What are the treatment options for brain metastasis?

Management of Brain Metastases

Initial Symptomatic Management

All patients with symptomatic brain metastases should receive dexamethasone at 4-8 mg/day for moderate symptoms, escalating to 16 mg/day for severe symptoms with marked mass effect. 1, 2, 3 This corticosteroid therapy addresses cerebral edema and should be initiated immediately upon diagnosis. 3

• Anti-seizure medications should only be prescribed if seizures have already occurred—prophylactic use is not recommended. 2, 4
• MRI with gadolinium is the preferred imaging modality due to superior sensitivity for detecting multiple lesions. 2, 5

Treatment Algorithm Based on Number of Metastases and Symptoms

Symptomatic Brain Metastases (Any Number)

Patients with symptomatic brain metastases must receive local therapy (surgery, stereotactic radiosurgery, or whole brain radiation therapy) regardless of what systemic therapy is being used for their primary cancer. 1 This is a strong, evidence-based recommendation that takes priority over systemic therapy considerations. 1

Asymptomatic Brain Metastases: 1-4 Unresected Lesions

For patients with 1-4 asymptomatic, unresected brain metastases (excluding small-cell lung cancer), stereotactic radiosurgery (SRS) alone should be offered as first-line treatment. 1, 2 This approach avoids the neurocognitive decline associated with whole brain radiation therapy (WBRT) while maintaining excellent local control. 4

• Local therapy should not be deferred unless specific tumor-directed systemic therapies are available (see below). 1
• Any decision to defer local therapy requires multidisciplinary discussion involving neuro-oncology, neurosurgery, and radiation oncology. 1

Asymptomatic Brain Metastases: 1-2 Resected Lesions

SRS alone to the surgical cavity should be offered to patients with 1-2 resected brain metastases. 1, 2 This provides targeted radiation to the resection bed without the cognitive toxicity of WBRT. 4

Multiple Brain Metastases (>4 Lesions or >2 Resected)

For patients with more than 4 unresected or more than 2 resected brain metastases, SRS, WBRT, or their combination are all reasonable options. 1 The choice depends on:

• Performance status: Patients with Karnofsky Performance Status (KPS) ≥70 are candidates for any of these approaches. 1
• Total tumor volume: Large cumulative volumes may favor WBRT over SRS. 1
• Expected survival: If survival is expected to be ≥4 months, WBRT should include memantine and hippocampal avoidance to reduce neurocognitive decline. 1, 2

Poor Performance Status Patients

Patients with KPS ≤50, or KPS <70 with no systemic therapy options, do not derive benefit from radiation therapy and should receive supportive care only. 1, 5 This represents a critical threshold where treatment harms outweigh benefits. 1

Surgical Indications

Surgery is a reasonable option for patients with brain metastases, particularly those with large tumors causing mass effect. 1, 2 Specific indications include:

• Diagnostic uncertainty when tissue diagnosis is needed. 1, 2, 4
• Large tumors (typically >3-4 cm) with significant mass effect, especially in the posterior fossa. 1, 4
• Symptomatic lesions refractory to corticosteroids. 2, 4
• Solitary accessible metastases in patients with controlled or controllable systemic disease. 1, 4

Patients with multiple brain metastases and/or uncontrolled systemic disease are less likely to benefit from surgery unless the remaining disease is controllable via other measures. 1

Tumor-Specific Systemic Therapy Considerations

For select asymptomatic patients with specific tumor types and targetable mutations, systemic therapy may be considered as initial treatment, potentially deferring local therapy. 1, 2 However, this approach requires:

• Prospective evidence of CNS activity for the specific regimen. 1
• Multidisciplinary discussion before deferral. 1
• Close monitoring for progression to ensure timely local therapy. 1

Non-Small Cell Lung Cancer (NSCLC)

Osimertinib or icotinib may be offered to patients with asymptomatic brain metastases from EGFR-mutant NSCLC. 1 These agents demonstrate CNS penetration and activity. 2, 4

Melanoma and Breast Cancer

Several regimens have shown activity in brain metastases from these primaries, though specific recommendations depend on molecular characteristics. 1 Immunotherapy and targeted agents are increasingly used as first-line options for asymptomatic patients. 2, 4

Small-Cell Lung Cancer (SCLC)

SCLC is specifically excluded from the recommendation for SRS alone in limited metastases. 1 These patients typically require WBRT or systemic therapy given the high propensity for multiple micrometastases. 1

Radiation Therapy Modifications to Reduce Toxicity

Memantine and hippocampal avoidance should be offered to all patients receiving WBRT who have no hippocampal lesions and expected survival ≥4 months. 1, 2 This combination significantly reduces neurocognitive decline without compromising survival. 1

Management of Complications

Radiation Necrosis

First-line treatment for symptomatic radiation necrosis is glucocorticoids. 2, 4 If unsuccessful or side effects are unacceptable:

• Consider bevacizumab as second-line therapy. 2, 4
• Neurosurgical resection or laser interstitial thermal therapy (LITT) for refractory cases. 2, 4

Neurocognitive Decline

Acetylcholinesterase inhibitors and cognitive rehabilitation should be considered for patients experiencing neurocognitive decline. 2 This is particularly relevant after WBRT. 4

Critical Pitfalls to Avoid

• Do not defer local therapy in asymptomatic patients unless specific tumor-directed systemic therapies with proven CNS activity are available and multidisciplinary consensus is reached. 1
• Do not use prophylactic anti-seizure medications—only treat patients who have experienced seizures. 2, 4
• Do not offer radiation therapy to patients with KPS ≤50 or KPS <70 without systemic options, as they derive no benefit. 1, 5
• Do not omit memantine and hippocampal avoidance when using WBRT in patients with expected survival ≥4 months. 1, 2

Follow-Up Protocol

Patients with a history of brain metastases should undergo neurological assessment and neuroimaging at 3-monthly intervals. 1 This allows early detection of progression and timely intervention. 1