What is the standard treatment for glioma?

Standard Treatment for Glioma

The standard treatment for malignant glioma (WHO grades III-IV) is maximal safe surgical resection followed by focal radiotherapy (60 Gy in 30 fractions) with concurrent and adjuvant temozolomide chemotherapy, which significantly improves survival compared to radiotherapy alone. 1, 2, 3

Treatment Algorithm by Glioma Grade and Type

High-Grade Gliomas (WHO Grade III-IV)

Initial Management - Glioblastoma (Grade IV)

• Surgery first: Perform maximal safe surgical resection when technically feasible with low risk of permanent functional deterioration to obtain tissue diagnosis and improve survival outcomes 1, 2
• MRI timing: Obtain brain MRI within 24-48 hours post-surgery to distinguish residual tumor from post-operative changes 4, 2
• Exceptions to aggressive surgery: Avoid surgery in patients with high physiological age, multiple comorbidities, poor performance status (Karnofsky <70), multifocal lesions, or tumors in critical functional zones—offer biopsy or palliative care instead 1, 2

Standard Postoperative Regimen for Glioblastoma

The Stupp protocol is the established standard 3:

1. Concurrent phase (starting within 1 month of surgery): Temozolomide 75 mg/m² daily for 42 days (maximum 49 days) during radiotherapy 3
2. Radiotherapy: 60 Gy delivered in 2 Gy fractions over 30 treatments to the tumor bed with 2-3 cm margin 1, 3
3. Adjuvant phase (starting 4 weeks after radiotherapy completion): Temozolomide 150-200 mg/m² on days 1-5 of every 28-day cycle for 6 cycles 3
4. Critical requirement: Pneumocystis pneumonia (PCP) prophylaxis is mandatory during concurrent temozolomide and radiotherapy, continuing until lymphocyte recovery to ≤Grade 1 3

This regimen improved 2-year survival from 10.9% to 27.2% and 5-year survival from 1.9% to 9.8% (HR 0.63, P<0.0001) 3, 5

Monitoring During Treatment

• Complete blood counts: Obtain prior to each cycle, on Day 22 of each cycle, and throughout treatment 2
• Liver function tests: Perform at baseline, midway through first cycle, and before each subsequent cycle 2
• Follow-up imaging: Brain MRI every 3-4 months is standard practice 4

Special Considerations for Molecular Markers

• MGMT promoter methylation: Patients with methylated MGMT promoter are more likely to benefit from temozolomide therapy 1
• Testing recommended: Consider MGMT status to guide treatment decisions, though treatment should not be withheld based on methylation status alone 1

Anaplastic Astrocytoma (Grade III)

• Standard treatment: Radiotherapy (60 Gy) is the foundation 1
• Chemotherapy options: Mono-drug nitrosourea chemotherapy, PCV (procarbazine, lomustine, vincristine), or temozolomide can be added 1, 2
• Better chemotherapy response: Anaplastic astrocytomas respond better to chemotherapy than glioblastomas 1

Anaplastic Oligodendroglioma (Grade III)

• Standard treatment: Radiotherapy (60 Gy) 1, 2
• PCV chemotherapy: Proven efficacy, particularly in tumors with 1p/19q codeletion 1, 2, 5
• Prognostic significance: 1p/19q codeletion predicts better survival and treatment response—probable 20-year survival of 37% with PCV plus radiotherapy versus 14% with radiotherapy alone 5

Low-Grade Gliomas (WHO Grade II)

Risk Stratification

Poor prognostic factors 1:

• Age >35-40 years
• Low Karnofsky performance status
• Intracranial hypertension or functional deficit
• Uncontrolled epilepsy
• Large or rapidly increasing tumor volume
• Involvement of deep structures or functional zones
• Contrast enhancement on MRI

Treatment Strategy for Grade II Gliomas

If optimal resection is possible 1:

• With poor prognostic factors: Perform surgical resection (standard approach)
• Without poor prognostic factors: Consider surgical resection or surveillance with/without biopsy

If optimal resection is not possible 1:

• With poor prognostic factors: Options include partial resection, partial resection followed by radiotherapy, radiotherapy alone after biopsy, or chemotherapy
• Without poor prognostic factors: Consider surveillance with/without biopsy, partial resection, or partial resection followed by radiotherapy

Radiotherapy dosing when indicated: 50-54 Gy (range 45-54 Gy) 1

Chemotherapy for oligodendroglial tumors: Can be considered for symptomatic tumors, preferably within clinical trials 1

Recurrent Glioblastoma

No standard treatment exists—individualize based on performance status and prior treatments 2:

• Repeat surgery: Improves overall survival in selected patients with symptomatic circumscribed relapses, good performance status, and possibility of gross total resection 1, 2
• Lomustine (CCNU): Standard chemotherapy with confirmed single-agent efficacy 2
• Alternative chemotherapy: Temozolomide rechallenge, bevacizumab, other nitrosoureas, or carmustine wafer implants 1, 2
• Timing consideration: Avoid re-operation within 6 months of initial surgery due to risk of pseudoprogression 2

Recurrent Low-Grade Glioma (Grade II)

• Temozolomide: Suggested as initial choice for recurrent WHO grade 2 diffuse glioma to improve clinical symptoms 6
• PCV: May improve symptoms, with strongest evidence for oligodendrogliomas 6
• Radiotherapy: Suggested at recurrence if no previous radiation treatment 6
• Re-irradiation: Consider in previously irradiated patients as it may provide benefit in progression-free and overall survival 6

Special Glioma Subtypes

Pilocytic Astrocytoma (Grade I)

• Treatment: Optimal surgical resection is standard and often curative 1
• Prognosis: Excellent with complete resection; slow or absent growth, particularly in neurofibromatosis type 1 1
• Incomplete resection: Annual follow-up with clinical examination and MRI; consider radiotherapy only if progression occurs 1

Ependymoma

Localized lesions 1:

• Surgery: Standard treatment with complete resection as favorable prognostic factor
• Grade 2 with complete resection: No complementary treatment necessary
• Grade 3 with complete resection: Localized postoperative radiotherapy (option) or follow-up
• Incomplete resection, Grade 2: Options include follow-up, further resection, or localized radiotherapy
• Incomplete resection, Grade 3: Localized radiotherapy is standard

Critical Pitfalls to Avoid

• Never delay treatment: Begin postoperative therapy within 1 month of surgery 2
• Never omit PCP prophylaxis: Mandatory during concurrent temozolomide and radiotherapy regardless of lymphocyte count 2, 3
• Pseudoprogression awareness: Enhancement on MRI 4-8 weeks after radiotherapy may represent pseudoprogression rather than true progression—confirm with repeat MRI 4 weeks later before changing treatment 4, 2
• Avoid dose escalation beyond 60 Gy: Higher radiotherapy doses have not shown benefit 1

Modified Regimens for Special Populations

Elderly patients or poor performance status 1:

• Consider shorter hypofractionated radiotherapy regimens (e.g., 40 Gy in 15 fractions)
• Radiotherapy (50 Gy in 28 fractions) superior to best supportive care alone in patients >70 years