Malignant melanoma is one of the most common primary tumors to spread to the brain.
Keith Black, MD
Malignant melanoma is one of the most common primary tumors to spread to the brain. In close to 50% of patients who have metastatic melanoma, the disease can be found in their brain.1
For example, in former President Carter’s case, the cancer was first found in his liver and later removed. During his press briefing last month, he announced that the melanoma had metastasized to his brain, and he was beginning treatment with pembrolizumab immediately.
In order to learn more about melanoma metastases to the brain,Targeted Oncologyinterviewed Keith Black, MD, chairman and professor, Department of Neurosurgery, Cedars-Sinai Medical Center, director, Maxine Dunitz Neurosurgical Institute, director, Johnnie L. Cochran, Jr, Brain Tumor Center, and Ruth and Lawrence Harvey Chair in Neuroscience.
What is the best treatment for patients with melanoma and brain metastases?
Treatment is dependent on a number of factors, and those factors include the number of metastases that have spread to the brain, their size, and the condition of the patient, in terms of both his or her overall medical condition, as well as his or her control of systemic cancer outside of the brain. If there are less than three tumors in the brain, and they are very large (ie, greater than 3 cm), then one can certainly consider surgical removal of those tumors, if they’re in a surgically accessible area followed by a radiosurgery boost to the tumor margin.
If the tumors are smaller than 3 cm, one can certainly also consider surgery followed by radiosurgery or radiosurgery alone. The results and prognosis are slightly better, if one can remove the tumors, followed by the radiosurgery boost, rather than relying on the radiosurgery alone. If there are more than three tumors, and they’re all less than 3 cm, one can consider a radiosurgery treatment to multiple tumor sites, without doing surgery, or one can do sort of a hybrid therapy. If one [tumor] is greater than 3 cm, it needs to be removed, and others can be treated with radiosurgery; that’s an option as well. Typically, when they [tumors] get to be more than 5 to 7 cm, radiosurgery tends not to be preferred. One tends to look at the possibility of whole brain radiation, unless one of the tumors is very large and symptomatic and needs to be surgically removed to allow the patient time to get through the radiation therapy. It depends overall on the size of the tumors, their location, whether or not they’re surgically resectable, and how well the systemic disease is controlled.
What toxicities are associated with these treatments?
Surgery is invasive, and there will always be a risk. There is also a 3% to 5% risk of getting some radiation necrosis from focus radiation, typically about 9 to 14 months after the treatment, which could cause swelling in the area around the radiation necrosis. Sometimes, that’s [the swelling is] limited to a few months, and it can be treated with steroids. In rare occurrences, it gets to a point where the radiation necrosis needs to be removed, in order to control the swelling.
Do you think immunotherapy would be appropriate in this instance?
Yes. It sounds like the systemic disease is limited in President Carter’s case. The lesions in the brain have been treated with focus radiation, and using the checkpoint inhibitors has been very successful in treating melanomas, particularly outside of the brain. There’s also some evidence that they may be effective within the brain itself. Once a T-cell is activated, it can actually get into the brain and cross the blood-brain barrier and be effective. I think that it’s a good choice of treatment for President Carter, and if he gets a response to the radiation treatment, then he has the potential of having that be a very durable response.
Do you think President Carter is at more of a risk because melanoma was found in other parts of his body?
Certainly having systemic spread impacts the prognosis, but if it’s only limited to one site, and if that site is under control, then that attenuates that risk to some extent.
What clinical trials are available for patients with melanoma that has spread to their brain?
Well, I think one of the more exciting ones is the use of checkpoint inhibitorsipilimumab and programmed cell death-1 (PD-1) inhibitors. I think they are really showing some of the most promising results.
What do you think is the most significant information for medical oncologists to know, when treating patients with melanoma that has metastasized to the brain?
Melanoma is not particularly radiosensitive, unlike some tumors that are more sensitive to radiation therapy. We prefer using focus radiosurgery or radiation on these tumors to get a high enough dose to be lethal to the tumors within the brain, and we think that’s an advantage. We try to defer whole brain radiation, unless we’ve exhausted all other options. The approach of combining surgery for some of the larger tumors that are beyond the limit of radiosurgery with treating others that can be treated with radiosurgery is a very compelling strategy, being more aggressive with the number of tumors inside the brain. Typically, in the past, we would limit radiosurgery to one, two, or three tumors, but we’re seeing promising results now that are expanding the numbers higher, to potentially five or seven tumors within the brain.
Where do you hope to see the treatment paradigm progress for melanoma metastases to the brain?
Using strategies to get therapies across the blood-brain barrier is particularly appealing. The use of immune approaches where we’re seeing good systemic results outside of the brain, applying those approaches to tumors within the brain, is also very compelling.