It's perfect. It looks great. Okay, perfect. Okay, so, as I say, I was sort of asked, I think, just to give an overview really of radiotherapy for cervical cancer. And, and some of the issues and just sort of, it's just a quick reminder, I love always going back to the history. And we can see that historically, cervical cancer really is key to the development of radiotherapy. Radium, once it was isolated by the curies was first used the potential of putting it in the uterus. By 1905, we had long term survivors. But it was recognized that you really needed to treat the pelvic lymph nodes as well to get a decent proportion of patients with long term survival. So by the 1920s, we have the principles that we still follow for cervical cancer, in that we do pelvic external beam radiotherapy to treat the pelvic lymph nodes. And then ideally boost the tumour with brachytherapy. And the sort of indications when do we use radiotherapy in cervical cancer? Well, we would be using it if we have bulky tumours, if we know that the tumour is lymph node positive, or if there's parametric extension. As I've said, the sort of standard radiotherapy approach we use is to use a combination of external beam radiotherapy to the pelvis. And the dose we can deliver is limited effectively by the tolerance of small bowel if we go too high, there's too much toxicity. And then we boost with intrauterine brachytherapy. And again, the dose we deliver is limited typically by rectal bladder toxicity. And the basic principles when we're treating is that as we all know, lymph node spread occurs early and is common in cervical cancer. We're typically treating a large volume of normal tissue, and we're trying to get enough dose to sterilise microscopic disease. And then we're going to boost, as I say, to a higher dose. And the issues are that the volumes are often very large, we're hitting a lot of normal tissue. Our tumour is very close to mobile organs at risk, like the bowel and the bladder. As we've heard, late toxicity has significant impact on quality of life to the patient. But you have to balance that with the fact that uncontrolled pelvic disease is very difficult to palliate. And so local control is really important. And that's really our sort of principles. So I was just going to do a couple of slides, I think, and it was back to the discussion we had earlier in terms of why do certain patients get more toxicity. And it's thinking about our principles. And our aim is always balanced with getting in sufficient dose to kill all the malignant cells within that specific target volume, but also trying to spare the surrounding normal structures. And how we can balance that then depends on often what resource we have available as to what techniques we are using. And that's sort of highlighted here. This is our one sort of big key to when we're looking at the principles of radiotherapy. Let me just try and use the highlighter and the pointer here. So this is what we call a dose response curve. And basically, the features are that as we increase the dose of radiotherapy up to a certain point, we are not going to kill off all the cancer cells, and therefore we have no impact. And then we hit a stage where for a small increase in dose, you're getting a steep improvement in your local control and your control of the tumour. And that goes up very steeply. And then you get to a certain dose where actually you're not going to improve things, you've got 100% control. And this is a shape for all tumours that we see this typical dose response. But we also have a similar shape for the risk of complications and where they sit depends on the particular tumour. And where we offer for most of our common cancers, we're actually sitting around that steep point of the curve is the dose that we could get in with an acceptable risk of complications. And typically an acceptable risk would be a 5% risk of sort of moderate pelvic toxicity. So if we can separate those curves out, either by shifting the curves either way, then you either have less toxicity for the same control, or the same complication rate, you're going to improve your tumour control. And this is where all of what we do in survival cancer. So what shifts the curve to the left is giving oxygen. So where the hemoglobin is important during radiotherapy, it's the most potent radiosensitizer that we have. And also chemotherapy. So cisplatin is a radiosensitizer, it again is shifting the curve to the left. Now back to the discussion earlier, they both also shift your complication shift to the left, but not as much. And so you're separating the curves. But it is true that if you give concurrent chemotherapy, your toxicity can be less and you sometimes have to compensate for that. So how do we shift the complication risks? Well, that really comes down to the radiotherapy technique. So if you can avoid more of your normal tissue with your radiotherapy, you're going to reduce toxicity. So when we go through in terms of this sort of an example, here we have an example of a 35 year old woman. And usually we use the MRI just gives us the best imaging of the tumour. And this patient has a five centimetre tumour extended to the parametrium. And it's a squamous cell carcinoma. So when we're thinking about the radiotherapy, we think about what to include, what dose to deliver and how we can deliver the treatment. I'd say for the first two, what to include and what dose really is the same discussion wherever, whatever your resource level, but how we deliver the treatment, what technique is used clearly may vary between. So just in terms of what we include in the target volume, we have to think about the pattern of spread and that might be direct spread. And so we would include the uterine body, the upper vagina, the parametrium, we wouldn't typically want to include the rectum and bladder, but if there is involvement, as we have down at the bottom here, then we would need to include that area. And we think about which lymph nodes to involve. And when we sort of then starting to define the tumour, we think about what available imaging and clinical examination is available. So we would think about our GTV. So that is our macroscopic disease and that will be defined clinically and primarily clinically from an examination. But we may use MRI or PET or CT to help define where the tumour is. Now, I'm just going to sort of give a quick example of when we started to think what to include, because when we changed to start having CT cross sectional imaging, you can see that this was an inter-observer study. And I just like to show how that there can be variation between individuals in terms of thinking about what to include. And so we have different people drawing on the scans. And the shaded area here is the part that everyone agreed on. And this is back in 2003, when when the standard of care everywhere really was using x-rays for defining where to treat. But what you can see, and when we come lower down as well, is that there is wide variation. Everyone agreed to be treating probably the top of the vagina. But there was a difference not only in where the target volume is, but probably what to include in the target volume. So on the back of that, we've been developed consensuses in terms of thinking about what to include, and which lymph nodes in particular. And that's really what defines often how big our field is. So we would want to treat involved lymph nodes. And that may be defined, may be changed if we do a PET scan that changes where we need to be treating, but also the nodes that the high risk of microscopic involvement. So we tend to treat the lymph node stage above the group that are involved. And as a minimum, we would treat the pelvis. So if we look at different ways of defining which nodal groups are at highest risk, and these are looking at autopsies or sentinel lymph nodes, often for earlier stage disease, the most common lymph node involvement groups, as you would know, would be the common iliac nodes, and then the parametrium, but also your external, internal, and adulterated lymph nodes. So we would always include these groups of lymph nodes within the radiotherapy target volume. We would think about whether we need to include the paraitics, and we would treat the paraitic lymph nodes if there's common iliac nodal involvement, or if it's a very bulky tumour where there's definite pelvic disease, we may extend up to include paraitics. We would include the presacral nodes if the utero is sacral or the rectum is involved. And we would include the inguinal nodes if the tumour is coming down into the lower third of the vagina. So really, again, touching on what we talked about a bit earlier is radiotherapy planning. So how do we then deliver the treatment? And the approach that we can use would be conventional radiotherapy. And this is based on bony landmarks. And the fields can be based on the bones where we know the lymphatic groups sit. And that may be delivered either with two fields where you're coming through and through and making sure you treat the whole pelvis. And that is the safest approach if you do not have cross-sectional imaging. Or you can use a four field approach where you treat a brick. Now I would just I was just gonna highlight a bit about the two field distribution in that if we're putting fields going through and through, and it's back to the question of why may you get toxicity, because you're trying to get dose to the middle of the pelvis with only two fields, there's a lot of dose going in from either side. And actually the hot spots, which is the red here, can typically be at the front and back. And as you can see on this patient, it's got quite a large separation, that it's very hot over the small bowel, it's hot over the rectum, and it's hot over the sacrum. And so this may account for some variation between patients is that if we are using two fields without modifying the dose, whereas if you start having three dimensional approaches, you can start reducing your hot spots. And we can then move to three dimensional where we look at the dose across all the fields. I've sort of done quite a lengthy overview of how we go with radiotherapy. And I was just going to sort of not go into too much about then the rest of the volume, but just to give an overview of where we go, in terms of planning the treatment. So if we have cross section imaging, and if we have a CT, we would then draw on each slice the areas that we want to treat. And the benefit of that is you can start shaping your fields to fit much more to your target volume. With conformal radiotherapy, you can shift the fields, but it's still four fields. But it does improve the dose, it makes it much more even and avoids those hot spots. And then you can also further reduce if you have intensity modulated radiotherapy, which is a next step on in terms of technology, that allows us to shape the radiation fields around and avoid a lot more of the normal dose. And it also has the potential is if there is a lymph node involved, you can deliver a boost directly to that lymph node. So a typical treatment, as you've heard, would be sort of dose, so typically 45 to 50 grays sufficient to eradicate microscopic disease. And so that would be given in a dose of 1.8 or two gray per fraction over five weeks, patient gets weekly suspected chemotherapy, we maintain the hemoglobin above 120. So keep it high with transfusion, if need be, and try and avoid gaps. And then we want to give a boost because we've given enough dose to the microscopic disease, but we want to give a boost to the actual primary tumor and that's ideally done with brachytherapy. So brachytherapy is again a very important part of the treatment when we can use it. And we look again, we have a patient here who had a very bulky tumor. Initially, by the time they've completed five weeks of treatment, what we can see is there's been very marked reduction in the size of the tumor. So whereas before it'd be very difficult to get a tube into the uterus, we now have a much clearer intrauterine canal, and we're able to pass the tube into the uterus. And so with brachytherapy, we're going to pass the tube directly into the uterus. And these are sort of typical intrauterine tube and ovoid where we put it in. And again, this can be done from the 1930s, what was established was point A conventional points where we know if we deliver a set dose to a set point, that we have a very good delivery of dose closer into the tumor. And this would be conventional brachytherapy where there's fixed geometry, but able to deliver dose and that works very well when there has been good reduction in the tumor and it's central. I was just going to sort of this is just an overview with brachytherapy in terms of the IAA sort of recommendations and the levels that we recognise that may be available in terms of resource. So level one, you would have fixed the applicators are placed in no imaging and you have library plan. So it's pre planned, it's very simple, very effective in terms of delivering a standard dose. The next level, you would take imaging to see the points and see what dose you're delivering the point, but you're still not in a position that you can individualise the dose. And then finally, we have volumetric planning where a bit like I've just shown with the external beam, you can move to planning with either CT or MRI to see what dose the tumor is receiving. So it's just very quickly a sort of feel for where we have in that we now have applicators that are CT and MRI compatible. And so that you can take imaging and here's an example of a patient where we have the tube in the uterus. And then it's possible then to actually see where the residual disease is. As we Paula was talking about, as mentioning, when we do the insertion, we will put packing in to try and push away the rest of the vagina. And at the back here is is a sort of paddle that we will put in the in the vagina. And you can see it's pushing the rectum off and away from the brachytherapy tube. And even that sort of five, seven millimetres significantly reduces the dose that the wall of the rectum will be receiving. So when we plan, we can then look and see what dose both the rectum and the bladder are receiving. And we try and balance what doses and so there are guidelines where you aim to get as high a dose as possible into the cervix. But we have limitations in terms of what dose we would give to the bladder and the rectum. And just a sort of very last bit is a quick example again, this is a similar patient with a tube in place. And we would then draw away the residual disease, we can then see where we want to be delivering the cervix. And the dose that it gets covers everything very clearly. Just wanted to show an example of a patient where there's been less of a response at the time of brachytherapy. And what you can see here is that the tumour is still extending out to the sidewall and off to one side and the tube itself is is a long way away from where we want to deliver dose. And so an option we have for that is that we have applicators where we can then put needles. And as we see here, we can sort of add additional needles up into that side and improve. So we give the treatment, we then need to let it work. And typically the radiotherapy works for about three months. So we would normally assess response about three months out from treatment. And again, another example of a large tumour that was causing hydrometra extension of the uterus. And at three months, we can just see that there's been a complete response, there is some sickening of the bladder, and the bowel consistent with radiation change. So we do see changes, but we've seen a complete response. And it's just really a reminder that our outcomes, I mean, this is 2006 for Figo, so internationally, that even with high stage disease, so stage three, stage four disease, you can still achieve 40 to 50% five year survival. Thank you. I think I'll stop there.

radiotherapy

cervical cancer

brachytherapy

pelvic lymph nodes

conformal radiotherapy