Brain Metastases: A Documentary | How Brain Metastases Develop and Promising Treatment Options

Brain Metastases: A Documentary | How Brain Metastases Develop and Promising Treatment Options

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Cancer. The. Emperor of all maladies it, is. A frightening, disease for which currently, there's no cure. However. We. Are unquestionably. In one of the most dynamic and exciting periods, of medicine. For cancer treatment. I felt. That something was a little off with, my right breast. It. Turned out to be breast. Cancer, I, went. Through seven months of chemotherapy a, mastectomy. Radiation. I. Got. To a point where there was no evidence of disease. My. Oncologist, suggested. A brand scan because I hadn't, had that tested. Since, my original PET, scan when I was first diagnosed. There. Were three tumors a. Brain. Metastasis. Is a collection, of cancer. Cells that. Have traveled, from, some, part of the, body where, it started, they caused a lot of swelling and that pressure on the brain and the swelling in the brain causes. Neurologic, symptoms and, can, actually even cause death if not treated appropriately. First. Thought was, okay. You know what's what's. Gonna happen next what's, my, quality, of life gonna, be and, actually. I was prepared, to die and it's, terrifying, they're, scared. That they're gonna die soon, they, are scared, of the, treatments, that we might be offering them we did a study a number of years ago where I where I took my own patients, and I tried to predict how long somebody would live and we, share that data with 17. Top people in the world was, fascinating, because what we found is that the, doctors really couldn't pick at an, individual. Level who was going to beat the odds and who, was going to struggle, maybe, we're not that good at predicting how long people are going to live we'll, find the cure for cancer eventually, but, in the meantime you. Know we want people, to be, able to live with their cancer as opposed. To for their cancer, we, now have capabilities. In, radio surgery to, treat tumors that are in deep, and inaccessible. Areas, with almost, relative, impunity we can do it with such targeted, approaches. That, the side-effects are no. Longer, significant. This is revolutionised. Neurosurgery. And radiation oncology because. Prior to that there, was, only the options of open surgery, or radiation, to the whole head as opposed to precise, targets, the, advantage, of radio surgery, by. Focusing, radiation, is sparing. The surrounding, structures in the brain from, radiation. Injury, patients. Are surprising, us they are living longer they're beating the odds we're, seeing things we never saw before we. Have a high confidence that, we can eliminate, the cancer in the brain and return. You to your, quality, of life and. Activities. Of daily living. There. Are different kinds of brain tumors it's, important, to discriminate, between primary. Brain cancer, which is a tumor that's born in the brain and that's actually pretty rare and enders, metastatic, brain cancer, which, is five times more common. Part. Of what makes, cancer cancer, is that. It has the ability to spread, throughout the body so the tumor might start in the breast and it gets to a certain size and it. Develops, some, mutations, and then the cell will split off get, into the blood and then, stop. Somewhere, in the brain and, deposit. Inside the brain and form, other tumors, and that would be the process of metastasizing. There. Is a blood-brain, barrier and, that barrier, works. Very well at keeping toxins. And infections, and other things floating around through our blood out of the brain but, cancer has developed, a mechanism, which, it can penetrate that. Barrier, and certain, cancers in particular, better penetrating. It than others which is why we. Tend to see most metastatic, tumors, from, lung cancer breast cancer melanoma. And, testicular, cancer if. You remove, one of these metastatic, tumors, from the brain surgery, and you look at it under, microscope, it looks like the cancer from, the original, source so, a breast, cancer metastasis.

Looks Like abnormal, breast tissue rather. Than brain tissue they're. Growing, into, a ball of cells that is the cancer but, they're not incorporating, themselves, into the brain their. Unwanted. Neighbors, of fuel our. Goal is to find those tumors early because as the tumors get bigger the, success, rates drop. Typically. With, radio surgery people have quoted success, rates at stopping a brain tumor in the range of 85%. So. When we say how do we get that to 95%. To 98% to, 99% it's. With identifying. The tumors earlier and that means. Getting, a periodic, brain scan to check because. Missing. A brain tumor, if. It grows can cause neurologic, symptoms that we'd like to avoid. Typically. When you're diagnosed, with metastatic cancer. Or cancer that's spreading throughout your body you're, put on a systemic, chemotherapy and, this drug is supposed to kill the cancer all, over your body wherever it is but. Those drugs don't get into the brain because, of the blood-brain, barrier you. Want a cancer, drug to have a significant. Impact and if only a fraction of it gets through because the blood-brain. Barrier. It makes chemotherapy. Much more challenging and so, we have to treat the tumors in the brain as completely. Separate, from the tumors everywhere, else in the body so, the tools that we have before us to treat brain, metastases. Are. Radiation. And, surgery in certain, types of situations, certain research. Protocols. Drug, therapies, are being evaluated and tested we, hope that any drug therapies, that are being received are, providing, benefits of the body particularly, with. The goal of preventing new tumors from coming in the future. All brain radiation is, as it sounds we're treating the entire brain, with radiation. Conventional. Radiation the way it's been given for a long time is that a little bit of radiation is given every day and that's repeated, five. Days a week up to seven or eight weeks in that process, there's, a lot of healthy cells that, receive the same amount of radiation as the cancer cells but the, healthy cells are better, at, repairing. Between, the different radiation treatments so if you give a treatment today and you, give another one 24 hours later between those two treatments, the healthy cells are repairing, at a faster. Rate than the cancer cells, unfortunately. When a patient is diagnosed, with brain, metastases. There are many more lesions that are not detectable.

On, An MRI or any, imaging, modality, that we have today you have the potential to grow, and some, have referred to this as the dandelion effect. When you blow on a dandelion all these seeds, shower, an area, it's, not dissimilar, to that phenomenon. Where there, is a primary, cancer. Somewhere in the body and, therefore there's the possibility, for cancer. Cells to seed, and deposit, multiple, areas of the brain so, whole brain radiation therapy, is used to try to sterilize. Not just, the visible brain, metastasis. But also the microscopic. Brain, metastasis that we just can't see yet the, radiation has been around for about a hundred years and it's been a really important part of treating, cancer for. Some people that's an appropriate treatment. But it comes with a lot of side effects almost, everybody's, tired sometimes really, severely, tired you, lose your hair you, can get inflammation in your ear sometimes that leads to hearing. Loss it makes people nauseous, sometimes, and what's worries patients, the most and what, causes us the most concern is it can have an effect on memory concentration and. Brain, functioning, whole, brain radiotherapy, has a devastating, impact on, cognition. We're targeting the areas where, new memories are formed the hippocampus, as well. As all of the interconnections. Between different, parts of the brain that are critical, for higher-level. Thought and memory you, can't expose, that much of the brain to toxic, radiation and expect, to have no consequences. So. If. We are going to strive for a cure or at least long-term suppression, of cancer and keep patients alive for years and years we, really have to think about what their quality of life is going to be and quality. Of life starts, with what's up here. Now. With our modern imaging, technology, where we can see, really. Really small tumors, inside. The brain we. Can actually now avoid. Whole brain radiation altogether. And treat. Those tumors, with radiosurgery. Stereotactic. Radiosurgery, is, a technique, of delivering, radiation very specifically. To, a target. Inside the head the, concept. Here is you're destroying, tumors. Inside the body with. Frankly, the, accuracy. Of the blade of a knife you're. Destroying, a tumor deep inside, the body almost. Like cutting it out but you're using a non-invasive. Way there, radiosurgery, devices. Are usually accurate, to about a millimeter. And about. A millimeter is about how accurately, we can pick out where the tumor is anyways, on the MRI, or CT scan so that's about as accurate as they need, to be it, uses, multiple, beams, of, radiation that all converge on a single point what I tell patients this is very analogous, to. Taking a magnifying, glass and a leaf and if you hold a leaf out into the Sun it, won't spontaneously. Combust, and catch on fire but if you take a lens and focus that low-dose Sun power down on a point it'll burn a hole in the leaf and so, that's in its essence what stereotactic, radiosurgery machines. Do the. Radiations coming from all these directions and it's being concentrated in that one spot but around, that spot there's not a lot of radiation so the damage is really focused, on the tumor brain, metastases. Are one of the few targets that we treat in the brain that can absolutely disappear. With radiation, the. Tremendous, advantage of radiosurgery is it does not interrupt systemic. Treatment, whereas. Somebody. That's undergoing standard, whole brain radiation must, suspend, standard. Treatment. The. Gamma knife is the first, hospital-based.

Dedicated. Radiosurgery, system. The gamma knife treatment is, a one day treatment they're, gonna come to the hospital early in the morning we, give them a little sedative we, will clean the skin and I. Inject some local anesthetic in the forehead in the back of the head prior, to placing what I call a guiding, device for a stereotactic, frame it's, like a halo, with. Little pins that anchor into the head in these, numbed areas, the patient will wear that during the procedure the, stereotactic, frame guiding, device prevents. Head movement, the, second thing that the frame does is it essentially creates a GPS device for, the head so, that we know where the tumor is inside the brain mathematically. In 3-dimensional, space exactly, what that coordinate, is we have 192. Sources, in a. Gamma Knife and they're all still, focused, at one point in space each. Of the different radiation. Devices, create. This conformal. Irregularly-shaped. Plan, in. Different ways with. The gamma knife we, use what are called Isis. Centers or shots of radiation, which each shot is sort of like a ball, and if. One wanted to make an, irregular. Shape you might make a series of balls that mathematically. Integrates. In three, dimensions, to be that shape once. That's done the. Group will then choose an amount of radiation that, they think is best suited for that, tumor in that location in that patient, and there's. Many factors, important. Including, do, they have radiation before the. Size of the tumor its. Location, are, there any other options should, this not work if. There are risks how would those be managed once, the treatment is done they have the head frame taken off they. Get some dressings for the pin sides the head wrap and then, they go literally, right home from there. Another. Way to deliver stereotactic. Radiation is, the Linear Accelerator and, it, uses, accelerated. Electrons, that are channeled, into a collision, with a heavy metal target, and out of this comes, high-energy. Photons, when, they slow down they actually emit x-rays not. Like the x-rays that you would use. To take a picture of somebody in, a chest x-ray for example, there are about a hundred times, more, energetic, these. X-rays are designed to kill cancer cells, once. We had the linear accelerator, we had a whole wealth of new tools we were able to direct radiation, beam some different angles and overlap. Them we. Don't actually have to deliver all the beams at the same time the, biological. Effect of depositing. Dose is additive. Even, if we deliver, those beams sequentially. We. Do this quite quickly we, do the whole series of beams and deliver, the entire treatment within. About, 15 minutes to half an hour. Benefit. Of frame. Based radio surgeries, that the patient is held rigidly, on the table with the assurance, that the patient isn't moving and that. The target, is going, to be accurately, identified, frameless.

Radiosurgery Uses. A thermoplastic mask, that, is custom, molded to the patient, by heating this, plastic, molding. It and then cooling it so that it becomes rigid, it. Still holds the patient on the table but does still allow about a millimeter, to two millimeters of, micro, motion that's, much, more comfortable, than being rigidly affixed, to the table but it does introduce the possibility, of some air there, are endless technologies, that track the surface of the patient, and use. That to then somehow triangulate. An internal, target that you can't see optical. External. Surface, tracking, technology, can be quite compatible, to various sites for, example in treating breast cancer, in, treating brain tumors we, have the most demanding. Spatial, tolerances. Of any site within the body the sensitivity. Of the technique can be affected by skin, colour that skin can move, it. Can deform it, can stretch and ultimately. That's the limitation of that, surface. Matching our product one, option to accommodate, limited. Precision of surface. Matching is to actually add a margin around. The tumor that we're treating but it's our goal to actually minimize those, margins, since. That expansion, equates, to knowingly. Treating, healthy brain tissue and, if. We can imagine for a second, brain, metastasis, that is 15. Millimeters, across if. We were to add a margin that is just 2 millimeters, we, would be approximately, doubling. The volume of the tumor that we would, need to treat what, we really, would like to do is have a more direct means. Of monitoring, where, the tumor is actually, located with, an image guided frameless technique, like, exact, track in real-time you, actually see where your beam is pointing. So you, can constantly monitor the patient if they were to move for some reason cough jump whatever you, know it and you can adapt your treatment to that when. You add, imaging. And micro motion adjustments. Into, the, thermoplastic. Mask you, really achieve the same level of accuracy as a frame based system this, can be done through a system, such as exact, track that, uses inline x-ray, imaging, combined, with a robotic Lea moving couch to, make minor adjustments in patient position, to account for any movement of the patient in. My opinion treating, hundreds, of patients with both frame, based and frameless technologies, the. Patient and provider experience. Is better with the frameless, immobilization. From, the patient's, perspective they, don't have to have a painful, anesthetic.

Injection They don't have to be sedated they, don't have to have the discomfort, of wearing the frame for the entire day of the treatment they, are only, immobilized. While, they're on the treatment, table under treatment delivery then, it doesn't matter if you're giving one treatment three treatments five treatments you can get the same accuracy. And you can choose the number of treatments that's, best for it a patient and their tumor. The. CyberKnife, is a robotically. Mounted small linear accelerator, that delivers. Radiation therapy. At a much lower, dose rate, and it. Does it in a, node-based. Pattern. So it moves from one location to the next location, to, the next location, not in a sweeping, action that, results, frequently. In treatment, plans that are. Qualitatively. Similar. Meaning, that if, I want to deliver 18, GRA to, a small tumor, whether, it's the gamma knife or, the Novalis system or the CyberKnife, system, they can all do that the. Way the dose is spread out and the way it's delivered is. Really. The crux of the differences, and the speed so treatment times are the important, part much like the nivalis system the CyberKnife, does have stereoscopic. Imaging, that allows us to image the patient and confirm, that the patient's in the right location, during, the entire course of treatment. The. Next iteration of beam shaping, technology. Is what's called a micro multi-leaf, collimator the. Principle, behind it is not, all tumors are exactly, spherical, so a circular, beam can ideally, treat a spherical. Target but, if you think of a hot dog for example it's spherical in one view but it's linear in another view and so, the multi-leaf collimator allows. Us to vary these shapes according. To the view of the tumor because. We can't use. Magnets, to steer. X-rays. And we can't use lenses, like light, what. We have to do is simply block, the regions where the x-rays aren't supposed to go and create, an opening where they are supposed, to pass through and so, what micro multi-leaf collimator stew, is use. Multiple. Leaves that, block part of the beam to shape the beam into the exact, beams eye view of the tumor so the edge of the beam is exactly. Aligned with the edge of the tumor through that view and it can do that on the fly as the beam is moving, and an arc of radiation, around the tumor if we actually control these leaves dynamically. We can vary the intensity, of the radiation that's, emitted, from the linear accelerator, in my opinion, the development, of the micro multi-leaf, collimator has, been the biggest advance in radio surgery in my, lifetime because, it allows more. Precise. And homogeneous, delivery, of the radiation to just, the target and so you're delivering a minimum of radiation, to the normal brain tissue around it. It's. Not meaningful. If. A patient has to have 36. Hours of radio surgery, with. Marvelous techniques on the Linear Accelerator, we. Can perform treatment. Of ten metastases. In no, time at all in a half an hour the current. Mode, of practice, to treat multiple metastases. Is to treat one, after the other and you can certainly do that on a gamma knife you, would do that conventionally. On a linear accelerator, you would treat one after another and that. Treatment would take fifteen, to twenty minutes for. Each one and so. If a patient came in with 12 you can have the patient, being treated on the device for three hours four hours that, might not matter when it's two. Or three tumors but if we, come to a point where we want to treat ten or fifteen tumours it's, really inconvenient to, treat them one at a time and it's a lot easier to, have a technology, where they can all be treated at once historically. Treatment, planning has been a manual, process that's, done with, the knowledge and experience, of the physicists. Who's sitting down at the computer and, you go through this manual, iterative. Process, until, you get a plan not. The best plan because, you know you could probably spend, some more time to. Make a better plan but you you get it what's a clinically, acceptable, plan and there's, no reason to do that once, we had computers, that can do this optimization.

Automatically. New. Approaches, allow, us now to treat. All of them, metastases, with, a single ISO Center and one, of those techniques, is called volumetric. Modulated. Arc therapy. As we. Are rotating the gantry of the linear accelerator, we, can create very. Complex openings. To, allow, irradiation. Of all of the metastasis. Depending. On the orientation of the multi-leaf, collimator it. May be challenging, to actually create two, separate, apertures, without, creating an unwanted. Region, of exposure, in between. Another. Technique that is gaining popularity takes. A different approach in. Choosing, subsets. Of brain. Mets to be treated in a single gantry rotation. Let's. Imagine a patient who has seven brain metastases. The. Algorithm, would look at that set and decide, on maybe three of the seven to be treated in a, single gantry arc and then in a second gantry rotation, of the algorithm, might choose the remaining four and, that decision would be based on minimizing, the. Area or amount of normal brain tissue that. Would have to be exposed. Increasingly. We're faced with more, complicated. Complex, tumors larger. Tumors and tumors. That are in close proximity they're. Very close to critical structures, for, instance say the optic, chiasm, or the brainstem or, one, of the major cranial. Nerves, and giving. A single fraction would be problematic, would cause too, much of a side effect and so, the, technologies, that we have today with our relocatable. Frame with, our image guidance, on our, ability to vary the intensity, of the radiation beam, has. Allowed us to. Give. An effective, dose of radiation by, breaking, it up into smaller. Fractions. Something. Called hypo, fractionation. For, instance, for. The smallest tumors, we may give 21, or 24, gray and that's. A measure of radiation, in a single, fraction but, for a tumor, that, say, 3, centimeters. We, may give you a much lower dose which. Is 16. Grey and that doesn't make any sense because a bigger tumor, will, have more cells that need to be killed so. Why. Are we giving the lower dose it's. Because if we tried to give 24. Gray to. That three. Centimeter, tumor the, side effect meaning swelling. And necrosis which, is dying. Brain, tissue would be. Unacceptably. High in, between, the treatments, the normal brain can repair, in between. The treatments some areas of the tumor that were more resistant, to radiation may be because they weren't getting enough oxygen can. Get more oxygen and become more sensitive to radiation all cells. In the body require. Oxygen and. Tumors. Themselves, have a higher, demand, on oxygen. Consumption. Just because they're. Growing so rapidly. They. Can actually outgrow. Their blood supply and when they outgrow, their blood supply they, become what's called hypoxic. So, there is little. Oxygen. Towards, the centres of the the tumor, incidentally. By giving, a smaller dose of radiation. But. Giving it in multiple fractions. We'd. Get the benefit, of having. The tumor, shrink, and, then. That portion that was hypoxic. Actually. Has no more blood supply and as, its further, shrinks, it gets even more blood supply so, the radiation is, now. More, effective, because there's more oxygen around there's, more free radical, to damage the, cancer, cells and you. Get a better. Response to, treatment, for some large tumors, the. Future, might be to be giving three and five treatments, as opposed to just one treatment and again, if you have a system that doesn't rely on screwing, something to the patient's head then, you have that flexibility, of what's. Best for this tumor if it's three treatments we'll give three treatments if it's one we'll give one and the, quality and the accuracy, will be the same. The. Whole, brain rage there be paradigm, is very much ingrained, in, many, radiation. Oncologists. And this is how it's been for many years, radiation. Therapy when. Not focused. Delivers. Collateral, damage to surrounding tissue. Why. Continue, using a technology, a treatment. Approach that. Results. In significant. Long term irreversible. Side-effects, of memory. Loss dementia. When. With a carefully, constructed clinical. Approach of radiosurgery. And close, and careful, follow-up.

The, Outcomes, are, identical. So it's unconscionable. For me that an insurance company. Would, deny good. Therapy. In fact one, of the reasons why there's, so much whole brain radiotherapy. Is that, even, in the centers that have radio surgical capability, and the staffing it. Gets denied, for. Patients receiving radio surgery upfront it doesn't preclude, any additional, treatment you can always have full variation to every later if, it's appropriate my, personal, opinion is that whole brain radiation therapy, will, always. Occupy. Some. Role in the, management of metastatic brain disease but, I think that its role is going to become more and more limited, to those patients, who have very. Advanced. Presentations. Of brain, metastases. If, you just give someone radiosurgery and you never see them again well. Unfortunately it's about 50/50, that they'll get new brain metastases, and if you don't follow them the only reason you'll see them back is because they're sick and they need emergency room but if you see them every few months and you do an MRI and you might find that new metastases when it's only a few millimeters, and you, can zap it before it causes any trouble and, often. The patients have, despite having advanced cancer and brain metastases are not going to die from the brain metastases because we can control them by, following them and treating them when they're small and that's, really, part. Of managing, cancer is more of a chronic illness with. These periodic, tests, it's been part of the care of the body PET. Scans periodic. CT scans it needs to be part of the care of the brain if you have a garden and you notice a couple of weeds you can either go. And pull those couple of weeds or you can tear up your entire lawn there. Might be two or three other weeds that you didn't see if they, grow up later you'll just pull them out later. There's. No doubt that patients, want to avoid surgery, the prospect, of having your head cut open and somebody going into your brain is very scary if, the tumor is larger, and symptomatic. Causing. Disabling, headache or frequent, seizures or, balance, problems, and it's, in a location that's suitable for removal, it may be that the recommendation, is to surgically, take that tumor away and decompress. The brain now, many patients are immediately thankful, because when I tell them that this is the, fastest, way to make them better, that's good news for them, that's. When we think about surgery to, solve a problem the patient has as, soon as we remove the tumor that swelling, starts to regress so, the patients, who have brain metastases. Removed can feel better the, day after their operation, the way we stay minimally, invasive is, by making small craniotomies. Just immediately, over where we need to be we're. Able to do that in the modern era using something that we call intraoperative, neuro navigation, and that, way we can find the shortest. Distance from the surface of the skull down to the tumor and make the smallest opening we possibly, can. With. Surgery we can never guarantee that we removed 100%, of the tumor sometimes. Even when we remove everything we can see on the MRI we know that there are microscopic. Cells left behind the, data is very clear on this that patients do better if, they receive radio surgery to the area where we've surgically removed a tumor, treating. With radiation before, actually. Doing surgery, is really. An intriguing idea that's, starting to gain some traction the. Concept. Is that if we treat with radiation before we do an operation we, start killing tumor cells with the radiation, so, that when we go in there to remove the tumor much, of the tumor. Is already dead and the cells that get spilled during the operation, can't, spread and set up new tumors when. We treat with radiation, before surgery, it's, much easier to draw, a line around the boundary of the tumor and know exactly what the border between the tumor and the normal brain is. Radiosurgery. Is still somewhat. New 20. Years is fairly new there is a wide, variety, in, the standard, of care that you can get radiosurgery. Has evolved, quite a bit and it's. A double-edged sword that, radiosurgery. Especially, for brain metastases, can now be done in relatively. Small clinics. With general. Radiotherapy. Equipment, and. The. Quality, might not be exactly the same in, that, setting, than in a large institution, that has a device, dedicated.

To Radio surgery and it's not easy for a patient, or even for myself walking, in the door to know is this. A quality radiosurgery program, well, there's never a guarantee, that. There's not going to be a problem, nevah certified, is the only program in, the world that. Has, an independent group, come, in and look at your program and say yep, you, really. Perform. Stereotactic, radiosurgery. At a universally. High level, from a clinical perspective from. A technical, perspective physics. Quality, Assurance all. Of these things, that. That that's a very, valuable indication. It's, very, early on in, a, movement. To really address the, treatment of metastatic cancer. And metastatic brain, in particular, the. Importance, of a film like this and the American brain tumor Association, being a part of it is really gets back to our mission if, people understand, that, there is time for them to understand, their tumor that there is time for them to understand, that diagnosis, and there is time for them to better. Understand, their treatment, options it's, a better trajectory it's, a better outcome and I, think that that is a mission fulfillment, for the organization, if. We give, treatments, that are toxic and cause cognitive. Decline and. Those patients won't be able to enjoy the extra, years that we've bought them with our new therapies, and so, when. Treating cancer patients in the modern era we really have to consider the quality of life for, the time they have left. We. Want for people to continue to live continue, to work continue, to do all the things that are meaningful for them radiosurgery. Is, an essential, component to, the next wave of cancer, care. I no, longer think, about, dying. You. Know I don't. And, that's. I think pretty dramatic. If. We can give you that plateau of survival. Imagine. What new protocols, might be available to you that weren't available even three years ago and that, provides patients with realistic hope, technology. Has evolved, to the point where we can treat them quite well and often, cure, their intracranial disease, most. Patients with cancer, who have brain metastases. Are going, to find that their ultimate, prognosis, is really dependent on what's going on with the cancer and the rest of their body the future is really bright for these people because, our systemic, therapies, are really. Progressing. And, survival. Is better than it ever has been in the past I think the future is really, going to be changing, cancer, from, a fatal disease to, a chronic disease. You.

2018-02-08 18:10

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Very informative. Thank you for sharing.

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