 So, one of the changes that's occurred in cancer and specifically in kidney cancer is there's some novel ways that we deliver radiation therapy today that's different than the way we delivered it five and ten years ago. And although historically when we've written chapters and books on kidney cancer, kidney cancer is often considered a radio-resistant disease, but I think we need to be thinking about re-looking at that, especially in light of some of the new technology. So, we've invited Dr. Hakimian, who's an expert in radiation oncology here at Cedars-Sanai Medical Center, to talk to us about some of these approaches. Thank you. Thank you very much, Dr. Figlain. First of all, I'm not a radiologist, so we usually don't read X-rays. We use radiation therapy to actually treat cancer. What are the new techniques that we have developed in radiation oncology? Just to give you a little bit of historical data, in the old days what we did was we used radiation treatment for treatment on a daily basis. We figured out that radiation, if you give a small amount of radiation on a daily basis, you can actually kill the tumor cells, whereas you're able to sparse a lot of normal tissue. Now, to give you a little bit of history, what exactly is radiation? It's basically everything that you see around us. Radiation is everywhere, sound, light, cell phone, X-rays, sun rays, and we utilize very specific amount of radiation in the very high energy to actually utilize that, and we use that part of the radiation to actually kind of sterilize the tumor. As I mentioned, the intensity of radiation therapy increases as it enters the cell, and then all of a sudden it starts giving up its radiation to the normal tissue, and as it exits the other side of the body, it actually kind of decreases. What it does is actually as it deposits its energy in the cells, it damages the DNA of these tumor cells, and unfortunately also can damage the DNA of the normal cell, so it can actually cause some damage to the normal tissue, and unfortunately the radiation doesn't differentiate between what's a normal cell and what's a cancer cell. So the trick for us is to actually find out different ways to actually differentiate between how we can actually manipulate this radiation that we're giving to kill more of the cancer cells and spare the normal cells. For the many years what we have done is we actually figured out if you give standard dose of radiation, which is about 1.8 or 2 gray, and that's not a color gray, but rather the units of radiation, you can actually do more damage if you escalate the dose, and you give small amount of radiation, let's say on Monday, you give small amount of the radiation Tuesday, and you keep on doing the same kind of radiation over day after day for like six weeks, you can actually kill a lot more cells in the tumor and spare the normal cells, so there's really not going to be any damage long term to the, let's say, colon or rectum or any other structures, lungs. And that has been what we have been doing for many years. Now, as we increase the daily dose of radiation above 2 gray, 2.5, 3 gray, nowadays we've even give like 15, 20 gray of radiation, there's going to be a lot more damage of radiation to the area that we radiate. So the trick is actually if you spread the radiation from different areas, you can actually do a lot more damage to the tumor cells, and hopefully can spare the normal cells. So unfortunately not all cells are the same, and renal cells traditionally considered one of the areas that is relatively radio resistant. We have on one area spectrum lymphomas and seminomas which are extremely sensitive and we don't require that high dose of radiation, whereas melanomas, sarcomas, and renal cells which are considered radio resistance requiring a very high dose of radiation on a daily basis, maybe seven or eight weeks of radiation, and usually most of the normal cells are not able to tolerate this much radiation. So traditionally we have not been using radiation treatment for definitive treatment or for treatment of renal cell. Until recently with the nurses actually has been resurgence of this, mainly because there are better techniques, we have better definition of the volume, we have CT scans which are much better in terms of defining, we have MRIs, our computers are becoming very sophisticated. Nowadays we can actually do a very large number of calculations in a very short period of time and we also can figure out different angles of radiation that can come from different areas, all concentrating on one area and basically blasting the tumor without causing any damage to normal cells. Our machines have been also becoming very sophisticated. In the old days we used to use the machines that actually were able to give the radiation only. Nowadays we have machines that we can actually do a CAT scan on the head of the machine so we know exactly where the radiation is going beforehand. We are using CAT scan on a regular basis to better define the volumes that needs to be treated and also there is newer techniques that we have, if you imagine if you are taking a deep breath in and out, your whole chest moves, your abdomen moves and if you are trying to be very precise with the radiation in a small area, you are talking about the moving targets and that moving target needs to be addressed and we have the new technology that we can actually beam the radiation while the radiation is on during a certain period of breathing pattern or we can actually define the volume of the tumor during different phases of breathing so we can actually have a better understanding and we can make sure we can treat the tumor very well. So what exactly do we treat when we are treating somebody with a renal cell? Unfortunately there is no benefit of radiation therapy for an adjuvant setting so if somebody has their kidney removed, there is no benefit of giving radiation treatment. Usually when we have tumors that are metastatic or causing problems, that's when we start coming into play. One of the areas that actually we see most of the radiation given is usually chemotherapies or other agents do not cross the blood-brain barrier so the brain becomes a sanctuary site and often times we find that there is going to be tumors that are metastasized to the brain. Now it's kind of very difficult for us to treat these patients with a traditional way of treating with a whole brain radiation therapy mainly because if you're going to be eradicating your tumor which is relatively radio-resistance and you have to treat the entire brain with the radiation, you're going to cause a lot of patients who are going to be having a lot of cognitive problems and we may end up causing a lot of brain damage. So there are actually things that we can do for that and also if somebody has let's say bony metastases, they are in pain, radiation treatment is extremely good in terms of controlling that, pain and relieving the pain. So again, this is just a spectrum of the radiation beam that we see. You can see that it's everywhere, anywhere from microwave, visible light and x-rays, gamma rays and going back to Iran, I guess this is like nuclear powers and what we are using is actually some radiation that is actually in this area, gamma ray and x-ray to treat the patients. So what will happen is when we do the treatment, the radiation goes in at certain distance, this is the skin of the patient, this is the depth of penetration, if you give let's say 180 units of radiation, the skin is relatively spared and then there's a maximum response of radiation to certain depth and then it deposits its energy going as it goes out. So if you are treating a patient whose tumor is right here, you have to give a very high dose of radiation to this area or even the skin to do the damage to that. So what will happen is in the old days, what we ended up doing is if you are going to be treating from the back, you ended up having a ulceration in the skin which was very bad and would never heal. Now in order for us to do that, this is a patient who has a prostate cancer, as you can see, the prostate itself is located here, the rectum is sitting here, the bladder is sitting here. Instead of giving the radiation from one side, you can actually give the radiation from different sides and what will happen is you end up getting distributional radiation. Now imagine instead of giving four radiation beams, you give radiation from like 360 different angles or 720 different angles, what we call rotational arc. We can basically concentrate on the radiation on the tumor and minimize the dose of radiation to the tumor cells. And the idea here is you really want to make sure that the toxicity of radiation is damaged to the normal cells and the response is actually what we are trying to do is which is basically killing the tumor cells. So what we are trying to do is actually separate these two curves from each other. The idea is if you want to control the tumor with very accuracy, you want to make sure that you do enough damage to this and have a very minimal toxicity at the same dose. Now what can we do to actually separate these two curves from each other so we can actually get a much better response? One is what we get some help every now and then from our medical oncologist, what we call radius sensitizers, drugs that can actually help us to make the radiation more effective, fractionated radiation treatment. Those were what we used to do up to recently. Now a few things that happened in the old days when we were treating patients, we used to cut blocks. And these blocks were probably about 10, 15 pounds. And you could only put it in front of one radiation beam. Now this is part of our machine and that actually shows us these leaves that you see. There are about 120 leaves that you see over here. And what will happen is these leaves can be open and close. And these are blocks that actually can come in front of radiation beam as it comes out of the machine. So if you have a tumor here and you have a structure that you're trying to avoid, you can actually in the old days we used to actually cut these blocks to actually treat from one angle. Nowadays we can put these blocks that you saw previously and that can actually block the tumor pretty much very similar to this. The advantage of these blocks is that you can actually have more angles of radiation that you can treat simultaneously. You're not just limited to treating from the front, back, right and left lateral. You can treat from, as I mentioned, 360 degrees angles. And radiation can actually come from what we call arc therapy, which is basically rotate around. And these blocks can actually change positions simultaneously. And we can give the treatment over, let's say, five, ten minutes and deliver a very high dose of radiation treatment. And the other thing that we can do is we can actually change the intensity of radiation. This is an x-ray. And by just changing the intensity of radiation during the certain time, we can actually develop x-rays and you can actually see this is Albert Einstein. The picture of Albert Einstein actually developed on an x-ray. So it's a great way of doing the treatment. We can actually pretty much brush the radiation treatment the way that we want it. Now, it's great if you can do that on a machine. But what about, we also need accuracy. And we certainly don't wanna be inaccurate with the radiation. So accuracy is extremely important for us. So what can we do to increase this accuracy? First thing first, I did mention brain. I do a lot of gamma knife cases. And one of the things that we can do is actually we can have these devices pretty much screwed on their local anesthetic. Believe it or not, actually, this is not very painful. And we put this frame on. Now with this frame on, we can actually get images. And from these devices that we put on this device, we can actually have a fiducial marker and know exactly the exact location of every structure inside the brain. So if there's a tumor in the brain, we can actually pinpoint it. We use that for gamma knife, we use that for x-knife. And if you are pretty much knowing that this frame is in the same spot, which this thing is not gonna move, then you can actually deliver the radiation treatment. And once the patient is ready to get treated, you basically put them on the head of the machine. Frame hasn't moved that much. We can actually do your quality assurances and then subsequently do the delivery of the radiation. Now what you see here is basically these are arc therapy, as I mentioned. Basically the radiation starts from here, goes into the different angle. Then we turn the table of the machine and do another arc and then another arc. So what it does for us is actually, it gives small amount of radiation from each beam. And where they converge, we get a full dose of radiation. So imagine this is where our target is. We give a very high dose of radiation. And as you can see, these lines that you see are what we call isodose lines. These lines actually drop farther and farther. So if you are treating, let's say the trigeminal nerve, which is sitting right here, we can blast it, give like about 67th grade of radiation, which is tremendous amount of radiation. And if I do that in anywhere inside the body, I can pretty much make a hole or cause damage to that area. And the structure that is next to it, which is a brain stem, gives very minimal amount of radiation. So we can actually do a very good job of delivering high dose of radiation to the brain in this structure and do a very small damage. You don't have to take my word for it. These are actually some of the real patients that we treated. This is one of the cases that this stuff that you see the white stuff is actually where the tumor is. This patient had one tumor here, one tumor here, another tumor up down here. And once we did the treatment several months later, we actually did MRIs. And you can see the structures that were here are pretty much gone. And what you see is actually just necrosis and dead cells. So this actually worked very well for this patient. So for brain metastases, we can do a great job of delivering high doses. And depending on the size of the metastases, we can actually control them, these lesions up to about 80, 90% of the time, which is remarkable. So somebody has brain metastases, chemotherapy doesn't work, whole brain radiation therapy really doesn't work as well. The gamma knife or X knife or other forms of radiation therapy can deliver very high dose of radiation and do a very good job of damaging the tumor. Now, if tumors are too big for us, we don't consider gamma knife as the choice. We like to make sure that we can resect them if possible because the collateral damage from the radiation to the normal tissue can be substantial and we like to give either smaller volumes of treatment. So anything that is above 3CM, we don't like to treat with gamma knife. We either recommend that they get multiple radiation treatment or alternatively we like them to actually have a surgery. Now, moving on, the brain we can actually put frames on people's head. What else can we do? This is what we see here is actually the tritical dimensional structure of the body. You can see the lungs are here, the white. The trachea is here. Just before that is just the lung and then we have other structures where the tumors are. And over here, what we see is basically if you have a body here and you're looking at the tumor volume here and this is a spinal cord, what you see the 95% and 30% is actually the actual dose of radiation that is given. So I can deliver a very high dose of radiation treatment to the spine where the tumor might be causing severe pain, damage that and give a very small amount of radiation therapy to the, well, the third of the dose of radiation therapy to the spinal cord without causing any spinal cord injury. So this is remarkable. Saying that again, let's say this is a tumor that we see in the spinal cord, spinal column. This is a spinal cord and you can see this tumor is actually pressing on the spinal cord, pushing it backwards. And these are the spine itself. So if I draw the volume of the tumor that I can have here, I can basically do the treatment to this side and I can treat it. And this is just what we call a color wash of this tumor. You can see the red is where we get the full dose of radiation. Blue is where the radiation beams are coming in from different angles. And we can basically pinpoint the dose of radiation to this vertebral body. And nowadays, we can actually give about 18 grade, which is very high dose of radiation therapy to the spine, eradicate the tumor in that spine without causing any injury. Advantage of this is actually we get a relief very fast. It's very effective and it's very durable. The standard dose of radiation, when I do the treatment, 30 grade and 10 fractions, I can actually control the pain, but usually the pain is not gonna be achievable or last beyond a year or two. And usually the tumor can come back in the same spot. Whereas if I do the radiation this way with a high dose of radiation, what we call stereotactic radiotherapy or stereotactic radiotherapy to the body or SBRT, we can actually deliver a very high dose of radiation treatment. And there are different machines. Cyberknife is one basically that can deliver the radiation. It's a machine that actually travels and deliver the radiation through different angles. Or alternatively, there are different things that we have. So if I have a treatment and I can actually deliver the radiation here, is it gonna be exactly in the same spot? I put this back again. I wanna make sure that I'm accurate with the body as well. So one of the things that we do have is stereotactic body radiotherapy, as I mentioned, is respiration. I'm concerned about respiratory gating. If we all take a deep breath in and out, we know that the whole abdomen and chest moves. And if I have a tumor in the lung, that can actually move up and down. It can move anterior posteriorly or front and the back. We can actually sometimes move to the sides. So part of the job that I do, if I really wanna be accurate, I wanna make sure I include all the tumor and I wanna make sure that I exclude as much of a lung or intestines or any other structure that are out there. And we are discovering that some structures move a lot, some structures don't move at all. And we can actually use respiratory gating. We have devices that we can use. So the patient actually take a deep breath in, out, and then they can actually visualize exactly when the radiation's going in. And we can actually cycle the radiation beam as they are breathing at certain phase of the breathing. So they're exhaling, they're holding their breath for 10 seconds, 15 seconds, the radiation is on. Then they take a breath back and then we ask them to take a deep breath in. Takes a few minutes longer for us to treat, but at least we are much more concentrated and we are much tighter with our field of radiation treatment. This is the device that we have here at CDERS. This is a trilogy. This is what the radiation machine looks like. What you see here is actually a CAT scan that we have on the head of the machine. And the purpose of the CAT scan is we do acquire images from the CAT scan every time we do the treatment. And what we need to do is we need to make sure that what we are treating is the exact same spot. So if you notice here, there are about four images that you see. Two of them are the same as the other two. Two of them are the ones that we acquired at the time of the CT scan and two of them are the ones that we are actually getting at the time of the treatment. And before we turn the machine on, we may need to move the patient about half a C.M. or one C.M. And we know that the treatment is gonna be going in the same spot, an exact same spot. We make the adjustment before we turn the machine on when we get into the treatment. And we can see it actually in three dimensionally, not just one image, but rather three images, axial, sagittal, and coronal images. Now, what can we do with the radiation? We do treat patients who have brain metastases, spine metastases. Nowadays, I think with the technology that we have, we can treat some of the patients who have tumors that are in the lung. I think somebody who has isolated lesions and we have exhausted other options, certainly static body radiotherapy can deliver very high dose of radiation. And I think we can actually control the tumor in that site. So hopefully we can actually improve on disease-free survival. We can actually control some of the symptoms that may happen if the tumor is in the lung, if the tumor is in the bone, if the tumor is causing bleeding. We can deliver a very high dose of radiation therapy. And I reassure everybody that we are not gonna cause any problem. Nobody's gonna have like three hands here. And thank you. What questions can I answer? Questions. I understand when you say you can target to a specific spot. Do you control, like if you were shooting at this thing here, you control the depth of it as well so it don't go all the way through or something? Correct. So you control it all? Well, as I mentioned, the radiation goes in at certain distance and if I put a radiation beam coming from this side, it's gonna exit from this side. So the trick is you wanna have multiple different beams of radiation. So with gamma knife, you have like 201 radiation sources. Each one of them give a very small dose of radiation. So implication of that is this small dose of radiation is not gonna cause any damage to the brain itself. Whereas where all these are converging, that's where we get a very high dose of radiation that can actually eradicate the tumor. Okay. Thank you, Bruce. Thank you.