P03.003 Brain metastases

Brain metastases occur when cancer cells spread from their original site to the brain. They are more common than primary brain tumors and can arise from various types of cancer, including lung, breast, melanoma, renal, and colorectal cancers. Understanding the presentation, diagnosis, and management of brain metastases is crucial for clinical practice.

Epidemiology

• Brain metastases are found in 10-30% of adult cancer patients.
• The most common primary sources are
  • lung cancer (40-50%),
  • breast cancer (15-25%),
  • melanoma (5-20%),
  • renal cancer (5-10%), and
  • colorectal cancer (5%).

Pathophysiology

• Cancer cells spread to the brain via the bloodstream.
• Metastases are typically localized at the junction of gray and white matter due to the rich vascular supply.
• The blood-brain barrier (BBB) may be compromised, facilitating the entry of cancer cells into the brain tissue.

Clinical Presentation Patients with brain metastases can present with a variety of neurological symptoms, depending on the location, size, and number of metastatic lesions.

Common Symptoms

1. Headache: Often the initial symptom, is due to increased intracranial pressure.
2. Seizures: Occur in 15-20% of patients.
3. Focal Neurological Deficits: Such as weakness, sensory loss, and aphasia, depending on the tumor location.
4. Cognitive Dysfunction: Memory loss, confusion, and personality changes.
5. Nausea and Vomiting: Resulting from increased intracranial pressure.

Diagnosis Diagnosis of brain metastases involves a combination of clinical evaluation and imaging studies.

Imaging Studies

1. Magnetic Resonance Imaging (MRI): The gold standard for detecting brain metastases, providing detailed images of brain structures.
   • T1-weighted MRI with Gadolinium Contrast: Enhances visualization of lesions.
   • T2-weighted and FLAIR Sequences: Help identify edema and smaller lesions.
2. Computed Tomography (CT): Used when MRI is contraindicated; less sensitive than MRI but can detect larger lesions and hemorrhage.
3. Positron Emission Tomography (PET) is sometimes used to detect primary tumors and evaluate metabolic activity.

Additional Diagnostic Tests

• Biopsy: Rarely needed if the primary cancer is known; used when diagnosis is uncertain.
• Lumbar Puncture: To evaluate cerebrospinal fluid (CSF) in cases of suspected leptomeningeal metastases.

Treatment The treatment of brain metastases aims to control symptoms, improve quality of life, and prolong survival. It involves a multimodal approach.

Medical Management

1. Corticosteroids: Reduce edema and intracranial pressure, improving symptoms.
2. Antiepileptic Drugs: Manage seizures, initiated in patients with a history of seizures.
3. Chemotherapy: Limited efficacy due to the BBB, but newer agents and targeted therapies are showing promise.

Surgical Management

• Resection: Considered for accessible single or few metastases with mass effect, especially if they cause significant symptoms.

Radiation Therapy

1. Whole Brain Radiation Therapy (WBRT): Used for multiple metastases; improves symptoms but has cognitive side effects.
2. Stereotactic Radiosurgery (SRS): Delivers high-dose radiation to specific targets, used for limited number of small metastases.

Emerging Treatments

• Targeted Therapies: For tumors with specific genetic mutations (e.g., EGFR inhibitors for lung cancer).
• Immunotherapy: Boosts the immune response against cancer cells, showing promise in melanoma and lung cancer metastases.

Prognosis The prognosis for patients with brain metastases varies widely depending on the primary cancer type, number and size of metastases, and the patient’s overall health. Median survival ranges from a few months to over a year with appropriate treatment.

Points to Remember

• High Index of Suspicion: Brain metastases should be considered in any cancer patient presenting with new neurological symptoms.
• MRI with Contrast: The preferred imaging modality for diagnosis.
• Multimodal Treatment: Involves corticosteroids, surgery, radiation therapy, and possibly chemotherapy or targeted therapy.
• Symptom Management: Focus on improving quality of life and managing symptoms like headaches and seizures.
• Emerging Therapies: Include targeted therapies and immunotherapy, offering hope for improved outcomes.

Bibliography

1. Posner, J.B. (2000). Neurologic Complications of Cancer. F.A. Davis Company.
2. DeAngelis, L.M., & Posner, J.B. (2009). Neurologic Complications of Cancer. Oxford University Press.
3. Wen, P.Y., & Loeffler, J.S. (2010). Management of Brain Metastases. UpToDate.
4. Chamberlain, M.C. (2017). Neuro-oncology: The Essentials. Cambridge University Press.