Lung surgery for colorectal cancer metastasis: Dr. Atay (2023)

This is an automatically generated transcript.

Julie Clauer 0:05
Hi everyone. Welcome. I’m Julie Clauer, a patient as well as colontown cabinet member and also admin of various and assorted colontown groups. And it’s wonderful to have you all here today, and I’m very excited to introduce our doc talk today, because for a couple reasons, one is liver. The liver folks seem to be getting a lot of information from the doc talks, and we don’t want lungs to be left out. So very happy to learn more about what’s happening with lungs for colorectal patients, and then also, because our guest is my surgeon. So let me tell you a little bit about him. He specializes in thoracic surgery at USC, the Keck School of medicine at USC. He focuses on malignancy, malignant diseases of the chest, and he completed his training at Beth Israel Deaconess Medical Center, Harvard Medical School, and did fellowships at MD Anderson Cancer Center, as well as further training at the National Institutes of Health and doing a clinical research fellowship in surgical oncology, so he has a lot of amazing experience. And I would tell you that my last conversation with Dr Atay after my surgery was something like this, you’re amazing. Thank you for the exceptional care, for saving my life, and I hope I never get, never have to see you again. So goodbye forever, I hope. But I’m so excited because it’s not goodbye forever, because this is a very exciting reason to get to see him, and it’s not because my disease has has created issues so good to see you again. Dr Atay under these much better circumstances. So now I’ll turn it over to you.

Dr. Atay 2:02
Well, thank you very much for all those kind words. I appreciate that. And thanks for having me to kind of give this, this talk here, and try and avoid, like I said, we don’t want to ignore, ignore the lungs. So I will go through kind of a little bit about surgery for metastatic colorectal cancers, lung surgery, that is. And then I think we had some questions that I’ll run through some of those already with some answers then, you know, obviously go over any additional questions that people have. So hopefully this will be relatively informative. Try not to make it too technically dense. So it should be, you know, shouldn’t be an hour of falling asleep, I hope so. I will share my screen here and make sure that this is, I think we should be working. Okay, so yes, as stated, so I’m one of the surgeons here at USC, and we’re fortunate because we have a great team, which is a big part of this, and we’ll talk about that a little bit more too, but we work very closely with our oncologists, our radiation oncologists, everybody here and I function as one arm of a pretty big team here. So so the first thing that often I get asked is, am I in the wrong room? So what does a chest operation have to do with colorectal cancer? And as a lot of you know, you know the liver is typically the most common distant metastatic site for colorectal malignancies, the lung follows thereafter pretty quickly, and so in a large percentage of patients who will be presenting with either live, liver and lung or lung only metastases, we’ll see them in consultation to discuss if there’s therapeutic options that exist. And so I guess, just to run through, kind of what I want to touch base about today, we’ll talk a little bit about sort of the incidence and presentation of lung metastases, and then when we do surgery or the indications for it. We’ll talk a little bit about the types of surgery, the techniques that are out there that you might expect to hear about, and then the outcomes and the expectations for for longer term, and then, obviously, to answer any questions that anybody might have to try and kind of get you more informed and moving forward. So what’s the incidence of metastases? Well, we know again, liver is the most common. Lungs comes next. It’s hard to know the exact incidence of lung metastases, but somewhere for those who do develop metastases, between 10 and 40% are going to end up with disease in the lung. And the reason I say it’s hard to know is often patients at end stage will have diffuse metastases, and so we don’t always want to account for that when we’re thinking about the, you know, disease that’s intervenable. So again, somewhere in this 10 to 40 range is what you’ll kind of see quoted. Any of those numbers is probably more or less correct rectal cancer as the rectal part of colorectal it’s even a higher incidence of lung metastases, often isolated, and that’s because of a little bit of difference in the physiology of of that location, anatomically. And I’ll mention, I’ll show some pictures about why that’s the case and why that represents an even higher percentage of patients, frequently that I will see for surgical evaluations, because the unique behavior of rectal tumors. So colon cancer is unique. And this is this paper that came out a few years ago is a great one, because it really helped validate a lot of what we think you’ll hear about, a couple different ways that tumors spread from point A to point B in lymph nodes. So draining lymph nodes in the region of the tumor, which your colon surgeon, your general surgeon, your you know colorectal surgeon is going to try and get a bunch of lymph nodes out. And I’ll talk to you about those after your your surgery. And then what we call hematogenous, or blood borne, and these are via draining veins. We think back to the liver, which is the drainage pattern of the colon, or directly back to the lungs, which is specific to the rectum. And this, there was a big study by people markedly smarter than myself, who looked at the origins of these and they noted that actually about 65% of the distant metastases had a totally different genetic makeup than those that were in the lymph nodes. So there’s something different about the disease when it spreads to liver, lung or distant than when it spreads to lymph nodes. And so maybe when we look at these diseases, when we look at colorectal cancer that goes to lymph nodes and colorectal cancer that goes to liver, that they’re not exactly the same disease. We bundle it all into one big picture of cancer, but really, there may be something separating them genetically, and that can help us understand who and how to intervene more effectively. This is a little schematic about rectal cancer. Why it’s even more interesting? As a surgeon, I think it’s interesting. Here’s a little schematic of the rectum. I didn’t probably weren’t planning to look at this today, I’m sure. But when we have colon malignancies, the majority of patients that would drain into the what’s called the portal system, and that system of drainage of portal vein and the mesenteric vein that drains back to your liver. And so if you have tumors and they are hematogenous, and they’re spread, then they’re going to end up first place. First filter is your liver. Your liver is a big, giant filter, and it’s going to get trapped there, and you’re going to get metastases that grow, and then anything that gets past filter number one, then it’s going to make it to the next filter, and that next filter is going to be your lungs. And so that’s why we frequently see liver and lung but for tumors that are down lower in the rectum, they don’t drain to the liver first. They actually drain right back into the vessels that drain your legs, what are called the iliac vasculature, and those drain and go right past the liver, they skip it entirely, right to your heart and then to your lungs. And so for patients with rectal cancer, again, it may be a totally different disease biology or behaves differently. And these are individuals who we see with isolated lung metastases. And maybe another reason why they have even more opportunity for intervention from a surgeon such as myself. So what does it all mean when we think about this? Well, in my mind, it means that metastatic colorectal cancer can be treated with local therapy in the appropriately selected patients. And when I say local therapy, and I’ll probably use that term a lot today, I’m talking about either surgery, talking about radiation, talking about ablation, even things like isolated lung perfusion, really things that are local, meaning they’re just addressing disease in one specific location, as opposed to systemic, which is what we think of when we talk about chemotherapy or immunotherapy or anything, where really the distribution of that treatment is to anywhere in your body where blood or fluid goes. And so even though colon cancer somehow is getting into the bloodstream or into the lymphatics, we’re finding ways to locally treat it. And so that’s what I take away from this again, and what makes colon cancer unique and interesting as a as a clinician. So that’s why you’re here. That’s why you’re in this room, is because there are options for you with people like me so understanding cancer. So how do we understand cancer? I don’t understand cancer. And that’s another big thing that everybody I think should know, is that if anybody your oncologist, your surgeon, your radiation oncologist, tells you they understand how cancer behaves. They’re they’re lying, or they’re a genius. And it’s, it’s probably, maybe it’s somewhere in between, but we don’t totally get it, and so everyone’s case is very unique, and that’s why, what, what I’ll talk about today is what I’d call surrogate markers for disease behavior, which is we’re trying to understand. Understand how you and your specific case is going to behave, and we’re going to use some sort of blunt instruments to help predict that. And so we don’t know exactly what it is. And again, that that little schematic and study I showed about the different gene profiles, that was a nice a really nice study, like I said, by some very smart people to understand it, but we still don’t know exactly why that 65% is the way it is. We know it, it exists. We just don’t know why. So we’re closer, but we’re not, but we’re not there. And so, so there was a really smart surgical oncologist named Blake Katie, and this is a quote that anyone who does a lot of cancer surgery has heard a lot of times, but it’s, it’s very valuable here is “biology is king and patient selection is queen. Technical maneuvers are the prince and princesses who try and fail to usurp the throne”. What that means is the biology of the disease, that’s what’s going to drive the outcome, and then selecting the right patient for treatment, that’s what’s going to help technical maneuvers, that’s surgery, that’s radiation, that’s ablation, those are things we’re going to try all these different ways, and we’re going to fail unless we understand the biology. And so that’s where, again, we work together to try and get the best possible maneuvers that are going to match that biology. And so cancer is a systemic disease. We’re treating it locally. For some reason that works again. We don’t understand that, but it’s the way it is. So, so what more can we do? So we found this tumor. It’s in your lung. What do you do now? Well, the first thing is, always talk to your oncologist. Systemic Therapy is usually the first line. And so when I see patients for with metastatic cancer, if they’ve never received systemic therapy, a lot of the times I’m going to tell them, even if this is a resectable tumor, if I say, I can take this out, it’s not a big deal. Still getting systemic therapy first is often the right choice, because we want to make sure that disease is controlled. So you may hear that, but as soon as you get a tumor in your lung, talk to your oncologist and ask if you have lung metastases. See a surgeon you know, someone who’s typically thoughtful in your oncologist thinks highly of I’m sure will have that conversation with you about when the right indication is because deciding whether to get a lung operation is always multidisciplinary. It’s not just the surgeon making the it shouldn’t just be the surgeon make the decision. It should be the surgeon and the oncologist and the radiation oncologist and everyone together putting a comprehensive plan together. And what is that comprehensive plan? That’s what we’ll talk about. How do we select, and this is always a big the biggest question is, how do we know who is right for removal of lung metastases? This may be the more interesting part of it. These are the criteria I as a surgeon use. And these are, I think, the criteria that really the majority of people will use is one you need to control the primary tumor. This can be with surgery. This can be with definitive chemo, radiation. But the bottom line is, the primary tumor, that colon, or that rectal tumor, has to be managed. And if you can’t manage that, then there’s no point in taking out the metastases, typically, because you’re going to just get more because these metastases all come from that primary. So if we’ve met criteria one, then we look at two, ability to control all sites of disease. If it’s liver and lung, that’s okay. You just need another surgeon. You need a good habitability surgeon. So the point is, you got to have a plan for everything. You can’t just kind of wing it and say, we’ll do one, we’ll do two, we’ll see what happens. You want to have a comprehensive plan. Again, whether that’s all surgery, or surgery and radiation or whatever it is, all sites of disease need to be controlled three and this is the hardest one to predict, and this is why we fail, is control of systemic disease. So what I as a surgeon want to see or not see, really, is I don’t want to see new tumor each time you get a scan, because then it means systemically we’re not controlled, because if you get a new I can go take out all the lesions on your on on one side of your lung, and then by the time we get to the next one, your lungs filled up again with tumor. So we need to control it systemically. And this is often the hardest thing to do, or or to know if we’ve done, but progression as it’s defined, or what you might see when you read a CAT scan report, when you’re looking at them, and I say progression of, you know, lesions, progression of an of a lesion that’s there that doesn’t bother me, or shouldn’t bother most surgeons, which is if it was there a year ago and it’s just getting bigger, that doesn’t imply systemic disease is not controlled. That just means the local diseases are controlled, and that’s what we do best, is local control. So progression of identity of known lesions is not a problem new development of lesions. That’s where we slow down and start thinking twice about doing surgery. So. So those are the general criteria. So say you’ve made this decision. We think you’re a good candidate. Well, local consolidation comes into a lot of different forms. Can be surgery, but gotta resect. Everything can be radiation, that can be sbrt or IMRT or saber, or any, any number of acronyms that, honestly, I couldn’t even tell you what half of them mean, but something with radiation or ablation, microwave, cryo, RFA, they’re all very good, and the best choice of treatment is patient and lesion dependent. So the best cancer therapy is not always the best specific treatment for the patient. Meaning, we might say you need an operation to take this out, or I could offer you an operation to take it out, and that’s the best therapy for the cancer, but if it leaves you debilitated, it’s not the best choice for local control. So this is where we balance the risk and the benefit of these operations. So now we’re thinking about we’ve decided we’re going to do surgery. So we said that’s the way to go. How do we make decisions about how to approach it? Well, one can we address all the lesions as as mentioned before, number of lesions, that is prognostic, but it’s not a hard stop. Okay, isolated lesions are best. So if you have one, that’s the best case scenario. Well, zero is the best, but one is good. Any after one, anything less than four is is probably falls into what I call the good prognostic group. Greater than four. We know that the tail of that sort of survival curve peels off, but it’s still acceptable if you have the right patient, meaning, if they meet everything else, which is primary control, systemic control, ability to tolerate it all sites the disease. Then it doesn’t matter the number. You just have to be able to meet the criteria and get it done. So there’s no hard stop. You just have to address all of them. The lungs don’t regenerate the way the liver does. So the liver hypertrophies And you can get function back. You can take out two thirds of the liver, I think is what they say, and you you, you can get most of that function back. The lungs don’t really regenerate the same way the but the lungs do hyper inflate their balloons, and so the balloons will get bigger and fill up your chest, but you don’t get the same recovery of function. And so we really work hard to preserve volume when we’re doing these operations. And in some cases, we decide it’s too much volume, but we still want to address all the lesions, and that’s when we do a hybrid approach surgery for some radiation for others, and we try and get everything treated that way. So that’s the decision making when we’re approaching it. So what is it now? What is the operation going to look like? Well, you’re going to hear terms like vats or robotic or thoracotomy or sternotomy. Vats and robotic typically imply a minimally invasive approach. So that’s using a camera, some small instruments, or a robot. Thoracotomy, that’s going to be a rib spreading type of operation, usually an incision along your side, under your shoulder blade, and sternotomy is going through the middle, so a sternal split. They all have a role, and depending on the location, the type and the comfort of your surgeon, you might see any of these being done. Okay, you’ll see incisions that look kind of like this. So this is a thoracotomy incision along someone’s side. This here is from a robotic operation. So a couple of these things here. This is from a vast operation. You know, one, you add up the length of the incisions, they’re all probably about the same. The scar is going to be the same. So the morbidity of these operations, and not the size of the incision, the morbidity is what’s going to happen on the inside, which is how much year long we’re going to take out. So we want to minimize the morbidity, but we also want to do a good operation. And so you may get offered a variety of techniques, and it’s really the one that’s going to get you to that outcome is what’s going to be best. So I have a before I play it. I do have a little video show some surgery. So if anybody is a little squeamish around blood or doesn’t want to watch it, you can look away here for a few seconds. But this is just to kind of see what one of these operations, when minimally invasive one might might kind of look like. Okay, so this is how it looks when we’re doing this, as a left lower lobe lesion that’s being done with a robot. And so these arms here are being controlled by a surgeon at a console sitting in the side of the room. These are some arteries that are being dissected that are going to the part of the lung that needs to be removed. That big thing coming in that’s a stapler that staples and seals. And you can see that’s, that’s the arteries that are getting cut right here. In a minute, we’ll see they’ll cut the bronchus. That’s this right here, the windpipe that goes to it, and that frees up that entire piece of the lung. So this is what a minimally invasive surgery looks like on the inside. So again, it, it might be a small incision on the outside. It’s. Still, still something on the inside, but the the robotic approaches, minimally invasive, are very good. It gives us a lot of flexibility, and I think the outcomes are great with it. So, so when we talk about these different types of resections, what are the extent of the lung resection? Well, you’ll hear terms like wedge, segment, lobe pneumonectomy. This is how much lungs coming out. And so a wedge is just that. It’s like a little piece of pie. You kind of just grab a little bit of the lung and sort of chip chip a bit off. That’s the preferred technique for metastatic tumors, the wedge resection. And the reason for that is it preserves the most amount of lung and ideally gets you the same outcome segment. That’s the lungs divided into lobes, and the lobes are divided into segments. It’s just how the blood supply and the windpipe goes to it. That’s a bigger piece of lung, but it’s still, I’d say we call it sub low bar, or less than a low. Meaning, if we if we have a lesion that’s a little deeper in the lung, we might consider doing a segment, and that’s way to try and preserve, again, more of the lung. A lobectomy is removal of an entire anatomic lobe of the lung. You have three on your right. You have two on your left, and that’s probably reserved for tumors that are very central or close to some vasculature, some windpipes, where you just can’t get to them any other way. And that’s a substantial component of the lung. It’s not, it’s not totally inconsequential, but it’s a pretty well tolerated operation. Typically, the lobes, on average, are about somewhere between 30 and 50% per lung. So the left side, it’s basically 5050, the upper and the lower. And on the right side, it’s about 30 on the upper and then 50 and 20 in the middle and the lower. But if you take out you know, a half of your left lung, you’re still only losing about 20% of your total lung function. So it’s a tolerable thing for the majority of patients. Pneumonectomy, that’s a whole lung gets reserved for really specific and extreme cases. It’s pretty uncommon to do that for metastatic cancer, although it is done if someone has a very difficult to treat lesion otherwise and has isolated disease and can tolerate it. It is a an operation that is done, and we will do it if necessary. So what should we expect? Well, it is surgery and recovery is dependent on the type of the operation, the amount of lung that’s removed in someone’s functional status beforehand. We do always check your lung function for people who’ve been through it, you do these breathing tests. They’re not the most fun things to do, but you check your breathing beforehand to make sure you’re not debilitated afterwards. And debilitated is a relative term. We that means you you may notice that you had surgery, meaning you might get a little winded, you might be a little more fatigued, but we try and get you to a point where you’re you’re still going to have a quality of life that’s valuable to you. Okay, the operations can be 45 minutes to five or six hours. It depends on how many lesions we got to take out hospital stay one to seven days. Most people, it’s like two to four is about average. Will it hurt? It will, will be manageable. It will, can you breathe afterwards? Absolutely. You can breathe. You can walk, you can run, you can kayak, you can dance. If somebody does a lot of yoga or yoga instructor, you can do any of those things once you recover. And that takes time. It’s not the next day, but six weeks most people are doing their normal activities of daily living, can be three to six months before the lung function fully recovers, or you’re kind of past some of the more sort of annoying side complications that come with it, but it is a manageable thing. So this, you know, there were a lot of great questions that had sort of come up that I’ve been for. And so I wanted to run through those, because I think it captures a good component of what we talked about and what people really want to know. And so one of them was surgery or observation. So if you’ve got a small nodule and it’s isolated, should we watch it? Should we take it out if it’s isolated and can be resected with low risk? I think taking it out is a good decision. If it’s if it requires an extensive resection, then observing it for stability is a good call to be and the reason for that is you rarely will lose the ability to resect small, peripheral lesions. When you observe them, it’s unlikely, with close follow up, that they will go from zero to 60 so fast that you lose that intervention. So I think small nodules it’s okay to observe. How long should you monitor it for? There’s no real, great, hard number. But if you have a nodule that hasn’t changed in a couple years, usually, let’s say two, and it’s a low risk, meaning you don’t have other sites of disease that are active. Then at that point, we usually extend surveillance where we’d be looking at a lesion every year, as opposed to every three months or closer, but that’s how long I usually watch it, pretending we took away the known history of a lung cancer or of a of a metastatic cancer, a five millimeter nodule at two years. We don’t worry about it anymore. Surgery or ablation for the lung, so sbrt, cryo, RFA, well, when you’re a hammer, everything’s a nail. So I’m a surgeon, so my nail is to do operations. So it’s easy to it’s easy to say surgery is the best. It’s probably better, but it’s better for certain things. So when we look at resections, surgery has a lower risk of local recurrence. That means recurrence infield or at the site of the operation. And there’s a big series of this stuff done at MD Anderson that demonstrated that that differential outcome, but there’s a higher risk of treatment related morbidity, higher risk of perioperative morbidity. Ablation, on the other hand, has a higher local recurrence rate or in field recurrence rate, but the treatment toxicity is much less. And so which one do you do? We it’s a decision that you make. It’s a decision you make with your surgeon, with your oncologist, what’s the best? What’s the best treatment for you? And that that’s where understanding these, the the disease behavior, that biology, is really important to know what’s going to be the best. Do we take a lot of risk, or do we have a concern that there’s going to be more disease later, and we should do something less invasive? One does not preclude the other. You can resect now. You can ablate later. You can ablate now you can reset later, so you don’t have to worry typically about that. As a surgeon, we used to try and avoid operating after sbrt. But that’s it’s become so ubiquitous that now we’ve gotten pretty used to it, and we do it frequently so it does not preclude it. So here’s a little case of this. Just this is a real, a real case of a patient who had that four lesions. They had surgery on all four, and then they had a local recurrence. And so I’ll show you the on the scan. So this little dot right here, this is a tumor, very small, on the right upper lobe. They went underwent surgery. You can sort of see some scar over here on the left where they had done it. And this little dot here starts to come back. This is about two years later, so they got sbrt, and then another two years later, it looked like this, because the sbrt failed, they had an infield recurrence there. And so they got surgery after this, and we removed the entire lobe this. This was a wedge resection here. So you can get surgery more than once. As you saw here, you can get surgery, and then you can get radiation, and then you can get surgery again. So you can get multiple operations, and you can have multiple modalities, and that’s a very acceptable practice, if need be. So this is a good example. A very small lesion, again, in and of itself, would not be problematic, okay to observe, progressed very slowly over the span of a few years. A lot of this is radiation related changes. The tumor is not actually this big, although it looks a little bit ugly, but that’s mostly from radiation.

Dr. Atay 28:12
So like we talked about recurrence rates, what are the recurrence rates after surgery? Local recurrence rate, I quote patients somewhere around 10% maybe 15% and that means that either the margin is too close and they will recur at the margin, or there is missed disease that we just didn’t see, but around 10% that’s supported by most, most studies, but recurrence rate distant is a different number, and that’s the one again, That’s hard to predict. So recurrence in the lung, again, somewhere brand new, that really depends on the individual to start that you started with. So did they have one lesion to start and they were five years out from their primary? Or did they have eight lesions to start and they were six months out from their primary? Those are different patients. And even though the local recurrence rates are the same, the distant recurrence rates are going to be different. And so that really depends on other factors on top of it. But for local recurrence rates, I say around 10% and that’s that’s reasonably well supported. What about size? Size of the lesions? How big can you can they be? Doesn’t matter. Size doesn’t matter. The biggest consideration, again, is location and the ability to identify them all and resect them while preserving enough lung for you to function. That’s what’s most important. So if it’s a really, really big lesion, we can take it out. If it’s a really, really small lesion, we can take it out. But you might have a really small lesion in a really bad location, and that becomes a more difficult thing to address, and I’ll try. I think I have an example of that here too. So, yeah, here’s, here’s a good example. This is, and this goes back to the waiting question. Too different. There’s another patient. These are this the lesion. Is this little dot where my cursor is, right here. This is in the right upper lobe. Here’s another scan. This is a little more than a year later. So they’ve progressed a very small amount, like a millimeter over a year, because there’s a good candidate for surgery, not really. They’re not great. And the reason for they have a couple other lesions, but the reason for that is this is very deep in the lung. So doing a wedge resection would require me to cut all the way into this lung and around it, and you’d lose a big chunk. And you say, well, is that amount of lung loss worth it for this patient? And this patient had a lot of other lesions, and would have lost a lot of lung, too much lung, in fact. And so this was a lesion We opted as a group to do radiation with. Instead, we said it’s too much lung, and we’re worried the recurrence is going to be too high or meaning we’re worried they’re going to recur. It may not be worth the risk of the operation, so they this patient underwent radiation instead. Okay, so size isn’t as big an issue as location too frequently. What about combining resections? So liver and lung, absolutely, you can do that, and it’s really dependent on the extent of the disease that’s necessary. So if you have a big liver tumor and a small one in the lung, sure, doing both. If you have a big lung tumor but a small one in the liver, do them both. If you have a big lung and a big liver tumor, maybe do those separately. So it’s really, can you do it safely? We don’t want someone to get to have a bad outcome, because we tried to do too much at once. But if you have tumors that are progressing quickly, where you say, I don’t think that it’s a good idea to do a liver operation, recover for three months and then do a lung operation, then we wouldn’t we would try and do them together. But it’s mostly related to how complex the operation would be. So we do that here. If we have isolated liver, small lung, we’ll frequently do those as a simultaneous operation. Sometimes we can even do them through the diaphragm, which saves the patient’s incisions on their chest the liver. Surgeons do their work, and we just cut a hole in the diaphragm from below, and we do it that way, and then no incisions on the chest. So there are ways to do it. What about some other experimental options, or sort of less common ones that maybe people hear about? So one of them is isolated lung perfusion, or what’s called lung suffusion. So this is a technique that’s been around for probably, I mean, 30 years or more. It was trialed for a variety for things. Initially it was actually for metastatic sarcoma, and the thought process behind it was just giving enormously high doses of chemo that would otherwise not be well tolerated systemically, to just the lungs, where maybe the burden of the disease for these patients are. Sarcoma was unique, similar to colon, in that it often goes only to the lungs. So it does work in the sense that if you get an isolated lung perfusion and they’re able to technically accomplish it, it will work, but it doesn’t always lead to durable regression, so meaning the metastases will get smaller, but it doesn’t always lead to them not growing back. So it does have some value there. It may have more value in the setting of the small micro metastatic disease. So this is where, like, maybe we just don’t see it on your scan yet, but there are some tumor hiding out in there. So maybe you’re going to resect some tumor, and then you do it isolated perfusion to treat anything that might be left over that you can’t see, that might have a broader effect and a better long term outcome. So it is done. There are some centers that do it. It’s been around for a while, and it’s never really picked up a huge amount because of the the technical difficulty in getting it set up. It takes a little bit of work, and some you gotta have some specific equipment for it, and it’s unclear what the exact outcomes can be, but, but it, there are trials gone, going it’s a reasonable thing to be doing lung transplant, was another question. So lung transplant for lung specific malices has been around for a while. There’s a type of pathology called adenocarcinoma in situ, or bronchial alveolar carcinoma, that’s a lung specific cancer. And transplants had been done for this before, and it is still considered an indication for transplant. Recently, it has been used for more advanced tumor, and that has been a couple cases that were done at Northwestern they were publicized in the news. Those they never published those outcomes outside of the like press releases, so we don’t really know what happened to those patients. The reason that transplant surgeons are, or anyone in the transplant community is hesitant to transplant in the setting of malignancy is because you have to give someone very high doses of immune suppression in order to not reject the organ. And we now know that the immune system is a huge component of tumor treatment. That’s why immunotherapy exists, and that’s why many of you who may be aware of those it’s very effective in specific types of colon cancer. So if you give someone a lot of immune suppression, one of the side effects of it is development of malignancies. In fact, that’s the most common thing to happen to patients after transplant is they will develop malignancies of a variety of kinds. And so the worry is that if you, if you immune suppress someone with metastatic cancer, you may just uncouple that cancer from the immune system, and they will blow up with metastatic disease. So it has not been done, as far as I know, for colon specific, these were lung specific cancers, but that it may become a viable option in the future, depending on what the outcomes from from Northwestern show. But we don’t have the, we don’t have any real specific information about those two cases that they’ve done? Yeah, surgical approach to disease in both lungs. So great question. It’s very dependent on the surgeon and the extent to the disease. My personal preference, I do two operations. Space them four to six weeks out, if we’re you know, if patients recover, you can space them longer if you need to. Why do I do it that way? Because the person who taught me to do it told me to do it that way. But it’s also because I, my personal belief is that it the disease rarely progresses in that short a period of time. You gain a lot of information every time you operate on somebody, and sometimes you gain an information that might change or change the direction of your treatment, in addition one surgery on your chest comes with a certain set of complications, but if you have one, you’ve got one good lung that’ll get you through. If you do two surgeries or operate on both sides of the chest and you have complications, you don’t really have a lot of reserve. So I I personally space them out. But one of my partners, who’s very experienced surgeons. Well, he will do simultaneous a little bit more frequently, but then again, that’s just his personal approach to it. I don’t think either one is wrong. I think it’s just however you however you want to do it, and whatever the patients are most comfortable with, consideration for vats or open a robot. How do we decide what you do? Same thing surgeon and extended disease. So what I asked myself at surgeon, before I’m going in to try and resect a lung lesion, is, can I find it? Because your your lungs are just sponges. And if you think about or the way I describe it is, imagine if someone took a P and put it on the inside of a dish sponge, and now ask you, where’s that? P, you can see it great on the scans, but you can’t see it in real life. In fact, I don’t ever want to see the tumor, because if I see the tumor, it means I’m too close. And so we need to be able to find them. And some of them are big enough that they can be seen on the surface. They kind of indent to the surface of the lung. You can see it, in which case you can do a minimally invasive operation and just remove that area. Sometimes they’re deeper in the lung, or they’re small, in which case you you gotta get a hand or a finger or something on it to be able to feel it, know where to cut. And so that’s how I try and determine the best way to do it. Now, similarly, if I want to, if I’m going to remove an entire lobe of someone’s lung, for example, well, then it doesn’t matter if I can feel the lesion or not, because that whole anatomic structure is coming out, and I know how to remove that. And so we that gets done minimally invasive. But it really depends on those those issues some surgeons, and historically, this was from some surgeons at Memorial Sloan Kettering in New York, had found that if they did an open operation where they got their hands in there, they would find more lesions than we’re seeing on the scans. And that probably was true historically when CAT scans were a little bit lower quality and we were not getting as fine a cuts or basically there were the images were, were a little further apart, so there were sort of gaps in the images, so to speak. And so they were finding lesions that they didn’t see on the scans. Nowadays, with our very high resolution, thin cut scans, we probably don’t have that same degree of an issue, but nonetheless, I think there is value to it in the right case, because my experience has been, you will occasionally find a lesion you didn’t see. You occasionally find lesions you didn’t see, and the only way to find it is systematically kind of feeling the lung with your hands, liver and lung. What’s the concern? Why does everybody worry so much about that? Well, again, biology is king. So if you have liver and lung, it suggests the disease is going to be more aggressive. But it doesn’t mean it can’t be managed, and so you stabilize it, and if it’s completely resectable, then you address both whether simultaneously you’re in a staged fashion and so you can do it. But you know, oncologists and surgeons all when we see that sequential progression from liver to lung, you worry, are you, are you capturing the disease at a point where it’s sort of stop at the lung, or is the next spot you’re going to get a scan and you’re going to see a bone metastases, you’re going to see something else. So how do you know that you’re catching it before it’s kind of broke loose? And so that that’s really, I think, what the worry from a lot of providers is, when you start seeing that more aggressive biology, do you how do you address it? And can you address it? I think the answer. You can in the right patient, you just have to find or understand that biology. So we talked about this maybe a little, or, I don’t think you talked about this quite yet, but Yeah, can you have multiple surgeries on the same lung? You can, hopefully you don’t, you don’t need it. So here’s an example of a patient. This circle right here, this is a tumor in the middle lobe of the right lung. And this right here, this white line, this is a scar from a prior surgery. So they’d had a wedge resection, and they developed a new tumor in the other lobe, and so we took them back to the operating was about two and a half years later, and we removed this additional lesion. And so you can have surgery on the same lung more than once. I think the most I’ve ever done has been both lungs twice on somebody, and so if they have the lung reserve, and we think that we’re able to manage the disease, and it is something that definitely can be done. One more video if, and again, if anybody’s concerned or doesn’t want to see any look away here for a minute. One of the questions I get asked is, What about lymph nodes? Because you’ll hear your oncologist will say, Well, you have tumor in the lung, but we see it in some lymph nodes in the chest too, and that oftentimes is where they there will be a sort of a hard stop, or not quite a hard stop, but a soft stop. You say, are we going to resect this if it’s involving the lymph nodes? And the short answer is, we know that if it’s involving the lymph nodes, then it’s the likelihood of controlling it goes down. It doesn’t mean you can’t, but it means it’s harder to control. And so this video, the reason I show it is we see lymph nodes on a scan, and there’s this sort of thought that it’s a very discrete structure. But in reality, when you’re looking at them, they’re really not. It’s kind of this sort of nebulous network of stuff. And so these are, these are lymph nodes that are being removed here. This, this black circle here. This is a lymph node, but all of this sort of yellow fatty tissue around it. This is lymphatic tissue. And so as we’re going we’re cutting through these lymphatics. But how do I know that that node stopped right there? Because now here’s the next node, this big one, here is the next one in line. So there’s you just kind of keep going. And you could these lymph nodes will go on forever and ever and ever, and you’ll never quite get every one of them. So how do you know you’ve you’ve got enough? And that that’s why there’s a worry that if the lymph nodes are involved again, the biology of the disease might be different. And that’s what that that that study that I mentioned before shows. Here’s what an evolved when a known involved lymph node looks like. It’s a little bit stiffer, that sort of dark, black pigment. There’s not quite as much of it. And so this is removal involved lymph nodes. Again, we do, we do do it in the right setting, but this is, this is kind of what it looks like. This is all being done, again, with with a surgical robot. So that’s, that’s what this looks like. And so I’ll jump forward a little bit. You can see here’s another node sort of hiding all the way up here. So we could keep going forever. Again, that’s where it’s hard to know if you’re really getting everything out. Sometimes we do, but that’s where coupling with systemic therapy is very important. Alright, so that video is all done for folks who had looked away. That’s it. So that covers, I think, most of what I had already questions we ran through, but if there’s more questions or comments, I’d be happy to take him or address him now.

Julie Clauer 43:24
Great. Thank you. That was super informative. Thank you. Okay, so there are questions, so I’m gonna running through them. Can you operate on lungs if there are a few resectable lung nodes and hilar and para tracheal lymph nodes?

Dr. Atay 43:44
Yeah, great. Good question. So that last video that was actually a combination of both of those. So one was a para tracheal lymph node, the one that was the bigger involved node at the bottom, the last part of that video that was a para tracheal lymph node, and then the first part was kind of the one that was coming out right at the start, that was a higher lymph node. So you can, again, the really what, what it boils down to is, do we believe that we’re able to achieve control? And so if we see lymph nodes where it seems to be sort of tracking from point A to point B to point C to point D, where you know that you’re not going to get there’s going to be another node, point E, then we’ll say, You know what, systemic therapy is going to be a better choice. But if we see isolated nodes, and that’s it, meaning they progress, and it’s just that stuff, and they’re not going to other levels, we give levels to the lymph nodes, so we know when we’re talking to other providers or surgeons, that where things are. So if it’s not going to different station or different level of lymph node, then we’ll consider removing those if that’s our only site of disease, and we feel that systemically we’ve got good control.

Julie Clauer 44:50
Great. So another similar question is about pleura and sub plural?

Dr. Atay 44:56
Sure, so pleura and sub pleural? So sub. Role. If you have what’s called a sub pleural nodule, the pleura is actually two surfaces. There’s a pleura on the lung, it’s basically like a sausage casing on the lung, and then there’s a pleura on the inside of the chest wall. And so those two pleura are very sort of smooth, slick surfaces that allow the lung just move and rub up and down on the inside of the chest smoothly. If you have disease sub plural on the lung, that’s just a lung metastasis. It’s in the lung. It’s just right at the edge. That’s perfectly fine to remove. In fact, those are easier for us as a surgeon, because we could see them if it’s on the other surface of the plural. That is a much different sort of problem, because when you see pleural based disease, the pleura is a huge surface. I mean, the actual surface on the inside is about yay big if you sort of unfolded the inside of the chest. And so if you see one or two nodules on that pleura, it means there’s probably 1000 more that you don’t see. And so we worry when you have pleural based disease that you can’t control it because that whole surface is involved. That’s what we call surface based malignancy. Now in the abdomen, there is the peritoneum, and that’s the surface. It’s the surrogate of the pleura in the abdomen. And there are procedures for the abdomen. That’s where people discuss things like hipec surgery that may have been under the intraperitoneal chemo for surface malignancies that has been tried in the chest, but it has not been as effective as it seems to be in the abdomen. And so pleural based disease, we frequently don’t try and resect because we’re never really able to control it pretty well.

Julie Clauer 46:43
How often is cleanup chemo used?

Dr. Atay 46:46
So post, I assume that means sort of post resectional. That’s great question. It’s very dependent on your oncologist and a couple of the other markers of the disease. So I’ll give a few examples. If you have somebody who is a colon malignancy. Primary was taken out and on their surveillance scan Three years later, they have one new lesion. Maybe it was even there the year before, but it’s been just watched, and it’s finally gotten big enough someone decides to do a biopsy. It says it’s a metastatic lesion that patient might be reasonable for a primary resection you remove that lesion, and you could reasonably say, I don’t think we need to treat with chemo, because the disease interval has been so long that if there was more tumor, it should have progressed as well. And so maybe adding chemo won’t help, whereas, if it’s someone who six months after the primary, they’ve got three lesions, they got some chemo. They got a little smaller. There’s nothing new. We might take those out and say there’s a risk. There’s still disease, additional chemotherapy on the back end is, is probably a reasonable thing to do. So it’s a little it’s very disease specific, or patient specific, I think.

Julie Clauer 48:02
Great. A question about two approaches. You already talked about suffusion, but there’s also in vivo lung perfusion that’s being done in Canada at trial.

Dr. Atay 48:15
Yeah, so the MO, those are more or less different flavors of the same soda. So it’s essentially the whole the whole premise behind it is you isolate the lung. The lungs a good organ. It’s actually, oddly enough, a very close surrogate to the liver in how they’re they behave. So you have a singular blood vessel going to it, and you have essentially a singular exit point, two exit points, but more or less one. And so you can completely control the blood flow in and out, or near completely control the blood flow in and out of the lung. And if you do that with clamps and things like that, you can then infuse almost anything you want into the lung, high doses of chemo, whatever it might be to try and treat tumor that exists in that lung. And so whether you call it in vivo perfusion or infusion suffusion, they’re all really more or less the same thing, which is isolating the lung away from the rest of the body, so different blood flow, so that you can give enormous doses of it, that if you gave systemically, would make somebody very sick, or they wouldn’t tolerate or too much marrow suppression, etc, but that that would be the reason for where that suffusion infusion, it’s all roughly kind of the same, same sort of thing.

Julie Clauer 49:41
Okay, what is the percent of morbidity for surgery versus ablation, and the percent of recurrence of surgery versus ablation?

Dr. Atay 49:52
Sure, so, um, let’s do the second one first, the recurrence rates for, I can say for stereotactic rate. Which is probably going to be very similar to what percutaneous ablation would be. But for ablative procedures, the recurrence rates at three to five years, probably three years is about 20% maybe 25% in field, okay, that was from a large series done in MD Anderson. If you look at surgery, the recurrence rate locally after resection is somewhere between 10 and 14% so the difference is about 10 or 15% between the two in terms of local recurrence, I will say the caveat to that, or the caution to that, is with the with the ablations or with the surgeries and well as well, for those patients that recurred locally, a good percentage had new distant disease as well, which means it didn’t really matter if they had an if their lung tumor recurred, because now they had three new tumors in their liver. So they kind of the treatment of the lung turned out to not actually be a driver of their outcome. So there is a higher local recurrence rate with ablative procedures. That is just, we just know that exists. But your the second part of that question, or the first part of that question, is, what about morbidity? So morbidity of resection is dependent on the extent, but in general, for a wedge resection, the major complications, meaning heart attack, stroke, death, re hospitalization, is probably around one per well under 1% for a low back to me, removal of an entire lobe of the lung, it’s about one half to 1% and then for major complications, and then probably on the order of like five to 8% for any type, meaning you have to you have fluid in your lung that builds up. Your lung collapses a little bit, you get an infection, probably in that range. For ablation, and I can’t speak to percutaneous ablation very well for this, but for stereotactic or radiations, sbrt or saber. The morbidity is, I’m not going to say zero, but it’s very close to that. Most people have some fatigue and a bit of a dry cough. They can get a little what’s called radiation pneumonitis, so that’s inflammation in the lung that’s managed with steroids, but it’s pretty low risk. So that’s the big differential between the two. Is one is a better local therapy, or, I believe, again, I’m a I’m a hammer. It’s the nail, right? It’s a better local therapy, but it definitely has more risk radiation, better from a risk perspective, tolerated better for the individual, but higher risk of local recurrence. And so you should really, this is where you talk to your oncologist, or, you know, if talk to whoever you you trust and and get a real handle on your disease. Because I tell patients if, if I’m concerned that you’re going to recur in six months, then get radiation. Because if you don’t recur, and maybe a year later, that field of radiation does start to grow, we’ll remove it. We’ll take it out. Then that’s not a big deal. But if I take it out, and you struggle to recover, and three months later, you’re finally back to your normal life, and you get your surveillance scan, and you have two new lesions, I didn’t do you any favors. I just ruined your quality of life. So knowing how your disease is behaving is really important, and really talking with your oncologist so that you have a good, true picture of the expectation, and then you can make an informed choice about the modality.

Julie Clauer 53:29
Great. Um, so question about lung transplants, which you talk to, but I’m going to follow up on that with a question around you know, live donor, living donor, liver transplants are becoming more common with colorectal patients. I’m assuming you cannot do a living donor transplant for lung

Dr. Atay 53:46
Well, believe it or not, there are living donor or what’s called a low bar living donor. Low bar that was actually initially the first living donor low bar transplants were done here at USC. We actually started that program, that technique, about 2530 30 years ago. So you can do living donor, low bar transplants. So what does that mean? You’re right. You can’t take out an entire lung from someone to give someone else. That would they would not be a great call for either one. But you can take a single lobe out, the lower lobe, in fact, of a large donor, put it into a smaller recipient, and that’ll be enough lung for them. You have to do both, typically. So you have to get a lower lobe from two different donors, one lower lobe on the left, one on the right, and then they go into the single recipient. So it is done. It there has not been a low bar a living donor. Low bar transplant done in the US for a while. And the reason is, in the transplant community, it had fallen out of favor a little bit because it requires essentially three people or three patients at risk. You have to have two separate donors and a recipient. That’s a lot. You know, liver, you have one donor, one recipient, and for donation. Of an organ, there needs to be 0% mortality for those donors. You cannot hurt those donors. And lung resections, just the risk is still there. You can’t get it quite to zero. And so people falling out of favor because of the ability to obtain a deceased kid ever oddly enough, in Japan, they do a lot more living donor than they do here, but that’s just because culturally, there’s fewer donors there.

Julie Clauer 55:24
And then based on what you talked about, the about the immunosuppression nature of post transplant, will the learnings from liver transplants in CRC be helpful in terms of what could happen with lung or is it totally different in terms of – –

Dr. Atay 55:41
yeah, good question. I mean, yeah, that’s a good question. The short answer is yes, we do learn. We have learned a lot. The downside is the liver is a is a liver is a special organ for a couple reasons. One is that regeneration ability, but two is the liver is actually like a giant immune organ. It’s filled with immune cells, and so you can actually do mismatched donors. For example, in the lungs, we have to be matched, otherwise they’ll reject. Liver, you can actually do a mismatched donor, especially in kids. Liver, they can be weaned almost completely off of immune suppression, because the organ itself will not reject the same way because of the white blood cells or the lymphocytes that come from the donor. So all of those things actually make a difference for why you can get less immune suppression. For lungs, we unfortunately have not gotten that far. Lung transplant was the last solid organ to be transplanted. So liver, kidney, heart, pancreas, were all done successfully, and in fact, most the first successful bilateral lung transplant was done, probably in most of our lifetimes, was 1981 so it wasn’t that long ago, and so we haven’t gotten to a point where we’re able to reduce the immune suppression enough to reduce that risk.

Julie Clauer 56:59
Thank you. You mentioned diffused, diffuse disease versus isolated mets in lungs. Can you tell more about the difference?

Dr. Atay 57:07
Sure. So when I talk about that, it’s kind of a little bit of, a little bit of dealers, a little bit of semantics, a little sort of dealers choice, but isolated meaning just one, if they’re just one met that, when I say isolate, I mean is singular diffuse. You know, what does diffuse mean? That really just means more lesions, or enough lesions, that I would say there’s a systemic problem that’s existing. So if I see diffuse disease, I mean, I see six lesions on the left and there’s eight lesions on the right, but there might even be some microscopic lesions that you know on the scan, you may or may not be seen. That’s a more diffuse process, which suggests that there’s probably a higher burden of disease, but to the original point number isn’t the hard stop, which is you might have that many lesions, but if month six you still have that many, and at six months later, you still have that many, then it’s fine. Then that’s controlled but diffuse disease, in my mind, usually means you’re seeing a lot of you’re seeing a lot of disease, and you’re seeing progression of new sites, which would imply the systemic problem still exists.

Julie Clauer 58:14
What are the complications of removing mutts from lung lungs? What are the chances of spread into the pleura. And what are the outcomes for such patients? Could there be spread into adjacent tissue, like ribs, etc, and what about Mets in the bronchial tree?

Dr. Atay 58:30
Sure, okay, we’ll go try and go through those. So risks for the removal of the lungs. So if you have a positive margin, meaning if you cut and that you’re like, say, you cut straight through the tumor, then it is possible for that tumor to see the pleura, because you will have divided tumor and sort of spilled it. So that can happen if you have a negative margin, meaning you’ve cut through and there’s nothing there, so that the tumors totally encased, you never saw it, then the risk of that pleural based seeding should be pretty low. Now, if you have a tumor that is on to this on the pleura, or what someone earlier asked about sub plural, if you have a sub pleural tumor that is eroding through the pleura, and often we can’t see that visually, that’s something they only see microscopically, they can develop pleural based disease. And that’s just because the disease biology, it’s eroded through and it spills tumor. What are the outcomes for those patients? They’re not as good, to be frank, because we can’t find a way to control that disease very well. And so it’s not it’s not locally controllable, unfortunately. So yes, you can develop that in the event that you had a grossly positive margin, a microscopically positive margin, the likelihood of that is markedly lower. And I don’t think I’ve personally seen that before, but it can happen if you spill tumor grossly into the pleura. There were a couple questions there. Did I answer all of them?

Julie Clauer 59:55
last one – What about spread into adjacent tissue?

Dr. Atay 59:57
oh, yeah, and bronchioles? Right? So. Um, adjacent tissue, yeah. Similarly, if you have a if you have a local recurrence, it often means, like, if you cut through on the staple line, and then so you cut, and we have a staple and, and so then the lung sort of falls back down on top of that area. You can have that local recurrence happening at that surface. So it could grow into the lung from that area. So if that happens, then again, that’s where we would say, Well, you can reresect if you have to. You can radiate if you have to. Those are, those are appropriate. And then, in terms of the bronchial, metastases to the windpipe or into the airway is relatively uncommon. You can see it from time to time, but it’s not frequently seen. And so spillage of tumor to like into the airway is pretty rare.

Julie Clauer 1:00:46
Is there a difference in technology across major centers, for example, are there better robotic tools at specific hospitals or the same everywhere? Good question.

Dr. Atay 1:00:57
So short answer is, there’s basically one robotic platform that exists in the United States. It’s called The Da Vinci platform, which is made by Intuitive Surgical they are effectively in a monopoly there is, like a couple other very small startup companies that have a few robots out there, here and there, but there’s, that’s basically the only one that the majority of centers use. I honestly, I personally, don’t know any center that uses a different a different robot in terms of other technologies for the treatment of the malignancies, some of those other things, like, like isolated perfusion, that’s something that’s only done to certain centers, transplant only certain centers. Robotic bronchoscopy is something that exists now, and that’s a handful of centers have that that is helpful for diagnostic purposes, but it’s also going to become probably more important for ablation, because you can actually find difficult to identify lesions and ablate them through the windpipe. So having robotic bronchoscopy is probably an advantage at certain centers if they offer, if they offer, trans bronchial ablations through it.

Julie Clauer 1:02:08
And is it lapm, whatever it is in Germany that – do people need to go to Germany because they do something there that they don’t do here.

Dr. Atay 1:02:15
So this is the like, laser assisted. I honestly don’t exactly know what they I think what they do is use something called the argon plasma coagulator, which is a device that we have here, and it’s a way of just sort of carving these lesions out using an argon beam. The it’s not a bad technique. In fact, it’s probably pretty akin to what the liver surgeons do sometimes, which is they use the argon to sort of carve out lesions in the liver. We don’t use it as much in the lung, just because we have to seal the lung afterwards. And so any type of thing that sort of cuts or burns into the lung can then lead to leaking of air afterwards. And so stapling, or wedges using staplers are effective in that manner, but for lesions that are hard to identify or you can’t get a staple around it, we do carve them out in a similar manner, but I believe that’s what that technique that they’re doing is. I’m not 100% familiar with it is, but I’ve heard it before. I’ve had a few patients who actually have had surgery overseas and they had that done. I actually operated on one a second time after they had that done for another tumor and the operative field looks similar to what wewould normally see.

Julie Clauer 1:03:26
Why do oncologists and oncology surgeons sometimes say they’re more concerned with liver mats versus the lung, even if there’s multiple mets in the lung?

Dr. Atay 1:03:37
if I were to hazard a as a non liver surgeon, which is, if I when I see the liver, I made a wrong turn. And so as a non liver surgeon, I would think that one of the concerns is probably the ability to achieve a complete resection. And so just like the lung, you have to leave enough behind for someone to survive. And the liver, similar to the lung, has these sort of anatomic subunits where you could do a lobe of the liver or a wedge of the liver, again, it’s very it’s very akin to it. They’re sort of very analogous. But often, I think their concern is the liver is a little bit of a smaller organ, and so there’s just less space. And if there’s a bunch of metastases, they may not be able to get them all, and if they can’t get all those lesions, then, as we said before, there’s no point in addressing the lung if we leave a bunch of tumor behind, because we won’t have a plan for everything. And so that’s where that comprehensive sort of strategy becomes relevant. But that would be my thought as to why they’re very worried about the liver over the lungs sometimes.

Julie Clauer 1:04:39
Is there a pattern for where lung Mets tend to progress, like to the liver, peritoneum, bone, brain.

Dr. Atay 1:04:46
Yeah, so good question for patients with like rectal malignancies that bypass the liver entirely, then bone metastases or lymphatic involvement, tends to be what you see occasionally. It tends to be. That we don’t think the metastases kind of lead to new metastases all that frequently, but if you have very big progressive like lung lesions, we sometimes will see them then in the lymph nodes within the center of the chest. We don’t know if that’s a chicken and egg phenomena, which one came first, or maybe they’re two different things, but occasionally you, you can, you can see that, I guess. But we are.

Julie Clauer 1:05:26
For liver surgery. Uh, KRAS and TP five, three mutations are relevant for recurrence and SMA, d4 are there any mutations prognostic in lung surgery?

Dr. Atay 1:05:36
So, um, I don’t think there’s anything prognostic specific to lung. But yes, those, those different genetic driver mutations are relevant for the tumor overall. So for folks who have MSI high, for example, so that microsatellite instability is termed, sometimes people hair those tumors where we expect them to have a lot of genetic instability, so they’re very immunogenic, where they’re going to respond well to immunotherapy, for example, those are patients where I’ll have a discussion with the oncologist, and say, we have a we have someone who’s MSI high, has a couple lesions, and we’ve got a good opportunity for therapy with immuno maybe will be more aggressive with resection, because the recurrence rate globally is going to be different. But I’m not familiar with any driver mutations that would alter lung specific surgical interventions,

Julie Clauer 1:06:35
In liver, there is data that would that says there’s better overall survival for patients who have had resection. Is there something similar in lung

Dr. Atay 1:06:41
good question. So the short answer is, is sort of and the longer answer is, it’s complicated. So what do we mean by so I guess I’ll put it like this. If you take a population of patients, and they develop lung metastases, and you resect them, and you fulfill the criteria, systemic control, all disease resected, primaries, managed. Then you know, depending on which series of patients you look at, somewhere between 20, 40% of patients will be disease free at five years or effectively, you say cure at five, right? And so those patients, we think, do better than the patients that you didn’t resect. The problem is, there was only one trial ever done to try and compare directly operating on patients or not operating on patients. It’s called The Paul Mick trial. Is done in Europe, they didn’t accrue enough patients. It took them, like, 15 years to do it. And when they did a comparison, the outcomes were very similar. But nobody really believes it, to be honest, because the numbers were so small. And so we have data that supports it retrospectively. So we, you know, we have a lot of data that supports it retrospectively, that if you operate in these patients, they do better than patients you don’t, but we don’t know if we’ve already pre selected them, meaning if you get to see a surgeon, it means that you didn’t progress long enough, so maybe you’re going to be fine no matter what we do. But yes, so it’s very similar to the data and liver to be honest, which is, it’s all retrospective, but it does support resection in the appropriately selected patients.

Julie Clauer 1:08:24
Two last questions, thank you for staying longer. If you’re doing watching wait for rectal cancer and you develop develop lung mets, does that mean watch + wait failed?

Dr. Atay 1:08:35
No. Short answer to that one, no, it doesn’t mean watching weight failed. Because you know, this is where, when I say I don’t understand cancer, I think it’s being honest. And you can completely treat a primary, you can take it out, and you can have no tumor for a year or 18 months, and then all of a sudden you start to see tumor grow. Why did that happen? Because that tumor in your lung, it didn’t show up that month. It’s been there since your primary tumor was there. So there was no way to predict that really. Well, again, we’re trying to learn surrogate markers to predict it. And so I think in general, it’s, I wouldn’t call it a failure. I would just say this is the disease biologist, where the biology is king, and so we don’t know how to predict that. We don’t understand it. We do think it’s something with your immune system, where, for whatever reason, the immune system is able to keep that tumor at bay long enough, and that’s what happens. But, um, no, I think a failure of of those is not as much a failure of your treatment. It’s just a disease behavior that we just don’t like to grasp. But those patients who quote, fail in the sense that they do progress, they’re still candidates, right? Because you say, well, they progressed here, but that’s it. And you get the systemic and nothing else changes. Then you take them out, and then you reset the clock, and we go back to watch and wait, and we. See what happens.

Julie Clauer 1:10:04
We have another question is in terms of when to seek a surgical opinion. I know you talked about talk to your oncologist first, and then, you know, and also seeking surgical opinion but we have a lot of patients, right? That’s who their oncologist will say: you’re not a candidate for surgery, So what are your thoughts in that, in terms of how early do you like to see patients in that

Dr. Atay 1:10:25
Sure, I would say oncologists are very they’re smart individuals, and so I wouldn’t want to doubt the judgment of those individuals. But I will also say this, oncologists aren’t surgeons, just like surgeons aren’t oncologists. If someone asked me what chemo to give, you’re going to get a blank stare. But if somebody asks an oncologist what surgery to get, you’re going to get the same answer. And so I think that if you have any concern or any doubt, not even a doubt, if you just want to hear an opinion just I would ask for it, because it’s from my side. If I see a patient and they’re unresectable, that’s, oh, I’m not, I’m not upset about it. I mean, the patient’s the one who’s got to deal with that. But it doesn’t, it doesn’t bother me to say, Look, I’ll give you this information, and maybe there’s some other options that are available that we can help provide for local for for symptomatic control, and things along those lines, if you are symptomatic from the Mets. But there’s really no reason not to, because you will find that there are oncologists who are more aggressive in asking surgeons to see their patients, and there are others who are less aggressive, and you will find surgeons who will say, Yeah, this is definitely resectable, whereas an oncologist might have had a concern that it wasn’t. And so it’s not that they’re wrong, it’s just it’s not exactly their field. It’s just like, again, I’m not going to tell them what kind of chemo to give. And so if you have any worries or you just want to hear from it, just ask to see a surgeon. I don’t think most of them would really be averse to that. In fact, a lot of them would be more than happy, because if you’re interested in surgery, then and they know, and someone says there’s an option, I’m sure they would be thrilled.

Julie Clauer 1:12:04
Well, thank you so much. This was super informative for me, and I think a lot of people are commenting the same. So thank you so much for your time. Thank you for all your thoughtful responses and information. I think it’s extremely helpful to all of us.

Dr. Atay 1:12:19
You are very welcome. If you whatever’s left over, shoot me an email or whatnot. I can happily, I’d be happy to respond.

Julie Clauer 1:12:59
Okay, bye, everybody