Chapters Transcript Video SABR for Oligometastatic Prostate Cancer and Localized Kidney Cancer Back to Symposium Doctor Wong is next. She is really an expert, um, general to urinary radiation oncologist. She's an assistant professor in the department of radiation oncology at, uh, Fox Chase, and, uh, certainly we collaborate on a tremendous amount of patients and, um. As you probably know, there's been a lot of sort of progress in uh stereotactic ablated body radiotherapy for both prostate cancer and kidney cancer, really trying to go after all go metastatic sites, uh, trying to actually use radiation for kidney cancer which has been like a taboo in the past, so she's gonna talk to us about that. Hi, very nice to meet you guys. um, I'm excited to be talking about, uh, newer options for radiation therapy, particularly for oligometastatic prostate cancer and for localized kidney cancer. So going over things, we got to start with the radiation basics of why this is new and why this is different and applications for both prostate cancer, kidney cancer, and going over our newer adaptive treatment workflow. So starting with the basics, uh, radiation works by damaging DNA, causing double stranded DNA breaks, and there's a differential between how normal tissues can repair these sorts of damage and tumor tumor tissue cannot, um, so we take advantage of a therapeutic window where we're hopefully not harming too much normal tissue as well, uh, while fully taking care of the malignant cells. So, This is, uh, an alpha beta curve for modeling radiation. Uh, you don't have to know too much of the details of it, but you can think of the red top line as being how normal tissue responds to radiation and that green of how tumor tissue responds. So it's a little bit more sensitive. That first two gray line is where normal conventional, uh, fraction of radiation is, so typically 2 gray per day. Um, and so if you think of cutting that curve right along that line, there shouldn't be very much effect on the, uh, normal tissue, but it should have a significant effect on the, uh, on the tumor cells and then you repeat that and repeat that and repeat that to get all the way through your course. Problem is it takes a really long time. So this is talking about doing something on the order of like a 4 to 8 week course of radiation to get you through like that. So some of the newer thoughts in radiation is how do we do it faster while still being just as effective and just as safe. So that second line that's on there around 4 gray and beyond is, uh, is more hyperfractionated techniques, uh, which gets you through faster by giving you more radiation each time. So this is sort of like how that how that multiplies out over a whole course of radiation, right? There shouldn't be on the left is the more conventional fractionation, right? Takes you 1234567 or so to get across that, um, that graph. And so that's repeating that same part of the graph again and again and again, giving you that small fraction of radiation again that doesn't really affect the normal tissue but can fully take care of all of the, uh, tumor cells that are there. The the graph next to it shows more more hyperfractionated course, right? It takes fewer steps to get all the way across the graph, um, to fully uh affect those tumor cells, but there can be a little bit more effect on the normal tissue. So that's why conventionally in the past. We went with those smaller bites of radiation instead of kind of bigger jumps, um, to be as safe as possible on normal tissue, but there's been a lot of, uh, ways that we can do this better with newer technologies to be able to have less effect on normal tissues even when giving those bigger doses of radiation. So talking through what actually happens when you say somebody needs radiation to them getting that very first radiation treatment. First thing that happens is a simulation, which is sort of a dry run, uh, a practice of how you're gonna set the patient up for radiation every day and acquiring images to make sure that everything gets planned on how their anatomy looks at the time of treatment. It usually involves a CT scan. Sometimes we fuse that with things like MRI scans or PET scans, um, and newer ways of tracking where organ motion is with throughout the respiratory cycle and other things that can account for organ motion. So that we can take into account where all of the normal tissue may move during the respiratory cycle, where tumor cells can move during the respiratory cycle. This is really, really important for things like lung cancers, but can affect, um, abdominal contents as well. So from there, the physician contours out, um, and actually draws on the CAT scan all of the tissues that we want to be sure that we know where the radiation is going to. All of the normal tissues, all of the targets, we work with a, uh, a whole team that helps us put these plants together. There are dosimetrists that are really experts at, um, the optimization software that we use to be able to design out the radiation treatments, um, and it goes through rigorous amounts of, uh, quality assurance and safety checks before the first patient. Um, ever gets their first treatment. So the, uh, bottom picture is actually a phantom, um, which is a fake patient. Every time that somebody gets a complex treatment of radiation, so IMRT or SBRT, um, we do a. I'll run on, uh, a phantom, which is, which is not a real patient but made out of plastic. It has a bunch of sensors inside and make sure that we deliver the radiation as we expect to before they ever get on the table. So that happens for every single patient that gets, uh, a complex form of radiation. Then with delivery, most everything we do is external beam radiation therapy as a reminder that's done on a linear accelerator, which generates the radiation in the room only at the time of treatment. So anytime you're there and the machine is off, as soon as you get off the table, there are no issues with radiation safety. It's only on while the patient is getting their treatment. So there's a number of different types of radiation. A lot of these go into acronyms if you've probably heard a lot of these acronyms and not really know what they refer to. So it's all determined by the complexity of how we design out the radiation. Um, so traditional was two dimensional radiation therapy, which was designed on X-rays, so a two dimensional image. Um, 3D conformal is when we moved on to, uh, actually getting CT images and being able to design, um, volumetric spaces to get radiation and to be able to target, um, particular organs, um, as well as, as tumor volumes in three dimensional space. Intensity modulated radiation therapy is sort of the next step up from that. Um, it's still doing things in three dimensions, um, but it lets us plan things in a much more complicated way involving many more variables, all of the different organs at risk, as well as the tumor volumes, and how do you optimize your treatment, uh, with, uh, changing the intensity of the beam within one single beam. So it's not like one flashlight. There's little beamlets that's broken up that each have a different intensity. There are different locations where you can give the radiation sort of the beam angles as well as, uh, a number of different things that go into how do you make this plan, um, image guided radiation therapy lets us double check that we're being as precise as we can possibly be, uh, with imaging every single day to make sure that we're hitting the target that we want to, um, and stereotactic radiation, um, uses a stereotactic coordinate system to be as precise as we possibly can be and allows for a lot more of that dose escalation that I was talking about. So this is, uh, sort of the, the view of more conventionally fractionated radiation. Um, a 3D conformal plan and an IMRT plan, uh, both of them are a little old, um, but they get the job done a lot of times you'll use more conventional fractionation for things where there are a lot of normal tissue in the area that you're trying to treat. So these are showing, you know, media sinal masses where you're really worried, uh, that you're going to have to go through a lot of normal tissues like the heart, um, esophagus, spinal cord, things like that that are nearby that you can't miss and you have to do them in that slow and steady, more conventional way of treating. These are examples of image guidance. Um, if you've heard of orthogonal X-rays, a lot of times, um, patients, uh, use, uh, uh, get implanted markers. Um, this is a prostate plant. Um, for both, uh, orthogonal X-rays, which is just the black and white image, um, some linear accelerators get plane films and we line up to where, uh, we planned for on the day of simulation. So because you can't see a prostate on a plane X-ray, that's why a lot of times, uh, people will get fiducial markers placed to make sure that you know that you're lining up properly. Um, we actually don't do that Fox chase anymore. Um, the, uh, image, the colored image, um, is a cone beam CT, um, so we do get three dimensional imaging to check, uh, patient set up every single day. You can actually see the prostate, you can see the bladder filling and all of that sort of thing to make sure that you're being as precise as you possibly can be. So sometimes when we're doing extra precise things like the, um, adaptive treatments that I'll talk about later, we do still get. Uh, those fiducial markers on top of getting, uh, cone beam imaging to make sure we're being extra, extra precise. Um, but a lot of times patients don't need to get implanted markers to be able to get conventional radiation. That last way with stereotactic body radiation therapy or stereotactic of blade of radiation therapy, which is often abbreviated as saber or SBRT, um, refers to, um, stereotactic guided radiation treatments that is typically done in something on the order of 1 to 5 treatments. These are, uh, further down on that curve where we're giving you a lot more radiation at once to get you through. Um, and you take advantage of being able to break up that beam into a number of smaller treatments. So just teeny tiny bits of radiation are passing through your normal tissues to get to all build up, um, right in the area where you want them to be treated. We take advantage of a steep dose gradient, um, so that it can get really, really hot in the middle of the tumor and that radiation can fall off very quickly. So even if there are normal tissues nearby, but not right nearby, they won't get the exposure to the radiation. So this is sort of an, um, isodose color wash between more conventional radiation as well as SBRT uh, you can think of it kind of like a topographical map, uh, so it's sort of the heat map of where the radiation is. So the closer to red you get, the higher the dose is. Um, as you can see with the more conventional treatment, you can see the entrance and the exit paths of the beams that you're using. And so it isn't full dose, but certainly there is significant dose that's passing through those normal tissues to get to where you need to. Um, on the other image, it gets, uh, broken up so much that the small amounts that are passing through those normal tissues actually don't show up on this color wash. And so it just builds up very closely right where you're, uh, trying to treat. So this kind of goes into the wording of a lot of what I talked about, uh, the comparison between those kinds of radiation. So, uh, for use for Olga metastatic prostate cancer in the past, metastatic prostate cancer was, uh, treated mainly with systemic therapy, uh, saying, you know, once it was not where it started, that's all you really needed to do. There's been more of a recognition of an allga metastatic state, um, where the use of local therapy is more indicated. Um, saber is particularly useful for these sorts of scenarios because you're just treating a small area of the body that is hopefully farther away from normal tissues and then you do your best to try to get all of the disease that's still there. Um, oftentimes we use this in, uh, go metastatic disease where there's 5 or fewer, um, sites of disease, typically bones or lymph nodes. Um, a lot of the data is for all over recurrent setting, uh, more than sort of the upfront setting, although there's, there's more and more data that's coming out. Um, I'll zoom through most of this data because I think the techniques of radiation are the more important part for you, but there has been. to show, um, that radiation to local sites can be used to delay initiation or change of, uh, systemic therapy. So a lot of times guys don't want to start on ADT and this is a way to potentially delay that as much as you possibly can, uh, as well as having, uh, improvements in survival. It is on the relatively early side. A lot of the data that we have is somewhat small phase two, sorts of trials, but there's a lot in development and hopefully we'll get a lot more of those bigger trials that are currently, um, in production to, to be done soon. Um, for kidney cancer, uh, it's an area that radiation was almost never used in the past. Um, surgery continues to be standard of care for, uh, a localized disease, but not everyone is a surgical candidate, and what do you do for these people? In the past, uh, you know, kidney cancer was thought to be more radio resistant. It behaved a little bit more like that normal tissue red curve than the tumor tissue green curve. And so when you keep giving those conventional fractionation and it just laughs in your face, um, so you have to use more of those. Higher dose per fraction techniques to be able to treat it and now that we have ways to do that safely, even though there's a lot of normal tissue, uh, that you gotta worry about right around these tumors, they are often inside an organ that you're worried about, uh, preserving. So how do you preserve part of the kidney while still getting the radiation to where you need to and that's where this technique comes in, uh, it's allowing us to do things that we couldn't do in the past. So initially that this started out uh with uh a consortium of uh of centers that started doing this on their own and kind of pooled their data to show that it was safe and feasible, um, showing that patients treated with something like 1 to 5 treatments, uh, would have, uh, good outcomes with this sort of thing. Um, the things that you're uh with low toxicity rates because one of the organs at risk is the organ that you're treating, um, a big worry is what is kidney function gonna be after getting, uh, a treatment like this, and there can be decreases in GFR, um, typically on the order of about 10 to 15, um, and depending on where you start, that could certainly be significant, um, but certainly it is possible to treat these sorts of patients without requiring dialysis. The big new trial is the fast track 2 trial which looked at doing this in a prospective manner. Um, patients were treated with either single fraction or 3 fraction treatments, um, and there were treatments of, of tumors up to 6 centimeters. I think they allowed for up to 10, but none were actually on this trial, um, and, and treating. Showed, uh, local control at 12 months of 100%. Um, grade 3 toxicity rate was low. There was no grade 4 or 5 toxicity. There were no treatment-related deaths, and there were no cancer-related deaths on, uh, on the study. It is a short period of follow up, but definitely very promising in an area where we didn't think we could do anything in the past. So a little bit more about our adaptive radiation, uh, therapy workflow that's how we do a lot of our SBRT treatments nowadays. Um, we have a variant ethos machine which is an adaptive linear accelerator. it does all of the things that the normal linear accelerators can do. Um, it has a little bit better imaging, so a more diagnostic quality CT scanner on it, and, uh, works with a whole package of software that allows for, uh, a lot of the treatment planning that I talked to you about that can happen on the fly with a patient on the table. We're using it in a number of different, uh, scenarios. uh, most, uh, applicable to this talk are, are for prostate cancer as well as starting to do, uh, a localized kidney cancer as well. This is what the machine looks like. Um, the, all of it is contained within that ring. Uh, those are the guts of the machine when it was being installed. Um, so it has both the linear accelerator head as well as, um, image capabilities on it at the same time. As a reminder, this is a regular radiation workflow. They get their simulation at the beginning with their imaging. We do all of the planning behind the scenes while, uh, waiting for the radiation to get started and then on the daily treatments that they get their plan as we planned it out. We do the confirmatory imaging as long as everything looks good, we hit. Button you get your radiation. If things don't line up properly, we have to work on, you know, maybe having you take a break, fill up your bladder if your bladder is not full enough, uh, and set you back up, see if it's working and worse comes to worst, we cancel a treatment for that day and you have to come back another day after doing a different preparation or something like that. With this new adaptive radiation work flow that we have, all of that stuff still takes place. Everything on the previous slide still happens, but when they get, uh, on the day of treatment, we get a little bit better CAT scan, um, and then readjust all of the contours, everything that the physician, um, circled out and said, yes, this is what I want to treat and this is what I don't in case the anatomy is slightly different on that day you can adapt what you're. Aiming at, um, and what we're trying to avoid, uh, the, the, it goes through an optimization. It gives you a new plan. You can pull the two, the scheduled plan as well as the new adapted plan up at the same time and compare all of the different things, um, that we're looking at organs at risk, target coverage to see which one of the two you think is better for the day and which one we're gonna go with for that day. Uh, the doc is required to do all of these things and be on the machine. Um, we do a confirmatory CAT scan at the end and make sure that the patient hasn't changed during the time that we've needed to do this. This, uh, workflow can run from something like 10 minutes to something like 45 minutes, um, depending on how complex that plan is, and then the patient gets their treatment. So ways to, uh, when we go with the adapted plan, it's either better target coverage or better organ sparing. So there's a number of things that go into whether we do this for a patient or not, um, how complex the plan is, how often we think the anatomy is gonna be different between the different days and just like the logistics of can there be docs there at that time to be able to do the work, um, but we are really expanding out, we're doing a number of these sorts of things in all different disease sites. So here's an example. This is an actual patient that I treated, uh, with allome metastatic prostate cancer to a lymph node. Um, this is his only side of disease. And so just this one small dot if you can see, uh, maybe a little bit hard to see there, but that red line, um, is a 100% isose line. Um, what's inside it is the lymph node that we're treating, and then you can see those, uh, that sort of color wash that goes off over to where, um, those lower doses of radiation are to be able to get to where we need to get to. And so these are, uh, that was, you know, his 3rd treatment. The the standard, uh, plan is on the left and the adapted treatment is on the right. Um, they may not look very different, uh, when you look at them on, uh, on imaging, but they also pull out, uh, all of the data for what we're looking for. So we have criteria for every single organ system. Of what's an acceptable, um, dose that they can get for this treatment or not and which one is lower and kind of making that judgment call of which treatment plan you go with. So for this one, because of decreased dose, uh, to the surrounding small bowel, large bowel, um, and nerves, we ended up going with the adapted plan. So for prostate cancer, um, we are typically using this sort of a treatment, uh, for early stage localized disease, um, for doing, uh, radiation treatments just to the prostate itself. So that's typically for early stage, um, low risk and favorable and immediate risk. We're also using this for olgo metastatic disease, typically, um, to sites of bones and lymph nodes. And same thing for kidney cancer. We are starting to do them for early stage non-operative patients, as well as for metastatic or locally recurrent disease. Thank you very much. Created by Related Presenters Jessica Wong, MD, MEng Assistant Director, Radiation Oncology Residency and Fellowship Training Program Assistant Professor, Department of Radiation OncologyAssistant Director, Radiation Oncology Residency and Fellowship Training Program
