MRI-Guided Radiotherapy in the Management of Abdominal Metastases from Colorectal Cancer: Dr. Basree (2025)

Betsy Post 0:00
So I’m just going to do a little introduction about how tonight’s going to work and introduce you, so good evening, everyone. I’m Betsy post. I’m part of the COLONTOWN cabinet and the community leader for the metastatic groups within COLONTOWN. So I’m excited to have folks here live tonight. Also, of course, this is being recorded. We do recordour doc talks and then make them available in our community, as well as on COLONTOWN University in our lecture hall, so that this can benefit many more patients and families in the weeks, months, years ahead. So the way that it works, if you’ve not been to one of my doc talks that I host, everyone has been auto muted. Just request that you stay muted during the presentation. You can put questions in the chat, and then at the end, we will have time for Q and A and I will take your questions and read them. So definitely, we will get to your questions, I promise. And without further ado, I will introduce Dr Basri. I hope I pronounced your name properly. I apologize. We’ve only communicated via email, but just so everyone knows, great. Just so everyone knows I connected with him through a poster for ASCOGI 2025 this year. It was a very interesting poster to me that was really relevant for our stage four population, especially those that have been heavily treated, and they may have liver mets, maybe distant lymph node mets, some different types of metswhere this therapy I thought it was very interesting and maybe could be useful for our community. So we’re so excited that you would make time for us tonight. I know it’s late in the day, but we really appreciate it, and we’re excited to learn from you. So thank you for being here, and I’m going to pass the ball to you.

Dr. Basree 1:53
Thank you, Betsy, for that kind introduction. I’m really excited and thrilled to be talking to you all about something that I think is a great tool in our toolbox to help patients. So my name is Mustafa. I’m a fourth year radiation oncology resident at University of Wisconsin. This is, you know, beautiful Madison here, and I’ll be talking to you about MRI guided radiotherapy. Are you seeing my screen as a full screen, or is it the lecture notes? Full. Okay, great. So I have no disclosures. Those are the learning objectives. We’ll talk a little bit about, just broadly speaking, the management of colorectal cancer, and then dive into the advantages of MRI guided radiation therapy, talk about our experience using this modality or tool, and then the few ongoing studies in this space, and then who would be the ideal patient population for this. I like to start with looking at trends. And, generally speaking, trends and rates, probably, as many of you know, are decreasing for colorectal cancer, both in terms of diagnoses, so incidence rates, both men and women, as well as mortality rates over the past, now, 50, 60, years or so, we are seeing increasing rates of colorectal cancer in younger adults, however, especially those between years 20 to 24 both in terms of incidence, this is from about 20 years or so 1998 to 2019 and same thing here. In terms of mortality, those patients do not necessarily make the bulk of colorectal diagnoses compared with, say, 65 plus, where you have somewhere between, 300 to 400 per 100,000 but still, this trend is certainly worrying and I think the recent change in the colonoscopy starting age, from 50 to 45 is kind of borne out of this att least a little bit. Same thing here, where, in general, diagnoses across different stages are decreasing, the rates of localized and metastatic cancer are increasing in younger adults. This is all ages. And then this here, looking at regional in terms of the primary diagnosis as well as local or regional lymph nodes, or localized, or even distant. Those rates are increasing over the past 20 years. Thankfully, those rates are more or less stable from 50 to 64 but more importantly, decreasing in the 65 plus patient population. And those patients are presumably captured in the colonoscopy screening, so maybe some of that is mitigated by the colonoscopy compared with patients who are not within that age.

Dr. Basree 4:58
So treatment decisions for Stage IV colorectal cancer can be complex and really beyond the scope of this talk, but I included them here for completeness sake, just to illustrate how complex they are, and if, certainly, if anybody has any questions, they depend on genetic markers, sometimes like micro satellite status as well as the presence of mismatch repair proteins or deficiency alternatively, but by and large, backbone of chemotherapy as first line and then followed by different treatments, depending on the response. You may have seen in the news, immunotherapy made waves in this space right here. It’s predominantly in patients who have micro satellite instability that is high or deficient in the mismatch repair protein proteins. Those patients tend to derive the most benefit from immunotherapy across different cancers, and certainly Colorectal cancer is no different. But if you’ll see here, it’s a really small patient population here, and then there are other treatments here, as you go down the line, or specific patient groups, in terms of patients with liver limited metastatic disease, multi disciplinary discussion is certainly the key here. Roughly 20 to 30% of patients with colorectal cancer and liver metastases are candidates for surgical resection. That means the vast majority of people are not, unfortunately, are not candidates for surgical resection, which can be potentially curative, especially in patients with liver limited or oligo metastatic, which we’ll be talking about, that colorectal cancer. Multi disciplinary tumor conference discussion is critical to make sure the patient has the best treatment option for their particular situation, and the treatments are really tailored to the overall disease biology and the the clinical scenario. Oftentimes, a combination of treatments and sequences are employed to help achieve the optimal outcome. Broadly speaking, patients with low metastatic burden but unresectable may be treated with SBRT or ablation. Those with higher disease burden, then you could consider radio embolization like y 90. Those local therapies are often done after systemic therapy to ensure that the systemic control is upfront, because we don’t want to focus on one organ while ignoring the rest of the body. Systemic therapy, be it chemotherapy, targeted agents, are really paramount in addressing all sites of disease.

Dr. Basree 7:44
So then, what is oligometastatic disease? I tried to find a colorectal specific picture, but I couldn’t. So my apologies, this is lung cancer, but oligo metastatic disease refers to cancer that has spread beyond the original site, but only to few spots, so commonly one to three or sometimes one to five lesions, depending on what reference you look at. So assuming this is the primary tumor right here, when it spreads to the regional lymph nodes, then it’s considered loco regional disease, still not technically metastatic. Once it spreads, it spreads beyond the primary site or the regional areas like nose and whatnot, then it’s considered metastatic. But if you have one to three or one to five, then that is considered oligometastatic or limited metastatic burden, and then poly metastatic, or diffuse metastatic or systemic disease. It basically means that the cancer started here and then ultimately ended up in other parts of the body, for in this particular graph or figure, and the different lobes of the of the lung, as well as different lobes of the liver, adrenal gland. It is thought that patients in this particular stage, in the oligometastatic stage, may have slower growing disease and could potentially benefit from treatments aid that the long term control, like surgery or radiation.

Dr. Basree 9:12
I just tried to jot down some ideas here. It was inspired also from from this particular presentation, but oligometastatic disease may be less biologically aggressive, we don’t know for sure. It may be more treatable with local therapy. If you treat small foci or small areas, small lesions, maybe then you’re mitigating that shedding or that sloughing off of cells, and then you’re reducing the risk of seeding other areas. That’s a theory. We don’t know for sure, but you maybe the patients with oligometastatic disease have favorable tumor microenvironment that does not allow the cancer to grow to the poly metastatic stage. Maybe those cancer cells are that are seeding other organs are simply just cells that have sloughed off, as opposed to, cells that have developed the mechanisms to break away from the primary tumor and try to seed other areas. There’s also the soil hypothesis that maybe even though you have cells in there, the soil is not hospitable to kind of that sprouting of cancer cells in that particular organ. Maybe they don’t have good blood supply, maybe they have high immune surveillance, and those things would would prevent that cancer cell from taking off, versus other organs that may not have those things. So this is a pooled analysis of two phase three studies out of Italy. They enrolled close to 1200 patients with metastatic colorectal cancer. This was a chemo study, essentially, but they found that patients with oligometastatic disease. So if we look at this graph here. Y axis is overall survival. X axis is months. Patients who have oligometastatic disease in red did the best compared with patients with non oligo disease. There was about 16 month difference in survival. And then when you look at this specific group, the numbers become smaller when you start dividing groups even more. But when you look at this particular group, patients with oligo metastatic disease specifically benefited the most from the addition of locoregional therapy like surgery, SBRT or radiation or ablation. So they had five years of survival, compared with about three years for those who did not receive this particular treatment

Dr. Basree 11:46
So this was intriguing. So if that’s the case, then is it the biology of those tumors that are different? So if we look at oligometastatic disease, are they biologically different. This was a review of about 130 patients with new metastatic colorectal liver mets, mostly, patients with one to two liver metastases who had surgery for their liver lesions. So now wehave tissue from the liver, and they basically did molecular analysis, and they followed those patients to assess overall disease outcomes. The figure here showed that the integration of molecular subtypes with clinical outcomes can resolve three different patient populations so patients divided in three groups, the red group here has the worst overall survival compared with the group here in in blue. But even then, if you look at the patients in the red group here, which is considered high risk, the x axis here is years, so up to 10 years, roughly 20% of patients are still alive. Those are patients with metastatic disease. So that was really, this is very interesting, tells you that maybe we should be treating all those patients aggressively. But more importantly, they’re not all the same, right? So maybe you can intensify treatment in one group versus the intensify in others to preserve quality of life. We’re certainly not there. This is just a hypothesis, and if we look here to Panel B, this further shows this trend. So for instance, among patients in the high risk group here, 86% of them have either recurred or died, compared with about half of patients in the in the low risk group. Similarly, patients in the high risk group had more recurrences compared to those in the low risk group. What’s interesting when they look at the molecular features of the primary tumor that came from the colon or the rectum, they found that they have limited prognostic ability in terms of how those patients are going to have metastatic disease, suggesting that the biology of the metastases that are in the liver are different than those in the in the primary tumors and and that could be important to help us understand some of those mechanisms that lead to patients developing metastatic disease.

Dr. Basree 14:24
This is again another graph from the same paper, the same group, they ran some fancy integrated analysis that is called similarity network fusion, or sniff. This is what this is algorithm where they combine different data sets that individually are not very helpful, but when you combine them altogether, they help describe distinct groups of cancer behavior. And this was done interestingly, independent of what the pathology looked at after surgery or the survival data. So after doing that, they found that patients ultimately fell into three groups or three buckets. They called itsubtype one, subtype two and subtype three, that are all molecularly different if you look here. Despite those groups being developed entirely on molecular features, they found that patients in those group had substantially different clinical outcomes. For instance, majority of patients in subgroup two, the green one right here, who had immune signaling, they were alive at 10 years, compared with group three here, or subtype three, which is only 20% who are alive at 10 years.

Dr. Basree 15:41
I just want to point out that the color coding is unfortunate. It does not really correlate with this. Those are two separateanalyzes. But at any rate, this particular analysis demonstrate that not all liver metastases are created equal, and that some patients may benefit from more aggressive, intensive treatments upfront to clear their metastatic disease before entertaining locoregional therapy. So then what is the evidence? I mean, this all sounds great, but what is the evidence for treating oligometastatic disease? Unfortunately, we do not have phase three or large scale trials yet for treating oligomostatic disease in colorectal cancer. There’s one trial that I’ll mention later that is currently enrolling, but phase three studies are the gold standard for changing practice. We don’t, do not have that right now. We have smaller, earlier studies, and we have observational studies that help us, kind of guide us into this, this treatment space, and shed light on who might benefit from this particular treatment. One of those studies is a phaseII study in oligo metastatic disease. It’s called the CLOAK EORTC trial. It’s phase two, and started enrolling about 20 years ago, and enrolled 120 patients with unresectable liver metastases, they were randomized to systemic therapy. So chemotherapy or targeted agents with or without ablation. So this was an ablation study, not radiation. Ablation here also included surgery if it was possible. So those patients had chemotherapy initially and then were randomized more chemo or locoregional therapy. The conclusion was that the addition of local therapy in addition to chemo, had survival benefit in those patients, basically roughly about 25% improvement in survival. There are two papers here. If you look at the first paper, there was no difference. But then we look, when you wait long enough, it seems like those curves separate here. So same thing here, survivability fraction, y axis, time in years on the x axis. And if you look at 10 years here, or at least we could look at eight years, because we have the numbers. About 10% in the group that did not receive locoregional therapy, compared with about 35% or a third were alive at eight years, if we included local therapy.

Dr. Basree 18:17
So SBRT is a highly focused form of radiation. It delivers high ablative dose. It has sharp dose drop off. And the reason why I’m shifting gears is start to talk a little bit about SBRT and whether it has a role in oligometastatic disease. It’s typically low fractions, so one to five in the US, maybe a little bit longer if you’re in Europe, the the course is short. So for patients who have metastatic disease who need to go back on chemotherapy or other systemic agents, this is a good option, because it doesn’t cause a lot of disruption. There is some radio biology and radiation damage that might be slightly different with using SBRT versus this longer course of radiation. This one particular review back in 2023 that looked at SBRT in the patients with oligometastatic disease, and they deemed that the quality of the evidence is low. Remember, there are no phase three trials, really, not a lot of, if any, phase two trials in this particular patient population. And so we rely on smaller studies, rely on observational study. The local controls were relatively low in this those studies. So overall survival isaround 65% at one year, and then maybe 50% at two years. Patients who receive SBRT have at least, typically or historically, have received other treatments first, and they’re not resectable, or they’re not candidates for y 90 or other treatments, and so they’re referred for radiation. So inherently, the patient population may be a little bit more advanced.

Dr. Basree 19:59
So, I like to have this slide. The basics are simple. The goal is to hit the bad guys and spare the good guys. It’s a local treatment modality so it damages cancer cells while trying to avoid harming normal tissue in the abdomen. This could be tricky. Organs move and shift every day, so we need to target those tumors precisely, we address this by either including additional tissue. So for example, if we’re trying to target, let’s say this one here, if you’re unable to see the lesion very well, then you might include a margin around it so that you’re not missing that you know is not optimal in some organs, because you might be close to a critical structure. And if you are, then we’re forced to lower the dose tonot to cause harm and toxicity. Instead, we can use image guidance with real time visualization to help us adapt every fraction, each radiation treatment to any given day anatomy. So those four pictures here, are MRI guided radiation. It’s different from CT, and I’ll show you some pictures of CT in that you can see soft tissue much better. You know, this is a liver. This is the kidney we’re targeting. Only portion of the kidney here. This is a PET scan. And this is a tumor of the kidney right here, but then that’s how you pee out the contrast as well. So it’s kind of hard to tell where the tumors stop. And so certainly you can rely on other images and try to delineate the target better. But you can see, if you have an MRI, you can delineate it just a little bit better.

Dr. Basree 21:47
Other times you’re close, especially in the liver, you’re close to critical structures here. So in green, this is part of the duodenum, or small bowel. You can see the target where we’re radiating is in this area right here. So the pink is what we’re targeting. Those concentric lines are how the dose is dropping off. The red denotes a specific dose distribution. But see how it’s curved around the stomach. So this is what MRI allow us to do if the patient comes in and they’re for treatment and their stomach or bowel is close to the target, then we’re able to kind of carve out the dose to minimize toxicity that particular day. So I guess I talked about some of those things just help us deliver that high dose with minimization of normal organ dose exposure, it helps us see soft tissue more clearly and adapt plans in real time. Adaptation doesn’t typically happen in CT based radiation, there’s a new machine. It’s called Ethos, which tries to adaptthe radiation plan based on CT radiation. It’s newer technology. It hasn’t caught on necessarily, but certainly more and more facilities are using CT because you can treat a lot of patients on CT, as opposed to MRI, which could be a little bit more selective there.

Dr. Basree 23:25
So this slide is a little bit older, but now probably close to 90 or 100 centers in the world that treat with MRI guided radiation therapy. In our practice, back in 2022 we treated up to 1000 patients. Almost all of those patients were adapted, meaning that we changed the plan based on that day’s anatomy, and then the majority of those patients were high doses per treatment, so it allows us to put more dose in while respecting healthy tissue. If you look at the breakdown of what we use the radiation that the MRI machine for: oligomets, nodes, liver, pancreas and GI, so predominantly abdominal based sites. GU, so kidneys, bladder. This slide highlights how MRI guided radiation offers advantages over traditional X ray guided radiation, again, by better soft tissue visualization and tumor localization. So if we were treating a liver metastasis with X ray, or with, sorry, on CT based machine, it’s hard to see the lesion here. So this is an image that we typically we would get to localize and lineup the patient correctly for the treatment. It works great for kind of soft tissue, organs like this, bone, that’s what we use, that’s the bread and butter of radiation oncology. But if we’re treating an area right in the middle of the liver it’s hard to see, and the way to go about this is to put some markers here. So those bright spots, typically we could use, gold or anything that lights up on CT to help the radiation oncologist know the extent of what we need to treat. You can see those seeds right here as well. Those seeds remain in the patient. They’re harmless. They’re just there. Versus on an MRI, you don’t really need those seeds. You can see the tumor clearly here, and you can see that with the CT, that margin may be a little bit bigger compared with here in the MRI, where we can probably make it tighter. So better visualization, I guess, is just the take take home point here. Functional imaging. There’s actually more development in having some functional imaging, so PET on top of the radiation machine machine or other diagnostic sequences. With MRI, that’s possible with X ray. Historically, that’s not possible. But there are new machines that aim at doing that. There are two machines currently in the US and, I believe in the world. There’s a V Ray Meridian system, which is what we have at University of Wisconsin. And then there is the Electa unity system. I included this here for those of us who are physics inclined, but we certainly don’t have to go over that. Some practical considerations. The blue things here are the coils. We put them directly over the area that we would like to target. It provides the best visualization. We typically don’t use a mold. If you’ve had radiation, you probably sat on a mold. For radiation, the board is kind of small, and the table is not, we can’t use it a lot of times because of collisions, sometimes could happen. And also it kind of interfere with the quality of the image.

Dr. Basree 27:08
Another thing we do with MRI treatment is to do breath holds, especially for abdominal locations, or certainly for treating in the chest. Why breath holds? There’s some technical physics related things here, but in a nutshell, it really helps improve the image quality. I’ll show you some images here shortly. But the quality of the image becomes better when the organs are not moving. If the organs are moving, then you take multiple slices and you can average them, which could show kind of like a smear. The margin is also smaller when we’re treating with breath hold, because we don’t have to encompass the entirety of the path that the tumor is taking with every breath. So this further allows us to deliver high dose radiation while sparing critical structures, because we’re focused on the radiation. So this is an example of a pancreas cancer case. So this is the cone beam CT, or the image that we basically get at the machine when the patient is at the table. Again, you can see kidneys. Well, you can see bones here, really well, bowel, heart. To see pancreas. If I’m scrolling up and down, I could probably find it, but it’s more challenging. This is free breathing, so kind of an average scan. If you look here, the image looks better. it’s a breath hold image. You can see the liver here much better. You can see the kidneys, the spleen. Make out some bowel loops. Now, if you go to the MRI, it’s even better. You can clearly see the pancreas right here, some bowel loops, part of the kidney, gallbladder and whatnot. This is another example of hepatocellular carcinoma. This is using Cone Beam CT.

Dr. Basree 29:00
Where is the liver, where is the heart? It’s hard to know, but you can somewhat make out this lesion right here, so you can certainly line it up, but probably from day to day, we would have to include a bit for margin. On an MRI, it’s easier to see. You can clearly see the delineation between the liver and the heart right here. Here’s an example of a liver metastasis we treated. We typically use IV contrast in those cases. For for liver metastasis, they take up contrast real well. And you can see the distinction, or the contrast, between normal liver and where the tumor is. So it allows you to draw the target well, deliver that high dose and spare toxicity to normal liver. This is another video of pancreas radiation. This is a side image. It’s a video. Let’s see. So, you know, this is what we see typically, when we’re having the patient under treatment. So we have drew the target on here, which is the the pancreas. The blue is where the radiation is turned on, and the patient can see. During the radiation, the patient sees exactly where they are, and they time their breath to this blue box so that we trigger the radiation. And the breath is held, typically for 15 to 20-25, seconds, and we’re able to deliver that radiation, then resume normal breath, and then we repeat this. So, the patient could see very well where the tumor is, compared to where we turn the radiation on, we have spared the normal bowel loop here, normal structures that will loop here, part of the stomach here, the liver, is not getting radiated. As opposed to that, we could treat this whole volume with radiation to encompass the entirety of the motion, but that would be radiating more healthy tissue. On the left side of the screen, you see how a tumor moves out of target with free breathing. I know you just saw it on the video, this is a liver, and see it still moves. Again, we can encompass all of that, but that’s more healthy tissue. On CT, this will be a bit harder to see you can certainlydo breath holds on the CT treatment. And a lot of times we do that, especially if we have a large tumor or multiple tumors. And sometimes we place those fiducials or those gold marks to help us see. On the right, this is an example of peritoneal metastasis, or peritoneal deposit. It’s below the liver. This is the liver edge right here. The area right here is incredibly small, but you see it really well on the MRI. And you could trigger the radiation only when the target is within the radiation parameter.

Dr. Basree 32:17
So another example here is that your body is not the same every day. So this shows that how your anatomy can change over time during treatment. This is an example of stomach cancer. So on day zero, the stomach was this pink volume, right here, and this is the radiation dose that we’re delivering. Different colors correspond to different dose levels. On day nine, you can see the stomach’s changed. And we don’t control that, those things just happen. Our bodies are fascinating. But on day nine, the anatomy changed, and then all of a sudden, this particular, on the blue this new target is uncovered, and so we have to readapt the treatment to make sure that we’re covering and we’re sparing other toxicities. Tumors also shrink during treatment. Sometimes. This is an example of GE junction, or gastroesophageal junction tumor, where the start of the treatment, we treated this whole area right here. This is part of the stomach. This is part of the liver. And then three weeks into treatment, you can see how this tumor basically melted away. With CT, you can certainly, if you see that, you can adapt by bringing the patient back for a CT simulation, replan the treatment. But with an MRI, we can do that right there on the table.

Dr. Basree 33:50
So when patients have just few liver lesions, high dose SBRT, or sometimes called SABER, if you’ve seen that, in three to five sessions that could control tumors really well, especially when we can escalate the dose safely with MRI guidance. Sometimes that’s a bit more challenging with multi sites. This is just another example to show, specifically liver metastasis, how much it moves in terms of the adaptive workflow. In a nutshell, I think I like this picture a bit better. We will actually talk about this first. So the patient is simulated first. So this is similar to a CT simulation, similar with the MRI. We also get a CT simulation to help us with the dose calculation, but we’ll get the those images, they’ll come to us to draw them and make sure we’re targeting the area we want to target, and then we send it to the dosimetry team to come up with a plan that allows us to put in the dose where we want it, and avoid radiating other tissue. And then, when the patient comes in for treatment, we’ll take an image and compare the treatment image that day compared to the simulation image. If it’s different, then we would adapt the treatment right there and then. And then we would recalculate the dose, assess the quality of the image, take another image to see if we can track it. Those kind of the pictures, the videos I showed. And then if everything looks great, then the patient will be receiving this treatment.

Dr. Basree 35:31
This is another graphical representation of this process, this is the original image. This is the new image of the day, of the fraction. This is redrawing, calculating the dose. If we can use the original plan, great. If not, then we have another plan, and then we make sure that we can deliver this safely. And then the patient looks at their anatomy, and we deliver the treatment. For multi site SBRT, MRI guidance is especially helpful to treat multiple sites safely, even if they’re moving differently, because you’re able to draw them every day they come for treatment. And so those the challenges are, you can’t really see all of them, but you can at least draw them every day and make sure that you are within some acceptable margin of error that allows you to focus on one lesion, add a margin of error to the other lesions, but deliver the radiation at the same time to treat all of them. This saves time for patients. You don’t have to come in for weeks on end, for multiple spots, we can treat basically all of them at the same time. It’s called a single ISO center plant, or a single, basically focal point where we deliver the radiation. And then adaptation can also be sometimes challenging for having multiple lesions, the time to draw and calculate the dose could be a little bit longer. And so that’s, you know, the patient is on the table. And I know, I personally do not like the MRI being in it. And then there’s some things that we work closely with our physics team to mitigate. So the distance from the ISO center. So if you have a tumor, if the ISO Center is here, but then the lesion is somewhere far lower in the liver, we have to introduce a margin to make sure we’re not missing the target. This is just a panel of what we look at when we evaluate the plan. We have different parameters here, so normal structures, chest wall, duodenum, esophagus, heart. And then we have GTVs, or gross tumor volume, and this is the area that we see. So this, if we would draw this, this will be a GTV. PTV is a planning target volume, which is the GTV, plus a margin so that we’re not missing. It’s a small margin with the MRI, because you could see the target well, although that margin could be a little bit larger depending on how far the lesion’s from each other. And then we look at this and say, Okay, this is the proportion of the structure receiving the dose in x and so 60 Gray, for example, which is the unit of radiation. I would say, this, PTV is receiving about 95% of it, and I would make a decision, yes, this is good. If not, we need to push on it a little bit more, or we need to protect some of those structures more. So it takes a little bit time for for the patient on the table to come up with a safe plan and to complete delivering it.

Dr. Basree 38:42
So why do we care about delivering high dose radiation? Dose is associated with local control. And so this is an observational study, a retrospective review of 70 patients who had about 100 colorectal metastases they were treating with SBRT at a single institution. I think it was in Korea they follow those patients for a median of about three years, and they found that the dose predicted their local control. And so they were able to kind of look at three different groups. Group one has a dose of 80 gray. Group Two somewhere between 100 and 112 and group three is 132 those are just, those are biologically effective doses, the dose for SBRT. So for this one, it would be somewhere like 40 and five fractions, or something like that. This one would be about 50 to 55 gray and five fractions, this one would be 60 gray plus in five fractions. So just to give you some perspective, you can see here that group one which is the solid line, had the highest risk of tumor recurrence compared with the group that had the highest dose of radiation. So this tells you that colorectal liver metastases may be a little bit resistant, and they need extra dose to control them, and so that given that data, we set out back in 2018 to run a study on escalating dose to those liver lesions, and at the same time trying to relax some of the bowel and liver tolerance constraints or goals that we have in mind, because oftentimes we’re limited by those things, but those could be very, very conservative, and so the study was trying to increase the dose, while at the same time trying to increase the tolerance to those structures. So this is the schema. It’s a four by four design, which is kind of typical for dose escalation, where you enroll patients in a cohort of four at a time. The goal that we wanted to prescribe was 80 gray, which to put it in perspective. This is certainly in this group right here. It’s about, I believe, 200 or something BED and then we’re trying to escalate the tolerance of those structures. If once we have a dose that makes sense and is safe, then we would take this to a larger study. This study is currently in review in our IRB so, and it’s not currently live, but hopefully soon. We put together this preliminary analysis of the small cohort of patients that we had. The MRI machine was being serviced, and so we figured, let’s look at our experience here and see how we’re doing. So only 16 patients we were able to look at. We followed them for just under two years. About 80% of them were patients with colorectal cancer, and the SBRT dose was quite high. It was 80 gray to at least half of them. I’ll show you a little bit of a graph here. About half of the patients had one to two lesions, and half of them had more than two and then the size of the lesions were also a little bit large. So four centimeters, the largest was about 13 centimeters.

Dr. Basree 42:18
This graph here is graphical representation of those patients. So patients 1 through 16, the majority of them were good performance status, except one patient had a little bit poor performance status in terms of the number of lesions, almost half of them have three or more. So those are slightly more advanced compared with the other paper that I showed, the paper from Korea. The dose in the majority of patients were escalated, so higher than 60 Gray, majority were somewhere 70-75, or 80 gray. And, more importantly, toxicity. If you see here, adverse events, almost all patients have some degree of side effects. But when we look at the side effects that almost all of them were grade one, and that’s, it’s, we don’t want to see toxicity. It’s good, though, that the toxicity was not severe enough to persist. Those who are grade one here, majority fatigue and GI symptoms. There are some lab values as well that increased with radiation, which is not unusual, but those typically went back down. Grade two toxicities, so nausea that was probably severe, or diarrhea also occurred. There was skin reaction in one case. And then there was some abdominal pain also in one patient. There were no dose limiting or grade three or higher toxicities in those patients up to two years, or I should say, a median of 21 months. Looking at the control data, the two year local control is 85.2% this table here might be a little bit busy, but overall survival was about 50% at two years. Again, this is patients with one of them with breast lung, and Ibelieve this was sarcoma, if I remember correctly, but still, those patients had several liver lesions. Distant relapse was very common, and that’s not unusual. We are focused on the liver, but there’s cancer outside the loop, and so distant metastasis, at one year, was about 63% and at two years, it was majority of patients. The IFLC is in field, local recurrence, so basically how well we’re controlling what we’re treating. And at one year, it was about 94% and at two years, 85%. And those are the Kaplan Meier plots, forgive me, I don’t have the x axis. This is the time in months. So one year, two years, three years, you can see the survival is about close to 50% at two years. In field recurrence here is also about 85% here up to two years. And then any recurrence, so that includes both outside what we treated in the liver, as well as distant metastasis, that was quite high.

Dr. Basree 45:33
So then how about multi site SBRT?. This is not typically done on CT based radiation machines, because of the difficulty in localizing lesions, toxicity concerns, because we’re treating a large volume of tumors, we might be causing harm to the liver function. And what we typically do is, if that’s the case, then we would have to reduce the overall dose to make sure that we’re not causing harm. So we’re unable to safely escalate dose when we have a lot of liver lesions like that. Those concerns are somewhat mitigated with MRI guided radiation. So we looked at our experience with doing this. We looked at patients with four or more liver metastases, and whether or not we were helping those patients. What was interesting, as I was going through this, was trying to score local control. If patients have 10 liver metastases, and then if we’re following local control, then we should follow every individual’s tumor, every tumor that was radiated, and track to see when that particular tumor has grown. That would be considered a per lesion analysis. Alternatively, we can look at per patient, and if any one of those treated areas recurred, then that would be considered a local failure of the treatment. And so that’s what I ultimately did. So it’s a very conservative, I think, approach to kind of see how many patients are progressing in the areas that we’re treating, even though we’re not capturing every individual lesion. And this was 24 patients with close to 160 lesions. If I can remind you of the of the Korean study they had, I think 70 patients with 100 lesions. So we have significantly less patients, but significantly more lesions. The median follow up was just under a year. The majority of them were men. Were good performing status. The majority of patients had metastatic disease at diagnosis. And you know, initially we talked about algo metastatic disease, 80% of the patients we looked at were considered poly metastatic. So those are patients with systemic, diffusely metastatic disease, who were offering local therapy to. The median number of chemotherapy lines, half of patients had three or less, and the other half had more chemotherapy. So that’s a lot of chemotherapy. Two patients had Y90 before radiation, and then one patient had after. Those patients had a lot of liver lesions. The most was 11, the least was four. And the size also varied from point one centimeter to 14 centimeter. As you can imagine, 14 centimeter tumor is relatively large. And then, three patients had three courses of liver SBRT. So this patient population is a little bit more advanced compared with everything else that I’ve been discussing so far. The rationale for why we’re doing this, they’re referred to our clinic either to control tumors that are growing. Patients have toxicity from the chemotherapy and they needed a break, or patients have derived great benefit from the chemotherapy. But then there are a few areas that have not responded, or have not changed, and so we’re doing radiation as a consolidation to kind of give it an extra hit.

Dr. Basree 49:42
Acute toxicity was a little bit lower than the other study, was about two thirds or half of patients. Those were predominantly fatigue and nausea, those thankfully resolved shortly after. In terms of late toxicity, it’s kind of hard to look back into the chart and assess this, but looking at grip fracture, bleeding, ascites or liver failure, including, biliary ductal dilation. There’s only one patient who had dilation of the biliary duct. This happens typically, let’s see if I have thepicture here. If we’re treating in the center of the– not a perfect picture, but we can pretend that there’s a duct right here. If we treat right in the center, there could be some scarring where that duct might narrow, and then you’re unable to drain the bile. That’s a problem that could ultimately lead to liver failure. Unfortunately, tumors cause this as well. This particular patient had radiation and then this particular toxicity was noted about nine months afterwards in the context of multiple liver metastases. So it’s kind of hard to know 100% but it’s certainly worth noting that radiation may have worsened it. In terms of the liver function and health. Child Pew, is a surrogate that sometimes is used it’sdeveloped to predict mortality and cirrhosis, but sometimes can also be used as a surrogate for liver health. At the time of consult, the majority of patients had healthy liver or compensated liver. Child Pew classification is A, B or C, A is the best, C is the worst. And then within even those there are numbers five and six in a seven to nine in classification B and then C is higher. So three to six months after radiation, for the most part, majority of patients were the same classification. They did not have worsening of their liver function, but in at least two patients, that were progression to classification B, both of those incidents happened in the context of progressive disease, unfortunately,

Dr. Basree 52:12
and so in this you know, heavily pre treated patients with multi site metastatic disease survival was low at 36% and you know, it’s hard to know what to make of survival when we’re talking about local therapy in the context of a systemic disease. But nonetheless, even at two years and you know, patients who’ve had multiple lines of therapy, I think third of them being alive is still good. We certainly need to do better. But if patients fail and if the liver fail, then patients are unable to receive further therapy. Local Control was also lower compared with the other studies that I shared at one year, about 50% of patients had control of their disease, or another way to say this is 50% had a progression in at least one of the irradiated tumors. Similarly distant relapse is very common, and so PFS here is progression free survival in the liver, as well as overall. So progression free survival is if basically the patient did not progress and are alive. So that number is very low in one year, and zero at two. Another thing that I think is relevant is looking at the interval where patients do not have chemotherapy, because that certainly has quality of life implications. And so when we look at the chemotherapy free survival, so the interval that patients are alive and without using chemotherapy at six months, that’s that was about 30% of patients, or a median of four months, in half of the patients, they were off chemotherapy. So we, you know, ideally, this number, we hope, is higher, but you know, that’s, that’s the data with a small number of patients. It’s really hard to make any you know, biological analysis, like what was done earlier, looking at those two mutations, a PC mutation, port 10, better overall prognosis in terms of survival, compared with with no APC mutation. And this is really overall survival, you know, I don’t really suspect it’s related to radiation, but, you know, maybe BRAF is another common mutation. We had only few patients with BRAF, maybe two actually, with BRAF mutation, but those with the mutation, unfortunately, did worse compared to patients without. Year of mutation. So in this small series of patients with four or more colorectal liver, MS, MRI, guided radiation appears safe with nausea and fatigue that resolve post radiation, we are limited by the sample size, but there is a rationale, I think, to aggressively treat, you know, well selected patients, even if patients have have had multiple courses of systemic therapy before, multiple resections or ablations and they come with multiple liver lesions, I think there’s still that option of at least discussing with radiation oncologist, is it possible to do radiation here? You know, ultimately, what’s the impact that we have on the overall disease trajectory? That’s still unclear. I think we need to do, you know, larger, better studies that is able to understand who’s benefiting the most, and who is you know, coming spending a couple of weeks with us or a week with us in radiation, but we’re not necessarily causing them any benefit. We’re causing them fatigue and nausea. So what is the consensus about SBRT and liver metastases? The International stereotactic radio surgery society just recently came out with a practice guideline that came out in 2025 it included 33 studies and 3000 patients with close to 4500 liver metastases of all histologies You know about, you know 57% of them were colorectal patients, and only, only only one study used MRI guided radiation. They found that severe toxicity occurred in 3% of patients. I don’t recall seeing, you know, grade one and two, which are still very relevant, but the three and four they noted were 3% if you look at the entire population, they reported that, you know, two year local control was about 75% overall survival was about 50% if we look at the colorectal cancer cohort, specifically, the local control was a little bit lower owing to the fact that it’s probably more radio resistant, and we may need to escalate those there based off of all of this, those studies, they came up with those practical recommendations. They, you know, recommended SBRT with priority in allego metastatic disease, you know, not necessarily polymetastatic That’s still on a patient basis, they considered SBRT In patients with an anatomically difficult level liver location. So if you’re unable to get a needle in there with for ablation or resect because close to major vessels, biliary tract or the diaphragm, then SBRT would be a good option, certainly overall disease status and disease health, or sorry, patient health, technological recommendations. They recommended modern Radiation Technology as a with image guidance, MRI guided, as opposed to other non image guided radiation techniques, motion management is very critical. You know, breath holds to minimize liver radiation and only focusing on the on the tumor. 40 simulation, this basically means that we’re taking a CT scan through all phases of breathing, and it helps to see how much the tumor moves if we’re unable to do breath hold because, you know, not everybody can hold their breath, then at least the 40 CT tells you, gives you a sense of how far that tumor moves. And then we can have that volume large enough so that we’re not missing the tumor. And then lastly, they recommended a BDD, or a biologically effective dose of more than 100 gray. And so that kind of correspond to 50 gray in five fractions, and that will be associated with, or at least might be associated with, improved local control for radio resistant tumor like colorectal cancer. There are few ongoing studies in this space. One of them is a phase two randomized study. This is a study that’s trying to demonstrate that MRI guided radiation is as good as CT based radiation this I think paper would help us, or this study would help us demonstrate that not only we can deliver this in an equal manner in terms of efficacy, but also hopefully some of the secondary endpoints here would include safety and toxicity assessment, and hopefully that will demonstrate. Eight in a you know, a larger study that indeed, using this particular technology is helpful for patients. Another study that I’m really excited about is an ongoing phase three randomized clinical trial that is the gold standard for changing practice. So this is an alliance NRG gi 009 study. It’s looking at patients with newly diagnosed, limited metastatic colorectal cancer, and they define limited as four or less sites of disease, and they don’t have to be liver only disease, so they could be any oligo metastatic disease. They would receive chemotherapy for four to six months, and then if there’s no disease progression, so if patients progress, then they would come off of study for, you know, but different treatment paradigm. But if the patient does not have disease progression, then you’re, you know, selecting patients who might benefit from this local therapy. You randomize them to either standard of care systemic therapy, so kind of like the tribe trial that I mentioned earlier, or experimental, which is standard of care, systemic therapy, which is this plus total ablative therapy. And what I really like about this study is that total ablative therapy could be anything. You know, it doesn’t have to be radiation, it doesn’t have to be surgery. It certainly does not have to be interventional radiology or ablation. And so it, it’s, it’s this epitome of the multi disciplinary discussion. And what they’re looking at, the primary endpoint is overall survival, I think, patient. And you You all know very well, you know, we don’t really care about radiographic findings in a clinical trial as much as we care about overall survival. Are we making people live longer and the quality of life our patients living living better?

Dr. Basree 1:01:54
And so, in summary, I’m sorry for taking a lot of time here, oligometastatic colorectal cancer refers to disease with limited spread and local therapy here can extend survival. MRI guided radiation really helps us see tumors well or bettercompared to CT and can improve safety and precision, especially for abdominal metastases. What I just talked about, even though it was all liver can certainly, are certainly relevant for patients with lymph nodes in the abdomen, anyone in the abdomen, peritoneal metastases, if they’re one or two of them, or if they’re symptomatic, or something like that. Studies such as the study that we’re doing here, shows that MR guided LINAC is relatively safe and is well tolerated for the most part. We really want to maximize selection of patients who would benefit the most from this, but the ongoing, this ERASur study, I think, would be really helpful in telling us who would benefit the most. Personalized care is certainly key, and with that, I will end, thank you very much. This is my email. If you have any questions, feel free to touch base. Thank you.

Betsy Post 1:01:57
So we do have some questions for you in the chat. First, thank you. That was so thorough. I learned a lot.

Dr. Basree 1:02:20
It took over an hour.

Betsy Post 1:03:26
That’s okay, that’s okay. We are all about education and learning, so that’s great. So in your opinion, is surgery the preferred treatment relative to SBRT? That’s our first question.

Dr. Basree 1:03:39
So it depends on the context, if the patient is able to receive surgery, then yes, surgery is potentially curative, especially in the right patient population. I think if we’re able to remove that tumor, then the local recurrence is essentially zero.Now, depending on the surgery, there’s certainly that margin recurrence. And so if it’s clean surgery, negative margins, everything is out with a healthy margin around it, then local recurrences could be zero, but we see a recurrence at that marginal resection. And so I think it offers a potential for cure. Unfortunately, there is 20 to 30% of patients who are resectable, and at some point we can’t keep doing surgeries, even though the liver does actually have capacity to regenerate. Sorry, that was long winded answer to depending on the context, if the patient has limited disease and is able to get surgery, surgery is certainly an option.

Betsy Post 1:04:42
Okay, so can this be performed on liver and peritoneal lymph nodes simultaneously? Is there a maximum number of lesions or nodes that would make someone not a good candidate for this?

Dr. Basree 1:04:55
Great question, the more targets, the more complex and difficult it becomes to try to line everything correctly, and at the same time, I should say, not correctly, but at the same time, if we’re having two areas that we could see on one image, then we can treat them both at the same time. Sometimes we would treat one area up here, if it’s in the liver, and the other one is, say, pelvic lymph nodes right next to the bladder, then we would treat the liver and then come down and treat the bladder. It could be the same day, but it would be two separate ISO centers or two separate plans. So if one, I guess I did not talk about time, but it would be basically an additional 45 minutes or so of door to door,

Betsy Post 1:05:48
Great. And then for this patient, she’s been told she has too many lesions all throughout her liver, and radiation doesn’t seem like an option for her. Does this work for people with multiple tumors spread throughout the liver.

Dr. Basree 1:06:03
It depends on what multiple means, how many lesions? Y90 Well, technically, it’s technically radiation. It’s an option for patients with multiple liver lesions. It’s sometimes hard to do Y90, if there are too many liver areas, if there are areas in the right liver as well as in the left liver, then Y 90 can have difficulty. Because you can’t put radiation through the entire liver through all the blood vessels. So sometimes what they could do is treat one side of the liver and then do chemotherapy in the interim, as the liver heals and regenerates, and then come back and do the second half of the liver with Y90. So that’s one option depending on how many lesions. We we treat four plus. I think the maximum we had in this particular study was 11. It becomes more challenging, and the disease overall, if it’s not controlled, if there are multiple liver lesions, then becomes more challenging to to treat and and to direct benefit, I should say, from the treatment .

Betsy Post 1:07:24
Great. Another question, is there a role for radiation in the treatment of peritoneal metastases, and if so, which modality is the most promising?

Dr. Basree 1:07:36
For peritoneal metastases? It’s harder to do radiation because the the tumors could be anywhere along the peritoneum, and radiation works well when you’re pointing exactly to where you want to treat. If there is disease along the entirety of the perineum, then radiation would not be a good target, or radiation would not be a good treatment for this. If there are one or two spots that are not responding to chemotherapy, or they’re causing symptoms, or everything else has responded except those two areas, then certainly we can do radiation. But typically with peritoneal disease, it could be anywhere along the wall of the abdomen. It could be within the peritoneum itself, and so it becomes very challenging to localize what we need to treat.

Betsy Post 1:08:32
I think this is really good to know, though, for our patients with peritoneal meds, because it’s good to know that if they have problematic spots, like you said, spots that aren’t responding to treatment there aren’t a ton of options for those patients. So I think this is definitely good for me to know and for them to know.

Dr. Basree 1:08:50
And radiation works fantastic for symptoms. And so if the goal here is not necessarily to cure and that’s okay, that’s fine. But if we can improve pain, if there is an area that’s close to a critical structure so that if that area grows, it could cause more symptoms, then you we can certainly treat that. And the goal would be to either improve symptoms, to provide local control that, so that it’s not progressing and causing worsening of the symptoms. And those are valuable for quality of life.

Betsy Post 1:09:24
This patient’s asking, I think you talked about radiating multiple areas of peritoneal disease, but this patient’s asking, if they have liver, peritoneal distal lymph nodes, is that something that those could be treated by radiation? Would that be in one session, multiple sessions, is that something you’d have to look at just depending on the number of spots?

Dr. Basree 1:09:46
Yeah, I would say it depends on the overall disease process, overall disease trajectory, the number of spots. It’s really hard. Radiation would work best if there are limited areas of disease and the benefit of doing radiation, of the benefit of doing local therapy would not cause harm for the overall body while we’re having metastatic cancer growing outside the radiation field, if that makes sense.

Betsy Post 1:10:25
Sorry about that. I was talking but I was muted. I said, I think that’s the last question. That’s the last question that I see in chat. So I just want to thank you so much for your thorough presentation for all of us, and thanks for taking time to answer the questions. Thank you for educating us on the trials that are out there, and I really appreciate it. And for all the folks that attended tonight, he was generous enough to provide his contact information. So if you have additional questions, you can feel free to reach out. So thank you again, and we really appreciate your time. Have a good night.

Dr. Basree 1:11:00
Absolutely you too, bye, bye.