What are the treatment options for astrocytoma?

Treatment Options for Astrocytoma

The treatment of astrocytoma depends critically on IDH mutation status, WHO grade, and 1p/19q codeletion status, with maximal safe surgical resection as the foundation followed by grade-specific adjuvant therapy. 1

Initial Surgical Management

Maximal safe surgical resection should be performed whenever technically feasible without causing permanent functional deterioration. 1, 2 The primary goals are:

• Establish accurate pathologic diagnosis and molecular characterization (IDH mutation, 1p/19q codeletion status) 1
• Achieve gross total resection when possible, as complete excision improves survival and may delay malignant progression 1, 2
• Postoperative MRI within 48-72 hours to assess extent of resection 2

Surgery may be deferred only in exceptional circumstances such as elderly patients with multiple comorbidities, poor performance status, or tumors in eloquent brain regions where resection would cause unacceptable neurologic deficits. 1, 2

Grade 2 IDH-Mutant Astrocytoma (1p/19q Non-Codeleted)

High-Risk Patients (Age >40 years, incomplete resection, or symptomatic)

Radiotherapy (50-54 Gy in 1.8-2 Gy fractions) followed by adjuvant chemotherapy (PCV or temozolomide) is the standard of care. 1 The RTOG 9802 trial demonstrated prolongation of overall survival from 7.8 to 13.3 years with RT plus PCV in high-risk grade 2 gliomas. 1

Low-Risk Patients (Age <40 years, gross total resection, asymptomatic)

Observation with close surveillance (MRI every 3-6 months) is reasonable after complete resection. 1 However, if any high-risk features develop, proceed immediately to RT plus chemotherapy. 1

Grade 3 IDH-Mutant Astrocytoma (1p/19q Non-Codeleted)

Radiotherapy (54-60 Gy in 1.8-2 Gy fractions) followed by adjuvant temozolomide is the standard treatment. 1 This recommendation is based on the CATNON trial showing benefit of adjuvant temozolomide in anaplastic astrocytomas. 1

• Temozolomide dosing: 150-200 mg/m² for 5 days every 28 days for 6-12 cycles 3
• PCV is an alternative if temozolomide is not tolerated 1

Grade 4 IDH-Mutant Astrocytoma

These tumors may be treated either as grade 3 IDH-mutant astrocytomas OR as IDH-wildtype glioblastoma depending on clinical context. 1 For aggressive presentations, follow glioblastoma protocols with concurrent chemoradiotherapy. 1

IDH-Wildtype Astrocytoma (Glioblastoma)

The standard regimen is radiotherapy (60 Gy in 2 Gy fractions) with concurrent temozolomide (75 mg/m² daily) followed by adjuvant temozolomide (150-200 mg/m² for 5 days every 28 days for 6 cycles). 2, 3 This is based on landmark trials showing improved survival with combined modality therapy. 2

Critical Requirements During Treatment:

• Pneumocystis jirovecii pneumonia (PCP) prophylaxis is mandatory during concurrent chemoradiotherapy and should continue until lymphocyte recovery. 3, 2
• Weekly complete blood counts during concurrent phase 3
• Liver function tests at baseline, mid-first cycle, and before each subsequent cycle 3, 2

Elderly or Poor Performance Status Patients (Age ≥70 years, KPS <70):

Hypofractionated radiotherapy (40 Gy in 15 fractions) with temozolomide is reasonable. 1 Alternatively:

• RT alone for MGMT promoter unmethylated tumors 1
• Temozolomide alone for MGMT promoter methylated tumors 1
• Best supportive care if prognosis/toxicity concerns outweigh benefits 1, 2

Recurrent Astrocytoma

No standard treatment exists for recurrent disease; therapeutic decisions must be based on performance status, prior treatments, and resectability. 1, 2

Surgical Options:

Repeat cytoreductive surgery improves survival in selected patients with 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 for recurrent glioblastoma 2
• Temozolomide rechallenge if not previously used or if initial response was favorable 1, 2, 4
• Nitrosoureas if not previously administered 1, 4
• Bevacizumab (though not recommended for newly diagnosed disease) 1, 2
• Local carmustine wafer implants 1, 4

Special Considerations for Oligodendroglioma (IDH-Mutant, 1p/19q-Codeleted)

Grade 2:

Radiotherapy (50-54 Gy) followed by PCV chemotherapy for patients requiring treatment. 1 Temozolomide is a reasonable alternative when PCV toxicity is a concern, though evidence is weaker. 1

Grade 3:

Radiotherapy (54-60 Gy) followed by PCV chemotherapy is standard based on EORTC 26951 and RTOG 9402 trials. 1

Critical Pitfalls to Avoid

• Never delay treatment beyond 4 weeks post-surgery 2
• Never omit PCP prophylaxis during concurrent temozolomide and radiotherapy 2, 3
• Do not assume radiographic progression within 6-9 months of RT completion is true progression—consider pseudoprogression 2
• Do not use bevacizumab as standard first-line therapy for newly diagnosed glioblastoma 1
• Ensure molecular characterization (IDH, 1p/19q) before finalizing treatment plans, as this fundamentally alters management 1