Initial Treatment Approach for High-Grade Glioma Brain Tumor
Maximal safe surgical resection followed by radiotherapy with concurrent temozolomide (TMZ) and then adjuvant TMZ is the standard initial treatment approach for patients with high-grade glioma. 1
Diagnostic Confirmation
- Histological diagnosis is mandatory and should include sufficient tissue for molecular tumor characterization 1
- Key molecular markers to determine include:
- MGMT promoter methylation status
- IDH mutations
- 1p/19q co-deletions 1
Treatment Algorithm
Step 1: Surgical Management
- Attempt maximal tumor resection provided neurological function is not compromised 1
- When microsurgical resection is not safely feasible (due to tumor location or patient condition), a biopsy should be performed 1
- Fluorescent marking of the tumor using 5-amino-laevulinic acid (5-ALA) during surgery improves complete resection rates and progression-free survival 1
Step 2: Post-Surgical Treatment
For Glioblastoma (WHO Grade IV):
Concomitant Phase: 2
- TMZ 75 mg/m² daily for 42 days with focal radiotherapy (60 Gy in 30 fractions)
- Pneumocystis pneumonia prophylaxis is required during this phase
Maintenance Phase: 2
- Begin 4 weeks after completing TMZ+RT
- Cycle 1: TMZ 150 mg/m² once daily for 5 days followed by 23 days without treatment
- Cycles 2-6: TMZ dose can be escalated to 200 mg/m² if toxicity criteria are met
For Anaplastic Oligodendroglioma:
- Radiotherapy followed by adjuvant chemotherapy 1
- PCV (procarbazine, lomustine, vincristine) or TMZ may be used 1
For Anaplastic Astrocytoma:
- Radiotherapy is the standard treatment, with no proven benefit of adjuvant PCV chemotherapy 1
Special Considerations for Elderly Patients (>65 years):
- Hypo-fractionated radiotherapy (10 × 3.4 Gy or 15 × 2.66 Gy) is preferred over standard fractionation 1
- MGMT promoter methylation status guides treatment choice:
- Methylated MGMT: TMZ chemotherapy alone may be considered
- Unmethylated MGMT: Hypo-fractionated radiotherapy is the treatment of choice 1
Alternative Treatment Options
- Implantation of carmustine wafers (chemotherapy-impregnated polymers) into the resection cavity has shown marginal improvement in median survival compared to radiotherapy alone, but has not been prospectively compared with the standard TMZ/RT regimen 1, 3
- Increased wound healing and infectious complications have been reported with carmustine wafers 1
- The combination of carmustine wafers with TMZ/RT has not shown additive efficacy in retrospective comparisons 1
Follow-up Recommendations
- Clinical evaluation with attention to neurological function, seizures, and corticosteroid use 1
- Taper off steroid use as early as possible 1
- MRI every 3-4 months is standard practice outside clinical trials 1
- Monitor for venous thrombotic events, which occur frequently in patients with residual or recurrent tumors 1
Prognostic Factors
- Lower tumor grade, younger age (<50 years), good performance status, intact neurological function, and radical tumor resection are favorable prognostic factors 1
- Molecular markers provide additional prognostic information:
- IDH mutations indicate a more protracted natural history
- 1p/19q co-deletions in oligodendrogliomas are associated with better outcomes
- MGMT promoter methylation predicts benefit from alkylating chemotherapy 1
Treatment Efficacy
- The addition of TMZ to radiotherapy significantly improves median and 2-year survival in glioblastoma patients 2, 4
- In the pivotal study, median survival increased by 2.5 months with TMZ/RT compared to RT alone (14.6 vs. 12.1 months) 2, 4
- The hazard ratio for overall survival was 0.63 (95% CI: 0.52-0.75) in favor of the TMZ arm 2
High-grade gliomas remain challenging to treat despite advances in surgical techniques, radiation therapy, and chemotherapy. The multimodal approach of maximal safe resection followed by concurrent chemoradiation and adjuvant chemotherapy offers the best chance for improved survival and quality of life.