Brain Metastases in Melanoma Patients: Treatment with Adjuvant Postoperative Whole-Brain Radiotherapy

Incidence of Melanoma Brain Metastases

Brain metastases (BMs) of melanoma are associated with a relatively poor prognosis and can affect quality of life. Unfortunately, BMs are a common event in metastatic melanoma. Symptomatic BMs represent the initial site of metastatic spread in 20% but may occur at any time during the course of the disease ( ). Autopsy data have shown that up to 75% of patients who died from metastatic melanoma had BMs ( ; ). Two large institutional series of 686 and 702 patients ( ; ) indicate a generally poor outcome, with the majority (up to 95%) dying directly from BMs. The median survival of patients with multiple metastases in these series was approximately 3–4 months with treatment. However, some patients can survive for a long time following treatment of BMs.

Predictors of Survival in Melanoma BMs

A small percentage of patients survive more than 3 years and are characterized by the presence of a locally treated (by neurosurgery or by stereotactic radiosurgery [SRS]), single BMs and the absence of other visceral disease ( ). The number of cerebral metastases is a significant prognostic factor, with better prognosis seen in single or oligometastatic disease (two to three cerebral metastases). The Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classes have been validated in melanoma ( ).

Other factors that predict for better survival post BM treatment are age less than 65 years at BM diagnosis and absence of all of the following: leptomeningeal disease ( ); neurologic symptoms of weakness and fatigue; ulceration of a cutaneous primary; extracranial disease ( ), especially bone disease; and a serum lactate dehydrogenase (LDH) level less than twice the upper limit of normal ( ).

Usually melanoma units will develop clinical pathways for patients depending on their prognosis, which is based on their presenting characteristics. It is helpful to keep in mind that the treatment intent in BMs is palliative—patients with melanoma BMs will invariably succumb to their cerebral disease and so consideration must be given to minimizing treatment-related toxicity.

Recent Paradigm Shifts

Therapies for BMs include surgery, radiotherapy, and systematic therapy. The good news for patients is that all of these techniques are constantly and rapidly improving in terms of increasing survival and quality of life, with ever-decreasing toxicity from treatment. There have been a number of recent paradigm shifts. Better imaging, such as magnetic resonance imaging (MRI), has led to more BMs being found at an earlier stage. Therefore, patients with multiple BMs on MRI now may have been classed as having a solitary BM in pre-MRI days. This may lead to the assumption that the survival of those with multiple BMs has improved, making comparison with studies done over time problematic. Patients are also being imaged earlier in their disease journey, even when asymptomatic. This is because there are better therapies that are more effective when lesions are smaller, for example, SRS, and drugs that target BRAF -mutant tumor cells with activity in the brain. Trials to test these new therapies are actively looking for accrual among the asymptomatic patients who are at high risk for BMs.

Other paradigm shifts can take place almost without being noticed. The increasing incidence of melanoma means more patients are in need of follow-up and that therefore a greater number of patients with BMs are found. Practice can differ around the globe, usually because of historical factors and therapy availability. For example, different departments can have different ways of triaging patients to different treatments. Even within a given department, the clinical pathways for similar patients may differ greatly even in a short time, because of different breakthroughs filtering into clinical practice.