ alone, or palliative care alone

      The American Society of Clinical Oncology (ASCO) and Society of Neuro-Oncology (SNO) have published treatment guidelines for diffuse astrocytic and oligodendroglial tumors in adults. [293] The guidelines contain the following recommendations for treatment of glioblastoma:

      • Offer concurrent TMZ and RT to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS World Health Organization (WHO) grade 4.

      • Offer six months of adjuvant TMZ to patients with newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4 who have received concurrent RT plus TMZ.

      • Alternating electric field therapy may be added to adjuvant TMZ in patients with newly diagnosed supratentorial glioblastoma, IDH-wildtype, CNS WHO grade 4 who have completed chemoradiation therapy.

      • Bevacizumab is not recommended for treatment of newly diagnosed glioblastoma, IDH-wildtype, CNS WHO grade 4.

      • In IDH-wildtype, CNS WHO grade 4 glioblastoma, when the expected survival benefits of a 6-week radiation course combined with TMZ may not outweigh the harms, hypofractionated RT combined with TMZ is a reasonable alternative.

      • In patients with IDH-wildtype, CNS WHO grade 4 glioblastoma with older age, poor performance status or with concerns about toxicity or prognosis, best supportive care alone, hypofractionated RT alone (for MGMT promoter unmethylated tumors), or TMZ alone (for MGMT promoter methylated tumors) are reasonable options.

      • No recommendation for or against any therapeutic strategy can be made for treatment of recurrent glioblastoma, IDH-wildtype, CNS WHO grade 4; these patients should be referred for participation in a clinical trial where possible.

      Progressive glioblastoma

      Congress of Neurological Surgeons guidelines for the management of progressive/recurrent glioblastoma include the following recommendations [294] ;

      • Gadolinium contrast-enhanced magnetic resonance imaging (MRI) is recommended for diagnosis of progressive glioblastoma (pGBM). Diffusion-weighted imaging should be considered as part of the standard MRI sequences used.
      • 18-Fluorodeoxyglucose (FDG) is not recommended for routine diagnosis. Techniques using newer radiotracers may assist in the diagnosis.
      • Cytoreductive surgery is recommended for patients with symptomatic pGBM. It is also recommended to improve overall survival in pGBM patients.
      • Repeat assessment of 06-methylguanine-DNA methyltransferase ( MGMT) methylation and isocitrate dehydrogenase ( IDH) status is not indicated.
      • Programmed death ligand (PDL) 1/mismatch repair enzyme activity is not a useful component of standard diagnostic testing.
      • If epidermal growth factor receptor (EGFR) amplification was not previously measured, its assessment at progression may be of diagnostic value.
      • Large panel sequencing may be considered in patients who are eligible for or interested in molecularly guided therapy or clinical trials.
      • Benefit may be derived from treatment with TMZ, especially with progression after > 5 months off TMZ.
      • Fotemustine is suggested in elderly patients with methylated  MGMT promoter status.
      • Tumor treatment fields (TTFs) with other chemotherapy may be considered for adult patients.
      • The following are not suggested: (1) TMZ combined with other cytotoxic agents as standalone therapy; (2) other chemotherapeutic agents (including platinum compounds and topoisomerase inhibitors); (3) other cytotoxic therapies (eg, perillyl alcohol or ketogenic diet) as standalone therapy; and (4) oncolytic virotherapy.
      • Re-irradiation should be considered for patients with pGBM; it can be safely used in elderly patients. Bevacizumab does not provide increased overall survival when used to treat pGBM. There is not sufficient evidence to identify benefits and harms associated with its use in combination with other agents.

      Palliative care

      European Association for Neuro-Oncology (EANO) guidelines for palliative care in adults with glioma include the following recommendations for treatment of complicating signs and symptoms [295]

      • Headache: Corticosteroids (dexamethasone) are the mainstay of treatment for headache in patients with gliomas. Analgesics and co-analgesics could also be considered in the treatment of headache (in accordance with the World Health Organization cancer pain ladder [296] ).
      • Seizures: If oral administration of antiepileptic drugs is not an option, intranasal midazolam and buccal clonazepam are a feasible way to treat seizures in the end-of-life phase, when patients often have difficulty swallowing.
      • Venous thromboembolism (VTE): VTE prophylaxis with low molecular weight heparin should be started postoperatively within 24 hours. No data support extending primary VTE prophylaxis beyond the postoperative period; in brain tumor patients who have experienced VTE, the duration of secondary prophylaxis should be planned individually, but is lifelong in most patients.
      • Fatigue: There is to date no proof of efficacy for any pharmacologic or nonpharmacologic intervention for fatigue in glioma patients.
      • Mood and behavioral disorders: Limited evidence supports the use of several pharmacologic interventions (eg, methylphenidate, donepezil) for mood disorders in glioma patients. Multimodal psychosocial intervention may improve depressive symptoms.
      • Neurorehabilitation: Brain tumor patients may benefit from postoperative early rehabilitation, as well as rehabilitation after tumor-specific treatment.
      • Cognition: Medical treatment to prevent or treat cognitive decline in brain tumor patients is not recommended. However, cognitive rehabilitation has modest positive effects and should be considered, especially in young glioma patients with relatively favorable prognosis.

      Since the 2017 EANO guidelines, new findings in palliative care in neuro-oncology include the following [297]

      • Seizures: Levetiracetam is more effective than valproic acid as a first-line, anti-seizure monotherapy; additionally, lacosamide and perampanel are effective antiseizure drugs with generally tolerable adverse effects
      • Fatigue and cognition: Pharmacologic agents to improve fatigue and cognition remain elusive, as no randomized controlled trials have shown significant efficacy in these areas
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