brachytherapy and I think that's what you guys are doing too, but I just want to go over why we're doing it and what we're doing. Again, short talk, but a brief talk about advances in brachytherapy. So first of all, the key, which is the whole point of me doing this talk, was to tell you how important brachytherapy is in the treatment of cervix cancer. And in fact, this is a study that was done looking at patients with cervix cancer, and they looked at patients who got radiation therapy alone and patients who got radiation therapy plus brachytherapy. And patients who got no brachytherapy had a decreased overall survival than compared to the patients who got brachytherapy. So brachytherapy is one of the most important points of treatment of cervix cancer. So really cervix cancer is 50% dose comes from your radiation from the outside and 50% comes from brachytherapy. And again, it's just same thing, another study that showed as brachytherapy utilization went down, survival went down. So brachytherapy is, and actually the reason why brachytherapy is utilization is going down, especially in the United States, is that we thought that we could replace it with SBRT or VMAT, but you can't. If you can do brachytherapy, you got to do it. So let's talk about how we're doing brachytherapy now. And I think some of the gynecologists who are on the call probably still remember the 2D or the 3D versus what we're doing now, which is image-guided brachytherapy. So our brachytherapy planning has completely changed from when the gynecologists who are actually on the call know before and what they were told to talk about when they get their boards. So why are we doing image-guided brachytherapy? Well, with image-guided brachytherapy, whether it's CT or MRI, you can see all the normal tissues, so you can reduce the doses to the normal tissue. But because you can see the normal tissue, you can actually maybe, and you can see the cervix and uterus, you may be able to increase the dose to the area you want to treat, which is the cervix and uterus, while limiting the dose to your normal tissue. The images that we're using are either MRI or CT, and we're now actually contouring, and I'm going to go over with the definitions of everything, but the key is we're contouring bladder, we're looking at dose to the rectum, and now we know the dose of sigmoid and small bowel is just as important. So image-based brachytherapy helps you define the disease, it helps you define the normal tissues, and it helps you shape. So just an example of where we've gone, right, so in probably prior to 10 years ago, we did plain films, right, and all we could see was just the bony structures and our instruments. With CT, you can see all the normal tissues, and you can see the uterus and the cervix, but you can't really see the gross disease, so the MRI is the best to see the gross disease, but, and the normal tissue, but CT is pretty good at helping, so if all you have is CT, CT is good enough. So let's talk about what we're looking at now and what we use. So we don't use point A anymore. Even though we're getting dose to point A, we're actually not using that to help dose out our fractionation. So what do we dose it out to? So what are we looking at? And I'm going to show you another picture. So one, you look at the gross tumor volume, which is called the GTV, and you can only see the gross tumor volume if you're doing MRI with the brachytherapy. So if you're not using MRI, you're not going to have a gross tumor volume, okay? So what do you have if you're doing CT and MRI, and what are you dosing now instead of point A? So what we give, what we're looking at dose-wise is to our high-risk CTV, okay? So the high-risk CTV is the entire cervix plus whatever is left at the time of brachytherapy. So if there's still parametrial disease, you're going to outline the parametrial disease. If there's still vaginal disease, you're going to outline that, but if it's all gone and you have a normal cervix at the time of brachytherapy, all you're going to do is outline the cervix. So what we're dosing now is not to point A. We're looking at 90 grade to the high-risk CTV. We also look at the intermediate risk CTV, which I'm not going to talk a whole lot about. Some people do that, and it's really more that point B dose, but it's a little bit more narrow. So you're looking at some disease microscopically outside of just the cervix and what's left. And then you also conjure, like I said, the bladder, rectum, and sigmoid. So this is actually a beautiful example of what I'm talking about, but on MRI. So the red, that's your GTV. So that's the gross tumor volume that's left at the time of brachytherapy. The orange is what I'm dosing my prescription to, which is the HRCTV, the high-risk CTV, which is the entire cervix, which is usually about three CMs in length and whatever's left at the time of my brachytherapy. And then the intermediate risk CTV, which is based on a lot of volume metric distributions, but it's basically your point A. Again, ask questions, or if you have any questions, please stop me. So as we talked about, most people use CTs. I actually use CTs because it's very hard for me to get MRIs, right? So the CT overestimates your cervix and uterus and your tumor volume. So it overestimates your HRCTV, but it's still a very good tool to use for image-guided brachytherapy. CTs are very good for your normal tissue. It does show you every, all your normal tissues. The only, but the big thing is you cannot see your gross tumor volume, and you may have a slightly bigger HRCTV if you use just CTs. So, and this just shows you that, right? So this is your HRCTV if you use just CT versus your HRCTV if you used MRI. So you can see that with the CT, you're going to have a little bit bigger HRCTV, so we actually recognize that because all we do is use CTs. So we will work on trying to make our, we actually really do use our physical exam at the time of brachytherapy and use that measurement to know what the width will be instead of just using the CT. So if I examine this patient at the time of brachytherapy, and the cervix width is 4 cm, I'm going to make sure that my brachytherapy makes sure that my HRCTV is not bigger than 4 cm because a CT, it's really hard to find the borders. But just, you can see how big of a difference there is with the HRCTV using CT versus MR. Anuja. Yes. Anuja, I have a question. Yes. What does CT stand for? I'm sorry? What is, what does CT stand for? Clinical Tumor Volume. Clinical Tumor Volume. Right. So it's the high risk clinical tumor volume, which is what we're prescribing to, which is the entire cervix and whatever residual disease is left at the time of brachytherapy. And that's what we're giving our prescription to now and not point A. Good question. Again, you guys ask, because I do talk fast. So let's talk a little bit because I'm going to show you why we are changing some things. And I don't know if you guys are doing this or not now in Vietnam, but this used to be the old volumes that we talked about. And this was when, you know, pre, actually true pre-image guided brachytherapy. So this is really was when we were still doing really pretty much 2D. Okay. But this has all changed. And again, I think it's a little bit different in Japan because they do go a little bit lower, but it's not that much different now that they're using image guided brachytherapy. So, you know, we used to say, and I'm going to say this, we used to say when I started doing radiation therapy for point A, you wanted to get to 85 to 90 gray, right? But, you know, data from Japan came out are, when we started moving from low dose rate to high dose rate, we started getting more toxicity and we actually dropped our point A doses down to between 80 and 85. So we weren't actually going so high because we saw increased toxicity with high dose rate. And the data from Japan showed that you could maybe get away with lower dose. So that became our thing was not, instead of going 85 to 90, we actually dropped it down to 80 to 85. And they actually saw some increased recurrences, especially with high dose rate. So they've actually a big study called the embrace study has looked at just high dose rate and image guided high dose rate and looked at what doses you really need. And what they have found is that it's based on volume and it's based on stage. Okay. So stage one and two, you probably can get away with 80 to 85 to the high risk CTV, but stage three and four, you really need to try to push it above 85. The other thing they found though, is that volume is a big thing. So what is left at the time of brachytherapy? So if you have anything bigger than 35 CCs volume of the cervix, you need 85 or higher dose to the HRC-TV. Okay. So both stage and volume make a big difference on what dose you're going to push your HRC-TV to. And then the intermediate risk is also become relevant because that is your point A and point B. We actually threw it away when we decided not to do point A and point B, we go, okay, we don't need point B, but you do need point B. And they actually found that you really do need a little bit higher dose again, based on stage. So if you have stage two, you want your intermediate risk CTV to get about 70 grade, which is what we talked about when we did point B, you want 65 to 70, right to the pelvic sidewall. So higher dose, you're going to go to 75 to 80 to that pelvic sidewall, because you need that dose for that gross disease. I forgot you had medical students there. So if they have questions, please have them ask me. And I, like I said, please ask. So let's talk about how we've changed things around and why, right? So this is a patient and I know you can't quite see it, and I'm going to have to work on this, but this patient has residual disease at the MRI. You can see this posterior disease right here, right? So if I was just going to use my tandem and ovoid or tandem and ring to try to treat it. So this yellow volume right here, I'm just using my tandem and ovoids or tandem and ring to treat it. What happens if I push that dose? What is happening is I'm pushing it and it's going to overtreat and give a higher dose to that rectum. The key is that sigmoid, right? And I won't be able to get enough dose into my HRC-TV without over-exceeding my dose to the sigmoid and to the bladder, right? So you see that dose to the bladder. So how can you fix this? And this is the new thing that we've got. How can you fix this? Well, the way to fix it and what we're now doing, right, is instead of just using tandem and ovoids or tandem and rings, we're adding needles. So you can see here, because of that posterior disease, we added the needles. So we can now load the needles and not load the tandem and ring so hot. So you can see, like, here's that sigmoid again. I know it's a different angle, but still the sigmoid is right there. So you can see the dose of the sigmoid is actually less and that dose to the bladder is less. By adding those needles and loading those needles, I can actually reduce the dose to my normal tissue. And this is where image-guided brachytherapy has made the biggest difference. It has shown us how we can add little things to reduce the dose to the normal tissue without reducing the dose to the area we want to treat. And in fact, again, EMBRACE has looked at patients who got interstitial plus tandem and ovoid versus just getting tandem and ovoids alone. And here they found that patients who got a combination of interstitial plus intercavitary, if they had large volume disease, actually did better than patients who just got intercavitary. So for all patients, it was a slight advantage for intercavitary interstitial, but if you had volumes bigger than 30 cc's, adding the needles actually improved overall survival and local control. The other thing it did, and that's more important, is it actually reduced toxicity, bladder, bowel, and vagina. And so actually the recommendation is that you really should use interstitial if you have large volume disease or if you have asymmetric disease, whether it's, you know, posterior or some vagina or is anterior that can't quite be treated just by tandem and ovoids. Just another example of where needles are important. So you can see the cancer right here, right? Adding the needle will help you treat that and give a higher dose. So let's talk about, again, like I said, it was a short talk and I'm happy to do a longer talk later, but let's talk about doses now and what doses, especially for the gynecologist, because you guys need to know this. This is what you're going to take. You're going to look at your reports and say, did my radiation oncologist give the right dose or did they give two less or did they give two more? And that's why my patient's failed or has increased toxicity, right? So key is you want to look at your HRC-TV and as we talked about, it is volume dependent and stage dependent. So if it's stage three and four or greater than 35 cc's, your HRC-TV D90 should be 85 or above. The IRC-TV we talked about, right? So these are all very relevant. And, but let's talk about normal tissue as well. Normal tissue is really important. And this is the data. What we learned was that you kept your rectum less than 75 gray. By keeping your rectum less than 75 gray, you reduce fistula rates. But we actually found by doing image guided brachytherapy to reduce grade two or less GI toxicity, you really want to keep your rectum below 65. Now that's very hard. And I'm going to tell you right now, we try to keep our rectum below 70 because we have a hard time reaching 65, but the goal really should be 65. And just key is less than 75, you're reducing your fistula rate, but you really want to reduce it 75, 70 or less to reduce your other GI toxicities. And just what are the GI toxicities, especially for our medical students? The incidence is about two to 39%. Most patients present with rectal bleeding and the risk is the dose to the rectum. And as we mentioned, it is really truly dose related. So rectum, you want to have your D2CCs less than 65 for grade two, D2CCs less than 75 for grade three are more toxicity. So the other two things that we have added for image guided brachytherapy that is important for HDR, sigmoid should be less than 75, but we're also looking at small bowel. So you've got to look at your small bowel doses and keep your small bowel doses less than 65 as well, because that's important in HDR because it's a point dose. I mean, that's a point time where when we did low dose rate, the bowel moved everywhere. So it was irrelevant. Now with HDR, because it's a static dose, your small bowel dose is important and you've got to contour your small bowel. But last but not least, the most important structure for all of our very young patients, and especially for their quality of life is the vaginal dose. And this again was something that we threw away when we went to image guided brachytherapy and we started using needles and rings and we decided, you know what, local control was more important than the vagina. And when that was happening was all of our patients were coming back with vaginal stenosis, inability to have sex and everything else. And they've actually shown that vaginal dose is so, and so important. So we're back to documenting our vaginal dose and you've got to do that. And you've got to limit it, whether you use the rectal vaginal point and keep it less than 70 to 75, or you actually outline the vagina and leave it less than 110, but vagina, the vaginal doses are just as important as everything else you look at because it's so relevant to our patients. So I think that's it. Cause I was told to keep it short and sweet. So questions.

brachytherapy

cervix cancer

radiation therapy

image-guided brachytherapy

interstitial techniques