Good morning, everybody. Welcome to today's IGCS Radiation Oncology Echo. I'm Hannah Simons, and I'm just the moderator for the session. And today we were hoping to reach out to our colleagues in the Asian Pacific region by being in a bit more of a friendly time zone. So that's wonderful if most of you have managed to join us today. We're going to have a case from Dr. Sakiti about recurrent endometrial cancer. And Dr. Kuo is her supervisor. We'll also join the presenter, Distillation. And then the four of us will have a panel discussion regarding the case. Please feel free to pop some questions into the Q&A box at the bottom of your screen. We'll try to answer them as we go at the end in our discussion session. And also, if you'd like to join in the discussion, please pop your hand up and we'll unmute you so you can join them towards the end. So I think if Dr. Sakiti is ready to go, we're ready to go. Thank you, Hannah. I will share my screen. Sorry. Okay. So our case this evening is a lady that we are currently managing at the moment, who is 52 years old, who initially was presented to one of our private hospitals in June last year with heavy vaginal bleeding. She's been paired with irregular medicines. She's got heart flashes at times, so at the moment she was in transition. And she claimed to be up to date with her smears. She denies any medical comorbidities, don't smoke, and had no family history of cancer. Those are only the prejudice issues that I put forward. On examination, she was noted to be comfortable. Her vital signs were unremarkable. From general examination, heat examination was unremarkable. Her chest, heart sounds was clear, lung fills was also clear. Abdominally, she was slightly tender at the abdomen. She was noted to have a large uterus. On internal examination, her cervix looks normal, normal vaginal hole, with moderate bleeding at the time. Her uterus feels a bit bulky. So she was assessed as abnormal uterine bleeding, secondary to likely tri-fibroid. So she had her baseline bloodstain. It was noted to be endemic. They also did a CA125, which was quite elevated. Her radiology imaging, chest x-ray was normal. She had a CT scan, which shows multiple fibroids in her uterus. It's a cystic mess. Apologies, I don't have the detail of CT images. And her abdominal organs were normal. So the plan was to optimize her hemoglobin, and she was offered surgical treatment. So she had her surgery done in July last year. And what was done to her, she had to HPSL peritoneal washing, and she had some emergent biopsy. According to the surgeon, it was quite a difficult surgery. She had a lot of extensive adhesions with distorted anatomy. The general surgeons were involved intraoperatively for bile adhesiolysis. Her uterus was quite large. She received about six units of packed red blood cells. So this is just six pictures of her pathology, which shows actually, if there's a pathologist who sees something else, you can interrupt me. But what it shows is that she's got endometrioid endocardioidoma with some squamous differentiation. It's just some high power pictures, which is a typical feature of that. So her detailed histology assessed her as, again, endometrioid endocardioidoma with squamous differentiation was assessed as grade two. Depth of biometrial invasion at the lower transcendent was 13 out of 17 millimeters. She had more than 50 percent invasion. The distance of the tumor from the closest uterine cereals at a lower transcendent was 0.4. She had no cereals involvement, but she had some lower uterine segment involvement and also survival stromal involvement. The peritoneal fluid was negative. All margins were clear. Elgicide was present. So she was assessed as endometrial cancer stage two disease. She was reviewed for postoperatively. It had been well. And I was, according to the private hospital, she was lost to follow up. She represented to another private clinic on the 8th of December, which she was referred to us with history of abdominal pain, bloating. They had done her baseline investigation. Hemoglobin was 10, sorry, 108. That was her EGFR and her CA125 was 64. When we had seen her, even though she looked a little bit thin, she was comfortable. No distress. Heat examination was no palpable. Chest exam was unremarkable. On abdominal exam, we can appreciate that there was a vague mess felt on the left side. It was slightly tender. It was slightly tender. It was quite fixed as well. Internal exam showed a normal vault, but mess was appreciated on the left side. When we did a bimetal exam and it feels like it was adhered to the side wall. So we had done an imaging for her. This is a pelvic CT scan, a pelvic CT scan with contrast. And you can see on this picture that she seemed to have nodal recurrence, lots of enlarged pariotic node. And you can also appreciate that she had an abdominal wall hernia as well with some hernia cortex. There was a mess on the left side as well in the left node. And this is what you can see on such the picture. It's just lots of nodes and a mess on the pelvis. So the official CT scan showed that she's got a 3.3 by 2.8 centimeter node on the left iliophorus. There were two midline abdominal wall defect. The upper defect shows, they say, radiation of ovantum. The lower one shows bowel and ovantum. She had metastatic nodal lip pelvic side wall. It also had the paracable, otocable, pariotic and also left iliophorus. Otherwise, the lung bases and other abdominal organs were normal. So we had assessed her as recurrences of endometrial cancer. At the moment, she's currently on palliative care. She's on pain management. We have discussed chemotherapy with her, but more of a palliative approach. So I think the last time we had seen her was about two weeks ago when she came into emergency department with severe pain. And she's been managed not only by us, but also with our Fiji Cancer Society as an open door policy. So that's the end of the case this evening. Thanks, Dr. Sikiti, for an interesting case. Dr. Cole, would you like to carry on now with your distillation? Good evening to everyone. I've got the interesting job of trying to dissect what we've been presented with and offer up some conversation on how could this patient have been managed. So I have broken this into the two time points. What potentially could have been offered when she was first operated on and there was an opportunity for some adjuvant therapy and then to discuss what are the options now that she has presented with recurrence. So what did we know? So initially she was a stage two, grade two endometrioid adenocarcinoma. There was over half myometrial invasion with cervical stromal invasion and there was LVSI. What may have assisted us in helping us make some decisions would be to find out what her lymph node status was at that time and that could be by any modality, sentinel node, lymph node, sentinel node biopsy. You could potentially have looked with CT, MRI and or PET. It would be useful to have had her hormone receptor status and now in this newer era if we had access to molecular profiling. So at present what we were given was that this patient has just had a hysterectomy and a BSO. So in absence of any further information, the data would suggest to us that standard of care would be to offer this lady pelvic radiotherapy. So what evidence do we actually have to support that particular recommendation? And if we go to the ESGO-ESTRO-ESP guidelines published in 2021, we can see that she meets the criteria for high intermediate risk. So she has stage two disease but what we don't know is if we could further classify that with any of the molecular classifiers as expected because we just don't have access to it in this particular situation. So what we do know from GOG249, which as you remember compared adjuvant pelvic RT with chemotherapy plus volt backytherapy and the PORTEC3 data, which again compared adjuvant pelvic RT with adjuvant chemoradiotherapy followed by adjuvant chemotherapy, was that for stage two patients they did better with pelvic RT. Now GOG249 we know is a non-inferiority study and the recommendation from that group was to offer adjuvant pelvic RT as chemo plus volt brachytherapy was not found to be superior. What could we have done had we had a little bit more information? If our extra information had confirmed that there indeed was no further nodal disease, then we would stay with that recommendation of adjuvant pelvic RT. But what could we have done had that had we known whether or not this lady had nodal disease? So we could have treated using the PORTEC3 schedule which is the chemoradiotherapy to the pelvis plus or minus wherever the nodes may have been detected followed by the adjuvant chemotherapy. Knowing that they hadn't been dissected, the practice at my particular centre is to follow that protocol with a simultaneous infield boost to any nodal disease that we might detect on say in our case PET imaging post-operatively. Had she had a sentinel lymph node biopsy it would just have been, and the sentinel lymph node biopsy was positive, it would have just been PORTEC3 schedule. Had you been somewhere else the recommendation might be to offer adjuvant chemotherapy. She has nodal disease, the risk of further metastatic disease is there and there may be no, the consensus might be there might be no benefit to add radiotherapy into that setting. Then you could go, yet another potential schedule would be, well let's deal with the risk of systemic disease by giving chemotherapy first followed by consolidating chemoradiotherapy to either the pelvis, what we like to call reverse PORTEC or the GOG258 type protocol. If there is nodal disease then residual disease you might want to consider boosting at that time. But what say this patient was hormone receptor positive? Is there a role for chemotherapy? Could she have just been managed with hormone therapy alone? Again that is another discussion that could be had with the patient and in a multidisciplinary team meeting. And now with the newer data there could be some consideration for whether or not you add immunotherapy to this whole discussion. So what if we had access to molecular profiling? So the latest 2022 ESMO guidelines are giving us some indication now on how we can start to utilise this information that is coming to hand. We know that the majority of the patients are likely to fit into MMR deficient or NSMP groups because they are the largest cohorts but then we also want to find those patients that are poly mutated because we are starting to learn that that is actually a good mutation to have. The one we probably don't want to find is the p53 abnormality. So ESMO has come out with a nice treatment algorithm that should you have access to all of this molecular profiling could be useful in helping make those decisions with regard to what adjuvant therapy you could offer the patients. And again if we fall down and we look at the risk categories for this particular patient as a stage 2 she again still falls into a high intermediate risk group. She's grade 2 endometrioid. It would be useful to know if she was MMR deficient or NSMP because that will help determine what we do. If we're lucky enough that she's poly mutated then perhaps we could consider de-escalating therapy but again we don't have the data for that yet. The trials are starting to look at that and hopefully when rainbow blue or taper finally open and recruit when we get that data we'll be more confident in being able to offer de-escalation therapy. If she's p53 abnormal I think the trend is now to offer most of these patients chemotherapy. So this table again is kind of summarizing what we would do had we had that information with molecular profiling. Unfortunately we weren't able to offer that to this particular patient so we're now in a situation where we're going to have to deal with recurrent disease. So she has extensive nodal disease with quite a bulky left-sided pelvic side wall node, nodes up to periortics. Interestingly no vault recurrence and no distant disease to the best of our knowledge given that we've only got a CT. If we had access to it in my centre the recommendation would be to undertake a PET CT to make sure that we didn't have distant metastatic disease. If she had localized recurrence which is not the case in this situation then consideration may be given to using MRI to determine if localized radiotherapy might be a good option in this setting or if there was a surgical option. Again not relevant for this particular patient but something we would consider in the event of isolated recurrence. So had we had the isolated pelvic side wall disease only which was what was clinically initially found then we might be been able to offer definitive radiotherapy to this mass because most surgeons that I've encountered would be unlikely to want to dissect this. Hypothetically speaking there might be a role for the addition of concurrent chemotherapy as a radiation sensitizer. You could also then consider whether or not you want to add hormone therapy if she's hormone receptor positive. The situation though is that we're facing is that we have a significant nodal recurrence so do we consider radiotherapy to those sites of known disease? Predominantly for symptom control we would imagine that she's going to get some pain. There's the potential for her to develop lymphedema which can be quite debilitating so all of these decisions would be about maintaining quality of life for her. Could that better also be managed with chemotherapy alone or even hormone therapy with just Provera may be useful and again consideration now for whether or not one adds immunotherapy to the chemotherapy regimens. But what if we find widespread metastatic disease? I guess that is still our biggest concern so normally one would head towards giving chemotherapy plus or minus hormonal therapy depending on what resources would be available. If we couldn't access chemotherapy is there consideration for chemotherapy alone? If you could get funding and you had access to the drugs the addition of immunotherapy and then again of course thinking about radiotherapy for symptom control. If we look at a centre that has all these resources available though again we can go back to this algorithm provided by the ESMO group and look at all the different options that may be available to us to manage a patient with recurrent disease and as you can see that they are quite numerous now and as we go along perhaps this will get further tailored now that we're adding in the molecular profiling to the equation. But I will finish with just bringing up a couple of interesting papers that were presented recently at the SGO meeting in the US and again it comes back to molecular profiling and what is the role for the addition of immunotherapy and both of these papers are very supportive now even in the absence of MMR deficiency so an MMR proficient patient suggesting that immunotherapy does have a role to play in recurrence or advanced disease and even metastatic disease. So I'm going to close by saying there are multiple options available. It is going to be dependent on what resources are available to you wherever you might be located. In my centre because I have access to the vast majority of these treatment modalities we would probably try and throw as many of them as are useful at this particular case but even in my centre we don't have access to Pembro or Distella for these patients. They have to be MMR deficient before they will get access to immunotherapy because of the restrictions in Australia to access immunotherapy so even here we have limitations so it's going to depend on where you are and self-funding is very expensive. So I will stop there but happy to take any questions from anyone with regard to the options presented here. Wonderful, thanks so much Pearlie. It's a brilliant catch up on where we are with endometrial cancer. I think five years ago that would have been just slides about PORTEC so things have really changed a lot. I'm going to start with Alex just to share her thoughts about the case and what she might do in her centre, what she might have considered for the patient along the road and I'm also going to come back to you Alex just to have a chat with us about the role of SBRT in relapse of endometrial cancer as well. Yeah, thank you, thank you Dr Sagiti for a really interesting case. I think it's giving us a lot to talk about today and a great presentation and as we've already heard from Pearlie that there's again different aspects to talk about so I was sort of thinking we'll focus first on the first aspect and maybe there will be questions on this and again just to remind if you want to put questions through we can discuss that. So I think probably we think firstly about my comments on managing stage 2 disease of endometrial cancer and again we've seen very clearly the data and the recommendations of what information we have. So here again we have a woman who had a grade 2 endometrial cancer. We already know there was deep myometrial invasion lymphovascular space invasion was present. We know in the ESGO guidelines the ESMO guidelines it is now divided into whether it's substantial LVSI or focal LVSI and that's based on we have the PORTEC3 data and PORTEC group have also looked on the extent of LVSI may help guide but it's being present and we know that significantly it increases the risk of being lymph node involvement. We have cervical stromal invasion, so it's stage two disease and as we heard the lymph nodes were not assessed. So I absolutely agree, we would have recommended external beam radiotherapy and vaginal brachytherapy for this patient and it's underlying that you certainly would add brachytherapy when there is cervical involvement. Again, we can have debate whether we do that for all patients, but it's definitely when there's cervical involvement. I think I was just going to raise, and again we can discuss, I think we agree in this position, we would offer external beam. We do have cases, again just to differentiate with stage two disease, that maybe they've had surgical staging of the lymph nodes, either with sentinel lymph node or lymphadenectomy, and then it comes back with very focal cervical stromal invasion. And if they've got negative nodes, a grade one tumour, and do not have deep myometrial invasion, there would be an argument here for giving just brachytherapy as opposed to external beam. And so it's very important to consider all the factors, not just the stage. And then I suppose the other point is, again, those that have access to molecular profiling, just thinking in terms of adjuvant therapy. I would be interested, and I'll put it to Hannah and Pearlie as well, in that if you have molecular profiling and if the patient was polymutant, would you still be recommending radiotherapy for this patient? Because I'm going to say I would probably feel we don't have data yet, and with all of these high risk features, we would consider it. There is the ongoing, as you say, TAPR and Rainbow Blue trials, where they're looking at observation. And in that protocol, radiotherapy is allowed by a centre of choice for the higher stage tumours. But I think the molecular profiling may not impact so much here, but if there was p53 mutation, you may have considered chemotherapy. But I think you have to underline with molecular profiling that if you're going to base that, you need to have all four molecular categories because you can have double mutations. So, if it's p53, then you ideally have access to poly, but that can be much more challenging for all of us to have and to have it in a timely manner. So, I suppose that those are my thoughts on stage two disease, really, and I might open it up if there's questions or Hannah, if you want. Yeah, so we don't have any questions in the box yet, but I think that it's an early morning for everybody in Europe and very early for people in America. So, just about the molecular pathway. So, I think for some people are a big believer in the new data and some, the rest of us are waiting for the real evidence for it. And I think that when you have the patient in front of you, can you hand on your heart say, you're poly, you don't need treatment, it's all going to be fine. No, you can't. And I think that I too would not make a big treatment decision change as yet without the information. And the only one that like you is that if somebody's p53, you think this may be not going to go very well for you. And I just think the case that you've presented to us today shows us the one thing about endometrial cancer, it's so unpredictable. You have a patient that it all looks great too, it all looks lovely. And you say, fine, you're going to have some radiotherapy, I'll see you in six weeks. And then you see your planning CT, and boom, there's lymph nodes everywhere. And I had a case very similar to this, a lady who was essentially supposed to be a grade two, we did a planning scan, she had pelvic lymph nodes. So, I started her on adjuvant chemotherapy, as it were. And she just grew through her chemotherapy. And interesting enough, she was a DMMR patient, which there is some evidence that they're not responsive to chemotherapy. And then I decided to give it a go with the radiotherapy. So, I actually did a big plan, lots of boosts to all these lymph nodes everywhere. And actually, she's radiotherapy responsive, which again, is totally unpredictable in endometrial cancer, when you've got macroscopic disease, who's going to respond and who isn't. But occasionally, they do. And it was worth the chance for her, she was a young patient. And now, as Polly said, if you happen to have the DMMR, you can get access to Dostolimab. So, she's just started that. I mean, her long term prognosis is not good, because she relapsed very quickly and in this unusual pattern, but they behave unpredictably. And sometimes you need to think out the box a little bit, not necessarily follow a protocol and say, okay, radiotherapy is still very useful in this situation. I think most of us work a little bit like clinical oncologists that you have access to both, but our core is that we are radiation oncologists. And it's still an extremely useful tool and available wherever you are, if you have a machine. So, it doesn't really matter whether you have all the fancy drugs, if you have a machine with some decent MLCs, you can do radiotherapy even to these macroscopic chunky lymph nodes. And what the future will hold when we finally have the evidence for all these molecular pathways, we'll have to see. But still, the occasional case, and maybe even a lady like this, you have to do something that's probably a little bit colouring outside the lines. And the other thing that's a very interesting debate in endometrial cancer, particularly those of us who love radiotherapy, is the COG versus the PORTEC families. And I think that probably the ladies on the call are PORTEC families. But a lot of the COG protocols are a little bit more heavily weighted towards chemotherapy and less for radiotherapy. But again, it's your personal preference, how you interpret the data, how you manage your patients. But I think that endometrial cancer used to be very straightforward. And it's really not anymore. And it's become quite complicated. There's lots of choices, which is wonderful for the patients that they have lots of choices, but it doesn't make it so straightforward as it used to be. We don't have any questions in the box, but maybe Pearlie, you want to have a chat about what you feel about integrating molecular pathways into your current practice without the evidence? Before I start, Nneni, you put your hand up at the moment. Did you want to add something before I start talking? Yes, Pearlie. I'm not sure whether I've asked you this already. I have a buddy question. I think it's obvious from the case that I presented on how limited we are in terms of assessment, in terms of preoperative assessment, pathology, and also the treatment available. And this is unfortunately, this is a reflection of what we have here in the Pacific as we don't have radiology services, pathology services is quite limited. So I was just wondering with patients who's got early stage endometrial cancer, stage one or two disease that has high risk features, that we're supposed to be recommending adjuvant radiation, whatever form of radiation treatment, and we don't have access to that. Most of them will never have access to that. Is there a role of offering them chemotherapy alone? We know that PORTEC3 and GOG trial has shown some benefit, but in mostly stage three disease, but rather than doing nothing from our side, is there a role of giving the chemotherapy, which is what we have available here? Given the early stage disease, I wouldn't offer them chemotherapy. I think I'd keep that in your back pocket for when you have to use it. Similarly with hormone therapy, I would keep that in my back pocket as well, in case you need it, because, and this will come back to Hannah's question about, you know, how much weight do we put on the molecular profiling? It could still be that some of those patients that you have, who have these early stages, when you operate on them, even though you don't have access to the molecular profiling, they may still have some of those good profiles and they may not relapse. So you want to keep your, I guess, your tinder as dry as possible until you need to light it, for want of a better analogy, and not go there before you have to. So I wouldn't offer any extra treatment, even though if I saw the patient and they met the guidelines, I would offer volts or external beam. But you have to remember too, that when we offer those, we're offering it as a also as a local control. We know that radiotherapy does not change survival. So yeah, that's what I would say. Hannah or Alex, do you have anything you'd add? Only just the caveat is, it obviously depends on the cell type. So if you had a stage 2 serous, you may consider to treat them a little bit as a chemosensitive disease. If you have the pathology services to be able to differentiate between, but those are basically the p53 tumors anyway. And they are should should just be a tiny handful of what you see as a routine. I was just going to ask Dr. Sakiti, do you have access to radiotherapy at all in your? Okay, so if you if you needed to, the patient would have to travel? Yes, they have to travel. It's very costly. Sure, sure, sure. So to answer Hannah's question about what we would do in Melbourne, we standard of care would, at the moment, we do get MMR status on our patients. We do get p53 on our patients. We don't get poly. So that is the one we are missing. The cost here can, for some patients, be prohibitive. In Australian dollars, it's roughly about $380 to $400 to get the sequencing done. We would hope that we could open something like taper in the very near future so that we could participate in that to get the knowledge to allow us then to make that decision whether or not we would look to deescalate and then hopefully make a case to get poly as part of standard of care testing. You know, Australia doesn't have access to next gen sequencing as standard of care. Would I deescalate if I knew she was poly positive? I wouldn't drop radiotherapy completely. I probably would follow the taper algorithm, which would allow me to deescalate from external beam plus brachy to just brachy alone. I'm not sure I'm game enough to drop radiotherapy completely. That's my qualified answer. Alex, I mentioned earlier that I was going to come back to you just to talk a little bit about the role of SPRT and endometrial recurrence, particularly those who've had previous radiotherapy, just to discuss a bit your experience and some evidence for that. Yeah, I think it is. I mean, obviously, in this situation, I mean, we'll talk a bit more about more extensive recurrence. But yes, I think it's an interesting question. Now, when we think about recurrent disease for endometrial cancer, you have to consider what treatment they've had before. And therefore, if they've had prior radiotherapy, so if we had given adjuvant treatment in this situation, and then the patient has a side wall recurrence or a lymph node, what treatment options are there? And we always have to think about whether surgery is an option when someone's had prior radiotherapy, but that can involve extensive surgery. But if we have a lymph node, and I'm talking about re-irradiation here, there is increasing experience with re-irradiating an isolated side wall disease. I suppose we're getting to my issue, I know that this is the other end of sort of what's available, but I think it's worth us thinking about the options. So we think about in the pelvis of re-irradiation, the disease free interval. So if they have been at least six to 12 months into prior radiotherapy, what would be the doses available? And we now have very much increasing international consensus of what the dose could be that you could deliver. And certainly my experience has been that you can deliver 30 brain, five fractions, it's very atactic, with very limited toxicity. It's important you consider the nerve doses, because quite often they're not resectable because it's involving the sciatic nerve. But again, by thinking about those nerve doses, then we would think about this. I mean, I think we've got a bit more if we need to. In terms of other options, I suppose where stereotactic radiotherapy comes in is if you have oligometastatic disease, or if you have an isolated periodic lymph node. And again, it's a debate, if you have a lymph node recurrence in someone's pelvic radiotherapy, but an isolated lymph node, would you then treat all of the periodics with external beam? Or would you treat a single lymph node? We have case theories that suggest that again, you can get good long term control with stereotactic treatment. I'm just conscious that it's still in the order of case series that we have on this. We do not have large data, but I think you can pull the data for stereotactic with other tumor types in terms of safety. And the data is you tend to get very good local control. But I think in endometrial cancer, if you have a solitary recurrence, what we see compared to cervical cancer is a much higher risk of also more widespread systemic relapse. And so the question is, at what point do you think about chemotherapy as well? Sorry, I'm sort of touching around different places. But I think it's important for us to think about stereotactic treatment. I think I'm also going to underline when we're talking about relapse when someone's had prior radiotherapy, and again, I'm conscious we can talk about the other areas, is, and we consider this in the ESCO guidance is if someone's had prior vaginal brachytherapy and then they relapsed in the lymph nodes, what do we do? And I must say my experience and we would say is we would almost ignore or take into account that they've had prior brachytherapy and actually if you've got pelvic recurrence despite having a vaginal brachytherapy then I would still treat radically with radiotherapy or chemoradiation and I think it's important to think about this as an option and so when you're thinking about adjuvant treatment in your way you're not excluding future external beam treatment if you just give vaginal brachytherapy. We have a couple of questions in the chat box, can Pearlie and Alex can you see them both? The questions, Pearlie I'm going to give you the first question, so the question is for a case of endometrial cancer with lymph node metastases pelvic and vaginal spread undergoing pelvic radiotherapy prior to surgery, so neoadjuvant pelvic radiotherapy which is a situation we've not discussed. Would you suggest to do the brachytherapy after the surgery, so postponement or post-op, and what chemotherapy regimen would you recommend post-op? So I would reassess based on the pathology after surgery as to whether or not there is value in giving any brachytherapy. I guess when you've given external beam in kind of like a pre-op setting your intent is to try and sterilize that area and hopefully make the disease easier to resect for the surgeon. What the question I would ask myself is what value does brachytherapy add after surgery in that setting and I'm not sure that the standard adjuvant brachytherapy dose would be of value in that situation, so I probably would err to not giving it rather than giving it. As far as chemotherapy is concerned I'm probably not the right person to answer that question because I'm not a clinical oncologist unlike you two, but what I have learned is most of the time it's carbaplatin, Paclitaxel, that's my answer. Yeah, Alex do you want to talk a little bit about neoadjuvant treatment for endometrial because we haven't really touched on that. Yeah, because that's what I was going to say for this question, I mean I must say when we think about patients that present with advanced disease what's the approach and I must say that we and when I say advanced either with extra uterine spread even peritoneal spread or very bulky lymphadenopathy, then we would give neoadjuvant chemotherapy. I suppose that to phrase and again if you look at the ESGO guidelines we don't call it neoadjuvant, we would just call it chemotherapy so it's advanced disease and we would give chemotherapy and yeah probably sorry I think we're all using it at the moment carbaplatin and Paclitaxel is the standard of care but with reassessment in terms of if patients have a good response to treatment we apply the similar principles to treatment with ovarian cancer and whether to then proceed with surgery after three or six cycles of chemotherapy and I'm talking about that rather than neoadjuvant radiotherapy because I must say that that would be our approach. Again there are case series, in this there are again limited data, the data we have are predominantly actually patients with serious carcinoma that have been reported but in those patients that do have proceeds to have debulking surgery and if complete cytoreduction is achieved then the overall survival in the cohort that have surgery is far superior to those that have not had surgery but it's a selected cohort and so I think you have to consider those patients where there is a good response if surgery is feasible either just with hysterectomy or all sites of disease and then if it was because of nodal disease then radiotherapy subsequently. I must say I have rarely done neoadjuvant radiotherapy, the only times I've done that if someone's at a point they're not fit for surgery and then they may subsequently be available, it may subsequently be an option and so that would be very very case specific I think rather than something. Yeah from my own experience if they're inoperable then I treat them and they're fit for radiotherapy and it's incompatible then it's it's primary chemo radiation without really a thought to carry on to surgery later. But neoadjuvant chemotherapy for an advanced case or chemotherapy for an advanced case we know already for those high-risk patients if they had surgery you would have given them chemotherapy afterwards anyway so the logic is there to give them some chemotherapy up front to do it a little bit back to front but it's not evidence-based and it's not a routine practice but occasionally you get a patient where the disease is stuck into the parametrium and it's not suitable for surgery up front and that's and you can do it but I think that most of us wouldn't do radiotherapy unless it was our sort of primary endpoint aim to stop at radiotherapy alone. But just thinking about Dr. Sakiti's case I mean if she responded really well to chemotherapy you know she there's a she has no other metastatic disease I mean she's a young woman you know is there a role for her to have a secondary look surgery it's not routine but you don't have radiotherapy access so it's a possibility and then in a situation where you do have access to radiotherapy I would definitely if she responded nicely to chemotherapy I would give sort of a high dose palliative dose to her pelvis and nose potentially to give her maybe a little bit of lung control like I was just thinking she's 52 isn't she your lady so if she did well with her chemo it's a thought to try to do something a little bit again out the box for her. Okay so we start back with Pearlie so in a stage two with double molecular profiles pol E and p53 do you escalate or de-escalate? Thanks Martin for the tricky question. Based on the information that the ESMO group have published the answer would be that pol E trumps everything so you would de-escalate because the pol E is the dominant mutation. Would I actually do it? That's a different question. That's the one that makes me nervous I don't know yet is my honest answer I don't know if it's safe to de-escalate so I'm again like Alex one of those people that's going to sit back and go I need the data before Alex? Same for you? Yeah I agree I mean as you say double classifiers pol E trumps everything so that's that's sort of where it is again I mean I've said in this particular case I would be not de-escalating because there's so many risk factors so I would be not de-escalating where it is again I mean I've said in this particular case I would be not de-escalating because there's so many risk factors I think where I may de-escalate is but you have the cases with grey sort of a grade 3 1b but poly mutant and then then I would de-escalate and but I think in this particular situation I don't feel we have data of patients with these risk factors not having adjuvant treatment. I think we're having lots of conversations aren't we about poly but when you dig down so few actually have access to it yeah it's not it's not well it's only just becoming routinely available in the UK I mean we didn't have it in South Africa with South Africa we can get p53 not a problem we're doing it for a long time and we could get DMMR with a little bit of a plead to the pathologist and that's in the public sector in in South Africa but poly is a super expensive test to do and I know that the British pathologists have actually put out a sort of it's not a not everybody's going to get it you're going to have to pick your patient carefully so that you actually get the most value out of that information and at the moment people will start to do it in the UK without necessarily there'll be two camps some people will change their practice and some people will wait so it's it's it's still difficult isn't it when oncology is such a brilliant field things change all the time it's fantastic but but just to have their patients to sit and wait for the real world data as well sometimes it's it's tricky to do when others move on. Can I and Alex in the UK are they following those the solid the British pathology guidelines as to which patients they recommend to get the poly testing because there is a some adoption of that that that particular guideline here too in Melbourne Australia should I Yeah it's it's being rolled out and as you say it's it's recommended for patients where it is where it may change your treatment so they don't recommend doing poly for low risk patients because you're not going to give them any adjuvant treatment anyway so that's a lot of patients where you don't need to be doing this and similarly at the moment the data for stage three disease is case specific and so it it's uncertain um in practice I think it depends on your labs and the availability. I'm conscious we're talking about things that as you say a lot of people don't have but it's I think these are questions coming because we're being told to assess this with patients but but the guidance does also cover those that don't have molecular profiles and I think it's underlined that we also do have the risk groups if it's not available. I think that's the one can I just sort of I'm moving back to this case I was just going to reiterate what Hannah said really in terms of our particular case here um it's a similar thing to where we're talking about neourgic I think this patient's got exception very bulky recurrences and so at this point I would give systemic therapy um but absolutely if she had a good response we can encompass the pelvis and the paraitic lymph nodes in a in a radiotherapy field and and I would say you know actually local control may be very important and so I mean I agree I would treat this and actually depending on the extent of disease after the chemotherapy may even be more definitive with the treatment so just because depending on response obviously we've talked a bit about molecular if immunotherapy is an option and and things but but I think in what you have available I would start clearly with chemotherapy for this patient and then depending on response think about radiotherapy because you can see the extent of the paraitic nodal disease she must be very symptomatic or would be soon in terms of pain and radiotherapy can be very effective for this so either a sort of palliative dose or even a higher dose of those Would you add hormones if she was ARPR positive? At this point I wouldn't I think after chemo I would keep it as an option for the future I mean this patient has had a very short disease-free interval it's behaving aggressively so it doesn't fall into the cohort where hormones has the highest response but clearly hormonal therapy is very important as an option and we do sometimes think about using it afterwards either continued but I tend to introduce it as a second line. I'm thinking more in Nanny's situation whether there are limitations in terms of what chemo is available and correct me if I'm wrong Nanny at the moment you can only get CISPLAT isn't it? You can't get Taxol at the moment? No we Oh she's frozen whoops Whoops Oh absolutely I think if you're limited then of course I think it's important to think you know hormones is a very cheap option and certainly again it's underlining if you have a patient that's got a long disease-free interval and an ER positive tumour then hormonal therapy is often first line that you would use certainly for small volume long test disease or small volume disease then hormones would be my first choice for these patients whereas big volume after short disease-free interval I would tend to go to chemotherapy. So just to go back about resources I think that Dr Skeeth your case just reminds us how access to radiotherapy makes such a difference to women living with these pelvic malignancies because it is a very horrific way to live out the last months of your life with uncontrolled pelvic symptoms and how a radiotherapy machine even without the bells and whistles can make such a difference to symptoms and quality of life in those last few months and I know having worked in lots of different resource settings the thing I've always been most grateful for is access to radiotherapy even a single fraction makes an enormous difference for a patient because often people are not fit for chemotherapy and chemotherapy doesn't work all the time but the most important thing is to do the best you can with what you have and obviously you're doing that for this case. So I think we just have a couple of minutes left to round up so I'd like to thank Dr Sekiti for joining us wonderful first time we have somebody from the Pacific Islands on our calls and Pearlie thank you for being with us you've always managed to make it in the middle of the night before and thanks very much for your distillation and to Alex wonderful conversation discussion I think we all learn a lot and it's always great to discover that across the time zones we still have a lot of commonalities and all all the core of it is to do the best for the patients that we have in front of us. So thanks again for everybody listening in and also a reminder that this will be available on the 360 learning portal as a recording in the next couple of days so and look out for upcoming um radiation oncology MDTs that we'll be doing in the future and thanks everybody for joining today and we'll see you next time.

recurrent endometrial cancer

endometrioid endometrial carcinoma

adjuvant treatment

abdominal pain

nodal recurrence

palliative care

molecular profiling

chemotherapy

treatment options