What are the current guidelines for managing glioblastoma?

Current Guidelines for Managing Glioblastoma

The standard of care for newly diagnosed glioblastoma includes maximal safe surgical resection followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. 1

Initial Management

Surgery

• Gross total resection should be attempted whenever feasible to improve survival outcomes 1
• Biopsy is appropriate when resection is not possible or safe 1

Radiation Therapy

• For patients <70 years with good performance status (KPS ≥60):

  • Standard fractionated radiotherapy: 60 Gy in 2-Gy fractions over 6 weeks 1
  • Partial-brain radiation therapy is the standard approach rather than whole-brain radiation 1

• For elderly patients (≥70 years) with good performance status (KPS ≥50):

  • Hypofractionated radiotherapy (e.g., 40 Gy in 15 fractions over 3 weeks) is recommended 1
  • Hypofractionated regimens have shown similar efficacy to conventional fractionation with less treatment burden 1

Chemotherapy

• For patients <70 years:

  • Concurrent temozolomide (75 mg/m² daily throughout radiotherapy) 1
  • Followed by adjuvant temozolomide (150-200 mg/m², 5 days per 28-day cycle) for 6 cycles 1, 2

• For elderly patients (≥70 years):

  • With MGMT promoter methylation: Consider temozolomide alone or with hypofractionated radiotherapy 1
  • Without MGMT promoter methylation: Hypofractionated radiotherapy alone is preferred 1

Molecular Testing

• MGMT promoter methylation testing is recommended, particularly for elderly patients, to guide treatment decisions 1
• IDH mutation status should be determined for proper classification and management 1

Treatment of Recurrent Disease

• Surgical re-resection should be considered when feasible 1
• Systemic therapy options include:
  • Nitrosoureas (lomustine) 1, 3
  • Temozolomide rechallenge (particularly if good response to initial treatment) 1, 3
  • Bevacizumab (may improve progression-free survival but not overall survival) 1
• Focal reirradiation may be considered for younger patients with good performance status 1, 3

Therapies Not Routinely Recommended

• Bevacizumab should not be added to initial standard therapy outside of clinical trials 1
• Tumor-treating fields remain controversial despite positive phase III trial results 1, 4

Follow-up

• Clinical and imaging follow-up every 3-6 months 1
• MRI is the preferred imaging modality for diagnosis and follow-up 1

Prognostic Factors

• Favorable prognostic factors include:
  • Younger age (<50 years) 1
  • Good performance status (KPS ≥70) 1
  • Extent of resection 1
  • MGMT promoter methylation 1

Common Pitfalls and Caveats

• Pseudoprogression can occur within the first 3 months after completion of chemoradiotherapy and should not be mistaken for true progression 1
• Elderly patients often receive suboptimal therapy despite evidence supporting active treatment 1
• MGMT testing should guide treatment decisions in elderly patients but not necessarily alter standard approach in younger patients 1
• Steroid use should be minimized when possible to avoid complications and potential interference with treatment efficacy 1