By John F. “Jack” Gleason, Jr., M.D, radiation oncologist at Alliance Cancer Care
As a radiation oncologist, I am frequently asked to help care for patients who have brain metastases (mets). The first question is of course “what is a brain metastasis?” Metastasis (1) or metastases (more than 1) are tumors that have started in one part of the body and spread to another. In the case of brain mets, the cancer that started in another part of the body has then spread to the brain. There are also primary malignant brain tumors that start in the brain itself but these are actually less common than metastases to the brain. About 25,000 people are diagnosed with malignant primary brain tumors per year in the United States while approximately 170,000 to 200,000 people per year in the United States develop brain mets. Many types of cancer can cause brain mets but the most common sources are lung cancer, breast cancer, and melanoma. Some patients have brain mets at their initial diagnosis of cancer and others will develop them months or years later after an initial cancer diagnosis.
Brain mets are actually becoming more common. This is in small part because modern medicine uses more frequent imaging and our studies are more sensitive to find small tumors in the brain. It is mostly related to the fact that patients with Stage IV cancers (who have mets to other parts of their body) are living longer than before because of ongoing improvements in systemic therapy (better targeted therapies and immunotherapies in particular). Better systemic therapies mean patients live longer and there is more time for eventual brain mets to develop.
What tools do we have to treat patients who develop brain mets? The good news is we have many tools and they continue to be refined and improved. Possible options are surgery, whole-brain radiation (WBRT), stereotactic radiosurgery (SRS), and even systemic therapy in some select cases. In many situations, a combination of these approaches may be employed.
Surgery can be an option for some patients with brain mets. We tend to use surgery in two main situations: a single large tumor causing significant symptoms that needs to be debulked quickly OR if we need to do surgery to obtain a diagnosis because there are no other known areas of cancer or accessible areas to biopsy. Most patients who do have surgery undergo postoperative radiation to reduce the chances of local recurrence (regrowth of tumor) at the same site. Nowadays, we usually just treat the cavity focally with SRS but we first need to talk about SRS and WBRT further below so that even makes sense to you!
Stereotactic radiosurgery, which we call SRS for short because it is quicker to say, is actually not surgery. There are NOT any incisions or anesthesia. SRS means we are delivering highly accurate and conformal radiation just to the known areas of disease in the brain with treatment systems that are sub-mm accurate. That is right; we are talking 1 mm, which is less than the thickness of your fingernail. Modern engineering, computers, and medical physicists are incredible. In the past, patients treated with SRS required an invasive headframe screwed into their skull that was attached to the table during treatment for immobilization and to provide coordinates for targeting. Today we now have systems, including the one used at Alliance Cancer Care, which are frameless. We do use a relocatable plastic mesh head mask during treatment for some immobilization but we are able to target accurately on the table using imaging in the room and then alignment in 6 dimensions (6D) using a robotic couch. 6D means aligning the targets in x-y-z but also in roll-pitch-yaw like an airplane. SRS treatments are generally delivered in a single session of treatment but sometimes we will use 3-5 days to deliver the total planned dose. We often refer to that as fractionated SRS or fSRS. Either way, our modern frameless approach allows us to deliver SRS treatments in 20-30 minutes, even when treating multiple targets.
Whole-brain radiation (WBRT) is another approach for patients with brain mets where the entire brain is treated with lower dose radiation daily for 10-15 sessions over 2-3 weeks. Each session lasts 5 minutes. It is an approach that is older than SRS but still is an important tool in certain patients.
So your next question is likely…. well how do you decide on SRS vs WBRT for patients with brain mets? Many factors play a role. In general, I favor SRS for patients whenever it is feasible. I favor SRS because randomized studies comparing WBRT to SRS as the first treatment for patients with new brain mets show that SRS patients have fewer neurocognitive side effects (for example, short-term memory loss) and better quality of life. The average survival is the same with either approach. In fact, you can always use WBRT later after initial SRS if needed and vice versa. You can also use multiple sessions of SRS over time if new areas develop in the brain on later scans and need to be treated. Another advantage of SRS over WBRT is fewer treatments (1-5 versus 10-15), which is more convenient for the patient and less likely to delay important systemic therapies. While WBRT patients lose all their hair from treatment, SRS patients usually have no hair loss or sometimes some small focal areas of slight hair loss.
Above, I made the statement that I favor SRS over WBRT when it is feasible. When is SRS not a good option for brain mets? Some patients have so many brain mets that targeting them all with SRS is not feasible or could carry too many risks of damage if the treatment is delivered over such a short number of treatments. There is no exact number cut-off and the size and location of the mets also matter. As a rule of thumb: patients with 4 or fewer mets can nearly always have SRS, patients with 5-10 brain mets can frequently have SRS, and patients with more than 10 brain mets usually are better treated with WBRT as a first option. Part of the issue for patients with numerous brain mets is the safety of delivering the entire radiation dose in a short number of sessions. The other issue for someone with over 10 brain mets is there are very likely other small areas in the brain we cannot see yet and WBRT might prevent those from developing further.
If your radiation oncologist tells you they recommend whole brain radiation, it is not something to be frightened about as a patient. Uncontrolled cancer in the brain is much more of an issue than the possible risks of whole-brain radiation. Many patients who have WBRT don’t have significant memory issues or other side effects. Sometimes they notice no issues or very mild changes in short-term memory or other functions. The other great news is we have new tools demonstrated in randomized trials to minimize the risk of cognitive/memory issues after WBRT. We can offer two things, sometimes in combination, to reduce the risk of long-term effects of WBRT. One approach we utilize is delivering the radiation using a technique called VMAT (volumetric modulated arc therapy) that allows us to limit the dose to the hippocampal regions of the brain. The hippocampus plays an important role in forming memories and sparing the radiation dose was demonstrated to reduce the likelihood of cognitive/memory issues after treatment. The other thing we offer is a 6-month course of the oral drug memantine. Memantine is a drug that has been used for many years to treat patients with dementia. More recent studies showed that taking the drug for 6 months during and after WBRT had a protective effect for memory.
A final thing to mention is the potential role of systemic therapy for patients with brain mets. Historically, most drugs did not help patients with brain mets in large part due to the blood-brain barrier. This natural system allows our bodies to limit blood infections and/or toxins from entering the brain. It also keeps most systemic therapies (chemo, etc) out of the brain making them ineffective against brain mets. Some newer oral targeted drugs and immunotherapies do have activity in the brain for very specific types of brain mets. Discussions about delaying the use of radiation for brain mets to see if certain drugs may control the disease are made on a case by case basis and are best had with you radiation doctor and chemo doctor both on board. In general, the main situation where I would favor trying systemic therapy alone first would be a situation where three criteria are all met: the patient is asymptomatic from the brain mets, there are too many targets to allow for SRS (they would require WBRT), and the patient has a type of cancer where systemic therapy has been shown to have a good response rate.
In closing, patients with stage IV (metastatic) cancer are living longer due to better systemic therapies. This means more of them are alive long enough to develop brain mets. Fortunately, we have many tools to address a patient’s brain mets. Techniques such as SRS or hippocampal-sparing WBRT are excellent ways of treating brain mets in ways that maximize our ability to limit the risk of long-term cognitive and quality of life issues. By using radiation to treat brain mets and modern systemic therapy to address all other areas of disease, many patients with metastatic cancer, including to the brain, are living longer and better lives than in the past.