Um So next, I'd like you to induct Mark. Doctor Mark Holman. Uh Mark is a longtime colleague, um who is um recently at the institution took on a new role as the clinical director of our GU service line has done a tremendous job. Um He's gonna speak to uh the new Adaptive Radiation Therapy program that we have at Fox Chase. Agree. Thank you for that introduction, Alex. Um So we're gonna take a look under the hood of Adaptive radiation therapy, both literally and figuratively um specifically for prostate cancer. So, my disclosures and in outline of what we're gonna cover tonight, um I'm gonna talk about the rationale for adaptive radiation therapy. Why is it important and why are we looking to use it and why do we use it now? Um How does adaptive radiation therapy work? And we're gonna con contrast that to the current static treatments that have been used for decades. I'll go over some clinical examples because a lot of the benefits you don't really see and, and until you try this in practice and it, it's, it's quite impressive what it can do and we'll talk about ways to leverage those advantages uh to improve care in the future. So, radiation oncologists, like any other physician, we walk that tight rope in terms of trying to improve the uh the the the efficacy of our treatments. And for radiation, basically, that's dose escalation or other other means to be more aggressive with the radiation, uh perhaps in, in hypo fractionation. But at the same time, we also have to strive to minimize side effects to do this properly. And for radiation for prostate cancer fractionation, um you know, we'll, we'll save that for a different talk because it's somewhat unique to prostate cancer. Um But ma mainly what we do on a daily basis with any, any target is we want to improve our precision. And so we've, we've gotten very good at developing very conformal radiation treatment plans that really are shaped nicely to cover the target volume with minimize minimal radiation spillage to surrounding areas. But the best radiation treatment plan is no good unless it's targeted properly and aligned properly. So a lot of the precision these days is in accuracy of doing that. And that's adaptive radiation therapy is, is one of the epitome of that technology. So the benefits of increased precision is that it limits, limits the radiation dose of the normal tissues. This can improve the tolerability of the treatment. And it also allows for shorter treatment course. So that improves our access, improves our through through port and efficiency. It also provides us the potential to push the, push the needle a little bit harder and, you know, try and uh ex uh increase our radiation dose. And hopefully our disease control. We've done this for years, decades. With brachytherapy, brachytherapy is, is such a conformal radiation dose distribution that we can deliver HDR brachytherapy to a prostate in over a week in just a week. So it's one of the shortest most conformal treatments that we have uh most aggressive treatments for prostate cancer. And external beam has eventually started to catch up, you know, with, with increasing um uh precision of these treatments. We've gone from eight week courses where we could escalate the dose to to deliver 40 treatments. So five days a week over eight weeks, and we now have these very accurate uh precise um capabilities in terms of treatment planning and alignment, robotic linear accelerators, uh you know, daily com beam ct imaging gui image guidance that allow us to, to do this uh similarly aggressive treatments with external beam radiation. Now, there are five treatments uh every other day over the course of about a week and a half to two weeks. And it's all surrounds a, a very basic principle of radiation therapy, uh which is accounting for uncertainty, very much similar to my surgical colleagues that have to have some sort of margin to make sure they, they resect the entire tumor. We have to have a margin uh for uncertainty that goes on with our daily imaging and our our our targeting. So in comparison here, you know, with um prior radiation techniques such as 3D conformal radiation therapy from the, from the eighties and nineties uh shown there on the left, we'd have to have this uncertainty margin called the planning target volume. And basically, a lot of this accounts for the daily uncertainty in where the where the tumor is located when you set the patient up from day to day to day, um there is internal motion. But for the prostate, you know, when the patients actually internal motion is when the patient's laying there being treated, that's relatively minimal for the prostate. It does exist, but a lot of it's in daily set up. So with more crude alignment techniques, we'd have to do a two centimeter margin on the target here shown it's a prostate. We treat a lot of unnecessary bladder and rectum. But these days with more uh precise techniques, we can limit that uncertainty margin and it just you can see the difference there on the right with adaptive radiation therapy where we're using three millimeter uncertainty margins for our planning target volumes. So we've used techniques that, that help align the treatment plan. And again, you know, image guided radiation therapy, we use daily com B MC TS to align the patient. Uh and and of uh through, through uh very high resolution CT imaging of the prostate, we image the gold sea fiducials, which are markers that we can image with orthogonal x rays, radio frequency beacons where you use robotic gantries that can actually track a cratch, uh track a gold fiducial implanted in the prostate using orthogonal imaging. All these things have been used, but all they do is actually just align the treatment plan. That treatment plan never changes. The advantage of a ra adaptive radiation therapy is that we use that imaging to align. But then we can actually use that CH beam CT to change the shape of the treatment. And you have to have very efficient uh hardware to do this. And there are several platforms that have been used and they're all based around imaging. Now, CT imaging is what we've used um you know, on a daily basis in most radiation centers and certainly ours over the course of a couple of decades now. And it's the most efficient, most practical, but there are other platforms. Uh The MRI Guarded uh guided platform is currently uh not available. Uh Unfortunately, due to back bankruptcy of the uh the company that was manufacturing it, pet guided is uh a Adaptive radiation therapy is probably in its infancy. So we use CT guided and it's, it's based upon efficiency, efficiency is what, what makes this happen. So it looks like just a regular old cat scanner, but it's actually a linear accelerator an imager, it's actually an MV com beam CT imager. Uh and it, and it or I'm sorry, KV com beam CT imager. And it's all very efficient. The patient doesn't have to move and that, that, that allows us to do things quickly. And that, that's what allows adaptive radiation therapy. And I'll, I'll see, I'll show you how we can press that. So let's go through a description of the adaptive radiation therapy process. It's important to compare this to what we've previously done in terms of static radiation treatments where we start in the left hand side there with AC T and MRI simulation to generate, you know, a 3D model. In our uh in in virtual reality of our, our patients that we do the treatment plan process, we go through contouring. We developed a treatment plan, we optimize it. We have to do a lot of Q A our physicists uh treat a treat a um a de array that to make sure that everything is uh ma everything reality matches virtual reality that takes eight days. And then when we actually have that treatment plan, it can be excellent, but you gotta set it up. So we use daily com B MC T to align the patient, make sure that the prostate is, is is localized uh correctly within the target volume. But once it's there, it doesn't change and we do our best to align it. But you always have a static treatment plan with adaptive radiation therapy. The workflow is is very similar, it starts off with AC T simulation, Mr stimulation treatment planning. But once you actually have the daily com beam ct, the equipment is so efficient, they can act and uses uh A I tools to help us contour and replan and reoping that we can go through that whole process that used to take eight days and ret that in the course of 20 minutes. So once we have the patient aligned, we can actually adapt for daily uh anatomical changes in the patient set up. And that's where the magic is. So these are all the steps that happen within that 20 minutes and I won't go through all of them. But one important step is, is to note there, once we get the patient aligned to generate the new treatment plan, a doctor or a medical uh a radiation oncologist board certified has to be uh at the machine, at least in the policies of our, our department to make a clinical decision about whether or not the the current treatment plan, we call the scheduled plan, the, the static treatment plan that was developed initially, whether or not that would be uh uh a sufficient uh treatment or whether or not the adaptive radiation therapy plan has some benefits in terms of target coverage or in terms of uh organs at risk bearing. So that decision has to be made and then the patient, the Q A can happen and the patients treat and this all occurs within 20 minutes, but it's pretty resource intensive. So what you need to consider before selecting an adaptive radiation therapy for a particular patient or for that capability for your center in, in terms of the investment is you have to think, am I treating something that changes from day to day? Um It's, it's more appropriate for more hyper fractionated radiation schedules because it's so resource intensive. It's, it's better suited to SP RT. Although sometimes we do treat uh treat patients that are getting more fractionated radiation therapy over several weeks. But the trade off is different because the, the resource is so intensive to have uh an MD standing there for each treatment, imaging quality is important. So that's why all the different modalities are available. But when we use CT based adaptive radiation therapy, there's some uh image fusion and some fiducials that you can use to help highlight your target. But you have to be able to see your target and have to be able to see the organs at risk to be able to adjust them on a day to day basis. Based upon the cone B MC T motion management is important always with radiation therapy and a lot of times that the motion uh actually happening when we're talking about targets like lung tumors, it may be less advantageous when we're talking about daily set up because the mo respiratory motion is greater. But for prostate that, that doesn't come into play because it's such a complex treatment requires a lot of resources and you need to know, know that you have the staffing and the ability to support that. So, some clinical examples of the advan advantages that we can do with, with uh adaptive radiation therapy. I'm gonna show you bread and butter prostate patient. This is a favorable intermediate risk patient with prostate cancer. Um We plan to treat them with uh stereotactic body radiation therapy to 88 gray times five fractions to a total dose of 40 gray. And I'll show you what we look at from day to day basis. So this is what the first um uh fraction looked like. You can see. These are, these are the target goals that we have there on the left for the planning target volume. The reference plan is what we initially planned our goal uh and how we were able to meet those goals. The scheduled plan is what that treatment would look like delivered on the daily com beam CT. And you see sometimes it's surprisingly low. In this case, it was only 91% coverage compared to 95. The adapted pra uh radiation plan was clearly better with 95% target coverage there, there was improved rectal sparing at the same time. So clearly, this was a win for adaptive radiation therapy and a lot of that honestly is because we're using smaller margins. So that's where a lot of the advantage is. But adapt, adaption allows us to do that. The bladder sparing was similar. And so this is another case that, you know, prostates don't move a heck of a lot, but they, they can, but a lot of times they're pretty stable and they're probably even more stable when we're using rectal spacers. But this is a nice case. Um That really shows the, the really uh strength of adaptive radiation. This is a patient referred to me by one of my medical oncology, colleagues that has recurrent prostate cancer after failing um LDR back in 2019. Uh he has a recurrence in the left seminal vesicle and a left um uh external iliac lymph node there shown on the, on his uh ps ma pet CT. Um He tolerated ad T quite poorly um and really s uh within the first couple of months, really reduces quality of life. So he's looking for alternatives. So we plan to treat him with stere ttic body radiation therapy to both targets 50 gray and five fractions to the external iliac lymph node. And then we're also treating the seminal vesicle with uh with SP RT to 40 gray and five fractions. And we could actually image the, the LDR seeds, the, the, the prior uh radiation uh devices and actually develop a margin and an avoidance structure that we could look at in real time to do that. And the SV actually moved quite a bit. So this is an example of his first treatment plan. And what we look at when we're actually at the machine is what a dose volume histogram there. On the right, the reference plan is demonstrating our goals uh in dotted lines and the targets are all in the upper right hand corner at higher doses and increasing volumes. And you can see the solid lines are really not meeting those, those those uh dash lines, particularly the red lines um showing the the the the dose coverage of the targets is actually quite poor using the scheduled treatment plan. But using the Adaptive radiation plan, we were able to comp compensate for that. And you can actually see the changes here. The adaptive plan is on the left and the reference pan is on the right and you can see the anatomical changes particularly in the target shown here in color wash of the left F left SV. You can actually see there's a lot of rotation going on there on the bottom right hand corners of each respective panel from the Sagittal views. And so what are some of the applications we can use for adaptive radiation therapy? So for prostate cancer, you can try and move the needle a little bit further because it's so precise. We're starting to do urethral sparing SP RT that can increase the tolerance and perhaps we can increase the effect effectiveness by radiate, increasing the radiation dose. We could also probably broaden the SP RT indications into high risk patients, uh where we treat the lack of pelvic lymph nodes. And perhaps we can use the same fractionation to treat them in five fractions, which would be nice. Um Perhaps more effective as well. Oligo meta sag disease. Typically, when we're talking about uh nodal metastases in the abdomen and pelvis for prostate cancer. Uh the the small bowels are limiting structure and has significant daily variability. So there's opportunities to improve the disease can control by improving the, the precision and tolerability of treatment. And the bladder is a difficult target to hit. It changes from day to day, the filling can change actually while the patients being treated. So, being able to adapt to that on a daily basis really gives us opportunities to perhaps be more uh uh more aggressive in terms of dose escalation, but also hyperfractionation uh to improve access and uh perhaps disease control in those patients as well. And uh thank you all for your attention and thank you for, um, you know, the, the fox chase for supporting the, the the having these great tools that we can offer our patients. And um, thank you very much.
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