What are the current treatment approaches for brain metastases?

Current Treatment Approaches for Brain Metastases

The treatment of brain metastases should be based on a multidisciplinary approach with specific therapies determined by tumor characteristics, patient performance status, and extent of disease, with surgery, stereotactic radiosurgery, whole brain radiation therapy, and targeted systemic therapies forming the cornerstone of management. 1

Initial Assessment and Management

• MRI is the gold standard for brain tumor diagnosis due to its higher resolution and sensitivity in detecting multiple lesions when CT might only identify a single tumor 2
• Dexamethasone is the first-line treatment for symptomatic brain metastases with initial dosing of 4-8 mg/day for moderate symptoms, increasing to 16 mg/day for severe symptoms with marked mass effect 3
• Asymptomatic patients with brain metastases typically do not require prophylactic corticosteroids 3
• Steroid dose should be tapered as quickly as clinically possible due to toxicity associated with long-term use (>3 weeks) 2, 3

Surgical Management

• Surgery is a reasonable option for patients with brain metastases, particularly those with large tumors with mass effect 1
• Standardly-accepted indications for craniotomy include:
  • Diagnostic uncertainty where observation is not viable 1
  • Brain metastases causing symptoms refractory to steroids 1
  • Bulky metastases (typically >3–4 cm in maximal size) 1
  • Solitary brain metastases (one brain metastasis in the absence of extracranial disease) 1
• Patients with large tumors with mass effect are more likely to benefit from surgery than those with multiple brain metastases and/or uncontrolled systemic disease 1

Radiation Therapy Options

• For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma 1
• SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases 1
• SRS, whole brain radiation therapy (WBRT), or their combination are reasonable options for other patients 1
• Memantine and hippocampal avoidance should be offered to patients who receive WBRT and have no hippocampal lesions and 4 months or more expected survival 1
• Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy 1

Systemic Therapy Approaches

• Systemic therapy as monotherapy is now a first-line consideration for subgroups of asymptomatic patients with certain tumor types 1
• The efficacy of systemic therapy depends on the primary tumor type and the presence of targetable mutations 1
• For non-small cell lung cancer (NSCLC), particularly adenocarcinomas with targetable mutations or gene rearrangements, small-molecule targeted drugs can achieve intracranial penetration 1
• For EGFR-mutant NSCLC, osimertinib has demonstrated efficacy in brain metastases with a CNS objective response rate of 76-80% 4
• Patients with brain metastases from melanoma, breast cancer, and NSCLC may benefit from specific systemic therapy regimens 1

Management Algorithm Based on Symptomatology

For Symptomatic Brain Metastases:

1. Initiate dexamethasone (4-8 mg/day for moderate symptoms, up to 16 mg/day for severe symptoms) 3
2. Consider surgical resection for:
   • Large tumors with mass effect 1
   • Accessible solitary lesions 1
   • Diagnostic uncertainty 1
3. Local therapy should be provided regardless of systemic therapy used 1

For Asymptomatic Brain Metastases:

1. For patients with 1-4 brain metastases:
   • Consider SRS alone (excluding small-cell lung carcinoma) 1
   • For resected metastases (1-2), offer SRS to the surgical cavity 1
2. For patients with >4 brain metastases:
   • Consider WBRT with memantine and hippocampal avoidance if expected survival ≥4 months 1
3. For patients with driver mutations (EGFR, ALK, BRAF):
   • Consider targeted therapy with close monitoring 1

Management of Complications

• For radiation necrosis:
  • First-line: glucocorticoids 1
  • If unsuccessful: consider neurosurgical resection, laser interstitial thermal therapy, or bevacizumab 1
• For seizures (occurring in 15-20% of patients):
  • Anti-seizure medications should not be used prophylactically 2, 5
  • When required, prefer agents that don't impact hepatic metabolizing enzymes (levetiracetam, lacosamide, lamotrigine) 3
• For neurocognitive decline:
  • Consider acetylcholinesterase-inhibiting medication (donepezil) 1
  • Cognitive rehabilitation has shown positive results 1

Common Pitfalls to Avoid

• Failing to taper steroids appropriately, leading to unnecessary long-term side effects 2
• Using prophylactic anticonvulsants in patients without seizure history 2, 3
• Delaying steroid administration in patients with significant cerebral edema 2
• Overlooking the need for gastric protection in patients on high-dose steroids 2
• Deferring local therapy for asymptomatic brain metastases without specific recommendations based on multidisciplinary discussion 1

The management of brain metastases requires a careful consideration of patient factors, tumor characteristics, and available therapeutic options. With advances in systemic therapies, surgical techniques, and radiation approaches, outcomes for patients with brain metastases continue to improve, though prognosis remains guarded for many patients 1.