So we'll start with the case presentation and I am going to go through the new staging guidelines, which I'm sure you guys know, but let's talk about the new staging. So this is a 46-year-old female who presents with a bleeding and a pap smear was abnormal. On exam, she did have cervical and endometrial involvement that came back positive for squamous cell carcinoma. On exam, it's a 16 tumor involving the upper one-third of the vagina. So in the old staging system, she would have been a 2A, right? So this is her PET scan. And just to show you what, so these are normal ureters that light up. This is actually a positive pelvic node. And you can see where actually she really did have uterine and cervix involvement. And as I said, in the old FIGO staging, she would be a 2A. So what is it in the new FIGO staging? So let's talk about the new FIGO staging. And I think what I'm only going to talk about is where the changes have happened. So the biggest changes happened in stage 1Bs. So now the 1Bs are broken up into three categories and it's by size. So as you can see, less than 2CM is 1B1, 2 to 4 is 1B2, and now 1B3 is anything bigger than 4CM. And this is really traditionally now what we would treat with radiation therapy, or these are patients who have a high risk of needing post-op radiation therapy after a radical hiss. And that's actually why they've broken it down because prognosis is related to size. So one of the key reasons why we have now added it to our staging system. The other big change is in stage 3. So in stage 3, if you know in the past, it was 1A, it was just A and B. And now we've added a C, just like we have done for endometrial cancer. So stage 3C is positive nodes, and it can be based on radiology or by pathology. So 3C1 is pelvic nodes and 3C2 is periodic nodes. Again, just like endometrial cancer. So our patient, because she had positive pelvic nodes, would actually be a 3C1R. So that is now what the new staging system has changed. And again, because nodes are prognostic, nodes decrease survival. So that is why they have added this to the new staging system. So let's talk about treatment. How would I treat this patient with now stage 3C1 cervical cancer? So radiation therapy. Radiation therapy is the mainstay treatment for locally advanced treatments. But radiation therapy has to be done well. And you need to know this, even if you don't have radiation therapy, because you need to tell the people who are going to treat these patients on the outside how to treat it. But if you do have radiation therapy, you need to tell your radiation therapist how to treat, right? Key, you've got to treat all the known disease and the microscopic disease. So in this case, I would treat the pelvic nodes. I would treat the uterus. I would treat the cervix. I would pretty much treat all the vagina, right? Because she had upper one-third vagina involvement. So you want to treat microscopic disease. You've got to get the right dose. And that dose is 85 to 95 gray to point A. And I will tell you what point A is in a minute. The biggest thing, and I'm going to show this to you, it has to include radiation from the outside and radiation from the inside. So it has to include external beam plus brachytherapy. It has to. And I'm going to show you data where there's decreased survival if you don't include brachytherapy. The other thing, and I'm going to show you this data as well, you really need to treat, finish everything, which means external beam plus brachy within 56 to 60 days, or local control goes down. And I'm going to show you this data in a minute. So let's just talk about radiation therapy alone. Okay. Even before chemotherapy was added to radiation therapy, radiation therapy cured cervical cancer. As you can see, this is data with just radiation therapy alone. We cured over 50 to 60 percent of our patients just with radiation therapy. So even before chemotherapy, we were still curing our patients. This is the field, and my fellows need to know, and you probably do too, this is probably the field that we would use for our cervix patient that I just showed you. So this is your typical field. The radiation comes from the front, the back, and the sides. So here's your lateral field, and here's your anterior field, right? So I'm treating all my pelvic nodes. I'm treating the uterus, the cervix, and the vagina. Again, just, again, showing you the standard fields for a pelvis. Now, if you had positive pelvic, common iliac nodes, you increase the superior border. So if it's positive common iliac nodes, I'm going to change this border to the top of L2. Okay. If it's positive parotid nodes, I'm going to go above the renal hilum, because I want to treat all the parotid nodes. So it's really important to know where the nodes are and what you want to treat. But this is your typical fields, and again, like I said, my fellows need to know it. They're asked this on their oral exams, but you guys need to know it so that you know that your radiation oncologist is treating the right fields, right? So it's really important, because they may not be treating it, and then you say, hey, what about this? Why are you doing this, right? So this is just our approach to the treatments, but it can, you know, you do whatever it's the right way to do it. But the thing is, you want to get between 45 and 50 gray from the radiation from the outside, and you want to include brachytherapy. So you get a total dose, again, of 85 to 95 to 0.8 for locally advanced tumors. This just shows you how well the radiation works. Huge tumors. See this big tumor, not the same case, but a different case. Three months later, all gone, patient's in ED. So radiation does work. Here's the data on treatment time. This is multiple studies, and they have shown 1% decrease in local control per day, every day after 60 days. Every day after 60 days. So it is important to try to finish all your treatments within 60 days, and that includes both the external beam and the brachytherapy. So I'm going to talk about toxicities first, and then we're going to go over some other data, but toxicity during treatment is really diarrhea, burning with urination, and fatigue. But this is more important to you guys. This is what you're going to see, right? So I radiate the patient, I've cured the patient, and the patient comes back to you in a year, and she's having blood per rectum, right? So what is the toxicities? The toxicities are about 11% at 10 years. The most common toxicities are GI toxicities, either rectum or a small bowel, but bladder also is a toxicity as well. But what I need you to look at is, look at this. You can see the rectum and the small bowel. Most of the toxicity occurs within the first two years. So you need to know the recurrence rate and the GI toxicity most common within the first two years after radiation therapy. That's when you're going to see that, right? It continues to go up, but most of it occurs around that time. Bladder, though, as you can see, this is that line, bladder continues to go up even up to 20 years. So the bladder continues to rise, but most GI toxicity and most recurrences occur within first two years after treatment. So that's why you have to follow these patients every three to four months for the first two years. Then it's every six months for the next three years, and at five years, they're really considered cured, even though they're still at a high risk to getting bladder toxicity. And we did a study to see who was at risk for some of these toxicities, and what we found, and this is American, so remember, this is American patients, right? We found that African Americans had a higher risk for GI toxicity. We found smokers, patients who smoke more than a pack of cigarettes a day during treatment had a higher risk for GI toxicities. We found also skinny patients, patients who had a BMI less than 22 had a higher risk for GI toxicities. Interestingly, the patients who were obese had a higher risk for bladder toxicity. So those are key things, and those things you need to know, because that's when you, those are what you're going to have to see and treat. So the first two years, as I emphasized, so important for toxicity, and you guys really need to follow these patients. So let's talk about treatment. As I said, I can cure over 50 to 60 percent patients with radiation therapy alone. So how can we improve that? Well, we improved it by adding chemotherapy. And as all you guys know, in 1999, all these studies came out showing that chemotherapy with radiation was better than radiation therapy alone. But let's talk about one study, and the reason why I want to talk about it is we still have room to improve. We still haven't hit a home run, especially for our stage three patients. So this is 9001, which is a little bit different. It treated patients with extended field and pelvic radiation therapy plus chemo. The chemo was a little bit different, too. It was just platinum and 5-FU. Radiation was done very well. But this is the data that you need to know. So what, this is one of those five studies, right? The studies showed that chemo radiation was better than radiation therapy alone, okay? It was really significant in patients with stage one and two, 79 versus 55. But here's the thing. For threes and fours, it just trended to significant, 59 versus 45. So there was an improvement, but it wasn't quite significant. And in fact, in that same time, there was one study that showed there was actually no improvement in adding chemotherapy if you did good radiation therapy. But overall, the multi-meta-analysis showed that chemotherapy plus radiation therapy is better than radiation therapy alone. And it really doesn't matter what chemotherapy you use. You can use platinum, or you can use mitomycin and 5-FU. But adding chemotherapy to radiation is better than radiation therapy alone. Here's this table that I need you guys to know about. This is what you need to look at. So for stage, overall survival was, benefit was 8%, right? But you can see that most of that benefit is for those ones and twos, not for the threes. The threes, the benefit was only 3%. So there's definitely room for us to improve. And the question is, how can we improve this, right? What can we do, especially probably because this is a stage that you guys see in Uganda, right? The stage threes. And in fact, even in Texas, those are the most common patients that we see, right? So how can we improve on this? Just from the meta-analysis, there were the patients who did recur, recur both distantly and locally. It did though, tell us a way maybe how we could improve on therapy. What they did look at is the patients who got chemo-radiation versus the patients who got chemo-radiation followed by more chemo. And they found a slight benefit in this meta-analysis that if you gave more chemo afterwards, there may be some improvement in survival. So conclusion, chemo-RT is the way to treat these patients, but we got a big area to improve, especially for our stage three patients. So how do we improve? In the United States, we're actually using this drug called triopine and we're doing a phase three study looking at triopine plus cisplatinum and pelvic radiation. But let's talk about what's going on internationally, because I think this is more important for you guys. This study, the Outback study, the Outback study is looking at that question, which I told you, right? That more chemotherapy may be beneficial. So what Outback has done is it's compared chemo- radiation versus chemo-radiation followed by four courses of carboplatinum and taxol. A thousand patients have been randomized in this study, finish accrual a year ago, results will be presented next ASCO. So then this will actually help answer whether adding more chemotherapy afterwards improves survival. Another study that's going on internationally, this study is still accruing, is looking at, based on a phase two study that the Koreans did, where the Koreans looked at giving cisplatinum every week versus giving cisplatinum every three weeks, and they found by giving cisplatinum every three weeks, there was a little bit of benefit in survival. There was also less toxicity. Again, something that may be easier to do in Uganda, right? So this is a study called TACO, where they're randomizing patients giving chemotherapy every week compared to giving chemotherapy every three weeks. This trial should finish accrual by the end of this year, and we should have results within the next two years. The last trial is looking at neoadjuvant chemotherapy, and I can go over data on neoadjuvant on another talk. And I have some great data, and we shouldn't really go over, especially now with the new ASCO studies that's come out. And I know that you guys are doing a lot of neoadjuvant, or may be doing a lot of neoadjuvant, but I just want to show you this study, and then we can talk about neoadjuvant data on another talk. But this study is randomizing carboplatinum and taxol, followed by standard chemoradiation versus standard chemoradiation. Again, this trial is ongoing in Mexico, in India, and in Europe. It should actually complete accrual by the end of this year as well, and hopefully we'll have those results. But we should talk about neoadjuvant, and we will in another trial, I mean another talk. So just saying, we've done better by adding chemotherapy to radiation, but we can still do better. Results are pending on three different trials, and hopefully we'll have some answers on how we can improve survival. But let's talk about brachytherapy. Didn't I just tell you that radiation includes external beam plus brachytherapy? Brachytherapy is so, so important. This is a study that was done in the United States, and what we've seen is a decrease in the use of brachytherapy in patients with cervical cancer. And what we're seeing, look at this, the survival difference between patients who get brachytherapy versus patients who get no brachytherapy. Patients who get brachytherapy have a huge survival difference. So it's so important to do both radiation from the outside and brachytherapy for these locally advanced cervical cancers. Again, another study just showing you the survival difference between doing brachytherapy versus just doing external beam alone. Huge difference. Brachytherapy is very important in local control and survival. So we're just going to kind of briefly go over some films. So this is a tandem and O-void, and what we're looking at is point A and point B doses. Point A is usually two CMs above the cervical os and two CMs over, and that is where the uterine artery crosses the ureter, and that's really your parametrial dose, okay? That's what point A represents, is your parametrial dose. Point B is your sidewall dose, and so it's three CMs over from point A. Your bladder point and your rectal point, your rectal point's usually about five millimeters away from the O-voids or away from the pachy, and your bladder point's the midpoint of the Foley bulb, okay? These are the doses that we want. This is what you guys need to know. These are the doses that we want to achieve. Point A, we want 85 to 95 gray. Bladder, you can actually probably go up to 80 gray. Rectum, you really want to keep at 70 gray, really, and the vaginal surface dose at 125. And this just tells you what the side effects come from. Key is, yes, you have to do brachytherapy, and brachytherapy is important, but you've got to do it correctly. So that's the other thing where you guys as fellows can help your radiation therapist in making sure that the brachytherapy is done correctly and it's right up against the cervix, right? Because it shows you if you don't do the brachytherapy, well, you're also going to have decreased local control and survival. You have to do, you have to put the radiation in the right place. It's really important. So you can do either HDR or LDR. So most places are not doing HDR. Most common fractionations are right here. Usually it's five to six gray times five in the United States. Everywhere else is seven gray times four. A lot of places are doing eight gray times three. All equivalent, really no difference in survival or local control. We are moving from image-guided brachytherapy, I mean, sorry, from film-based brachytherapy to image-guided brachytherapy. The advantage of image-guided brachytherapy, which means we're doing CTs and MRIs with our brachytherapy, we can see the organs. So you can see the bladder, you can see the rectum, and you can see the disease. So then you're not guessing. You're not like putting things in, right? And you can use anything. And they've shown that if you use image-guided brachytherapy, you actually have better local control and survival because you can really see the disease. But film-based brachytherapy is, if that's all you can do, is still better than no brachytherapy. And that's really important. And that's it. Thank you. Questions?

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radiation therapy for cervical cancer

brachytherapy for cervical cancer