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Is brain metastases Stage 4?

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

aimatmelanoma.org - Brain Metastases - AIM at Melanoma Foundation

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Treatment Options

Your doctor will discuss a treatment plan with you. The treatment options for brain metastases are determined by the number of metastases, their size and location, the presence of extracranial metastases (melanoma outside of the brain and spinal cord), any prior treatment for melanoma, whether your melanoma is known to have a BRAF mutation, and your performance status. Treatment plans may involve a single approach or combine multiple approaches but ideally the decision should be taken by a team of specialists including a neurosurgeon, a radiation oncologist, and a melanoma medical oncologist.

Surgery

Surgery is a standard treatment for melanoma brain metastases. It is potentially curative for patients whose melanoma is otherwise controlled and who have a limited number of brain metastases. Generally, surgery is reserved for patients with fewer than three metastases, particularly if they are too large to be effectively treated with focal radiation therapy (described below) or for patients that are having significant symptoms from the tumor It may also be used for tumors that re-grow after previously being treated with radiation or that are causing bleeding in the brain. Patients with many tumors, or tumors in critical areas of the brain, are usually not candidates for surgery.

Radiation: SRS

Stereotactic radiosurgery (SRS) targets certain spots in the brain. One newer type, gamma knife, is able to treat metastases more quickly than previous radiation machines. Compared to whole brain radiation therapy, it has a significantly lower risk of damage to normal brain tissue and subsequent impact on cognitive function. SRS can result in long-term control of brain metastases for some patients. In the past, SRS was reserved for patients with three or fewer brain metastases; at some institutions, gamma knife is now being used to treat higher numbers of brain metastases. Generally, it is most effective for brain tumors that are less than two centimeters in diameter, but specific size limits/guidelines can vary between different institutions. It may also be used after surgical removal of a brain tumor to reduce the risk of tumor recurrence.

Radiation: WBRT

Whole-brain radiation treatment (WBRT) treats brain metastases that can be seen, as well as tumor cells that are too small to be identified by MRI or CT scans. WBRT is likely to slow the growth of tumors, but it is generally not thought to be curative. WBRT works better for patients with brain metastases from other cancers like breast cancer or lung cancer but has lower efficacy for melanoma. WBRT is typically used in patients who have too many brain metastases to be suitable for surgery or SRS, patients with leptomeningeal disease, or in patients who have several tumors grow after having been previously treated with SRS.

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WBRT has a significant risk of causing damage to normal brain tissue, resulting in neurocognitive decline. New techniques (hippocampal sparing RT) and medications (memantine) are often used to reduce the impact of WBRT on cognitive function.

Steroids

Brain metastases can cause swelling in the brain which can result in a variety of symptoms, including headache, nausea, vomiting, and/or confusion. Steroids can reduce swelling in the brain and, therefore, are often used to treat the symptoms caused by brain metastases. The steroids will not treat or eradicate the tumors themselves. Steroids can reduce the effectiveness of immunotherapy, and they can cause a variety of side effects (fluid retention, difficulty sleeping, increased, or excessive energy). For patients who need steroids to control swelling in the brain, there are good reasons to try to find the lowest possible dose that will be successful in controlling the swelling. For patients who have been on steroids for a prolonged period of time (more than three to four weeks), it can be dangerous to suddenly stop steroid treatment, as the body’s ability to make normal amounts of steroids may be suppressed by prolonged treatment. For these patients, steroids are decreased (“tapered”) over time to allow the body to recover its ability to make steroids itself.

Immunotherapy

Most FDA-approved checkpoint inhibitor-based immunotherapies can achieve significant shrinkage of melanoma brain metastases. These responses often last for more than two years. Immunotherapies that have shown such benefit include Yervoy, Opdivo, Keytruda and combination treatment with Yervoy and Opdivo. Most patients who experience significant shrinkage of their brain metastases also experience similar shrinkage or control of tumors growing in other parts of the body. In clinical trials in patients who did not require steroids to control swelling of the brain and/or symptoms from brain metastases, significant shrinkage of melanoma brain metastases was seen in approximately 20% of patients treated with single-agent Yervoy, single-agent Opdivo, and single-agent Keytruda, and more than 50% of patients treated with combination immunotherapy with Yervoy and Opdivo. Immunotherapy may not be the best initial treatment for patients who need to take steroids to control swelling of the brain or other symptoms caused by brain metastases. Clinical trials have shown that for patients who require treatment with steroids, the rates of tumor shrinkage were much lower with Yervoy (approximately 5%) and with Opdivo (approximately 5%). Limited results in patients on steroids have been reported on combination immunotherapy with Yervoy and Opdivo showing decreased rates of response.

Targeted Therapy

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There are multiple FDA-approved targeted therapies for patients with metastatic melanoma with a BRAF mutation in their tumor. Standard of care targeted therapy regimens for such patients include combined treatment with a BRAF inhibitor and a MEK inhibitor. The three approved combination regimens are Tafinlar (dabrafenib) and Mekinist (trametinib); Zelboraf (vemurafenib) and Cotellic (cobimetinib); and Braftovi (encorafenib) and Mektovi (binimetinib). These treatments are NOT to be used in patients who do not have a BRAF mutation in their tumor. In a phase II clinical trial of Tafinlar and Mekinist in melanoma patients with new or growing brain metastases, more than 50% of patients showed significant shrinkage of their brain metastases, and approximately 80% of patients achieved at least slowing of tumor growth. The treatment can be used and be effective in patients who need to take steroids to control brain swelling and/or symptoms from their brain metastases. Although initially effective in most patients, data from clinical trials suggest that the response to targeted therapy in the brain is less durable (long lasting) than the response to targeted therapy in tumors in other parts of the body.

Chemotherapy

Drugs such as Temodar and Fotemustine are able to get into the brain tissue and may be used to treat patients with brain metastases. These therapies achieve significant tumor shrinkage in only a minority (less than 10%) of patients, and they generally are not durable or curative.

Supportive Care

Supportive care is used when the physician feels that active treatment will do more harm than good, or if it is the patient’s preference not to be treated. It’s intended to reduce pain, confusion, and/or seizures, but not to slow or eliminate the growth of the tumors. Steroids are an example of supportive care, as they are frequently used to reduce swelling in the brain caused by metastases, which may help ease symptoms of pain, nausea, and confusion. Other medicines may be used to control seizures, which can be caused by brain metastases.

aimatmelanoma.org - Brain Metastases - AIM at Melanoma Foundation

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