How melanoma brain metastases are found and treated with radiosurgery, surgery, and immunotherapy, plus what to know about steroids, seizures, and driving.
Melanoma spreads to the brain more often than most other cancers do. AIM at Melanoma estimates that more than half of people with stage IV melanoma develop brain metastases at some point. In the TNM staging system, spread to the brain has its own category, M1d.
A decade ago this diagnosis left few options, and AIM at Melanoma notes that typical survival was 4 to 5 months. Care has changed in 2 ways: precise radiation that treats individual spots, and the finding that immunotherapy works inside the brain. Some patients now live for years.
Symptoms depend on where a tumor sits and how much swelling surrounds it. They include:
Many brain metastases cause no symptoms and turn up on a scan. That is an advantage, because small, silent tumors are the easiest to treat.
MRI of the brain with contrast dye detects much smaller tumors than CT does. Doctors usually order a brain MRI when stage IV melanoma is diagnosed, and often for higher-risk stage III disease. They repeat it at intervals during follow-up and any time new neurological symptoms appear. How often to scan varies between centers, so ask what schedule your team follows.
A PET/CT scan of the body does not replace a brain MRI. The brain uses so much sugar that small tumors can hide against the background.
Stereotactic radiosurgery (SRS) involves no incision. It aims many narrow radiation beams from different angles so they meet at the tumor, which gives the tumor a high dose and the surrounding brain very little. Treatment takes 1 to a few outpatient sessions. SRS works best on small tumors and can treat several at once.
Surgery suits a different situation: a large tumor, a tumor causing pressure or symptoms that need fast relief, or a case in which doctors need tissue to confirm the diagnosis. Radiosurgery to the cavity often follows. Whole-brain radiation, once standard, is used much less now because it affects memory and thinking and because better options exist. It still has a place when tumors are too numerous for SRS.
Doctors long assumed that cancer drugs could not reach the brain well enough to help. For immunotherapy, the activated T cells do the work, and they can cross into the brain.
CheckMate 204 (Tawbi and colleagues, New England Journal of Medicine, 2018) treated 94 patients who had untreated melanoma brain metastases and no neurological symptoms with nivolumab plus ipilimumab. The brain tumors shrank or stayed controlled for at least 6 months in 57% of patients, and they disappeared completely in 26%. Tumors elsewhere in the body responded at nearly the same rate. In the final 3-year report (Lancet Oncology, 2021), about 72% of patients without symptoms were alive at 3 years.
An Australian study known as the ABC trial (Long and colleagues, Lancet Oncology, 2018) enrolled 79 patients. Brain tumors responded in 46% of patients given the 2-drug combination and in 20% of those given nivolumab alone. When brain metastases are present and a patient can tolerate it, oncologists therefore tend to favor the combination, which carries more side effects.
For small tumors without symptoms, some teams start immunotherapy and watch closely with MRI, keeping radiosurgery in reserve. Others treat with both up front. For melanomas with a BRAF V600 mutation, BRAF and MEK inhibitor pills also shrink brain tumors in more than half of patients, according to AIM at Melanoma, and they act quickly. Resistance develops in the brain as it does elsewhere.
Dexamethasone, a steroid, reduces swelling around brain tumors and can relieve headaches and weakness within a day or 2. It does not treat the cancer. Steroids also suppress the immune cells that immunotherapy depends on.
CheckMate 204 included a small group of 18 patients who had symptoms, some of whom were taking dexamethasone. Only about 17% of them benefited in the brain. Symptoms and steroid use often go together, so the trial cannot say how much of the difference came from the drug. Even so, doctors try to use the lowest steroid dose for the shortest time, and they may use radiosurgery or surgery to control symptoms so steroids can be tapered. Never stop dexamethasone abruptly, because the body needs time to restart its own cortisol.
Doctors prescribe anti-seizure medicine for people who have had a seizure, to prevent another. People who have never had a seizure generally do not need it.
Driving rules after a seizure are set by each state. The Epilepsy Foundation explains that most states require a seizure-free period and a physician's evaluation before a person drives again. Separate from any law, vision loss, weakness, or slowed thinking can make driving unsafe. Ask your doctor directly whether you may drive, and ask again after each change in your condition or medicines.
Family members should know what to do during a seizure: ease the person to the floor, turn them on their side, put nothing in the mouth, and call 911 for a first seizure or for any seizure that lasts longer than 5 minutes.
