What is the recommended treatment for grade 3 astrocytoma?

Treatment of Grade 3 Astrocytoma

For patients with grade 3 astrocytoma, the standard treatment consists of maximal safe surgical resection followed by localized radiotherapy, with adjuvant temozolomide chemotherapy for IDH-mutant tumors. 1

Initial Management

Surgical Approach

• Maximal safe surgical resection should be attempted whenever feasible
• Surgery serves dual purposes:
  • Obtaining tissue for accurate diagnosis and molecular classification
  • Cytoreduction to reduce tumor burden
• Postoperative MRI should be performed within 24-48 hours to evaluate extent of resection 1

Molecular Classification

Molecular testing is essential for proper classification and treatment planning:

• IDH mutation status
• 1p/19q codeletion status (to rule out oligodendroglioma)
• MGMT promoter methylation status (predictive of benefit from alkylating agents)

Treatment Algorithm Based on Molecular Status

For IDH-mutant Astrocytoma, WHO Grade 3:

1. Primary treatment:

   • Maximal safe surgical resection
   • Involved field radiotherapy (54-60 Gy in 1.8-2 Gy fractions)
   • Followed by maintenance temozolomide 1

2. Temozolomide regimen:

   • Initial cycle: 150 mg/m² daily for 5 days of a 28-day cycle
   • Subsequent cycles: May increase to 200 mg/m² if minimal toxicity in cycle 1
   • Continue for 12 cycles 2

3. Monitoring during treatment:

   • Complete blood count before each cycle
   • Liver function tests at baseline, midway through first cycle, and prior to each subsequent cycle 2
   • MRI every 3-6 months 1

For Incomplete Resection of Grade 3 Astrocytoma:

• Localized radiotherapy should be offered as standard treatment 1
• Further resection or chemotherapy can be considered as additional options 1

Management of Recurrence

For recurrent disease, options include:

• Repeat surgical resection if feasible
• Chemotherapy (if not used previously or different agent if used)
• Re-irradiation in selected cases
• Palliative care for patients with poor performance status 1

Special Considerations

Myelosuppression Risk

• Monitor absolute neutrophil count and platelet count prior to each cycle
• Geriatric patients and women have higher risk of developing myelosuppression 2
• Provide Pneumocystis pneumonia prophylaxis during treatment if lymphopenia develops 2

Hepatotoxicity

• Fatal and severe hepatotoxicity has been reported with temozolomide
• Regular liver function monitoring is essential 2

Prognosis

Current treatments with combined modality therapy can prolong overall survival to up to 10 years in patients with grade 3 IDH-mutant astrocytoma 3, representing a significant improvement over historical outcomes.

Common Pitfalls to Avoid

1. Misinterpreting pseudoprogression: Changes in contrast enhancement 4-8 weeks after radiotherapy may represent treatment effect rather than true progression; confirm with follow-up imaging 1

2. Inadequate molecular characterization: Failure to obtain IDH mutation status can lead to suboptimal treatment selection

3. Premature termination of chemotherapy: Maintaining dose intensity is important for optimal outcomes, so appropriate management of side effects rather than discontinuation is preferred

4. Overlooking supportive care: Anticonvulsants for seizure control and appropriate steroid management are essential components of comprehensive care