What is the standard multidisciplinary treatment plan for a newly diagnosed glioblastoma, including surgery, radiotherapy, temozolomide, molecular testing (MGMT promoter methylation and IDH mutation), and special considerations for older or poor‑performance patients?

Standard Multidisciplinary Treatment for Newly Diagnosed Glioblastoma

For newly diagnosed glioblastoma, the standard treatment is maximal safe surgical resection followed by concurrent radiotherapy (60 Gy in 30 fractions) with temozolomide chemotherapy, then adjuvant temozolomide for 6 cycles, with MGMT promoter methylation status guiding treatment decisions and prognosis. 1, 2

Initial Surgical Management

Maximal safe tumor resection should be attempted as the first therapeutic intervention, provided neurological function is not compromised by the extent of resection 1, 2. Surgery serves dual purposes: debulking the tumor mass and obtaining tissue for both histological diagnosis and molecular characterization 1.

• Obtain post-operative MRI within 24-48 hours after surgery to accurately distinguish residual tumor from post-operative edema and surgical changes 3, 1
• Extent of resection is a significant prognostic factor—gross total resection improves survival compared to subtotal resection or biopsy alone 2

Molecular Testing Requirements

All glioblastoma specimens must undergo molecular testing to guide treatment and prognosis 1, 2:

• MGMT promoter methylation status is the most clinically actionable marker—methylated tumors derive greater benefit from temozolomide therapy 1, 2
• IDH mutation status must be determined, as IDH-mutant tumors have significantly better prognosis 1, 2
• Additional markers including 1p/19q codeletion, TERT promoter mutations, EGFR amplification, and chromosome 7 gain/10 loss should be assessed 1, 2

Standard Radiotherapy Protocol

Fractionated focal radiotherapy delivering 60 Gy in 30 fractions (2 Gy per fraction) is the standard treatment after resection or biopsy 1, 2:

• Escalating doses beyond 60 Gy has not shown benefit 1
• Radiotherapy should be delivered concurrently with temozolomide chemotherapy 1

Temozolomide Chemotherapy Regimen

Concomitant and adjuvant temozolomide significantly improves median and 2-year survival in glioblastoma 1:

• Concurrent phase: Temozolomide 75 mg/m² daily during radiotherapy (approximately 6 weeks)
• Adjuvant phase: Temozolomide 150-200 mg/m² for 5 days every 28 days for 6 cycles
• MGMT promoter methylation predicts which patients will derive the greatest benefit from temozolomide 1, 2

Alternative consideration: Carmustine-impregnated wafers (BCNU polymer) implanted into the resection cavity show only marginal benefit compared to radiotherapy alone and have not been compared directly to standard temozolomide/radiotherapy 1

Special Considerations for Elderly or Poor Performance Status Patients

For elderly patients (>70 years) or those with poor performance status, treatment must be modified 1:

• Hypofractionated radiotherapy (40 Gy in 15 fractions or 50 Gy in 28 fractions of 1.8 Gy) is the preferred approach rather than standard 60 Gy regimen 1
• Radiotherapy in patients >70 years is superior to best supportive care alone 1
• For elderly patients with methylated MGMT promoter, exclusive temozolomide chemotherapy without radiotherapy may be considered 1
• For elderly patients with unmethylated MGMT promoter, hypofractionated radiotherapy alone is the treatment of choice 1

Multidisciplinary Team Evaluation

All patients must be evaluated by a specialized multidisciplinary team with particular attention to performance status and neurological function 1. The team should include neuro-oncology, neurosurgery, radiation oncology, and neuropathology specialists 4, 5.

Supportive Care Management

Corticosteroids (typically dexamethasone 8-16 mg/day) rapidly reduce tumor-associated edema and improve clinical symptoms 1:

• Taper steroids as early as possible to minimize complications (myopathy, hyperglycemia, opportunistic infections, psychiatric effects) 1, 3
• Monitor glucose levels during steroid therapy 1, 3

Antiepileptic therapy is indicated only in patients presenting with seizures—prophylactic antiepileptic therapy is not needed in asymptomatic patients 1:

• Avoid first-generation antiepileptics (phenytoin, carbamazepine, phenobarbital) as they induce hepatic metabolism and interfere with many chemotherapy agents 1
• Temozolomide does not interact with enzyme-inducing antiepileptics 1

Venous thromboembolism prophylaxis should be considered, as thrombotic events occur frequently in glioblastoma patients 1, 3, 5

Follow-up Protocol

MRI surveillance every 3-4 months is standard practice outside clinical trials 1, 3:

• Clinical evaluation should assess neurological function, seizure control, and corticosteroid use 3
• Beware of pseudoprogression: Enhancement on imaging 4-8 weeks after radiotherapy completion may represent blood-brain barrier changes rather than true progression—confirm with repeat MRI 4 weeks later before changing treatment 3

Critical Pitfalls to Avoid

• Do not use PCV chemotherapy (procarbazine, lomustine, vincristine) for glioblastoma—it has failed to improve survival in prospective randomized studies 1
• Do not escalate radiotherapy beyond 60 Gy in standard patients—no benefit has been demonstrated 1
• Do not continue high-dose corticosteroids longer than necessary—prolonged use causes significant morbidity 1, 3
• Do not misinterpret pseudoprogression as true progression in the first 2-3 months after radiotherapy completion—wait for confirmatory imaging 3