Brain metastases, a specific form of Stage IV melanoma, are one of the most common and difficult-to-treat complications of melanoma.  They differ from all other metastases in terms of risk factors, diagnosis, and treatment.

Who Is At Risk?

More than 60% of all Stage IV melanoma patients will develop brain metastases at some point but certain factors can increase that risk: (1-2)

• The primary tumor was on the head, neck, trunk or abdomen

• The primary tumor was ulcerated or deep or invasive.

• The melanoma was unresectable Stage III or Stage IV when diagnosed

• The melanoma has spread to the internal organs

• The LDH (serum lactate dehydrogenase) is elevated.

Why Are Brain Metastases So Difficult To Treat?

Brain metastases are difficult to treat. There are several potential reasons.

• There is growing evidence that brain tumors are very different from tumors in other parts of the body and need to be treated differently.
• The brain looks familiar. Melanocytes arise from the same part of the early embryo as the brain, so the brain might be a very natural environment for melanoma tumors to grow in.
• The brain has many defenses to reduce the penetration of harmful substances. This is called the blood-brain-barrier and it prevents many medications from entering the brain.
• Brain metastases tend to be very aggressive.
• Treatment options may damage surrounding normal tissue and have significant impact on the quality of life.

What Determines the Treatment Options and Prognosis For Patients With Brain Metastases?

• Certain characteristics of both the patient and the cancer will affect the patients' prognosis as well as their eligibility for treatment.  The following factors are associated with better outcomes: (3-5)

• Younger age: <60
• Fewer vs. more brain metastases: <3 lesions
• No extracranial disease: extracranial is the presence of disease outside the cranium
• Normal serum LDH
• High Karnofsky Performance Status (KPS) score (>70)

Risk 

Unfortunately, melanoma brain metastases carry a poor prognosis, with a median overall survival of about 4-5 months. Often a patient first exhibits multiple, symptomatic lesions, making the condition difficult to treat surgically. However, improvements in radiation and systemic therapies are offering promise for this challenging complication, and some patients are curable.

References:
1. Zakrzewski J, Geraghty LN, Rose AE, et al. Clinical variables and primary tumor characteristics predictive of the development of melanoma brain metastases and post-brain metastases survival. Cancer. 2011; 117:1711-1720.

2.Bedikian AY, Wei C, Detry M, et al. Predictive factors for the development of brain metastasis in advanced unresectable metastatic melanoma. Am J Clin Oncol 2010. Dec 13.

3. Fife KM, Colman MH, Stevens GN, Firth IC, Moon D, Shannon KF, et al. Determinants of outcome in melanoma patients with cerebral metastases. J Clin Oncol. 2004;22:1293-1300.

4. Nieder C, Marienhagen K, Geinitz H, Grosu AL. Can current prognostic scores reliably guide treatment decisions in patients with brain metastases from malignant melanoma?. J Can Res Ther [serial online] 2011 [cited 2011 Aug 18];7:47-51. Available from: http://www.cancerjournal.net/text.asp?2011/7/1/47/80458

5. Sperduto PW, Chao ST, Sneed PK, et al. Diagnosis-specific prognostic factors, indexes, and treatment outcomes for patients with newly diagnosed brain metastases: A multi-institutional analysis of 4,259 patients. Int J Radiat Oncol Biol Phys 2010;77:655-61.