What is the standard treatment for glioma?

Standard Treatment for Glioma

For newly diagnosed glioblastoma, the standard treatment is maximal safe surgical resection followed by radiotherapy (60 Gy in 2 Gy fractions) with concurrent temozolomide (75 mg/m² daily), then adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days for 6 cycles). 1, 2, 3

Treatment Algorithm by Glioma Grade and Type

High-Grade Gliomas (Glioblastoma - WHO Grade IV)

Initial Management:

• Surgical approach: Perform maximal safe cytoreductive surgery when technically feasible without causing permanent functional deterioration 2, 4. MRI should be obtained within 24-48 hours post-operatively to assess residual disease 1, 5.

• Standard postoperative regimen (Stupp Protocol): Begin radiotherapy within 6 weeks of surgery 4. Deliver 60 Gy in 30 fractions (2 Gy daily, 5 days/week for 6 weeks) to the tumor bed with 1-2 cm margin 1, 4. Administer concurrent temozolomide 75 mg/m² daily throughout radiotherapy (42-49 days maximum) 2, 3. Critical: Provide PCP prophylaxis during concurrent therapy regardless of lymphocyte count 2, 3.

• Adjuvant chemotherapy: Start temozolomide 4 weeks after completing radiotherapy 3. Give 150 mg/m² (cycle 1) or 200 mg/m² (subsequent cycles if tolerated) on days 1-5 of each 28-day cycle for 6 cycles 2, 3. This regimen improved median survival from 12.1 to 14.6 months and 2-year survival from 10.4% to 26.5% 6.

Special Populations:

• Elderly (>65 years) or frail patients: Use hypofractionated radiotherapy regimens: 40.05 Gy in 15 fractions, 25 Gy in 5 fractions, or 34 Gy in 10 fractions 1, 4. These shorter regimens provide equivalent survival with better tolerability compared to standard 60 Gy 4.

• Poor performance status patients: Consider palliative care without aggressive anticancer treatment for those with large/multifocal lesions or inability to consent 2.

Recurrent Glioblastoma:

• Surgical option: Repeat cytoreductive surgery improves overall survival in selected patients with symptomatic circumscribed relapses, good performance status, and possibility of gross total resection 2. Avoid re-operation within 6 months due to pseudoprogression risk 2.

• Chemotherapy options: Lomustine (CCNU) is the standard single-agent with confirmed efficacy 2, 7. Alternatives include temozolomide rechallenge, bevacizumab, other nitrosoureas, or local carmustine wafer implants 2, 7.

Anaplastic Astrocytoma (WHO Grade III)

Standard treatment: Radiotherapy is the standard approach 1, 7. Deliver 60 Gy in 2 Gy fractions 1.

Chemotherapy options: Consider mono-drug chemotherapy with nitrosourea (BCNU), PCV regimen (procarbazine, lomustine, vincristine), or temozolomide 7. The optimal timing and role of chemotherapy remains unresolved, but can be given as initial therapy after resection, adjuvant therapy after radiotherapy, or at recurrence 8.

Anaplastic Oligodendroglioma and Oligoastrocytoma (WHO Grade III)

Standard treatment: Radiotherapy is standard 1, 7. PCV chemotherapy has proven efficacy in this population 7. Patients with 1p/19q deletion have longer survival and better chemotherapy response 1.

Low-Grade Glioma (WHO Grade II)

Diagnostic standard: MRI is the standard for both diagnosis and follow-up 1.

Surgical approach: Optimal resection involves total or subtotal removal of tumor volume defined on T2/FLAIR sequences 1. When radiologically complete resection is safely achievable, surgery should be undertaken 1.

Treatment algorithm based on resectability and prognostic factors:

• If optimal resection possible with ≥1 poor prognostic factor: Perform surgical resection 1
• If optimal resection possible without poor prognostic factors: Consider surgical resection or surveillance with/without biopsy 1
• If optimal resection not possible with ≥1 poor prognostic factor: Options include partial resection, partial resection + radiotherapy, radiotherapy alone (after histological confirmation), or chemotherapy 1
• If optimal resection not possible without poor prognostic factors: Consider follow-up with/without biopsy, partial resection, partial resection + radiotherapy, or biopsy + radiotherapy 1

Radiotherapy dosing: When indicated, deliver 45-54 Gy, with 50-54 Gy recommended 1.

Poor prognostic factors include: Age >35-40 years, low Karnofsky score, intracranial hypertension, functional deficit, uncontrolled epilepsy, large/rapidly increasing tumor volume, functional zone location, deep structure involvement, and contrast enhancement on MRI 1.

Specific Glioma Subtypes

Pilocytic Astrocytoma:

• Should not be called "low-grade astrocytoma" 1
• Complete surgical resection significantly improves survival and often cures patients 1
• Perform optimal resection when operability criteria satisfied 1
• If complete resection confirmed on MRI: simple clinical follow-up 1
• If incomplete resection: annual follow-up with clinical and MRI evaluation 1
• If anaplastic appearance (grade 3) on histology: administer radiotherapy 1

Gliomatosis Cerebri:

Treatment options include chemotherapy alone, follow-up for asymptomatic patients without progression, or whole-brain radiotherapy 1.

Intracranial Ependymoma:

• Localized lesions: Surgery is standard treatment 1. Complete resection confirmed by early postoperative MRI is a good prognostic factor 1.
• Grade 2 with complete resection: No complementary treatment necessary 1
• Grade 3 with complete resection: Offer localized postoperative radiotherapy or follow-up 1
• Incomplete resection (grade 2): Options include follow-up, further resection, or localized radiotherapy 1
• Incomplete resection (grade 3): Offer localized radiotherapy; consider further resection or chemotherapy 1
• Metastatic disease: Offer craniospinal radiotherapy; consider optimal surgical resection before radiotherapy and chemotherapy 1

Critical Monitoring and Follow-up

Imaging surveillance: Perform cranial MRI every 3-4 months as standard practice 5. Contrast-enhanced MRI is the preferred modality 5.

Pseudoprogression awareness: Enhancement 4-8 weeks after radiotherapy may represent imaging artifact from blood-brain barrier changes rather than true progression 5. Confirm with repeat MRI 4 weeks later before changing treatment 5.

Laboratory monitoring: Obtain complete blood counts before each temozolomide cycle, on Day 22 of each cycle, and throughout treatment 2. Perform liver function tests at baseline, midway through first cycle, and before subsequent cycles 2.

Corticosteroid management: Gradually reduce steroid dosage as soon as possible to minimize myopathy, hyperglycemia, opportunistic infections, and psychiatric complications 5.

Common Pitfalls to Avoid

• Never omit PCP prophylaxis during concurrent temozolomide and radiotherapy 2
• Do not delay radiotherapy beyond 6 weeks post-surgery 4
• Avoid re-operation within 6 months of initial surgery due to pseudoprogression risk 2
• Do not escalate radiation doses beyond 60 Gy—no survival benefit demonstrated 1
• Stereotactic radiosurgery boost and brachytherapy boost have not shown benefit and are not recommended 4
• BCNU-polymer wafer implants show only marginal benefit 1