Current Treatment Options for Glioblastoma Multiforme (GBM)
The standard of care for glioblastoma multiforme includes maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide chemotherapy, which has been shown to significantly improve overall survival compared to radiotherapy alone. 1
Initial Management
Surgical Approach
- Maximal safe tumor resection should be attempted whenever possible, as it improves overall survival compared to lesser resection, provided neurological function is not compromised 1
- When complete resection is not safely feasible, stereotactic or open biopsy should be performed to establish diagnosis 1
- Fluorescent marking of the tumor using 5-amino-laevulinic acid (5-ALA) during surgery can improve complete resection rates and progression-free survival 1, 2
- Implantation of carmustine-impregnated wafers (Gliadel) into the resection cavity is an option but has shown only marginal improvement in survival compared to radiotherapy alone 1
Adjuvant Therapy for Newly Diagnosed GBM
For patients ≤70 years with good performance status (KPS ≥70):
- Fractionated radiotherapy (60 Gy in 30-33 fractions of 1.8-2 Gy) plus concurrent and adjuvant temozolomide is the standard treatment (Category 1 recommendation) 1, 3
- Concurrent temozolomide is administered daily (75 mg/m²) during radiotherapy, followed by 6-12 cycles of adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days) 1, 3
For elderly patients (>70 years) with good performance status:
For patients with poor performance status (KPS <70):
- Options include hypofractionated radiotherapy, temozolomide chemotherapy, or palliative/best supportive care 1
Management of Recurrent Disease
- Repeat surgical resection should be considered for local recurrence if feasible 1, 4
- Systemic therapy options for recurrent disease include:
- Reirradiation may be considered if prior radiation produced a good/durable response 1, 4
- Carmustine wafer placement during repeat surgery is an option 1
Molecular Stratification and Personalized Approach
- MGMT promoter methylation status is a predictive biomarker for response to temozolomide, with methylated tumors showing greater benefit 1, 4
- IDH mutation status and 1p/19q co-deletion should be determined as they provide important prognostic information 2, 4
- For anaplastic oligodendroglioma or oligoastrocytoma with 1p/19q co-deletion, fractionated radiotherapy plus PCV (procarbazine, lomustine, vincristine) is recommended 1
Follow-up and Monitoring
- MRI scans should be performed at 2-6 weeks post-radiotherapy, then every 2-4 months for 2-3 years, then less frequently 1
- Early MRI changes within 3 months after completion of radiotherapy may represent pseudoprogression rather than true tumor progression 1
- Advanced imaging techniques such as MR spectroscopy, MR perfusion, or PET can help distinguish radiation necrosis from tumor progression 1
Clinical Challenges and Pitfalls
- Despite optimal treatment, median survival for GBM remains only 14-16 months, with fewer than 10% of patients surviving beyond 5 years 1
- The blood-brain barrier limits drug delivery, contributing to treatment resistance 6, 5
- Pseudoprogression can be mistaken for true progression, potentially leading to premature discontinuation of effective therapy 1, 4
- Steroid use should be minimized when possible due to significant side effects, but may be necessary to control tumor-associated edema 1, 2
- Antiepileptic therapy is indicated only for patients presenting with seizures; prophylactic antiepileptic therapy is not recommended in asymptomatic patients 1
Despite advances in treatment strategies, GBM remains a challenging disease with inevitable recurrence in most cases. Ongoing research into novel therapeutic approaches including immunotherapy, targeted therapies, and tumor treating fields continues to evolve, but the current standard of care remains maximal safe resection followed by concurrent chemoradiation with temozolomide.