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Integration of Molecular Classification into Managment of Patients with Endometrial Carcinoma
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New adjuvant chemotherapy, so the outline is really, we're going to talk about both new adjuvant radiation therapy, which I know you don't have, but there is some data where you could do external beam followed by surgery, and I wanted to talk about that, and then just straightforward new adjuvant chemotherapy. Why are we talking about this? I know that you already know this. There's a lack of radiation therapy available throughout the world. The sad part, as you can see, and this is actually an old slide, but it just shows you how many units that we need. Not just units, radiation oncologists, physicists, and therapists to actually treat the people that will require radiation therapy up to 2020. We're really, really far behind. As you can see, we'll need 270 percent more, just radiation therapist units, 220 percent. We are really, really behind, which you don't need to know. There's a shortage of machines, staff, education, time, and a lack of brachytherapy equipment. Let's first talk about new adjuvant radiation therapy, which still is a possibility that you could at least send them to get external beam and then have surgery. There is some data, and actually all this data comes from Mexico. This is a phase 2 study that actually they did in Mexico, 80 patients, 40 in each arm. The standard arm was radiation therapy followed by brachytherapy versus radiation therapy followed by actually a radical hysterectomy. Because a lot of places don't have brachytherapy, or access to brachytherapy is delayed because of the number of units. They were actually randomized to these two arms. At the time of surgery, if there was a reason, if they had positive margins or other risk factors, they did get post-op vaginal brachytherapy. As you can see, the groups that were pretty even between surgery and brachytherapy, there was not much of a difference between stage, histology, or anything else. Interestingly, and I think this is important, is that there was actually no difference in overall survival or progression-free survival between doing brachytherapy versus doing surgery after external beam. But remember, it is a modified radical hysterectomy. It's not a simple hysterectomy. They are doing a full radical hysterectomy in this study. Toxicity, so hydronephrosis was higher in the surgery arm, and it's probably the ureter damage, where the patients who got brachytherapy had a higher incidence of proctitis and cystitis, very common for radiation therapy. This led them to actually doing a true phase 3, randomized study looking at surgery versus brachytherapy. Patients were stage 1B2 to 2B, so not 3Bs. They did do CT scans, and they did not have positive periodic notes. The chemotherapy that they used was this platinum ginsida beam, which is very common to use in Mexico. All the external beam was 250 gray. Again, very well, the stage, the histology, and the sides were even in both arms. This was important. I think this is the key thing. The pathological complete response was lower than they expected. I think this is one of the reasons why they haven't gone quite further with this treatment, but it's not bad. The pathological complete response was 72 percent. PR was 28. If you did intent to treat, it was 56. These were all patients. It was much lower than they expected. They hoped for, but it's still not bad. As you can see the positive margins, there was a 2.3 percent margins in the perimetrium, and there was definitely a 10 percent incidence of positive pelvic notes in the patients who received the surgery. At the end, there was no real true difference between the two arms. The conclusion was that a radical hysterectomy after chemotherapy did not improve, because their whole thought was, you add, their goal was that their experimental arm was going to be better than their standard arm. Well, it ended up not being that. Radical hysterectomy after chemotherapy did not improve survival outcomes compared to standard radiation plus brachytherapy. But key is that you can do a radical hysterectomy after external beam, and it is feasible and safe in experienced arms. It can be an effective treatment, especially if you don't have brachytherapy. It should not replace it if you do have brachytherapy, but if brachytherapy is not available, this actually is a feasible treatment option for patients with stage 1B to 2B. In fact, right now, they're actually doing a really interesting study, and I don't know quite exactly where they are with this study, but they're actually looking at hyper-fractionation external beam. Doing five weeks versus three weeks of radiation therapy, really important in the COVID setting, but also to try to get patients off the external beam. They're following it, both arms is followed by radical hysterectomy, and there's really been no difference in side effects. They've actually done really well, and I think they've accrued about 100 patients in this study. This is just the endpoints. Let's talk a little bit more about really more that's important to you, neoadjuvant chemotherapy. There's two big studies that have come out, and one of them was this study done in India. Again, these are stage 1B-2 to 2Bs, and they were all squamous cell carcinomas. In this study, what they did was they looked at, they randomized neoadjuvant chemotherapy, and it was carboplatinum and taxol times three, followed by surgery, versus primary chemo RT. That's important. This is what you're looking at. The patients got three cycles of carboplatinum and taxol, and they got surgery versus chemo RT. 635 patients were randomized. Most of them were stage 2B patients, so that's important to know. Again, it's really important, so you can see the response rate isn't as good as we want. It's 72 percent. That's a clinical response. You'd like to see it much higher. That's really important, which is the same thing as you saw even with external beam. The response rate is not as good as we want it to be. Twenty-three percent of the patients who did get neoadjuvant chemotherapy followed by surgery had to have post-operation therapy because of pathological factors. So, results. Chemo radiation was better than neoadjuvant chemotherapy followed by surgery, so disease-free survival was much better with chemo radiation. Now, there wasn't a difference in overall survival, so I think that's important to know. I think what's important is that for stage 2B patients, chemo radiation was 100 percent better than neoadjuvant chemo followed by surgery. In stage 1, and this is what I needed, so in stage 1B2, there really was no difference in outcome. So, it's the 2Bs that probably do better with the chemo radiation versus neoadjuvant chemo followed by surgery, and you're going to see this. This is probably the theme of this whole thing because in the EORTC study that I'm going to show you, exactly the same thing. Okay? So, key again to look at, where are these patients recurring, right? The patients who got the neoadjuvant chemotherapy followed by surgery mostly recurred locally, and that's important, right? And then remember, 23 percent of them got post-operative radiation therapy, right? So, the local recurrence is really still high in these patients who got the surgery versus chemo RT. So, the other study was presented at ASCO, and I have to look up. I'm wondering if it's written or not, and if anybody can remind me if it's gotten published, I have to look this up. So, this is the study, again, FIGO stage 1B2s, 2As, and 2Bs, right? They were also randomized to neoadjuvant chemotherapy plus radical hysterectomy versus chemo RT. So, in this study, they actually did use a different type of chemo, so they didn't use Taxol, right? So, they only used cisplatinum-based chemo. I think they did use actually Taxol, so I lied. It's cisplatinum and Taxol, but it was three courses of a cisplatinum-based chemo. Six weeks later, they got radical hysterectomy. So, for the whole population, no difference in overall survival, but there was definitely a difference in progression-free survival favoring chemoradiation, okay? Which, again, we know, right? Now, if you took the patients who just completed treatment, so you're taking the patients who did not complete treatment, right? So, you take away the intent to treat to just the patients who completed treatment. There was no difference in overall survival, and there was minimal difference in progression-free survival. So, these are patients who've completed all their treatments. So, in summary, so this is, and again, you can spin it however you want to spin it, and you'll see it spin the way that you want it. So, if you're a surgeon, you're going to spin it a certain way, and if you're a radiation therapist, you're going to spin it another way, right? So, you need to know that, but I think what's important, so the overall survival, 72% versus 76%, right? Progression-free survival for all patients is really low, 57% versus 66%. But, again, what you see is probably for the 1B2s, the neoadjuvant chemo followed by surgery, it's probably the equal to chemoRT. So, I do truly, truly believe that this is probably an equivalent treatment for this stage of patients. It's the 2Bs, and I know that's primarily what you see in the 3Bs that you're seeing. ChemoRT probably is better than neoadjuvant followed by surgery. And I'm going to let you guys talk in a little bit, but I'm going to finish this, so hold on one second. So, short-term toxicity, higher in the neoadjuvant arm. Long-term toxicity was a little bit higher in the radiation therapy arm. So, we know that, right? But key is also, how do you pick who's going to do well with neoadjuvant chemotherapy? So, this is actually several studies that they've looked at, and I think I'm just going to preach to the choir. Key is patients who respond early. So, when you're giving the chemo, if you're looking at the response, if they're responding to the chemo, they're going to do well. The patients where you see no response to the neoadjuvant chemo, they're not going to do well, right? And that's what all these data show is that patients who've had a great pathological response or even a clinical response will do well versus the non-responders. So, 89% optimal versus 63% suboptimal. So, overall survival, again, this is just comparing, but yes, the responders will do well, and maybe they will do well no matter what you do, right? So, here's just another thing on a response. Response to neoadjuvant chemotherapy, the responders do well, where the non-responders don't do well. And a meta-analysis shows the same thing. Responders do well, and the non-responders don't do well. So, my conclusions, and then I'm going to let people talk, because I think we really need to talk about how we're going to do this in VG where you don't have any radiation, right? For stage 2b, the data really does show that chemo RT is better than neoadjuvant chemotherapy followed by surgery. But for 1b-2s, I think it's equivalent. And doing neoadjuvant chemotherapy followed by surgery, you are going to have the same overall survival and progression-free survival. And I think it is actually a very good option, especially if you don't have radiation therapy. But you do need to follow these patients as you're giving the chemo, right? So, it's three courses of chemotherapy. You got to follow them and see how well they're responding as you're deciding what treatment to do afterwards. And that's it. So, the key thing is, is responders are really important, and you really need to be following those patients. So, questions and discussion, because that's the whole point.
Video Summary
The video content discusses new adjuvant radiation therapy and adjuvant chemotherapy as treatment options for cervical cancer patients. The speaker emphasizes the global shortage of radiation therapy resources and presents data from a phase 2 study in Mexico, which compared radiation therapy followed by brachytherapy to radiation therapy followed by radical hysterectomy. The study found no significant difference in overall or progression-free survival between the two approaches. The speaker also discusses a phase 3 study comparing surgery to brachytherapy, which found no improvement in survival outcomes with radical hysterectomy after chemotherapy. However, the study suggests that radical hysterectomy after external beam radiation therapy can be a feasible and safe treatment option, particularly when brachytherapy is not available. Additionally, the video presents findings from two studies on neoadjuvant chemotherapy, highlighting that chemo-radiation therapy may be more effective than neoadjuvant chemotherapy followed by surgery in stage 2B patients. However, for stage 1B2 patients, both approaches yield similar overall and progression-free survival rates. The speaker emphasizes the importance of monitoring patient response to neoadjuvant chemotherapy to inform treatment decisions.
Asset Subtitle
Philip Ip
December 2022
Keywords
adjuvant radiation therapy
adjuvant chemotherapy
cervical cancer
global shortage
neoadjuvant chemotherapy
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