Dana-Farber’s Young-Onset Colorectal Cancer Center's Gut Instincts series continued on Monday, September 26 with an educational workshop on Best Practices for Rectal Cancer. Topics include chemotherapy, advances in radiation and its side effects, surgical management of rectal cancer and a patient's perspective. This webinar is for healthcare professionals, patients, and supporters.
Hi everyone and good evening welcome to the next installment of our gut instincts webinar about young onset colorectal cancer. I am kimmy and I am the director of the Young onset Colorectal cancer center here at Dana Farber and I am pleased to present a session on best practices in rectal cancer today. This is a field that has really moved along quite quickly with fortunately a lot of different options for patients now. So I hope you find this informative. Just a couple of logistical questions. This zoom is in a webinar format so you won't be able to see each other except for the panelists on the screen and if you do have questions that you think of during the session please enter them into the Q and A uh part of zoom and we will address all of them at the end. At this time I'd like to introduce our panelists and have them tell you a little bit about themselves. So first dr slater Hi, thank you for joining us tonight. My name is Sarah slater. I'm one of the medical oncologists in the gastrointestinal cancer center at Dana Farber. I'm the person on the team that gives chemotherapy. Thank you for joining us. Dr martin. Hi there, my name is Neil martin. I'm a radiation oncologist um and I'm going to talk a little bit tonight about um some advances in how we deliver radiation. Some of the side effects about radiation. I'm excited to join you. Thank you and Doctor Melnichuk. Hi um, pleasure to be here. My name is I'm Colorectal surgeon at Dana Farber Brigham Women's Hospital. And I'll be talking about surgical management of rectal cancer. Thank you. And then Lauren. Hi I'm Lauren already. I am by day a clinical researcher in in cancer within biotech but I'm also a stage three colorectal cancer survivor. Thank you for being here. Okay without further ado let's get started. I think dr slater is up first. Okay thanks kimmy. Um So we're gonna be talking about chemotherapy and radiation therapy and surgery and there's gonna be a little bit of overlap. Um But we're gonna try to blend this together in a way that makes sense for everybody. So when we think about rectal cancer we're thinking about adenocarcinoma of the colon that occur at or below the peritoneal reflection And the absence of the visceral peritoneum means that there are fewer barriers to progression and rectal cancer accounts for about 30% of all colorectal cancers but it accounts for 40% of colorectal cancer deaths. So a higher percentage than you might expect. Next slide for locally advanced rectal cancers. Tri modality therapy has become the standard of care and we say try modality therapy. We we mean radiation often in combination with chemotherapy, surgery and Adjuvant chemotherapy. Um So all of those work together in order to decrease the risk of recurrent disease. Next side the conventional ordering of these therapies at least in the last couple of decades. Um has been for uh has been utilizing radiation and chemotherapy prior to surgery. So either long course um or short course radiation therapy, which dr martin is going to talk a little bit more about a surgery which is a total mess, erectile excision, either a low anterior resection or an abdominal perennial resection. And then followed by um systemic dose chemotherapy. Um That's usually given over a period of four months and that's um a regimen that we call full fox or an equivalent regimen that's known as box Next slide. And so that's sort of been our standard uh for the last couple of decades or so. Um And in the recent past there's been an interest in in utilizing what we call total neo adjuvant therapy. So that is um moving all of the treatment before the surgery. So the radiation therapy uh whether or not that's combined with chemo, the systemic chemotherapy um and then taking the patients to surgery. Um And you know, there are different reasons for considering this, one of which is that patients who undergo. Um This total neo adjuvant approach tend to have are more likely to have a complete clinical response to therapy. Um I should say that that's different than a complete pathologic response. Um And I think dr melnick is going to touch on that a little bit later in the course of our discussion next slide. Um So when we think about total new adjuvant therapy um uh We do not yet know what the optimal sequencing of these interventions is. So that hasn't been established at this point in time. Um The options are to do chemo, radiotherapy chemotherapy. Then surgery to do short course radiotherapy chemotherapy. And then surgery or chemotherapy radiotherapy. And then surgery. Um We do know that for patients patients getting their chemotherapy before surgery tend to tolerate tolerate that chemotherapy better. Um and are more likely to complete their chemotherapy. Which makes sense because sometimes patients will have complications after their surgery. Um Maybe maybe frailer may just may not be able to tolerate chemotherapy as well. And so when we're thinking about when to employ this this approach um We we take that into account. Um We also think about this when we know a patient has a larger tumor um where they may have a high risk for a positive margin at the time of surgery. So those patients may benefit from upfront chemotherapy and radiation therapy um in order to shrink the tumors down um and improve the surgical the ability to do a complete surgical resection. Um And and there are patients also that we worry about the possibility of micro metastatic disease. So disease that doesn't show up on our staging scans. Um but that we have concern given the size of the tumor or other factors such as an elevated C. E. A. That that might make us worry about micro metastatic disease and then one of the potential benefits of TNT. Although this is not a standard of care at this time is thinking about allowing for for organ preservation. Um So next time um this is just another slide sort of comparing or or comparing the two in how we might think about it when we're trying to make decisions. Um I think at the end of the day um whether we decide to do TNT versus the conventional approach to rectal cancer really depends on the clinical scenario. Um T. N. T. Is as as as I stated, associated more often with a complete clinical response. Um And TNT may allow for organ preservation. So consideration of sphincter preservation or um avoiding um operative management altogether. Um And is favored because it's a shorter duration of time and and cost. Um But the the data at this point doesn't show any benefit in overall survival. When we compare the conventional approach to a total neo adjuvant therapy next side. So you know when we've talked about um giving chemotherapy before surgery, the question that we often ask is you know would more chemotherapy do better. So if we intensified the chemotherapy regimen before we take patients two surgery um would that be associated with a better outcome? And this is a slide from the british study which compared two groups of patients with stage two or stage three rectal cancer. One group received a more intensive regimen of chemotherapy in the preoperative setting. Something called full fear knocks. Um And this group was compared to a standard of care group. So a patient population that received chemo radiation followed by surgery and then adjuvant chemotherapy. Um And what we saw from this study is that the primary endpoint, which was disease free survival at three years was better with TNT, but the the overall survival was not impacted. Um And this is the study was problematic um Uh in some ways because we we saw that um the patients in the intensified chemotherapy arm were more likely to get their chemotherapy. So 92% of those patients actually finished their neo adjuvant Your inbox um in the control arm we found that only 80% of the patients actually received any adjuvant chemotherapy at all and only 80% of those actually finished their adjuvant chemotherapy. So I think that it's it's difficult to compare those two groups. Um and so I don't I don't know that this this actually answers the question of whether more chemotherapy is better. Um But I definitely think that that more and more um we're thinking about utilizing this more intensive regimen um for patients who again we feel like can tolerate a more intense chemotherapy regimen and again who were looking to to try to downstage as much as possible prior to surgery. Um next slide. Um the last thing I wanted to touch on before we move on to the radiation portion of this discussion is the trial, the rectal cancel trial that was published in June in the New England Journal of Medicine. Um this was widely reported in the newspaper and on TV um and widely reported because the the patients um that were included in this trial all had 100% clinical response rates to the intervention. Um so this is a small group of patients less than 20 who had rectal cancer which was locally advanced. Um that was mismatch repair deficient and they received neo adjuvant immunotherapy, a drug called Starla Mob. Um and that was for six months. They did not receive chemotherapy and all of the patients in this trial were shown to have a complete clinical complete response. Um and this is this is early on. So we don't have any long term data for how these patients Um will do and whether these patients may require surgery in the future. Um and obviously this is this is very exciting because in oncology we never see 100% clinical response to anything. Um But I think we also have to be um careful about extrapolating this to to our other patients. So, so you know, we see mismatch repair deficient rectal cancers. Um about 5 to 10% of of the rectal cancer population. So it's a very low number of patients for which this might be a treatment strategy and uh it is exciting and I think we want to follow this data and and see how things evolve over time, but this might be a very important approach um to patients that do have mismatch repair, deficient rectal cancer and something um that will be probably talking about in future conferences next slide. Um so again, just to summarize um um briefly, when we think about utilizing TNT versus conventional management for rectal cancer, I think for most, most of us would still utilize conventional um uh sequencing of therapy for smaller tumors because a smaller tumor after surgery may not require the addition of chemotherapy. And so if we can avoid the toxicity of chemotherapy, um we definitely would want to do so. And I think um we would advocate for utilizing TNT or at least discuss it as a team, as we often do for patients that have very locally advanced disease. Where we're concerned again about positive margins, concerned about making sure um there they are able to have a complete resection. Um again, when we're thinking about down staging for possible sphincter preservation and also um in in a small subset of patients, um TNT may allow for non operative management and that's that is also data that is early, you know, so we have um there there was a trial done which looked at the possibility of um non operative management of patients that had received um uh TNT and a small subset of patients um were were had a complete clinical response and then were followed over a period of time. Um and a subset of those were able to avoid operative management. But I would say that that is that data is also not mature yet and it's certainly not standard of care at this point in time. Um to recommend against operative management. Um Next side I think passing the baton on to Neil. All right, thank you sarah. That was great. I think one of the themes you'll hear about tonight is um the treatment of rectal cancer, locally advanced rectal cancer like this went from a pretty steady state into something that's now a pretty dynamic. Lots of things going on with um with attempts to try and drop multiple things including sort of toxic chemotherapy radiation and surgery. So I'm gonna talk a little bit about radiations the next slide please. And we'll talk about fraction ation and then toxic toxicity event. So we'll go to the next slide. So radiation in the care of rectal cancer is designed to do two things. It's um it can help shrink tumors to make certain surgeries more likely and it can reduce the chance that the cancer comes back locally. And and both can play an important part sometimes in the same patient. Sometimes they get one or the other historically. There were sort of two broad ways that we treated this um in europe and mostly in Sweden they started with five days of radiation a week later people went to surgery and then they got chemotherapy afterwards and that we called short course radiation. So five bigger treatments a short break and then on to treatment. And in the US we were we were taking everyone to the operating room right away and then we would give long course what we call long course radiation and chemotherapy. Which is 5.5 weeks of everyday radiation um with some concurrent chemotherapy. And then at the very end that you would get sort of stronger chemotherapy and that was to determine the true stage. So these two major paradigms had had gone on for many years. The next slide In in around 2000. A study was done using the long course of chemotherapy and radiation, looking at whether it should happen before or after surgery. And what this study found is that it was a little bit more tolerable and maybe a little bit better to give the law Course of radiation and chemotherapy beforehand. And so the us sort of adopted this and for the next 15 years or so this was the approach that we used 5.5 weeks of radiation about an eight week break and then on to surgery and then chemotherapy afterwards. So we go to the next line um even though it sort of felt settled, there were still studies going on to try and look at should we bring back short course and there was a study in Poland and one in Australia and new Zealand and then again in Sweden looking at short course versus the long course. And then these randomized studies, a sort of virtual coin flips of science patients to one or the other to try and ascertain whether one is better than the other. And what the studies showed pretty consistently is that it's not clear that one approach is better than the other either in terms of um effectiveness on on the cancer. So tumor control or shrinkage of the tumor or in toxicity. And I'll talk a little bit more about that. Um The Swedish trial was asking a slightly different question, which was about how soon should surgery follow the radiation? And that was asking a question about should it happen right away or should there be a delay? The advantage of a delay after any form of radiation is that the tumor doesn't respond instantly. And so you can have continued downsizing of the tumor over time. And so if you're looking for maximum shrinkage, you might want to wait eight weeks before you proceed to surgery. And again, the cancer outcomes look very similar between those arms with some advantages to the sort of longer delay in terms of the downsizing of the of the tumor. So we go to the next slide when we think about both the short term and long term side effects of radiation. Um We we mostly want to go to studies that that randomized patients between the two and the reason that that's important is that um that way we're not introducing bias in sort of who got which treatment and therefore what side effects they might have. And that also significantly limits um the data that we have about what what happens to patients um and the toxicities. Because we're left with just a few studies and whatever questionnaires they asked. So this is coming from the polish study which did ask patients very detailed questions about their life in the years after the radiation. And this was comparing the short course radiation and the first column and the and the chemo radiation. The long course in the second column to ask whether there was any impact on on the bowel function for sort of impacting quality of life. And most most people felt like it impacted things that a little bit and that they're they're sort of bowel function was bad but acceptable. And that was the terminology that was used in this sort of questionnaire. And and without really the numbers in parentheses are the percentages without really differences between the two groups in terms of how much people were impacted by this to go to the next line. Um They also asked very detailed questions about sort of what um what symptoms patients were having. And this is from that same study. And these are just percentages of patients who reported any of these symptoms. It didn't mean they were too severe, but just any of these symptoms. So the use of anti diarrheal. So medication to stop diarrhea was pretty common in both groups both the short course and long course and um sort of leaking stool where they would spoil the underwear. There was pretty pretty frequently. People noted that in both groups, bowel urgency the need to go suddenly was relatively common. Abdominal pain happened occasionally for these patients and and then unable to differentiate gas and stool after radiation is pretty common as well. And I think the important message here is one side effects after radiation are pretty common. And we'll talk about sort of attempts to bring radiation out of the picture for this but that there really weren't differences between the short course and long course and that that was one of the big concerns about the short course in the U. S. Was would it be tolerable would patients sort of do well long term? And these are the data that we have. We can go to the next slide as well. We also the groups also ask questions about sexual impact and I think um in in hearing from patients in the past this is one of the areas that they wish that we had talked more about when when they were first diagnosed and and we need to do better about. But so did the treatment course sort of impact your the sexual function And um you know effectively the numbers were small between these two groups and so it's hard to make sort of comparisons between the short course and long course, but not not enough of a difference to really sort of jump out from these small numbers that that one approach short course of long course was more impactful. Um, for one group versus another. Um, you can see that on in sort of on average females felt that there was less of an impact on their sexual function than than men did. But the differences between the two groups in terms of short course versus long course really wasn't that different. So let's go to the next slide. One of the strategies to try and reduce some of the impact, including somewhat the sexual impact of radiation at least for women is to move the ovaries out of the radiation field. The ovaries are extremely sensitive to radiation, both in terms of the eggs themselves as well as estrogen production. And so moving the ovaries up and out of the radiation field can be a very successful approach to preserve at least the estrogen release. And so these are just sort of images of what a radiation plan looks like and the green and the yellow sort of ears on the top on that on that first figure are showing where the ovaries can be moved. And the other lines are denoting where the radiation is going, sort of highlighting that you can successfully move the ovaries away and preserve preserve function in that way. And that's something that, you know it's done relatively common commonly, especially in the pre menopausal patients. So we can go to the next slide. Great. So the question um that comes up is can radiation be omitted? And again we are trying to sort of piecemeal omit each one of these things as as best we can. This is a this is started as a small study and then turned into a larger study when when not enough of a sort of difference was noted that was randomizing patients with stage two or three cancers to either what we would have called standard chemo radiation followed by surgery followed by chemotherapy. That was the standard at the time or chemotherapy upfront. And then a look with an M. R. I. And if the M. R. I. Showed the tumor was shrinking patients continued on to surgery without ever having radiation. And if the tumor wasn't shrinking then they went on to chemo radiation, the sort of standard chemo radiation then onto surgery then on to chemotherapy. And so this study should help us answer. Um Are there patients in whom radiation may not be necessary. And um we are waiting for those results to give us some clarity about cancer control as well as toxicity of these two approaches to understand where this where this might fit into our are now sort of very busy list of things that we can choose from. So with that we'll go to the next slide. So decision making again, this used to be simple and now I feel like it's complex. Um There's I would summarize this by saying there's lots of good options. And um we are often left making decisions sort of in a shared manner with patients as well as sort of based on some of the things about the tumor or about the location of the tumor. So for um for long course there in one of the studies that suggested that lower tumors were a little bit better to have long course versus short course. And so I think that's still generally the preference, although it's not uniformly so. Um and then one of the short term side effects of the short course radiation can be a lot of feelings of bowel urgency and discomfort for several weeks, almost like a like a sunburn inside the pelvis. That's that can be quite bothersome for patients. And so if we're worried about tolerant of that, that might push us towards the long course. And then the preference for short course of a long courses. If we're really worried about the disease spreading elsewhere, we might want to get the radiation done more quickly and on to chemotherapy, which is addressing things more more broadly. And that's a situation where we will often sort of pick short course and just fit it in there. So I have a summary slide is the last slide um short of course in long course radiation are both used in rectal cancer. Again, the goal is to help prevent the cancer from coming back locally and to maybe shrink the tumor and allow a lesser surgery at times. The side effects after radiation include bowel dysfunction, sexual dysfunction. Um ovarian function can be preserved for premenopausal women through ovarian transposition. And then there's ongoing trials investigating a mission of the radiation. So I think I went a little over but I will hand it over to DR melnick. Thank you neal. Um So I'll be speaking about surgical management of rectal cancer. And next slide please. Surgical management of fractal cancer really depends on stage and the location of the tumor. I'll briefly touch based on a location on the sphincter preservation. Can you go back on? Perfect. I'll briefly touch based on sphincter preservation and watch and wait. And we'll talk about quality of life after surgery, such as volunteer reception syndrome. And life was an osce to me next slide. So as I mentioned before, surgical management really depends on the stage. Sometimes we can do localization versus radical reception. And then it also depends on the location of the tumor. So saying, the preservation is feasible with the tumors that are located slightly higher up in an act. Um and spain is not involved and is involved in the newer sections, permanent colostomy is bothered. Next slide as local excision, which is just removing tumor in the world of director can be offered for the tumors that are very very early. So those are T. One and zero tumors as we stage them based on M. R. I. And Director ultrasounds. They have to be around in the small tumors involved very small percentage of balls and confidence and should be very mobile on digital rectal exam. We also have to make sure that those tumors are very favorable histology so they are well differentiated. They don't have any any bad features that can signify that lymph nodes are involved. The good thing about local excision is that it's very low morbidity and mortality. Patients don't have the don't undergo abdominal operation and we can preserve the rectum and also sink the muscle. However, when we do this kind of surgery, we don't example annual implodes. So it's very very important to do this operation when the histology is favorable and the humor is small and because we don't sample the lymph nodes it does why have higher local recurrence rate. So this this is offered. But apparently not many patients are candidates for it but it is fairly humor. It could be an option. Next line please. It's a radical resection and that's the standard of the f flow of patients with rectal cancer includes two options. One is lava interior reception and with this kind of surgery we can preserve the sphincter muscle. The sphincter muscle is responsible for control for stool control. We with this kind of surgery. Very primary tumor with associated lymph nodes. So you do get sampling of the lymph nodes and you will know after the surgery if the lymph nodes are involved or not frequently. When we make a new connection between two ends of the bowel, we utilize temporary Elias to me, which is temporary bad to protect our connection. So it means that patients will have two surgeries. And when we do this the surgery we follow principles of total relaxation, which I'll show you pictures later. We want to make sure the video of the tumor with associated lymph nodes in a nice plane and follow a nice plane of the session. The issue with the surgery patients can develop low anterior resection syndrome and how cool function can have leakage of stool incontinence, frequent trips to the bathroom. So even though we are preserving center with this operation but the quality of life might be diminished. Next slide, please. The next operation that's also started of in rectal cancer surgery is called abdominal perennial reception. So here we offer this operation. Only if we are unable to preserve the specter muscle. So it's if it's involving state the muscle or if the patient has already pulled function before the surgery, that's when they would get this operation. What it means for the patient that the whole rectum and anus is removed and the patient will have permanent colostomy. Next slide please. And this is just a nice picture of what we mean by total rectal excision which is the standard of care in rectal cancer where you want to make sure that we remove this envelope of the lymph nodes within our tv playing and not get into it and not leave anything behind that can cause a local recurrence next night. And that is just another another picture showing the same the first picture that there's a studio humor and we wanna follow nice plane of the dissection and here as you can see the humor is trying to grow outside of the wall. So the same the same thing what we are what we're doing here and explain is actually called in colorectal surgery holly lane. Um Next slide. And one thing that both dr slater and Dr martin brought up a little bit is this approach called watch and wait. So that leads to organ preservation. That means that we can avoid the surgery in some selected patients with rectal cancer who underwent chemotherapy and radiation therapy before. Um And if those patients had what's called complete clinical response meaning that after the chemotherapy and radiation therapy there was no tumor found post on digital examination endoscopy and M. R. I complete clinical response can occur in up to 30% of the patients treated with stuff on your adjuvant therapy. But however some some some studies show even 50% complete clinical response such as opera trial. It does give patient opportunity to avoid surgery. So and avoid um keeping keeping the rafter in place how very important to know that this complete medical response doesn't mean that the tumor for sure went away. There is no way for us to know that the tumor for sure went away until we actually removed the act. Um which is frustrating for us. We would really like to know that assessment upfront. But complete clinical response is as close as two to that as as we have. And we are very careful following specific guidelines of what to call complete clinical response and when potentially to offer this option to the patients, what we are asking here. So if we don't do the surgery and we don't know sure that the tumor went away that could be microscopic cells left behind and it can look like it went away on endoscopy on M. R. I. And those cells with time can start growing again so they can develop locally growth, meaning that the tumor will come back again in the palace by then the same location where it was before or maybe in one of the lymph nodes that that was involved before. Um it will lead to the surgery in most of the patients and most of the patients were able to help with the delay surgery. However, we worried that during this time as the tumor was trying to regrow maybe the tumor can mutate or spread to other organs such as liver or the lungs and leads to decreased survival, possibly next one. So we do have we're getting actually more and more evidence on watching made approach. And and um the problem was our evidence that at the beginning that just single institution studies which included multiple rapid cancer stages, different protocols for surveillance and definitions of and therapy and clinical complete response. So it was part to make for us any good assessment if this is a viable option for our patients. We're getting more and more studies now looking into this. Looking into this approach and the data is actually encouraging. So what we know from the new new data that most likely the tumor will come back inside the meaning it will be easier for us to catch up the majority of this tumor growth happens within the 1st 23 years. So we have to be very careful of surveying those patients. But it's also encouraging that we can do our normal surveillance and if it had to come back it would come back earlier. About 50-30% of the patients who had complete clinical response and underwent watch and wait approach would develop local regrowth and what we also know that we can actually salvage. We can save 90% of those patients with surgery. So even though they will develop humor. Again, surgery, our radical resection surgery would help in 90% of the cases. And then we also know that pelvic recurrence rate of style, which surgery is low and less than 10% similar. I mean it's just slightly high and what we have in the upfront volunteer section or a pr and patients can develop to December the seven disease. What 88%. But that number ranges in different studies depend depending on what you're looking at next flight. And one thing that dr martin touched base in terms of the radiation, the quality of life for the patients who who had rectal cancer. So he was talking about quality of life after radiation and I want to briefly talk about quality of life after the surgery. So patients after the surgery either with a pr a low interior section can have blood dysfunction, sexual dysfunction and contribution to this can be both radiation and our surgery that we do. And majority of patients who had low interior recep Syndrome will have some form of low anterior resection syndrome, which can cause either in continents or frequent stools where you frequently run into the bathroom clustering when you have bowel movements every 5 to 10 minutes, urgency, paying discomfort. And some patients for on whom the tumor is very low, even if we are able to preserve their muscles, that function can be so poor that they actually might be better off having an Oscar me as having permanent colostomy when we consider patients to have when we offer the patient's permanent colostomy either because we cannot preserve the symptom a cell or there is a consideration of quality of life issues, it's very important to have those patients see our awesome nurses for preoperative marking, making sure that the austin is located in a convenient spot for them. Patients can develop for Istanbul corneas and they have issues with self image. But what I always tell my patients that they can still live a normal life and do everything that they used to do before the surgery. And that's what I try to emphasize. It's hard for patients to accept that to accept that choice. But sometimes if it's a better choice than very bad low anterior resection syndrome. Next slide please. So in summary as I'll echo what everybody else just had said we have many more choices for management. It's very nuance and shared decision making with consideration of quality of life is very important. So we have to discuss with the patient all of those considerations, surgical complications, radiation complications, um and what their lives will be after each. After each choice. And here Dana Farber, we do discuss applications with rectal cancer, the tumor board with the review of imaging and pathology and making sure that we are considering all of those, all of those choices which we just mentioned. So thank you. Okay I guess that is me. That is next. So um I will put one caveat that this presentation is more marketed for a patient to patient um conversation. So I apologize that this is a little dark humor for you. But um if we move on to the next slide, I'll tell you a little bit about my journey. Um so from March December of 2018 I had ongoing symptoms of frequency and bowel habits um mucus in my stool and extreme fatigue and lost weight. I went to my primary care doctor and we both chalked it up to work in life stress and we worked on adding in medication to help with anxiety that we presumed was causing this I. B. S. During this time it was actually training for a 10-K and ran it with a unbeknownst to me at the time line sized tumor in tow. Um you know from january to february of 2019, I get through the holidays, I start seeing blood in my stool. I go to my PCP. I say this is this is incorrect, this something's not right here. And I was fast tracked for a colonoscopy at my local hospital on the 12th of february. Um I had said colonoscopy while I was waking up from surgery, A packing nurse actually said the words to my husband, it doesn't look good before the doctor had even seen us. Um on valentine's day of 2019. I got a call after hours from my G. I. Doctor with the pathology results, which was a stage three rectal adenocarcinoma which had a was 4.7 centimeters with spread to lymph nodes. And the thing I will point out is the direct quote from my own PCP that said it's just I. B. S. You're too young. Um So if we move on to the next slide to talk about tally ho to treatment. So from february to March I was lucky enough to meet with my treatment team both at dana Farber and at Brigham to discuss the game plan. On the 11th of March I had my porch installed. So I went from the worst valentine's day present to the worst birthday present. Um From March through june of 2019 I went through eight bi weekly cycles of full fox. Um Moving into the beginning of july I actually did have the um ovarian transposition surgery to move my ovaries out of the radiation field prior to treatment. And then from July to August of 2019 I had 21 rounds of radiation um in combination with keep sight of being I did not make it to the 28 rounds due to side effects. But I I hung on for as many as I could until we get to the next slide and surgery. So on october 17th 2019 I had a four hour surgery to remove my tumor with clean margins and had placement of a temporary Elias to me. Then towards the end of the year I was had my Elias to me takedown in january 2020. I got a surprise which was that um There was an excision of the right sided abdominal wall, knowledgeable needed. So I fell into the 1-2% of people that have the ovarian transposition surgery that end up with a hitchhiker um and it Had lodged into my abdominal wall. Uh so that was the last surgery to date and as of now from 2020, 2022 forward and doing ongoing surveillance every few months um and long-term side effect management. So if we move on to the, I think my final slide again, this is more marketed for for um fellow patients, but again, not letting cancer define me. So since that um I actually started a team called Barry the bowel, you'll see a picture of him within their um for the uh colon cancer Coalition's walk we've actually raised this is a little outdated over $6500 over the last few years. Um And also in world and personal lives collide in 2019. I was lucky enough to attend his mo and actually listen to the colon cancer presentations and the ovarian cancer presentations with at the time were from my work. Um So I will uh pause there and I believe hand it back over to dr ng, thank you so much for sharing your story and I'm so glad you're you're doing well so many years later. Um So at this point um you know, happy to take any questions from the audience, Please type them into the Q. And A. And well. Happy will be happy to um ask any of our panelists to help give you some answers. Perhaps I can start by by kicking things off. So um clearly the management of rectal cancer is super complicated these days but of course it's great that we have so many different treatment options for our patients. One really huge advances is de escalation of treatment right? Trying to rem move certain parts of the treatment from the regimen including radiation with the prospect trial that you heard about from Dr martin and then also this watch and wait approach that all of them talked about. So I was wondering um because watch and wait is not quite yet standard of care but more and more patients are interested in this approach. Maybe I'll go through and and ask each one of you to tell me what is your approach to watch and wait. Are you offering it to patients off of a clinical trial now? And if you do, are you only offering it to certain patients? Um Maybe I'll start with DR Melnick chuck. So we discuss we discussed this this management strategy in patients who did what looks like have a complete clinical response based on M. R. I. After TNT. And if the patients are interested in it for those patients we would offer endoscopy to really make sure that even though M. R. I. Is showing complete clinical responses confirmed by endoscopy most of the time we discussed. It was patients who are candidates who have done whose state of preservation is not possible. So who are choosing between permanent colostomy versus versus this watch and wait approach for more proximal so more upstream rectal cancer. We still pay for surgery as uh even though they do have low interior sections syndrome. But the majority of patients will prefer certainty of uncertainty. And it's the majority of patients who are considering who whose choice experiment colostomy would consider watch and wait. Have ever been discussed it with all the patients and with the stuff risks and benefits and what's involved and how important it is to follow them afterwards to make sure that if something does come back we catch it early. So we're offering it to patients. We'll discuss it very very carefully and making sure that we can let patients make that decision but guide them as much as possible through that. Thank you. And do you want to maybe just go through what the surveillance schedule is for somebody who does qualify for the watch and wait approach because it's quite intensive and so a patient really has to be pretty compliant and um willing to go through frequent tests. Yeah. So surveillance will include rectal M. R. I. And flexible sigmoidoscopy. We usually alternate that so every three months they get something. So either M. R. I. Every six months and then endoscopy every six months but they're all uh they all just happen every three months or every three months patient is getting something. Either endoscopy or M. R. I would check their C. A. Level as well to digital rectal exam. And the tour was obviously lower enough to be able to feel it. Thank you dr slater what about you? What is your approach to watch and wait? Um You know I think it's it's very patients you know you have to believe that the patient's gonna be able to comply with the surveillance schedule. And so when I'm discussing it with patients I think that's one of the things I always worry about as some patients are extremely compliant and I know so that they'll they'll stay on schedule. And there are other patients that I worry um won't be able to adhere to the surveillance schedule. So that's one of the things I worry about. And then I think one of the other things I worry about although this isn't necessarily founded in any data is whether somebody has a very aggressive um pathology um like significance all or some some other pathology that makes me more worried that that tumor is going to metastasize. And so I might counsel a patient um uh maybe to consider surgery in that situation even if they. Technic qualify for a watch and wait protocol. Um And I think that that's um like I said not necessarily founded in in good data but just that there are definitely times when when we see tumors that just look really aggressive under the microscope. And I worry more about those patients. Yes agree. And then dr martin um I'll just add that this is hard for patients that have the most to gain from from Washington wait. Um We also worry the most uh there's you know mistake can be amplified for someone who's young for example and while we have pretty good data about salvage rates etcetera. Um You know even even a slight increase in the risk of a local recurrence or an elsewhere recurrence for young patient really has some sort of significant implications. So I think the conversation is a little bit easier for older patients all and there may be reasons to for watching weight whether it's surgery might be too much for them in some ways. Um But I think just to sort of build on what was what Dr and Dr slater said um you know we we also think about um what are the what are the risks of of a mistake here in in some way. And I think um that sort of buried in what they said but just to call that out. Great thank you. And maybe I'll stick with you for this next question that came in through the Q. And A about locally advanced rectal cancer. And whether short course radiation followed by chemo or induction chemo followed by long course chemo radiation is recommended? Well, perfect. Um That that is exactly the question that we ask ourselves every friday morning when we joined on tumor board. Um So so let's see. We actually choose to um our long course before chemotherapy and our TNT approach um for some sort of toxicity and and outcome reasons. Um But deciding between short course and long course in the TNT setting. Um I think higher tumors, tumors with more nodal metastases. Maybe I would steer a little bit more towards short course um as it gets you on to chemo a little bit more quickly. Um if there's a desire to have maximal downsizing to try and preserve sphincter function, then maybe long course would take a slight van but there's a lot of patient preferences and situation that can also play into this. And I think as a group we really don't have a lot of clarity about whether one is truly better than the other. And so have have settled on lots of different answers in sort of only slightly different situations for from a patient standpoint, thank you. Um And then maybe I will post the next question to Lauren. Um So from the patient perspective, you know, obviously uh you know having to face these treatments which are quite intensive and have you know implications for fertility and sexual health and and and your bowel habits, you know for the rest of your life. How how did you think about some of these issues as you um went through treatment or we're discussing the treatment options with your team. Sure. So, um in my particular case when I was diagnosed, I had was between 35 and turned 36 when I had my porch installed. So I had made a personal decision with my spouse that we were less worried about overall preserving fertility. However, I did want to avoid menopause at that age. So we consulted um in terms of having the plexi to move my ovaries to to give that the best chance so that I wouldn't then have the potential side effects of menopause in addition to long term chemo radiation, etcetera side effects. Um and then, um one thing and I think one of the physicians touched upon this in in an earlier slide is I do wish more gravitas was given to kind of the sexual dysfunction implications long term. Um, I don't think it necessarily would have affected my decision, but I think it would have definitely been a conversation I had had with my husband. Yeah, it's such an important issue that, you know, everyone is right, we we don't spend enough time counseling patients about either before they start treatment or during their treatment. And so that is one of the issues that are young onset colorectal cancer center is trying to address, really making available a sexual health counselor available to all of our patients and we will soon be offering regular webinar and support groups as well to talk about sexual health. So hopefully that part of our care improves for for our young patients great. And then we have just a few minutes and so perhaps I'll pose the next question to dr slater. Um You know, we heard about de escalation strategies and rectal cancer, but there are also some trials that are trying to intensify, you know, for example the chemotherapy that's given in T. N. T. To fulfill knocks. Are you using full fare knocks regularly And if so in which patients? Yeah, that that's a really good question. Um And and the answer is sometimes and again, I think that speaks to the sort of um uh changing landscape of how we manage these patients. So for some patients who um I think will tolerate intensified regimen and that and and that's not all patients, but some patients for whom I think they will tolerate it who have really large tumors who I'm worried may have occult metastatic disease that I'm that that we aren't seeing. Um And for whom shrinkage is really critical. Um I have been using full parallax but I don't use it for everybody. Um It's not my go to per se but I have used it in some patients. Um And I have seen really good results. Um But you know, it's hard to know over time if that would translate to an improvement in their overall survival. Um But I think certain patients for whom we're trying to get to surgery um and give them a best chance um uh for a good surgical resection and and um and who I worry, you know, they need all the help they can get with the chemotherapy. Um Those are the patients that I think about using full Furin oxen. And how have you found the tolerable itty to be in the toxicity compared to just full Fox? It's definitely a little bit more difficult. Um for sure. And you know, I think usually I'm choosing patients who for whom I think, you know, it won't be too much harder, but it definitely adds additional side effects. Um I think more diarrhea, um more fatigue, sometimes more nausea. So so it is a it's a tougher regimen for sure. And and when patients are already looking down the sort of landscape of a lot of intensive therapy, you know, I always want to be mindful about adding one more thing um to their treatment plan. Yes, that seems really like a reasonable approach and you know, on the topic of toxicity, perhaps I'll ask dr the next question about L. A. R. Syndrome. Um You know, unfortunately many of our patients deal with this and it can be really, really um negatively impact quality of life. What are some strategies to treat this and can you predict who is going to have a worst case versus you know, not have have this and what is the natural time course of kind of improvement in the symptoms. Um so can be predicted. It's a little hard actually to predict who will have and who will not heavily a syndrome. But some things that are associated with worse Celia syndrome will be depends on where the tumor was in the rectum. So that if you um low interior section is very low meaning we don't then leave much distance rectum behind. The low interior syndrome will be worse. If the patient had radiation before the patient had read radiation then low interior central will be worse if they already have somewhat poor function. The function will will worsen. So that's why for those patients we might consider actually a dominant premier reception up front. But we counsel patients about about that. And as I tell my patients the first year is usually the worst year and it does get somewhat better afterwards but it never goes back to normal. So, and you know, some of it might be the patients learning to live with it and they're using different strategies to mitigate it. And some some patients change their diet. Some we recommend adding fiber actually from majority of them we recommend adding fiber, identify Metamucil to bulk up stool and so it's easier and easier to pass. And hopefully that's lasting for those patients and then emoji um managing. But the thing is you also cannot taking on all the time. So just taking it around some special functions or some events that they really have to make it. But it's it's a very very long process. Majority of patients learn to live with it but it doesn't it does not go back to normal. Yes, thank you. And then you know, perhaps ending with Lauren um you know obviously you've also had to deal with a lot of these side effects as a result of your treatment. What changes have you made that have been helpful for you advice you would give to other patients? Um And you know, just in general how has your your lifestyle changed as a result of this diagnosis? Um You know, I would say be patient, I was a temporary estimate but after I had the Ostuni reversal I had to essentially retrain my body. So I think the key takeaway would be patients and to just teacher tell your patients to be patient. Um It sounds it sounds that doesn't sound very easy but like it's that that was the key for me because it did take some time and even some days I still struggle but it you know over time it will get better. So patience is key. And then just um re kind of learning some things that your body may or may not be into eating anymore. So your diet. Thank you and again so glad you're you're you're doing well. Um so many years after your treatment. Alright, well that brings us to 7:00. So thank you everyone for participating and sharing your wisdom. This is a complicated disease now. Um but lots of options for patients and thank everyone for attending and listening. The version of this will be recorded and available on the website for those to view afterwards. Thank you so much and good night.