All About Brain Metastases
What are Brain Metastases?
Brain metastases are the spread of a primary tumor to the brain. This is different from a primary brain tumor. Differing between these two types of brain lesions is a common source of confusion for many people. For example, a lung cancer is first formed in the lung tissue, but tumor cells can break off from the original mass and travel through the bloodstream or lymph system to other areas of the body, including the brain. This spreading of the tumor is known as "metastasis". When a lung cancer metastasizes to the brain, this "brain tumor" is actually lung cancer cells.
Primary malignant brain tumors are tumors that start in the brain. They are actually quite rare, with an estimated 24,000 new cases in 2016. Brain metastases, commonly called "brain mets," are far more common. The exact incidence of brain metastases is not known. Studies suggest brain metastases occur in 10%-30% of patients with cancer; an estimated 150,000-200,000 cases per year in the United States.
If the pathologist took a biopsy of the brain lesion and looked at it under a microscope, it would look like lung cancer cells. It is important to understand the difference between primary brain tumors and brain metastases because they are treated differently. The media may refer to a person who died of lung cancer and brain cancer, when, in actuality, it was lung cancer that had metastasized to the brain.
Among tumor types, lung cancers account for the highest number of brain metastases, with 25% of patients being affected at some time in their disease course. Other cancers that commonly metastasize to the brain include melanoma, breast cancer, colon cancer, and renal cell (kidney) cancer. Although these are the most likely types to do so, any type of cancer could spread to the brain.
The oncology community has seen a rise in the number of brain metastases in recent years. This may be due to better diagnosis of brain metastases using advanced imaging and also because people are living longer with metastatic disease due to advances in cancer therapy. Unfortunately, in most cancers, once a person develops brain metastases, the tumor is not curable. With current treatments, patients can live from months to years, depending on the number of brain metastases, the type of tumor, and the amount of cancer present in the rest of the body.
It is important to remember that not all cancers are equal. Some are more aggressive and/or less susceptible to treatments than others. For this reason, prognoses vary greatly from tumor to tumor and person to person. These variations are also important to consider when choosing treatments. For instance, primary lung cancers are quite sensitive to radiation, but melanomas are not. This susceptibility to radiation, or radiosensitivity, does not change once the tumor spreads to the brain. In turn, treatment decisions vary based on the primary (original site) tumor type.
In terms of chemotherapy, researchers have known for years that many of the chemotherapy agents commonly used are not able to cross the blood-brain barrier. This means the medications are not able to penetrate the brain, and therefore cannot effectively kill cancer cells in the brain. Because of this, most chemotherapy agents, are not very effective at treating brain mets, even if they are working well elsewhere in the body. For most patients, treatment of brain metastases centers around surgical and radiation techniques. We will review the various treatments available and the relevant supporting data.
Signs, Symptoms and Diagnosis
Common signs and symptoms of brain metastases include changes in cognitive ability (memory, attention, reasoning), behavior changes, gait ataxia (unsteadiness), visual changes, aphasia (difficulty finding words), headache, weakness, and seizures. Report any of these to your care team immediately.
If brain metastases are suspected, your care team will obtain radiology studies (MRI, CT scan). A biopsy may be needed, especially if the patient presents without a primary cancer or if there has been a long period of time between treatment for the initial primary cancer and the new symptoms that may be associated with brain metastases.
The danger of brain metastases is the space they take up in the brain and the pressure they put on surrounding tissue. This pressure can cause the symptoms associated with brain lesions, such as headaches, speech difficulties, seizures, nausea/vomiting, weakness of a limb, or visual disturbances. The goal of initial therapy is to relieve some of this pressure on the brain tissue by decreasing swelling using medications called corticosteroids (dexamethasone, prednisone), either orally or through an intravenous (IV) line. Some patients may see relief of symptoms quickly after starting steroids, however this does not mean the tumor is gone. If patients experience seizures as a result of their brain metastases, they may also receive anti-seizure medications to prevent further seizures.
Treatment decisions for each patient are based on several factors, including tumor type, general health, age, presence/control of cancer outside of the brain, and number of brain metastases.
For patients with a single brain lesion, surgery may be a good option, especially if the tumor is under control in the rest of the body. However, the lesion must be in an area of the brain where it is safe to operate. A study of patients with a single brain metastasis randomized to whole brain radiation therapy (WBRT) alone vs. surgery followed by WBRT found that patients treated with surgery and WBRT have fewer recurrences, and better quality of life than patients treated with WBRT alone. Life expectancy in these patients has also been shown to increase. However, these results do not apply to patients with radiosensitive tumors such as lymphomas, small cell lung cancer, and germ cell tumors (where surgery is generally not recommended).
Whole Brain Radiation Therapy
Whole brain radiotherapy (WBRT) is just what it sounds like – giving radiation to the entire brain. This is generally given in 10 to 15 doses (also called fractions), and is often used in patients with poor prognostic factors, patients who are not candidates for surgery, or patients with more than 3 brain lesions. Many patients may receive WBRT in combination with another therapy (surgery, radiosurgery). The motivation of treating the whole brain is that there may be cancer cells in the normal-appearing brain, but just not enough of them yet to form a mass and be seen by radiology studies. Thus, treatment of the whole brain attempts to kill all the cancer cells.
WBRT has been reported to improve symptoms of brain metastases in 70-90% of patients, although some of this benefit is also a result of the corticosteroids. Despite this symptom improvement, recurrence is common, and control of brain metastases may only be achieved in half of the patients. Patients with tumors that are more sensitive to the effects of radiation fare better (lung and breast, for example) than those with relatively radioresistant tumors (melanoma and renal cancers).
It is difficult to evaluate the long-term effects of WBRT, given the small number of patients that survive long-term. These effects could include dementia and a decline in cognitive and physical functioning.
Stereotactic Radiosurgery (SRS)
Stereotactic radiosurgery (SRS) is a confusing term. It is actually not surgery at all, but a highly precise administration of a large dose of radiation to the tumor site. Unlike traditional external beam radiation, which is usually given daily over many weeks, SRS is administered in a single dose (Gamma Knife®) or up to five doses (Cyberknife®) and other linear accelerator-based treatments). More than one brain tumor can be treated during one session (for example, if a patient had 2 separate brain metastases, both could be treated on the same day). Treatments are administered by a traditional radiation machine called a linear accelerator, or a specialized machine such as Gamma Knife®, Cyberknife®, XKnife® and ExacTrac®.
Gamma Knife® delivers several hundred beams of radiation from a cobalt source. To take you back to high school chemistry, cobalt is one of the elements in the periodic table. It is the radioactive source used in this technique. The radiation beams concentrate at the point where all the beams meet (see picture). The radiation beams travel through hundreds of holes in the helmet to converge on the tumor, allowing a high dose of radiation to be delivered to the tumor, while sparing the surrounding tissue from the high dose. SRS is highly dependent on accuracy, and requires that the patient's head be securely stabilized using a helmet (head frame), so there is no movement during the treatment. Finally, there is a size limit for Gamma Knife; the metastases should be 3 cm or smaller.
XKnife® is a linear accelerator- based treatment. Like Gamma Knife, it requires a head frame, which will remain on the patient for the entire procedure, providing a reference for the location of the patient's anatomy.
Cyberknife® is a form of frameless SRS using a specialized miniature linear accelerator with a robotic arm. It gets around the issue of using a frame for immobilization by using a custom mask for each patient along with skull-based tracking, allowing the robot to follow a target. Cyberknife can accommodate lesions larger than 3 cm, and can also be used to treat other types of cancer outside the brain.
Your care team will assess the best radiation option(s) for you and create a patient specific care plan to best treat your brain metastasis and control your symptoms.
Currently, no systemic chemotherapy treatments have received FDA approval for the treatment of brain metastases from solid tumors. It is widely believed that most chemotherapy agents are not able to cross the blood brain barrier. In other words, they move through the blood stream, but cannot enter the brain. As a result, the brain is a safe haven for cancer cells that "escape" the chemo and make their way there. However there are exceptions. Researchers have found that brain metastases from tumor types that are particularly sensitive to chemotherapy (for example testicular cancer, lymphomas, and small cell lung cancer) are also sensitive to chemotherapy. Research has also demonstrated that in those who have not already received a large amount of chemotherapy may have a greater reduction in brain metastases with chemotherapy treatment. This leads researchers to believe that there is some penetration of the blood brain barrier by chemotherapy, just not always in effective amounts. One chemotherapy agent, temozolomide (Temodar®), is an oral medication that is capable of crossing the blood-brain barrier. This medication is used to treat primary brain tumors and metastatic melanoma lesions.
Preventing Brain Metastases with WBRT: Prophylactic Cranial Irradiation
Small cell lung cancer is associated with a very high risk for brain metastases; approximately 50% of patients develop lesions within two years of diagnosis. For this reason, researchers looked at utilizing whole brain radiation as a way to prevent future brain metastases from developing. When whole brain radiation is given as a preventive measure, it is also known by the name "prophylactic cranial irradiation" or "PCI." Studies of PCI have shown significant decreases in brain mets (from 55% to 19% at 2 years and from 56% to 35% at 3 years) and increases in overall survival. Some have suggested there may be long-term neurologic impairment from this treatment, but long-term neurotoxicity data is lacking. PCI is the standard of care for patients with limited-stage small cell lung cancer who have complete remission after local therapy. Studies are ongoing to assess any benefits of this practice in other tumor types.
Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.
Use our Cancer Types menu to find more information about primary tumor types and their treatment.
Costa, D. B., Shaw, A. T., Ou, S. H. I., Solomon, B. J., Riely, G. J., Ahn, M. J., ... & Crinò, L. (2015). Clinical experience with crizotinib in patients with advanced ALK-rearranged non–small-cell lung cancer and brain metastases. Journal of Clinical Oncology, 33 (17), 1881-1888.
Gadgeel, S. M., Gandhi, L., Riely, G. J., Chiappori, A. A., West, H. L., Azada, M. C., ... & Ou, S. H. I. (2014). Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. The Lancet Oncology, 15(10), 1119-1128.
Gamboa-Vignolle C,Ferrari-Carballo T, Arrieta O, et al. (2012)Whole-brain irradiation with concomitant daily fixed-dose Temozolomide for brain metastases treatment: A randomised phase II trial. Radiotherapy and Oncology: doi:10.1016/j.radonc.2011.12.004
Gazit, I., Har-Nof, S., Cohen, Z. R., Zibly, Z., Nissim, U., & Spiegelmann, R. (2015). Radiosurgery for brain metastases and cerebral edema. Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia, 22(3), 535-538.
Kondziolka, D., Kalkanis, S. N., Mehta, M. P., Ahluwalia, M., & Loeffler, J. S. (2014). It is time to reevaluate the management of patients with brain metastases. Neurosurgery, 75(1), 1-9.
Lippitz, B., Lindquist, C., Paddick, I., Peterson, D., O’Neill, K., & Beaney, R. (2014). Stereotactic radiosurgery in the treatment of brain metastases: the current evidence. Cancer Treatment Reviews, 40(1), 48-59.
Nayak, L., Lee, E. Q., & Wen, P. Y. (2012). Epidemiology of brain metastases. Current Oncology Reports, 14(1), 48-54.
Ramakrishna, N., Temin, S., Chandarlapaty, S., Crews, J. R., Davidson, N. E., Esteva, F. J., ... & Lin, N. U. (2014). Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2–positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline. Journal of Clinical Oncology, 32(19), 2100-2108.
Saad, S., Wang, T. J., Jani, A., Qureshi, Y. H., Yaeh, A., Nanda, T., ... & Isaacson, S. R. (2014). BM29: Number of Brain Metastases Influences Survival Following Gamma Knife Radiosurgery. Neuro-Oncology, 16(suppl 5), v38-v38.
Sahgal, A., Aoyama, H., Kocher, M., Neupane, B., Collette, S., Tago, M., ... & Chang, E. L. (2015). Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis. International Journal of Radiation Oncology, Biology, and Physics, 91(4), 710-717.
Wegner, R. E., Leeman, J. E., Kabolizadeh, P., Rwigema, J. C., Mintz, A. H., Burton, S. A., & Heron, D. E. (2015). Fractionated stereotactic radiosurgery for large brain metastases. American Journal of Clinical Oncology, 38(2), 135-139.
Wong, E., Tsao, M., Zhang, L., Danjoux, C., Barnes, E., Pulenzas, N., ... & Chow, E. (2015). Survival of patients with multiple brain metastases treated with whole-brain radiotherapy. CNS Oncology, 4(4), 213-224.
Yamamoto, M., Serizawa, T., Shuto, T., Akabane, A., Higuchi, Y., Kawagishi, J., ... & Tsuchiya, K. (2014). Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. The Lancet Oncology, 15(4), 387-395.