Management of Colorectal Liver Metastases: What the Patient MUST Know: Dr. Ocuin (2025)

This is an automatically generated transcript

Betsy Post [00:00:00]: All right, 7:01, we will go ahead and get started. Welcome, everyone. Thank you so much for joining us live. And for those of you that are going to watch the recording, hello. We are excited to have you here to tonight’s Doc Talk, where we are going to get to hear a lot of great information on the management of colorectal liver metastases and what the patient must know.

So we have an amazing liver surgeon with a lot of great experience here. I know we probably have at least one of his patients here, just based on who I’m seeing in the room. so I’m gonna turn it over to him. He’s going to share his slides and do a presentation for us, give us all this information.

The way that it works is if you have questions, there is a Q&A, so I would ask that you put the questions in the Q&A, and we will get to the questions when we have time for Q&A at the end of tonight’s presentation. So thank you so much for being here. I’m gonna turn it over to you, and thank you so much for spending part of your evening with us

Dr. Lee Ocuin [00:01:02]: All right.

Yeah, it’s a privilege– It’s really a privilege, to be invited to do this. So, for those of you who don’t know me, I’m Lee Ocuin. I’m a hepatobiliary surgeon. I work for, Jefferson and Lehigh Valley Topper Cancer Institute in Allentown. I’m gonna go ahead, you guys can see that okay?

What we’ll go over tonight is the management of colorectal liver metastases and from being a patient, facing what I think patients should know to help them be their own best advocates. So I don’t have any relevant disclosures. Just a little about the Lehigh Valley.

So this is our hospital. This is Lehigh Valley Cedar Crest. It’s right off I-78 in Allentown. It’s your standard quaternary care center, 1,000-bed hospital with all of the resources. It’s about an hour north of Philadelphia, give or take, depending on traffic. We have a very large primary catchment area, extending all the way north of Scranton, and all the way east towards the New Jersey border, and then west into some the Central PA area, and then south into the sort of the northern Philly suburbs, where there’s some overlap with our main campus in our center city, as well as Penn Fox Chase and Main Line Health.

So, What we’ll go over today is describe the scope of the problem regarding colorectal liver metastases and the importance of multidisciplinary evaluation and second opinions, and why they matter. And then, we’ll go into how patients with colorectal liver metastases are clinically staged.

And I often share this information with patients when I see them in the clinic and then we’ll go over some of the liver-directed therapies for colorectal liver metastases. We’ll describe the evidence supporting metastasectomy or removal of metastases as the gold standard for treatment in appropriate patients.

And then we’ll spend some time talking about HAI as well, the evidence supporting the use of HAI, as well as what we don’t know and talk a little bit about the PUMP trial which we’re excited to open.

In terms of general overview and clinical staging of patients with colorectal liver metastases, colorectal cancer is the third most common cancer. There’s approximately one hundred and fifty thousand cases per year in the United States. It’s the third most common cause of death in both men and women. And for all comers, the five-year overall survival is about six out of ten. It’s much higher in patients with localized disease, up to ninety percent at five years.

It’s much lower in patients with metastatic disease, with fifteen to twenty percent. in terms of colorectal cancer metastases, the liver is the most common and often the only site of distant spread. One out of every four patients with a newly diagnosed colorectal cancer will have metastatic disease at the time of diagnosis, again, most commonly in the liver.

And then over the course of treatment, the several months initially and then years of follow-up, fifty to sixty percent or basically half patients with the diagnosis of colorectal cancer will eventually develop liver metastases at some point during their treatment course. So this is a very common problem, colorectal liver metastases are the most common cause of death from colorectal cancer.

Metastasectomy or removing all tumors when possible is the best opportunity for long-term survival, and sometimes cure in appropriately selected patients. And I’m gonna say this over and over again tonight, but multidisciplinary care is imperative. Patients with colorectal liver metastases, this is a big problem and I see this every day.

But, patients with colorectal cancer liver metastases are consistently under-referred to surgeons and then by extension surgically undertreated. So what is multidisciplinary care? So the definition is a collaborative approach to healthcare where professionals from different disciplines work together to provide comprehensive and coordinated care for patients.

So as far as a patient with colorectal liver metastases, All of the following should either be directly involved in your care or immediately available. So you need a liver surgeon, you need a medical oncologist, a colorectal surgeon, and then in certain cases, there should be a transplant surgeon available, or involved along with transplant hepatology, gastroenterology, for some patients, interventional radiology or radiation oncologist.

And then if you’re being seen at a comprehensive cancer center, you should have access to nurse navigators, social workers, and nutritionists. Under-referral of patients with colorectal liver metastases is a pervasive issue. Over a 10-year period from 1991 to 2001, only 6% of patients with colorectal cancer liver metastases underwent surgery or metastasectomy.

Dr. Dr. Lee Ocuin [00:07:09]: And, more recently, that rate is up to 15%. That’s still way too low. And why is that?W e see a high frequency of anatomical and biological resectability assessment being done by non-experts. So what does that mean? Here are some examples. So this is a study out of Boston, out of St.Elizabeth’s Medical Center a couple of years ago. I think it illustrates the point quite nicely. In this study, there were 72 patients with colorectal cancer liver metastases who were treated with palliative chemotherapy based on consensus from a multidisciplinary tumor board that lacked a liver surgeon. So two liver surgeons went back retrospectively and looked at all of the imaging, and what they found was about half of the patients who were told they were unresectable and received palliative chemotherapy, never saw a surgeon, never had a surgical intervention, half those patients were actually resectable or potentially resectable.

And that speaks to the issue. Another good example, this was a survey-based study done in Michigan, where community medical oncologists were surveyed on factors that were how they felt about certain characteristics that were either sometimes, always, contraindications to metastasectomy.

So the list included age, comorbidities, performance status, liver function, prior liver surgery, things regarding liver metastases, were they synchronous, meaning were they at the time of diagnosis or they developed later? How many metastases? How big were the metastases? Where were the metastases, in one lobe or both lobes of the liver?

Were there extrahepatic or outside of the liver metastases to the lung or the adrenal glands? How high was their tumor marker, the CEA level? How long was the disease-free interval from, time of index diagnosis to the time of the metastases? So on the survey, the majority felt at least sometimes or often age was a contraindication to liver resection.

Comorbidities, I guess whatever that means, were vast majority of those surveyed felt that these were sometimes, often or always a contraindication. Prior liver surgery, you have eighty percent plus thinking that that’s at least sometimes a contraindication.

More than four tumors, vast majority, we’re looking at ninety percent thinking that more than four, at least sometimes, often or always contraindication. Similar, larger metastases, bilobar metastases, and then the presence of extrahepatic metastases. I’ve given a couple of talks on this topic lately. I sometimes do audience surveys. So this was like a mixed audience, medical oncologists and surgeons. And I put this poll up and you can see the majority, think that bilobar more than four tumors or larger tumors, the majority of people think that that’s a contraindication.

And the truth is, none of these are actually contraindications to any liver-directed therapy for colorectal liver metastases. So how do we stage patients, with colorectal liver metastases or really any cancer that’s and my approach and many of my colleagues approach this similarly, we look at conditional factors, so that means, we look at the patient first.

So, is the patient healthy, patient not healthy? Do they have medical problems or other factors that will limit the tolerability of treatment, whatever that treatment might be, surgery, chemotherapy, ablation, et cetera. And then, the next thing we look at typically are biological characteristics of the underlying cancer that predict that treatment will or will not confer an oncologic benefit.

An example, if a patient is actively progressing on chemotherapy, is that a good time to take the patient to surgery? Probably not. Anatomical considerations are the last thing we look at. They’re important, but the question that anatomical resectability asks is, is complete clearance of the localized or metastatic disease burden technically feasible?

Can we technically accomplish removing the tumor or tumors? It’s an important distinction because removability is the technical feat. Resectability is the, the technical ability to remove tumors, but factoring in the conditional and biological constraints of the surgery.

So are we doing the right operation for the right reasons in the right patient? So, conditional resectability, this is a little bit of a busy table, but I, I think it’s relatively self-explanatory. So patients who are conditionally resectable are generally younger, fitter, they have good performance status.

They don’t have a lot of other illnesses, or if they do, they’re very well controlled. They’re not coming in with a ton of weight loss. They don’t have a lot of cancer symptoms, cachexia, rapid weight loss, pain, things like that. Patients who are conditionally borderline, are typically a little older.

They have worse performance status. They’re coming in, they look deconditioned. They’ll have multiple comorbidities, or poorly controlled comorbidities, but these are potentially optimizable. They have bad diabetes, but they haven’t really been taking their insulin or oral agents, or they have poorly controlled hypertension, et cetera.

They might come in with more weight loss, um, or they have some new, this sort of general category of cancer symptoms. And then patients who are conditionally unresectable, typically, they just don’t pass the so-called eye test. This is the patient that might live in a nursing home, have a very poor quality of life, very dependent on most of the day-to-day needs in their care, and they’re just not gonna do well with aggressive intervention.

And these are the patients that it’s important if you’re being, and seeing that it’s recognized, there still should be a multidisciplinary assessment. But in patients who are, where the treatment is gonna be worse than the disease, these are patients where goals of care discussion should take place, involvement of palliative care early, so that the focus can be more on symptom management rather than aggressive cancer management, which they’re not gonna tolerate well.

Biological resectability, I’ll try not to get too into the weeds, but this is, I put this paper up. This is the most cited surgical paper, in the literature, but this was out of Memorial Sloan Kettering, from, I’ll just point out the date, 1999. So this predates systemic chemotherapy for colorectal liver metastases. They looked at 1,000 consecutive patients that underwent liver resection.

And they looked at factors about the patients or the tumors that predicted recurrence or the tumor coming back. And five things were identified, so more than one tumor, a high tumor marker, larger size, positive nodes in the primary tumor, so in the colons, or a shorter disease-free interval of under under a year.

And they devised something called the clinical risk score, which is a zero to five scale based on the presence of one or more of these factors. And what they found is patients with lower clinical risk scores, lived a long time. So even up to a clinical risk score of two, almost half of these patients are alive at five years.

And then in patients with higher clinical risk scores, the survival was lower, but still outperforms systemic chemotherapy, maybe in the modern era, with the exception of patients with clinical risk scores of five. But that all being said, even in higher risk scenarios, and even if we’re not curing patients, if a patient is able to undergo metastasectomy, complete clearance of all of their liver disease, there is the possibility of long-term survival, even in the absence of cure in some of these biologically higher risk patients.

So again, it’s just it’s important that patients are being evaluated. And then anatomical resectability, and this is sort of, this is a debate. So nobody actually knows the definition of anatomical non-resectability. So, one of the residents, at Jefferson were putting together a systematic review.

So we looked at 50 prospective trials, randomized controlled trials. This is a very busy table. But we looked at the definitions in the trials that included patients with, quote, “unresectable,” colorectal liver metastases. And the majority of trials had no definition. It was just consensus opinion, consensus review.

In the trials and studies that had definitions, we categorized them basically, into categories of relationship of tumor to intra liver vasculature, the number of tumors, how much liver would be remaining after liver resection, the ability to clear the entire liver at one operation, or, how many sides of the liver were involved.

And even within studies that had those categories outlined, the definitions were very different. Okay, so basically, maybe two or three had similar overlapping definitions and, and they were all out of the same institution. So nobody really knows the definition of anatomical non-resectability. The ECOG 2222, the PUMP trial has I think probably the most practical definition of non-resectability, which would entail a margin negative resection, requiring resection of all three hepatic veins or veins that are draining the liver. That’s not possible. Or both portal veins also not possible. That’s the veins taking blood to the liver or the vena cava, the large vein that sits behind the liver. Or leave, less than two liver segments adequately, with blood supply and biliary drainage and venous drainage. So all of these things basically are not conducive to survival, if a patient were to undergo an operation that did this.

So that’s the definition, of non-resectability that I carry around with me when I assess patients. So a lot of things can affect resectability from an anatomical standpoint and we’ve talked about this. Size, number, location, distribution, overall disease burden. Depending what study you read, only about one out of five patients has anatomically resectable, liver-based disease.

But that’s based on the definition used in any given study. So we don’t actually know what this number is, because this definition has been so variable. Again, this isn’t… this is more illustrative than anything else, but, when a liver surgeon looks at a CT scan, we recognize patterns.

And there’s increasing complexity of operations we can do. But the key is, you need to have an eye for it. So, some patients have these two, a couple of peripheral tumors, that are easily, or straightforwardly removed, either with a partial hepatectomy, partial removal of the liver, or ablations.

Sometimes they’re more centrally located, but they’re small, and these are targetable with ablation or maybe there’s multiple superficial tumors. Maybe multiple superficial tumors, but one is taking up a portion of the liver where if you try to just ablate all three of these things, you’re not leaving much function.

So now you remove a portion of the liver, but ablate the other side et cetera. And you can get all the way up into the highly replaced liver parenchyma, the central location, et cetera. But you have to have someone reviewing these images, that has an eye for it and can see a pathway to clearance or not.

Again, it’s imperative. And then, in patients that may not have upfront anatomical resectability, there’s at least the way I think about, is it a tumor burden issue, or is it a liver volume issue, and how can we optimize one or the other? So if it’s a tumor burden issue, meaning there’s either too many tumors or they’re too big, we can start with chemotherapy, to try to shrink the tumors.

We can offer with chemotherapy, regional therapy, so HAI pump, TACE or, radioembolization. Is it a liver volume issue? Is there not enough viable normal liver tissue remaining if we were to try to remove all of the tumor at once? So can we modulate or get the other side of the liver, the remnant, to get bigger ahead of time to minimize the risk of liver failure after an aggressive resection?

And that can be modulated with portal vein embolization. Something that’s being used more frequently now is combined portal vein embolization and hepatic vein embolization. So we clot off, the right-sided portal vein and the right-sided hepatic vein, and that stimulates a lot of growth. There’s something called associated liver partition and portal vein ligation or ALPS.

That’s actually an operation where we partially divide the liver, and take the inflow, and that causes the other side to grow rapidly. And we can do something called a radiation lobectomy, where It’s basically high-dose tear to one side of the liver, stimulating the other side of the liver to grow.

But these are modifiable things, again, needing assessment by a multidisciplinary team of experts. So again, my little soapbox is it’s critical that patients with colorectal liver metastases see a hepatobiliary surgeon early in the disease course. Because the earlier we see patients, the more we can help guide treatment decisions, and avoid pitfalls, things that might burn bridges to some modalities of care.

And also avoid over-treating patients with chemotherapy before they get to a liver operation because chemotherapy at cumulative, over time becomes toxic to the liver. And when you try to perform liver resection after a lot of upfront chemotherapy, there’s just higher risk of liver-related complications after surgery.

So, there’s a very fine line and you don’t wanna over-treat a patient with a resectable disease burden, because you’re not gonna make it more resectable with more chemotherapy. But these again are all nuanced points, but they can’t get discussed if the experts are not involved.

Resectability is in the eye of the beholder, okay? So, this was a study that basically, presented several cases to a variety of subspecialists. But all of the patients had undergone metastectomy with or without ablation. So all of these patients had resectable disease. So, when these cases that were… Again, we already know the outcome, all the patients underwent resection. When these cases were presented to medical oncologists, only half of those medical oncologists thought the tumor burden was resectable. Colorectal surgeons, only about half the colorectal surgeons thought tumor burden was clearable.

A little bit better with the general surgeons, a little bit better with surgical oncologists, but when a hepatobiliary surgeon saw, 90% were able… so there’s 90%, agreement in the subspecialty that it should actually be delivering this care. So, it really does matter, if you have an eye for it or not.

And then the perceptibility of resectability affects treatment choices, and this goes back to that Michigan survey I showed you. And again, if these decisions are being rendered in the absence of expertise, patients never even make it to evaluation. So, this was a study, that where 190 medical oncologists were provided imaging, for 10 patients,and they were to determine resectability.

Three liver surgeons participated. Of the 10 cases, eight patients had resectable disease. The medical oncologists only thought one-third of those patients were resectable. Again, we keep seeing the same things, but, things that were associated with perception of unresectability were the number of tumors, size of tumors, and bilateral disease.

Again, we know that none of those things are true. And when they looked at the referrals basically to surgery, if a patient was deemed unresectable, there’s a less than 5% chance that a medical oncologist ever sending that patient to a surgeon for evaluation. And obviously, if a patient was deemed resectable, there was almost a 90% chance the patient was getting referred to a surgeon.

And this is with initially resectable disease, and then it’s a little bit more in the middle with patients who thought maybe with some downstaging, the patient might become resectable. But again, who’s making that assessment? So, I beat this drum at every tumor board, every outreach meeting that I go to.

It’s really just being able to get these know get patients evaluated. It doesn’t have to be a formal in-the-office evaluation. It’s just looking at the scan. They should be presented at tumor boards or a curb side, but the scan should be getting reviewed. But patients have to be their own best advocates.

So essentially, I understand a lot of the chemotherapeutics. It’s certainly the first, second, third line that are offered, but I’m not an expert in that, right? That’s the medical oncologist’s lane. And so, vice versa, medical oncologists should not independently be determining resectability, just like I shouldn’t independently dictate chemotherapy.

We should be working together to decide on a somewhat, in a consensus fashion what the best plan is. And if I don’t know something or any doctor doesn’t know something, you just have to say, “I don’t know. That’s a question for this other specialist” instead of either making something up, ’cause when patients start to get mixed messaging, that creates distrust in the team.

And it’s just a disservice to the patient. So it’s imperative that patients have a multi- disciplinary team that works together, and it’s also imperative to understand the patient is part of that team, right? So we discuss what we would recommend for Mr. Smith. This is the best, this is what we think would make the most sense.

We would potentially give them a pathway to the best possible outcome, whatever that outcome is. But the patient and the family have to be on board with that. If they’re not on board with that, then, you have to come up with something, an alternative that’s agreeable but still safe and still follows oncologic principles.

It’s essential that you trust your physician, your surgeon, your team, and if you don’t, find another one. And any physician you see should always be prioritizing each individual patient’s needs and best interests, and the needs of the patient always come first. That’s a non-negotiable in my book.

And it’s not… Unfortunately, it’s not always the case, but you should always feel like that the patient’s needs are being prioritized. And again, in terms of being your best advocate, okay? So academic centers or high-volume centers typically have the best outcomes, although there are high-performing lower volume institutions, just as there are poorly performing higher volume institutions, okay?

But in general, volume and outcomes correlate, so if an institution does more surgery, if a surgeon does more surgery, typically, they’re gonna have better outcomes. They’re just more experienced. So when you’re seeing a surgeon, colorectal surgeon or a liver surgeon, should ask questions, right?

Don’t just take them at their word. So how many patients do you see with colorectal cancer? How many liver resections do you do a year? If you’re doing less than 20 a year, that’s not a lot of liver surgery. How many liver resections does your hospital do a year?

Depending on how many surgeons there are doing liver surgery, that’s a fair or unfair question. Some hospitals do a high volume of liver surgery only done by one surgeon. How long has somebody been doing liver surgery? You can’t make the surgeon older than they are, but you hope that they have at least some experience under their belt.

And then, I think this is– what are that surgeon’s outcomes, right? I mean, how do your patients do? And the surgeon should know this relatively off the top of their head. You should know your mortality rate, at 30 and 90 days, bile leak rate, liver failure rate.

You should know these things. You shouldn’t say, “Oh, yeah, they’re fine.” I mean, that’s not an acceptable answer. And you should have a pretty good idea of what your own outcomes are. And then are patients being discussed at multidisciplinary conferences and tumor boards, or are these decisions just being made in a vacuum or between a single surgeon and a single medical oncologist?

Because we know that multidisciplinary conferences, improve recommendations and care to patients. So to sort of summarize that first part of the talk, okay, we know that under-referral of patients to surgeons persist, despite advancements in surgical technique and safety of liver surgery. Cinical staging for patients starts with conditional, followed by biological, and then lastly anatomical or technical considerations.

biology does matter, okay? But even in higher risk scenarios, metastatectomy, still affords patients the best possible chance for long-term survival. Anatomical resectability cannot be assessed in the absence of a hepatobiliary surgeon, and has a very historically variable definition.

Anatomical resectability is in the eye of the beholder. It’s modifiable and again, multidisciplinary evaluation is essential So, we talked a little bit about surgical management of colorectal liver metastases. It really should just be liver-directed therapy for colorectal metastases because surgery implies cutting something out and that’s not all we do.

So what is liver-directed therapy? So it’s a local cancer treatment that targets tumors within the liver, sparing healthy tissue and other parts of the body and minimizing systemic side effects compared to traditional, oral or intravenous chemotherapy. So, the metastatectomy, then there’s tumor destruction modalities.

So thermal ablation is commonly nowadays microwave ablation. Histotripsy gets a lot of press, and then stereotactic radiation. And, essentially these things all accomplish the same idea of destroying the tumor, with a margin of normal liver tissue, and should fully treat an individual tumor in a location the same way removing that tumor individually treats that tumor in that location.

And then there’s regional or intra-arterial therapy. So again, HAI pumps, TACE and TARE. U I’m not gonna spend much time talking about TACE or TARE today. And then transplant obviously, becoming more important. Every patient with colorectal liver metastases should be evaluated for liver-directed therapy.

So that doesn’t mean every patient with colorectal metastases should get liver-directed therapy, but it should be on the list of things you go down, like a checklist, right? Like, are they eligible for this? Should this be a consideration? Should this not be a consideration, and why? So liver surgery, it’s a still a very young field. So 1989, this editorial came out. Bill Seiling is the chair of surgery at Beth Israel for a long time. One of the giants in the surgical field wrote an editorial, and some of his conclusions were the morbidity and mortality of liver resection come close to offsetting any advantage that might be gained by resection.

And that current evidence does not support hepatic resection for colorectal liver metastases. Although, a conscientious surgeon might be coerced into resection for a patient, in excellent condition whose lesions are resectable. And then a year later, this paper came out in the British Journal of Surgery, so 1990.

Again, this is all predating the era of modern systemic therapy or any real systemic therapy for this disease. But, this paper looked at 902 patients with unresectable tumors, 62 patients that underwent surgery but had their tumor, tumors were left behind, and then 226 patients who underwent surgery and had tumors removed either with a negative margin or a positive margin.

And what they showed, again, this is all before any chemotherapy existed in patients who underwent curative intent resection, the average survival approached three years. So this is just surgery alone, okay? Average survival of three years. Patients who underwent exploration, but no surgery, had an average survival of about a year and a half.

And then patients who were unresectable, never underwent surgery had average survival of under a year, okay? And then when they looked at the patients who underwent resection, patients who underwent resection with negative margins, again, had average survival extending beyond three years. Patients who had positive margins had much worse outcomes.

And then in patients who underwent negative margin resection, whether they had multiple tumors on both sides of the liver, solitary tumor, or multiple tumors on one side of the liver, they all did fairly well. So this threw a little bit of wrench in that historical dogma. This is that paper I cited earlier, out of the Memorial Group, 1,000 patients.

Again, in 1999, so most of these patients never got chemo. Patients live a long time if they can undergo, liver resection. So, an average of six years. Okay? Obviously more tumors are worse, but if you can get them all out, patients still do quite well. So patients with single tumor live out to, almost approaching four plus years.

Two to three tumors, a little bit worse. More than four tumors, a little bit worse. But all of these numbers, again, were in the absence of any real systemic therapy. And even in the modern era of systemic therapy, this average or median survival, is better than anything we see in patients who just get chemotherapy.

Most patients are not living this long only getting chemotherapy. They went back and looked at the actual 10-year survival. So who’s living 10 years with or without cure, okay? Over 30% of patients are alive at 10 years. And then when they looked at that clinical risk score, not surprisingly, patients with lower clinical risk scores did a lot better than the patients with higher clinical risk scores, but still living a long time.

Again, so same theme. Even in these biologically higher risk scenarios, if you can clear all of the liver disease burden, patients are going to do better and then, here’s some modern data. This was recently published. This is the CAIRO5 trial. So to not overwhelm, too much information, but this is a lot of patients.

So 500 patients with unresectable, again, using quotes here because I don’t think I agreed with the–most of us don’t agree with the definition that was used. This is patients that either had right-sided tumors or mutated tumors, were randomized to one of these two chemotherapy regimens.

Patients with left-sided tumors and/or non-mutated tumors were randomized to one of these two chemotherapy regimens. The average number of tumors was high, 12, okay? So that’s just the baseline, just to understand. And the patients who underwent, liver-directed therapy, had metastasectomy, average survival, at three years, 50% of the patients were alive.

Patients who never underwent liver surgery, only 10%, okay? Regardless of side. And then, same thing in patients with left-sided tumors. Left-sided tumors are generally biologically more favorable. So now we saw up to 70% of patients who underwent local treatment, for their liver metastases alive at three years, in both arms.

And then, when they looked at all, the entire study population, patients who underwent, liver-directed therapy, and did not have early recurrence, or if they had early recurrence, underwent some kind of salvage liver-directed therapy, those patients lived the longest, and patients who never underwent any liver-directed therapy did the worst.

So this is in the era of modern chemo. So again, so now we’re incorporating modern chemotherapy, still see same patterns of outcomes. Patients who are able to undergo complete liver tumor clearance, and again, the median number of tumors in these patients was 12. That’s a very high disease burden, doing quite well if they get to the operating room.

A question that always comes up in terms of removing metastasectomy versus ablation, to me, it’s not an either/or. It’s just a tool in the toolbox. So the tumors that make sense to ablate, we ablate. The tumors that make sense to remove, we remove. But this was recently published, the COLLISION trial.

300 patients with fewer than 10 tumors, small in general, less than three centimeters or about an inch in size, randomized to either resection or ablation, with a what we call a non-inferiority endpoint. Basically, if one arm or the other did not have a higher risk of death, by a factor of 1.3, then that was considered non-inferior.

Again, and this is actually more important, just to illustrate the point of liver-directed therapy. Either arm, they had very similar outcomes. You could see these survival curves overlap pretty much identically. Median overall survival was not reached. Okay. So again, if you can clear the liver, patients are going to do better.

Now, what about transplant? Okay. So this is becoming, this is a question we’re seeing more and more. So this is the TRANSNET trial, that came out about a year ago. So this was conducted in Europe. Ninety-four patients with unresectable, tumors that had had their primary, their tumor. They already had their colon tumors removed. They excluded–these are important things to point out. They excluded patients with BRAF mutations. So these are patients who are much higher risk, from a biological standpoint in patients with any extrahepatic disease, so any metastases outside of the liver.

These patients were excluded. All patients had to have at least three months of chemotherapy, but fewer than three lines of chemotherapy, and they had to have at least stable disease, or responsive disease, meaning tumors were shrinking for at least three months. There were tumor marker cutoffs, and, there was a lot of protocol deviations.

That’s important to point out. The primary endpoint was overall survival. So patients were randomized to either Transplant or chemotherapy alone, in patients who receive transplants had longer overall survival. Interestingly, many patients still progressed, at a median in the transplant arm of about 18 months.

So a year and a half, new disease popped up elsewhere. But still, this is a big step forward considering these were patients that had unresectable disease. Although the definition of unresectable in the study was not clearly stated, in the methods. It was a multidisciplinary assessment.

So to summarize that part of the talk, metastectomy or really liver-directed therapy with complete clearance offers the only opportunity for long-term survival and sometimes cure, in subsets of patients with resectable colorectal liver metastases. Complete clear-clearance is the goal, but it doesn’t really matter how you get there. These techniques are all complementary, and they’re not competitive. So, taking large pieces of the liver out or less smaller pieces of the liver out and sparing more normal liver, have similar outcomes. Ablation and resection have similar outcomes if tumors are small, and then transplant outperforms chemotherapy alone in very highly selected patients with unresectable disease burden.

So now we’ll talk a little bit about hepatic artery and infusion pump therapy.

So the rationale, the sort of the logic behind HAI pump therapy is the normal liver is perfused by both the portal vein and the hepatic artery. But liver tumors and metastatic tumors in the liver are perfused by the hepatic arteries. This is a very classic picture, so this is a catheter in the hepatic artery.

So this is the left hepatic artery, this is the right hepatic artery, and you can see this well circumscribed tumor lighting up, off of the injection of contrast into this. So, liver tumors live off of the hepatic artery, nearly exclusively. So what hepatic artery and infusion pump therapy achieves is basically physiologic and pharmacologic isolation of the liver.

So this is an implantable pump with a catheter that’s sutured into a branch of the hepatic artery called the gastroduodenal artery, and at a very low flow rate of about one to one and a half mls per day, drips chemotherapy that goes up into the liver and perfuses the entire liver with high-dose chemotherapy.

A lot of drugs have been explored for HAI. Floxuridine or FUDr is the drug most commonly used. It lasts a very short amount of time, so it’s in the liver, half-life of less than ten minutes. But it achieves very, very high concentrations within the liver, and importantly, it’s cleared nearly immediately in the liver. So patients who are receiving FUDr through the pump do not get any systemic side effects or minimal systemic side effects from the chemo in the pump

So, what are the indications for HAI pump therapy? Similar to any liver-directed therapy, any patient with colorectal liver metastases should be considered.

Doesn’t mean they should get a pump or not get a pump, but they should just be considered. We’ll focus mostly on patients with unresectable or resectable disease. Principles of HAI pump therapy, ’cause this comes up a lot. Mainly it’s, I think a little bit of a knowledge gap, but typically patients who are getting HAI get both pump and systemic therapy.

So while the pump chemotherapy doesn’t add in much in the way of systemic side effects, so cold sensitivity, GI upset, mouth sores, et cetera, most patients are still getting systemic therapy. We never combine avastin or bevacizumab with HAI. There’s a very high rate of bile duct strictures.

The pump chemotherapy is FUDR, fluorouridine and dexamethasone, which is a steroid. Cycles are two weeks in length, and, and the flow rate is listed here. This is what an HAI pump looks like in cross-section. There’s a propellant chamber on the bottom. It’s filled with Freon. So, at body temperature, that liquid expands to gas.

It compresses on the drug reservoir, which is basically like a syringe or a bellows, and that expels drug out into the catheter. This is not a risk-free procedure. We’ll discuss some of this again, but, typically, I divide complications of getting the pump implanted into three categories.

We have to make a pocket underneath the skin for the HAI pump, and this can fill with fluid. Sometimes patients can have bleeding around the pump. The wound itself can sometimes either get infected or we could see wound breakdown. It’s all very rare, but certainly not a zero event.

We could see pump or catheter-related complications. So the pump, this is a highly reliable but handmade device, so you can have human error at the time of priming the pump in the OR. There could be issues internally with some of the internal mechanics. And then the catheters can clot, they can migrate out of the catheter. They, excuse me, migrate out of the gastroduodenal artery. They can migrate too far in. It can cause arteries to clot. The catheter itself can clot. Again, uncommon, I would say, depending on one’s experience, over time. And then, liver-related issues.

So hepatotoxicity or liver toxicity, the liver getting sick, that’s not really specific to HAI pump therapy. All chemotherapy, all conventional chemotherapy is toxic to the liver at cumulative doses. No one really knows what any given patient’s maximum tolerated dose of chemotherapy is, but floxuridine is just like 5-FU.

It’s actually the pro-drug to 5-FU, and the the liver converts FUDR to 5-FU, but at high enough doses over time, over long enough exposures, the liver can get sick. Specific to HAI pump therapy is biliary sclerosis or scarring of the bile ducts. The tumors live off of the arterial blood supply, so do the bile ducts.

And so the bile ducts are seeing very high doses of chemotherapy, and in about 5% of patients, we can see scarring or strictures develop. And, so anyone on HAI is having their liver function tests monitored very closely. There are well-described protocols for dose modifications, dose holds.

You have to try to stay ahead of issues as they come up or before they come up, the logistics of a pump program, so if you’re being evaluated at a place that has a pump program, it’s imperative as the patient you understand that they actually have the logistics and the infrastructure to support a pump program and do it at a high level.

So this involves multidisciplinary conferences, preoperative workup and imaging. This involves multidisciplinary surgical subspecialties, as well as trained OR staff, and OR teams. We often have a device representative present. It takes a lot of support within an infusion center.

Patients with pumps, their appointments are longer, because there’s a bit of a procedural aspect to pump refills. But it takes collaboration between the medical oncologist, the pharmacy, the treatment room, infusion nurses, et cetera. And then we have ancillary support from our nuclear medicine colleagues, interventional radiology, hopefully not often, as well as the surgical team.

So we have a very big team at Lehigh, which is why our program, while relatively new, has been extremely successful in a very short period of time. There’s been a dramatic growth in the number of HAI centers around the country. So for a very long time, it was just really Memorial Sloan Kettering, and then in the nineties, University of Pittsburgh, came online.

But over the past, let’s say ten to 15 years, this has just been exponential growth. I just updated a slide from Mike Lidsky, but there’s like 100 centers now, as part of our HCRN. So Lehigh and Jefferson are in it along with a lot of other great institutions.

So, just to summarize that part, HAI pump therapy takes advantage of the dual blood supply of the liver to deliver high-dose chemotherapy with minimal systemic toxicity. Any patient with colorectal liver metastases, obviously, we’re not talking about cholangiocarcinoma tonight, should be considered for HAI pump therapy.

Pump therapy is usually pumped with systemic therapy. There’s an FDA-approved device for drug delivery. Expertise is essential, as is multidisciplinary clinical, and ancillary support. And the HCRN or Hepatic Artery Consortium Research Network was created for multi-institutional collaboration for research.

And what we’ll talk about in a second is trial development in the modern era. All right. So, what’s the data for HAI pump therapy for colorectal liver metastases? So,this is sort of a timeline of systemic therapies. And, some of you are or will be on some of these agents. But 5-FU was described, systemic 5-FU really came into being around the year 2000.

We have some of our targeted inhibitors, and immunotherapy in 2016. Everything else in the middle, but HAI’s been around for almost fifty years. Initially described in the seventies and first really described in patients in the nineteen eighties.

So this is a very old therapy, but historically done at one institution. The indications for patients in metastatic colorectal cancer are really any patient with unresectable disease, potentially resectable disease or resectable disease. Again, consideration versus who should actually get a pump.

And we’ll talk about unresectable and resectable disease briefly. So what’s the data? So in patients with unresectable colorectal liver metastases, there’s a trial, from the early 2000s, 2006. This was multicenter, although most of the patients were treated at Memorial.

It was a hundred and thirty-five patients with unresectable colorectal liver mets. But it’s important to note here, assigned to first-line, HAI without systemic therapy or systemic single agent 5FU with a primary endpoint of overall survival and a secondary endpoint of quality of life.

So it was a positive trial. Patients who received HAI lived longer, so on median of four months longer, and the two-year overall survival was fifty-one percent versus thirty-five percent. So it’s a positive study. And also there was a improvement in, again, these are patients with unresectable tumors, but the progression-free survival was longer in patients who received HAI.

And then I think this is relevant regardless, but patients who received pumps in the black lines actually had at least as good if not better quality of life than patients who received systemic. So this question comes up, and I typically answer it that over time patients, if they’re gonna get a pump, they get used to it, and their quality of life is very acceptable.

But there’s problems with this trial when we look at it through the lens of 2025. So over ninety percent of these patients were treated at Memorial. neither 5FU alone nor floxuridine alone are standard regimens in the modern era. We would almost never give these options to a healthy fit patient.

There are rare exceptions when we have a patient who might only tolerate a single agent, where we would consider that. But this is not the standard. And also these are patients who are chemo naive, so this was a first-line study of outdated regimens, right? So what does it really mean in the modern era?

The answer is we’re not sure. This is some retrospective data out of Pittsburgh, in the second-line setting. So this is patients who received modern chemotherapy or modern chemo plus HAI in the second-line setting. It was a case control study, so more modern study period. These patients had unresectable disease, with a high tumor burden, looking at overall survival.

So we see in this study that combination of HAI plus chemotherapy is associated with about a twofold improvement in the average survival, which is great, except this is retrospective data. We don’t know why patients were selected for pump versus not pump. So this is not a highly controlled environment, so there could be a lot of things influencing the outcomes we see here.

And then more recently, this was done out of, again, out of Memorial, a phase two single-arm study of 50 patients with unresectable colorectal liver metastases. Most were pretreated, so either on second or third-line chemotherapy with a high tumor burden, and 90% of patients had a high clinical risk score.

What they looked at was conversion to resection, as well as overall survival, progression-free survival, and response rates. So over half of the patients converted to resectability, and there were pretty high response rates. Overall, 73% patients who were not heavily pretreated had an eight and almost nine out of ten patients, who were chemo naive or not heavily pretreated had response.

Patients who were more heavily pretreated, still a good number of them, had evidence of tumor shrinkage on imaging. The overall survival again, for all comers was about 46 months, so approaching four years. Patients who were chemo naive, lived a long time, so average survival extending beyond six years.

Patients who were heavily pretreated did not live on average as long, more closely approaching three years. And then patients who down-staged resectability and underwent resection by one year had five-year overall survival of 63% and median survival was not reached. So these patients did really, really well. Patients that did not get resected by one year had a much worse overall survival.

So what are the advantages and disadvantages? So, advantages of HAI. So we’re giving high-dose chemotherapy directly to the liver and liver tumors. It has high response rates even in previously treated patients, high rates of conversion to resectability, high rates of disease control, higher overall survival.

But I put asterisks by these things because we actually lack modern perspective randomized data to make these claims definitively. So it’s all associations. Disadvantages of HAI requires an abdominal operation, either open or robotic-assisted to implant the pump. There’s a commitment to maintaining the pump.

The refills at HAI centers are every two weeks. We often see dose reductions in systemic therapy, and there are complications. This is not a risk-free operation. So we need a modern trial because the most recent randomized trial is fifteen years old and uses outdated regimens, and most of the data come from a single institution.

And there’s just continuous skepticism. And I can say as somebody who did not train at Memorial, I think that’s one of the reasons I’ve been successful in getting HAI programs going is because, once you get a step beyond, there’s just a lot of skepticism, because everything is so heavily weighted towards one institution.

So, being a voice outside of that institution, I think has been helpful in getting people to buy into the vision and to study it at other centers. But we now have enough centers, nation and worldwide to conduct prospective multicenter, randomized trials, with the practice-changing goal of determining if HAI plays a meaningful role in the approach to patients with unresectable colorectal liver metastases.

And so that’s the PUMP trial, that’s being led by Mike Lidzky, where patients with unresectable, liver-only metastatic colorectal cancer, who received at least three but no more than six months of first-line chemotherapy, are being randomized to either, HAI plus continuation of standard of care chemotherapy or continuation of standard chemotherapy alone with the primary endpoint of overall survival.

And these are some of the main inclusion and exclusion criterias. But, the important ones are, have to have had some induction therapy, but not too much, liver-only disease. And then exclusion criteria, can’t really have any extrahepatic or outside of the liver disease or bulky lymph node disease. Other liver-directed, prior liver-directed therapy, is exclusionary. We’re not looking at patients that have MSI high colorectal cancer.

Now what about, adjuvant therapy?

So there were two large studies, done about a decade apart, that looked at patients that with resectable tumors, who either got additional chemotherapy or no additional chemotherapy around the time of their liver resection. And both studies essentially showed the same thing. So the older study showed very similar overall survival whether patients got surgery only or chemo before and after surgery, but slightly better progression-free survival in patients who got chemotherapy.

But the message here is that patients got more chemotherapy but lived the same amount of time. This more recent study, JCOG0603, very similar outcomes. Again, patients who got hepatectomy alone or hepatectomy plus chemotherapy, similar survival, overall, slightly better what we call progression-free survival in patients who got additional chemotherapy.

So patients are getting more chemotherapy but living the same amount of time. So as a patient, I think I would rather get less chemotherapy if I’m gonna live the same amount of time. But the same thing may not necessarily be true for patients who get resection of their colorectal liver mets and this concept of adjuvant HAI pump therapy.

So this is a very old study at this point. 1999, hundred and fifty-six patients, who underwent liver resection and then they’re either randomized to single agent 5FU, or 5FU plus HAI, with the primary endpoint of progression-free survival and two-year overall survival, and this was a positive study.

So patients who got combined study lived longer, and had longer progression-free survival in the liver. And then more recently, there was a study that looked at a large multi-institutional series, and again, this is retrospective. So again, why were patients selected for one arm or the other?

But there may be an advantage. But again, the same sort of message is true, which is we need modern trials, and hopefully we’re starting to put together a modern adjuvant trial. Just to summarize the last part of the talk, HAI pump therapy and systemic therapy may be associated with improved survival response rates and converted resectability in subsets of patients with initially unresectable colorectal liver mets.

It may have higher disease control response rates, than a corresponding line of systemic alone. Then the role of adjuvant HAI therapy still remains to be defined in the era of modern multi-agent therapy, but it may be associated with improved overall survival. But the key is modern trials are needed, but they are finally being conducted.

Again, HAI is a very specialized therapy for patients with unresectable colorectal liver mets, and EA2222 is the definitive trial to answer, at least for this subset of patients, if there’s any benefit to the addition of HAI. So if so, so patients should, if they’re need to be seen at an HAI center that has some experience, to determine whether they’re appropriate for HAI on any level and eligible for the trial.

So obviously have some acknowledgements, my colleagues in the division of surgical oncology, can’t do this without my medical oncology colleagues, and nursing support staff, Cancer Institute leadership, and then all of our other institutional ancillary support. And then, Mike D’Angelica, Mike Kabner, Mike Llidzky, and Nancy Kemeny were sort of critical, in my education and growth and experience in this.

And then Boston Scientific, and Intera has been very supportive of our programmatic launch at Lehigh. So with that, I’ll take any questions.

Dr. Lee Ocuin [01:08:05]: I’m just looking. Can you guys hear me?

Betsy Post [01:08:08]: Oh my gosh, I was talking to you and I was muted. I’m so sorry. Oh, sorry yeah, yeah. I was reading your question and then you said, “Can you hear me?” Okay, so this is a question from a patient with the BRAF V600E mutation. So this patient is asking about the best time for surgery with someone with that mutation.

She was responding well to the BREAKWATER treatment. Tumors are now mostly cystic. Several surgeons have suggested HAI for her. But when would this be a good time for surgery? Would they wait for ongoing shrinkage, or perhaps when she stabilizes? They’re trying to find the most opportune time for surgery and minimize time off treatment.

Dr. Lee Ocuin [01:08:53]: Yeah, I mean, that’s a great question. I don’t know that anyone really knows how to answer that other than the data from the BREAKWATER trial has really, we’re gonna have to see how things develop in the coming years. But I would just say historically speaking, patients with BRAF mutations, very highly biologically aggressive variant, and very few patients with liver mets would ever make it to the operating room for resection or for pump.

It would be a very, very, almost anecdotal. I think that’s gonna change now. In terms of time off treatment, so one question would be, is the liver tumor burden at this point resectable or not? If it’s not resectable, typically time off of any treatment for an HAI pump implant is usually about three or so weeks prior to surgery.

And then systemic therapy is usually on hold for around four to six weeks post-operatively, but we try to get the first round of HAI going at about two weeks post-op. So there’s not a huge gap there. If the tumors are cystic, that’s usually a pretty good indicator that there’s been a very good treatment response.

They typically won’t shrink because those cysts are usually just they’re filled with mucin or mucus, and that’s never gonna go away in terms of size. The mucus just doesn’t go away. I would look at other things like tumor markers, ctDNA, but I don’t know that anyone really has a definitive answer. But if she’s had, depending how much therapy she’s had to this point, if there’s continued down staging, then I would probably push…

I would say keep using what’s working. But if it’s plateauing a little bit, then, that might be the opportunity, to build in a little bit of a break. And, if HAI is a serious consideration, you have to fit it in around there. But in any cancer really, a few weeks isn’t gonna change a lot in terms of progression or not progression.

It’s really is that the best, that an option we think might actually help? And if so, when do you do it? Again, knowing that if HAI is gonna be explored, it’s not risk… And again, it’s overall low risk, if it’s being done by somebody, with experience, but it’s not zero risk, right?

So if a patient gets a pump and then has surgical complications, that could put a huge, that could derail getting back on systemic therapy if that’s the goal. So, again, so that’s a very long-winded answer to say I don’t, no one really knows that answer.

But if that’s being a serious consideration, it just has to be planned out carefully. But a lot of it, I mean, I would start with is, is the tumor burden resectable? Does anyone think it’s gonna downstage more to resectability? If it’s unresectable, never resectable, I don’t think, it’s probably also gonna change over time, but I don’t, BRAF patients are not gonna be transplant eligible right now, with this new data, with this new treatment regimen.

That might change down the road. But if, but if we think HAI is sort of gonna be the next step in her care to extend disease control for as long as possible, you just have to pick the right window. I would say that would usually be when you’re seeing more of a plateau

Betsy Post [01:13:26]: Thank you. We actually have more questions now. Yes, I have one liver spot and its tiny size, depth, and location make biopsy challenging. If it’s ablated, I won’t ever know if it was cancer. What is your thought on that?

Dr. Lee Ocuin [01:13:42]: Right. I mean, typically when on an operative ablation, you can get a biopsy and then ablate it.

Um, so it’s possible to, whether this is being done operatively, intraoperative ultrasound guided or, depending on the experience and skill of a good interventional radiologist, you can do an image-guided biopsy followed by an image-guided ablation.

There’s a risk of over-treatment, but, it’s a low risk. Or alternatively could get an image-guided biopsy. But if it’s that challenging, I’m not sure what approach one would take. But if it’s gonna be an operative ablation, just get a biopsy and then ablate it at the same time using the same needle track.

Betsy Post [01:14:45]: Thank you. Here’s someone that’s asking, “If I’m getting radiation IMRT to lymph nodes in my pelvis and abdomen, will that impact my liver resectability down the road?”

Dr. Lee Ocuin [01:14:58]: It shouldn’t. Depending, I’m guessing if this is, is this..I guess I would need a little bit more context.

If these are retroperitoneal, basically extra regional lymph nodes, from the primary tumor’s been removed. If this is part of TNT or rectal cancer treatment, it shouldn’t. If a patient has retroperitoneal nodes, typically, I would say most of us are gonna be less enthusiastic about aggressive liver-directed therapy.

But if those nodes are definitively treated, and stable over time and, I would view it not significantly different than a lung metastasis that gets radiated. And if that stays stable over time and there’s a disease burden amenable to resection, at some point it’s, it’s fair to consider that.

I think again, it’s more of a case by case basis.

Betsy Post [01:16:19]: Thank you. How would you compare the effectiveness of histotripsy to resection and ablation?

Dr. Lee Ocuin [01:16:28]: Yeah. So nobody knows. So histotripsy is a very new technology. I think the early data are reasonably exciting, on a sort of, I guess, on a per lesion treatment basis in the effect of, they’re able to successfully ultrasonically, destroy a target lesion, right?

If you ask me to predict the future, it’s just gonna be another tool in the toolbox. So histotripsy is gonna be an option, that will definitively destroy a given tumor in the correct location, and of the correct size, no different than thermal ablation.

And with that also comes the technical limitations of histotripsy, meaning, one, you have to find it on ultrasound, and it’s a transcutaneous ultrasound, transabdominal ultrasound, rather than an intraoperative like liver ultrasound, right?

So you have to be able to find the lesion. It can’t be next to other critical structures like the diaphragm, the heart, the lung. I think folks are a little hesitant to perform histotripsy on lesions that are in proximity to those structures. I think one advantage of histotripsy is that, I think we’ll be able to target lesions that are close to some of the major pedicles, because conceptually it’s not destroying the collagen-based blood vessels or bile ducts.

So if you have a small liver met sitting right at the liver hilum where the blood supply sort of goes to both sides or where the bile ducts are coming together, I get a little uneasy about ablating those with heat because you can cause a bile duct injury, you could cause a pedicle to clot and, you can get complications with that.

And sometimes rarely, you end up doing, major liver resections, because you don’t have another good way of treating that lesion. Histotripsy may be a workaround for that. But I think ultimately, they’re gonna be just… it’s gonna be a tool in toolbox.

They’re all gonna be effective techniques for treating the target lesion. And we have a histotripsy program at Lehigh. We’ll have patients get evaluated and they have six liver metastases, but only three are visualizable on transabdominal ultrasound.

The fourth is next to the heart or, and the fifth you can’t even find. And I can find all of those surgically. So again, this is all collaborative. And, in a patient like that, they’ll typically tell the patient, and there’s really no benefit to doing histotripsy on two of the lesions and leaving three behind, right?

Um, so it’s an all or nothing thing. So those patients will often come back to surgery. So there can be technical limitations, but I think it’s gonna end up proving to be as effective as thermal ablation. And again, resection and ablation are complementary techniques.

So for a patient with a small tumor on the very periphery on the edge of the liver, it doesn’t make a lot of sense to ablate that tumor because you risk tumor rupture. And if you rupture a tumor that’s not dead, you can seed it, right? So I’ll typically resect a small tumor on the periphery, but if that same size tumor, or a second tumor of the same size is deep in, inside, in the middle of a lobe or a segment, I’ll ablate it, because I’m gonna effectively treat that tumor, but I’m gonna spare normal liver tissue, not have to do a big liver resection to take out a small tumor. Now, for a big tumor, five, six centimeters, those are not amenable to histotripsy or ablation, and those need to be removed, unless you can somehow downstage them to something smaller with chemo or pump or whatever.

But typically we’ll resect the larger lesions because the technology just isn’t there to do something bigger than that.

Betsy Post [01:21:22]: Great. I think this is the last one. No wait, there are two. “I have an HAI pump for 22 months, and now I have two new lesions in the liver. I’m gonna get SBRT soon for those.

What would be next tools after?”

Dr. Lee Ocuin [01:21:48]: The questions I would have would be are you still getting active HAI, or you’ve had the pump, you got some active HAI, and it was stopped for whatever reason. If you’re getting active HAI and you started progressing, I think, but it’s just those two lesions, I would think, for the time being, SBRT right now would be the only thing, and then I’d go back to close surveillance.

If you’ve been off of pump therapy, there’s always the option again and not knowing a ton of detail about treatment course, the concept of re-challenging with HAI, after SBRT would be a reasonable thing

The last question I was sort of helping answer myself. So he asked, “We’re wondering if we should have the primary tumor in the ascending colon removed first prior to chemo. Is it possible to have HAI installed at that time? The primary tumor would be removed.”

Yeah, so any time, trying to find where..So, a synchronous primary, and what’s the liver disease burden? Five centimeters in the colon and four mets on the liver, with the largest being nine by six . Yeah, I mean, typically I would start with at least a couple, if the liver disease burden is resectable, I would probably start with at least a couple of months of chemotherapy to make sure things aren’t blossoming, if the primary tumor in the colon is not symptomatic, meaning you’re not obstructed.

If everything is stable or somewhat responsive after a little bit of chemo, then I would typically, move to probably in this case, if it’s a limited liver operation, do something combined. I mean, an adjuvant pump in somebody with four, certainly I mean, I think it’s a reasonable discussion to have, although, and again, no one can sit there and say it’s an absolute necessity.

I would not start in terms of… there’d be a very rare scenario that I would start with an upfront pump or upfront pump with a colon resection. it’s done. I don’t know that, again, I’d need to have a little bit more context about the case and understanding of the liver disease burden.

But I think I would typically say we should start with a little bit of chemo. You don’t need six months of chemotherapy before reevaluation, but I would do at least a couple of months just to make sure because, again, it’s not risk-free, right?

So if you have surgery, first and your colon leaks and this, and you might never get on systemic therapy, and then there’s no brakes on the train, so to speak.

Betsy Post [01:25:37]: Great. And this will be, I think, our last question. So we definitely want you to go. Enjoy your evening. Uh, but this person says, “I’ve gone from too many mets to count to a handful of small tumors, four to six, all less than one millimeter. Would this be a candidate for ablation resection? My oncologist and interventional radiologist doctors say no.” And there’s a little bit more context there. She’s had systemic chemo, that also eradicated the primary tumor in the colon and no cancer left in the colon based on biopsies.

Dr. Lee Ocuin [01:26:18]: I mean, that’s, that’s a pretty impressive response. I think it would be hard to find tumors that small on ultrasound, but it’s certainly doable. But the question is, are any of those even viable at this point? If there’s no viable tumor, in other areas, like if you’ve had a complete clinical response.

But those happen from time to time. Patients have complete clinical responses, so what you’re seeing on imaging is really just at that point scar. It’s not even viable tumor. So I don’t know that… I guess the no, I guess I would wanna know what they mean by no.

Because I would never say it’s certainly not something that we should evaluate, but it might not be, may not make sense to do anything aggressive now and basically give it some time. And then other things I’d wanna know, do you have an MSI high cancer?

Sometimes patients have these dramatic responses, and we end up over-treating them

Betsy Post [01:27:59]: Thank you. Thank you so much everyone for your attendance tonight and for your wonderful questions. I really appreciate your time and being here live. Of course, I know I have a lot of people already asking for the recording. So and thank you so much for being here and presenting for us and being so generous of your time, answering all of these questions.

I learned a lot, and I’ve been doing this a long time. So, it’s wonderful to have these options in Pennsylvania for our patients too. So thank you so much. We really appreciate it. And, again, good night everyone.

Dr. Lee Ocuin [01:28:38]: Yeah. Thanks for having me.

Betsy Post [01:28:39]: Thank you. Bye bye.

Dr. Lee Ocuin [01:28:41]: All right. Have a good night.