Brain metastases are among the most feared complications in cancer, because even small satellite tumors can be incapacitating.
30% of all women with metastatic breast cancer will eventually develop brain tumors. 30% of these women will not experience symptoms until their tumors are too large to be treated through non-invasive procedures. Herceptin and other
drugs may keep the primary cancer under control but do not cross the blood brain barrier.
The blood-brain barrier regulates which substances in the blood stream gain access to the brain and which do not. It is comprised of tightly packed cells that line the small blood vessels that reach into the brain and spinal cord, forming a
"wall" that prevents most bacteria, viruses and toxins in the blood stream from reaching the sensitive brain tissue. These cells also have the ability to pump toxins trying to get into the brain back into the blood stream.
Unfortunately, the blood-brain barrier also prevents most breast cancer treatments (and other drugs) from penetrating into the brain. This results in HER2 positive patients having a higher incidence of brain tumors. Statistics are showing that about 30 percent to 40 percent of women who are Her2neu-positive and are treated with Herceptin develop brain mets. These mets aren't caused by the drug, but rather are a consequence of the disease's progression. It is for this reason that HER2Support urges all with metastatic disease to have a brain scan as soon as possible. Also, report any symptoms to your oncologist immediately.
.As women are living longer with well-controlled metastatic disease in other organs, developing new therapies that penetrate the blood brain barrier has become an important priority. Already a few new drug therapies have shown promise in treating breast cancer brain metastases. Also under study are ways to disrupt or penetrate the blood brain barrier so that treatments are able to reach the brain.
General Symptoms of Metastases
Headaches are a common initial symptom. Typical "brain tumor headaches" are often described as worse in the morning, with improvement gradually during the day. They may rouse the person from sleep. Sometimes, upon awakening, the person vomits then feels better. These headaches may worsen with coughing, exercise, or with a change in position such as bending or kneeling. They also do not typically respond to the usual headache remedies.
About one-third of people diagnosed with a brain tumor are not aware they have a tumor until they have a seizure. Seizures are a common symptom of a brain tumor. Seizures are caused by a disruption in the normal flow of electricity in the brain. Those sudden bursts of electricity may cause convulsions, unusual sensations, and loss of consciousness. Focal seizures -- such as muscle twitching or jerking of an arm or leg, abnormal smells or tastes, problems with speech or numbness and tingling -- may also occur.
Mental and/or Personality Changes
These can range from problems with memory (especially short-term memory), speech, communication and/or concentration changes to severe intellectual problems and confusion. Changes in behavior, temperament and personality may also occur, depending where the tumor is located. These changes can be caused by the tumor itself, by increased pressure within the skull caused by the presence of the tumor, or by involvement of the parts of the brain that control personality.
These symptoms include vision problems such as blurred or double vision or loss of peripheral vision, hearing problems such as ringing or buzzing sounds or hearing loss, decreased muscle control, lack of coordination, decreased sensation, weakness or paralysis, difficulty with walking or speech, or balance problems.
Treatments for Brain Metastases
Whole Brain Radiation Therapy
Whole brain radiation therapy (WRBT) is used for the treatment of multiple brain metastases. This is the most frequently used therapy for breast cancer brain metastases. In this treatment, radiation is delivered to the entire brain. WBRT has been shown in research studies to extend life and improve the quality of life for those with symptoms. 30% to 40% of patients will achieve a complete reversal of symptoms while 75% to 85% of patients will experience some improvement or stabilization of their symptoms, especially headache and seizure. Motor loss (problems with walking, coordination, balance, etc.) is less successfully treated.
Immediate side effects of WBRT can include memory loss, particularly verbal memory (remembering what someone said to you), extreme fatigue, temporary baldness, skin rash, inflammation of the outer ear, and hearing loss. Longer term toxicities which can occur within six months to two years after WBRT, include memory loss, confusion, lack of urinary control, and lack of coordination. The most feared long term side effect, dementia, occurs in one to five percent of those treated. However, as women live longer after being treated for brain metastases, incidence of dementia is likely to increase.
Radiation is given daily Monday thru Friday for ten days to two weeks. Some doctors will give a lower dose of radiation over a longer period of time to women who have a good prognosis. Factors associated with a longer life expectancy include either well-controlled or no metastases outside the brain, and being able to carry out daily routines without help. Since most chemotherapy treatment is halted during WBRT because of increased toxicity, the trade-off of extending WBRT with smaller daily doses is not always beneficial.
It has been estimated that about fifty percent of those who receive WBRT have recurrences in the brain within a year. Treatments for brain recurrence include radiosurgery (see explanation below) or chemotherapy. A recent study shows that re-irradiation (doing WBRT a second time) can prolong life on the average of a few months safely in very select group of patients. Important factors to consider for re-irradiation include a good response to WBRT the first time and a longer time to recurrence.
Use of radiosensitizers (agents that supposedly make brain metastases more responsive to whole brain radiation) is experimental. None have yet been shown to be beneficial.
Whole Brain Radiation Therapy Following Brain Surgery or Radiosurgery (Gamma Knife, CyberKnife, etc.)
Until recently WBRT has been recommended after either surgical removal of a brain metastasis or radiosurgery, in order to reduce the risk of recurrence in the brain. Recently, this has become a hotly debated question. Unfortunately, there is no high-quality evidence on this question to help patients decide. In one study, recurrence rates in the brain were reduced from 70% for those not receiving WBRT to 18% for those who did receive WBRT. However, some radiation oncologists think a better quality of life is maintained if WBRT is withheld if and until there is a recurrence and that frequent scanning (every three months) will allow recurrences to be picked up earlier enough to prevent compromising quality of life or length of life. Brain recurrences can be treated repeatedly with radiosurgery as long as the metastases are small, holding off WBRT and its side effects indefinitely.
However, there is no guarantee that brain metastases. if they recur. will be small, even with scanning at three month intervals, and large brain metastases can severely compromise quality of life and length of life. Some doctors advise women with a longer life expectancy to wait until a recurrence to do WBRT, putting it off for as long as possible. Other doctors advise just the opposite. They believe women with a longer life expectancy should be treated more aggressively to lower their chances of getting brain recurrences. Recurrences in the brain without WBRT are believed to be very common and have been estimated in various studies to occur in 70-90% of patients. We await the results of a randomized clinical trial which is ongoing on this question. Until then, all studies are biased by the fact that women with the best prognosis are more likely to receive radiosurgery without WBRT.
Radiosurgery (Gammaknife, Cyberknife, X-Knife or Stereotactic Radiosurgery)
Radiosurgery, also called stereotactic radiosurgery or SRS, is a procedure that aims very high doses of radiation (higher than WBRT) directly at brain metastasis. Because the beams of radiation converge from many different directions on the metastasis itself, the rest of the brain is spared these high doses. The name “radiosurgery” is misleading because it is not surgery. Radiation is given from the outside the head without having to cut into the skull. Unlike WBRT, it targets just the metastases, not the entire brain, which minimizes toxicities. It can be used to treat metastases deep within the brain, for example in the brain stem where regular surgery cannot be done safely.
Radiosurgery is the name given to several different technologies including Gamma Knife, CyberKnife, or XKnife. They are cconsidered to be equally effective. Since radiosurgery is generally not used for more than three metastases at a time orcmetastases that are larger than approximately 3 centimeters, it is not a substitute for whole brain radiation or surgery. Some doctors do go outside the guidelines treating more than three metastases and up to four centimeters in size. Severe side effects occur in only 1-2% of those treated. They include seizures, edema, hemorrhage, and radionecrosis (dead tumor tissue). Treatments such as chemotherapy or Herceptin are usually not discontinued.
Because radiation takes several weeks to shrink tumors, symptoms caused by brain metastases are not alleviated immediately. Regular surgery is sometimes necessary to prevent serious brain damage from the pressure of tumor(s) in the confined space of the skull. Radionecrosis from radiosurgery can be hard to distinguish from recurrence. Though it is usually treated with a corticosteroid, sometimes surgery is necessary. Radiosurgery can be repeated if new brain metastases appear, and is thought to be as effective, and safer, than regular surgery for metastases up to three centimeters though no direct evidence exists. Radiosurgery can also be used after regular surgery or WBRT as a “boost” to prevent brain metastases from recurring. One of the most controversial issues in the treatment of brain metastases is whether or not WBRT is necessary after radiosurgery. For more on this, read the preceding section on whole brain radiation therapy following radiosurgery or surgery.
Brain Surgery (Craniotomy)
Brain surgery (a form of neurosurgery known as a craniotomy) entails having a neurosurgeon cut into the brain in order to physically remove the metastasis and a small margin of surrounding tissue. It sounds much scarier than it really is. Surgery has a very low complication rate, mainly infection, although a hospital stay of several days to a week is required. A longer time may be necessary if there are 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.
Brain surgery is used for one or two large metastases that need to be removed immediately because of potential brain damage or if metastases are too big for radiosurgery. Some doctors will surgically remove up to four metastases depending on their location. Surgery is also needed if the diagnosis of a brain metastasis is not certain, so that a biopsy can be performed on the tissue. About 10% of the time the suspected brain metastasis can be something else like a primary brain tumor, a non-malignant mass, or an infection. In some areas of the brain, such as the brainstem, it is too dangerous to do surgery.
Some, though not all, systemic therapy is stopped in advance of surgery and while the incision is healing. Whole brain radiation is often given after surgery to prevent brain metastases from recurring in the same location or in new areas. (See whole brain radiation therapy and stereotactic radiosurgery for discussion of this question). Radiosurgery after surgery can be used as a “boost” to prevent recurrence at the site of surgery.
Chemotheray and Systemic Therapy
Chemotherapy has not been extensively studied for brain metastases in breast cancer. The conventional wisdom has been that chemotherapy drugs are not able to cross the blood brain barrier into the brain. Recently, there has been renewed interest in chemotherapy because evidence is emerging that as brain metastases grow they can disrupt the blood-brain barrier, making it possible for chemotherapeutic drugs to get into the brain. Another problem has been that brain metastases usually occur late in the course of breast cancer when resistance to different chemotherapies is more likely. It has thus been unclear if and when drug resistance plays a role, or if inability of drugs to reach the tumor is more important.
Studies have shown that in some cases brain metastases do shrink in response to chemotherapy, but it is not known if this response actually extends life. Some studies have suggested that Xeloda (capecitabine), high-dose mexthotrexate, the platinum drugs carboplatin and cisplatin, and Adriamycin (doxorubicin) can be effective in shrinking brain metastases.
Hormonal therapies such as tamoxifen, letrozole (Femara) and megestrol acetate (Megace) have been shown to be effective in treating breast cancer brain metastases. However, the majority of women with brain metastases have tumors that are estrogen receptor-negative. Those women whose tumors have been tested as estrogen receptorpositive may have already built up resistance to the existing hormonal therapies. It is assumed that hormonal treatments will not work in these women. An important area of research is how often the hormone status of a brain metastasis has changed from the primary tumor.
Corticosteroids or steroids are usually the first therapy administered to women with brain metastases. Dexamethasone (Decadron) is the steroid of choice. It is given in pill form or as an injection to reduce edema (swelling in the brain). It can start working within several hours. The usual starting dose is 4 to 16 mg per day on a variety of schedules. It is usually best to give the whole dose with breakfast or divided between breakfast and lunch. Steroids may be continued for weeks or even longer. However, the longer they are used, the worse the side effects become. Side effects from steroids can be very serious, but the brain swelling they counteract can be even more serious and possibly life-threatening. Common side effects from long-term use include weight gain, muscle weakness (myopathy), insomnia, moodiness, acne, osteoporosis, hypertension, swelling of the face, cataracts, osteonecrosis (death of bone cells), impaired wound healing, muscle weakness, pneumonia, and diabetes. Physicians can check blood glucose (for diabetes) and prescribe medicine to prevent pneumonia if long-term administration of steroids is needed.
The steroid dose can often be tapered as other therapy kicks in. The dose should be as low as possible. A common short-term complication is steroid myopathy (muscle weakness) which can be mistaken for progression of brain metastases, triggering the use of more steroids which only worsens the myopathy. Physical therapy can be helpful for patients with myopathy. Those whose brain metastases are found by imaging and who do not yet have any symptoms can often avoid steroid use completely. Under study is the use of a lower dose of steroids. Do not get off steroids suddenly unless it is an
emergency. Doses should be tapered gradually.
|Last Updated on Thursday, 21 January 2010 10:16|