Welcome, everyone. I'm your moderator today. My name is Dr. Remy Naus. I'm a radiation oncologist and head of the department here in Erasmus Medical Center in Rotterdam in the Netherlands. Today on ECHO we will be discussing a case, a patient case with cervical cancer, a node-positive patient, and we will discuss challenges in the management of node-positive disease. Dr. Vinita Tempe will present this case, and then Dr. Thomas Ramm will share a distillation of this case. And after that, we will have a discussion with the panelists, and both Dr. Suzanne Matthews and Dr. Anuja Jhingram will join in on this discussion. Before we start with the case, I just want to go through very few housekeeping items. We would really like you to submit your questions, and this can go on all the time during these presentations. You can submit your questions in the Q&A, and we will use these questions also in the discussion later on. So make sure you ask the questions in the Q&A. If you, during the later discussion, would want to be unmuted to ask questions, please raise your hand, use that option, and you can join in on the discussion. And the recording will be later available in the IGCS education portal. So having said that, we would like to start with the case. Let's get started. Dr. Tempe, please go ahead with the presentation of the case. Thank you. Thank you, sir. I'll share the screen now. Sir, is it visible? The slides are visible? Yes, we can see them. Thank you. Okay. Good day to one and all. I'm myself, Vinita, and Dr. Aravind, my colleague, is also with me. Going to the case presentation, I'm presenting a 58-year-old post-menopausal lady with no comorbidities who presented with complaints of bleeding for vagina for five months, foul-smelling, white discharge for vagina for one month, and lower backache for duration. On physical examination, her performance score was EPOC 1. There was no pallor, ictus, pedundidema. There was no palpable neck knots, and the systemic examination was unremarkable. On pelvic examination, cervix was replaced by a proliferative growth of 5.4 centimeters, which was friable and bleeding on touch. Upper one-third of the vagina was in mold, and lower vagina was felt free. Bilateral parametrium was felt medially in mold, and the rectovaginal septum and the rectal mucosa felt smooth. On investigation, her hemoglobin was 12.5 gram per deciliter. Complete blood picture and the liver function tests were within normal limits, and HIV, hepatitis B, and hepatitis C, which we do as a routine, was negative. We have done an MRI abdomen and pelvis as part of a staging workup, which showed a large T2 intermediate signal intensity mass involving the cervix with upper third vaginal involvement and focal parametrium involvement on the left side, with associated restricted diffusion. The tumor size was about 5.1 x 6 x 4.7 centimeter, and there was a 12 mm left-sided paralytic lymph node. Bilateral common iliac lymph nodes up to 14 mm, left external iliac node of 16 mm, and the right external iliac node of 11 mm. CT thorax showed no evidence of lung metastasis, and she underwent a punch biopsy from the cervical lesion, which was reported as moderately differentiated stromocellular carcinoma. These are the axial, sagittal, and coronal MRI images of the patient, which shows the large pelvic nodes and the paralytic nodes, and also the intermediate signal intensity tumor in the cervix. The pointer shows the pelvic nodes and the intermediate signal intensity tumor in the cervix, in the sagittal section, and in the coronal section, and the T2-weighted images of the upper abdomen shows the involved paralytic lymph node. Based on the clinical and radiological findings, she was diagnosed as a stromocellular carcinoma of the cervix of PECOS stage III C2. Her findings were discussed in our multidisciplinary tumor board meeting, and she was advised neoadjuvant chemotherapy, followed by reassessment for external beam radiotherapy to pelvic and paralytic region, followed by brachytherapy. She received four cycles of neoadjuvant chemotherapy with paclipaxil, 175 mg per meter square, and carboplatin area under the curve 5 every 21 days, and she completed four cycles without any major side effects. Following the completion of chemotherapy, response assessment was done with the contrast-enhanced CT abdomen and pelvis, which was done as a planning CT. In CT, previously seen, the exophytic growth in the cervix had significantly reduced, and the paralytic and iliac nodes had also significantly reduced in size. There were no new lesions or distant metastases. Radiotherapy planning was done with patient in supine position with arms above the head, and immobilization was done with vac-lock and heel-lock, and a full bladder and empty rectum protocol was followed. Contrast-enhanced CT abdomen and pelvis with a slight thickness was done from diaphragm to mid-thigh. A renal scan with the DPA was done as part of the pre-RT workup, since extended field RT was planned, and it showed normal kidney function. Target volumes delineated where GTV primary was squandered, taking into consideration the clinical findings and the radiological findings from MRI. CTV primary included the GTV primary, entire uterine corpus, and 2 cm of vagina from the lowest extent of the tumor. Internal target volume was given to account for the organ motion uncertainties, and PTV margin of 5 mm was given as per institutional protocol. And nodal growth-involved nodes were considered as GTVN. 5 mm margin was given for the individual node as CTV cross node. Elective nodal station included where common iliac, external iliac, internal iliac, obturator, and the pre-sacral nodes. Parietic region of the T12L1 junction was also included, and the nodal volumes were contoured as per the guidelines. PTV margin of 5 mm was given. The organ surface which were contoured were bladder, rectum, sigmoid, bowel bath, femoral heads, bone marrow, kidneys, spinal cord, and the duodenum. She was planned with a VMAT technique with simultaneous integrated boost. Positive nodes with margin received 54 gray in 25 fractions. Up to the renal hilum she received 50 gray in 25 fractions, and the parietic nodal station up to T12L1 received 45 gray in 25 fractions. So, these are the volumes which were given for the nodal volume. GTV was contoured, and the nodal volume also was contoured, and the PTV margins were given 5 mm, sorry, CTV margins were given 5 mm. To that, an additional 5 mm was given as PTV margins. These are the dose color wash pictures showing the 95% coverage of the PTV45 and the PTV50 volume. And this shows the 95% dose coverage for the PTV54, which is the nodal boost, and also the DVS shows the adequate coverage of the PTVs. Following extended field RT, she was clinically assessed for brachytherapy. There was minimal central residual disease with the left parametrium being minimally involved. Vaginal and rectal mucosa were smooth. MRF pelvis was done with the T2HR and diffusion-weighted imaging, which showed significant reduction in the cervical mass and the nodes, which was suggestive of disease regression, and hence she was planned for intracarotid brachytherapy. She underwent CT-based high-dose rate intracarotid brachytherapy with a modified flexor-suit applicator with a central phantom and two semivoids, and the source used was iridium-192. The dose delivered was 7G, the full fraction to the high-risk CTV in two applications one week apart, and the biological isoeffective dose received by the tumor was 89.7G, and for the rectum was 64.4G, and for bladder was 71.4G. She completed the treatment in September 2022, and the follow-up MRI showed a T2 intermediate signal intensity in the region of cervix with no restricted diffusion and no significant pelvic parietic nodes or distant metastasis, and she is currently on a short-term follow-up. Thank you. Thank you so much, Dr. Sampy. This was an excellent, very clear presentation and images. I would just want to remind everyone, please put your questions forward in the Q&A option. You can find that in the below panel. You can open the Q&A, and you can ask your questions. Please do that, and then I would like to announce Dr. Thomas Ram for the panel discussion. Please, Dr. Ram. Thank you. Sorry for the desolation. Sorry. Thank you, Remy and IGCS for this session, and the reason we chose this particular patient, cervical cancer with nodal metastasis, as management challenges, is as we know that the imaging is increasingly used all across the world, and especially even in developing countries, and as imaging is getting integrated into the evaluation and also in the treatment, we are able to identify the nodal disease in a better manner. And this particular patient, which Dr. Sampy presented, just to summarize, the patient is a 50-year-old lady who had locally advanced carcinoma cervix, tumors of around 5 into 6 into 4.7 centimeters, and she had a 12-millimeter paralytic node and bilateral common iliac nodes up to 14 millimeters, and she had a left external iliac node 16 millimeters, and the right external iliac was around 11 millimeters. So, as per the staging, she will be, she will stay at stage 3 C2, and her performance status was ECOG 1. So, the discussion points, which I hope to elicit using this case for the presentation is, what is the optimal imaging, especially when we are dealing with the nodal disease in cervical cancer? Then, what is the role of neoadjuvant chemotherapy in this kind of patient, especially who have 3 C2 or paralytic nodes? And how do we approach the radical chemo radiation in these kind of patients? And how will we approach with somebody who has only a 3 C1 versus how will you approach somebody who has a 3 C2? And what kind of radiotherapy techniques and doses we need to consider? And also, we need to be cognizant of this issue that, how can we look at resource stratified approaches? Because there are a few centers who have optimal resources, but there are many centers who have very limited resources at their hands. And then, briefly about what are the toxicities we can anticipate in these kind of patients? So, we all know that from 2018, the FIBO staging has been adopted, and we now have 3 C1 and 3 C2 integrated into the staging, where 3 C1 is the pelvic nodal disease, and 3 C2 is the paralytic nodal involvement. So, the first question, which I would like to elicit in this discussion, what is optimal imaging in these kind of situations? And we have this data, which is coming out from EMBRACE, that when you look at the volumetric imaging, FDG PET, if there's an uptake, it indicates a significant, or I would say, positive limit node in these patients. If you are using a CT scan or MRI, and the short axis is more than a centimeter, we take it as a significant limit node. If the short axis is somewhere between 0.5 to 1 centimeter, we look at the pathological morphology, like the irregular border, high signal intensity, and the round shape to estimate whether this patient has significant nodes. Traditionally, some of us who have trained, we had only, those days, only ultrasound imaging available, and unfortunately, it is very operator-dependent, and the depiction of limit node status, it becomes very, very difficult, and we used to pick up only when the nodes are beyond 1.5 to 2 centimeters, so it was not an ideal imaging for staging of cervical cancer. Then we had the availability of a CT scan, and that improved the overall accuracy of CT for cervical cancer staging somewhere between 32% to 80%. Then the MRI became more readily available, and the specificity for MRI for metastatic nodes was estimated to be somewhere between 71% to 100%, and it is actually an optimal imaging, especially when it comes to assessing the tumor, parametrium, pelvic side wall extension, invasion of bladder, and rectum. Now we have the FDG-PCT also becoming increasingly available, and it has the highest negative predictive value for paralytic temporal devaluation, and has a specificity of 85%, and also it has a sensitivity of 42%, and it's been a preferred modality, especially for nodal assessment. Just to also make ourselves aware that we have a technology of PET-MRI, which is emerging, and it combines the advantage of the high soft tissue contrast and also the benefits of PET for nodal staging, but still it is not yet available in most of the institutions. So if you compare various imaging, especially for lymph node metastasis, PET-CT continues to be the desired investigation, which everybody prefers. And this was, again, a summarized usage, again, for pelvic and paralytic lymph nodes, if possible, PET-CT is recommended. There was a study with the National Cancer Grid of India, and they made consistent guidelines, and even in that, especially when it comes to paralytic nodes, when they identified on a CT scan or MRI, there's a note, it's mentioned there's a fine needle aspiration psychology, especially when there's a negative pelvic lymph node. So I just want to highlight this. The reason is, especially in some parts of the world, especially in India, if you don't have a pelvic node and you find a paralytic node or some nodal higher in the region, we need to also rule out other conditions like tuberculosis, which is still quite common in this country. So that's the reason they have suggested to do an FNAC. And as we move to the existing guidelines and what to say about how we manage this pelvic and paralytic nodes, NCCN still continues to recommend pelvic RT with concurrent chemo and even for stage 3-C2. And even the ESMO guidelines, somewhere they do mention if there is an uptake seen in the paralytic and PET-CT, then you may consider neoadjuvant chemotherapy followed by radiation therapy. Again, in our National Cancer Grid India guidelines, if there is a large paralytic node, they say you may consider 2-3 cycles of neoadjuvant chemotherapy followed by radiation therapy. So the optimal management in this kind of patients, they say that if the bulky paralytic nodes are somewhere between 3-4 cm, you can consider neoadjuvant chemo followed by radiation therapy. ASTHO also has come out with these guidelines and they also do mention about induction chemotherapy and they mention it has not been shown to be superior to this approach and the role of adjuvant chemotherapy is under study. So there is still, I would say, ambiguity about when do we use chemotherapy in these kinds of patients. Several trials have tried to look at this and there are some studies which are published. This is about a 10-year institutional experience where they use neoadjuvant chemotherapy followed by radiation and they found there was a decrease in the relapse rates in those who had neoadjuvant chemotherapy. And neoadjuvant chemotherapy followed by radiation, especially in 3C2, had a longer oral survival and progression-free survival. The current one interlace is looking at induction chemotherapy protocol plus chemo radiation as first-time treatment for locally advanced cervical cancer where they do weekly factory cargo followed by chemo RT. One interesting thing is in the exclusion criteria, they are excluding the nodes which are above the aortic backlocation, which means only the 3C1 stage is included in this study. So it will be interesting to see the outcomes of this study, which should be completed by May 2026. Again, some authors have looked into electropionic radiation. They found no survival benefit, no improvement in pyrotic relapse rates. Coming to this issue of 3C1 and 3C2, we are moving towards some kind of idea about risk stratifying the elective nodal regions where membranes are put as low risk, intermediate risk, and high risk, and to solve, for example, high risk is based on the nodal pathology where you have more than one node and the common allelic, or above, or more than three pathological nodes, and they have defined how we can plan the external RT lymph node regions. This is the risk stratification they have used, and this is the suggested schematic diagram for including the CTVs for various nodal regions. Before I kind of conclude, I just want to also tell the audience that we need to also be cognizant of the resource stratified approaches. Some of us have trained in COBOL-60 machines where there was conventional simulators. They used to use APPA fields and using a combination of four-field walks and pyrotegradation, these kind of patients were managed. There was one more technique which was called crossfire in a patient with a large pelvis who used to bring in oblique fields in his patients, and in the event of photons, we moved from conventional four-field walks 3D, and now we have IMRT, VMAT, and tomotherapy. And especially when it comes to conventional, we can use a CR-based or a DRR-based method to plan the patients. And then moving on quickly to show some of the, I can say, older ways, what we used to do earlier using radiographs. I used to use radiological landmarks to put our fields. Also, it's important in resource constrained countries where still they may be using these kind of techniques. But the challenges with this, I'll show you in a dose distribution. If you see, sorry, I'm just moving this slide quickly. Yeah, this is a dose distribution we had from the various techniques using COBALT-60, then using virtual simulation, and also 3D CRT. And you can see how the dose to the target was conformal, and also dose to the organ receptors was reduced using various techniques. And this is what Dr. Tampi has shown with IMRT, VMAT, how we can do a simultaneous integrated boost, not only to the noto region, but also to the rest of the parietic and pelvic field. With technology improving and various techniques evolving, we need to be cognizant of the various acute, some acute and late toxicities in such patients. And various authors have published the early toxicity and treatment outcomes. And with the upfront extent, IMRT cohort, you can have anything between 22.6% grade three hemoglobin toxicities, or up to 10% GI toxicity in these kind of patients. Also, a point which I like to share is when there is no cross-sectional imaging in some setups, when there's no IMRT, no 3D CRT. And earlier, this was one of the adopted method was we had only ultrasound process. And whenever possible, we use ultrasound-guided FNAC to establish neuronal metastasis. And we considered a neuroadjuvant chemotherapy for at least four cycles. And external feed RT was used up to T12L1 junction and using ATP fields up to 45 gray. And parity was given up to only 45 gray and the pelvic four-field box up to 50.4 gray. And intravenous neurogram was used to ensure that the kidney position and shielding is optimal. So I could just summarize this distillation that cervical cancer with nodal metastasis is a challenging scenario, especially in various resource-constrained situations. The role of neuroadjuvant chemotherapy is evolving. Wherever possible, IMRT with the nodal boost is preferable. And in limited resource settings, neuroadjuvant chemotherapy followed by external field RT can be considered. So thank you for your patient listening and wishing you all happy holidays. Merry Christmas from Belo, India. Thank you. Thank you so much, Dr. Ram. This was an excellent distillation and nice to see also your Christmas pictures. Excellent. So in the meantime, there have already been four questions in the Q&A box, but please, if there are more questions, please put them forward in the question and answer box. And then we would like to start the case discussion. Perhaps Dr. Matthews and Dr. Jingang, Anuja, you can join us both. Perhaps we can start with you, Anuja. Yeah, I think, yeah, sorry. Can y'all, okay. So I'm taking my mask off. I'm in clinic, so I apologize. Very interesting case. And I think the whole concept of neuroadjuvant chemotherapy is actually a really interesting question. You know, it's a big debate in the U.S. We rarely use neuroadjuvant chemotherapy even in stage 3C2 patients, but I'd like to hear what everybody else, I mean, Dr. Matthews and Dr. Ngoc, what are your thoughts about the neuroadjuvant chemotherapy? I mean, I think that's, of all those questions, that's probably most relevant to me. Yeah, so, so far, indeed, in the chat, that was, so there are, in the chat, basically two topics at the moment that is, or in the Q&A, that is, what is the role of neuroadjuvant chemotherapy? And also, I think an important question, would we, should we consider any confirmation of the suspected paroartic disease? And what would be the role of that? So I think that's also an interesting question, but maybe to start with a discussion on neuroadjuvant chemotherapy, Dr. Matthews, can you also hear us? Yeah, thank you. So our practice is, we generally don't go for neuroadjuvant chemotherapy, but in some situations, we are kind of forced to do it because of long treatment delays and in a very symptomatic patient. So a patient with a paroartic node, generally our protocol is to go with concurrent chemoradiation, with concurrent splatting. And now we have IMRT at our center, but previously we used to do the conventional field. And when we used to do the conventional field treatments, giving concurrent used to be a challenge. Most of our patients would not tolerate concurrent cisplatin in that situation, but with IMRT, that is a definite change, which we are seeing. We are able to push concurrent cisplatin with external BMR. And with this question of neuroadjuvant chemotherapy, like I said, sometimes patients present with big paroartic nodes that are causing symptoms, they can't lie down, there's a psoas spasm, so to say. And in those situations, if there is a delay in starting radiotherapy, we would give neuroadjuvant chemotherapy. And even there, we go with a short duration, short intense dose dense protocol. And so we give chemo once every two weeks, and then we try to start RT by the, after two cycles of two weekly neuroadjuvant program. So- Yes, thank you very much. Yes, no, sorry, go ahead, go ahead. Yeah, of late, initially we used to do, go with cisplatin and 5U as neuroadjuvant agents. And now for a few patients, we are trying weekly Taxol and cisplatin or carboplatin. And that again is a weekly dose, and we start chemo by the sixth, soon after the sixth weekly dose. Thank you. Yeah, thank you, Dr. Matthews. And I think you bring forward also some really relevant and interesting and good discussion points, because we have similar experience with the transition from, let's say, 2D, 3D radiotherapy towards IMRT-FEMAT with more conformal techniques and the feasibility of combining that with concurrent chemotherapy. And just to reflect also for Dr. Jinggang, also for us, we are predominantly more, I would say in the management of going for concurrent chemoradiation upfront and not using neuroadjuvant chemotherapy, but it would be also, yeah, interesting to learn some, maybe you could comment, Dr. Aram, also on your experience with toxicity, because what we often also notice in this situation that, let's say, patients have condition to also undergo subsequent concurrent cisplatin-based chemoradiation can be somewhat affected also by neuroadjuvant treatments. So just to understand, do you have any thoughts on that? Yes, I mean, one is like Susan was saying, based on certain scenarios because of the patient, one situation, like what we face here is like most of our patients are non-regional and they need sometimes time to start their radiation and come prepared to stay in our city. So that is one of the reasons where some of these patients started chemotherapy, neuroadjuvant chemotherapy. And yes, that is right, when you are doing neuroadjuvant chemotherapy, we need to understand whether this patient subsequently, whether he'll be able to undergo IMRT, because again, we have a situation where quite a few of our patients are out-of-pocket treatment. So all that is taken into account, whether they will be able to handle this kind of intense treatment of neuroadjuvant chemotherapy. And we do see quite a few neurotoxicities in our patient. And we prefer to go in for an IMRT where you can do as much as bone marrow spreading in this kind of patients. Thank you, Dr. Ram. And I think that's also what Dr. Matthews brought forward when let's say there is a gap to cover before you could start with this concurrent chemo radiation. I think that is exactly an argument that I've heard more often in also your resource limited situations and in situation where you have far distances to cover. Dr. Jingran, do you want also to comment on that? I mean, I totally agree. You know, again, we don't use neuroadjuvant chemotherapy, but I think, you know, I think that's where the hyper-fractionation can be used that you're using an embrace, right? That's where the 220 and the 230 per day helps with the long distances, right? And shortening your treatment time. Doing a concomitant boost really makes a big difference in shortening your treatment time. I do think, I think in resource limited settings, neuroadjuvant chemotherapy makes a lot of sense. I mean, where IMRT is not available, the delay in starting treatment, you know, where you have a wait list, all of that. And I do think the size makes a big difference. I mean, I 100% agree. I mean, a 3CM node in the periodics is going to be difficult to irradiate, eradicate with, you know, do we have the right doses to do that without causing major toxicity? We do try to push forward again, like I said, but it's a very interesting question. And I think it is, has to be taken patient by patient, but it'd be interesting to see what the results of, so Remy, the protocol that Mary McCormick was doing, do we know the results of that protocol yet? No. So it'll be really interesting to see what the results of that protocol are going to be, which is exactly this question, right? Yeah, well, it's not, yeah. So it is, I think, so that's actually the point that Dr. Ram also made that in the studies in interlaced, it does not include patients with 3C2. It does include patients with 3C1, but it will, I think, also give very important evidence on the value of neuroadjuvant chemotherapy, because I mean, so far and after, especially also after the results from the Outback, there is no evidence of a benefit in, let's say, in all comers on adjuvant chemotherapy in the context of chemoradiation for locally advanced cervical cancer. And I think, so this interlaced trial will at least also give some new insights on the role of neoadjuvant chemotherapy, but outside of trials at the moment, there is no, let's say, good data to advocate that, but I am aware, and I think that's the point, that there might be other arguments on a case-by-case basis, and that could be a time interval that needs to be managed, for instance, or in very selected patients that you can have situations of the, what you just mentioned about tumor size problems in very locally advanced disease. And I think, again, that is maybe a little bit also towards the, let's say, the edge of such a case. So maybe it's also good to briefly come back to that question on would we want to confirm the nodal disease periodically? What is your view on that? We normally don't, but it's a good question. It does delay treatment, and I'm going to be honest, like we are so resource, we have so many resources, but it still takes us almost two to three weeks to get an IR biopsy. I'm going to be honest about it. And so it delays treatment. I think most cases is pelvic cancer, but there are cases where it may not be. It could be CLL, or it could be reactive. It could be TB, as in India's cases, right? So I do think, again, it is something that probably should be thought of. Again, I tend to push away from it just because we are having such a hard time getting the biopsy, but I mean, it's a good point, especially in areas where TB, HIV, right? If you have an HIV positive patient, they could be all reactive nodes and not cancer. So I do think it is a good question. And if it's feasible, probably the right thing to do. Dr. Matthews, any thoughts on that? Yeah, similarly, like in situations where you have a pelvic node positive disease and the PET test negatives, we need to realize that the data shows that the priority positivity can be as high as 20, 22, 23 percentage, but whereas if the pelvic node is negative and the PET is negative for pariotics, then the false negativity rate is somewhere around 12%. So having that concept helps us to plan our fields, like especially in our setting where we don't have, we struggle to get PET done for every patient. We can't have that. So this is something which guides our field, like whether to take a lower priority. So if you have a big pelvic node and we know the chances of pariotics being positive is high. So we place our field borders accordingly to include the lower priority. Yeah, and if I understand you correctly, Dr. Matthews, it's also, I mean, if you would have a case with let's say multiple pelvic nodes, especially at common iliac nodes, we know that the chance is very high that if we also see nodes at the pariotic level that they will be involved. And if you would get a result from a fine needle aspiration that's negative, would you then let's say exclude that part from your treatment field? Probably not. So I think that factors to take into account are the disease, the local disease and the presence of lymph nodes in the pelvis area that would also guide your decision. And if you would have indeed a more isolated lymph node in the pariotic region, you would look different towards such a question. But it's a good discussion. Okay, any additional comments on that Dr. Ram from your situation, from your point of view? Yeah, I think as I mentioned, if you don't have a significant pelvic node and if you find a pariotic node, we would tend to go ahead and do a guided FNAC to establish the diagnosis because of possibility of tuberculosis in our region. So I would, that's the only remark I have. I mean, if there is significant pelvic node and around 1.4, 1.5 centimeter pariotic node, then we need to consider that as a metastatic disease and plan our fields accordingly. Yeah, yeah. So maybe we could move on to another question that came also forward through the Q&A and that moves a little bit further towards the radiotherapy technique. And one of the question raised is What is the optimal nodal boost dose? And maybe again, we could start with our discussions. Any thoughts on that? Yeah, I'm going to answer that, or I'm going to try to answer that. I do think, again, this is, and again, Dr. Knott's a huge EMBRACE fan, so I'm going to comment on something that we have problems with when we were enrolling patients with EMBRACE. I do think there's a difference in nodal dosing. The periodics, I don't think you can go as high of a dose because you do have the duodenum up there, right? And I think your limiting factor is the duodenum. In the pelvis, we do try to push the nodal boost up to 66 gray, but that is a combination of external beam plus brachy. So I think where EMBRACE really does work where that 220 gets you to about 56, and you're hoping that the brachy will give you the additional, right? But if it's a bigger node than two CMs, that may not be enough. And those, I mean, those are nodes that you really want to take to 66. Problem is in the periodics, the duodenum is your limiting toxicity. And I think we, as GYN, radiation oncologists tend to push that more than the GI, right? We've done a paper where we have a dose of two cc's to 60 and 15 cc's to 55. That's really a lot higher than what most GI radiation oncologists take it. But I think in a periodic area, I'm not sure you can go higher than 60. And then the question is, is there a big difference between 60 and 66? And does it really make a difference? And I'm not sure it does. I think in my brain it does, but I'm not sure realistically it does, especially if we're taking the periodics to only 60. I'd love to hear what the panelists have to say. Yeah, maybe a quick question, just to understand how you do this treatment, because you just mentioned also the difference between sequential and simultaneously integrated boost technique. And also, would you take regression of nodal disease into account in defining what is the optimal dose to a node in a given patient? Right. So again, that's where, like I said, we had a little bit of problem with embrace when we were enrolling it. If we had patients who had two CMs or smaller nodes, then we did exactly what embraced it. So then we did the 220 a day, because the shrinkage really wouldn't have made a difference and you kept it, right? But if you have bigger than two CMs, we actually do sequential, and we do take regression of the node. And so then we take it at 200 a day, and then we resim, and then we boost higher. So that's what we do, because I think anything bigger than that, you do need to go to a little bit higher dose, and I do think they regress, and I think you get bowel coming in. So that was the one thing that we did, and that's our standard. We do look at the size. And Dr. Matthews? Actually, we struggle with even giving 45 degree with concurrent. So very often, boost is very challenging for us. So the maximum we go is with a SIP integrated boost to a dose of 55, and I think maximum 60. And personally, for one of the patients who I treated, where I went to 60, because she, to start with, she had lymph nodes as big as four centimeters in the pelvis, and she was very young. So I kind of slightly pushed the dose, and later on, very late, she developed a bowel perforation and sepsis, and we could save her, and she's still surviving, but with that experience, I kind of came down to 55 again, for my boost. And to the paramedic, the CTV is always only up to 45, and the GTV node gets a boost of 50. That's what I do. Thank you, Dr. Matthews, and maybe also to understand again, from your technique, because is it then, so you mentioned it simultaneously integrated. And what's also, I think, an important discussion when we talk about dose is volume. And we just saw some of the volumes in the case, where we have these different margins. So what is your approach towards these margins? For lymph node, you, so that is, in patients with very bulky, very large nodes, you actually have a scan taken prior to neoadjuvant, and then you give the dose-tense neoadjuvant, you have a planning scan after that. So I take the initial disease, and as the margin, and boost the whatever is remaining. So that is something which I do from a very practical implementation level. And what kind of PTV margin do you use? In that situation, I don't do a PTV margin. Okay, for the boost. Yes, yes. Okay. Okay. Okay. That's good. Because I think that is also something that is an important factor into our experience. And we just talked about when we go from the historic perspective, moving from 2D, 3D to more conformal techniques, that dose and volume are very important factors. And I think this is also very relevant for the discussion on the boost dose and optimal boost dose. And I think, so in general, what we try to put forward is that, if feasible, going for 60 gray is a good goal. I think it's important to comment that we do that with conformal techniques, and you have to have that also available then. So I think it's important to understand that these doses come also from experience with more conformal techniques. And that means that you have to have some image guidance also during treatment to allow for more reduced margins. Because for us, it will be like typical PTV margin of five millimeter. So we are quite narrow on these margins. And what is, I think, especially challenging if you have multiple lymph nodes that are, let's say, in a chain, more or less, still these boost volumes can become quite large. So then again, I think we have to think about how to do that in an optimal way. We have some literature data that also points out that residual disease after initial chemoradiation in the nodes of, let's say, one cm or more is, of course, it's quite logical, but a negative prognostic factor, also for the regional recurrence in this area. So that could be an argument to selectively patients that might benefit from a higher dose. So to strive for a higher dose. But having said, there is also not a lot of, let's say, high level evidence data at the moment on what is that optimal boost dose. So there are still some questions to be answered. And I think that also maybe is a bridge towards the toxicity discussion again, because you just mentioned, I think, a very difficult case, of course, to manage if you have these subsequent toxicities to manage in these patients. So maybe it will be also good to ask the question if there will be specific toxicities that you would want to take into account in such a situation where we do extended field irradiation with nodal boost also to, let's say, larger volumes. Maybe any comments on that, Dr. Gingan? Yeah. As I said, the toxicity, I mean, nausea and vomiting, especially with concurrent chemotherapy is huge, right? Especially nodal boost with larger volume. And we talked about this duodenal toxicity. The other thing in the pelvis that you have to worry about is your midline dose, right? And the bigger volumes that you have for your nodal volumes, the higher dose you're giving to your uterus and your cervix and vagina, which limits your brachytherapy as well, right? And which would increase your long-term toxicity. So I think all of this is, it's just, it's got to be such a patient by patient problem. I mean, and the reason why I emphasize duodenum is because I've had two patients who died of duodenal bleeds because I pushed the duodenal dose. I mean, so I had two patients that died. So, you know, and we had three almost in a row separately and they weren't all cervix. Two of them were endometrium, one was endometrium, one was cervix, and one was actually a recurrent ovarian. But those are just, you don't want a patient that you cured dying of toxicity. No, I think of course that is, you know, what we don't want to have happen. At the same time, it's also good to, you know, to be aware of experience, you know, in a broader context. And it's an important topic. I think you also raised related to technique and midline dose, because that is one of the advantages of doing this more integrated boost, of course, is that you can more elegantly make sure that this area around the central area where you do your brachy boost, that you avoid having these difficulties in, let's say, optimally aligning those from external beam and brachytherapy, right? Right. In fact, that's one of the reasons why we've actually moved, like I said, to the more, I mean, when we were doing embrace, we were using it, but even now post-embrace, when there's two CMs or smaller nodes, we're definitely doing the concomitant boost, because it does reduce your dose to the midline. And so it really does make a huge difference. And it really helps with doses. I mean, that is, we love it. You know, besides the shortening treatment time, it does, really does help limit the dose to the midline structures, which is so important. Yeah. So could you, one of the questions that's also coming in is what constraints do you use for the bowel? And maybe it would also be good to understand, are there any specific things also during the treatment and during follow-up that you, that you organize around the care for these patients with regard to management of side effects? Any recommendations? Yeah. You know, I think the big thing, I mean, I think one of the biggest, and I'm going to stop talking about everybody else type, but I think one of the biggest things that we do for our patients who are retreating extended field, is we do put them on an H2 blocker, right? And that, I mean, that's actually routine. Every patient is put on an H2 blocker. So that is, and that is anybody we're treating with extended field. So that is something that we do. And I don't know what everybody else does, but that is standard for us. And antiemetics? Oh, so everybody gets Sofran, you know, that's it. Yeah. I mean, that's for us is that Sofran. And that's what the chemo too, right? So we, everybody gets Sofran and compazine and they're told to use the Sofran, right? But I mean, I think the big thing that's a little bit different is we do put everybody on H2 blockers that we treat with extended field. Yeah. And, and do you see any problems on the longterm with regard to any dose in the pancreas, for instance, is there anything that you take? No, we haven't. Have you guys? We have not. Or have you noticed it in embrace? No. No, I know some anecdotal stories about, yeah, let's say pancreatic, yeah, reduced function. But that's just, that's very anecdotal, at least in my experience. But I would happy to hear also from Dr. Matthews and Dr. Ram on their experience. What we find challenging is diarrhea. And I think it relates to the amount of bubble, small bubble that's coming, that is receiving some dose. And so in our patients, especially lower nutritional status, and it is a huge issue. So if they are lose, start losing weight, so one of the things which I found very useful is to weigh them every week. And if they are losing more than 5% of their body weight to go slow on the concurrent, because otherwise they are not going to finish the treatment. So that is something which I found. And as ma'am was saying, we we put them on anti emetic, mild steroid. And prior to getting in on the in the first week, and subsequently, they they get adjusted. So the first week, it is important that they don't throw up much. So, so that the compliance is ensured. So first week we take care of H2 blockers, anti emetics and mild steroids. That is routine for all patients going on extended. I'm looking to the clock, and I'm just aware we have only five more minutes. And I saw one additional question in the chat that I think is relevant, and it moves to a bit towards follow up. So what would, how would we, would we image such, such a patient during follow up? And, and how would we do that? Any thoughts on that, Dr. Matthews? Do you have any protocol that you follow for imaging during follow up in these situations? Yeah, we do image once. So by the third, after completion of treatment, after two months, like six weeks after that, at least six weeks later, we, we, we do one imaging to see what has happened to the nodes. So that is... So directive, and what type of imaging for the lymph nodes, right? Yeah, what we do is we have a, we do MRI pelvis, and along with that, we do an abdominal screening. So, so to keep the cost in check, that is what we do. Yeah, okay. Okay. And, and Dr. Jingran, what are your thoughts on the role of imaging during follow up? Yeah, we always do a PET at three months. And depending on those results, we decide, but that's what, that's what we do. We do a PET at three months. That's our standard. And, and do you do that in all, let's say, locally advanced patients or in those that are no positive? Yeah, we do that in all of our services that we treat. They all get a PET at three months and pending those results, we'll decide when to repeat it. I mean, if they've had a complete resolution, we actually don't, we will do chest x-rays every year. But, you know, it's, I'll be honest, I also cheat a little bit. I may do a PET at two years again, right? Especially with patients with positive nodes, because you really do worry about those patients. Okay. So maybe, but maybe Dr. Ram, in your situation for such a patient, how would you do the imaging? Yeah, I mean, what Susan has shared some, the follow up of the surveillance similar protocol, but yes, we will do, again, based on the patients, we will do a PET CT as follow up, if, if it's possible. And I also agree with what Anuja made a remark, the patient is doing well. And somewhere around two years also, we do one more, at least a CT scan. And actually, we do annual CT scan on our patients who come for follow up. That's a routine thing what we do here. And MRI, we do documented at least three months after the treatment to assess the tumor response. And what Susan has just mentioned, we do abnormal screening to optimize the cost. Yeah, so we would just to give some perspective from our site, we would at three months image the focus on the local status more. So that will be an MRI to assess local tumor response. And in patients with, let's say, multiple nodal disease, in such a case, we would at six months or a year, also do imaging with a CT, just an ordinary CT scan of the thorax and abdomen to assess both nodal status, but also screen for, for this and metastasis at least one time. But normally, and especially also in non-negative patients, we do not routinely use imaging during follow up, we would be guided by any, you know, clinical symptoms and decide based on that, if there is any need for imaging. So I think on that side, we might be maybe more, yeah, conservative. But I think it's good to see to have that discussion. I'm seeing that we are at the moment now. Yeah, coming towards the end of the time that we have for this session. And I would like to thank all of you for attending this echo session. It was really great to see many, so many participants, and I hope we could provide some answer to your questions in the in the chat. And I was very thankful to Dr. Tempe for presenting the case, Dr. Ram for desolation, and both Dr. Matthews and Dr. Jingran also for their excellent comments in the in the case discussion. So thank you everyone. And I would also want to wish every one of you a good next year. Happy Christmas and all best wishes for next year. Thank you. Thank you. Thank you, Remy and Susan. Thank you. Thank you, Thomas. Yeah.

cervical cancer

node-positive patient

management

neoadjuvant chemotherapy

imaging techniques

PET-CT

nodal boost dose

toxicities

follow-up