Exploring brain metastasis treatments

For patients with HR+ breast cancer, abemaciclib (Verzenio®) is a drug that crosses the BBB and can stabilize brain metastasis as a single agent. Further studies are needed to determine if combining abemaciclib with other drugs will improve response rates. Other systemic treatments are listed in the table below.

For patients with HER2+ breast cancer, the groundbreaking HER2CLIMB trial led to the approval of the first targeted treatment for brain metastasis from breast cancer. Tucatinib (Tukysa®) in combination with trastuzumab (Herceptin®) and capecitabine (Xeloda®) is now the new standard of care for patients with advanced HER2+ breast cancer that has spread to the brain. Tucatinib is the only drug that is currently FDA- approved with a specific indication for breast cancer patients with brain metastasis.

For patients with triple negative breast cancer, systemic options are limited to chemotherapy, but other classes of drugs like immunotherapy are emerging as potential therapies for patients with TNBC brain metastasis.

Stereotactic radiosurgery (SRS) does not involve any incisions or surgery, but is a procedure that aims beams of very high-dose radiation from many different directions directly at the brain metastases, sparing the rest of the brain and minimizing side effects. SRS has different delivery methods including Gamma-Knife, Cyber-Knife, and Linear-accelerator-based delivery / X-Knife – all options are considered to be equally effective.

At this time, the American Society for Radiation Oncology recommends SRS for patients with up to four brain metastases, and in some cases for patients with even more brain metastases. For patients with a larger number of brain metastases, how quickly the brain metastasis spreads may impact which treatment is most optimal. The largest brain metastases eligible for SRS are typically no bigger than four centimeters; if such a metastasis is removed surgically it may be reasonable to pursue SRS thereafter. Your treatment team may decide with you to undertake SRS even if there are more and/or larger metastases. Ask your oncologist to discuss this with you further.

SRS can be repeated if new brain metastases appear later. One side effect of SRS is radiation necrosis, which is an inflammatory process that can arise in 10-15% of patients. Radiation necrosis can look very similar to metastasis in the brain, but can be treated with steroids, or sometimes with bevacizumab (Avastin). Surgery, including LITT, might also be considered, especially if the diagnosis is in question and a patient is having symptoms. Currently there is no definitive imaging tool to determine the difference between tumor growth and radiation necrosis in the brain. Oncology teams have expertise in this area, and can talk with patients on next steps depending upon personal history, needs, and preferences.

Whole-brain radiation therapy (WBRT) is radiation that is given to the whole brain over a period of 2-3 weeks. This type of treatment is preferred when the brain metastases are many in number, spread to the leptomeninges or when SRS is not safe to deliver. The size of metastases is typically not a reason to pursue WBRT but if metastases are causing symptoms and your doctors recommend starting radiation right away, WBRT may be the best option.

WBRT has been shown in research studies to extend life and improve the quality of life for those whose brain metastases are causing symptoms. It has short-term side effects including headache, memory loss, extreme fatigue, appetite loss, temporary baldness, skin rash and hearing loss. Long-term side effects that can occur within six months to two years after WBRT include memory loss, confusion, balance / coordination problems, and hearing loss.

For patients who require WBRT, the standard of care is a type of WBRT that will avoid the important learning and memory center of the brain known as the hippocampus. However, this may only be a viable option if there are no metastases in or near the hippocampi and if there is no leptomeningeal disease present. Most patients will also be prescribed an oral drug called memantine (Namenda®), which has already been FDA approved for Alzheimer’s Disease and can reduce the side effects of WBRT.

Brain surgery often involves a craniotomy, during which a neurosurgeon cuts into the brain in order to physically remove the metastasis. Surgery is reserved for patients who present with a limited number (one or two metastases) of large or symptomatic brain metastases that have the potential for brain damage. Surgery is done most frequently to relieve symptoms from mass effect or to remove larger lesions so that subsequent radiation will work better.

Some doctors will surgically remove up to two or three metastases, depending on their location. Surgery is typically followed by radiation therapy, either SRS or WBRT, as an extra protective measure to prevent recurrence in the same location.

When performed by experienced neurosurgeons, surgery has a very low complication rate. One important complication to ask your surgeon about is the risk of dispersing tumor cells to the meninges as a result of the surgery – this risk is typically very low, but may be especially relevant for tumors in an area called the cerebellum. A typical hospital stay can range from overnight to 3-4 days, even without complications. In recent years, imaging technology has been developed that makes it possible to view the precise location of the metastasis and surrounding tissue, which helps avoid damage to areas of the brain that are important for speech, coordination, memory and other functions.

Surgery may be required if the diagnosis of brain metastasis is not certain, so that a biopsy can be performed on the tissue. About 1-10% of the time, the suspected brain metastasis can be something else like a primary brain tumor, a non-cancerous mass, or an infection. However, in some areas of the brain, such as the brainstem, it is often too dangerous to perform surgery.

Laser interstitial thermal therapy (LITT) is an emerging FDA-approved technique for treating hard-to-reach tumors in the brain. LITT may also be an option for patients who do not respond to SRS or who have radiation necrosis.

It is performed by introducing a laser catheter into the tumor and heating it to temperatures high enough to kill the tumor. The procedure requires only a 1 cm or less incision in the scalp, and takes just a few minutes to complete. Doctors are still learning the best ways to evaluate patients for LITT, and to identify patients who would most benefit. It is generally only available at large medical institutions.