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Good morning all and hope you're excited for a series of break talks that we have planned for you today. It gives me a great pleasure to introduce our first speaker of the day. Professor Julie, who's um I actually travel all night to be here on time this morning. And um she is a professor um of imaging at in college. She's a consultant radiologist. She has a huge number of publications and we m you from the Mercury study and A N A number of other studies following that. And um it's uh great to hear from you today about MRI on rectal cancer and also imaging in colon cancer. So, thank you very much. Thank you. And it's a great pleasure to be here. I have been to many GS meetings in the past and it's um it's really great to see the next generation of surgeons in front of me and um gives me great uh uh it's a great feeling to see you also. So thank you for allowing me to come and talk to you. Um It's, it's uh I feel very old in this room, but um I was thinking about it. It's 29 years ago, almost to the day that I um uh did the first MRI scan and a patient with rectal cancer on, on the magnet in Cardiff. Um It was a high resolution scan. It was the first time we were able to do a high res scan. And at that time, and for at least five or six years after that, this was the method of staging rectal cancer. It's a bit hard to believe for you guys. But in the MDT S, um the only thing that was, was being asked of for, for, in part of the discussion was does the, does the tumor feel mobile or fixed or tethered? And that was it. And that was the whole basis of the decision making process. And at that time, also, there were a number of uh randomized phase three trials running, one of them was um the CR 071 in the UK. But then there was also a Dutch TME trial 1997 around then that these trials were, were in their sort of peak and they were using digital rectal examination. So if the tumor was mobile, you could have short course radiotherapy. If it was fixed or tethered, you would have uh long course chemoradiotherapy. So simple. Why did you need Mr? So um it was a magical thing. Yeah. And, and you know how your, your finger is, I'm sure it's been doing more training over the years. Um So the problem has been, uh is that in the subsequent years, is there still huge variations in practice around the country? I think that if I was to ask you whether you think that at three N one tumor always gets radiotherapy, y you really know what the answer was. Cos it would depend on which MDT you're sitting in, um, um in Basingstoke or at Saint Mark's absolutely never in leeds. I think pretty much always they would get some sort of preoperative treatment. And so, um how do we get to this? Um And the questions that we, we have to ask ourselves is, are we sure that we're doing the right thing and offering the right preoperative strategy to patients based on the TNM staging system? And there are some other questions as well, which I think um there are a lot of kind of myths that need to be debulked. And hopefully this talk will help you a little bit with that because hopefully I'll give you some evidence base. So this is a typical thing scenario in an MDT. Um There's a lymph node close to the mesorectal fascia, either one, everyone sort of holds their breath. Um because it depends on what the radiologist is going to say about it. Um And I think also, so it depends on how the surgeon was interacting with the radiologist because if they asked that fatal question, could it be malignant? Of course, 100% they're gonna say, yeah, it could be. And, and then, oh, well, if it could be malignant, I'd better offer this patient preoperative radiotherapy. And before you know, it, this patient is, is down a, a pathway, but maybe they didn't need to be. Yeah. Uh, the other, I mean, the thing that we have to remember is that the original mercury study looked at this question and found it was really impossible for a surgeon to produce a positive crm from a lymph node. It's really difficult because you not only have to dig in past the mesorectal fascia, you then get to expose the lymph node capsule and its contents to the margin. It doesn't happen. So what is even the mechanism for a local recurrence from a an encapsulated lymph node sitting on the mesorectal margin? There isn't one. So it doesn't make sense to be panicking about an innocent juicy little lymph node sitting in the mesorectal margin. And in fact, that's where they like to sit. If you look at scans most of the nodes, if their distribution is around the posterior mesorectum. So um it's not a cause. So the the other thing you'll you'll get is an enlarged lymph node. Perhaps you'll see a report saying, oh, there are lots of enlarged lymph nodes, at least none of them must be malignant. Um And that I think has been the basis of the um ESG A guidelines and a lot of international guidelines but you can see how the variation would happen because it would depend on which of those six different philosophies. Um, a radiologist might be following in, in the MDT. Er, and that's a bit disturbing, isn't it? So, you have the one patient in like five different MDT S or six different MDT S having a totally different treatment pathway. The actual evidence base for this is, yes, is not that this patient benefits from chemoradiotherapy. And I'll explain that in, in a moment, but essentially to me and hopefully to most radiologists in this country, we should be saying that based on lymph energy, it's benign. It doesn't matter what size it's got to. And actually primary surgery would be the best uh option for a patient with, with only this is the feature that you can see. So the the it leads us to this whole question are, are lymph nodes really the main cause of spread in rectal cancer. We'd like to believe that it was. So it's, it's how we've been taught. It's what we've been made to believe that Dukes. This is the Gigs Club. This is, this is the man himself and why, why did he become so famous? It was because he did survival outcomes in evaluating specimens from the 19 thirties. And you promoted the idea that if you saw Dukes c cases, any patients with lymph nodes, they didn't survive their cancer, only 7% survived. And that was the basis for TNM for Dukes and everything that we've come to ever since. But that was based on specimens from 19 thirties. That was not what we do nowadays and it was pre T me and, but how often he did a Survivor outcomes analysis, which I think in those days was pretty rare for people to be looking at that in this detail. But that's what the surgery was based on. Um, that was what was being removed and no wonder, you know, GP C was actually a surrogate for really bad surgery. Um And nowadays, we cannot find that relationship between lymph nodes and local recurrence. We just cannot find it. It's not there because actually, when we look into this, both the size and number of lymph nodes are a favorable problem. Stop factor, the more lymph nodes a patient has, the better their immune system is in terms of coping with a, with a diagnosed cancer. It used to be said that this was some sort of surgical prior, I've, I've removed 100 and 50 lymph nodes. I must have been super, you know, it's not, unfortunately, I mean, it may be a little bit to do with how well you've done with the section. But actually, in a, it's the patient's immune system and the patients who have lots of, of lymph nodes in the specimen. Sure, it could be that you removed a very nice specimen. But more likely it's the patient's got a very good immune system and they were doing well. So, um, what we've found out from looking at these and following them up and we've got 100s and 100s of patients and follow up with this data. Now is that the M vi status of the tumor is much more important than the lymph nodes. You can see it so well and you can see it probably better than the pathologist is attention to it because if they less the vessels and the anatomy is less than the specimen, um actually, it's the technicians that do the cut up, they don't always look out for it because they're being trained to harvest lymph nodes. That's what they're meant to be doing. So, very often don't even get seen by the pathologist on the m microscopy. So we have to be really careful about imaging and pathology as the gold standard because it all depends on how well it's being sampled. But when we um observe patients who've got emv I, we see a clear pathway of spread and actually, it does explain why patients with rectal and colon cancer develop metastases to the liver as the main cause of death. That's, that's what you observe when you see the patients who don't survive. It's mostly that we've developed lump or ambo liver met. And you're sort of saying, well as a surgeon, what can I do? That's bad biology. But actually, there are things that can be done and and one of the things is identifying those patients and making sure those patients do get the correct preoperative treatment. Um So getting those patients staged, I'm thinking this about how closely we survey them if they've got the MRI and it doesn't regress after radiotherapy, those patients are at such high risk. We should be keeping a very close eye on them because when they do get their solitary live down the line, at least that can be resected and they can be um have some chance of surviving in their disease. So, we previously would see a blood like that. And you can see it's, it's different to a lymph node, isn't it? It hasn't got a lymph node capsule. It's tracking no longer a vessel. We shouldn't be calling it lymph nodes, but we did in the past and probably half of the things that we called lymph nodes were not, they were actual tumor deposits. So you should call it what it is. It's an extra nodal tumor deposit. It's yet a lymph node. Um We are bound by the TNM classification. So we have to call it N NC. But actually, it's nothing to do with lymph nodes at all. So this is a focus of discontinuous embi, it hasn't got a lymph node capsule. It's trying to no longer vessel. It's part of the mechanism of this sort of concept of tumor being able to bypass the lymphatic system head directly into the veins. And directly into the systemic circulation. Of course, these tumors um need to be very carefully resected. There's a pathway of spread, the only mesorectum that we need to pay attention to. And that is why it is useful to offer these patients preoperative chemoradiotherapy to shut down that pathway of spread both lateral and upwards. So what we see in the scans is tumor growing into veins, that's E MDI, but we will see them s of metastasizing, literally sprouting into vessels forming these tumor deposits. So when I, when I ask radiologists um about how you should stage or um sort of help them to learn how to stage II say you look at the tumor, you don't look at the nodes, you look at the veins, you follow the veins, you track them, you see what's happening along the draining veins of the, of the rectum. Because once you've sens aside yourself that the tumor hasn't found its way into the veins and hasn't from these nodules, you can, you can say, ok, this is going to be a good prognosis tumor, but you have to resolve them. You need high resolution anatomic scans, not diffusion weighted imaging because you need that contrast and you need the anatomic detail to resolve a vessel to see the signal void of that vessel and spot that that's a tumor deposit. Because you can imagine if that was a low resolution scan, that would just look like a round blob and you wouldn't really be able to characterize it as a tumor deposit. So part of the thing is to get the technique right as well. When you do look for these, they're very characteristic, they haven't got a capsule and they seem to be sprouting and forming these kind of comet tail um shapes and, and that, that's the basis of understanding tumor deposits. So the further bit of information that you've learned about is when you look at the clonal origin of the metastases versus lymph nodes versus not, versus the tumor itself, you find that the lymph nodes and the metastases don't have a clonality, they are not following the pathway. So the thing to say you go from tumor to node to metastasis is actually incorrect in the majority of patients with colorectal cancer. It is tumor bone metastasis. And if we now realize that then this whole focus of, of treating patients on the basis of TNM staging becomes a bit defunct because you're not really treating the patients at risk. So you, you've got a patient with a benign lymph node, but that's not the problem for that patient. The problem is those tumor deposits that are creeping along the vessel, look at those and you see them heading towards the mesorectal margin. You know that patients in trouble and primary surgery isn't going to help that patient. They need something preoperatively to prevent uh an onward pathway of spread. So human, because it's a quite simple concept. You look at the interface that the nodule that you're looking at makes for a vessel. If it's aligned with the vessel and it's forming a sort of comet tail, then it's a tumor deposit. If it's got a convex angle with the vessel, then it's a lymph node, it cannot be in the vessel. So that's, that's how we separate the two. So um when you start looking for them, it's amazing how often you see them, they're present in about 30 to 40% of newly diagnosed rectal cancer patients. They usually happen with the embry I, but you can't see them without the embryon um particularly in early rectal cancers. So sometimes you'll see at one tumor perfectly innocent looking, but then you'll see a tumor deposit because those tumors have managed to find their way and seed into the vessel system. So this is how rubbish the M system is you, what are you, you know, you're trying to say to the patient. Oh, I need to give you adjuvant chemo because it's gonna help you. But you can't say that that's not actually correct. It's not true. The survival between somebody who's lymph node positive and lymph node negative is there's no difference. So, so why are you having that conversation with them? But if you have a conversation with a patient where they've got venous invasion or tumor deposits, it's a different conversation. You're unfortunately in the red line and we need to do something about that. We can, we can try to push you into the blue line. And one of the things that pushes patients into the blue line is the post treatment scan assessment of those stage stagings. So if you go from em bi positive to negative, you go into the blue line. If you go from tumor deposit positive to negative, you go into the blue line. And how do you maximize the number of patients who go from positive to negative? It's not what you might think. It's not through chemotherapy. It's not enough to push those patients into the blue line. It is through giving chemo radiotherapy. And the what we're, what we're noticing is it's the radiotherapy, that's the most effective. So, so giving chemo first, you think it feels good because you're dealing with a systemic risk, you're not actually dealing with the tumor and its biology in the pelvis. So that's why giving radiotherapy first is always going to be better than um giving the chemo first. So, so the origins are not the same, the pathway of spread is not the same, but there's hope for these patients in that if you reverse their status before surgery, they will do better. So, I in a way what we've got to from that sort of uh the finger and the mobility is a whole sort of stratification. In rectal cancer, we can use the tumor deposits in the M bi status to identify those patients who need preoperative treatment and of course margin positive patients need need chemoradiotherapy. But I would also argue that the tumor deposit positive and embi positive patients do better with chemoradiotherapy than with chemotherapy alone or chemotherapy followed by radiotherapy. Um We should restage and the post treatment stage is more prognostically accurate than the baseline stage. So that means there is an effect of down staging and that is that does translate to an improvement in survival, but you won't, you won't see that in the normal trials because they're just giving everyone everything. And, and of course, there's a half of those patients with the T you know, T three N plus who were never going to go into, get into trouble because their lymph nodes were actually beneficial. And, and so you don't see a, a survival advantage from giving preoperative treatment to every single patient. You only see it in those high risk patients. So, um that's what we used to do. And unfortunately, that's what the nice guidelines tell us to do in 2024. So, um they've, they've done this because they saw that there was a wide variation and they thought that the solution to that was to just give everyone preoperative treatment. I think there's a problem with that in that we will not be able to advance our treatments if we keep doing that because we will not be able to highlight those patients at particular risk and to actually give them something more. Not only that we end up over treating a bunch of patients who are not going to benefit and we're creating problems for ourselves down the line with excess morbidity. If we follow these guidelines, you end up treating 80% of patients with preoperative treatment. That's just too much, it's too much of a resource drain. And also you will, you will see the complications of chemoradiotherapy and not just for the patients but also perioperatively. So um good, we know that imaging has a number of prognostic variables that we can use to make our treatment decisions. We know about CRM from the mercury studies. We we know also that if you reduce crm positivity, you effectively reduce or eliminate local recurrence. And Dino this afternoon will be talking about the beyond TME approach for those patients who still have a persistent involved CRM. At the end of their treatment, we also can see and I'll just show you the survival benefit. So this, these are patients who are EMV positive um at the beginning of treatment and who become EMV negative after treatment, you see their disease free survival improves. And this is what we're aiming for. We're aiming to maximize the number of patients who can be regressed through preoperative treatment. But what you also see is that the pathologists are not picking up those patients with persistently involved embi positive status. It's very difficult for them to see that. So, so imaging is actually a gold standard for EVI status. So, um there we go. That's TNM. That's Dukes. Unfortunately, we may have to lay him to rest in terms of staging. But what we are now seeing is that either tumor deposits or embi are a poor prognostic factor. But if you have both, that's the bottom curve, that's the worst of all. Um But if you're negative for both, look how good the survival is. It's about 80 to 90%. So that same applies to the pelvic side wall lymph nodes. If you look at those nodes, we see that those patients um they will have enlarged lymph nodes. But if you have tumor deposits, there is a different pathway of spread. This is not a lateral pelvic sidewall lymph node. This is vascular invasion. You can see the comet tail, you can see the vessel signal void around it. That is something very different is removing that on its own, going to prevent that patient from coming to harm in the future. No, you're going to have to do a full pelvic sidewall clearance. It is because this is a whole pathway of spread. It's not just an isolated nodule. It has found its way into the vascular system of the pelvic sidewall compartment and removing and plucking out that lymph node doesn't really get you any further to curing that patient. Actually, the better treatment is to offer radiotherapy and to make sure you can obliterate that pathway of spread. So that's how we think of lymph nodes. They're doing a good job, they're trapping the cancer, they are prognostically favorable and the tumor deposits, the embi are the villains. And that's what we have to think about um in terms of the, the way in which we stage and stratify patients. So when we look at um this is work by Jess Tan and it continues on from work from Amy Lord who did this work on tumor deposits. But she's looking at the lateral lymph nodes and we found that actually uh lateral tumor deposits um are the prognostic important um lesions that we need to look out for. They're quite rare um out of the 100s and 100s of patients, we found we saw 15, but it, those are the ones that may benefit from AAA rigorous and aggressive preoperative treatment strategy. So the the sort of algorithm really is is are they lymph nodes, are they tumor deposits if they're tumor deposits, radiotherapy and if they don't respond to the radiotherapy, then a clearance of the pelvic side will probably by an exenterative surgeon is, is the better way of managing those patients. So um I think I will finish this bit of the talk cos I don't think there's time for me to talk about post treatment assessment, but um I'll skip forward um and take some questions if, if um if you want before I do my next talk. Any questions from the floor? That was fantastic. Thank you so much. Um If we're putting Dukes to rest, when are you bringing out the Brown classification? Yes. So, in fact, we are um about to launch Mercury three, which is exactly 30 years, well, 30 years since my first MRI scan. But um that will be um a national study. Um And what we're going to be doing is comparing the prognostic accuracy of TNM versus T DV in a multicenter prospective study. But what we will do is as part of that is each center will give us the staging of the 2019 patients so that we can immediately say what's happening from that 2019 cohort and then prospectively validate the use of T DV in the, in the 2025 cohort. So that's mercure will have an answer. I think that should take 18 months to give you an an answer that TNM is no good and it needs to be laid to rest. But we, the arguments against TNM have been about reproducibility, sorry against T DV, have been reproducibility. Not every radiologist can do this la la la la blah, but actually, I think it's deeper than that. It's, it's what the M DTs do with that information. So if they're presented with TNM and they're presented with T DV at the moment, they still feel obliged to act on TNM, even though in their minds, they know that those patients with the EV are going to do badly, but they, they feel a bit constrained about any kind of guidelines to tell them they must give um preoperative treatment to those patients. So we're, we're doing a two pronged attach. So it's not just the radiologist, it's the MDT decision making. And we're going to see if, if implementation of T DV changes those decision making processes as a result of seeing their own and patient outcome data and whether that changes their minds in, in terms of their treatment, I sense there is AAA Duke's name change coming if the Dukes being sent T to TTV. Yeah. Thank you very much for excellent talk. Uh I was just wondering in those slides uh somewhere you mentioned uh quite rightly that the lymph nodes makes sense. Now does t three other class ABCD? Yes. Um If the person does not have the lymph node metastasis are embi positive. Does C and D qualify for? Yeah. So yeah, that's a really good question. We haven't. So on multivariable analysis with, you know, 400 patients when you, when they were negative for tumor deposits and embi just having five millimeters or six millimeters of spread was not in itself enough to put them into the poor prognostic category. So it does seem like probably what's happening is that the tumors that have managed to spread more than five millimeters have also managed to find their way into the veins. So there's, there's a big overlap with those. So in other words, if you can identify patients who, who've got tumor deposits and the MVI, you've identified the poor prognostic group and there isn't anyone else to find as it were. Ok. Um From the T three CS and Ds. And then another thing on the slides, as you mentioned about T one T two cancers and then you mentioned that um if they don't have tumor deposits, it still, you said local excision and then post accessioned plus minus. I didn't understand that. Yeah. So, so that, that's, that's another trial. Actually, that's the preserved trial. Uh which we are, we are running in, in about 20 or 30 hospitals in this country. It's just starting. So we opened our first site last week. Um The, the p the purpose of that study is to, is to confirm that if you identify an early rectal cancer, even if you've got lymph nodes in the mesorectum, that they're probably doing a good job. So, having done the local excision and with a deep clear margin, you, you can have a conversation with a patient about surveillance versus adjuvant radiotherapy at the moment. A lot of places are giving these early rectal cancers radiotherapy in the belief that you can get them into a complete response. But actually, it only happens in half and in half of those they regrow. So you're not really doing as well as if you just remove them surgically by local excision by a full thickness thames or Tamas type procedure. Um So that, that, that's the basis for, for that in the algorithm as it were. Yeah, just last thing. So when we remove the specimen for Tamus, yeah. And if that is specimen, which is a thick, full thickness especially does not show embi right? Are we quite confident enough to say maybe it's not involved and the provided the MRI was negative? Yeah. So I think, I think you can allow those patients to have the benefit of the doubt because the old data didn't put those patients through any kind of surveillance. They, they came back, you know, years later with a recurrence and nobody was keeping an eye on them. So I think if you're if you're willing to put a patient through radiotherapy and a three monthly watch and wait program for at one or at two cancer, then it should be even easier to do it where there's no no tumor left. And actually the risk of them recurring is very low. And actually to move that to a say six monthly MRI instead of three monthly and just keep an eye. Um You, you can have a conversation with a patient if they've got a lot of tumor budding intramural vascular invasion as to the benefit risk of giving chemoradiotherapy preemptively or waiting until something pops up. Um You know, I think the thing is is that we've learned from watch and wait in post chemoradiotherapy patients that you can monitor the mes or rectum. And, and that's something that I think we should be more comfortable with because there's nothing more disappointing than doing a local excision, doing it really carefully doing it really well. I mean, the pathologist tell you there's all these high risk factors removing the entire rectum only to find there's nothing in the specimen. It does not give you a good feeling. And um I think the patient is even even more disappointed. So I think we, we need to sort of shift our, our, our boundaries a little and think about the use of surveillance in that setting. OK. Can I ask a question as well? I know you work through the Orico and how fantastic it is to get all the MDT people involved. Um How do you think the oncologists are responding to all of this? I think the, the very open minded, I think, you know, oncologists are great because they need data and they need evidence. And if they are having a conversation with a patient and there's evidence that TNM isn't prognostically useful, they're not going to be comfortable saying we should give you preoperative chemo rads. They follow the guidelines and those guidelines are evidence based. But if we change the evidence base, if we, if we change our prognostic accuracy to say that TNM is inaccurate and T DV is accurate, then then they've got a basis for saying, well, we've got a system here that doesn't give you an any evidence that this thing is gonna help you. But here we've got something that we know you're at high risk and we should treat you accordingly. Any other questions looks like I'm the only one with the confusion. So regarding this Oreo thing, I've been to a recent Orico meeting in Scotland and uh after passing exam, I thought I know about the correct cancer and I got all the concept, right? But going to that MDT meeting it confused me more. Yeah, all the oncologists in the room were like saying different things and everybody was coming up with the data to support their argument. Yes, literally four or five of us who recently passed the exam were confused more than anything else before. So I think they were adamant for the first time. All those oncological treatments that has been happening in the past somehow work for them, not work for others. They don't know how. Yeah. And and that I think is the problem with a lack of a prognostic biomarker, but we have them. It's just we need to prove that it's a something that can happen in a multicenter setting. And B that the MDT can show a change in treatment decision making processes that, that actually improves outcomes for patients. So at the moment, there's no difference in survival for patients who you irradiate for T three N one versus those who don't, it makes and it makes no sense. And that's why you're seeing all this variation up and down the country. So once we prove that with Mercury three, hopefully things will start to make sense and, and people will, will have an evidence base to make those statements and, and decision making. Great. Thank you. Um Shall we move on to? Yes. So, oh, not that one. I wish I could talk pal out loud. So we're going to talk about colon um CT staging. Um And it, it's kind of very similar to, to the rectal ones. So, and I think Jordan very um cleverly pointed out that once you've understood the rectal concept, it does, it's not so much of a leaf of faith to, to move on to colons. But actually, um it's interesting with colons because the, the colon survival is now poorer than rectal cancer survival, which is very mystifying and that we do probably need to think about stratifying treatment. But also we need to think about the prognostic factors that we understood in rectal cancer and whether that applies to colon cancer. So we've got all this range of treatment options in rectal cancer that we talked about, but there isn't very much for colon is there. Um And the, the problem I think is that there's always been this obsession again about lymph node staging. And also the fact that CT isn't, isn't as good as MRI in staging um cancers because you haven't got that sort of resolution. Um But you can still have an assessment of a primary tumor. And I just want to go through some of the evidence of how we would do that. So here's an example of, of a good prognosis, early stage T two, T three tumor. We're not really interested in knowing whether it's T two versus T three. We know that if it's not gone out a fair distance, then it's going to be a good prognosis tumor. And we also know that if it hasn't breached the peritoneum, it's also going to be a good prognosis tumor. So we can, we can see the peritoneal reflection on the CT, we can see whether the tumor is on the mesenteric border or on the um on the peritonealized surface. We can look at where the invasive border is. And for example, here it's on the um peritonealis surface. So that tumor is definitely at four, we can see also that there are vessels draining these colon tumors. And we can see when they're expanded irregularly by a tumor. So tho those things are possible and when you look for those things, and then again, instead of measuring the size of lymph nodes, but instead looking at the tumor and the veins, uh you start to, I identify the high and the low risk factors. So we, we started doing this a long time ago back in 2006. And we, we basically stratified patients very simply based on tumor spread more than five millimeters and em V present or not, the lymph nodes we knew was gonna be inaccurate. And that, that proved to be the case. But, but the, these were the two criteria that we sort of clung to and it on pathology, it did rather well, this good and poor prognostic stratification. But on CT, it also did very well. Now this is different to Foxtrot, which amalgamated all the T three tumors into one category. If you actually separate them like that in and look at the depth of spread, you do get a prognostic separation. And although it doesn't agree with the pathology 100% it's still performed in terms of prognostic accuracy. So, um the main thing is that what we saw was that if you saw tumor spread beyond the muscularis more than five millimeters or you saw it along the peritonei surface, there was only a 53 per cent three year survival compared with 87 per cent for the T one T two and less than T three. And this is, I suppose the basis for what we should be doing in terms of preoperative stratification, whether or not those patients are going to benefit from a preoperative treatment strategy is another matter. So, so here we've got an example of tumor growing into a vein which you can see and again, with CT, you've got the advantage of multiplanar, you can look at it in different aspects and you can see if the tumor is growing into a vessel. Um So the, the traditional mindset was that um you know, just operate um and you wouldn't necessarily be able to stratify these patients. But I think we can now think about a preoperative stratification and potentially the use of preoperative chemotherapy in those patients. And, and the same as in rectal cancer, we can look at an alternative staging system to TN MTD V. Again, tumor tumor deposits and EMV I and the high risk group would be those patients with tumor deposits and with the M VI and what if you could look at this on the CT routinely? And what do you do in terms of how does it perform compared with TNM? So the way in which we, we look at this is we look at the cancer, we look at whether or not the tumor is invading along the mesenteric or the peritoneal surface, you look for the invasive border and you measure the depth, you then look at the vessels and whether or not there are tumor deposits. So um if you, if you look at something like this, you're basically looking at the tumor itself and then whether or not vessels are expanded by, by tumor growing directly into them, it's a lot of noise on CT, there's a lot of normal vessels that are quite difficult. But if you have to see definite sort of expansion by the tumor of those vessels before you can call it the MV. So something like that, which is definite and it's a regularly expanded and a tumor deposit, which is uh growing along the course of the vein. Those are the things that we look out for. And it's the same principle as we see on the MRI, if you've got this acute angle against the vessel, then it's a lymph node. If you've got this um obtuse angle as it were, and if it's following the course of the vein, then it's a tumor deposit. And so um it, we can test that and we can look at the difference between the tumor deposits and the lymph nodes on imaging. And we published this in, in uh this was Nigel's work and um we did this um based on about uh more than 300 cases. Um And what we found was um we, we compared rather like we're gonna do in mercury three, the performance of TNM versus the performance of T DV. And same, same thing, you know, it doesn't work, it doesn't work in MRI. It doesn't work in CT either CT TNM staging isn't prognostically accurate at all. There's no difference in survival. Um But you see a survival difference if you use the T DV classification. Um So again, what, what we noticed was, in fact, the tumor spread of less than five millimeters could be superimposed on the T one and T two colon cancers. They were almost identical survival and the patients with tumor spread of more than five millimeters or the T four tumors had a different survival. So that, so in a way, it doesn't really matter if it correlates with pathology, you've got a survival difference and you've got a prognostic accurate method of stratifying patients and on multivariable analysis, the, the only things that really matter are the EV and the state of tumor deposits on CT. Um And we've now done this on the colon cancers, on the right colon cancers. And uh just to say that um if, if you look at it in, in colon cancers, what's, what's very interesting now is that the CT stratification stops being prognostically accurate. In other words, there's no difference in survival using T DV in those patients that go undergo CME surgery. So in other words, there's a prognostic feature that shows up in all patients with colon cancer, but in the group that undergo CME surgery, it ceases to be as important. So it's, it's positive proof that the quality of surgery in colon cancers is a major feature and a major factor for preventing both local and distant recurrence. So, um what what I would say is I think TNM has to go to bed for, for both colon and rectal cancers that T DV is going to be useful in colon cancers mainly so that you are aware when you're surgically planning how it is to do a really careful dissection plane that doesn't disrupt the vascular drainage of these colon tumors. And that removes the whole of the mesentary intact with, with including the, the veins that are draining that colon. And, um, when you produce a specimen like that, it seems from the data that the risk of that patient having a recurrence is dramatically reduced. Um So, II think that sort of makes the case more for surgery than it does for chemo upfront. But we'll, we'll probably need to test that in the future. Thank you. Um Thank you. Very interesting. Couple of talks actually, um the slides a couple of slides ago where you were um looking at the T three A and B versus T one and two was that irrespective of the tumor deposit and the EMV I status was that just literally looking at the T stage? No. So those, those were patients who um I'm just trying to remember, I think the, these were just T one and T two, irrespective of the tumor deposits. Yeah, so, but on multivariable analysis, I think the thing with colon cancers is that you tend to only see these tumor deposits in the more advanced in the more T three. So, so that's why it knocked it knocks out the T three C and D in the multivariable analysis. Um So you almost say it's just at stage. And that's, that's the only prognostic indicator you need it. In fact. Yeah, the, the um the favorable prognostic indicator is, is limited tumor. So tumor less than five millimeters. So you can breathe a sigh of relief when you see a tumor like that. And the unfavorable prognostic indicator is e vi tumor deposits because you're more likely to see them in the more t more advanced t three tumors. But in a good prognosis, T three sort of more than five millimeter tumor. If there's an absence of embi and tumor deposits, they're also going to do well. So yeah, it, it, it's a sort of combination of the two. Yeah. Thank you. Mm Hi. Um uh Thank you very much for elaborating the E three stage in colon cancer. I'm not sure like, how do you see T three ABCD? Yeah. On a CT scan. Is there a program that you use? Because I asked this question, reading one of your papers. Yeah, you are radiologist and they're like, oh, med is like two or three. Yeah. No, I think that it is literally that um when you are saying something is T three A tumor, it's literally the muscularis is effaced. You can't, you can't see the edge of the, you see the edge of the tumor, but you don't see it projecting beyond the muscularis. So there's going to be an overlap between T two and T three A. We know that it's the it's the five millimeter cut off. So if you're seeing a tumor that's extending more than five millimeters, that's, that's the point at which you start to be concerned about it being a high risk tumor. And then you, you also look at the vessels and whether or not there are tumor deposits. So in, in other words, there's a sort of incremental, worsening of prognosis in, in how you're looking at these tumors. So if you, if you're satisfied that it's confined to the colonic wall, the chances are you're not gonna see tumor deposits, but you check in case and usually you don't see them. Um If, if it's more than five millimeters, you look really carefully to see if there is um also E vi. So in a way, it, it's, it's very binary. Is, is this a good looking tumor or is this a bad looking tumor? And, and usually you can do that quite well on the CT. Another thing like those guys who are doing the CM E, they still believe this is a totally different perspective that you just highlighted today. Those who does do the CME, they believe because their lymph node yield is great. That's how the CME works. Yes. Now you tell us that, yes, maybe the tumor deposit, maybe the vessels coming through. Yes. Three different concept. I think those guys who are selling CME, they don't sell, no, they sell it on the right basis. But um Nicola Nicola Hodges is the um research fellow who's been doing this work. She's just submitted these, these papers for publication and it, they're the only, it, it's probably the first result to show that CME is a prognostically important operation in the high risk patients. But across the piece, there's no difference in survival. So in other words, if you look at all it a bit like um radiotherapy and T three tumors. If you do a CME in all the tumors, there's no survival difference. But if you, if you look for the high risk tumors, you see a benefit in the, in that group. So in other words, people were getting away with non CM E surgery and having good survival in low risk tumors makes sense. What, what is the role of chemo in colon cancer then? Well, exactly. We don't know. I think we're going to have to start to start a starting point of CME in high risk tumors. What is the added value of chemo in that setting? Um And II know I'm not sure that we'll necessarily get an answer from that if the CME is, is, is as good as good and as effective as at removing that risk as we can see from those survival curves. Thank you very much. Thank you. I think there's one more question. Two more. Hi. It's just about the CME statement because that's quite a big thing for us actually that correct surgeons. Yes, you say there is no difference in the overall survival. Is that correct or am I just? Yeah. So this was, this was a group of patients with right colon cancers which we know that that from previous data, the right colon cancers for some reason were doing not as well as left colon cancers. So what Nicola looked at was the um outcome of those patients having um CM E versus non CM E. So she looked at two populations of patients. One was in ACM E enthusiastic Center and in another where they just didn't worry about it. Um And what she found was that the two cohorts, if you just looked at them as, as an entity, there was no difference in survival. However, when you, you looked at them by the T DV stratification, both on histopathology and on imaging, the patients who had non CME operation T DV was prognostic. In other words, about half of those patients developed some sort of recurrence or metastatic disease in that same high risk group of patients having CM surgery. There was no difference in survival between TV, positive and T DV, negative patients if they had CME. And how big were these two groups? And was it like statistically, yes, it was the, the it was statistically significant. So the survival curves are, are the hazard ratios were significant. So, and, and that's what's interesting is the fact that you, you saw this powerful difference from CME surgery in T DV, positive patients when he would be very happy to hear that when he would not. Right. That's why. Thank you. Yes, I think there was a gentleman. Thanks for, for the talks. Um My question is about rectal cancer if that's ok. So, um just with regards to tumor deposits and em versus lymph nodes, um are you advocating that um if there is obvious enlarged lymph nodes, even if they're close to a crm in at one or t two tumor in the absence of vi they should go straight to surgery. Is that how? Yeah, I II would suggest not only that, but it's a favorable prognostic feature. So the more lymph nodes you have and the bigger they are, the better that patient is going to do. And, and actually, if it's at one tumor and you, you undertake a local excision and that happens to be enlarged lymph nodes, it shouldn't be a reason to panic. You know, when you follow those patients up, you find that those lymph nodes are still sitting there and they sit there for 20 or 30 years. So it's not really. Um I think that we, we overestimate the importance of lymph nodes in recurrence. Sure. They may, they may harbor tumor and eventually the tumor may overcome the node and grow beyond it. But that takes time and it doesn't always happen. And that's the thing is, is, do you want to prevent something that you know, may or may not happen or do you want to monitor it and do the thing when you actually can see it happening? So, so that's the beauty of, of surveillance really is that you, you don't have to think about a risk. You can actually look for that risk and see if it becomes a reality. So, just to follow up and what about adjuvant chemotherapy for people with lymph node positive disease in the absence of other uh high risk features? Yeah. Well, the, the, the the clinical trial, I mean, pharma is, is kind of pulling out of rectal cancer a little bit in terms of adjuvant because there's never been a survival impact from the use of adjuvant chemo in rectal cancer. Nor has there been a survival impact in the use of preoperative treatment in rectal cancer? So if you do a a one size fit all approach and you put all these patients who are never going to benefit into a trial, you wouldn't be surprised that there's no benefit. And you know that the same cor with, with cm, you know, we're all, you know, we instinctively think it's a good operation but the proof is lacking. And, and, but if you, if you look for the high risk cases, you find that there is a benefit from these treatments and, and that's what that's the only way we can move forward is by, by really good staging and really good stratification And at the moment TNM is not really fit for purpose on that. Excellent. Thank you. I just have one more hair as well. Thank you. That was really interesting. Um I was just wondering, oh, maybe here. Um How long do you think it will take for things to change? This is very revolutionary. And I think what you explained about the Mercury three trial was really interesting and getting everybody on board. What's your kind of idea of a timeline? Ok. So we've got funding for the first bit of the trial and we're going to put it through ethics in October November. We're going to have all the sites and we'll invite everyone that's on our email list. I'll forward it to the Dukes Club um to attend a kickoff meeting probably in January, February. During that next year, we will collect all the 2019 data. We will stage it using TNM and TV. And we will also collect the five year follow up data having proven that TNM is no good in a multicenter setting versus T DV. We will then um ask the radiologist to score cases each to show that they can do T DV better than TNM and that they're more prognostically accurate. Once we've done that, we will approach all the MDT S that have taken part in this study with their patients. So we'll have a stakeholder meeting to say, what would you like to follow the nice guidelines or A TDB stratification will allow the MDT S to make their own minds up based on the evidence they see before them. That will happen maybe halfway through next year, depending on how quickly we can get the sites enrolled and opened and then we'll do a six month change in implementation. So each MDT implements their treatment strategy. We will look at the resource utilization how much radiotherapy is being used, what the patients think about the the staging information they're receiving versus how it was before. And then if as we predict TV proves not only to be more prognostically accurate, but actually is more easily implemented in the MDT S and the patients accept those decisions better than previously. Maybe by the end of next year, maybe we, we we will have a change. Um But I think those changes will happen over the next 12 months because we're gonna be training the radiologists and also informing the MDT S of their own patient outcome data. Because that's one of the things that I think is a barrier is is it's, oh well, this is only just expert centers, blah, blah, blah. But actually if, if we show it in the smallest DGH to the largest teaching hospitals that it can be replicated in the same way that we did the original first Mercury study, then I think people will accept the change quite quickly. Thank you. We have one final question. Thank you very much. Um I know we were short of time. But first, do you, do you believe that we have the CT quality, the quality of the CT scans are standardized across the country or do we need to do something like MRI scans to look at the tumor deposit? And the Yeah, I think it's a really good question. Um One of the things that we are also going to be studying again in the next year and Nicola and, and the group at Saint Mark's will be, will be leading on this, I think is, is the question of whether CT colonography CT C gives you a better quality image for staging these colon cancers than an ordinary CT our subset of 50 patients. And it wasn't enough to, to really make a firm conclusion, suggested that the CTC was more accurate, more prognostically accurate. So we, we, we know that some hospitals and one of the hospitals that we're, we're chasing down is stoke who routinely do CTC um against um normal CT. And if we can prove in, in more than a few 100 patients that CTC is more accurate, then that may change the way in which patients are staged. So they may go straight from, you know, suspected two week wait list of, you know, uh high risk instead of going to colonoscopy, they may go to CT C for staging and prognostication followed by a colon um study. And the my understanding now of the CM E and the um the tumor deposit is, if you don't look for it, then you better do a ACM. E I think the difficulty is, is, is persuading people to do that when, when, you know, maybe they have qualms about it. So I think providing the evidence base by better staging will, will enable us to uncover the fact that those patients who get the CM E or having a better survival. Um And if we can do that, then it's more likely to gain acceptance. Um II II, I'm aware of, you know, there's enthusiasm, but there's also a lot of, you know, reluctance to take on C So, thank you. Ok, great. Thanks.