Diagnosis and Treatment Options for Brain Metastases

Tests

Several types of brain scans can be used to diagnose melanoma brain metastases, including CT scans, MRI, or PET scans.

Learn more about imaging studies

Symptoms to Watch For

Specific neurologic signs and symptoms might indicate brain metastases. These include headache, muscle weakness, and behavioral changes such as changes in judgment and reasoning.  Physical problems can include vision changes, hearing loss, dizziness, nausea or vomiting, language disturbances, difficulty walking, and seizures.

If you have been diagnosed with melanoma and have any of these symptoms, you should contact your medical oncologist as soon as possible.

Treatments 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), and the performance status of the patient. Treatment plans may involve a single approach or may combine multiple approaches.

Treatment Options

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 (i.e. less than 3) of brain metastases.

It is usually reserved for patients with 3 or fewer brain metastases, particularly if they are too large to be effectively treated with focal radiation therapy (i.e. SRS, described below). 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

SRS (stereotactic radiosurgery) targets certain spots in the brain; one newer type, gamma knife, is able to treat metastases more quickly than previous radiation machines; SRS can result in long-term control of brain metastases for some patients.

It may also be used after surgical removal of a brain tumor to reduce the risk of tumor recurrence.

In the past, SRS was reserved for patients with 3 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 2 cm in diameter, but specific size limits/guidelines can vary between different institutions.

In comparison to whole brain radiation therapy, it has a significantly lower risk of damage to normal brain tissue and subsequent impact on cognitive function.

Radiation: WBXRT

WBXRT (whole-brain radiation treatment) treats brain metastases that can be seen as well as tumor cells that are too small to be identified by MRI or CT scans; WBXRT is likely to slow the growth of tumors, but it is generally not thought to be curative.

It is typically used in patients who have too many brain metastases to be suitable for surgery or SRS, or in patients who have a tumor grow after having been previously treated with SRS

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

Steroids

Brain metastases can cause swelling in the brain which can cause 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 metastates. However, 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 achieve this.

For patients who have been on steroids for a prolonged period of time (i.e. more than 3 to 4 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

Many FDA-approved immunotherapies can achieve significant shrinkage of melanoma brain metastases. These responses often last for long periods of time (more than 2 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 (i.e. outside of the brain).

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 ~20% of patients treated with single-agent Yervoy, single-agent Opdivo, or single-agent Keytruda; and ≥ 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 and/or symptoms caused by brain metastases. Clinical trials have shown that for patients that require treatment with steroids to control swelling and/or symptoms from brain metastases, the rates of tumor shrinkage was much lower with Yervoy (~5%) and with Opdivo (~5%). Results in patients on steroids have not been reported yet for treatment with single-agent Keytruda or combination immunotherapy with Yervoy and Opdivo.

Targeted Therapy

Targeted therapies are only used in patients who test postive for the BRAF mutation.

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); 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, up to 60% 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 can be effective in, patients that need to take steroids to control brain swelling and/or symptoms from their brain metastases.

Although initially effective in most patients it is rare for targeted therapy to last for long periods of time (more than 2 years) Data from clinical trials suggest that the response to targeted therapy in the brain may be 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 (i.e., less than 10%) of patients, and they generally are not durable or curative.

Supportive Care

Often 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

Intended to reduce pain, confusion, and/or seizures, but not to slow or eliminate the growth of the tumors.

As described above, steroids 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.

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What to Ask Your Doctor About Brain Metastases

It is important to use the time with your doctor to learn as much about your cancer as you can. Find questions you may want to ask him/her.

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