What is the recommended management for a focal high‑grade brainstem glioma?

Management of Focal High-Grade Brainstem Glioma

For focal high-grade brainstem gliomas in adults, maximal safe surgical resection should be pursued when feasible, followed by radiotherapy to 57-60 Gy, as this approach provides significantly better survival compared to biopsy alone. 1, 2

Surgical Approach

Aggressive resection is the cornerstone of management for surgically accessible focal brainstem high-grade gliomas. The evidence demonstrates that:

• Gross total resection (GTR) provides a fourfold survival benefit compared to biopsy alone (median OS: 16 months vs 8 months), while subtotal resection (STR) provides a threefold benefit (median OS: 11 months) 2
• Maximal safe resection should be attempted provided neurological function is not compromised by the extent of resection 3, 1
• The use of brainstem safe entry zones has made focal lesions surgically accessible, particularly for exophytic or dorsally exophytic tumors 4
• When complete resection is not feasible but the patient is symptomatic from mass effect, subtotal resection is recommended for tissue diagnosis and debulking 3

Critical distinction: Focal brainstem gliomas differ fundamentally from diffuse intrinsic pontine gliomas (DIPG). While DIPG carries dismal prognosis and surgery offers no benefit, focal lesions—particularly those that are exophytic, tectal, or cervicomedullary—may be amenable to meaningful surgical resection 5, 4

Postoperative Imaging and Molecular Testing

• Obtain postoperative MRI within 24-48 hours after surgery to confirm extent of resection 3, 1
• Ensure sufficient tissue is obtained for molecular tumor characterization, including MGMT promoter methylation status, IDH mutations, and 1p/19q co-deletions 1

Adjuvant Radiotherapy

Radiotherapy to 57-60 Gy using partial-field external beam or intensity-modulated technique to a 2 cm margin is standard treatment following surgical resection. 6

• Standard fractionation radiotherapy up to 60 Gy is recommended for high-grade gliomas 3
• For elderly patients (>65 years), hypo-fractionated radiotherapy is preferred over standard fractionation 1

Role of Chemotherapy

The evidence for chemotherapy in brainstem high-grade gliomas is limited:

• Concurrent and adjuvant temozolomide (TMZ) with radiotherapy is standard for supratentorial glioblastoma (TMZ daily during RT, then 5 days every 4 weeks for six cycles) 3, 6
• However, postoperative radiation showed no survival benefit in multivariable analysis specifically for brainstem HGG (HR = 1.57, p = 0.161), suggesting the biology of brainstem tumors may differ from supratentorial lesions 2
• MGMT promoter methylation status should guide chemotherapy decisions: methylated MGMT tumors are more likely to benefit from TMZ 3, 1
• The role of combined radiotherapy and chemotherapy has not been thoroughly evaluated specifically in adult brainstem gliomas 4

Supportive Care Considerations

Seizure management (if applicable):

• Antiepileptic therapy is indicated only in patients presenting with seizures; prophylactic therapy is not needed 3
• Third-generation agents (levetiracetam, lamotrigine, pregabalin) are strongly preferred over first-generation drugs that induce hepatic metabolism and interfere with chemotherapy 3, 7

Steroid management:

• Steroids are necessary only in patients with increased intracranial pressure or neurological deficits 3
• Taper off steroids as early as possible 1

Prognostic Factors

Key favorable prognostic factors include:

• Younger age (<50 years, particularly 18-30 years) 3, 2
• Good performance status and intact neurological function 3
• Greater extent of resection (GTR > STR > biopsy) 2
• Low-grade histology (though the question specifies high-grade) 4

Age is a critical prognostic factor: Patients aged 50-60 years have 2.77-fold increased mortality risk, while those ≥60 years have 5.30-fold increased risk compared to younger patients (18-30 years) 2

Follow-up Protocol

• Brain MRI every 2-6 weeks post-radiation initially, then every 2-3 months for the first year, then every 3-6 months indefinitely 3
• Be aware of pseudo-progression, which may occur within 6-9 months after radiotherapy 3
• Clinical evaluation should focus on neurological function, seizures (if applicable), and corticosteroid use 1

Recurrent Disease

• Enrollment in clinical trials is strongly preferred for recurrent or progressive disease 3
• Surgical reresection of locally recurrent disease is reasonable if feasible 3
• For patients with poor performance status or where aggressive therapy is unlikely to provide meaningful survival benefit, palliative and best supportive care with attention to quality of life is recommended 3

Critical Pitfalls to Avoid

• Do not assume all brainstem gliomas are inoperable—focal lesions, particularly exophytic or tectal tumors, may benefit significantly from resection 4, 2
• Do not perform biopsy alone when safe resection is feasible—the survival difference is substantial (8 months vs 16 months for GTR) 2
• Do not use first-generation antiepileptic drugs (phenytoin, carbamazepine, phenobarbital) as they interfere with chemotherapy metabolism 3, 7
• Obtain histological confirmation when possible, as radiological classification alone is imperfect and differential diagnoses are broad in adults 4