What are the treatment options for managing brain metastases?

Management of Brain Metastases

For patients with brain metastases, treatment should be determined by the number of lesions and performance status: stereotactic radiosurgery (SRS) alone is the preferred approach for 1-4 unresected lesions, surgery followed by SRS to the cavity for 1-2 resected lesions causing mass effect, and whole brain radiation therapy (WBRT) with memantine and hippocampal avoidance reserved for multiple lesions when SRS is not feasible. 1, 2

Initial Diagnostic and Symptomatic Management

• MRI with gadolinium is the required imaging modality due to superior sensitivity in detecting multiple lesions compared to CT 2, 3

• Initiate dexamethasone immediately for symptomatic patients: 4-8 mg/day for moderate symptoms, escalating to 16 mg/day for severe symptoms with marked mass effect 2, 4

• Do not use anti-seizure medications prophylactically—only administer if seizures have already occurred, and prefer agents that don't impact hepatic metabolizing enzymes 2, 4

Treatment Algorithm Based on Number of Lesions and Performance Status

For 1-4 Unresected Brain Metastases (Excluding Small Cell Lung Cancer)

Offer SRS alone as first-line treatment 1, 2, 4

• This approach avoids the neurocognitive decline associated with WBRT while maintaining disease control 4
• Patients with asymptomatic brain metastases should receive local therapy and not defer treatment unless specifically indicated 1
• For symptomatic lesions, local therapy should be given regardless of systemic therapy status 1, 3

For 1-2 Resected Brain Metastases

Offer SRS alone to the surgical cavity 1, 2, 4

Surgery is indicated when:

• Large tumors (typically >3-4 cm) with significant mass effect are present 2, 4
• Symptoms are refractory to steroids 2, 4
• Diagnostic uncertainty exists and tissue diagnosis is needed 1, 4
• Solitary accessible metastases require immediate decompression 1

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

For More Than 4 Unresected or More Than 2 Resected Metastases

SRS, WBRT, or their combination are all reasonable options for patients with good performance status (Karnofsky Performance Status ≥70) 1, 3

When using WBRT, always offer memantine and hippocampal avoidance if:

• No hippocampal lesions are present
• Expected survival is 4 months or more 1, 2, 3, 4

This combination significantly reduces neurocognitive decline associated with WBRT 1

Performance Status Thresholds

Do not offer radiation therapy to patients with:

• Karnofsky Performance Status ≤50, OR
• Karnofsky Performance Status <70 with no systemic therapy options 1, 3

These patients do not derive survival benefit from radiation therapy 1

Systemic Therapy Integration

Systemic therapy is now a first-line consideration for asymptomatic patients with certain tumor types 2, 4

• For non-small cell lung cancer with targetable mutations (EGFR, ALK, ROS1): small-molecule targeted drugs achieve intracranial penetration and can be considered as initial therapy 2
• Efficacy depends on primary tumor type and presence of targetable mutations 2, 4
• For patients with symptomatic brain metastases, local therapy should not be delayed regardless of systemic therapy plans 1, 3

Management of Treatment Complications

Radiation Necrosis

First-line treatment: glucocorticoids 2, 4

If glucocorticoids fail or cause unacceptable side effects:

• Consider bevacizumab 4
• Neurosurgical resection 2, 4
• Laser interstitial thermal therapy (LITT) 2, 4

Neurocognitive Decline

Consider acetylcholinesterase-inhibiting medication and cognitive rehabilitation 2

Critical Pitfalls to Avoid

• Do not defer local therapy for asymptomatic brain metastases unless specifically indicated—this decision requires multidisciplinary discussion of potential benefits and harms 1
• Do not use WBRT without memantine and hippocampal avoidance in eligible patients (no hippocampal lesions, >4 months expected survival), as this significantly increases neurocognitive toxicity 1, 2
• Do not treat poor performance status patients (KPS ≤50 or KPS <70 without systemic options) with radiation therapy—they derive no benefit 1, 3
• Do not use prophylactic anticonvulsants—only treat seizures that have occurred 2, 4