I will start, how do I, how do I, yeah, thank you. I will start with some introduction to radiation therapy. As you know, radiation has been an effective and important tool for treating a cancer patient for more than 100 years. With more than 60% of the patient with cancer having some radiation therapy, at some point of the course of their disease. How do I move the slide? Yeah, thank you. There are multiple source of ionizing radiation. The most common source of ionizing radiation is the X-ray, which is generated by linear accelerator. This is the most common method for external beam radiation that we use daily. We also have the gamma rays, that they are basically a radio active atom that we use for brachytherapy. And there is also an increasing global interest with a proton therapy, which is part of a particle beam radiation. Can another slide? Sorry, I'm trying to get this bit larger, hold on. All right, go ahead, sorry. Okay, the next one. Okay, so proton beam radiation therapy is a kind of a radiation that has, as I said, that has gotten an increasing global interest in the past few years. Basically, it's a radiation with the high dose region. In this radiation, the high dose region will be deposited in a narrow range of deaths with a minimal entry and exit dose in contrast to the photon beam radiation, where you see that the entry dose is much higher. There are over 100 centers around the world that are able to deliver this kind of radiation. And mostly people use it for pediatric oncology and spinal tumor. With the using, gynecologic malignancy is not so common. However, if you have a disease in the paralytic area, where it's very hard sometimes to spare the kidneys, the bowel or the spine, this is a very good option to try to do it. Next slide, please. So again, in the past few decades, we developed in the radiation treatment planning, we started with the 2D-based planning, when we did an x-ray and used the bony anatomy to contour our field and the volume of interest. Next slide, please. From that, we moved to the 3D-based planning with CT, that on the CT scan, we contour the target volume that we want to radiate with the organs and trees. And then, next slide. And then we plan a 3D-based planning, which you see here. Usually you get a square with the high-dose region, which is inside the high-dose region, is mostly uniform dose, more or less the same dose. Here, for example, you have a treatment plan with three beams, two from the lateral and one from the posterior. And as I said, you get a square of high-dose region. Next slide, please. In contrast to this, from the late 90s, the IMRT technique was introduced. IMRT stands for Intensity Modulated Radiation Therapy. It's basically highly sophisticated form of 3D conformal radiation therapy, which allows the radiation to be shaped much more conformally around the tumor. Next slide, please. For example, if we looked at a tumor, for instance, if this is a tumor and this is the organ, the tris, which is very close to it, with the 3D conformal radiation therapy, for example, here, you radiate from three fields, from three direction. Each has a uniform intensity within the beam. And then you get the high-dose region. Here, you see it in the black, which the tumor, with the tumor and the organ, starts getting the same dose. But with the IMRT, you can plan it with different intensity within the same beam. And by this way, you can conform and you can shape the high-dose region here around the tumor and around your volume of interest, with sparing much more of the organs at risk. Of course, they are very close. There will be a radiation in this organ, but it will be much less than all the technique with the 3D-based. Next slide, please. This is an example. As I told you before, this is a pelvic axis. And with the 3D radiation, you get a square of dose, of high-dose region. And with the IMRT, you get much more shape radiation around your volume of interest, which here is the lymph node. And you have anteriorly the bowel, which is much more spared than in the old technique. Next slide, please. Another thing that we can do with the IMRT technique is giving a simultaneous boost. What do I mean? If in the past, when we want to add more radiation to the growth disease, except from the cervix, for example, lymph node, we would finish the five or six weeks of the external beam radiation. And then we added a small volume to, for example, to the growth disease, for example, lymph node or parametria. And it will take three to six more fractions. Here with the IMRT, we can do everything in the same plan. Here you can see a pelvic plan. And you can see that she has a higher dose of radiation to the enlarged and positive lymph node. And she can finish everything within those five to six weeks without adding any more fractions after the external beam treatment. The next slide, please. The IMRT for cervical cancer has also evolved in the past few decades. It took time for people to adapt this technique for cervical cancer because people in the world was worried about the movement of the endometrium. But lately, many centers have started to use it. And here is a meta-analysis that was published a year ago that showed that basically the IMRT has equivalent efficacy, but if you use it, you can reduce the toxicity, mainly the acute toxicity, but also the chronic genitourinary toxicity. Next slide, please. Another external beam technique that are growing in use in the last few years is the stereotactic body radiation therapy. If you are familiar with the SRS technique, the stereotactic radiotherapy that we do for brain tumor, it's very similar, but when it's in the body, you call it an SBRT. It's basically an ablative dosage of radiation almost similar to the surgical effect. It's a form of IMRT, but when you give very high dose to a small volume with few fraction, and we have an excellent, especially excellent local control result here. You see the most common site that we use the SBRT is lung. And as you can see, you get a very high dose within the tumor. It's very low doses around it. Next slide, please. The SBRT for gynecological malignancy, it's useful for mainly two indication. First of all, is a lymph node that is very close to, for example, here you can see a lymph node very close to the bowel, to the kidneys, and to the spinal cord, and you can give a SBRT to these nodes with a good response. Here you can see it disappeared. Another indication is re-radiation cases in gynecological malignancy, mainly pelvic recurrences in the pelvic sidewall. Next slide, please. Here you can see, this is a table of using SBRT for re-radiation cases. You can see in the red square, you can see the local control results, which are very good comparing to this population with more than 60% local control and very acceptable toxicity. Next slide, please. Okay, now I wanna move a little bit to the BRCA therapy. This is usually the treatment scheme for a drinking local event cervical cancer with external beam radiation combined with weekly cisplatinum when it's not contraindicated, and then combining BRCA therapy procedure. You can do it either toward the end of the radiation, starting from week three or four, or you can do it after you finish the whole external beam course. However, you have to remember that according to retrospective data, you should finish everything, all the treatment from the first day of radiation to the last day of BRCA therapy within eight weeks. Next slide, please. Okay, so next slide. So BRCA therapy has two major developments in the last decade. This is the old conservative BRCA therapy applicator, which is the most common use in the world. This is a tandem and ovoid applicator, the Fletcher one, with, as you can see here, it has a tandem intrauterine applicator combined with two ovoids that goes into the vaginal fornices. And next slide, please. And then you get a dose distribution that looks like this. It's called the apple shape with the cervix in the middle and very low doses to the bladder and the rectum. Next slide, please. This is a very similar principle of a BRCA therapy applicator, but instead of the ovoid, you get a ring going into the vaginal fornices. Next slide, please. With dose distribution that is very similar to the previous one. Next slide, please. So the new thing that we have in the past few years is the implementation of the hybrid applicator. The hybrid applicator, what we call them, is a combination of intracavitary applicator, like the ones you saw before, with interstitial component. What is interstitial BRCA therapy in general is taking some needles that go into the tissue very close to the tumor, and they can conduct the radiation, they conduct the radioactive source of radiation, and they bring the radiation very close to the tumor. By combining the intracavitary all-technical BRCA therapy with interstitial, we can cover with radiation much more the parametria and the pelvic sidewall is a very good technique for stages 2B to 3B cervical cancer. Next slide, please. And we noticed a difference in local control with this technique. First, I think it was four years ago that they published this paper. Next slide, please. That showed that when you combine interstitial and intracavitary technique, the ICIS, compared to the intracavitary technique, you get much higher local control rate. Especially for large tumor. Next slide, please. With the same toxicity rate. And next slide, please. And since then, more and more applicator like this have emerged and introduced. This is another form of this hybrid applicator. Next slide. With, again, you see a dose distribution, which is very good. As you can see, it's very colorful. In the bottom right, you can see how beautiful the dose distribution shape around the tumor with the right parametrial involvement. Next slide, please. Okay, the second development that made a huge difference in the BRCA therapy and the result of the treatment was the introduction of the MR-based planning for BRCA therapy. What... Oh, it looks like we might have lost her. We'll give it a second. technical difficulties will be. Hopefully she can just join quickly back. It did drop off a couple of times earlier. Oh was it? You know when we were getting set up she was kind of on and off on and off. Okay. I see if she emails too. Ofer you might have to finish the lecture. You're muted Ofer. Well it's either that you or Ram. I cannot finish the lecture. I bet Ram could do it. Sure, sure. No problem. Ofer, do you want to try calling her? You can call her. Yeah, hopefully she's still not talking. Right? I want to call her. Ofer, I'm calling her I think. Got her, her, her, her computer broke down. Oh, that's hard to recover from. Oh, my slides are up Susan. It looks like there are like 10 more slides. Yeah, I'm sorry. I'm sorry. I'm sorry. Oh, you're back. There we go. I didn't have any electricity. I'm sorry. That's okay. Maybe that was just a little bathroom break, right? Okay, so when did I stop? When did you stop? Right here. Brachytherapy, yeah. The MR-guided brachytherapy. Okay, so sorry. The MR-guided brachytherapy was the second development that we had in the past few years. Next slide, please. As you can see here, this is a tumor in the cervix. In the bottom, you can see an MR imaging where you can see the tumor very clearly with the tumor in gray and the normal uterus is in the dark gray. However, in the CT scan, it's the same tumor with the same applicator inside the uterus. But you hardly see the differentiation between the tumor and the normal uterus. Next slide, please. And this is a study. This is a prospective study, an observational study that recruits more than 1,000 patients looking at the results and analyzing the results of MR-guided brachytherapy for local advanced cervical cancer. Next slide, please. First of all, they took the data of this patient and looked at the local control. Next slide, please. And they saw an excellent local control rate. As you see here, for 2B or 3B cervical cancer, you get an excellent result with more than 75% local control at five years for 3B cancers. Next slide, please. The second thing they figure out from analyzing the data from EMBRACE is that they were able to find a correlation between the late toxicity and the dose from the combined external beam treatment with brachytherapy. As we all know, the long-term toxicity of a cervical cancer patient treated with chemoradiation therapy is a major issue. Most of them have a long-term toxicity with the bowel issue and bladder issue and vaginal stenosis. And what they found from the EMBRACE trial, it's the correlation between the dose given to those late toxicity. For example, here you can see a study about the long-term rectal toxicity. Next slide, please. And as you can see here, when a patient got more than 75 gray, they had almost one quarter of them had more than grade 2 toxicity, a long-term rectal toxicity. Compared to a patient that got less than 55 gray that had less than 4% toxicity. Next slide, please. The same they had for vaginal toxicity. Next slide, please. And again, they were able to correlate the dose to a point called the vaginal rectal point. But they were able to correlate the dose in this point to the long-term vaginal stenosis. And next slide, please. After they published all of those papers, they built a new protocol called the EMBRACE tool, where they adopt and published a new guidelines constraint for the organs, mainly the bladder and the bowel and the rectum. And we all hope that by adopting those constraints for the future planning, we will see much less long-term toxicity and much better quality of life for these patients. Thank you very much. I'm sorry for the break. If you have any more questions, I am...

radiation therapy

IMRT

cervical cancer

SBRT

brachytherapy techniques

EMBRACE protocol