What is the standard treatment for a patient diagnosed with glioblastoma multiforme?

Standard Treatment for Glioblastoma Multiforme

For newly diagnosed glioblastoma multiforme, the standard of care is maximal safe surgical resection followed by concurrent radiotherapy (60 Gy) with temozolomide chemotherapy, then adjuvant temozolomide for 6 cycles. 1, 2

Initial Surgical Management

• Surgery is the first therapeutic intervention, aiming for maximal safe tumor resection to obtain tissue for diagnosis and molecular characterization while preserving neurological function. 1
• Tumor resection carries prognostic value, though the benefit of attempting maximal versus subtotal resection remains debated in the literature. 1
• Obtain MRI within 24-48 hours post-operatively to distinguish residual tumor from post-operative edema and surgical changes. 3
• Histological diagnosis must include sufficient tissue for molecular tumor characterization, specifically MGMT promoter methylation status and IDH mutation status. 1

Standard Chemoradiotherapy Protocol

The Stupp Protocol (established by landmark randomized trial):

• Concurrent phase: Temozolomide 75 mg/m² daily starting day 1 of radiotherapy, continuing through the entire radiation course (42 days, maximum 49 days). 2
• Radiotherapy: Fractionated focal radiotherapy delivering 60 Gy in 30 fractions of 2 Gy each, targeting the tumor bed or resection site with 2-3 cm margin. 1, 2
• Adjuvant phase: Begin 4 weeks after completing radiotherapy with temozolomide 150-200 mg/m² on days 1-5 of each 28-day cycle for 6 cycles. 2
• This regimen demonstrated a hazard ratio of 0.63 (95% CI: 0.52-0.75, p<0.0001) for overall survival, increasing median survival by 2.5 months and significantly improving 2-year survival. 1, 2

Critical Supportive Care Measures

• Pneumocystis pneumonia (PCP) prophylaxis is required during concurrent temozolomide and radiotherapy regardless of lymphocyte count, continuing until lymphocyte recovery to ≤Grade 1. 2
• Prophylactic anticoagulation with low-molecular weight heparin and compression stockings is recommended perioperatively to prevent thromboembolic complications, which occur frequently in glioblastoma patients. 1, 4
• Taper corticosteroids as early as possible to minimize long-term complications including myopathy, hyperglycemia, opportunistic infections, and psychiatric effects. 3
• Antiepileptic prophylaxis is NOT recommended for patients who have never had a seizure; only treat after documented seizure activity. 5
• If antiepileptic therapy is needed, levetiracetam is preferred due to lack of cytochrome P450 interactions that would interfere with temozolomide. 5

Special Considerations for Elderly or Poor Performance Status

• For elderly patients with methylated MGMT promoter: Consider temozolomide chemotherapy alone as an alternative to combined modality therapy. 1
• For elderly patients with unmethylated MGMT promoter: Hypofractionated radiotherapy (e.g., 3 Gy × 10 fractions) is the treatment of choice rather than standard fractionation. 1
• Shorter hypofractionated regimens are commonly proposed for patients with low performance status. 1

Molecular Biomarkers and Treatment Selection

• MGMT promoter methylation status is predictive for benefit from temozolomide, with methylated tumors showing improved survival with chemotherapy. 1
• IDH mutation status should be determined as part of molecular characterization, though IDH-mutant tumors are rare in primary glioblastoma. 1
• These molecular markers help stratify prognosis but do not currently change the standard treatment approach for newly diagnosed disease. 1

Follow-Up Protocol

• Clinical evaluation with neurological examination every 3-4 months is standard practice outside clinical trials. 1, 3
• MRI every 3-4 months using identical protocols and RANO criteria for response assessment. 3
• Monitor for pseudoprogression during the first 3 months after chemoradiotherapy; enhancement on imaging 4-8 weeks post-radiotherapy may represent blood-brain barrier changes rather than true progression. 3
• If pseudoprogression is suspected, obtain repeat MRI 4 weeks later before modifying treatment. 3
• Surveillance for venous thrombotic events should continue throughout follow-up as these occur frequently with residual or recurrent tumor. 3

Treatment at Recurrence

• No standard of care exists for recurrent glioblastoma; options include repeat surgery, re-irradiation, systemic chemotherapy (nitrosoureas if not previously used), or bevacizumab depending on patient circumstances. 4
• Repeat surgery with carmustine-impregnated wafer (Gliadel) implantation may prolong survival in selected patients. 1
• Chemotherapy shows some benefit in patients with adequate performance status who have not received prior adjuvant cytotoxic therapy, though anaplastic astrocytomas respond better than glioblastoma. 1

Important Pitfalls to Avoid

• Do not escalate radiotherapy doses beyond 60 Gy—higher doses have not shown survival benefit. 1
• Do not use PCV regimen (procarbazine, lomustine, vincristine) for glioblastoma—prospective randomized studies failed to show survival improvement. 1
• Do not perform lumbar puncture or systemic staging as these are not necessary for glioblastoma management. 1, 3
• Do not continue corticosteroids longer than necessary—aggressive tapering prevents significant morbidity. 3