Betsy Post 00:00
Welcome everyone, to tonight’s DocTalk. I am really excited about this one. I love all of our talks that we get to do, but this one, I think, is really special because we have a physician-patient panel. I think this is probably the first time I’ve done one of these. We get to hear from our expert physicians as well as our very experienced patients with their first-hand knowledge of HAI therapy for colorectal cancer liver mets. I’m going to have Keith help me to advance to the next slide. I’m going to do a few introductions and tell you how this is going to work, and then we will get started. This evening we’re very pleased and honored to have a medical oncologist from Indiana University, Dr. Anita Turk. She has a lot of experience with HAI from the medical oncology standpoint so she’s here to help us in that regard. And then we have one of her colleagues, Dr. Ryan Ellis, also from Indiana, and he is a surgical oncologist with of course, experience placing the pump, including in a robotic fashion, which I think is really interesting as well. And then, of course, for our patients, I’m going to go ahead and introduce our patients: we have one that I think hasn’t made it yet, but we’re going to go on without her, and hopefully she can join us. But we have Hope Brooks, and I think if you are a member of COLONTOWN, I think it’s okay for me to say that you probably know Hope. She received her HAI pump back in 2022 and we’re going to hear a lot from her tonight, about her experience with the pump. And then Michael Riehle, who received his HAI pump back in 2020. I think it’s really important to know that the pump helped him so much that he was actually able to have his pump removed in 2023, so he’s long-time disease free and had his pump removed. He can even speak to that from the very beginning to the end, truly. And then hopefully Megan will be able to hop on. She received her pump in 2022 and she is also a longer term NED patient as well, so hopefully she’ll be able to join us. Before we get to the next slide I wanted to tell you how this is going to work. This evening, we have a fireside chat-type of setup: I have a lot of questions for our panelists, I’m going to ask those questions, and then please put your questions in the chat or Q and A. You should see a button that will say either “Chat” or “Q and A”. Keith is here. He’s helping run the tech this evening. He can answer any questions that you have about that. You can send him a message and he’ll be happy to help. At the end, we will take those questions that you put in the chat or Q and A feature. So with that, I’m going to turn it over to Dr. Turk. She’s going to set us up with some slides and some knowledge of HAI and then we’re going to resume our Q and A.

Dr. Anita Turk 03:00
Thanks Betsy and hello everyone joining us today. Appreciate you all logging on, and those who may be joining us later, appreciate your time. So as Betsy said, I’m a medical oncologist. I specialize in taking care of patients, especially with advanced colorectal cancer, and we are a main site in the State of Indiana to provide hepatic arterial infusion pump therapy. So what does that exactly mean? Many patients have a port that allows them to get chemotherapy conveniently throughout the body; Patients have to wear 5-FU pumps over 48 hours – this is is very similar. How it’s different is that it’s placed in the abdomen instead of the chest, and instead of going into a vein, it’s actually going into an artery, specificly the hepatic artery, or the liver artery, which is one of the blood vessels that supplies blood to the tumors, as well as the liver. What’s unique about the liver is that you actually have two types of blood flow. You have ‘portal vein’ and you also have ‘hepatic artery’. Your normal liver actually requires mostly the portal vein for blood flow, whereas the hepatic artery will differentially supply the tumors inside the liver and that’s how we are able to take advantage of this therapy. When we deliver the drugs, specically Floxuridine-it’s a very, very potent form of 5-FU, and we’re able to do that directly in the liver for a couple of reasons. One, because of its unique anatomy, with two sources of blood flow. We’re able to try to target the cancer cells over the normal liver as much as possible. And number two, only a small amount of the drug is actually exposed to the rest of your body, so the fancy terminology for that is called, “first pass pharmacokinetics”. Essentially, what happens is that medication is taken up by the liver, is affecting the cancer cells, but the normal liver is then able to metabolize the chemotherapy into a benign substance that’s not harmful. So as it’s spreading through the rest of the body, you’re not getting effects like nausea, vomiting, diarrhea or low blood counts, and that’s why patients are largely able to tolerate this therapy pretty well. (Keith, you can do the next slide. …Oh yeah, we can play the sample. ) (Video begins to play on screen.) So I think what this video is essentially showing is that the chemotherapy goes directly into the hepatic artery, and because of that special blood flow I talked about, the chemotherapy is being exposed more to the cancer cells than it is to the regular liver. So the pump that’s currently approved right now is the Intera 3000 Hepatic Arterial Infusion Pump. It’s about the size of a hockey puck, fts in the size of your hand. And basically how it works is that there’s a chamber of gas that expands at body temperature, that pushes the chemotherapy into the body at a certain rate, usually about one or 1.4 CC’s per day so it’s kind of going through the liver continuously. You don’t need to worry about it. You can continue your regular activities. The pump does have to be filled every two weeks when it’s actively being used and the rate is very sensitive to altitude and heat changes. So if patients have a fever, or, if a patient steps in the sauna for too long, that is going to affect the rate. So we always like to counsel our patient about those things so we can take that into account when they’re doing their doses of chemotherapy. So generally, how this works is if a patient is considered a candidate, you usually start with meeting a hepatic arterial infusion pump team that’s going to involve both a medical oncologist and a surgical oncologist. We review the history/where did the cancer start/where has it spread/specific parts of the biology, often involveing DNA analysis/making sure there aren’t other, better options are available on the table/and what treatments the patient has already received/and probably the most important thing, what’s the baseline liver function of that patient. We then want updated scans, whether that’s a PET scan, CT or MRI, to ensure that we’re treating a patient where at least a majority, if not all of the disease that we’re concerned about is in the liver. As I mentioned, this drug is not going to spread throughout the rest of the body and isn’t going to kill cancer cells outside of the liver. Usually a couple of weeks before the pump is placed, chemotherapy’s stopped, so your body is recovered, your blood counts are up. You’re ready to go to the the OR, and then you head to the OR with someone like Dr. Ellis. And maybe I’ll turn things over to Dr. Ellis to briefly explain the procedure and anatomical considerations for patients.

Dr. Ryan Ellis 07:40
Sure. So thanks, and again, I’ll reiterate, I appreciate everyone’s time tonight. But for the operation itself, a lot of it is dictated by exactly what the operation entails. This can include a liver resection for some patients, meaning we do some liver surgery or remove some tumors, as well as placing the pump. Or it can be the pump by itself, and within that context, there can also be open and robotic approaches. So the range of the surgical experience can be pretty wide, but overall, I would say the vast majority of patients receive some sort of open operation with or without removing any tumors from the liver. Some patients may even still have a colon tumor that needs to be removed at the time of the pump placement and then when you wake up from surgery, you would have an incision from usually about your breast bone down to your belly button, if not a little bit longer, depending on the operation. And as Dr. Turk mentioned, the hockey puck is underneath the skin, usually on the left side of the belly. You recover from surgery, hopefully relatively quickly. And we can, maybe later in the talk, go through some of the real details of what can happen with this operation, both immediately after the operation and later down the line and during your hospital stay, we get a special scan that is among the most important studies in this entire pathway, where we verify that any medication that we put inside of the pump go to the liver, and only to the liver. The surgery involves essentially me, reconfiguring the arterial system to the liver so that any chemotherapy that goes in does not go to other places. Places like the stomach or the pancreas, because those parts of the body are not going to tolerate the level of chemotherapy that we’re delivering. So once we get that study done in the hospital and you’ve recovered and are eating and moving around and taking great care of yourself, then we send you out, and usually about two weeks later, or I should say, exactly two weeks after we put the pump, you come back to the office and see the team again and start talking with Dr. Turk about putting some medications in the pump.

Dr. Anita Turk 09:59
Thanks Dr. Ellis. Yeah, the two weeks after that pump was last filled, it is really important that the patient’s able to come back to be seen to have that pump filled. These pumps do need to be filled every two weeks. We don’t want them getting emptied and dry, because that puts the pump at risk for developing a blood clot and then making it difficult to use again in the future. Typically at that first visit, depending on how the patient’s doing and liver function tests are doing, if the patient’s doing very well, we can even start chemotherapy right away. But regardless of when you start, you’re coming in every two weeks for a pump fill, alternating between chemotherapy and then a two week break with heparin and so on and so forth. Most physicians recommend doing this course for about six months of treatment, so that’d be six rounds of floxuridine. Now, depending on the clinical scenario, that can be pretty variable: Patients are doing really well, the liver is doing fine,some patients may have a longer course. If they have a complication, some patients may have a shorter course. As we’ll get into this, there are some risks and complications from the chemotherapy itself with specific implications on the liver. Fortunately, things have gotten a little bit easier. Patients come from all over and may not be close to a tertiary cancer center where they have easy access to this pump therapy. Now there are nursing agencies that are able to do these pump fills at home, which makes it a lot easier for patients to get this type of treatment when they live hours and hours away where coming in every two weeks can be challenging, and we have increasing experience using these teams that come to your home at Indiana University. I know other institutions are doing it as well. Some patients may actually be on systemic chemotherapy at the same time, and again, depending on what the need is for that patient. Once the course of that hepatic arterial infusion pump is done, whether that’s six to eight months, again, depending on that clinical scenario, chemotherapy can be restarted if needed, kind of the routine, whether it was FOLFOX, FOLFIRI, a targeted agent, depending on, again, the biology or what’s going on with the patient. And then we follow the patient, whether that’s on or off chemotherapy, and monitor the liver closely. We have many patients that the liver will be in good shape, no active disease for a long period of time. In very rare scenarios, but it certainly does happen, you’re going to hear about today, there are people who have complete responses to the pump therapy where we can stop all the chemotherapy altogether, but this pump therapy can be repeated. So again, you’ll hear from one of our patients, even when we do one course, we do not remove that pump right away. We often keep it in for several years to ensure that the patient’s disease is stable or clear. And if the unfortunate situation does happen that the cancer does start growing again, we can always use that again. And again, knowing that important relationship that you’re going to have with your arterial infusion pump team is really important. So making sure you have good communication and contact with your tertiary care center is really important when you’re considering this type of therapy. So, how are we using it for patients with metastatic colorectal cancer? Specifically when we think about this in our patients, it’s when it cannot be surgically removed. The gold standard, if you are unfortunately, a patient that has metastatic colon cancer to the liver that can be surgically removed, that’s still the standard of care. But for patients where that’s not an option because disease is on both sides of the liver or for some other anatomic reason can’t be removed, this is an option we can certainly consider for patients. There is data that shows that this can potentially prolong survival, but it certainly improves outcomes within the liver for patients that don’t have resectable disease, that’s one area where we use it. We particularly use it, the data supports using it after patients have had some round of chemotherapy and that’s no longer working in what we call that second or even third-line space, where the current standard options aren’t working, the cancer is growing in the liver, and we need to be more aggressive. The other common indication for this is patients who are very high risk that did have a surgery and had the cancer removed from their liver, but we’re really worried about it coming back and we’re concerned there’s probably microscopic cancer cells left behind where we will use the pump after surgery to try to kill any cancer cells that may be in the liver that are left behind. There’s data showing that that helps, again, with liver outcomes and can potentially improve survival in addition to chemotherapy. Those are the two big areas where we use it right now. There is an ongoing clinical trial called EA2222, or The Pump Study, and we are one of those sites, and it is open at most hepatic arterial infusion consortium sites actually trying to answer the question, “Can we use this in the first line setting when a patient first walks in the door, gets chemotherapy, they’re doing okay, liver function’s good. Can we add the pump in and help improve outcomes?” And that will be a really important trial to see, is this pump going to be helpful for patients earlier in their course of treatment? So in terms of safety information the pump is only really authorized to be used for Floxuridine, Heparin, and then we even use Glycerin for it. Glycerin is just a really thick solution to slow down the pump. So in that period when a patient is not using their pump, where we’re in the monitoring zone, so they don’t have to come in every two weeks, then you can really can really space out their fills to every three, even four months. We don’t use this pump for anything else, at least at this time. The pump is not considered for patients who have a lot of disease outside of the liver. Again, when you have cancer, if unfortunately, a patient has bone involvement, lung involvement, that Floxuridine and chemotherapy is not going to get there, so those patients generally aren’t considered candidates. I will hand off side effects of the pump placement itself to Dr. Ellis.

Dr. Ryan Ellis 16:14
So the pump placement, I break the problems that we can have sort of in the perioperative period into two groups. There’s what’s called pump pocket complications, which if you think of a port, essentially its the same thing, a little bit bigger. And then there are intra-abdominal complications. The pump pocket complications are primarily related to fluidaccumulating within the pump. We have things called a seroma, which is a benign fluid, almost like water, that can accumulate on the inside. It can make it a little bit problematic to access the pump. You can imagine, if the pump is floating in a bubble of fluid, it’s hard to find with a needle after that, but that is not a particularly dangerous complication. In the same areas is hematomas– a little bit of bleeding around your pump immediately after surgery creates essentially a blood clot around it that can also cause some trouble. And then the third thing we worry about that happens is infections. It is hardware, it is not a natural substance to have under your skin. The rate of all that is, overall, quite low– infections, in the low, single digits. But all those things can happen. Regarding the issues that we canhave inside of the belly the most obvious one is some bleeding. This is essentially a vascular surgery operation that happens on the liver, so there is a small risk of bleeding around the pump insertion site within the arterial system, after surgery. And related to that are development of things called aneurysms, which usually occur at the site where the catheter enters the arterial system. Those are the bigger issues that we can have with the pump. Of course, if anybody has any more specific questions, we can talk about it later, but those are the ones to really consider when you’re when you’re thinking about having one of these placed.

Betsy Post 18:27
All right, so here we are at the Q and A. I’m going to turn my video back on, hopefully my internet’s going to cooperate. It did say that it was unstable, so if I go off camera, it’s just because of that. We’re going to kick off the Q and A and I’m going to start with a question for our doctors. Thank you for that awesome introduction. I think maybe we’ll just get a little bit more specific. On deciding to get HAI therapy, I know you talked a little bit about extra hepatic disease and maybe some of those limitations, but I’d love to know a little bit about who is generally a candidate for HAI. So, who might be a candidate, that’s the first question. And then it’s a two-prong question, because the other half of that is, what are some of the other factors that patients should consider when they’re considering a pump?

Dr. Anita Turk 19:20
Absolutely. With the data that we have, patients that seem to benefit from this therapy are patients that have liver-onlymetastases, meaning the cancer has only spread to the liver, and ideally, the original tumor is out. There are some small exceptions to that rule, as there is it to anything in medicine. I certainly myself, have patients where they have one little,tiny lung nodule, or two nodules where they may or may not be cancer, where we’ll certainly sometimes make some exceptions if a majority of the cancer is in the liver, knowing that that’s going to be the issue if the cancer grows, that liver failure is going to be the issue that will unfortunately take that person’s life. So those are generally the people that we think about. The data strongly supports it in that second and third line setting, meaning you kind of had your standard of care chemotherapy with some biologic agent, whether that’s Avastin or bevacizumab or Vectibix or panitumumab, and that patient’s now progressing in the liver. What are next steps? I often include a pump chemotherapy through the hepatic arterial infusion pump. There are some anatomic considerations as well in terms of blood flow to the liver. I’ll hand that off to Dr. Ellis – what he looks for on the CT scan.

Dr. Ryan Ellis 20:39
Right. So I vaguely alluded to this, essentially a vascular exclusion of the liver because most fundamentally, when we put this pump in that floxuridine can’t be traveling throughout the rest of the body. It can’t be going into the stomach or the pancreas or the small intestine. So for simplicity sake, the the majority of patients have the arteries going into the liver shaped like a “y”. Now that’s not a vast majority. It’s a little bit more than 50% of patients have what we call standard anatomy, and the other 40-some % have a combination of blood vessels that is usually accommodating of a hepatic artery infusion pump, and in rare cases, actually can make inserting the pump anatomically impossible. The classic example of that would be, if there’s only one blood vessel feeding the liver, I would not have a place to essentially tie that blood vessel off to insert the catheter without also cutting off all the blood flow to the liver. So I have to take advantage of what I would say is relatively normal anatomy. That’s an exception, but I will say periodically, we will review patients who are otherwise biological candidates that anatomically cannot accommodate having the pump placed.

Dr. Anita Turk 22:05
Now, getting to that second part of your question, — (speech interrupted with a brief interjection from Betsy Post)

Betsy Post 22:09
— I just wanted to say, (Didn’t realize that Dr. Turk had started speaking due to connection lag.) — go ahead. I’m sorry. We have, oh, sorry about that. I thought you were finished, and I do apologize. I did want to say for anyone that came late that we do have a Q and A, so I do see five questions already in the Q and A, and we will get to those. So I just want to make sure everybody knows we see them.

Dr. Anita Turk 22:25
I was just going to get to the second part of your question. You know, when you’re evaluating a patient, of course there’s a surgical component, the cancer biology component with the medical oncologist, there’s also the patient component. Part of this does have a dedication of time in that you’re coming in for a pump fill every two weeks, and we have to staypretty close to that as possible. There is some flexibility there, because we don’t want that pump to empty so I always emphasize with patients that you need to maintain a relationship with the institution that you’re going to, if that’s far away,that’s something you really need to take into account. Again, I did allude to the nursing agencies that will help take care of these pumps at home, but that doesn’t replace going and seeing the physician, making sure that pump is operating appropriately, that your liver numbers are doing okay, and that you’re getting appropriate dosing. So as much as I’d like to say, it’s a one time visit and we could do it all at home, it’s not that simple.

Betsy Post 23:26
Thank you. Have a question for one of our patients, or both. I think that I’ll start with Hope and then Hope when you’re finished, Michael, I’d love to hear from you as well. So how did your doctor decide that you were a candidate for HAI therapy? Well, I don’t think that we have Hope’s audio, at least I don’t. Can anyone hear her? No, okay, I don’t know if you can hear us Hope, but we don’t have your audio. Well, you work on that. Maybe I’ll go to you Michael, how about you? Can you answer that and Hope work on your audio?

Michael Riehle 24:27
Sure. I know Dr Turk has spoken a lot about it being like a second and third line treatment. Mine was like a second line treatment, but it wasn’t necessarily because I was progressing with my cancer or anything. MSK wanted to try to get ahead of the ball since I was doing so well on FOLFOX and Vectibix and that my liver tumors were responding so well and decreasing so much in size, they wanted to get in there and really just get the pump in to try to get them down the rest of the way to be able to get to a liver resection. So it’s more of, just to get ahead of the game, instead of a last ditch effort for me, which was really nice.

Dr. Anita Turk 25:16
Absolutely. It’ll still be exciting to see what that clinical trial shows but in many patients, where if we really throw everything we have at the tumor, and where there’s a place where we can get to resection, that’s another special circumstance where Dr. Ellis and I would certainly consider up-front pump placement to get that patient to the OR to surgically clear the disease.

Betsy Post 25:40
Yeah, not sure if Hope has audio, so I’m just gonna see, do you have audio? I don’t hear you. So sorry. Maybe she can join on the phone. We’ll try to figure that out. Oh, I’ll say, I’m gonna ask, …okay, Keith is gonna send you a message…. We’ll try to figure this out. Michael, I’m gonna go back to you for just one other question. I know that you did live somewhere where you had to travel. And I would just like to hear what a few of your considerations may have been when you did decide to make that commitment and get the pump.

Michael Riehle 26:26
Yeah, absolutely. I live in Buffalo, New York and obviously go to Sloan Kettering, New York City, so it’s a five plus-ish hour drive something like that, or fly, and like you said it’s an every two week commitment. There’s no ifs ands or buts. You have to go, you have to go. So knowing that the HAI pump is what was one of my only options that could help me get to NED, I basically just buckled down and said, “I gotta figure this out. I gotta make this work to be able to get this pump”. Luckily, I was able to utilize a non-profit charity here in Buffalo that actually flew me for free from Buffalo to New York City. And I know that there’s a lot of places all over the country that have these organizations that fly patients for treatment. So I definitely urge a lot of people to look into air charities, to try to get themselves to treatment for this, because it’s a big cost, it’s a big time dedication. It’s really all of those things above. So really that helped me be able to commit to it and know that it was something I was gonna be able to do.

Betsy Post 27:46
Thank you.

Hope Brooks 27:56
Is my audio working? Yes. I had to get out of the meeting and get back in the meeting. I’m so sorry.

Betsy Post 28:05
That’s okay. It’s no problem. That’s why Keith’s here to help me-help you. So that’s much appreciated. Let me go ahead and ask you, because I think it’s important, how did your doctor decide you were a candidate for HAI and then what considerations did you have when you were thinking about, “Do I want to do this or not? Do I want to make this commitment?”

Hope Brooks 28:28
At my first oncologist’s office, they didn’t offer me HAI, so I found it, and I moved to a different oncologist after doing some research, and I immediately was asking for it. And when I met Dr. Chung, he said I was a perfect candidate. I had already gone through FOLFIRINOX and had a remarkable response. So my tumor was roughly 10 by 8 centimeters on my liver, and it had gone down to about 7 centimeters to one tumor from that large amount just with FOLFIRINOX and I didn’t have other disease. So he gave me a list when I first met with Dr. Chung that said these are the things we can look at, and HAI was at the top of the list. A week and a half later, I met with the surgeon, and he said the same thing, if anatomically I could accept the pump, then we talked about what it would look like to get it and how my life would be afterwards. And I was already sold on it, I think before I actually had that meeting.

Betsy Post 29:32
Okay, so we wanted to talk a little bit about the surgery to implant the pump, and my question is about what patients can expect for that surgery. But we have a question in the chat that I want to tie into that, if that’s okay. We have a patient that was asking about recovery time. I just want to make sure Dr. Ellis, when you talk about that surgical aspect, maybe talk about that recovery time, maybe robotically versus open, with or without resection, I think is important. And then one of the other questions was, when you were talking earlier about some of those complications with the surgery, a patient was asking: How would I recognize, are there symptoms of an issue after that pump placement? What can patients look out for with regard to a surgical complication with pump placement? So hopefully Dr. Ellis, you can shed some light on it?

Dr. Ryan Ellis 30:34
Yeah, sure. So I’ll start out with surgical recovery. They I’ll start with an open operation, which, is in general, a vertical incision from the belly button to the breastbone. In some cases, if you have a complex liver resection, you may have what called a hockey stick incision, where it goes down and then around to the to the right underneath the rib cage. But the difference between those two doesn’t affect recovery all that much. For an open operation, you’re usually in the hospital around four or five days, depending on the overall recovery trajectory and having any small complications after the fact. The Pump Study, the special study I was talking about, is usually done on the third day after surgery. Everything’s gone well after your operation, you’re usually eating and drinking and moving around by the time you have a pump study, and then by the time you can tolerate a diet, move around, take care of yourself and your pain is controlled with oral medications you go home, again, around four or five days after surgery, for an open operation. The robotic operation is is a little bit faster. Again, in most patients, it’s a little bit of a struggle to get a pump in robotically. Those are primarily done at more experienced centers, or especially for patients who have not had a lot of surgery before. But if that is the case, when I put a pump in minimally invasive, I actually do the pump study often the day after surgery, and those patients can generally go home, sometimes even the day after surgery, but more often, I keep them one additional day, which will tie into the complication timeline we were talking about. After any type of operation the limitations are very similar. I say for the most part, common sense. Don’t lift anything heavy to risk tearing your incisions open. Don’t go in hot tubs or swimming pools or anything like that, and risk causing your skin to break down after the operation. But thinking a little bit about complications and what you would look out for, part of my job as a surgeon, and all the surgeons’ jobs, is to keep you in the hospital to watch for the earliest possible complications that is primarily bleeding, but the vast majority of bleeding happens in the first 24 to 48 hours after surgery. The other types of complications within the pump pocket that I talked about are generally not particularlydangerous, and the things you notice is new swelling, fullness, some people even notice a sensation that their pump is floating in that fluid. And then standard times of infection, redness, a little bit of drainage from the pump pocket and things like that. There are also some longer term complications that we haven’t really discussed, which is actually once you’ve recovered from the surgery and you’ve been getting floxuridine, a percentage of patients do have toxicity from the chemotherapy to the liver. Dr. Turk, when she initiated the conversation, talked about how the hepatic artery preferentially feeds blood to tumors, which is what we take advantage of to use this for treatment. But on the other end of that, the hepatic artery also supplies blood to what are called the bile ducts. So some patients will find andagain, this is fairly rare, months and months after their treatment, they start to get a yellow tinge to their skin, to their eyes, underneath their tongue, and that can be indicative of a longer term complication. That is something called biliary sclerosis that we can come back to if there’s more interest. But for the most part, we keep you in the hospital or the duration of the scariest complications, then after that, it’s mostly sort of common sense. It looks like the skin is infected, or maybe long term having some skin discoloration.

Betsy Post 34:40
Thank you. And for our patients, we can start with Hope and then move to Michael. I want to know, based on what Dr. Ellis said about surgery, what your experience was with that, and what he said about the hospital stay, the scar, the surgery, the recovery, how does what he said compare with your experience?

Hope Brooks 35:03
For me, it’s pretty spot on. We were going to do my surgery robotically. My body didn’t cooperate, so he did this open incision after we were already in the operating room. I went into the regular room after recovery. A few hours after surgery, an hour or so, I was up walking almost immediately, and for myself the pain meds put me to sleep, so I asked them to turn that off. They had done epidural. We turned the epidural off. We started managing pain the first night withmedication, oral versus intravenously. Removed the epidural the next morning. After surgery, I spent that day in the hospital managing pain. For me, a muscle relaxer actually worked a little bit better than some of the narcotics. I’d never had abdominal surgery. Those of you who know me, I work out every single day. You know I’m picking up 100 plus pounds of kettlebells off the floor on a regular basis. So it was kind of a joke that my abdomen freaked out a little bit, so the Robaxin helped me, and then I went home the next day. So I was in the hospital two nights, and I went home the next day. It was uncomfortable, because it is a large metal object. I think the attachment to the abdominal wall was more uncomfortable than the incision itself. Just having it there. It has to settle in a little bit. Every week that went by, it got a little bit better. Probably after about the third week I was like, I can tolerate this. By two months, we got to know each other, and we became friends.

Michael Riehle 36:43
Yeah, for me, my surgery was robotic to have the the pump placed, but it was also done at the time of my colon resection. So my recovery process was a little different, obviously, than just the pump itself. I was in the hospital for maybe five days. I think, like you said, I do remember the pump study being the day following the implant being placed. So that was surprising to me, just because it was my first surgery ever in my life, and I’m like, “Oh, they already want to poke me with stuff”, but no, it was a pretty straightforward recovery. I just had some typical nausea and the normal pains that would come with with incisions, and then my bowels, waking back up from the colon resection, but I was back at work within five weeks, lightly going at it a little bit at a time, not jumping right into it, and as Hope said, within a couple of months. For me personally, I learned to live with it, and it almost just became part of me. I could hardly ever feel it was there unless I was squeezing into a tight place and I bumped it by accident, or the only time, oddly enough, I would ever really feel it would be if I was sitting on the ground and I would bend over at a weird angle to tie my shoe. That’s the only time I would ever actually feel it inside my body, which is weird to say, but yeah, it was pretty straightforward, and the recovery was pretty much what I would have expected.

Hope Brooks 38:12
I want to add on to that. My pump study was done the week after. So, it was a: Wednesday surgery; home on Friday; pump study on Tuesday. So I had to go back for that. But the tying of the shoes is accurate. I started working out four weeks after surgery, modified lighter weights and things, but tying my shoes still is the thing that gets me.

Michael Riehle 38:41
Yeah, it doesn’t hurt, but it’s just that one time where you actually can feel it just wedge a little bit in your body. Yeah.

Hope Brooks 38:47
And my pump was installed, stand alone. I had no other surgery with it.

Betsy Post 38:54
Thank you. And Megan’s here.

Megan Stevens 38:56
I am so sorry.

Betsy Post 38:57
Megan, that’s okay. We are very happy to have you here. I’ll get you in on this next round.

Megan Stevens 39:26
I absolutely apologize. Absolutely.

Betsy Post 39:27
That’s okay. So in the next round of questions, I’m going to tap you in. The next question, we have on initiating the HAI therapy. I know Dr. Turk, you actually talked about this a little bit, but how soon does HAI therapy start following the surgery?

Dr. Anita Turk 39:48
I think it depends on the surgery the patient has. In the patients where they’re just going in to get their pump placed, we’re not removing any segments of the liver to try to clear disease, you can often start at that first follow up visit in two weeks, as long as liver functions look okay. For patients who are planning to do pump after a complex liver resection, and we were worried about their remnant liver being high risk for still having cancer, sometimes it’d be challenging to start right away, and those folks usually need four, five weeks-ish to recover before we could start putting in floxuridine mainly because we just want those liver numbers to start coming back down, make sure those bile ducts are healed up, before we start administering the agent. The main concern that Dr. Ellis alluded to the risk with this therapy is called biliary sclerosis. So for those who may be less familiar, you have the liver itself and then there are tubes running through the liver that help form bile and excrete that into your stool. And that biliary tree is supplied by the hepatic artery so those cells are also getting exposed to this really strong chemotherapy agent. And whether it happens while you’re on the chemo, and it can even happen several months afterwards, those bile ducts can scar down from all the inflammation, and then the bile just doesn’t have anywhere to go. It’s almost like, when you see patients with end stage liver disease from hepatitis or something like that, they can develop a cirrhosis-like picture, where there’s a lot of scarring, the bilirubin goes up, and then options can, unfortunately, become very limited. So we’re very, very diligent about that to make sure we minimize that risk as much as possible. Going in with good liver numbers and your medical oncologist being familiar with how to dose this medication is very important. Again why I say go to a place that does this regularly. You don’t want to be going to a small volume center, not only from the expertise of the surgeon, but the expertise of the medical oncologist,

Megan Stevens 41:47
You’re muted Betsy.

Betsy Post 41:51
Sorry, I always mute so no one can hear my dog… So, with the systemic chemotherapy that’s generally done at the same time, we’d love to hear about the management of that, and then the treatment regimen during active HAI therapy. And one thing I want to tag into that, one question we see quite a bit is folks asking about side effects. So I’d love for you to talk about side effects, just as it relates to the HAI versus the systemic.

Dr. Anita Turk 42:23
Yeah. So again, whether that’s paired with systemic or not, would be a risk/benefit discussion with your medical oncologist. And the big picture in patients where I’m worried there’s cancer also outside the liver, but the liver’s problem number one in that moment we’ll often combine systemic chemotherapy with the pump. Chemotherapy to emphasize treatment to that liver, but also address other sites of disease. Commonly, what’s paired with the pump is irinotecan sometimes also 5-FU with the 48 hour pump. The reason we don’t like to do oxaliplatin, is because oxaliplatin also can hurt the tubes in the liver, all the bile ducts, so we want to avoid overlapping those as much as possible. Often when I pair it with the FOLFIRI chemotherapy, I do reduce the dose. There is a phase one study showing that that is safer for the bile ducts and liver function in general. So normally we dose that pump at full dose. If you pay attention to your dosage, I know many patients do that, it’s 2400. We’ll often bring that down closer to 1500 and irinotecan down closer to 100 where normal is 180 to try to mitigate those risks of liver toxicity. Now in the pump, in and of itself, side effects. It’s not often I get to tell my patients pretty much nothing, most of the toxicity, so to speak, in terms of acute side effects, is related to the pump itself. So, tying your shoe and feeling it. I had a patient whose grandson kicked him right in the pump and it flipped over. Mechanical issues can certainly happen, but from the Floxuridine itself, if that’s the only thing you’re getting, and I’m sure Michael and Hope can comment on this, it’s incredibly well tolerated. I’ve actually really never had a patient with symptoms acutely from that medication, outside of that biliary sclerosis issue.

Betsy Post 44:13
I’m going to switch to a patient question, and I’m going to put Megan on the spot here. What was your experience with getting your pump refilled?

Megan Stevens 44:30
You blanked out a little bit, but I understand that the question was, what’s my experience with getting my pump refilled.

Betsy Post 44:35
…Megan is a patient at Duke.

Megan Stevens 44:37
Yeah, I’m at Duke. When I was in active treatment, I would get my pump refilled at Duke. And it, oddly, doesn’t hurt for the needle to go into your belly. It’s awkward and you feel nervous. But then when it actually happens, it’s a bit of pressure, it’s a little pin prick. Like that. It doesn’t really hurt, and they would fill my pump up, and my oncologist was really conservative. I would get it refilled every six weeks, and I still am getting it refilled every six weeks. I’ve been off active treatment for three years now. I am a three year colon cancer survivor, and I attribute the HAI pump to my survival. At this point, I have a group called “Pentec” that comes to my house, and they do it on my couch. And so when I first started getting it refilled, I would go to Duke and I’d get my blood drawn on one level, I’d talk to my oncologist, or get scans on the next level, they would figure out what my liver levels were and decide what kind of infusion I needed, and then go to the next level and get it infused. And it was amazing, because it was all in one building. It was all on one day. And so I would go deal with my cancer in one day, deal with the side effects of the treatment after the fact, of course, but it wasn’t spread out. So I really liked that about Duke. And once I left active treatment and went on surveillance, we need to keep the pump – I call it changing my oil… We got to keep changing my oil, and I was going down to Duke every six weeks just to get my oil changed. And now they come to my house, and instead of getting lifted up on a table and having the whole room hush and the bright lights come on, they say, “All right, get on the table and grab a pillow”. And she’s very professional. She’s become a friend, and they do it in my house. That’s great.

Betsy Post 46:55
A question that someone had in the chat, Dr. Turk, I’m going to point this to you, because it goes with this. And that’s, how many days can patients extend beyond two weeks due to vacations or other obligations?

Dr. Anita Turk 47:07
That’s a great question. When I counsel a patient, before we get started, I really emphasize the importance of the every two weeks. I don’t like to deviate more than a couple of days from that. Again, running that risk of it running empty. So with these Intera pumps, I can’t program the rate. I’m calculating that rate when I empty it, so I see how much comes out. And I think, “Okay, how many days ago did I refill it?” And I do the math and see how fast it’s running. Knowing the approximate rate of a patient, assuming their body temperature has recently been stable, I can do the math and see how safe it is to extend it, depending on that patient’s pump, but it’s usually not more than a couple of days. Anytime I have a patient with a trip coming up and things like that, we try to adjust their pump fills to make sure, whenever they’re going out of town or they can’t come in, I know their pump is safe and that it’s going to be full with, whether it’s Heparin, glycerin, chemotherapy, wherever they’re at in their round of treatment,

Betsy Post 48:12
Great. And one other question before we move on to the next topic: Can a patient get the pump after having Y90?

Dr. Anita Turk 48:23
Great question. I get a little bit hesitant. It depends. I guess first, let me say it depends on the type of Y90 they had. There’s several different ways Y90 can be administered. It really depends on, were they going after the whole lobe? Were they going after assignment of the lobe? It really depends on what was going on: if they had gotten what we call a bilobar, or Y-mining, means they targeted both the lobes, and they got a pretty high dose where they have some liver issues chronically afterwards. That’s the patient I’m going to be nervous about, that their bile ducts aren’t going to be handling this. But patients who either had an IR doctor that was mindful of their doses, and the liver functions are doing okay? Or it was what we call segmental Y90. Where only a segment of the liver got it, not the whole liver, those patients would still be considered candidates. Ryan, anything to add there?

Dr. Ryan Ellis 49:13
Yeah, I would say people who have undergone Y90 more recently, as our technologies advance, -we’ve been a little bit more selective – are more likely to be candidates. I have certainly put pumps in patients who have had Y90 before. I will add one thing, which is the anatomic considerations can be complicated by Y90 in a small number of people, because of some of the arteries that I have to tie off and the way that I have to reconfigure the system if an artery that I absolutely need for the pump also was the main artery that the Y90 was delivered, that can rule it out, but it’s a case by case basis.

Betsy Post 49:55
Thank you. There are some questions in the live chat as well as some things that I had prepared to ask the patients. And I know I’m trying to look at the clock and make sure we stay on a good pace here, but this is about living with the pump, your daily life, your activities and your quality of life while living with a pump. And I think that this is really important. So I definitely want to talk about that. Also in the live Q and A, there are questions about what kind of physical activity can folks do with the pump? There’s a patient that says, “If I get this pump, I have a 13 month old baby… will I be able to lift my baby, put him on my hip, things like that?”. I would love to hear, I think we’ll start off with Michael just about physical activity, day to day life with the pump, and then move to Hope, if that’s okay with you?

Michael Riehle 50:45
Sure. Yeah, so, day to day life for the pump with me was after the that kind of learning period of a couple months, was pretty normal. I worked full time. I have a pretty physical job where I was climbing all over my trucks and getting into tight spaces and everything like that. My wife and I like to travel a lot, go hiking, go camping. We have some four wheelers. We like to go play in the woods and everything else. There really wasn’t… — I had to stay away from my hot tub, which we had unfortunately just gotten a month before my diagnosis. So that was kind of ironic. But other than staying away from the hot tub and stuff, really, nothing changed in my in my day to day life. You get used to where the pump is and certain things that you can or cannot do. Not that there wasn’t much that I couldn’t do with it, but you just would do it a little differently. If your body would want to move one way, you just have to remember where it was and how to react to it. So yeah, for me personally, it was almost like it wasn’t even there once you get used to it.

Betsy Post 51:56
Thank you. Hope?

Hope Brooks 52:00
I was actually afraid of that. That was the only hesitation I had when I was discussing the pump and getting it implanted. But come to find out, I was testing all the waters. I started out with, I don’t know, 10, 20, pounds of weight, and then worked my way back up. I went back to yoga. I don’t practice quiet, sit down yoga. I’m very active style yoga, and so I’ve been able to do everything I did before the pump. And again, just like Michael said, there’s a few postures or movements that you do have to adjust, just like the shoe – putting it on, you find a new way to do it if it works for you. Certain things don’t work. The twisting to the left doesn’t work as well. I can’t go as far. Certain things I would do on that side I just avoid if it bothers me, but I do everything that I did before. There’s not one thing I can think of other than a hot tub that I don’t do. I also practice hot yoga. So that was a difficult step. My surgeon and I discussed it at length, and I did a few tests on temperature, and I keep track of all of my usage of the pump in a spreadsheet like Dr. Turk was talking about, to figure out what my daily consumption was, and it was average, whether I was in the room once a week or if I was there six times a week. It didn’t change my core body temperature. Didn’t affect the pump and how it operated. So for me, I really was able to do everything. I go swimming in the summer. I’m a big water person. Nothing I can think of that I’m really missing other than a hot tub. I do take a bath, though. At first I was afraid I couldn’t take a bath, but I do take a bath.

Betsy Post 53:45
Megan, if you want to answer quickly as well. There’s also a question for Megan in the chat, so I’m going to tack it on here to this for you, and that’s that you had talked about, you’re just doing surveillance now. Are you just getting glycerin now?

Megan Stevens 53:59
I am just getting glycerin and it’s going well. I don’t know when we’re going to talk about taking the pump out. I’m hoping we’ll start talking about it. I’m actually, two and three quarter years, but I think I’m starting to get ready to have it out if I can. I mean, it’s a luxury to be able to be seeing the light at the end of the tunnel on this, but it’s also pretty awesome to know that that is possible, and that’s a thing that’s out there, that it’s real, and science gets better every day. I personally have been very weary about my movements with the pump. I have an 11 year old, and he was seven,- six and a half, seven, – when this all began, and I’ve just been really careful about it. I think it just depends on — everybody’s always on board saying they’ll do anything, and that’s great, and it’s wonderful. I think it’s a psychological thing for me. I’ve been very, very conservative with my exercise, which is showing because I’ve gained some weight, and I need to figure out how to get it back in line. But I’m alive. …That’s what I did.

Betsy Post 55:26
There are a couple questions in the chat that I think we should definitely answer. And this is something that comes up inCOLONTOWN as well. You’re talking about the biliary sclerosis, some of those chemo toxicity issues that can happen. So I’m going to weave a couple of questions here into one. This is something that comes up all the time, the discussion of the role of Ursodiol following HAI placement. And are there any others with Ursodiol? We’d love to hear your thoughts on that, but also any recommended standard of care medications that you can take while on pump chemo to help prevent with any of those liver toxicities. Or are these things that maybe you just get if the liver numbers rise? And then also, what liver function numbers do you specifically watch out for?

Dr. Anita Turk 56:20
Great question. So yes, the rates of biliary sclerosis are probably around 20% so it’s not an insignificant number. I’ve unfortunately lost one patient to that complication. So we are very, very vigilant about it. There is no data, unfortunately, about preventative measures. Of course we will use ursodiol if we are seeing signs of that problem, and really work closely with hepatology to help manage the health of your biliary tract. But right now, I don’t have great data to support any medication to help it be preventative. I will say the healthier you’re walking into it the better. And of course, it’s not just dealing with the cancer itself, but your general body. So hearing patients like Megan, Hope and Mike going into this, following up on their appointments, being really active, eating a balanced diet, things to minimize having a liver that’s already ill at baseline in the background, I think probably does help. Patients who have underlying cirrhosis walking into this, or with fatty liver disease, are more likely to have outcomes related directly to the chemotherapy than those who don’t have those baseline problems. So I think general health is probably the best thing in our pocket going into something like this. Again, I cannot emphasize enough the importance of physical activity to help with all of that, and I apologize, what was the other question? Think it was not just the ursodiol, but if there are any other medications that you recommend or could take. But then also the other part was, at what point do those numbers become concerning, and is it a specific number you’re looking for, like the alkaline phosphatase? Right, yes. So the most important number–we look at all the liver numbers but the most important ones are the alkaline phosphatase, the bilirubin, we do also look at AST and ALT. I’m sure many people on this meeting today are familiar with looking at those numbers while they’re on chemotherapy, but they don’t have to be in the red to be a problem. So I have patients where I start this medication, and their alkaline phosphatase is in the 90’s, but they jump to the 120’s that’s still normal at our lab at IU. But that’s just the fact that it went up is a problem. So we take any rises very seriously. So the other medications that we use, in addition to ursodiol, would be for very severe cases, but where the patient’s doing fine, their liver numbers are still technically okay but have gone up from baseline, is adding steroid to those heparin days to help bring those numbers down and dose reducing that chemotherapy once those liver numbers have improved to make sure we don’t cause repeat injury. So again, I’ve said this again. I’m going to say it again. It is very important you’re going to a center that is familiar with how to dose floxuridine and manage these toxicities, because they can be very serious.

Betsy Post 59:22
This is for the patients: I would love to know what you would like to tell other patients that are considering the HAI pump, and then, along with what you’d tell them to consider, what might you want to tell them to ask their oncologist? Anyone want to go first? Hope maybe?

Hope Brooks 59:48
Oh, just one second, let me think. I guess my question would be, “Why am I a candidate for the HAI, if it is an opportunity for me?”, becausefrom what I understood when I met with Dr. Chung, because I had a good response to the FOLFIRINOX, it was assumed that I would likely have a very good response to the FUDR. So that’s a question for me is, how does that work? Had I known more than I know – the list of questions on the patient questionnaire that’s been recently published. Those are questions that a lot of them came from me, that I asked. Those are things I wish I had known outside of the single question. There’s several of them that I wish I had asked ahead of time, but I learned later. So hopefully that’s a guide to somebody.

Betsy Post 1:00:38
Great. Megan, anything you think patients should know?

Megan Stevens 1:00:55
It’s hard. So I had gone through several doctors before I made my way to Duke, and I’m driving three hours to get there every time, three hours back. And it was worthwhile, because I trusted them, and as soon as I knew I was in hands that I fully trusted, I just let go of all need to control, and I put my faith in them and let it be. But I think I would want to know if this was closing down any other opportunities for treatment. With the advancements of technology and medicine as it is, you want to always keep as many options open, and if something closes down options, to me, that’s a red flag, because the more options you have, the longer you will be able to fight this, and the closer you’ll get to having a solution and a resolution to it. So I guess that would be my question: “Does getting the HAI pump close down any options for me moving forward?” Because you’re always playing the long game, there’s not a short answer, there’s not a fast answer. You are in this for the long game, and you’ve got to have as many options as you can to get to the end. That’s what I would think.

Betsy Post 1:02:31
Thank you. Michael, anything to add?

Michael Riehle 1:02:34
I guess my biggest advice would be kind of similar to what Dr. Turk said about making sure you go to a reputable place for something like HAI therapy, instead of just going to maybe just your local center that they started picking them up last year or the year before, and they don’t have as much experience in it. Because the potential of risk is so high, you really want to have someone that knows what they’re doing and has the utmost experience with it. So if it’s something where you have to travel, try to find a way to make that work, to get to the best place, to give you the best care, as difficult as it may be. I mean, a lot of us are here because we got ourselves to these places to get these things done, through these top places. So that will be my biggest advice.

Betsy Post 1:03:25
Thank you. And it’s 8:04, so I’m going to wrap up a tiny bit, but there is a question in here I definitely think we should answer, and that’s if you have a recurrence with the pump. Can you still have resection or ablation, or is it more favorable to treat with chemo only? So I think that’s an important question for us to answer. Maybe Dr. Ellis, you could take that one.

Dr. Ryan Ellis 1:03:55
Sure. I apologize, my internet has been on the fritz, so if I fade away, that’s the issue. So yes, it is. It’s totally appropriate to have additional procedures on the liver after the hepatic artery pump has been placed. If I remember his story correctly, sounds like Michael actually started with a pump alone. There are multiple pathways, wherein when I see someone who we’re considering, Dr. Turk talked in general about the indications being unresectable disease, adjuvant disease, and in all cases, there’s chances that even after you’ve had all of your disease cleared either before or after the pump is placed initially, the disease can come back, and we do routinely do additional local therapies. Y90 is more or less off the table once a pump is in but the resections and ablations can absolutely happen if you have a local recurrence in the liver after the pump is placed.

Betsy Post 1:05:09
So I just want to leave it to the patients to wrap up. Is there anything Hope, Michael, Megan, that we haven’t talked about tonight, anything you think is important that you’d like to say to any of the patients that are watching tonight or in the future, but it’s okay if you don’t either. That’s okay. I don’t want to put you on the spot too much, but parting words from from our patients that have done this therapy and have had different types of results. You’re all from different centers and and your stories are all a little different.

Hope Brooks 1:05:47
I would like to say, because I’m not on active pump treatment right now. -We’re dealing with a few questionable lung mets, but otherwise, I’m clear of disease at this moment. I’ve two times used my pump for a recurrence, and it worked wonderfully. So I look at it like you have to know that you’re going to get married to this pump for three to five years and be ready for that long haul and be able to ask the questions. And there’s a lot of tools out there that weren’t even out there a year and a half ago or in December of ’22 when I got my pump. So ask for those materials. Ask to be educated on the pump. If you have hesitations, ask to speak with a patient. There’s a lot of oncologists and surgeons that will have patients of theirs that you can speak to, that might be local to you, or somebody in the groups in COLONTOWN that can help you as well. So one, don’t be afraid to ask the question. Two, don’t be afraid to travel and try to utilize the tools that are out there to see if this is the right fit for you. It changed my life. I don’t think I’d be here without it, I’m 99% sure of that.

Megan Stevens 1:06:51
Yeah, I think there’s one thing I’ve worked with, – I’ve been friends with, been close to other cancer patients, and a lot of times they were nervous that they would hurt the feelings of their doctor if they got a second opinion. They didn’t want to offend anybody by getting a second opinion. Doctors are not going to be offended by you getting a second opinion. You are in your absolute right to get as many opinions as you want from doctors all over the globe. And doctors are good people. They want to save your life. They want to give you an opinion. And you shouldn’t fear reaching out to other people.

Michael Riehle 1:07:45
I’ll echo what Megan hope said, just don’t be afraid to reach out to anyone, whether it’s another patient or other doctors, because they’re your lifelines. So don’t be afraid to reach out.

Betsy Post 1:07:59
Thank you, Dr. Turk, Dr. Ellis, thank you so much for being here on the panel this evening. I know I’ve learned some things too. And thank you so much to our patients. Hope, Michael, Megan, we really appreciate your time. And thanks to everyone that attended live and of course, all of those that will be watching the recording. And I just wanted to leave the final word to Dr. Turk, Dr. Ellis. Is there anything that you’d like to add, anything that we didn’t cover tonight that you think is important?

Dr. Anita Turk 1:08:32
No, I can’t think of anything. I think we’ve covered at least the basics of pump therapy. Again, a lot of it’s a case by case situation. And just get that second opinion. I promise you your oncologist is not going to be offended. We all just want to help.

Dr. Ryan Ellis 1:08:48
Likewise, great discussion. I thank the panelists for their time.

Betsy Post 1:08:55
Thank you all so much. Have a great evening. Thank you.