This transcript is automatically generated.

Betsy Post 0:00
Welcome everyone to EPL, our first in-person. So exciting. I had wanted to be there today in person, but due to COVID with our presenter, I decided to just wait for the next one, but I have my medal on. I attended the first CPL that we did in Washington, DC, in 2018 and if you’re not familiar with me, I am the I’m on the COLONTOWN cabinet and the community leader for the metastatic groups in COLONTOWN. And then I personally run the liver groups. Livers are my passion. So I’m really happy to be here today. It’s really just my honor to introduce our esteemed presenter, Doctor Soares from Memorial Sloan Kettering Cancer Center, and he’s also an assistant professor of surgery at Weill Cornell. So we’re really honored and blessed to have him with us today. Also he’s going to let us record this and make this available for COLONTOWN. I have everyone is so excited to see it. But EPL gets, of course, the gets this first. So I think that’s a really great privilege for everyone, but this will be recorded and made available later. So just a couple things. Of course, I said he is at some cutting. He’s a liver surgeon there. I actually met him personally when my sister was under the care of some cutting. So I just know him personally as a wonderful human being and surgeon. He was also a general surgery resident at Johns Hopkins and got his MD at University of Massachusetts. If we have anyone from the northeast, from Massachusetts, since this is a New York, New Jersey area, I’m sure that there are a lot of feelings on the next slide, he is a Boston sports fan. I don’t know how popular that is in the room, so hopefully we can forgive him for that. He’s also a dedicated husband and father, but his bio that really touched my heart, and I think it’s why he’s here today and presenting to patients and caregivers for COLONTOWN. He really values patients and caregivers, and he really wants to make sure patients and caregivers have the best experience they can have when they’re going through the most difficult times of their lives. And I know that to be a personal truth, because I know him personally. So without any further ado, I will pass it over to you. Thank you so much for being here, and we really appreciate your time.

Dr. Soares 2:22
Thank you so much. Betsy, it’s honestly, it’s great to see you again, and that was such a kind introduction. I really, really appreciate it. I’m so sorry as well. I can’t be there in person. That had been always my plan, and unfortunately, because of COVID related risk reasons with our kids, I have to self quarantine. But I’m really happy and pleased that I can do this via zoom and be with you today. All right, great. So again, it’s really a pleasure and honor to be with you today, and I really do appreciate this invitation with such an esteemed group. I talk to patients all the time about how much everything you do helps them and to meet you now, unfortunately, virtually, but still to meet you and know all the great work you do, it’s a privilege to be a part of this, so I have no disclosures, but my main point today is really to try and talk about what we’re doing in the modern day and age for colorectal liver metastasis, how we’re approaching the disease, but also ideally empowering the patient with the information, understand what the debates are in the disease and different ways to go about this, because I think only with information can you really understand what your options are and really get a better sense of what the risk benefit ratios are for the different things we can do. So as all of you, I’m sure, where colorectal cancer has about 130,000 cases per year, and about 25% of those patients have liver, liver metastasis when they present, a quarter of which are actually resectable in presentation United States, so about 15 to 20,000 cases per year. And you know, historically, the role of liver resection and its benefits were initially debated. This wasn’t that long ago that many thought that the role of liver surgery was too dangerous, as stated here in this quote from Dr Foster in 1977 they described their experience saying the following, 20% percent of patients will die in the operating room because of sanguinating hemorrhage. 14% die post operatively as a consequence of blood loss during the operation. Another 15% can die of liver failure, not you know, caused by technical factors or other issues. So really, since the 70s, we’ve come a long way in making this safe. But in addition to the technical aspect of liver surgery, it wasn’t understood whether liver surgery could be helpful for the disease, even if successful. This was a quote by Sir Ogilvie in the 50s saying “liver resection partial of technique for malignant disease can rarely be justified. There are always secondary metastases multiple and it can be assumed that many seeds of cancer still still in palpable or scattered throughout the liver and basically pointing out micro metastatic disease and the high risk of the recurrence”. But we’ve come a long way when it comes to this, and the outcomes for liver resection have improved dramatically. And in high volume centers, it’s it’s very safe. And this looks at outcomes for major liver resections in a more modern series here over the years. As you can see, even for the major liver resections, that the more extensive ones, the left trisectionectomies and the right trisectionectomies, the mortality rates are now 6% and as you move further down and do less extensive liver resections, you’re getting your mortality rate as low as 1% of times if you’re doing less than or equal to four segments or section. And really, that has a lot to do with the way we started to approach this disease in the modern era, and more specifically, parynchymal sparing liver surgery, where you perform less extensive resections of the liver that allows for preserving as much of the normal liver as possible, allows us to treat patients with tumors on both sides of the liver that have multiple tumors, and it also means lower blood loss, lower complication rates, lower mortality, and as we’ll get to later, a chance at cure for these patients. And this paper evaluated what’s happened over time as we’ve gone to the parenchymal sparing approach, where we’ve seen the changes in morbidity after or mortality after liver resection here at MSK, when we’ve introduced parenchymal preservation. So from 1993 to 2012 there were 3900 patients of those who underwent 4 152 liver resections, and the most common diagnosis for this patient population was indeed metastatic colorectal cancer. And firstly, as you can see here, and consistent with this parenchymal preservation approach, we’re doing a lot less major hepatectomies have come down significantly from 65% initially down to 36% more recently, also, the number of segments goes along with it, whenever a median of four segments were second, initially now down to median of two, all statistically significant. And with that, we see a common decrease in estimated blood loss as well as complications, both minor and major, and very importantly and at the bottom, the mortality rate overall has gone from 5% down to 1.6 and a very acceptable 1.6% at this point. So this evaluation demonstrates the difference in approach and what’s happened as a consequence, with the differences in complications with this and these smaller segmental resections, as well as utilizing other modalities to do these resections and treat these liver tunes, one of which is using ablation or irreversible expiration. So here’s a description of irreversible expiration, also known as I.R.E., which allows us to treat tumors that are small but in very difficult locations, near critical structures that would have otherwise in the past, caused us to have to do large of a resections or rendered a patient unresectable or untreatable. And what this technology does is essentially uses electricity to cause the cell, the tumor cells, to have holes created within it, and eventually causes a tumor cell death, but at the same time, spares the very nearby critical structures of the liver. So we can treat these small tumors in terrible places, and take a patient who may be deemed incurable and unresectable, potentially transition to a curable treatment paradigm. And the reason for all this is really because this disease the only curative component, despite it being stage four, is resection. Patients who can be resected can achieve a cure, and up to 20% of the patient population, as we look back at our data for 10 year overall survival in a set of 1211 patients with a pretty long follow up at this point of 10.9 years. So it’s important to not only safely and thoughtfully use these different treatments, but also use data to understand which patients can benefit from these aggressive approaches, and this is an analysis published out of MSS in 1999 it’s still commonly used today, despite the many changes that have happened in therapy over the time where nomogram, or clinical risk score was created so that we can understand, based on factors of the patient’s primary tumor and their liver metastases, how likely they are to survive. So these five factors are given a point each, and depending on where you are on that curve, the clinical risk score, if your curve, if your number is low, zero to two, you appear to have a much better survival compared to patients with a high clinical risk score. So this is important because we can use this information to have a conversation in the clinic about what we’re trying to do as well, as you know, talk about the real benefits that may come with that approach, and put the risks in perspective for patients, which I think is actually one of the most important things we can do in our in our interactions together. So clearly, understanding how to use everything at our disposal is key for what is a very complex disease. So I will discuss a little bit more about the role of systemic therapy chemotherapy, and particularly understanding how to use it around surgery, which is ultimately the goal, the goal, and this includes neoadjuvant chemotherapy or surgery or chemotherapy before surgery, recurrence rates are high after even after surgical resection of all your liver metastases anywhere from 50 to 75% so this prompts consideration of chemotherapy, as I mentioned to you in the beginning, about the possibility of the microscopic disease coming up later and recurring. But the data for these are not robust. It’s really based on stage three colon cancer data. We know in stage three data and patients, where they get systemic chemotherapy, appears to improve outcomes, but in stage four, it may not be as clear and also the another rationale for using chemotherapy in the setting is, well, we can maybe understand who would benefit more from surgery before we undergo major liver resections. Can the test of time help us in assessing their response to chemotherapy to better select patients. So I will tell you what you know, what we know so far, as far as you know, the benefit of this neoadjuvant approach. This was actually a randomized control trial that was done that randomized patients to either perioperative FOLFOX, which they got six cycles before and six cycles after, versus surgery alone, and they looked at the progression free survival in this patient population, and of those 181 randomized to the chemotherapy arm. Ultimately, 159 were taken to resection, and 80 completed their chemo. The other group received surgery alone, and of those 182, 159 were taken to resection, and their primary endpoint by intention to treat. Analysis showed that this was indeed a negative trial with no statistically significant improvement in progression free survival, but also, very importantly, and what we care about the most, both as providers and patients, is what what happens in overall survival? And there was really no benefit in overall survival in this in this study, with overall survival as a secondary endpoint. And what about this theory about can chemotherapy around the time of surgery, evaluate the response to treatment and improve our selection for patients who go to surgery? This is a retrospective study out of Germany. 160 patients that had chemotherapy before resection of their colorectal liver metastases. Only 40% of these patients had responsive or stable disease. But as you can see in the survival curve on the right, the tumor response and progression on chemotherapy really had no bearing on how long they survived. Rather, it was driven by their ability to get to a resection and other factors that we had mentioned earlier in the clinical risk score. And this is a similar study from MSK, where 111 patients were looked at, with 16% of patients having progressive disease while on systemic chemotherapy before surgery, and the median overall survival for responders was 58 months. The median overall survival for those of progressive disease on chemo was 61 months. Really no difference, and clearly, the response in the evaluative chemotherapy doesn’t help us really predict overall survival or help us better select patients. So it is important to understand when systemic chemotherapy can help us, but it’s also important to understand what the risks are that come with chemotherapy. Nothing in medicine comes without risks, as we’re all aware. So the question of how much chemotherapy can cause problems was addressed in this French study, where they looked at 67 major hepatectomies, and which 45 got varying amounts of pre operative chemotherapy. And then on their path analysis, they saw hepatic injury was twice as common in the preop chemo group. In addition, as you can see in the Biograph, increasing the chemotherapy cycles prior and duration prior to their surgery as a stepwise increase in the complication rates after. So we know that very prolonged chemotherapy can sometimes make surgery more difficult or impossible, and this was somewhat supported by that trial I mentioned, where they looked at their complication rates and there was no difference in operative mortality in the two groups, but the chemo group did have an increase in post op complications, as well as biliary (_?_) and intra-abdominal infections. Now this isn’t to say that chemotherapy isn’t necessary. There are situations where it’s it’s important, but in those situations, it’s also important. Now, how can we maximize the benefit, minimize those risks that we just talked about before we can get to a surgery, and those patients who are eligible, and this is a retrospective review of patients who had gotten both systemic chemotherapy and pump chemotherapy, plus systemic chemotherapy under in looking at their response to treatment, so that we can better understand what’s the topping of this response, and when have they maxed out their response. And this waterfall plot shows that the tumor reduction in the response really happens in the first two months after systemic chemotherapy, somewhat, you know, and that’s dictated by these lines that are increasing here toward the top of the Y axis. And you may see some continued response up to four months. But beyond that, you see that these lines tend to straighten out. Some even come down, indicating that beyond that, there may not be a lot more expected, expected response. And perhaps this is a time when we really need to consider, as both surgeons and medical oncologists, where we can move forward with different therapies, where the benefit becomes less with systemic and it’s similar with pump chemotherapy and responders overall, pre operative therapy, surgical resection really is considered about after two to four months of treatment in patients who are eligible, because we’ve maximized the approach with the neoadjuvant approach at that point based on the response data. So what about chemotherapy after surgery? You may have noticed that the trial that randomized patients to chemotherapy before surgery in the in the control arm had surgery alone, and that has a lot to do with the unknown about what the real benefit of any adjuvant systemic chemotherapy really is after complete resection. We know it shows improved survival for Stage Three colon cancer, but stage four colon cancer, it’s not so clear. And this summarizes a number of different trials that have looked at this space, randomized control trials, large number of patients, and throughout all of them, Progression Free, survival has trends or no difference whatsoever. And certainly there’s been no difference in overall survival. So despite theoretical benefits to systemic chemotherapy. The data have not really borne that out, and some of the reasons are really that some are cured by surgery alone. Some will have their cancer come back despite chemotherapy, and some will have some indolent disease that’s that’s manageable and possibly cured by repeat resections or ablations or techniques I mentioned prior, which really is a very small percentage of patients who can benefit, but we know that there’s still a high risk of recurrence, right? We talked about that earlier. So what else can we do to try and limit that risk of recurrence? And regional chemotherapy is something that’s been utilized at Sloan Kettering on many institutions now, more and more moving forward, to try and address this high risk of recurrence and help us be more effective in the treatment of this disease. This is not a new or experimental therapy. Pictured here is Dr Kelly, who’s really been the pioneer for this approach in this disease, who is at Sloan Kettering, and was working on this as early as the 1980s and publishing on this approach in the early 1980s but when you look in the NCCN guidelines at the indication for hepatic artery pump therapy after resection, it’s here as a footnote, and someone who’s not used to reading these may not even notice that it’s even there in the guidelines at all. So what’s the rationale for this approach? Well, metastases to the liver are typically receiving their blood supply from the hepatic artery, as opposed to the normal liver, which get, which gets most of its blood supply from the portal vein. And the drug that’s utilizing hepatic artery pump therapy is FUDR, which gives the liver approximately two to 300 times stronger dose of chemotherapy than it receives a systemic chemotherapy alone, and it’s completely eliminated by the metabolically in the liver. So by the time it leaves the liver, it’s no longer active. And so in many patients, as we mentioned, this is the only site of disease, and a very aggressive approach to the liver is warranted. And this is one such approach that we commonly use, and it’s actually been studied in randomized trials as well. This is a study of Sloan Kettering published New England Journal medicine in 1999 by Dr Kemeny and her team, where they looked at patients with a complete resection to colorectal liver medicine. At the time they either got pump therapy after surgery with 5fu systemic chemotherapy, and compared that to a group of patients that were randomized to systemic therapy alone. They looked at their two year overall survival as well as progression free survival in overall and in the liver. And at the time of their publication, progress, the median progression free survival in the liver was not reached versus 43 months in the chemotherapy group. The two year overall survival is 86% in the pump group versus 72% in the chemotherapy group. So this was a positive trial and met its primary endpoint of two year overall survival. And the conclusion from that study was, was that adjuvant treatment with combination of pump therapy and systemic chemotherapy improved survival at two years. It subsequently went on to look at the long term outcomes now with patients who had a minimum follow up of six years, the median follow up of 10.3 years, and again, saw similar findings where the median progression free survival in the liver was not reached at that time, and still, this is statistically significantly improved in the pump group, same with progression free survival, and although not statistically significant, the 10 year overall survival is 41% in the pump group versus 27.2% at the chemotherapy group alone. This was prompted other trials, not only in Sloan Kettering, but this was an ECOG study where they did a similar study combining pump and 5FU and compared it to surgery alone, in this case, again, a primary endpoint of progression free survival and hepatic progression free survival, the four year hepatic progression free survival was 66% versus 43% in the systemic chemo group, similarly significantly improved overall progression free survival, and the four year overall survival was 61.5% in the pump versus 52.7% versus chemo, in this case not statistically significant, but you met its primary endpoint. And so their conclusion was that the adjuvant use of pump chemotherapy and systemic chemotherapy was beneficial in prolonging time to recurrence after resection of their colorectal liver metastases. So we then looked at our experience overall, since we’ve been doing this for many years, looking at 2368 consecutive patients going to rank (?) curative resection. This was done prior to my time at Sloan Kettering. But essentially 1583 patients were treated without pump, and 785 patients treated with pump. And when they look at the subset of patients who were curative intent, resection only, meaning they could have all their tumors, or all their tumors were resected and utilizing modern systemic chemotherapy regimens, which really is multiagent chemotherapy, or FOLFIRI, we saw that the pump patients were – it seemed to have an improved overall survival, statistically significantly improved overall survival versus those that did not get pumped 67 months versus 47 months. And this was despite the fact that many of the patients in the pump group, although being younger, had shorter disease free intervals, had more tumors on average, higher tumor mark, tumor markers, the same but higher clinical risk score overall in the pump group. But they went on to further look at just matching, doing a rigorous matching analysis of pump patients versus systemic patients. And then, in this propensity score analysis, again, identified an independent association of pump therapy with an improvement of approximately 23 months in overall survival. And interestingly, it was the patients that had no negatives or low clinical risk score that seemed to potentially benefit the most from this approach. So this is how things have played out in the adjuvant setting, particularly when it comes to pump therapy. But what about patients such as these, where they present with extensive amount of liver metastases, there is no real avenue to liver resection at that point. But what’s the best approach, and how can we potentially get them there? In those situations, the standard of care would be to start with systemic chemotherapy, which we all know, though, is limited in the sense that chemotherapy is not curative in this disease or many others. And so although the response rates are high, the median survival time remains rather low and usually will progress on average, eight to 12 months afterwards. And as you start moving on to other lines of chemotherapy, your response rates really get much, much lower, 20% at best, for second line therapies. And when you’re on to third line therapies, it’s really responses are rare, but what we’re hoping for patients like these is to be able to convert them to resection, which can occur, depending on your definition of unresectable, anywhere from 10 to 60% of the time. But importantly, when you resect patients, no matter how they present, their survival can approximate those who are initially resectable as well, and it’s requires techniques to do this, including the techniques we discussed before, paragonal spurring (?) approaches, ablation and IRE, now understanding what the data shows in these in these types of patients, is hard, because the definition of what’s unresectable can can change and sometimes be hard to identify in a published report, but our institution did a trial, which looked at patients such as these, a prospective trial, phase two trial that took patient, unresectable liver-only metastasis. And these were patients that were technically unresected, meaning their tumor involvement of the liver was extensive, so that they could not be left with enough normal liver behind to survive after a surgeon. And so these patients would get pump therapy as well as the best systemic chemotherapy available. And these were patients that, for the most part, had presented with liver tumors at the time that they had their diagnosis made. And 95% of the patients, two thirds of them, had prior chemotherapies already. They had an average number of 13 tumors in the liver, and 91% had a high clinical risk score, so greater than three as seen earlier. And in this prospective protocol, half, about half the patients eventually were converted to resection with a response rate of 73% with the use of pump and systemic chemotherapy together. And if you look at their overall survival from treatment start, the median overall survival for the group was 46 months, and the five year overall survival was 36% and this analysis also seems to indicate an association of a better overall survival if patients are human naive as they get started on pump therapy versus those that have been. On prior systemic chemotherapy. Look at their survival by landmark analysis by 12 months nine and 64. Patients were had no evidence of disease. One had had a complete response to pump. Five had no evidence of disease after the resection. And three were with no evidence of disease, but had another treatment, whether it was resection or ablation. So clearly these patients, despite presenting with very advanced and unresectable disease and high risk disease, can have responses that can potentially render them resectable in select cases. But what about the patients that have essentially progressed through all these lines of chemotherapy, as I mentioned, third line therapies have a very, very low response rate in general, and actually, responses in that situation are rare. So we looked at, well, what can the pump do for these patient populations? And 110 patients that were treated with at least three prior systemic chemotherapy regimes were evaluated. Half of the patients had liver only disease, the other half had some evidence of extra hepatic disease as well, but all had liver disease and were had a pump therapy placed. And even in this highly treated a pre treated patient population, the response rate was 35% so needing an overall style for 20 months in these patients, if they have liver only disease, in 11 months for patients with extra hepatic disease. So this is what we’re hoping to see when we initially, after we initially see that patient, is that these responses can go over time and eventually get to a point where the diseases become small enough to combat it can be handled through these different approaches, such as parenchymal sparing approaches, ablations and IREs that potentially treat all the active or residual or visible disease in the liver. And in these situations, we understand that recurrence is high, the risk of recurrence is high, at least 70% and it typically will happen in the first year to second year after their treatment. But this does not mean that we can’t then still aim to try and resect, or depending on the nature of these recurrences, treat these recurrences rather effectively. And this analysis out of Sloan Kettering looked at that, you know, the median follow up of 59 months in patients who were in 952 reception, 62% had recurred. Of those, 27% had salvage therapy, whether it was resection again, ablations or other treatment modalities that we can use and another, the rest of the patients were went on to palliative therapy. And when you look at the strategy as you go down 952, resections of the 594, recurrence is 160 at salvage therapy. And you look at those patients that had enough follow up at the time, which was released three years, 36 out of 145, patients were NAD after last salvage in total, that’s 6% of recurrences and 24% one in four patients who had undergone a salvage therapy. So in summary, to put things in a bit in perspective. My point today was to really give you a sense of what where we are in the field and what the debates are. And it’s a few things are rather clear at this point, hepatic resection of these liver metas can be potentially curative and appear safe with our modern day approaches and parenchymal preserving approaches really the only proven strategy to limit recurrence in the liver after resection of colorectal living metastases appears to be hepatic artery pump and systemic chemotherapy at the time, and it also appears to be a promising strategy for patients with unresectable disease. And I’m happy to see that there’s been a very large focus on hepatic artery pump therapy and a better understanding how it can help patients, and this is one example of that, which is the hepatic arterial infusion consortium that’s being led by Dr Lidsky at Duke and Dr Angelica at our institution, where a number of leading institutions across the country and the world are working together to really analyze and study this so that we can get some more robust data and know how to really use this moving forward. So I’ll finish with this slide, which I think is actually the most important slide for what we’re talking about today. And the point today was to tell you that there are so many different ways and many different things we can approach this disease, and it really is patient specific. What works for one patient is not right for another patient, and the only way to get to the bottom of what makes the most sense for your particular case is understand to ask questions very early and often, right? Because we know, when asking questions, having more discussions, we can get better and clear information, and that information is power. It’s things like today, where you understand what the debates are, and that will empowers you to discuss this with your medical providers to do that, and I can’t stress the next one enough about obtaining a multi disciplinary opinion. Think not enough patients with this disease see a surgeon early on in their disease. And as I mentioned, you know, things such as the amount of systemic chemotherapy can have major implications for how the cancer can be treated. Moving forward, so making sure to get a multi disciplinary opinion right from the beginning and seeing a medical oncologist, seeing a surgical oncologist and a liver surgeon, as well as anyone else that would have a role in your care, including radiation oncologist at time, I think this is critical so that you can know that you got a well rounded opinion and understand your options now and what may be possible in the future. As doctors, we’re here to help. We’re here to give you information. It’s really about understanding what the risk benefit ratios are to what we’re contemplating doing. And many times, there may be more than one approach that’s reasonable, and so that’s our job, is to help you and your family and the patients in their family make the right decision as to what works and what what really will improve and keep the quality of life while treating their cancer aggressively. And there’s always a question of second opinions. I get asked this a lot, and every time I answer is, always, there’s no harm. It’s it’s a very smart thing to do. I I see no downside to it, and fully supported. And I think as patients, that’s one of one of the things, in addition to a multi disciplinary opinion, that that getting second opinions should be high on your list, as far as your checklist, as you get moving along in the course of battling this disease. So thank you very much for your attention. Appreciate again, the opportunity to be here, and I’m happy to answer any questions you guys might have?

Participant Question 31:26
Thank you again. Dr. Soares for sharing, I’m going to reserve the right to ask the first question. I’m from Kentucky, and in 2019 I was thinking about hai pumps. I don’t know. I don’t know exactly when the consortium, the group of different hospitals, started doing that, but I do know that I’ve seen so much progress, even since I had that consult in 2019 with the HAI pumps and the availability in locations across the United States, and it being used more practically by doctors. And I also get these so when I have discussed it with my surgeon. He also has mentioned, you know, that this group of hospitals also can, like problem solve together, issues that they might see in their local cases about so I just think it’s it’s not something we hear about a lot as patients, that doctors are working together across different states on how to problem solve for patients devices like this or local options like this, and I think that’s something that’s taken a huge step in offering patients more options. So now Hai is when I first started talking to him. It was not yet available in Kentucky. Now, he does offer hai pumps in Kentucky, and he also has that network of other doctors to share with and to problem solve with all of that to say, what do you see? Do you see any prep like, are there any goals concerning the future with hai pumps? Or what do you see as the next big thing with hai or with just local treatment? Liver treatments are there? I’ve seen so much, sometimes I think patients get discouraged because they feel like there are not many options. But I just want to say that since I’ve been stage four for the last four years, I’ve seen progress in this HAI pump as an example of that. So do you see anything coming down the pipeline that you can share about?

Dr. Soares 34:04
It’s’s a great, great question, great points you make. You know, it’s funny, yeah, the consortium has come together recently. It’s, it’s, it’s a lot of people, as you know, Sloan Kettering trains a lot of fellows that go on to do liver surgery and and a lot of this has come from the enthusiasm of people who have graduated from here to start the programs at their own institution. It’s always been there, but in the past, has been difficult to get these programs up and running. But there is certainly a renewed interest, not just from Sloan graduates. At this point, it seems to be more widespread, and that’s what’s facilitated the ability to open these pump programs at these different institutions, and I think this approach with the consortium is key, and is actually what’s going to lead to better implementation of this, this liver directed approach across the country and the world. One of the drawbacks that’s been stated about the data when it comes to pumps is, well, it’s all been done to Sloan Kettering, kind of the. Done anywhere else, and it’s only through consortiums like these that we can really work together to provide the scientific data that that really points to what we’ve seen already in a number of the trials I pointed out here, that there appears to be an improvement of outcomes with pumps and the development of this consortium through the work of Dr Lidsky and Dr. Angelica, with a number of people have already worked together in the past, a number of other projects is really going to lead to us better understanding when and where to use the pump and how we can use the pump safely, but also as we implement it at other centers that that point about being able to go back and forth, about troubleshooting is important right there. There are risks to everything in medicine and pump is no different than that, and understanding how to deal with those really takes collaboration. And this consortium is aimed at not only doing the studies, but collaborating effectively so that these pump programs can be open safely at many different institutions,

Participant Question 36:00
I will say, as a follow up to that I had a lot of concerns in 2019 because I was like, you know, I’m hearing these issues and these issues and these issues. And when I brought those questions to my doctor, he was able to clearly say, you know, yes, we were aware of these kinds of issues that are happening bile duct or with and working with oncologists on dosing, you know, has helped to remedy that situation. And so I guess I want to say that also, you talked about second opinions and things like that. Don’t be afraid. I’m kind of talking to the people, and just like getting your opinion at the same time, don’t be afraid to ask educated questions to your team. Some people are scared to ask, you know, I’ve heard this and this and this, but they don’t want to ask, you know, what are the dangers of a procedure? Or can you explain how they would problem solve with this? But that’s not necessarily that can help give feedback to the surgeon on what the patient is expecting, and those kinds of things. So I just want to, I just want to say that I do appreciate the work that you’ve done. It’s not a light task to to not only champion help change, you know, champions, HAI pump, but also to like continue the research and continue making the data more available, and to continue training surgeons across the states that can use them and to problem solve it together. And I’m just really thankful for the work that you’re doing, and I appreciate that. But also, as you mentioned, you’re very patient friendly, so like, you’re not going to be freaked out if I’m like, this type I call, you know, you’re not going to be freaked out from like, but what if this happens and this happens and this happens, that’s something that you’re saying. You know, according to what I’m reading into what you’re saying with your profile and getting second opinions, that that’s not a bad thing to ask about what your concerns are specifically.

Dr. Soares 38:19
Yeah, I completely agree. You know, when you talk about any treatment, whether it’s pump or systemic therapy or surgery, the conversation has to revolve around a few critical things. One is, what’s our likelihood that we’re going to help and two, what’s the likelihood that we’re going to hurt you? Right? Because everything in medicine has risk, and so every consult should address that for every proposed, in my opinion, every proposed intervention, whether it’s medicine, surgery, whatever it might be. So if you don’t come out of there, if you don’t have that information, it’s your right, and you should ask for that information. And there are data behind these numbers, these these values, right? We can give you what the percentage is. These things happen, what the percentages of benefit, what the likelihood of the complications are, in specific complications. And again, taking it a step further, as you mentioned, how to manage those, right? So I really do want to stress what you just said, too is, if you don’t get that from you know your conversation initially with the physician, that’s a perfect question to ask, because you shouldn’t walk out of any any console without having a good sense of what’s the chance that this is going to make them better and what’s the chance that can

Betsy Post 39:33
A couple of questions also. So I know people there might have questions, but I have a couple, one of them being one of the things we hear a lot in patient advocacy is actually, I just heard this today. They really get to know or trust or care about a care team, right? Like I love my oncologist or I really trust my team, but I want a second opinion, and they feel like they’re cheating on their care. Team or their that their oncologist or their surgeon will be offended or upset. So I just want to know from your mindset, because you know, one Kettering is one of the best institutions out there, yet you’re saying, Go get a second opinion. Just wondering how you feel about that as a surgeon. And you know the communication that you feel would be valuable from a patient or caregiver when they have that conversation, that we think you’re great, but we really want just peace of mind or to know what else is out there to get that second opinion. I’d love to hear your thoughts on that.

Dr. Soares 40:33
Yeah, it’s a great question. Betsy, you know, I get, I get this question all the time. Some patients will actually say just that to me. They’ll say, Look, you know, I love being here. I love your team. I love working with you, and this is where I want to work. But would you be offended if I get a second opinion or and some don’t mention it, and I can, you know, my my, my work. The way I work with them is I always mention it to them. I say, look, there are many ways to treat this disease. I there. The bottom line is, there is no drawback to a second opinion. And any physician who takes offense to that would surprise me, because, you know, no one’s perfect. There are the treatments, and what works for one patient doesn’t work for another patient. And most critically, finding where you’re most comfortable getting your treatment is going to going to be what leads to your best chances of success, and you can’t really get more opinion. So as a patient, I would hope that that concern about, you know, hurting the physicians feelings, would not be there, although, understandably, I get it, why I would be there. But as physicians, we understand this, and it’s just like with anything right? No matter what you’re doing, buying a house, buying a car, less important decisions in your life. You’re usually getting multiple opinions or getting multiple looks at things. This is no different, certainly actually more important. So no physician should be hurt by that. In fact, they should facilitate these opinions, and that’s what I do. If patients say I’d like a second opinion, but they don’t know where to go, what to do. We all have colleagues we work with that can facilitate these second opinions, and should and will do that, because only by doing that can patients and their families really feel confident in understanding of what what approach is right for them.

Betsy Post 42:17
Also, I guess I have one other question, and I definitely hope others have questions. But I have a question about the IRE I’m not as familiar with that, so I’d just love to hear a little bit more about why you would choose that particular modality of treatment. We are starting to hear a lot more about SBRT versus ablation for, you know, limited number of mets, or, you know, things like that. But I’d be really interested just to hear a little bit more about that modality and why you why you choose that?

Dr. Soares 42:47
Yeah, it’s, it’s, so it’s another good question. So in some ways, is like ablation. It’s something we can do in the operating room. It can also be done through interventional radiology. The reason to choose IRE over things like ablation or resection have a lot to do with location and size of the tumor. So if the tumor is just located in a very tough spot, meaning it’s in a spot where removing it would require removing a very large area of liver. Now the tumor is small, but because of where it’s located, you can’t just take that one spot out. You have to take a very large piece of liver that otherwise has no evidence of disease, and that, as I mentioned earlier, increases your complication risks. It can also make it harder for salvage therapies down the road. And so there are opportunities to use IRE instead of ablation or surgery, just given the nature of the technology, where you can actually use probes, put them around the tumor, use the electricity in that spot and treat the tumor effectively, but leaving everything else nearby intact and lowering and having a very low risk of injuring the bile ducts, injuring the major veins and arteries In that area that would not be possible with ablation. And thus you can use ire and prevent a major liver resection. So it’s case specific, and it’s really aimed at doing whatever we can to treat all visible disease, preserve as much liver as possible. And I re is just one tool. Radiation is another. We are using that more and more as well, and it takes some creativity. And this is why, again, second opinions are key, because having all these things at your disposal can help one approach versus another. And so making sure that you you understand what’s what’s available, and try to account for all these different modalities to get your tumors treated entirely is key. So that’s why I re has been utilized more for us moving forward.

Betsy Post 44:45
And just one quick follow on to that. What is there a size limitation for a tumor?

Dr. Soares 44:50
For IRE there’s no clear size limitation. What we know is that, and this is the same for ablation as the tumors get bigger than their recurrence rates after ablation for IRE get significantly higher. So for small tumors, one centimeter tumors, you can treat those rather effectively with chemo, with either ablation ire or resection, and the recurrence rates are likely not that different, but as you get bigger and certainly over three centimeters, probably over two centimeters in size using things like ablation and I re tend to then be associated with a very high risk of local recurrence and are not as effective. And so there you up for reception, if possible, or potentially other things like radiation, if there’s a strategy to use that to get everything treated.

Participant Question 45:38
Can I also ask related to that is so IRE is nano knife, right at the same time, it’s the machine that does IRE? Is that, right?

Dr. Soares 45:52
Yeah, it’s the machine very similar to ablation in the way that you you know it’s, it’s a probe that’s hooked up to a machine that the surgeon or the image radiologist who’s using it in search the probes in the appropriate locations, and then the the treatment is is given through those probes from the machine.

Participant Question 46:10
I just wanted to make sure I was talking about the right thing. So then does radiation. So for those of us who have checked a lot of the boxes in the local treatment to our livers, um, bingo card, does prior radiation does prior radiation keep you from getting using IRE?

Dr. Soares 46:45
Not necessarily. And so that’s that’s a very complex question, because it very much has to do with what else has been done, what’s been going on, where the radiation was, a number of other factors that you know are very patient specific. But to say, just because you got one treatment modality or automatically disqualified from another, that’s not the case. It’s very patient specific, very specific to what, where the disease patterns are, and and other patient related factors that would be assessed by the specific treating physician.

Participant Question 47:20
Yeah, the I’m always trying to figure out I’m learning that radiation seems to automatically kick you off of certain things, be it clinical trials or different, you know, treatment options. So I was wondering if I already it sounds like there are more criteria to that than just if you’ve had radiation, you can’t have something like it.

Dr. Soares 47:49
There certainly are. You know, your point about clinical trials, it’s getting at it gets at a different component. Clinical trials are very regimented, and who can be in and who can be out, they will specify the treatments that can be done prior to your ability to enroll into the trial and the inclusion exclusion criteria. But it doesn’t always mean it’s from a technical reason. Sometimes scientific reasons are behind it, safety, a lot of times behind all this. But when you’re talking about just your general approach to the disease, all these different things we use, resection, radiation, chemo, I re not one completely excludes the other, which is why, you know, it’s always important to get a thorough assessment of what what’s been done and where we stand, because there may be other options that are there, and blanket statements like that don’t usually apply. Thank you.

Participant Question 48:41
That’s very helpful. I have a question about the ire, have they been used for lymph nodes? Yet? My husband has two lymph nodes that are in a spot that it’s a recurrence that are in a spot that they say doing surgery because of how close the lymph nodes are to veins and the arteries, it could potentially cut off blood supply to the legs. So if he’s done another – he did second line treatment. Now he’s doing radiation and zilda, could I already get to the point that it might help or?

Dr. Soares 49:34
Not to my knowledge. You know, it’s using the liver. It’s also been used in the pancreas, for pancreas cancer, but beyond that, not not in a situation like the one you’re describing, or lymph nodes that I’m aware of.

Betsy Post 49:49
I did want to call out we have one Sloan Kettering patient with a hepatic clump there today. I know we do. You see him waving, and he is currently no evidence of disease, so I just wanted to give a shout out to him.

Betsy Post 50:48
Well, I don’t hear any other questions, and I just want to thank you so much for your time today. I loved your presentation, and I know this is going to be invaluable for so many of our patients and caregivers. So this will be made available in COLONTOWN and also in COLONTOWN University as part of our Lecture Hall. And I already have probably at least 100 people telling me they want to watch it. So I really appreciate your time and dedication today.