What is the current treatment approach for gliomas?

Current Treatment Approach for Gliomas

The optimal treatment for gliomas requires a specialized multidisciplinary team approach with initial maximal safe surgical resection followed by appropriate adjuvant therapy based on tumor type, grade, and molecular characteristics to maximize survival outcomes. 1

Classification and Diagnosis

Gliomas are classified according to the WHO grading system:

• Grade I-II: Low-grade gliomas
• Grade III: Anaplastic gliomas (anaplastic astrocytoma, anaplastic oligodendroglioma, mixed anaplastic oligoastrocytoma)
• Grade IV: Glioblastoma multiforme (GBM)

Diagnosis is made through:

• MRI imaging of the brain (preferred imaging modality)
• Tissue diagnosis via biopsy or surgical resection
• Molecular testing (MGMT methylation status, 1p/19q co-deletion)

Prognostic Factors

Several factors influence prognosis and treatment decisions:

• Tumor grade and histology (lower grade has better prognosis)
• Age (<50 years has better prognosis)
• Performance status and neurological function
• Extent of surgical resection
• Molecular markers:
  • 1p/19q co-deletion (favorable in oligodendrogliomas) 2
  • MGMT promoter methylation (predicts better response to temozolomide) 2, 1

Treatment Algorithm by Grade

High-Grade Gliomas (Grade III-IV)

Initial Management

1. Surgical Approach:

   • Maximal safe surgical resection is the initial approach for debulking and obtaining tissue for diagnosis 2, 1
   • If complete resection is not possible due to location or patient factors, biopsy should be performed 2
   • Post-operative MRI within 24-48 hours to assess residual disease 2, 1

2. Adjuvant Treatment for Glioblastoma (Grade IV):

   • Standard treatment: Fractionated focal radiotherapy (60 Gy in 30 fractions) with concurrent temozolomide (75 mg/m² daily) followed by adjuvant temozolomide 2, 1, 3
   • Temozolomide is administered at 150 mg/m² for cycle 1, then 200 mg/m² for cycles 2-6 if well tolerated 3
   • This approach has demonstrated significant improvement in median and 2-year survival 2, 4
   • For elderly patients (>70 years) or those with poor performance status, shorter hypofractionated regimens (e.g., 40 Gy in 15 fractions) are recommended 2, 1

3. Adjuvant Treatment for Anaplastic Astrocytoma (Grade III):

   • Radiotherapy is standard treatment 2
   • Options include:
     • Radiotherapy alone
     • Radiotherapy with concurrent and adjuvant temozolomide
     • Anaplastic astrocytomas are more likely than glioblastoma to respond to chemotherapy 2

4. Adjuvant Treatment for Anaplastic Oligodendroglioma and Oligoastrocytoma (Grade III):

   • Radiotherapy is standard treatment 2
   • PCV (procarbazine, lomustine, vincristine) chemotherapy has shown efficacy 2
   • Options include:
     • Radiotherapy followed by PCV
     • PCV followed by radiotherapy
     • Chemotherapy alone for selected patients (large unresectable tumors, elderly patients, or those with complete response to neoadjuvant chemotherapy) 2

Low-Grade Gliomas (Grade II)

Treatment decisions are based on risk factors including:

• Age >35-40 years
• Uncontrolled epilepsy
• Deficit symptoms or intracranial hypertension
• Large tumor size with mass effect
• Contrast enhancement on imaging
• Low Karnofsky score
• Functional zone involvement 2

Treatment options:

1. For patients with no risk factors:

   • Radio-clinical follow-up with or without biopsy 2
   • Surgical resection if feasible

2. For patients with risk factors:

   • Surgical resection when feasible
   • Partial surgery followed by radiotherapy
   • Radiotherapy alone after histological confirmation 2
   • Chemotherapy for symptomatic patients after histological confirmation 2, 5

Management of Recurrent Disease

For recurrent gliomas, five therapeutic options can be considered 2, 1:

1. Repeat surgery (decision should be made after multidisciplinary consultation)
2. Systemic chemotherapy
   • Temozolomide for temozolomide-naïve patients 3
   • Nitrosourea-based therapy if not previously used 2
   • Clinical trials are strongly recommended 2
3. Local chemotherapy (carmustine implants)
4. Second-line radiotherapy (newer techniques like stereotactic radiotherapy)
5. Palliative care without specific anticancer treatment

Supportive Care and Monitoring

• Prophylaxis against Pneumocystis pneumonia (PCP) is required for all patients receiving concomitant temozolomide and radiotherapy 2, 3
• Regular monitoring of blood counts:
  • Weekly during concurrent chemoradiotherapy
  • Prior to each cycle and on day 22 of each cycle during adjuvant temozolomide 3
• Anticoagulant prophylaxis with low-molecular weight heparin and compression stockings is recommended for preventing perioperative thromboembolic complications 2
• Liver function tests should be performed at baseline, midway through the first cycle, prior to each subsequent cycle, and after treatment completion 3

Common Pitfalls and Caveats

• Pseudoprogression: Radiographic worsening 4-8 weeks after radiation may mimic tumor progression and should be re-evaluated after 4 weeks 1
• MGMT testing: While MGMT promoter methylation predicts better response to temozolomide, treatment should not be withheld based solely on unmethylated status in the absence of better alternatives 4
• Myelosuppression: Temozolomide can cause severe myelosuppression; dose modifications should follow established guidelines based on blood counts 3
• Elderly patients: Age alone should not exclude patients from treatment; hypofractionated radiotherapy with or without temozolomide has shown benefit in patients >70 years 2, 1
• Clinical trials: Patients with recurrent disease should be considered for clinical trials as established options are limited 2