The risk for the development of brain metastases is very high in melanoma, and more likely than any other common solid malignancy.
Between 30-40% of patients with metastatic melanoma have brain metastases at the time of diagnosis.
Up to 80% of patients with metastatic melanoma have a brain metastasis at the time of death.
Tumors in the brain can cause swelling and pressure that affect neurologic function manifested by headaches, numbness, weakness, difficulty speaking or swallowing.
Melanoma brain metastases is associated with significant neurologic morbidities and disease related mortality.
Historically patients with melanoma and brain metastases have had a median survival of just 4-5 months.
With the advent of immunotherapy and local therapy improvement with the stereotactic radiosurgery the prognosis has been significantly improved with patients with MBM with a median overall survival now exceeding two years.
The usual treatment is local with surgery or radiation, followed by systemic therapy.
Surgery is the best choice for large and symptomatic metastases, especially those that have intratumoral hemorrhage.
Surgery is considered if the tumor is surgically accessible, if the condition involves a solitary brain lesion, all of the lesions are symptomatic going to vasogenic edema and has a mass effect.
Brain metastatectomy is associated with an improved overall survival.
Brain metastatectomy improves response of subsequent immunotherapy.
Studies suggest surgical management for multiple metastatic brain lesions is also associated with improved quality of life and longer overall survival.
Patients considered suitable metastectomy if they have a Karnofsky performance status of 970 or greater, controlled extracranial disease, surgically accessible brain lesions, and up to 3 to 4 brain lesions.
Stereotactic radio surgery is highly effective to control brain metastases.
Stereotactic radio surgery only works for the lesions that are targeted and does not help lesions elsewhere in the brain.
Approximately 90% of patients who have brain metastasis and lesions outside the brain.
Whole brain radiation can provide palliation, but produces cognitive decline and studies do not show significant clinical benefit in terms of survival or preservation of performance status.
Melanoma cells are particularly resistant to radiotherapy owing to their DNA repair ability.
Whole brain radiation may be considered in patients with more than four metastatic brain lesions, and for those who stereoscopic radiotherapy may be difficult, or any patient to have leptomeningeal disease or are at high risk for it.
Toxicity from whole brain radiation include cognitive dysfunction with memory and reduced performance status.
Whole brain radiation toxicity can be reduced by avoiding therapy to the hippocampus, and the use of memantine hydrochloride, which is a NMDA receptor binder.
In patients who are a BRAF V600 drug inhibitors debrafenib and vemurafenib can shrink brain metastasis in 40-58% of patients.
Single agent immunotherapy with ipilimubab, pembrolizumab , or nivolumab have response rates of approximate 20%.
Ipilimubab and pembrolizumab in combination as a intracranial response rate of 46%, and responding patients tend to have a very durable response.
Ipilimubab and nivolumab in combination had a response rate of 57% for intracranial disease with the median follow up of 14 months.
Patients with asymptomatic brain metastases do the best with immunotherapy.
The response to immunotherapy for brain metastases is reduced in the presence on corticosteroids.