What are astrocytomas and how are they treated?

Astrocytomas: Diagnosis and Treatment

Astrocytomas are a diverse group of primary brain tumors originating from astrocytes in the central nervous system, with treatment requiring maximal safe surgical resection followed by appropriate adjuvant therapy based on molecular classification and tumor grade. For optimal outcomes in terms of morbidity, mortality, and quality of life, maximal safe surgical resection should be attempted for all astrocytomas when feasible, followed by grade-appropriate adjuvant therapy based on molecular characteristics, particularly IDH mutation status.

Classification and Characteristics

Types and Grades

• WHO Classification:
  • Grade 2 (Low-grade/diffuse astrocytomas)
  • Grade 3 (Anaplastic astrocytomas)
  • Grade 4 (Glioblastoma multiforme)
  • Pilocytic astrocytomas (Grade 1) - distinct entity with better prognosis

Molecular Characteristics

• IDH-mutant astrocytomas:
  • Better prognosis than IDH-wildtype
  • Tend to progress to higher grades over time
  • About 50% undergo anaplastic transformation within 5 years 1

Clinical Presentation

• Seizures (common presenting symptom, especially in low-grade tumors)
• Neurological deficits based on tumor location
• Symptoms may develop gradually (6-17 months from onset to diagnosis) 1
• Headaches and signs of increased intracranial pressure in larger tumors

Imaging Features

• Low-grade astrocytomas: Non-enhancing, low-attenuation/low-signal-intensity lesions on CT/MRI 1
• Diffuse astrocytomas: Poorly circumscribed and invasive 1
• Higher-grade tumors: More likely to show enhancement, necrosis, and edema

Diagnostic Approach

Imaging

• MRI with and without contrast is the gold standard
• Post-operative MRI within 24-72 hours is essential to assess extent of resection 1

Pathological Diagnosis

• Tissue diagnosis is critical for proper classification
• Review by an experienced neuropathologist is highly recommended 1
• Molecular testing for:
  • IDH mutation status
  • 1p/19q codeletion (to rule out oligodendroglioma)
  • MGMT promoter methylation status (for treatment planning)

Treatment Algorithm

Surgical Management

1. Primary goal: Maximal safe resection whenever possible

   • Provides tissue for diagnosis and grading
   • May delay or prevent malignant progression 1
   • Improves survival in most retrospective studies 1

2. Biopsy considerations:

   • For deep or critical brain regions
   • May underestimate grade due to sampling error 1
   • Should provide adequate tissue for molecular testing

Post-Surgical Management for IDH-Mutant Astrocytomas (Grade 2)

1. Low-risk patients (age <40-45 years, asymptomatic or seizures only, gross total resection):

   • Observation alone is appropriate 1
   • Regular MRI surveillance

2. High-risk patients (age ≥40 years, subtotal resection, tumor ≥6cm, tumor crossing midline, neurological deficits):

   • Involved-field radiotherapy (50-54 Gy in 1.8-2 Gy fractions) followed by PCV (procarbazine, lomustine, vincristine) chemotherapy 1
   • This approach significantly improves overall survival (13.3 years vs 7.8 years) 1

Post-Surgical Management for IDH-Mutant Astrocytomas (Grade 3)

• Radiotherapy (54-60 Gy in 1.8-2 Gy fractions) followed by temozolomide 1
• Consider second surgery at recurrence before additional therapy

Management of Anaplastic Astrocytoma (IDH-wildtype, Grade 3)

• Similar approach to glioblastoma
• Radiotherapy (54-60 Gy) with concurrent and adjuvant temozolomide 1

Management of Refractory Anaplastic Astrocytoma

• Temozolomide is FDA-approved for patients who have progressed on nitrosourea and procarbazine regimens 2
• Dose: 150-200 mg/m² for 5 consecutive days of a 28-day cycle 2
• Response rate: 22% with 9% complete response rate 2

Prognostic Factors

• Favorable factors:

  • Younger age (<40 years)
  • IDH mutation
  • Complete surgical resection
  • Good performance status

• Unfavorable factors 1:

  • Age ≥40 years
  • Astrocytoma histology (vs. oligodendroglioma)
  • Tumor size ≥6 cm
  • Tumor crossing midline
  • Presence of neurological deficits

Treatment Challenges and Pitfalls

Common Pitfalls

1. Undergrading from small biopsies:

   • Gliomas have varying degrees of cellularity and mitoses across the tumor
   • Small samples may not represent the highest-grade areas 1

2. Delaying radiation therapy:

   • Early vs. delayed RT shows similar overall survival but better progression-free survival with early RT 1
   • Decision should be based on risk factors and molecular profile

3. Inadequate molecular characterization:

   • IDH status and 1p/19q codeletion testing are essential for proper classification and treatment planning

4. Insufficient follow-up:

   • Regular MRI surveillance is critical, especially in the first 2-3 years
   • Initially every 3-6 months, then less frequently with stable disease

Special Considerations

• Pilocytic astrocytomas (Grade 1) are often curable with surgery alone and rarely transform to higher grades 1
• Gemistocytic astrocytoma is a distinct variant of IDH-mutant astrocytoma with potentially more aggressive behavior 1
• Chemotherapy alone as frontline therapy remains investigational but might be an option if radiotherapy is not feasible 1

The management of astrocytomas continues to evolve with improved understanding of molecular characteristics and development of targeted therapies. The treatment approach should be tailored based on tumor grade, molecular features, and patient-specific factors to optimize survival and quality of life.