Oligodendroglioma

Oligodendroglioma is a diffuse glioma defined by an IDH mutation and combined deletion of chromosome arms 1p and 19q, graded 2 (low grade) or 3 (anaplastic). Incidence is about 0.3 in 100,000 people a year. Peak age is 35 to 50 years, and about 50 to 65% arise in the frontal lobe. Additional features are TERT promoter mutation and CIC and FUBP1 mutations.

It is the glioma with the longest survival, with a median of over 12 years for grade 2 and about 10 years for grade 3. About 60 to 80% of patients present with seizures. Natural history is slow growth with progression to anaplastic disease over years. Complications: refractory epilepsy, cognitive decline, hemorrhage (uncommon) and neurotoxicity of treatment.

• A first seizure (focal or generalized) in most patients
• Headache, personality change, executive dysfunction and mild weakness
• Slow progression over years
• Red flags: new enhancement, rapid growth, raised pressure and sudden deficit from hemorrhage

1. MRI brain with gadolinium: a cortical and subcortical frontal mass, T2 hyperintense with a mixed signal, calcification (confirm with CT in about 70%), and enhancement in higher grade. Perfusion MRI shows raised relative cerebral blood volume.
2. Histology: round uniform nuclei with perinuclear halos and a delicate branching capillary network.
3. Molecular confirmation: IDH1 or IDH2 mutation, 1p/19q codeletion, CDKN2A/B status (a homozygous deletion marks aggressive behavior), MGMT promoter methylation.
4. EEG for epilepsy characterization.

Differentials: IDH-mutant astrocytoma, glioblastoma, ganglioglioma, dysembryoplastic neuroepithelial tumor, infarct, cortical dysplasia and encephalitis.

Surgery: maximal safe resection, using awake mapping for tumors near language and motor cortex. Postoperative MRI within 72 hours.

Grade 2

• Low risk (age under 40 and gross total resection): observation with MRI every 3 to 6 months.
• High risk (age 40 or over, or residual tumor): radiotherapy 54 Gy in 30 fractions of 1.8 Gy, followed by chemotherapy with PCV (procarbazine 60 mg/m2 orally days 8 to 21, lomustine 110 mg/m2 orally day 1 and vincristine 1.4 mg/m2 IV on days 8 and 29, maximum 2 mg, every 6 weeks for 6 cycles).
• Vorasidenib 40 mg orally once daily after surgery for residual or recurrent grade 2 disease when immediate radiotherapy and chemotherapy can be deferred. Check ALT and AST every 2 weeks for 2 months and then monthly for 2 years. It makes hormonal contraception unreliable.

Grade 3: radiotherapy 59.4 Gy in 33 fractions of 1.8 Gy with PCV for 6 cycles, or temozolomide 150 mg/m2 orally days 1 to 5 every 28 days (rising to 200 mg/m2 if tolerated) for 12 cycles.

Drug precautions: procarbazine causes myelosuppression and a disulfiram-like reaction with alcohol, so avoid tyramine-rich foods. Lomustine causes delayed myelosuppression at 4 to 6 weeks and pulmonary toxicity (limit total dose to 1000 mg/m2). Vincristine causes neuropathy and constipation. Check blood count weekly during procarbazine. Temozolomide needs ondansetron 8 mg orally 30 minutes before each dose and pneumocystis prophylaxis during radiotherapy.

Epilepsy: levetiracetam 500 mg orally twice daily, increasing to 1500 mg twice daily, or lacosamide 100 mg orally twice daily (maximum 200 mg twice daily). Avoid enzyme-inducing drugs (carbamazepine, phenytoin) during chemotherapy. Dexamethasone 4 mg orally two to four times daily for short courses of edema.

Follow-up: MRI every 3 to 6 months. Counsel on driving restriction after seizures and on sperm banking before PCV.