What is the management approach for glioblastoma (GBM) with encephalopathy?

Management of Glioblastoma with Encephalopathy

Corticosteroids should be administered to reduce symptomatic tumor-associated edema causing encephalopathy, using the minimal effective dose with regular re-evaluation, while proceeding with standard glioblastoma management including maximal safe resection, radiotherapy, and temozolomide. 1

Immediate Management of Encephalopathy

Corticosteroid Therapy

• Patients with clinical or radiological evidence of brain edema should be treated with corticosteroids to address the encephalopathy 1
• Methylprednisolone or prednisolone should be prescribed as single daily doses in the morning 1
• The minimal effective dose should be determined and regularly re-evaluated to minimize side effects 1
• Prophylactic corticosteroids can reduce the risk of radiation-induced encephalopathy (radiation-induced edema) if radiotherapy is planned 1

Alternative Measures

• Osmotic agents can be considered less frequently if corticosteroids are insufficient 1
• H2-receptor blockers or proton pump inhibitors should be used to prevent gastrointestinal complications in patients receiving high-dose corticosteroids 1

Critical Diagnostic Consideration

• If primary CNS lymphoma is suspected, corticosteroid therapy should be avoided prior to obtaining histological confirmation, except when the neurological status requires urgent treatment 1
• This is a critical pitfall as corticosteroids can obscure lymphoma diagnosis

Diagnostic Workup

Imaging

• Gadolinium-enhanced MRI with diffusion-weighted imaging is the standard diagnostic tool 2
• MRI should be performed within 72 hours after any surgical intervention to assess residual tumor 1
• Perfusion MRI and amino acid PET can help distinguish true progression from treatment-related changes 1, 2

Tissue Diagnosis

• Histological confirmation should be obtained because neuroimaging is not sufficiently specific 1
• Clinical decision-making without tissue diagnosis should only be considered in exceptional situations: elderly patients with deep-seated lesions, very poor systemic/neurological condition, high burden of comorbidities with rapid neurological deterioration 1
• Molecular testing should include MGMT promoter methylation and IDH mutation status 2

Evaluating Altered Consciousness

• Electroencephalography can be helpful in determining the cause of altered consciousness and monitoring tumor-associated epilepsy 1

Definitive Treatment Strategy

Surgical Management

• Maximal safe tumor resection should be performed to improve overall survival, alleviate symptoms, and decrease the need for corticosteroids 2
• Optimal tumor resection with margins as wide as possible should be achieved while avoiding major functional risks 1
• Technical aids including preoperative functional MRI, neuronavigation, and intraoperative brain mapping can optimize surgical resection 1

Radiation Therapy

• Standard fractionated radiotherapy is 60 Gy in 2-Gy fractions over 6 weeks for patients under 70 years with good performance status 2
• The dose should be adapted according to histological type and grade, not exceeding 60 Gy total 1
• Prophylactic corticosteroids can be used to reduce the risk of acute or early-delayed encephalopathy from radiation-induced edema 1

Chemotherapy

• Concurrent temozolomide during radiation followed by adjuvant temozolomide is the standard regimen 2
• MGMT promoter methylation status should guide treatment decisions, as methylated tumors benefit most from temozolomide 2

Management of Progressive Disease with Encephalopathy

Distinguishing Progression from Treatment Effects

• Clinical and/or radiological deterioration within 2 months after radiotherapy should be interpreted with caution and not automatically considered treatment failure 1
• Pseudoprogression should be considered if MRI changes occur within 6-9 months after radiotherapy 1, 2
• Diffusion-weighted imaging should be included in surveillance MRI to detect progressive disease 1

Treatment Options for Progressive Disease

• Repeat cytoreductive surgery is recommended to improve overall survival in patients with good performance status and possibility of gross total resection 1, 2
• Reirradiation should be considered to provide improved local tumor control and maintain neurological status 2
• Systemic therapy options include lomustine, bevacizumab, and temozolomide rechallenge in MGMT promoter-methylated tumors 2

Monitoring and Follow-up

• Clinical and imaging follow-up every 2-3 months is recommended 2
• The clinical and radiological evaluation should account for variations in corticosteroid dose 1
• MRI is preferable to CT scanning for follow-up of disease progression 1

Common Pitfalls

• Risk factors for late neurological complications (radionecrosis, radiation-induced leukoencephalopathy) include age over 50 years, previous vascular disease (hypertension, diabetes, hyperlipidemia), and high radiation dose per fraction 1
• Cognitive impairment as initial symptom is often misinterpreted in primary care, leading to delayed diagnosis and is associated with reduced survival (median 6.4 months) 3
• Corticosteroid side effects require monitoring, and the dose should be regularly re-evaluated 1