When cancer spreads to the brain

MD Anderson Cancer Center
Date: 10-07-2013


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Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas MD Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. And today, our guest is Dr. Ivo Tremont. He is an assistant professor of neuro-oncology here at MD Anderson. And we're going to talk about cancers that metastasize or spread to the brain. Welcome Dr. Tremont.

Dr. Ivo Tremont: Thank you Lisa and thank you for having me here.

Lisa Garvin: And let's talk about--well, first of all, metastasis means spread and there are certain cancers that tend to spread to the brain. Can you talk about those?

Dr. Ivo Tremont: Yes. Metastasis is this process of the certain cells from the primary tumor that migrate elsewhere away from the location of that primary tumor, and they can settle in different organs. Namely: liver, lungs, bones and brain. The most common primary tumors that tend to metastasize to the brain are lung, breast, melanoma, renal cell carcinoma, and various cancers from the GI tract, the gastrointestinal tract, above all the colon, colon and rectum. Finally, there is a small group of endocrine tumors like the thyroid cancers that can also metastasize to the brain. Annually, approximately 150,000 new cases of brain metastases are diagnosed in the United States, and I think this is a big, big problem that has now been solved.

Lisa Garvin:  Let's take breast as an example. It's a very common cancer, affects a lot of women. What is the typical path of progression as it moves from the breast to the brain? Does it do it through your lymph fluid, or how does it spread?

Dr. Ivo Tremont:  It's difficult to pinpoint exactly the migration route of breast cancer. But most experts are convinced that the spread is through the blood via the bloodstream. So, what we call hematogenous spread. So that's the most likely source of dissemination and invasion into the brain by breast cancer. And also by lung cancer and melanomas, they usually have that route. Other cancers like prostate and retroperitoneal organs can have the lymphatic pathways as the most likely source of or pathway of invasion for brain metastasis.

Lisa Garvin: Typically, when cancer spreads from the primary site, does it--when does it do it? I mean does it do it early on, later on, or does it vary by patient or disease?

Dr. Ivo Tremont:  It is one of the complexities of cancer. It can do so before the primary is found. And as I was initially having our dialogue, our conversion of--in general, three out of 10 patients have a diagnosis of cancer when the brain metastasis shows up first. So, others have brain metastasis while the--after the tumor has been found, the primary has been found, and they are undergoing treatment or they short--they have stopped treatment already and they have had a response. And then suddenly, boom, you have a brain lesion that corresponds later to the primary, the breast, or lung, or whatever the primary is.

Lisa Garvin:  Obviously, you know, if you're--if somebody is coming in and being treated for breast or lung cancer, we're focusing on the tumor site. Is it part of the standard treatment to look for metastases, or how do you deal with that big question mark that may or may not happen with people?

Dr. Ivo Tremont: Yes. We--the--we need to tailor the--how far to look for a brain metastasis. Not all patients have that tendency with--for example, within a specific cancer. For example, breast. There is a subset of women called triple-negative breast cancer who have a tendency to metastasize to the brain. So we need to be on the watch. We need to be very malicious when they start having symptoms like headaches, dizziness, new onset of neurological symptoms that they didn't have before, then we need to be on the alert that we need to order the adequate--the corresponding tests to look for a brain metastasis. There are--for example, there is a group of patients with lung cancer and that's the so-called small cell lung cancer that has an exquisite tropism for the brain. These cells seem to like colonizing and settling in the brain. And that is why, in the very beginning, the workup, even if they don't have neurological symptoms, we recommend neuroimaging studies because these patients could have already brain metastases and they maybe asymptomatic.

Lisa Garvin: And let's make it clearer about brain metastases. Once a primary cancer spreads to the brain, it doesn't become brain cancer, correct? It's still the same type of cancer, just in a different location?

Dr. Ivo Tremont:  Yeah. We may refer to that as brain cancer because it's a cancer that is in the brain. But this is very different from a malignant tumor or a cancer that arises in the brain that does not come from anywhere else outside the brain and has settled in that organ. So those are also called brain cancers, but these are primary, primary brain cancers. Like for example, astrocytomas of different grades, medulloblastomas, or other primary brain tumors including benign brain tumors like meningiomas. Those are primary brain tumors. Yet, they are not cancerous. Meningiomas, for example.

Lisa Garvin: Now, how do brain tumors--secondary brain tumors behave? I mean, do they progress differently? Do they present differently? How are they different than a primary brain tumor?

Dr. Ivo Tremont:  Lisa, I think you mentioned a term that is important to remember and take into account, and that is of a secondary brain tumor. In this situation and then drawing an analogy with what we were talk--discussing a few minutes ago, you can call them secondary brain cancers. They undergo a multistage process that includes penetration of the blood-brain barrier into the brain. Digestion and invasion of the solid substance of the brain so that these cells can grow and can flourish in that environment at the expense of using normal blood vessels in the brain or already preexistent, or create new blood vessels. The concept--

Lisa Garvin:  Angiogenesis.

Dr. Ivo Tremont:  --of neoangiogenesis or angiogenesis, yes. These cells then start by growing in one place or in several places scattered in the brain, something that a primary brain tumor does not do. Primary brain tumor arises within the brain, not penetrating any blood-brain barrier, because he is--the tumor is within the brain. These tumors may take a considerable longer time to grow. It may take years for them to grow and become more malignant, even if they're malignant from the very beginning. And they invade and use the tracts, the white matter tracts, something that brain metastasis do not do. Finally, I mean, it's more difficult to treat the primary brain tumors just because of that invasiveness that they do have in the brain. But those more--those are more or less the distinguishing features between primary and secondary, other than the histology.

Lisa Garvin: So, can some brain metastases progress very quickly, like some astrocytomas do, or do they progress more slowly? Do they seem to have any sort of characteristics that define them from primary brain tumors?

Dr. Ivo Tremont:  Yeah. Well, there is a range. Like everything in medicine or like any disease in medicine, there is a spectrum you see. And I think it depends on the generic makeup of that tumor or the biology of that tumor. Some tumors--let's talk about this situation, metastatic disease. Some metastases seem indolent. They seem like they grow lazily in the brain. They're comfortable. And depending on where they are, they could be disabling or not. They could cause seizures. They can cause speech problems. They could cause behavioral problems. And some of them are in areas of the brain called non-eloquent or silent areas of the brain where there is no immediate clinical translation into a movement, for example, or speech. Those are eloquent areas of the brain. And this silent, so-called silent areas of the brain, like that frontal lobes, there is enough space for these lesions to grow and--to a big size without being detected. By the time they are detected, they're large. They are obstructing the cerebrospinal fluid pathways. And they are causing problems like headaches, nausea, vomiting. But at that time--I mean there is no--it's very difficult to apply prevention strategies for these tumors when they grow in those areas.

Lisa Garvin:  What do you tell a patient? I mean, obviously--and this happens a lot with cancer patients, once they are finished with treatment and they're feeling pretty good, they tend to ignore their follow-up exams, and so on and so forth. What should cancer patients do if there might be some risk of a brain metastasis? What do they do after they've been treated?

Dr. Ivo Tremont:  I believe a good role for us as, not only physicians, but also nurses and every health care, a life profession is to tell patients that this is a long battle, a long fight, that they should never be taken by surprise, and they should never abandon the follow-ups thinking that they are free of disease and it's not going to come away. Unfortunately, cancer behaves in non-predictable ways. And the best way to prevent problems and treat, when those problems are there and to treat them most efficiently is to be on the watch and always continue with follow-ups--with periodic follow-ups. If there is a symptom and if we investigate it and we do find that there is a brain metastasis, at least we detected it at a point where it's still small. It can be easily--more easily resolved than, for example, a patient comes back after being lost to follow-up with a huge lesion that is unmanageable at that time. So, we need to tell patients that they should never abandon the follow-up that is this is a chronic illness.
Perhaps it's not going to give them a hard time any longer. But we do need to watch that on a permanent basis.

Lisa Garvin:  Is there anything on the horizon? Is there any possibility of biomarkers or other predictors that might be able to allow you to choose which patients are more likely to have metastasis to the brain?

Dr. Ivo Tremont: This is an area of active investigation. Lisa, I have to say that brain metastasis has been an area of neglected research. Beginning, for example, with the clinical trials, many of the standard clinical trials all these years have neglected patients with brain metastasis because there was this belief that patients with brain metastasis would do poorly. They would've negatively affect the results of the study. And that the patients would be having a low performance status. That would be negative or against the selection process in the clinical study, and it would negatively affect the drug. However, there are many patients with brain metastasis who function very well. They don't have any cognitive problems. And these patients represent an enormous and potential resource for investigation on new drugs that can penetrate the blood-brain barrier. Only now are physicians and researchers realizing that we need to include these patients in clinical trials. And these trials are not exclusively devoted to patients with brain metastasis because precisely of that neglect that happened decades ago and it's still going on, that's why we have lagged--I have the impression that we have lagged behind in the treatment of brain metastasis just because these patients have not been included in the largest or promising trials with new drugs.

Lisa Garvin:  Are treatment strategies the same for primary and secondary bran cancers?

Dr. Ivo Tremont: Treatment strategies? Yes, and let me clarify that. The standard of care or the main stay of treatment of a patient with a primary brain tumor is surgery and, in many instances, radiation therapy. In metastatic brain tumors, well, when the lesion is in a respectable area, it's a single lesion, or sometimes it can be up to two or three lesions, the surgeons can operate on that, especially if there is a lesion that is causing damage, that is causing weakness, or is causing symptoms, and we call it a dominant lesion. That lesion can compromise a patient's quality of life and then it's important for the surgeon to operate. When it's a single or solitary lesion, it's easier for the surgeon to go and remove it. In fact, for some time, we know that surgery for metastatic brain lesions do prolong survival in these patients. More recently, we have found too that, well, whole-brain radiation therapy used to be the standard of care of patients with brain metastasis, even before the surgery trials. We now know that stereotactic radiosurgery in these patients is also may be as effective as surgery. And it has replaced surgery in many places around the world, not only in North America, as the treatment for patients with brain metastasis, obviating all the costs of hospitalization, the surgical risks. For example, many of these patients with brain metastasis may have co-morbidities that will increase the surgical risk. And by doing stereotactic radiosurgery, those risks are minimized. A difference here with primary brain tumors is that stereotactic radiosurgery has technically can be given with a--to any primary brain tumor like a glioblastoma, for example. But for stereotactic radiosurgery to work most effectively, you have to target a specific area. For example, the brain metastasis is relatively circumscribed in a--what is called a pseudocapsule or a false capsule. It's relatively circumscribed. The lesions, may be smaller than four centimeters, and so they are ideal to be targeted with stereotactic radiosurgery. Instead, a primary brain tumor, like a--let's call a malignant glioma, be it a grade II, grade III or grade IV, is not a good target for stereotactic radiosurgery. Why? Well, just because of the tendency of those cells to mix with normal cells invading the normal tissue and spreading all over without a specific limit. I mean they're not circumscribed. They are infiltrating, invading adjacent areas. So the stereotactic radiosurgery can be used in primary brain tumors, but it does not translate in any benefit precisely because of the biology of that tumor.

Lisa Garvin:  Well it sounds like in closing, and I think we see this a lot with cancer patients, once they're treated successfully, they're out the door, never to return. So it sounds like the message here, because some cancers can metastasize to the brain after treatment that they really need to be vigilant and treat cancer as a chronic disease. Is that correct?

Dr. Ivo Tremont:  That is absolutely correct. And there is one factor to never forget about this. It is that the existence of a wall, of a barrier that separates the brain from the rest of the body, and it is called the blood-brain barrier. We call it BBB, but it's the blood-brain barrier. It's a selective barrier that we have that filters nutrients that need to go to the brain like, for example, glucose, oxygen, and other oligoelements that can penetrate that barrier, going to the brain, be used for the normal brain metabolism. And they have very small windows that do not allow the entry of big molecules like drugs, for example. That is why many of these chemotherapy drugs are ineffective. I mean, they do not prevent the development of brain metastasis. A patient with breast cancer may respond beautifully to the anti-cancer treatment and yet she can still have brain metastasis. Why? And it's seen over and over again. Why? Because of the inability of these drugs to penetrate brain and exert a therapeutic effect. So that is the reason why many patients, even though they have a systemic disease, is--by systemic, I mean the primary tumor or any other extracranial metastases they may have. That is why many of these patients, even though their systemic diseases is controlled, they get in trouble with the brain just because there was no vigilance in the brain. And we see this every day.

Lisa Garvin:  So the watch word to our patients would be "be ever vigilant".

Dr. Ivo Tremont:  Exactly Lisa.

Lisa Garvin:  Thank you very much for being with us today.

Dr. Ivo Tremont:  Well yeah, thank you. Thank you.

Lisa Garvin: If you have questions about anything you've heard today on Cancer Newsline, contact Ask MD Anderson at 1-877-632-6789 or online at mdanderson.org/ask. [Background Music] Thank you for listening to this episode of Cancer Newsline. Tune-in for the next podcast in our series.