What are the natural history, symptoms, and treatment options for pilocytic astrocytoma?

Pilocytic Astrocytoma: Natural History, Symptoms, and Treatment

Complete surgical resection is the definitive treatment for pilocytic astrocytoma and often results in cure, with excellent long-term survival outcomes. 1, 2

Natural History

Pilocytic astrocytoma (PA) is a WHO grade 1 brain tumor characterized by:

• Slow growth pattern, sometimes with no growth at all, particularly in neurofibromatosis type 1 patients 1
• Excellent prognosis compared to other astrocytomas, with 5-year survival rates of:
  • 94.6% overall 3
  • 96.5% in patients 5-19 years old
  • Declining to 52.9% in adults over 60 years 4
• Rare malignant transformation, unlike higher-grade gliomas 2
• Mean time to recurrence or progression of 2.2 years when it does occur 5
• Typically follows an indolent course with potential for spontaneous growth arrest 1

Anatomical Distribution

• Most commonly located in the cerebellum, especially in children 6, 7
• Can also occur in:
  • Optic pathway (optic pathway gliomas are common in NF1 patients) 1
  • Spinal cord
  • Basal ganglia
  • Cerebral hemispheres 6
• In adults, more likely to involve brain stem and basal ganglia compared to children 3
• Equal distribution between supra- and infra-tentorial spaces in adults 7

Clinical Presentation

Symptoms depend on tumor location and size:

• Headache (90% of adult cases) 7
• Visual deterioration, strabismus, proptosis, papilledema, and nystagmus (in optic pathway gliomas) 1
• Increased intracranial pressure symptoms
• Focal neurological deficits based on tumor location
• Seizures are uncommon (notably absent in one adult series) 7

Radiological Features

• MRI is the gold standard for diagnosis and follow-up 1
• Characteristic appearance:
  • Well-circumscribed mass
  • Often presents as a cyst with a mural nodule, especially in cerebellum 6
  • Variable contrast enhancement
  • Low signal intensity on CT
  • May have solid or predominantly cystic components (cystic tumors have better prognosis) 5
• Post-operative MRI within 24-72 hours is essential to assess extent of resection 2

Risk Factors for Recurrence or Progression

The following factors are associated with higher risk of recurrence or progression:

• Subtotal resection (most significant factor) 5, 3
• T2 invasion on imaging 5
• Predominantly solid tumors 5
• Presence of an exophytic component 5
• Adult age (worse prognosis than in children) 4

Treatment Approach

Surgical Management

• Optimal surgical resection is the standard of care and should be offered to all patients meeting operability criteria 1, 2
• Complete resection significantly improves survival and often results in cure 1, 2
• Even if complete resection is not possible, partial resection should be considered 1
• Postoperative evaluation with MRI is mandatory to assess extent of resection 1

Post-Surgical Management

1. If complete resection is achieved:

   • Simple clinical follow-up is indicated 1
   • No adjuvant therapy is needed 2

2. If incomplete resection:

   • Annual follow-up with clinical assessment and MRI should be undertaken for many years 1
   • If residual tumor shows progression:
     • Consider re-operation if feasible 1, 3
     • Radiation therapy may be considered to suppress recurrence 3
     • Chemotherapy may be considered, particularly in younger children to avoid radiation-related developmental issues 6

3. For optic pathway gliomas requiring intervention:

   • Chemotherapy is traditionally the mainstay of therapy
   • MEK inhibitors (selumetinib, trametinib) show promising results 1

Novel Targeted Therapies

• Emerging therapies target the MAPK signaling pathway dysregulation common in pilocytic astrocytomas:
  • BRAF inhibitors
  • MEK inhibitors 6
  • Selumetinib is FDA-approved for children ≥2 years with symptomatic, inoperable plexiform neurofibromas 1

Prognostic Factors

• Favorable prognostic factors:

  • Complete surgical resection 3, 5
  • Cerebellar location 5
  • Predominantly cystic tumors 5
  • Younger age 4

• Unfavorable prognostic factors:

  • Subtotal resection 3, 5
  • Solid tumor composition 5
  • T2 invasion on imaging 5
  • Exophytic component 5
  • Older adult age 4

Follow-up Recommendations

• Regular clinical and MRI follow-up is essential, especially with incomplete resection 1
• Long-term surveillance is necessary due to risk of late recurrence 1
• Radiation should be avoided when possible, especially in children and NF1 patients, due to risk of vascular and developmental complications 1