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All right, good morning. Everyone. Can somebody just post in the chart if you can hear me? OK, hoping that you can hear me. OK, perfect. Um Always a little tricky to set up all of this. So, um welcome. I see folks are still trickling in. So over the next hour, hour and a half, we're gonna be speaking about colorectal cancer. Uh I am a medical oncologist. I'm based in North America. Um So uh that may influence some of what we speak about but try and make it helpful to everyone here. So over the course of this talk, this is a bit of a higher level talk. I've given talks previously, I think more at the medical student level. Um And in this talk, we're really gonna be focusing mostly on work up and then treatment. So, uh not so much on things like epidemiology and risk factors. Um But more if you're a practicing physician, if you are a resident, you're an intern, you work in oncology. What do you need to know um about colorectal cancer? And we will be discussing some of the literature as well. Um Colorectal cancer, especially colon cancer is in an area where there's a lot of exciting new research, but we'll go through some of the major um historical data and um some of the new data that's come out as well that's potentially practice changing. So we're gonna start with colon cancer. And then at the end, we'll do a little bit on rectal cancer and how it's different. And this is a very interactive talk. So first question for the audience is when you're doing a workup for colon cancer, what test would you order? And you can list of the different things that you would order. If you suspect somebody has colon cancer or someone's coming in with symptoms, suspicious for colon cancer. This is something that you can post in the chart and I'll give everyone a few moments to think about it and put their answers down and we'll see what folks are thinking. All right. So some interesting answers coming into the chart. Um biopsy, colonoscopy C ea and then some uh fecal occult blood test. So fo BT and fit tests. So, um perhaps this question is in the best word, but if you're suspecting somebody has colon cancer, someone's got symptoms of colon cancer. Uh You're very right. You want to do a colonoscopy, you need a, a piece. Uh you need tissue confirmation for most kinds of solid tumors. Actually, probably with the exception of hepatocellular carcinoma, I would say. And II think most guidelines would say if you suspect somebody has a cancer. So they've got symptoms, um, they've got bleeding, I MS uh FOBT or fit testing is not really indicated. So this is going to be more for screening. So, if you have somebody with absolutely no symptoms, and you're wondering, uh, if they could have colon cancer, in that case, a fit test, if you're able to get it or a screening colonoscopy would be standard FO BT. The fecal occult blood test is really falling out of favor just based on the sensitivity and specificity. And if you're able to get your hands on a fit test, this is a better test for screening purposes. However, if we're doing diagnosis, there's not really any role for that and it's really gonna be colonoscopy, visualization, tissue biopsy. And then when you have somebody again that you're suspecting of colon cancer, you've confirmed it on the tissue, you're gonna want full blood work. So that's CBC. So your blood counts, um all of your electrolytes, liver function, kidney function C EA, which is a tumor marker that's associated with colorectal cancer. And then you're going to want full body imaging CT chest, abdomen and pelvis to look for metastasis or rule out metastases before you engage in some sort of infe intervention. So along those lines, I mentioned that you'll need full body CT scans. Do you think you would be ordering those with or without contrast? And this is a bit of a higher level question. Um Oh, wait, I have a call for this. Do I? Yes, I can open the pool. There we go. So you can walk in the pool. All right. I see the answer is coming in. Yeah, a few more seconds. Cross your vote. All right. So this is interesting and it really boils down to which guidelines you look at in my personal opinion. And I think the opinion of most of the guidelines doing the scans with contrast, if the patient is able to tolerate, it is the most helpful because it gives you the clearest picture. And when you're dealing with cancer that you're going to treat for curative versus um uh no uh incurable intent or more palliative intent, you really want to know what you're dealing with because sometimes one of the worst feelings is when you put somebody through this whole very intense curative intent treatment and then lo and behold, they actually have metastatic disease or they develop it shortly afterwards. Now, the NCCN guidelines, which is one set of guidelines does say you can do CT chest without contrast. As long as the abdominal pelvic uh CT is with contrast. I don't personally agree with it, but technically, it's not wrong. So just some things to think about um what is the role of pet scans. Um So this is another thing to think about that. Um Sometimes patients will ask you or sometimes you'll ask yourself. So we spoke about imaging modality is usually ct chest, abdomen and pelvis when we're dealing with the colon cancer. Uh MRI S are not standard. Pet scans are not standard unless there's a question on the CT scan. So unless there's something that we're worried about, we're concerned about, we're not quite sure what this is. We want a better picture. Um in general, MRI S and pet scans don't give you a whole lot that CT scan uh doesn't unless there's a question or something that's gonna put on the CT scan. So pet scans and MRI are not standard part of the workup for somebody with a biopsy, proven colon cancer or suspected colon cancer. All right. New question. So this is one that you can type in the chart. So I kind of mentioned this before but um we can have uh the exercise to write out. You have somebody um they come in to see you. They've had their colonoscopy, they had a biopsy and now they have proven a colon cancer or rectal cancer. What blood work are you ordering for them? Uh at your initial consultation with them and it doesn't matter who you are. If you're the surgeon or the oncologist or surgical oncologist, what, what would you be asking for? Yeah. Can you elaborate on what, what UE is? I'm not familiar with that acronym. Oh, thank you. So we have some triline in. Give me a few more moments for anybody to think or cast the vote. All right. So I see full blood counts definitely. Um as we know, colorectal cancer can be associated with bleeding. So you want to see, are they anemic? What's the hemoglobin? You also want a baseline white count and platelet as well, especially if we're going to be thinking about something like giving chemotherapy, um full electrolytes including calcium, including magnesium. Um You want to know sometimes when folks have um bowel changes, uh diarrhea, the electrolytes can go out of work if you're not eating well, the electrolytes can be out of whack uh liver function tests and liver enzymes, definitely kidney function. Uh Definitely we always wanna make sure remember t markers in applicable disease sites. So C EA um C RP is interesting. Um I'm not sure that I would order this right off the bat for everybody who has colorectal cancer because we know they have a cancer. It doesn't tend to add much. There are some people and some schools have thought that if you are treated with immunotherapy, talk about that. Uh later on in the talk that trending C RP can be helpful for predicting and managing toxicities. But I think that's not standard. So um probably I will not order it right off about for everybody. Maybe if immunotherapy was on the table. OK. Nice sweet. All right. So last workup. So your scans, you need the tissue, you need your blood work and you need to assess the patient, um look at performance status, functional status, take into account as well, the patient's wishes and goals as it pertains to treatment and work up. So now going after localized colon cancer treatment wise, again, questions for the group. Um So this is another one post in the chart. So if you have a stage one colon cancer, stage one colon cancer, um I will tell you that this would be surgically resected. Let's assume that it has been what Adjuvant treatment would be recommended for a patient with stage one of colon cancer that's been surgically resected. You can post in the chart. It, we're getting crickets. Let's take a step back then. What does adjuvant mean? Because that might be a place to start instead. So says crickets has no treatment recommended. That's fair enough. So it is a trick question. So adjuvant refers to treatment after the surgery. The adjuvant refers to treatment before the surgery for stage one colon cancer. Yes, exactly. The treatment recommended treatment is surgery alone because the survival rates are very good. Um And uh there is no proven benefit to any treatment other than surgery. Now that changes as we go up in the staging. Um This is something I call a picture slide because unfortunately, if you are in oncology, it's something that you just have to memorize, especially for your board exams. Um, but when we get to stage two colon cancer, this is a bit of a mixed bag. So on one hand, we have very low risk T three and zero colon cancers that can be treated successfully with surgery alone. On the other hand, we have very aggressive high risk T four and zero. colon cancer is where the patient presents with obstruction or a surgical emergency. And we know actually that some of these patients do worse or the promos is worse than somebody with a stage three colon cancer at three and one, for example. So there are lists of high risk features where adjuvant chemotherapy for stage two colon cancer could be recommended. So this will be your t four primary if somebody has a tumor that's high grade or poorly differentiated. If there's lymphovascular invasion or perineural invasion, if people present with a bowel obstruction or tumor perforation, that's a big one if less than 12 lymph nodes are sampled. And the reason for that being that it's possible if you on, if you get less than 12 lymph nodes, that one of them may be positive may have been positive. So you may actually be dealing with a stage three colon cancer, you just don't know. And then again, the guidelines uh start to deviate. So if somebody has elevated preoperative C EA according to asthma guidelines, that's a higher risk feature, someone has positive margins. According to the NCCN, I think in general, positive margins would be seen as a high risk feature. But more because the surgery was unsuccessful. Um or the surgery did not eliminate all of the cancers, you know, you have some cancer behind. That's a matter of semantics and then um tumor budding as well. Uh from the AO guidelines, if you work in a center that reports to my body, so bit more about stage two colon cancer. So again, stage two colon cancer is always gonna be a discussion between you and the patient regarding adjuvant therapy. Um Other notes are the duration of treatments. So some on the line may know and we're gonna talk about that in a minute that there is some discussion about whether three or six months duration of adjuvant chemotherapy in colon cancer is recommended. If you are treating stage two colon cancer in general, the recommendation is to aim for six months, we still know that the bulk of the benefit happens in the first three. But if you're calling somebody's cancer high risk in general, you should be aiming 4 to 6 months of treatment. Uh Along with the patient, we also know in stage two that MSI high is a protective factor. So microsatellite instability, um patients with stage two cancer seem to do better. Uh And that's something that's not quite in the list that we have here, but something else to consider. Now, if you have something on here is MSI status enough to say that you shouldn't treat probably not. But again, just discussions. Uh oh the other point I had to say, oops, if somebody has MSI high cancer and you are treating, the recommendation is to treat with a doublet. So something like a Xelox. So, Capecitabine or Seoda and Oxaliplatin or Folfox. So you're five fu plus your oxaliplatin. There's a third caveat about uh subgroup analysis from a trial called the mosaic trial. The mosaic trial was comparing single agent chemotherapy five fu based chemotherapy versus doublet therapy and they found in general people do better with the doublet therapy which makes sense in, in general. Um very, very broadly speaking, of course, there's many exceptions. But if you give more chemotherapy, you should hope people do better anyway. However, some group analysis from this trial called mosaic um said that in patients who are over 70. So the elderly patients oxoplatin who double it, the oxaliplatin does not seem to add benefit. And in stage two, colon cancer specifically because we're still speaking about stage two, if you have somebody who is elderly, there could be a role to give single agent five or few based chemotherapy alone, things get a bit sticky when you have somebody who's over 70 who has MSI high because then does the oxaliplatin help or is it uh uh unnecessary? Again, this boils down to a conversation between you and the individual patient that you're treating. So stage two colon cancer, adjuvant therapy, it is a bit of a mixed bag. All right. So in terms of newer trials. This was a trial that came out, oh, a few months ago, I think one of the uh the Oscos, I think. So, this was a study called cobra. So circulating tumor DNA does somebody in the chart want to say what circulating tumor DNA is otherwise, I'll describe it myself, but just trying to gauge where the audience is. I'm not boring everybody. Oh, it's OK. Um So I wrote down circulating tumor DNA in the chart. This is some, this is an area where there's a lot of research and oncology going on. Uh what this is, this is DNA that's released from cancer cells into the blood and this can be detected on assays. So, blood tests, what we know from studies is that if patients have positive circulating tumor DNA, so you can detect tumor DNA in their blood. The chance of the cancer coming back in the future is very high, very, very high. It's a circulating tumor DNA cannot be detected. That does not mean the cancer won't come back, but the risk is lower. So we have this test that can prognosticate um cancers that have been treated with curative intent, which is fantastic. Now, there are many, many studies going on to see, well, what can we do to try and mitigate these risks? Right. Unfortunately, there's not really been a study that's shown very successfully that if somebody has positive circulating tumor DNA, this is what you can do to improve their outcomes and you know, decrease the risk of the cancer coming back. One such trial was cobra. So Cobra took patients with stage two, a colon cancer. So your t three and zero, you're low risk colon cancer patients who would normally not get adjuvant chemotherapy and they randomized them to two arms. So one arm, they took the blood, they analyzed the blood for circulating tumor DNA, but they did not tell the patient the result. And the patient just went on surveillance. And the other arm, they took the blood for a circulating tumor DNA. And then they informed the patient and the healthcare team and based on the result, if it was positive, the patient underwent chemotherapy. If it was negative, the patient just went on surveillance. This travel stopped early. Uh I believe this trial stopped early for fertility because they found that between the two arms, there was no no difference, there was no difference in the survivals and the cancer coming back. Um And it did not seem helpful to direct care based on circulating tumor DNA. This is a pattern that we're seeing in other studies as well that are reporting giving more intense chemotherapy or giving more chemotherapy to patients who have positive circulating tumor DNA does not seem to decrease the risk of the cancer coming back or in the available studies that we have um seem to help patients live longer. Either it's a bit frustrating because we have this test. But if you do it all, you're telling the patient is, oh, look, there's a higher likelihood that your cancer comes back or lower likelihood will not zero. So, doesn't seem to change a whole lot. But scenario was more work is still being done. All right. Moving on from stage to colon cancer to what is the definition of stage three colon cancer? So, a bit more of a easy question and I'll open the pole here and folks can vote. All right, we'll give it 10 more seconds. All right. So let's see the results come and see the results. So, uh yes, majority go to right. So the definition of stage of colon cancer is that you have either a positive lymph node or you have a tumor deposit. Tumor deposit refers to cancer cells that are detected in the same area but outside of the the tumor, um maybe in the tissue outside or um on the wall, et cetera. So it can be either a lymph node or a tumor deposit. Um that makes something a stage three colon cancer without distant metastases, we should at that point. So, one of the biggest trials in stage two. So for stage three colon cancer, the recommendation for most people is going to be adjuvant chemotherapy. And there's different ways to do this in general. The standard of care is considered double therapy with either four folks, either a few in your oxaliplatin or Kal through X, your cap size to be an, the ideal collaboration was uh a meta analysis where they took all these studies and combined all the data because I wanted to know it's three months of treatment, non inferior to six months of treatment. So this is where the duration of treatment comes. And you may have seen this if you worked in our medical oncology clinics previously. And the results of the study showed that for Xelox or K Fox, specifically, three months of treatment is noninferior to six months for patients with T three N one disease. So kind of uh the most indolent of the stage three. If you have T four disease, if you have N two disease, uh six months will lead to better outcomes. Interestingly, in the study, the four folks do not have the same known inferiority as the xerox. But I think in practice, most people will do either way. So if you see someone with T three or T two or T one, N one disease, uh often they will be offered three months of treatment because there is this ideal collaboration that showed no inferiority compared to the six months. Again, we know that the bulk of the benefit or we suspect the bulk of the benefit is in the first three months. But if folks are doing well, they want to keep going, six months would be considered the recommendation. All right. So we've spoken a couple of times about five F US, you can get four folks or you can get Capecitabine or soda. Um which is the pill version. There are slightly different side effect profiles. So something for the group you can post in the chart, a side effect that you think or you know, is associated with kitine and not five fu All right. So there's a pancreatitis. I've just looked that up because that's actually not one I've heard of before, but you're, you're right. Um There are case reports associating Kitine with pancreatitis. So, kudos for that one, allergy, of course to everything that we give. Um a big one is hand foot syndrome. So, Capecitabine can cause a very bad peeling rash on the hands and feet. Uh It's usually recommended if someone is going to go on cape side that they moisturize, use a good moisturizer several times a day. If they're working with their hands, they're outside doing work or they're washing up to wear gloves. Um We don't see that with five fu. If somebody has bad hand foot syndrome, you can use urea cream. There's also new evidence coming out to use Voltaren or uh Diclofenac uh NSAID gel that also seems to help or you may need to just end up decreasing the dose. Um Yes, definitely. So, the gastrointestinal symptoms do tend to be a bit worse with Capecitabine than five, a few simply because it's an oral route. So a bit more stomach upset, nausea, um uh uh reflux symptoms, diarrhea. Some people do report constipation. Um The throat spasm is more from the oxaliplatin. So the core sensitivity and the neuropathy is actually more from the oxaliplatin. Some people will blame Capecitabine, but uh it's not typically associated with the capecitabine per se. It's more the other chemotherapy it's given with. Uh Yes, absolutely. So, it's hand foot syndrome. There's also another more technical term. I'll tell you in a second. I can't spell it. Yes. OK. OK. Yeah. This one. So once and I don't know how to say this either. I apologize. But this is the more technical term, palmar, plantar erythrosa or just hand foods and milk. Um You can get a hair thinning but hair thinning more with both kitine and five, a few A I review itself though because it's given intravenously. There are slightly higher rates of things like fibro neutropenia or your coronary vasospasm. So you say Capecytabine can have more knowing side effects, but five, if you can have a bit more, just slightly slightly more of life-threatening toxicities. The other thing with Capecitabine to keep in mind is that you need to have adequate renal function. So somebody's estimated glomerular filtration rate. So their eg fr is less than 30 in general, they cannot receive Capecitabine. So if you have someone with renal failure, it's something to think about. Ok. But these again, these are the, the thoughts I have to go through our mind when we're working in oncology, even though we have guidelines, even though we have algorithms, it's very much trying to figure out where the individual patient is and make sure we meet them on their level and are individualizing treatment, uh keeping their goals, their priorities, their wishes in mind if we ever make any recommendations. All right, another pool making your folks work. So this isn't stage three specific, but just in general, is there evidence for giving full theory in the adjuvant setting? So we've spoken about four folks, we've spoken about Sealock or Capox four F with IEC given the five of you with Irt. Is there evidence for this in the adjuvant setting? I give everyone a few moments to think about this. Mhm Yeah. And give another five seconds. Get your final vote in. All right. Interesting. OK. Mixed bag of responses. So there is evidence that it doesn't work. So a bit of a, I guess a poorly worded question I can. Um So there are studies that have used Folfiri uh and it doesn't work. So there's not a role to give Folfiri in the adjuvant setting. It's going to be Folfox or Xerox. If patients have neuropathy or their failure performance status, it can give keep or five. If you're alone, there is evidence for this. We know that the outcomes on a population level and a study level are worse than double it. But for the individual patient that may be uh the best decision. Yes. Ok. Uh I'm not quizzing you guys about new adjuvant treatments for colon cancer, specifically in general. This is another mixed bag of evidence. There was the Foxtrot trial that showed some improval and two year disease free survival with perioperative chemotherapy similar to what you might see with gastric cancer. However, than two other trials showed no benefit to the neo artery component. So in general, this is not something that's done. Um at least done routinely if you have a patient who has unresectable disease or metastatic disease as we speak about, that's different. All right. So the bottom line of everything that we've spoken about with treatment. Stage one surgery only, no role for adjuvant therapies. Stage two, you want to consider the risks. If you have somebody with a higher risk. Uh stage two cancer, it can be a role to give adjuvant chemotherapy. Stage three. In general, the recommendation is adjuvant chemotherapy. Gold standard is a doublet with um five. If you based and then your oxaliplatin, there can be a role for a failure patient to give a single agent or for some patients. Uh Of course, no chemotherapy is an option as well. And what if the patient is failure? This is what I'm saying that we always have our studies, we have our trial, we have guidelines and gold standards, but you have to personalize the treatment to the individual patient for someone who is very frail. It may make more sense just to go on surveillance and to pursue chemotherapy. Um as a side note, uh in general, from the studies, adjuvant chemotherapy for colon cancer decreases your risk about a third um for the cancer to come back. Uh And if you give single agent alone, that halves that so, not fantastic numbers. Um Certainly not. If you're used to breast cancer clinics where you give adjuvant therapy and the cure rate is 99%. Those aren't numbers. Unfortunately that we see in the colorectal ward, but it can be helpful. Uh, some patients will certainly benefit from it. Ok. At this point, I think we're over halfway through now. So I'm gonna pause there and see if there are any questions at this point about anything we've spoken about. So we've spoken about the workup. We've spoken about treatment for um localized colon cancers. All right. Well, we'll keep going then. So next part is going to be metastatic treatment for, oh, there's a question. Ok. New adjuvant therapy is not recommended for colon cancer in general. So, stage two, stage three, if it can be resected, the um uh standard of care is to resect the colon cancer and then to consider adjuvant therapy afterwards, when we get to rectal cancer, it's different. But for colon cancer, there's no standard role for neoadjuvant chemotherapy or neoadjuvant treatment for resectable disease. Good. So now we're going to go to metastatic um colorectal cancer because to be fair, it's really the same treatment and then we'll do a quick little spiel about rectal cancer and how it differs from what we've spoken about. So, when we're speaking about metastatic colorectal cancer, there are many, many options. There are many, many trials. There are the tribe trials that used Full Fox Series. So that's given you five fu your uh and your Leuco, of course, your oxaliplatin, your renal tec can all in one go. What we know from these trials is the outcomes are good. But i it's hard to tolerate. It's very, very hard to tolerate. And oftentimes folks will need breaks. Um Even in the tribe trails, actually, people didn't go uh straight through, they were taking breaks. Um It's toxic. Uh and you are using up all of your chemotherapy options uh in one go. So someone has progression of disease on Folfox theory, they can't then switch to Folfox or Fol theory. The other problem is in the real world populations. Um It's very hard for people to tolerate full dose, full, full dose, full Fox. And you start to get to the question of, is it better to get 60% dose for Fox and have to take breaks or is it better to get full dose Folfiri? And for Fox, and again, these are individual conversations with individual patients. I personally have only given full Folker a handful of times. And it's usually to very young people who we have a definite end goal and I'll talk about that in a second. Folfiri and F folks are kinder um they still do have their symptoms uh and their side effects for, for urine or the big one is going to be diarrhea for, for folks. The big one, Doxyla is going to be um your neuropathy. Mostly that's going to be dose limiting. You can always give xelox as well. I have done X with a question mark because Capecitabine plus I know can tends to have a lot of diarrhea. Um We, we spoke about how when you give oral root, it can give you worsening side effects. I've certainly seen people get ciliary. I've seen people who were OK and I've seen people who weren't OK. It's not my favorite. Um But technically, it can be prescribed um when we're thinking about chemotherapy as well, sometimes we want to add on helper drugs. So all of these drugs have trials um in terms of survival, the benefit is usually AAA few months. So if somebody is able to tolerate often we will add Bevacizumab is a Vegf inhibitor, uh Panitumumab or cetuximab or EGFR inhibitors. Um Bevacizumab, you want to be careful with people who are bleeding because as a VEGF inhibitor, that is one of the side effects that it can contribute to bleeding, uh decrease wound healing. Um Also with your EGFR inhibitors, you're going to want to be careful with people who are going for surgery who have just had a surgery, who have just had a procedure. Um, fistulas is another one that you want to be careful with people who have fistulas, uh, especially Bevacizumab. Uh, there's a risk of fistula risk of perforation, again, risk of bleeding. So, selecting your patients very carefully, we are giving adjuncts to but, uh, they can be helpful in somebody who does not have a risk factor preventing their use in some places. Um I've seen some people give chemotherapy and then at the point of progression, they'll add in an adjunct. This is a strategy. I have not personally seen that it works very well, but some people will do that too. They'll um save the adjunct to add in at the point of progression. So we spoke about bevacizumab as a Vegf inhibitor. We spoke about Panitumumab and cetuximab as EGFR inhibitors. Uh you cannot give panitumumab or cetuximab to someone who has a Kras mutation. Um This is a common board exam question. Uh I have here the diagrams. It's a bit of a poor quality here. Uh But the reason that this works or this doesn't work, I guess you can see here in the A diagram we have the EGFR part. When you see EG fr you see uh ligand there coming to the receptor and activate Kr the way the pan mo riTUXimab works. As you can see in uh slide B here is that it blocks the G Fr receptor, right? So it can't be activated. So you can't activate K RS in that pathway. However, when you have a Kras mutation, the Kras is on, it doesn't need the Egfr receptor. So even if you block it, it's not going to work. So that's why there is no role for panitumumab or cetuximab in somebody who has a Kras mutation because it's just not going to work. That might be a little bit advanced for some folks. But if you're in oncology, you're looking at boards. This is a very popular board exam question. So pretty simple, I want you to take a look at the diagram and understand why you cannot give panitumumab or cetuximab to somebody with a Kas tissue. It's simple to me. Anyway, if I had somebody has a biochemistry degree, it's probably much more complicated. So when we're talking about metastatic colon cancer, there are many ways to approach it, right? I've given you all these chemos, I've given you all these adjuncts and different people will have different approaches. You also have to tailor your approach to the patient that you're working with. So when I meet people for the first time, I often ask them, you know, what are your goals here? Um what things are important to you and you try to come up with a treatment plan for that individual patient in general in general. And we'll talk about the exception in a minute. But in general, metastatic solid tumors are not curable. Most patients who come to you with metastatic colorectal cancer will not be cured. Cured means that they have uh prolonged period. Uh That is diseasefree usually over five years. Cancer never comes back and they die of something else. Um In general, my go to because this is the regimen that I see works for most people and of course, I will tailor it to the individual patient is to start with four theory because the first treatment is usually the one that works best for longest. Um It's hard when you get dose limiting neuropathy or crippling neuropathy that people have to push through or live with. Um The diarrhea with FFI is usually controllable uh especially with Imodium lo metil, these kind of agents. So let's just start with for and then use Folfox as a second line. Many people prefer to start with four Foxx and use for as a second line. There's no right way to do it. Uh Third one is Loan Surf. Um So there is good evidence. Do I have the trial here? I do not have the trial here. Uh The trial is called I Believe Sunlight. Yes, the Sunlight trial um that showed B Surf, which is an oral chemotherapy. I will put the generic name in the chart, Trifluoridine, tipiracil. Um So of syllables. So most of the time we just say on surf, this is oral chemotherapy that uh in the more recent sunlight trial was combined with Bevacizumab. Although there is a role to give it alone if somebody has Bevacizumab contraindications. Um This is a very standard third line uh especially after the sunlight trial came out. There is uh now again, depending where you work, you may have access to some of this, you may not have access to some of this. Um I think five, a few based chemotherapies are quite standard across the world. Uh Here in North America. Uh Common fourth line is Regorafenib, which is an oral tyrosine kinase inhibitor. And then in the United States, specifically, flutin is a oral Vegf inhibitor which was approved, I believe in December. I have not seen very good responses with it. Um It, it is a last line therapy. Um and as I mentioned, as you go through the treatments in general, but less and less. Well, you can also start looking at clinical trials as well for patients if they're very fit and you want treatments. But really, I find that once you get past it won't surf, people tend not to do very well and then it becomes an individual patient's choice about whether they do want to keep trying treatments. Because for some people being on treatment is very important versus focusing more on quality of life, spending, quality time doing things that matter. However, with your five a few based therapies, you can get very good results um that really help extend both the quantity of life as well as the quality of life. All right. And again, depending where you work and what kind of access you have, there are some studies coming out for targeted therapies. So I think especially medical oncology, this is uh big field um where the drug companies and the trials are looking at targeting certain mutations. So a common one if you've worked in Melanoma or other fields, honestly, now to B RV 600 E. So this is a very specific mutation in B RF. There's a trial called Beacon uh based on the final results from the B control, cetuximab and Carfene is a viable second line for patients with V 600 E mutations. It's important to note if you're familiar with the literature. But um uh there was an older version of the B control, an interim analysis that had triple therapy with Encorafenib, Bib and cetuximab. So, you know, in Melanoma, the doublet that they gave is Encorafenib and Bib. However, this was not superior to the doublet. So the usual regimen now that is given to someone with B raf B6 100 E mutation is cetuximab and and Cara po 177, which is a few years old. Now for people with MSI high colon cancer. So, microsatellite stability in microsatellite instable instability. Um uh Th this uh study put pembrolizumab on the map. So pembrolizumab is an immunotherapy. There's not a lot of rules for immunotherapy in gi cancers. This is one of them if somebody has MSI heart disease, pembrolizumab as first line was put on the map from chemo 177. And again, patients can have a good response to the pembrolizumab. Also patients with MSI high just seem to have a worse response to chemotherapy. So if you're able to use immunotherapy, uh this may be better for the patient. There is no evidence for ipilimumab and the bone ma trickling through, but we don't have survival data on that as yet, but stay tuned, that's probably coming. Um And then if you have access to next generation sequencing, you can look for things like her two status or tumor mutational burden, but these are rarer and nothing is really standard in these cases. It's a individual discussion with the patient um in the context that you're working in, there's a new trial out of OO which I'm particularly excited about. So this is a collision trial. Um So this relates to patients who have oligo metastatic colon cancer. Um not necessarily the study specifically, but we'll have a quick chart about oligo metastatic colon cancer. So I'm gonna write Oligo Metastatic in the chart for those who aren't familiar with that term. So, Oligo metastatic means you only have a couple of points of metastases classically. This is 1 to 3. Sometimes tumor boards surgeons, individual practitioners will I try to extend that. Um If you are somebody who has metastatic colon cancer that's only spread to a couple of points. There is a small chance that this could be cured. So when we have folks who only have a couple of metastases, sometimes there will be a rule to treat them with surgery with chemotherapy with radiation. And this will be a tumor board discussion. Oftentimes they'll get some chemotherapy, go for surgery, maybe some chemotherapy afterwards or have some radiation, then get some chemotherapy. Occasionally. Occasionally people can get long term survival. And I say it like that because often the intent with all these patients is to cure, but most of them will not be cured. So it's important to balance quality of life while you're going through this paradigm because keeping in mind if you give people folfirinox and you make them so sick, um and you go through a really aggressive surgery and you make them so sick, there is still a very appreciable chance that the cancer may come back or may not actually ever go away. And um that can put you in a type sport. So this collision trial was taking patients with less metastases, fewer metastases. And they were comparing surgery with ablation and what they found. Uh because usually the the thought is that surgery is the gold standard, right? You need to cut it out to get the long term survival, get the survival. And what they found in this study is that the ablation on and the surgery arm, the, the ablation arm was noninferior to the surgery arm. So patients don't seem to benefit from getting this really aggressive surgery. Um, the ablation seemed to work just as well and this is good news for our patients who may not want to necessarily undergo really aggressive surgery when they can just undergo an ablation. So, stay tuned. Um, because this has the potential at least to change how folks are managing this population. I, we spoke about circulating tumor DNA. All right. So that's colon cancer before we go to rectal cancer. Are there any questions? All right. So just a few slides on rectal cancer now, because rectal cancer does have some differences compared to colon cancer specifically. And the first question is going to be a home. So here we go. Stage by stage, which one is more aggressive rectal cancer or colon cancer? I want a few minutes to think about this. All right. So yes, rectal cancer is considered more aggressive stage by stage. Rates of recurrence for localized or locally advanced rectal cancer are going to be higher than the colon cancer. So, there is a role in rectal cancer for neoadjuvant treatments as opposed to colon cancer where the studies don't really support using neoadjuvant treatment in rectal cancer by and large. Uh, and we'll talk about some of the trials in a moment, but especially in the last few years, the thoughts have shifted to giving neoadjuvant che or neoadjuvant treatments before surgery. And there are many options. So there's a short course of radiation, which is usually a five fractions, five days of radiation. Um, it can be helpful if someone is having a lot of bleeding, it can be helpful if someone is a bit frail and doesn't wanna come back and forth to the cancer center. Um, on the first side, you have chemo radiation, which is where we give chemotherapy, a five fu based chemotherapy along with radiation that's usually over a period of 5 to 6 weeks. Um lower dose per fraction but more fractions chemotherapy as well. Um Some people will do radiation short course and then chemotherapy, there's also immunotherapy. I think I'd speak about that trial in just a moment. So there are different options in general if you have somebody with a rectal cancer, depending where you work, often. Um their case will be presented at a multidisciplinary tumor board. And decision will be made between a surgeon, a radiation oncologist and medical oncologist about how to proceed for this particular patient. Total neoadjuvant therapy or TNT has really taken off in the rectal cancer world over the last four years. This is based on several trials that we'll see in a second. Um And this is giving radiation plus chemotherapy before the surgery. So giving everything all the treatments before the surgery in the trials. Those who were candidates for total knee adjument therapy had either clinical t three or T four staging had positive lymph nodes or they had certain margins or certain sphincters that would make a surgery very difficult. Three big TNT trials that really put on the map. Big one is Oprah. So this was a trial that uh used TNT. They are, they did, they compared chemo radiation followed by chemotherapy. So consolidation chemotherapy to induction chemotherapy where they give chemo first and then do the chemo radiation. The chemo radiation followed by chemotherapy uh did better in the trial. And many centers have adopted this as a new standard practice. So to get the chemotherapy and the radiation together followed by chemotherapy total about six months of treatment followed by surgery in the trial as well. Patients were given the, well, some patients I don't know if they were given the option necessarily, some patients underwent surgery. Some did not, they just went on surveillance, surveillance uh for folks who have had TNT is not standard, it is used, but we don't have the studies reported as yet to know. Is this better? Is this worse than having surgery who can safely not have surgery? So people will avoid surgery sometimes and just go on surveillance for folks who have had TNT but that is not considered standard. So Oprah is one of the biggest TNT trials that really put it on the map influence what we do. There's also Pra and Ma so P used this strange neoadjuvant adjuvant combination. Um Rapido used a short course of radiation as opposed to the chemo radiation that was done in Oprah. So it's a bit tricky um to combine all these trials together because they all did slightly different things. And that's part of the reason too why there's not really a good consensus about this is when we should do TNT. This is what TNT looks like. This is when we should do short course radiation, et cetera. There is also a widely publicized trial using Sterle. So immunotherapy for patients who had rectal cancer in a neoadjuvant setting, um They did not do chemo radiation or chemotherapy or radiation. They just gave them this immunotherapy patients who had MSL high uh microsatellite unstable rectal cancers and there was a complete response in 12 patients. This is optimistic news, but we don't yet have survival data. We don't know if they need surgery. How do they do without surgery? So it's pretty premature. Some places are adopting this as a standard of care to give immunotherapy to patients in rec with MSI high rectal cancer. But I would caution you um to make sure that you do your due diligence, discuss it with the patient. Consider all the options, speak to the rest of the team because this cannot be considered standard as yet without survival data, without more data. This is more something to just consider. All right. Um So I was a little you about rectal cancer. I think this is the last question just about surveillance. Oops, not there. Um So if you're still with me, you can write in your chart. So if somebody has been treated for colorectal cancer, um what would be your surveillance strategy? What would you recommend for them followup, scans, blood work? What would that all look like? I will know here too, the guidelines differ from what they say. So what would be your personal recommendation? Of course, again, we tailor this to the individual patient. But just to get you thinking at the end of the talk, I think I've sent everybody to sleep. So in general, I for us to summarize all of the guidelines, recommendation would be clinical checkups every three months, including blood work, including ce so full blood work including cea every three months for at least the first few years, maybe 1st 2 to 3 years. Then after that, you can probably extend it to every six months for another two years. So you want to follow patients with history of colorectal cancer for at least five years. Colonoscopy should be done within one year of diagnosis and then as needed at the discretion of the colonoscopist, the colonoscopist, the person doing the colonoscopy. Um and then ct scans in general, the guidelines say every 6 to 12 months um depending which guideline you look at and again, depending also on the patient I should have mentioned. And I did not, I'm only realizing this now that we mentioned that MRI and pet scan are not used in the workup of colon cancer. You do need an MRI for the workup of a rectal cancer because the MRI is really what's gonna help you see staging T three T four positive lymph nodes, certain sphincters, et cetera. You wanna make sure that you have a good picture before you do or don't go on the TNT route. All right. So that was a whirlwind tour of colorectal treatment. Workup. Oh Colorectal cancer workup and treatment. Happy to take any questions. Um Happy to let folks just rest and digest all of the information. I'll stay here for a few minutes just in case you're thinking things over and you have any questions otherwise. Thank you so much for listening. Hope you learned something. Um No. Uh there is a feedback link. I think it's sent to you afterwards. Let me see, send feedback form by a chat. Maybe I can do that too. Yes. OK. I think one is in the chart too. So you'll get it in the email or you can click here too. All right, everyone. Well, you've been a wonderful audience. Thank you so much. Hope you have a good rest of your days.