Brain Metastases (Mets, Secondary Brain Tumors)
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Metastases, "Mets", or secondary brain tumors (tumors from other parts of the body)

Copyright © 2003 Paul M. Zeltzer MD - Posted 8/13/2003 on virtualtrials.com/brainmets.cfm

Is it a brain tumor or a tumor in the brain? What is the difference?

One of the most frequently asked questions on the WWW.Virtualtrials.com website is about the difference between primary and secondary brain tumors. A primary brain tumor starts from actual brain cells. Most are astrocytomas or gliomas (See Table). Secondary brain tumors are called metastases (mets) and spread from other organs in the body. The latter are named by their tumor of origin: breast, lung, colon carcinoma etc.

It is very important for you to know whether your tumor started in the brain or it came from elsewhere (a metastasis), because the treatment plan will be different. About 10% of the 150,000 people diagnosed with lung cancer each year (15,000) will first find out they have a lung cancer, because the lung tumor cells traveled by the blood stream to their brain and caused symptoms. Or the problem could arise long after the primary tumor (in breast, ovary, or colon) was successfully treated. This is really a sign of success. Why? When treatment for breast cancer was not as good as it is today, people did not live as long. The "penalty" for longer life is that it gives more time for some errant tumor cells to either travel to the brain or set up shop and grow there. (More on that later.)

Where do mets come from?

Mets are the most common "tumors" that appear in the brain in adults (about 150,000 yearly in the USA) and are rarer in children. The most common types of cancer that metastasize to the brain originate in the lung, breast, colon and prostate. Malignant melanoma, an aggressive form of skin cancer, also has a high rate of metastasis to the brain. (or Prados, or Kaye). See Fig _ for types of mets in adults and children. They reflect the commonest types of tumors in those age groups. (Mehta slides). Fig for most common types of mets

What are the seven typical signs and symptoms for a brain or spinal metastasis?

In any patient previously diagnosed with cancer, the following should raise the suspicion for a brain tumor:

  1. A persistent headache with or without vomiting.
  2. Seizures (Change in type or frequency )
  3. Double vision, mental changes, speech difficulty.
  4. Stroke (brain hemorrhage). Certain brain metastases, such as melanoma, renal carcinoma, and choriocarcinoma bleed easily.
  5. Confusion
  6. Any numbness, arm or leg weakness, back pain, difficulty walking.
  7. Loss of control of bowel or bladder.

Numbers 6,7 are more common with spinal metastases.

The types of symptoms, which may occur with a metastatic tumor, usually signify the tumor's location within the brain, not from where it came. The MRI scans confirm this suspicion. Tumors in or near the motor areas can cause weakness on the opposite side of the body; while tumors around the language areas (located on the left side in 90% of adults) can cause difficulties with speech or understanding.

How are mets detected? What tests are needed for initial evaluation?

Suspicion of a new tumor may be due to new symptoms, findings during the neurological exam, or as part of a screening CT or MRI scan of the brain in a patient with known cancer. The gold standard for scans for decision-making purposes are both enhanced and unenhanced MRI of head and spine. The MRI scan may find either single or multiple metastatic tumors. Usually, metastatic tumors are located near the surface and can be removed quite easily by the neurosurgeon.

Of great importance is the need to have adequate staging. Thus, at a minimum, the following should be performed are usually performed in any patient with a metastasis:

  • a brain and spinal MRI
  • spinal fluid analysis
  • search for the primary tumor


How are metastases classified or graded? Is biopsy important?

The tumor type and grade are performed by a Pathologist and are critical to your treatment. They decide exactly which therapies you will receive. If either one is off, then you will not receive the correct therapy. For example, a lymphoma can look like a malignant astrocytoma under certain circumstances. The successful treatment programs are very different. This is yet another reason why a biopsy can be so important. Do not make assumptions about your tumor type without a biopsy! Sometimes what looks like cancer on the MRI or CAT is not even a tumor!

Pathologists who study these tumors under the microscope assign family types (breast, colon, lung, lymphoma etc) and grades (high or low) to a metastasis following biopsy or removal. Sometimes both a primary brain and a secondary tumor can occur in the same patient over different times and even more rarely at the same time.

What are my treatment options if I have metastatic brain tumor(s)?

There are no standard recommendations for anyone with a brain metastasis. For this reason it is important that you consult with a major Brain Tumor treatment center which has a large experience and preferably clinical trials for this condition. Most Neurooncologists recommend surgery, if feasible and of direct benefit to function and quality of life, followed by radiation therapy. This can be either whole brain and/ or Stereotactic radiation (Fractionated or one dose).

In general,

  1. Surgery is advised for anyone with a single brain metastasis and an undiagnosed primary tumor.
  2. Surgery is also advised, if reversing the symptoms to preserve function needs to be accomplished immediately. (See below for emergency treatments)
  3. Radiation therapy is almost always advised for rapid relief of symptoms for patients with multiple metastatic nervous system tumors and when surgery is not indicated.
  4. Chemotherapy (and immunotherapy) can also be advised, especially for types of Lymphoma and other cancers.


Do I have any options to try before deciding on surgery?

Yes!

The option of whether to have surgery or not really depends on the severity of your symptoms. Emergency Neurosurgery to remove pressure or blood on the brain can be lifesaving and reverse your symptoms. Except for highly unusual and rare circumstances, a biopsy should be obtained to know what kind of tumor you are dealing with, if the primary tumor has not been diagnosed.

After the emergency is resolved, the team can give you input into the next sequence of treatments, if any are necessary. This usually occurs after the surgery, but with a metastasis it can also take place beforehand to discuss the different options. Many times if there are multiple brain tumors, the decision on which tumor to operate and which to give radiation can be challenging. There is usually time to get opinions from the local tumor board, or consultations at a major medical center which specializes in treatment of brain tumors.

Which treatments are performed in an emergency?

  1. Rapid administration of high dose dexamethasone (16-48 mg/ day) can relieve pressure and reverse symptoms like paralysis, pain, speech arrest, nausea/ vomiting.
  2. Emergency surgery can remove the tumor or obstruction.
  3. The neurosurgeon can place a shunt to divert spinal fluid under pressure.
  4. For arm or leg pain and paralysis, or bowel / bladder paralysis from a tumor pressing on the spinal cord, emergency surgery in the first 48 hours has the best chance of providing complete recovery.

Does the location of my met make a difference?

Yes it does. For example a met on the surface of the brain or outside of the spinal cord is easier to remove compared with one deep in the brain stem, where the surgeon has little room to maneuver. Bottom line: Successful therapy, and specifically surgery to remove the tumor, is dependent equally on location and tumor type.

What is the role of Neurosurgery for a metastasis?

Surgery is important initial therapy for three reasons:

  • to preserve or improve your neurological function
  • to remove the tumor, completely or partially.
  • to obtain a piece of the tumor to confirm the diagnosis (biopsy).

One advantage for the Neurosurgeon (and patient) in the operative removal of a metastasis, as opposed to other malignant brain tumors, is that mets tend to be superficial and near the surface. There is usually a good separation or border between the tumor and surrounding normal brain tissue. This minimizes the need for retraction and touching of normal brain and makes it safer.

If my metastatic tumor cannot be completely removed by surgery, which other therapies can be used?

Generally, if tumor removal is not advised, then there are not clear-cut choices, and the decision-making is more complex and should have input from the different specialists involved in your care. This clinical setting also gives the opportunity for experimental clinical trial- based therapy.

The options you can consider are many:

  • Local Radiotherapy, whole brain radiotherapy, and / or radiotherapy to the entire spine.
  • Local, inserted radiation therapy (Gliasite®).
  • Regional chemotherapy (Gliadel®).
  • Systemic chemotherapy
  • Immunotherapy with antibodies alone or attached to radioactive atoms, Interleukins, and Interferons; This can be administered systemically, into the tumor, in the spinal canal or through a reservoir ( a tube that leads to the ventricles of the brain).
  • Additional surgery at another institution (second or third opinion)

The best choices depend on whether the tumor is in a thin layer and could respond to medicine in the spinal fluid, or if it is "bulky" and would need stronger therapy as radiation therapy, systemic chemotherapy, or immunotherapy.

For lymphomas, antibody therapy (Rituximab®) has been effective. For spinal tumors causing paralysis, one study showed that removal of the pressure caused by the tumor within 48 hours led to a better chance for complete recovery.

RADIATION THERAPY

Radiation therapy is the most extensively used treatment for all brain tumors, including metastases. Newer techniques have focussed on giving higher doses of radiation to only the local area or empty cavity of the metastasis, instead of to the whole brain. The major debate among Radiation Oncologists continues to be what type of, and how much radiation to give. Issues specific to metastases are discussed below. The more complete explanation of the different types of radiation therapy will appear in Chapter 8, Traditional Diagnosis and Treatment I an upcoming book (spring 2004)

Why do I need to know about the different types of radiation therapy?

Only for the quality of my life… after the therapy!

  • Will my brain still work?
  • Will my memory be affected?
  • Will I recognize my spouse or friends?
  • Will I still be able to care for my daily needs like getting dressed, fixing a cup of coffee, going unassisted to the toilet?

These are such basic questions about your "quality of life." Yet, often they are not in the discussion of informed consent before accepting the therapy. Certainly there are situations where both choice A and choice B are not to our liking. But all of us have a right to determine if the (side effects of) "therapy" will be acceptable to our life style.

With advice of experts the National Guideline clearing House has developed "best practice" guidelines for treatment of many medical conditions including brain tumors. One for single metastases is referenced below. In the 7 examples which are listed, all have rating scales for appropriateness of therapy type: surgery, Radiosurgery, whole-brain radiation. Not one mentions "No Therapy" as an option! Not one mentions 'quality of survival" when whole brain radiation is compared with Radiosurgery. Just because these are government -sponsored guidelines, it does not mean they are best for you. Ask…Ask… Ask …questions. <<<<Click HERE for the guidelines.

Whole brain Vs. partial or focussed radiation therapy?

This is a hot button topic among specialists. No one would want to give any therapy, if it were not needed. But this also reflects the difference between older and modern approaches with much for you to lose…. if the wrong choice is made. This is why you MUST be informed.

A major debate exists as to whether people with 4-6 metastases or fewer should receive whole brain or individual radiation beams to each tumor. The tumor type and location, and your age are variables in this equation. The issue is quality of life and brain function. There are several trials currently available in North America to study this question. At this time the correct answer is not known. This is another reason to be at a major treatment Center that understands these issues. Then you can make an informed decision about what treatment alternative to choose, rather than having someone else makes this decision for you. Only you will have to deal with the consequences, both good or (possibly) bad.

What is the status of radiation sensitizers?

These are drugs which add to the effect of radiation in causing cancer cell death. I quote Dr. Minesh Mehta, M.D., professor and chairman, Department of Human Oncology, University of Wisconsin Medical School in his opinion of recent results of a Phase1 clinical trial. "It is the first study to demonstrate that substantial neurologic and neurocognitive deficits exist in patients with brain metastases. In this randomized trial, Xcytrin® delayed neurologic progression when added to standard whole brain radiation therapy in patients with lung cancer.

Can radiation cause harm?

Recent evidence is that radiation to the entire brain for any type of tumor, or specifically to the frontal lobes, can cause significant damage in the very young, the elderly, and everyone in between. It is a matter of degree. Thus some major Centers offer experimental approaches which offer reduced or highly focussed and radiation, customized to the exact shape of the tumor (IMRT, Peacock etc). Alternatives such as chemotherapy or immunotherapy (experimental options) also are being studied.

I am not suggesting that you should blankly avoid all radiation therapy because of the potential for longer-term side effects. What I am saying is that you need to ask the radiation therapist very directly what is the likelihood that the therapy will cause you/ your loved one to be unable to perform tasks 1-4 above. This is tough stuff, but it is critical to know the information when making very difficult decisions about how you may want to live, or how you may not want to die.

What Are My Chances of "Cure" with a met?

Having a brain metastasis is a serious complication, but being in expert hands can increase your chances for survival. Yes, many people will die from this progression of tumor. But it is also fair to say that people with lower grade tumors and those with fewer or solitary mets and those tumors can be completely removed, will usually live longer and have better quality of life. I have patients alive five years later who had metastases.

There are nine important elements in predicting a successful result:

  1. location and number of tumors
  2. grade and type of tumor,
  3. whether there are tumors in other areas of the body
  4. your age
  5. if the tumor developed while on or off chemotherapy
  6. Amount of the tumor that can be removed by surgery (skill of the neurosurgeon).
  7. The response of the tumor to the new therapy
  8. Other medical conditions or complications
  9. Your functional state (Karnofsky) before and after surgery.

Remember, no matter how severe the situation, no physician or anyone else can predict for the individual what will happen with treatment. We are accurate in predicting for populations of patients but never for the individual.

Treatment approach will depend on staging results and also differ in the following three scenarios:

  • Single metastasis near the surface
  • 6+ metastases in both hemispheres
  • Diffuse seeding along the spinal cord.


What are the options for a solitary metastasis?

The basic recommendations have been surgery, Radiosurgery, and whole brain radiation. Recent (2003) developments are GliaSite®, an implantable, local intra-tumoral radiation treatment which is FDA- approved therapy for metastases and primary gliomas. The latter is a balloon that is placed inside the tumor, after the surgeon has prepared the area to receive it. It is then inflated with high concentrations of radioactive iodine, which radiate or "cook" the tumor from the inside. For a lymphoma, treatment recommendations and their order are quite different.

Principle: Even patients who had a single metastasis , which is completely (surgically) removed, should have radiation therapy as there are always individual tumor cells remaining after surgery. The role of chemotherapy for mets is discussed below.

What are the options for 4-6 metastases?

Surgery could be helpful to reverse acute symptoms from a bleed or pressure by the metastases. After or instead of surgery, current clinical trials are seeking to find if single focussed beams to each metastasis or whole brain radiation is the more effective therapy having less side effects.

Can chemotherapy be used to treat metastases from lung, colon, ovary, breast or melanoma?

The answer really depends on answers to the following five questions.

  1. Was the original tumor in the original site sensitive to chemotherapy? If so then chemotherapy is more likely to shrink the tumor.
  2. Was the tumor in control? That is, had the original tumor either disappeared or was it getting smaller when the brain met became known?
  3. Did the met appear when you were off your chemotherapy for more than a year? If so, then it is more likely that it might respond to the original type or other chemotherapy.
  4. Did the met appear while you were actively receiving chemotherapy? If so then it is unlikely that the tumor is sensitive and then other drugs or approaches should be used.
  5. Your overall health and other medical problems

You should have a consultation from a Neurooncologist or oncologist who treats at least 25 patients a year with brain tumors to be sure you are receiving up to date therapies.
 THINGS YOU NEED TO KNOW ABOUT YOUR METASTATIC (SECONDARY) TUMOR
  LOCATION IN BRAIN AND/ OR SPINAL CORD ?   1. NUMBER OF METS  2. IS IT THIN LAYER OR BULKY DISEASE?  TUMOR TYPE?
WHERE DID IT COME FROM?
 RECURRENCE OFF or ON THERAPY?   THERAPY CHOICES THERAPY SIDE EFFECTS-WHICH FUNCTIONS WILL BE LOST?
 Symptoms to treat or compensate for  This will Affect therapy Choices:
  • intrathecal or
  • radiation and/ or steroids
  • systemic chemotherapy
 
  • lung
  • breast
  • Colon,
  • prostate,
  • melanoma
  • Lymphoma,
  • other?
  Affects therapy choice for new Vs previous drug  Radiation-
-whole brain
-local
Radiosurgery
Stereotactic Fractionated
Radiation implant
Chemo wafer
Systemic Chemo
Intrathecal/ other
 Memory Self feeding/ care Getting dressed Making tea/ coffee Decision-making Current job skills
 
  • Paralysis,
  • Weakness
  • Eyesight
  • blind spots
        Immunotherapy
-Local
-Systemic
 Remembering spouse
Wakefullness/ alertness
 
  • seizures
  • headache
         




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