Astrocytoma

Astrocytoma is a glioma of astrocytic lineage. The two clinically distinct groups are IDH-mutant diffuse astrocytoma in adults (graded 2, 3 or 4) and pilocytic astrocytoma in children. IDH-wildtype glioblastoma is a separate disease.

IDH-mutant astrocytoma: onset at 30 to 40 years, frontal and temporal lobe, ATRX loss and TP53 mutation without 1p/19q codeletion. Homozygous CDKN2A/B deletion defines grade 4. Median survival is about 10 to 12 years for grade 2, 8 to 9 years for grade 3 and 3 to 5 years for grade 4. It progresses over time to higher grade. Seizures occur in about 70%.

Pilocytic astrocytoma: children aged 5 to 15 years, cerebellum (about 60%), optic pathway (strongly associated with neurofibromatosis type 1) and hypothalamus. A KIAA1549-BRAF fusion is typical. Ten-year survival is over 95% after complete resection. Malignant transformation is rare.

Complications: seizures, hydrocephalus, visual loss and cognitive effects of therapy.

• IDH-mutant: seizures, headache, focal deficit or personality change
• Pilocytic cerebellar: headache, vomiting, ataxia and head tilt over weeks to months
• Optic pathway: visual loss, proptosis, nystagmus, and precocious puberty or diencephalic syndrome in infants
• Red flags: hydrocephalus, rapidly falling vision and sudden hemorrhage

1. MRI brain with gadolinium: IDH-mutant astrocytoma shows a T2/FLAIR hyperintense infiltrating mass with a T2-FLAIR mismatch sign, with enhancement only in higher grade. Pilocytic astrocytoma shows a well-circumscribed cyst with an enhancing mural nodule.
2. Histology and molecular testing: IDH1 R132H immunohistochemistry (sequence IDH-negative cases under age 55), ATRX loss, p53 overexpression, CDKN2A/B status, BRAF fusion, methylation profile.
3. Spinal MRI if dissemination is suspected, and visual assessment in optic pathway disease.

Differentials: oligodendroglioma, glioblastoma, ganglioglioma, medulloblastoma, hemangioblastoma, abscess, demyelination.

IDH-mutant astrocytoma

• Maximal safe resection.
• Grade 2, low risk: observation with MRI every 3 to 6 months. High risk (age 40 or over, residual tumor): radiotherapy 54 Gy in 30 fractions with temozolomide 150 mg/m2 orally days 1 to 5 every 28 days (increasing to 200 mg/m2 if tolerated) for 12 cycles. Vorasidenib 40 mg orally once daily is an option after surgery for residual grade 2 disease (check ALT and AST every 2 weeks for 2 months, then monthly).
• Grade 3: radiotherapy 59.4 Gy in 33 fractions then temozolomide for 12 cycles.
• Grade 4: radiotherapy 59.4 to 60 Gy in 30 to 33 fractions with temozolomide 75 mg/m2 orally daily throughout, then temozolomide 150 to 200 mg/m2 days 1 to 5 every 28 days for 6 cycles.
• Precautions: ondansetron 8 mg orally 30 minutes before temozolomide, blood count weekly during radiotherapy, and trimethoprim-sulfamethoxazole 160/800 mg orally three times a week during concurrent therapy.

Pilocytic astrocytoma

• Gross total resection is curative. Observe residual tumor with MRI at 3 months, then every 6 months.
• Progressive or symptomatic disease: carboplatin 175 mg/m2 IV weekly for 4 weeks followed by 2 weeks of rest, with vincristine 1.5 mg/m2 IV weekly for 10 weeks. Alternatively dabrafenib 2.625 mg/kg orally twice daily (maximum 150 mg twice daily) with trametinib 0.025 mg/kg orally once daily (maximum 2 mg) for BRAF-altered tumors.
• Avoid radiotherapy in young children and in neurofibromatosis type 1 because of second tumor and vasculopathy risk.
• Hydrocephalus: endoscopic third ventriculostomy or external ventricular drain.

Epilepsy: levetiracetam 500 mg orally twice daily, increasing to 1500 mg twice daily. Children 10 mg/kg twice daily, increasing to 30 mg/kg twice daily.

Follow-up: MRI every 3 to 6 months for 5 years in adults. Counsel on fertility, driving restriction and prognosis.