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 is high
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.
- Often, by the time the patient first exhibits symptoms, they already have multiple lesions.
- Brain metastases tend to be very aggressive.
- 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.
- 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: 3,4,5
- Younger age: <60
- Fewer vs. more brain metastases: <3 lesions
- No extracranial disease: extracranial is the presence of disease outside the cranium
- LDH is normal
- High Karnofsky Performance Status (KPS) score (>70)
Until recently, melanoma brain metastases carried a poor prognosis, with a median overall survival of about 4-5 months. However, improvements in radiation and systemic therapies are offering promise for this challenging complication, and some patients are curable.
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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.