What is the standard treatment for a patient diagnosed with glioma of the brain?

Standard Treatment for Brain Glioma

The standard treatment for a patient diagnosed with glioma of the brain includes maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide chemotherapy. 1, 2

Initial Diagnosis and Assessment

• Histological diagnosis through biopsy or tumor resection is mandatory and should include sufficient tissue for molecular tumor characterization 2
• Key molecular markers to determine include MGMT promoter methylation status, IDH mutations, and 1p/19q co-deletions 2
• MRI is the preferred imaging modality for both diagnosis and follow-up 1
• Prognostic factors include:
  • Age (<50 years is favorable) 1
  • Performance status 1
  • Neurological function 1
  • Tumor grade (lower grade has better prognosis) 1
  • Extent of resection 1

Treatment Algorithm by Grade

High-Grade Glioma (Grade III-IV)

1. Surgical Management

   • Maximal safe surgical resection should be attempted when technically feasible 1
   • Fluorescent marking using 5-amino-laevulinic acid (5-ALA) during surgery improves complete resection rates 2
   • If optimal resection is not possible, a biopsy should be performed to obtain tissue for diagnosis 1

2. Radiotherapy

   • Standard fractionated focal radiotherapy (60 Gy, 2 Gy × 30 fractions) should be started within 6 weeks after surgery 1, 3
   • For elderly patients (>65 years) or those with poor performance status, hypofractionated regimens are recommended:
     • 40 Gy in 15 fractions 1
     • 34 Gy in 10 fractions 3
     • 25 Gy in 5 fractions 3

3. Chemotherapy

   • Glioblastoma (Grade IV): Concomitant and adjuvant temozolomide has been demonstrated to significantly improve median and 2-year survival 1, 4
     • Concurrent phase: 75 mg/m² daily during radiotherapy 4
     • Adjuvant phase: 150-200 mg/m² for 5 days every 28 days for 6 cycles 4
   • Anaplastic Astrocytoma (Grade III): Options include temozolomide or nitrosourea-based chemotherapy 1
   • Anaplastic Oligodendroglioma and Oligoastrocytoma: Radiotherapy followed by PCV (procarbazine, lomustine, vincristine) chemotherapy is recommended 1

Low-Grade Glioma (Grade II)

1. Surgical Management

   • Optimal resection should be attempted when safely possible 1
   • For patients with poor prognostic factors (age >35-40 years, uncontrolled epilepsy, deficit symptoms, large tumor size, contrast enhancement), surgical resection is standard 1

2. Radiotherapy

   • When radiotherapy is proposed, the dose should be between 50-54 Gy 1
   • Consider radiotherapy after partial resection, especially with poor prognostic factors 1

3. Chemotherapy

   • Chemotherapy can be considered for symptomatic oligodendroglial tumors 1

Management of Recurrent Disease

• Five therapeutic options can be considered for recurrent high-grade glioma 1:

  • Repeat surgery
  • Systemic chemotherapy (temozolomide if not previously used)
  • Local chemotherapy (carmustine implants)
  • Second-line radiotherapy (in selected cases)
  • Palliative care without specific anticancer treatment

• For recurrent oligodendroglioma after radiotherapy and PCV chemotherapy, temozolomide can be considered 1

Special Considerations

• MGMT gene promoter methylation status may help select patients likely to benefit from temozolomide therapy 1
• Tumor treatment fields (TTFields) is the newest FDA-approved treatment that has shown improved overall survival compared to standard care alone 5
• Pneumocystis pneumonia prophylaxis is required during concurrent temozolomide and radiotherapy 4
• Monitor for and prevent thromboembolic complications, which occur frequently in patients with glioma 2

Common Pitfalls and Caveats

• Delaying radiotherapy beyond 6 weeks after surgery may negatively impact outcomes 3
• Escalating radiation doses beyond 60 Gy has not shown benefit and may increase toxicity 1
• Brachytherapy and stereotactic radiosurgery boost to external beam radiotherapy have not shown benefit in newly diagnosed gliomas 3
• Early tapering of steroids is recommended when possible to minimize side effects 2
• The diffusely infiltrative pattern of growth in gliomas makes complete resection challenging, requiring a balance between extent of resection and preservation of neurological function 6