Lung suffusion: Dr. Demmy (2024)

Betsy Post 0:01
Welcome everyone to tonight’s DocTalk. We are so excited to have Dr. Demmy from Roswell Park with us this evening to talk about the lung suffusion trial, specifically for our audience of metastatic colorectal cancer lung mets. It’s a real pleasure and an honor to have him here to talk about this treatment option for a highly selected group of patients. I did get some questions that folks submitted in advance, and so we will make sure that those are addressed here tonight. And also, if you do have questions, like in our other DocTalks, please put the questions in the chat. We’re going to make sure that everyone is muted, just to make sure that we’re really respectful of Dr. Demmy’s presentation and time. So please just make sure that you put your questions in the chat. At the end of the presentation, we will go through the questions that are in the chat, and the questions that were pre-submitted, he’s pretty much going to cover during the presentation, but if not we will add those to the questions at the end during the Q and A portion. So with that, I’m going to turn it over to him, and I really appreciate everyone being here tonight, and especially you, Dr. Demmy, thank you for being with us and for your generous time and your presentation. We’re really excited to hear what you have to say.

Dr. Demmy 5:59
Well, thank you. Well, listen the thank you really goes out to the audience because, to be a scientist, you have to have ideas and infrastructure, but you also need for clinical trials, you need patients, and it’s this COLONTOWN group, as far as I can tell, it’s really been greatly responsible for the success of this trial, especially in the last couple of years. Because the idea of suffusion, I’ve been pitching for a while, but it wasn’t until a patient met one of my colleagues at Mass. General Hospital and heard that I was doing this for sarcoma patients and then I got all these inquiries about colon cancer. So I actually changed the trial for this group of patients, including some of that might be on this call. And then the information I’ve gotten and the success really wouldn’t have happened if it wasn’t for this. So I, again, it’s the honor’s for me to to do this. I have been investing my own money to try to do an invention to make this happen, easier for patients too. That’s the suffusion. So that’s my disclosure. I got this money for selling an invention to Medtronic that doctors use. So that’s kind of my disclosures.

Dr. Demmy 1:24
Now I’m going to talk today like I’m talking to a patient, hopefully with some humility, because the the biology of cancer, is one that makes every doctor humble, but especially surgeons, because we are fighting against a disease that is something we can cut out in some areas, but often a disease is in a lot of other places. And I try to express this little slide here. These are slides I use for medical students and things, but I just speak very simply to it. But most of these concepts are pretty easy to understand that if you start with a tiny, microscopic tumor that doubles, it goes to 4, then 8 and 16, it lives most half of its time in a patient and doubling it’s still only a million cells, which is less than a poppy seed. And it’s only when it gets up to half an inch or a centimeter where it’s a billion cancer cells, and it’s starting to release tumor cells. And those cells are not just the same type of tumor all the way through. They’re changing, they’re mutating, and they’re getting filtered out by the lung and the liver, and so we know there’s always a lot more disease, even if we think we’re cutting out a stage one cancer out of a patient, we know there’s always a lot more disease floating around. And for whatever reason, the combination of surgery and the patient’s immune system, sometimes chemo, other things altogether, help the patient get cured, but it’s with a lot of humility that we were thinking about offering surgery to people. The other thing, I get patients come back, and you may have heard someone say, ‘the doctor operated and let the air get to the tumor, the lungs full of air’. It’s not air per se, but we can do things in surgery or medicine, even chemo or blood transfusions, that can let a tumor grow faster. And this is the fancy term for this. It’s called recurrence dynamics. But in general, if you do an operation, the bigger the operation you might generate chemicals called, ‘cytokines’ in the patient that can actually allow tumors to get blood vessels and allow them to grow faster. Sometimes tumors can’t grow unless they can figure out how to get extra blood vessels. All these things can make tumors grow faster. So we have to be very careful before we offer surgery in some patients, because we can actually make things worse. And I’ll mention briefly too, that lymph nodes are another system that can also sometimes, especially in colon cancer patients, can catch tumor cells. They can spread to the lung and then catch tumor cells in the lymph node system and suffusion has a potential for reaching those parts of the body as well. But the the lack of humility, I guess, as a surgeon, that would come from, this kind of very common sense idea that if you leave them in, I think a lot of patients are thinking you got something in there, that’s the only thing left, what’s going to happen if you don’t take it out? And there’s a lot of experience where people are getting some good results, they’re cutting tumors out and seeing people maybe live the rest of their life without any obvious cancer.

Dr. Demmy 1:24
There was a research study that was done, this is an older study, but it, was patients all over the world, and from the United States to Europe, different types of tumors. And they looked at a number of different variables for the these patients. And most of these patients had big, open incisions. Now we do a lot through small incisions, but these were the key things I talked to patients about, and they come to talk to me with metastases that, I say, “Look, the more number, the more cancer nodules you have in your lung, the worse it might affect your survival. It’s better if you find them a long time from when the first cancer was found”, that’s called the disease free interval, because if there was that long gap, that maybe is a better chance that there’s nothing else. And the most important things in the middle there is that obviously, if you can’t cut them all out, you’re not going to get as good a result as if you can cut them all out, or a complete resection. I’ll spend just a minute here also talking about, the approach. This was a lot of controversy at the time, the surgeons felt that you had to put your hands in the chest. And when I started my career was a part of a clinical trial that we were going to do a research study where patients would have a big incision or a small incision, it turns out is you would expect that most people didn’t want to be put in the group with the big incision. And there is this, still tug-of-war a bit, you will probably find a few more nodules if the hand is in the wound. But on the other hand, it’s a lot easier to come back and take that nodule out later if the patient only had small ones. So this will be talked about. And I’m mentioning all this surgical stuff, because that’s actually built into the suffusion trial, that we have to consider all these options when we’re talking to patients, because the suffusion is an enhancement on top of the surgery. Now we’re looking at more and more small incision surgeries for everything we do. Over 95% of our cases at Roswell for cancers are through the small incisions there, even through a single port. It’s called uniportal.

Dr. Demmy 8:16
And the other thing that will come up in the discussion as well is, what if you can’t get your hand in there and feel it? Well, then you sometimes have to put a marking wire in there, that little hook wire you can see in the middle, that hooks out, and the radiologist would put that in immediately before the surgery. And then a small spot there, it’s on the X-ray. On the right, you can see the wire actually going in and pointing to that area on the left part of the screen. And we use those kinds of tricks. Another trick that you can use is this navigational bronchoscopy you might see on the news, something called robotic bronchoscopy. But the way these technologies work is that we can load the patient’s CAT scan into a computer. It makes a three dimensional model, and then, using the same kind of GPS technology that you get around the car, you can actually drive things out into places of the lung where you can’t even see them. Here, you can see a little metal clip called a fiducial that gets put in. You can also inject dye there. This actually happened around Valentine’s Day. If there’s anyone’s squeamish in the audience, I hope no one is turned off by surgical pictures. A lot of audiences like to see some of these things. There’s an x-ray at the end showing that the little metal clip that was put by the small nodule actually came out. That’s often what they do when they mark women getting their lumps removed of their breast. And so these are some of the robotic systems, and I have a colleague that I work with, that can put multiple ones of those in so we can keep the incision small. Now, the other thing I talk about to the patients, well, if you can’t get them all just for the surgery, you don’t want to take too long. Then my colleagues in radiation oncology can use a technology called stereotactic radiation therapy that can target spots in the lung. It’s called ‘Saber’ or SBRT for doing ‘ablative’ or killing the nodules in the lung. And then I have another colleague, an interventional radiologist, that could put a needle in that generates microwave energy, it can kill nodules in the lung. So some combination of surgery and these technologies can be merged together. The microwave is being done experimentally now delivered through the windpipe, as you can see on the far left. So these are all the things that if patients would come see me for this Suffusion trial, I would be trying to cobble together some therapy where I could take out the lung nodules there, and try to take out everything that you can see and touch, and maybe even have to pull other technologies in to do that.

Dr. Demmy 8:16
But at the end of the day comes the question I was kind of alluding to, is it going to help the patient? And there’s a surgeon named Tom Treasures in the United Kingdom, and he’s been holding up the red flag for quite some time, saying, maybe it’s not the surgery at all, maybe people who live longer, who have the spots taken out, it’s just the fact that we now have better chemotherapy, and maybe their disease is not as aggressive. And he tried to do a clinical trial where the patients would get randomized to one/to the other, and they didn’t get the trial finished but the number of patients that went on in about 46 or 47 in each side, they did about the same. So there is this question out there, which I’m very frank with the patients and say, I can’t guarantee you that this surgery is helping you, but that’s why I’m offering the Suffusion, because I think that we we can add something on to surgery and maybe make it more curative in the future. This is the journey, if patients have the bravery to come and do something additional, it builds on itself, and then hopefully, I think, helps people, even if it may not help them, it may help people in the future.

Dr. Demmy 12:26
And I just actually had a meeting today with one of my colleagues that are doing CAR T therapy, which is a cellular based therapy where they modulate the immune cells. We’re very interested, in maybe starting to do that therapy in the future, using this type of technology, but that’s maybe not so far in the future, but still something that I’m trying to do. Alright, so I gave you the background. I’d like to spend the next few minutes talking about what people’s other options might be, and what’s been done for patients to try to improve the results beyond the surgery. There are the few things I’m listing there on the left, which are related to delivering drugs through the blood vessels of the lung. There’s a few other ones too, though, that I think are important for you to be aware of, where we are delivering drugs through other ways. And the one that’s called ‘Aerosol’, I’m not going to spend much time with that, but there are scientists that are trying to deliver chemo and other things through the windpipe. That gets a little bit tricky, because those drugs, once it’s airborne, other people can breathe it in. But this is something that’s done for liver metastasis called chemoembolization, where you can deliver a drug through the blood vessels and that gets clogged there and then slowly leaks out. That’s chemoembolization. This one I’d like everyone to be a little bit mindful of, because I’m going to bring it up later, because it’s relevant to people who have metastasis in their lungs, some of these lung tumors, especially ones that sit by the middle part of the lung called the ‘hilum’, which is next to the heart. They can find blood vessels that are coming directly from the high pressure blood vessels, the arteries in the body, and not the low pressure where I’m delivering the suffusion. And that can change, that can make some things tricky. Here you can see a very large tumor in the left lower corner there, filling up the X-ray screen (marked where it says ‘D’), and radiologists found these arteries going into it, and they were able to inject the chemo through the arteries, not the pulmonary artery, but these arteries coming off the aorta and the other high pressure systems. They were able to make the tumor regenerate. But this is an important issue, because all this blood that can get into these arteries can sometimes influence how the chemo that I’m trying to put in through the pulmonary artery, which is the low pressure artery, it can dilute it out, or make it harder to deliver it that way. So I’ll bring that up later, but this just shows that the results will be better if these patients who have tumors coming from the main arteries getting a lot of blush, meaning, with injecting contrast, they can see that those patients can respond to this other way of delivering chemo directly to the tumor.

Dr. Demmy 15:37
And you may have all heard of immunotherapy. It’s on the news. For now they’re thinking about just delivering immunotherapy directly to the tumor or in the lymph nodes. And that’s another aspect of what’s going on. I’m actually interested in immunotherapy in the long term future for Suffusion, because I think this is probably one of the more exciting places. Now going to just delivering it to the artery, this picture shows what doctors have been trying to do for a while. When the heart-lung machine came out, it was very natural to think about, could you just use the heart lung machine to pump chemo, a big vat of chemo, through the lung that has all these cancer spread nodules, the metastases. It took a big incision. It took sewing big tubes into delicate, small arteries. And the other thing that happened that these machines were not that kind to the lung, it would sometimes make the lung turn white, stop working, and also, because of all those connections I was mentioning to you before, the arteries going to the lung, a lot of that chemo would leak into the rest of the patient’s body, and could become toxic. But there are still surgeons that are doing this, mostly in Europe, they’re getting so-so results. It’s a pretty big operation to just get so-so results. But this is one of the things that’s also made it a little bit challenging to come up with a new research based in this area, because there’s been failures trying to use this technology before. A lot of the people that come see me have heard about a trial up in Toronto, which is not too far from Buffalo, where they were innovators up there using a pump to take lung transplants from donors that the lung was too sick to use, and they would resuscitate it and make it healthier using one of these pumps, and now they’re keeping the lung in the patient and using a larger incision and using the same pump to push chemotherapy through the lung. And then that’s another similar technique. It’s a similar idea. It’s a little bit more complicated, and that’s why I didn’t want to use it, because I didn’t know how widespread it could become if you stayed with this platform. But I think it’s something that everyone should know about.

Dr. Demmy 18:10
In Roswell, a long time ago, when the pulmonary artery catheter, which was used initially to measure heart function, and after open heart surgery, they got the idea to stick it in the lung and drip chemo through it. Unfortunately, there’s a lot of flow that goes through there, and it dilutes out very quickly. So there weren’t the best results for that. And then there was another surgeon a long time ago that tried to make it run through a little slower by blowing up a balloon and through some heart research I was doing before I became a mostly general thoracic surgeon, I figured out another way, and I’ll demonstrate that in a second, where we can get the flow to go through and the drug is sticking a lot longer, by closing off the veins as well. If you give it in the artery and close off the vein, it will kind of go down some open pass and then come backwards the other way, and fill the heart up so that you can get the heart to be protected. And you can see on the left there, of a patient, how fast that dye moves through there normally. And on the right is an animal, over 20 years ago, that’s when I first proved the concept. But you can see how the dye just sits there. And what’s happening is it will slowly work its way through the organ, fill up the artery, the veins, and that’s where I got the idea for suffusion, but it means to permeate something. You often see that authors say that the room was suffused with light. It’s actually a real word, and I thought it was good to change the word up, because a lot of those other technologies didn’t get the best results. I thought I’d give it a better word, or at least a newer word.

Dr. Demmy 19:53
What I found is that I could lock 75% of a drug in the lung for 30 minutes. And so instead of having to worry about a big pot of chemotherapy that was on a heart-lung machine making the patient toxic, you could take a safe dose of anything. And because the lung holds only about 5% of the total blood volume, you could take something that was safe and theoretically amplify it 20 times, because it’s just reduced to a smaller area, or if you had something that was very dangerous to give, you could reduce that toxic dose by 20 times. So that’s the idea behind behind suffusion. These are just pictures that show that after you release the clamps, the chemo then comes out into the patient. And the more you use, the less it’s bound up in the lung. And then that gets released to the rest of the body. But all in all, it is only a portion of what the patient would be getting, and we were able to find that using a drug like called Cisplatin, which is a relative of Oxaliplatin, which some people on this call could know as a familiar drug for colon cancer. We were able to get 25% of the systemic dose without seeing any damage to the lung. So we started a clinical trial. Initially. This was back in 2008 and we were actually looking at patients who had lung cancer too, because before in 2008 we didn’t have immunotherapy starting yet. So it was reasonable to try it for lung cancer patients. This was the first 10 patients that were a mixture of metastasis patients and lung cancer patients, and they all did very well. And the going home quickly has continued. There’s still been no deaths on the trial, we haven’t seen any damage based on testing we do before and after. As far as damage caused by the suffusion, we measure that by doing what’s called a split lung function test, which is a little injection of a radioactive tracer, and we see that that hasn’t changed much, except for patients where we took out a big chunk of lung as part of their surgery. And that’s the one graph on the right. Those were the patients that had a lobectomy. This gives you some example – These are patients that in the lung cancer part of the trial, where the tumors got smaller. Though some of these tumors got smaller because they were also getting chemo. After I was done with them, they were able to get back onto the chemo trial. And those aren’t necessarily the best examples, because, I’m not sure which one did the job, but there were four patients of that first group of 10 where the areas we did the suffusion on held their own, and then the metastasis got bigger. For instance, it would grow in the bone or lymph nodes elsewhere. And whereas the main tumor would change, and this is an example of a tumor in the lung that stayed about the same, but the tumor in the bone marked by the arrow got bigger. Another example: where that thing circled in the lower right corner got bigger. That’s the adrenal gland while the tumor stayed about the same. And more examples where the tumor stayed about the same, but a big lymph node got bigger in the belly. Another picture showing the tumor staying about the same up in the chest, but the lymph node that we suffused getting smaller and the bone metastasis is growing. So it’s called a differential response. So I went away from Roswell for a little bit to see if I could take this to another place in New Jersey. Things didn’t work out as far as getting my resources there. So I had to come back to Buffalo, and we started doing this, not for lung cancer patients, but for patients with sarcoma. And sarcoma patients’ drugs are a little bit more toxic. We had one patient who got a sarcoma suffusion, where the lung got a little bit swollen. The patient was able to go home after a week, still not quite sure if that was caused by the drug, but we made an adjustment. We haven’t seen that problem since, and we haven’t really seen major changes in the lung damage either with that same measurement. And so because, like what I said earlier, when this group that’s listening to this presentation, the COLONTOWN, got wind that I was doing this for the the sarcoma patients. I got all the emails very quickly, and I said, “Well, I was thinking about opening it to colorectal because I wasn’t getting quite as many patients as I like”, and “bam”, I added it, and I had this great support from patients in COLONTOWN and others that have heard about it.

Dr. Demmy 25:16
So this is the the how the study works. The patient comes, and they have to, at this point, have metastases that are able to be cut out, or at least controlled in some way. And we have to have a plan to control cancer elsewhere in the body, so preferably, the liver has already been brought under control, and the primary is under control. If they have cancer on both sides, then we randomize the suffusion to be done. And I’ll explain that in a second. We don’t do both sides because we don’t know if it works, number one. Number two, we could be doing harm with it too, like I mentioned in the beginning. You know, sometimes treatments have the opposite effect. So it’s actually the safest thing for the patient to not have both sides done, but to have one side done, and then compare it to the other side. And if we see that the cancer is coming back less on the side that we suffuse, then maybe we can take it to the next level, or we can bring the patient back and do the other side. We choose the drug based on the type of tumor. We have gemcitabine as a backup for the colorectal, but our preference is to start with the oxaliplatin, and we also going to look for other things, like disease-free survival and other types of metrics that we use to see if something might be working. Ultimately, if this does show some benefit, then the type of research you do after, that’s called a phase III trial, we actually randomize patients to get it or not get it. I might have some questions about this, but the biggest question is: Why don’t you treat both sides? And there’s a number. These are boring slides, in the sense that I’ll just summarize them. You have to be able to have good enough lungs to have the surgery. You have to be strong enough to have surgery, and the doctor has to think that it’s possible to deliver the chemo by the suffusion. And of course, if the patient is too sick, or the lungs are too sick, or has a heart failure or something else, we don’t think they could survive the surgery or the treatments. We can’t really have patients come on the trial in that situation because we’re more likely to hurt them than help them.

Dr. Demmy 27:50
This is called a phase I/II design, because we’re trying to get up to the highest dose. And the good news is that with all the support we’ve had, we’re up at the plateau. The top dose, the 15% for the oxaliplatin. So for the patients that come now, we’ll be giving them the highest dose level, and then once we reach the highest dose level, we’re looking for that long term. It’s going to take a couple years to see if we’re going to notice a reduced local recurrence in the patients who got the suffusion. I’ve got another busy, boring slide, but we do have what’s called correlative science, where we’re trying to determine if there is a difference, what might have caused it? is it an immune response? Is there something that the suffusion did that we can measure, and that is actually why it worked? If it did, of course, the participants for the suffusion trial are also potentially helping people with other diseases. If we can establish this, there are tons of other cancers or other diseases like pulmonary fibrosis, the COVID emphysema, asthma, pulmonary hypertension that a selective delivery of a drug could be very instrumental in changing the patient’s quality of life. Right now, we’re up to 20, I think, for our 27 suffusions, all told, and we’re trying to, again, get this catheter and these monitoring needles, everything into the next version of the protocol.

Betsy Post 29:37
Great! I don’t see any other questions. I just see in the chat, a lot of people saying, Thank you so much.

Dr. Demmy 29:44
Thank you! This is only rolling along because we’ve been on COLONTOWN or similar social media sites.

Betsy Post 29:56
Thank you so much for everyone that attended and for all of your great questions. Doctor Demmy, thank you once again for your time and your expertise, and I’ll be in touch shortly. Thanks everyone. Have a great night.

Dr. Demmy 30:09
Bye. Bye.