Drs. Frenette, Karvellas, and Gutierrez examine several HCC cases and present their follow-ups.
we will now have what I considered sort of a virtual tumor board. Um, what we, um, you know, we've done, I've done this and I did this actually at the HCC tag, which is in a specific HCC meeting. Um, and it really just lets us talk through cases which are cases that you would be seeing potentially in your office too. So we can sort of just have a discussion of, how do we think about these patients? How do we think through these things? And then I will use the opportunity to show you a little bit of data about the discussions that we have. Um, there's our, again, our faculty disclosures for all of our faculty and I will start with case number one. Um, this is a 50 year old gentleman who presented with end stage liver disease from hepatitis C and alcohol. He has a complications of, besides, he has a history of sbp recurrent encephalopathy and a remote various, he'll bleed that he's been banded. He previously drank 36 beers a day but did quit 18 years ago. He's had 35 alcohol related arrests. He has a 70 pack your tobacco history in a remote I. V. Drug use history. He came in with worsening asides and oedema and await increase of about £15 and you can see his labs show thrown beside a pina with a platelet count of 53. His I. N. R. Is a little bit elevated at 1.3. His albumin is low at 2.9. Billy Rubin is 2.3. You see his liver enzymes, there are elevated. His elk Foss is also elevated and his A. F. P. Is 35. This sounds like one of my patients. I was going to say, I literally was just going to say this is a patient that dr gutierrez would see. I think every day in the office I'm a honeypot. So um sorry? Okay, so he had a ct of the abdomen and he has a 3.5 by 3.1 liar. It's five lesion in segment three of his liver. Also at 1.8 by 1.2 centimeter mass liar. It's five in segment five and a large amount of the city's. Um He had a bone scan and a ct chest both with no metastatic disease. And um the question is, now, what are we gonna do with him? So we're presenting this case at tumor board? Um he's getting his act together and we need to figure out what we're going to do with this guy. So I will invite either of my two colleagues to give some input. So carrie preliminarily what I see is this is a patient with very advanced liver disease, at least probably a B nine I think. Right. Child Pugh B nine or so, very close to maybe being a see right. Um Certainly not a candidate for reception of any any by anybody's imagination. And I would of course be very curious to learn what my interventional radiology colleagues would be thinking in terms of local regional options for this patient. I agree Julio that's something I would think about to. Of course we always worry about. Are we going to make their decompensation worse by um you know, doing some local regional therapy. Um I also when I'm seeing somebody like this, I think about is there any way that I can improve their child be status? You know, sometimes they come in, they haven't really gotten good diuretic therapy, good management with protein intake, low salt diet. Um And and sometimes we can actually tune them up a little bit, so to speak. Um Dean would you would you guys do risk doing local regional therapy in a patient like this in Alberta? I think I think the other thing we would also want to clarify and I apologize for missing this from the stem is also their transplant status. If they are potentially a candidate for transplant or not, because if we could certainly if we could bridge them to transplant, then I think this probably falls in the window for thera sphere. Uh Sorry for today's assuming that that there's no portal vein thrombosis. So he didn't have any portal vein thrombosis. Um We, you know, in the US we use the milan criteria. So he is technically outside of the milan criteria with, you know, the 13.5 centimeter lesion, an additional 1.8 centimeter lesion. Um He does have a pretty exciting, I would say social history. But again, he really has um he quit smoking, he quit drinking, he's quit drugs, He's really, you know, sort of been tuned up quite a bit. Um So yeah, I think you're right. When I when I were thinking about doing local regional therapy on these guys, the question is, do we have transplant? Is that something that we can think about? Because that's also going to give us an idea. Well, if we do make them a little worse, are we going to be able to save him? Right. Yeah. I'll mention one thing too that I know that depending on the center, some people will push the envelope with with transplant here. We actually will will accept up to a total tumor volume of 115. We use the HGTV criteria. So I think also that's going to depend on your on on your center. Yeah. Um So this guy actually got a chemo embolization and he was listed for transplant. Um His follow up CT was done and he I think I messed up my slides here but he did have a good response to taste. Um I think the question is uh what is his chance of being able to stay within criteria? Do we think about doing a living donor liver transplant? Because otherwise he's going you know, in California, he's going to be waiting anywhere from a year to two years and his risk of decompensating and having progression of liver disease while he's waiting. Um What are your guys thoughts on that? Yeah, he's certainly in a high risk uh situation. You know, Dean kind of alluded a little bit to um to also the idea of doing uh atrium 90 therapy on this patient. What do you what do you think about doing that in a patient carry? Who already has societies and be compensated liver disease? Would you be comfortable Letting him opt for Y 90 instead of a taste? I think I would be a little nervous especially because he did have by Low bar disease. He had one on the right, one on the left. And those patients in my experience have don't tolerate it quite as much. And as billy Rubin was 2.3, which is a little higher. We usually use a cut off of around two. Um So I would worry that why 90 would make him decompensate worse. But that also depends on are we going to do a sub selective Y 90 versus a low bar Y 90. And I think the literature has been pretty clear now that moving towards sub selective is a better outcomes for the patients, both in terms of um our response as well as instability of liver disease. So um Well I did want to just show a couple of slides about down staging to transplant. And Dean, you had mentioned the total tumor volume up to 1 50. Which 1 50? Right. Um Yeah. 1 15. Right. Um And that's you know, that is used a lot in europe and also in Canada and the US we use the UCSF criteria. Um And this is also what you notice the united network of organ sharing uses. So that's one lesion Up to 6.5 and if you have three lesions uh largest is 4.5 total tumor diameter of less than eight. Um and this was data that showed that if you're within that criteria that you actually can have better outcomes very similar to the Milan criteria, as long as you can downstage them to within Milan. But interestingly what we do see is that there are about 16% of patients that are never able to be down staged to within Milan. Um and then overall there is drop out for tumor progression and also liver related death. And when we actually look at the risks of the risk of drop out while you're waiting, the biggest risk factors were actually not necessarily the size and number of tumors, but it was pre treatment FP of over 1000 and or having decompensating liver disease with child B or C. Which as you said and pointed out Julio um that would actually apply to this patient. So he would have Um a risk about 46% of drop out while he's waiting for a liver transplant at least in California. How do you present this to the patient? How do you think about this when you're giving your patients the various options that they might have for treatment of their cancer? Yeah, I think this is a tough discussion to have with the patient because it involves a lot of unknown variables on our part to write. And we we don't really know what's going to be the natural history of this patient authority, what seems to be decompensating liver disease. Over the next two years, we're introducing a therapy that is, you know, potentially could exacerbate the underlying liver disease. And then we're committing them to the a pretty long wait. So I mean, this is a tough situation, especially in the sunny, dry hot state of California these days where media melded transplant is is high. Um, and so, you know, I try to put lay this out with my patients. You know, I I like to walk them through the whole projected timeline. Um and really try to get an understanding because you know, many of our patients are very naive about transplant. I think you know that carried to that, you know that they think on the list in a week or two them to be getting my new liver and everything is gonna be great. And I think you know, this is really requires a very careful discussion with your patient. Yeah. Dean, do you feel like that the d compensated patients or the high aF P with using total tumor volume as you do. Does that hold true as far as their probability of drop out? Or are there other factors that play into it? So I was going to mention the other thing too is the other piece of it is the AFP you need an AFP of less than 400. So obviously there are some people that this becomes the issue that the AFP is above range and then we're not a candidate. So you have to downstage them and then you have to reassess them and usually it's 3 to 6 months. Um I think also that one of the interesting point you brought up about live donor. Um is that I think the hard part with that discussion becomes especially where you have somebody within let's say T. T. V. Or U. C. S. F. Criteria but not milan. So they're higher risk of of recurrence. You don't want to wait. You don't wanna even with the exception meld points on the transplant list it's going to take them ages. But now you have the problem of two patients you've got the donor and the recipient and you have to explain to them that you might get it live don't you might get a live donor transplant. But you've got a higher risk of recurrence. And on top of that there is not an insignificant risk of post transplant or even post hepatic to me uh complications to the donor to your to your to your sister, your your family member. Yeah I think that's very true. And you know I don't have the data on a slide here. But there was a really interesting study that was presented at one of the transplant meetings and published subsequently a couple of years ago that actually showed the short wait time patients who were transplanted have a higher rate of recurrence of cancer as compared to medium wait times or even the long wait times. They have a much higher chance of the cancer recurring. And it's thought that having that six months of natural history wait, time to see. Is this cancer really actually controlled before you transport them and put them on immuno suppression really makes a difference. Um And that's where they are the rule of the six months hold before the melt exception kicks in for HCC came from to really have that natural history. Wait time. Um To to see as this cancer controlled. Do you ever do you ever put a lot of weight in terms of what the pathologist reports in terms of the biology? Because I think this is the whole idea here is we're trying to estimate the biology of the tumor. Mm. Hmm. Yeah that's I mean that's so tough because you know, we've had patients that have we don't biopsy a lot of these patients. And so sometimes we don't have the pathology until X. Plant. And we've had patients with poorly differentiated disease where we you know the data says poorly differentiated has a higher rate of recurrence. And yet they do great. And then we have well differentiated patients that really should have been totally fine. And then they get a recurrence a year and a half after transplant. I have one of those right now, that's just heartbreaking. So I think that the differentiation from the pathologist is somewhat helpful. But I think there's a piece that we're still really missing in terms of the actual natural history and the biology of HCC. And I think that as we learn more in terms of you know genetics and genes that are turned on and off and more uh things like that I think will actually learn more about what actually is going on. Well let's move on to our next case. Um So this is a 57 year old gentleman he presents for treatment evaluation when he was found to have hepatitis C. On routine screening. And as I'm sure everyone knows it's now recommended that every patient get HEP C. Screening at least once and anywhere over the age of 18, he's otherwise totally healthy. He rarely drinks alcohol, He's actively working. He's totally unremarkable physical exam. But on his labs his cbc has a platelet count of 95. His liver enzymes are elevated and his A. F. P. Is elevated at 42. His ultrasound shows a nodule, her liver with a 1.9 centimeter mass and he has a four fe C. T. That demonstrates a 2.1 centimeter liar EDS four lesion. That has enhancement but no washout. So according to the guidelines for liars for lesions, it is recommended that these patients be discussed at a multidisciplinary conference to decide what's the next step. So here we are. So dr gutierrez, this gentleman with the lyrics for lesion, what would you recommend for him? Well, I mean I think there's a lot of opportunities here, Right. I mean we have a patient with active hep C. Infection with good liver function um and there's a chance we can even make it better by eradicating the hepatitis C. Um The platelet count, although a little bit marginal may leave him with some opportunities for additional therapies like surgery. Um And certainly you know what we would consider. I think here with a ct scan that's very concerning is another modality of imaging. I think that's a go to move, depends a little bit on your center and the machines you're working with. But you know, I think in our center an M. R. I. Um in similar fashion would also be very helpful. Like in Alberta would you see him or would you do an M. R. Or would you like three months? Uh We would we would probably do an MRI the other thing I find that interesting here is you're just around that two centimeter cut off. Which I think was probably because I know that this is often the cut off where you might be able to Get away with ablation if it's less than 2cm. So obviously this is going to be a bit of a problem. Alright? Unplug and re plug my mic. Hopefully it fixed. Sorry everyone. So just to remind everyone when we use the liar IDS criteria. So I think we're all pretty used to seeing this. But in terms of the risk, what we know is the liar. It's three about a third of them are HCC and about 40% malignant liar. It's four it's about 74% are HTC and 80% malignant. And then liar. It's five it's 94 97. So the light reds criteria are really pretty useful and we're pretty comfortable using those now for HCC. So a liar. It's four is probably HCC. And it's recommended to have a multidisciplinary discussion for tailored work up and you may include a biopsy or you could do repeat or alternative diagnostic imaging but no longer than three months. That's really the the time period I will say I just on friday had to do a peer to peer on a patient that the insurance wanted me to wait six months on a liar ads for a lesion. And that was fun. But I will not be told no. So you may have to be persistent. So this patient underwent an MRI he had a liar. It's five lesion. You can see here there's the arterial hyper vascular charity in the left lobe of the liver and then portal venous wash out with that nice pseudo capsule. Um So clearly a lie rats, five lesion. His liver tests again um elevated A. S. T. A. L. T. And his platelet count is 95. So the question is, what do we do for him now for treatment? There's lots of options with a lesion like this. So um Dean, what would you think about for treatment in this guy? I think the first question it goes up to what what dr gutierrez was messaging is ever mentioning is what what evidence do we have reported hypertension? So I didn't you know, it depends how big the spleen is on on on the MRI and Ct. Because if there is a potential for a for a limited reception, obviously that's got a lot of advantages because also were kind of it's a bit too big for for radio frequency ablation. I think probably, you know, in kind of combination obviously with Pepsi eradication. Um And then I guess the other question I probably would put into this is what's your backup plan obviously. So let's say you decide to go for a surgical resection. Is there a possibility of a transplant if the guide if the if the guy deteriorates? Yeah, I think all that's very uh apropo uh we're doing a lot of microwave ablation now as opposed to radio frequency. Um And with microwave we do get a little bit of a hotter burn and we can do a little bit larger lesions. So we may think about a microwave in this patient also. But I agree with you. I think resection if he can tolerate it depending on his level of portal hypertension would be really good to see Julio. How would you work up someone like this to see how much portal hypertension do they have? Well, you know, we we have access obviously the uh portal pressures through the trans jugular portal pressure method. Um you know, I think applying something like the bovino criteria here, we already see that this patient probably would have portal hypertension. I'm guessing that the fibers can we don't have that. But I'm just going to guess that this is a fiber scan of maybe 27 by looking at the guy, platelet counts, you know, 95. So I'm going to say this guy probably does have horrible hypertension and it's, you know, this is not a trivial surgery. I mean, this is a left load we're talking about here. So I'm with Dean on this one. I want to maybe consider this guy for transplant. Maybe you get them kind of ready if we're going to go to surgery. Um And but maybe maybe they do okay. And this is very common and high meld regions where people are finding these HCV patients with maybe early portal hypertension but mild and they're taking them for partial hepatic tumors when they find the agency. So I think this is a real thing. Yeah so um this is what the latest A. S. L. D. Guidelines say for the role of surgery in patients with HCC. They put together this really nice little flow chart um where you you know decide if there's portal hypertension and if there is or isn't you then also look at the extent of the hepatic to me whether it's more than or less than three segments reminder left low would generally be two segments, segment two and segment three. And then you look at the meld score um above or below nine to give you is at low risk and you can proceed is at intermediate risk and you decide or is it a high risk and you really should stop on those patients? Um So I mean I think I think we do a lot of this in our head without necessarily going through a flow sheet. Um But I think this is actually a really nice little way of thinking about doing a reception on these guys. Um The meld score of nine came out. We you know in the old B. C. L. C. We used to look at whether there billy Rubin was elevated over one. But now there's actually data showing the meld score of nine can be more helpful. So this patient underwent a robotic resection without complication. Um He had imaging one month after resection that showed a complete response. No tumor, no recurrence. So what are we gonna do now about his Hep C. Treatment or should he have started hep C. Treatment immediately? What do we do now? So Julio what are your thoughts on treating hep C. And someone with cancer? When do you treat? How soon do you start? And at what point do you say? This is time? Yeah. I mean this has been a controversial topic, right? Because initially there is some signals, especially we had a study from spain indicating that how to sell their carcinoma could be exacerbated by treating hepatitis C. The overwhelming data now shows that you can actually reduce the risk of HCC in the future and the tumor progression. And it makes sense. You know. But I think the just boots on the ground feedback I get from the surgeons is there's a big difference with the surgery when the patient has already had the heP C. Eradicated. And I've gotten phone calls, hey, can you treat this guy's Pepsi? What do we do? And I've even found surgeons who figured out how to treat Pepsi themselves because they feel like it's better to have the HEP C treated. So, I mean, I think this is I'm really getting that feedback. Do you start? Or maybe Dean, I'll ask you this question. Would you start treatment after he goes through surgery? He's recovered? Everything's happy, hunky dory. Or would you get him started while you're doing his work up to decide if surgery is even possible. How soon do you start? I it's a very good question. I think probably I would I would lean towards kind of starting as soon as possible uh Just because there are like you know, all the all kind of significant benefits with uh with treating the HEP C. Going even beyond just the tumor. Yeah. And then the other question that always comes up in my head is, well, how do we treat these people? You know, this guy is so erotic but he's well compensated, right. Um but we also know that active HCC decreases your risk of response to the direct acting antivirals by about 10-15%. So do you treat him with more of a regimen that you would use in a d compensated patient or um you know, should you use the normal regimen then you would use for any Sirat IQ. And if he fails then move on. Although doing treatment in a psoriatic that's already failed is difficult because you have to be careful of the protease inhibitors. So, what are your thoughts there? Well, I mean, I think that that's a that's a the million dollar question. You know, these these as you point out, there's an eight fold increased risk of hep C failure in patients who have HCC. And when I have a hep C failure, I immediately start panicking. Did I miss a tumor? Actually? That's what I think when I have a hep C failure. So, you know, I think it's challenging. But the cure overall, the cure rates are still very high. We're still talking about, you know, 88-9% chance of eradicating the virus. Um you know, and this is, you know, timing maybe is of the essence here. So, we know that cure rates are pretty high in the Sirat X with an eight week course of GDP, that might be desirable in this situation. But it does lend a little risk, right? Because we're putting the protease inhibitor in the mix, although this patient seems to be well compensated, would be ashamed to exacerbate things by exposing to a protease inhibitors. So I mean I think those are considerations I always think about, you know, when it's not clear to me that getting that, you know, if you're not doing surgery, you're going to do like a taste or a y 90. Getting that cancer under control increases your risk back up to baseline. I think it I think it probably does. Um So what I usually tell the patients is let's get your cancer under control first, then we're going to treat your HEP C. Um And the other reason is because if they have some complication from cancer treatment and they're on HeP C treatment and then you have to switch around therapies or you have to hold it or something like that. Um You know, the cancer is the thing that's going to kill them before the HEP C, even though the HEP C. Is the thing that caused everything. So um that's how I usually think about things. And that also gives me a chance to make sure that you get the insurance off and all that jazz for the Hep C treatment too. Um But again, there's not a huge amount of data or guidance on how soon to start that hep C treatment. Um Dean, are you starting pretty quickly? Uh Generally we and and to be to be clear, I generally for most of this stuff, but I'll be honestly, I don't have a I don't have a big Pepsi practice. So uh so generally I'll be deferring to colleagues to be completely honest. But generally we would try to start obviously that this is done after a multidisciplinary tumor meeting with with rods and with surgery usually. Yeah. Well I did want to just show a couple of slides. Um You know as as Julio said there used there was some I'll call it kerfuffle about maybe the direct acting antivirals worsening HCC outcomes. Um And this was actually a multi center analysis in north America. 31 centers. Almost 800 patients with HCC associated with hepatitis C. Who had a complete response of their cancer treatments. About half of them got D. A. Therapy and about half of them were untreated. And what this study showed is that clearly the direct acting antiviral lowered mortality. So it's definitely in the patient's best interest to treat them. The blue line here is the people treated with D. A. Is the red line. Is your D. A. Untreated? I'm sorry the blue line is untreated. The red line is you're treated and you can see the risk of death is lower. And the patients who are treated the treated patients had 4.6 deaths per 100 person years. And the untreated it was almost 20 deaths per 100 patient years. Um And and multi varied analysis. The mortality was cut in half if they underwent therapy with D. A. So I think that we really put this question to bed and it is in the patient's best interest to be treated Now reception um and really any therapy but except for transplant and even transplant. But the you know, the achilles heel of resection is recurrence. Um this is just one study that showed over about five years. There was about a 70% chance of recurrence. Um Our patient underwent Hep C. Treatment and did get an SVR, but he was followed with um surveillance imaging and he did well for about a year Then. Um uh go to here after a year. He was found to have multifocal recurrence. He now has four lesions, all between 1-3 cm, the largest of 2.7 total tumor volume 7.5 cm. Um And you can see his FP is elevated, but otherwise he's really, you know, his labs are in pretty good shape. So what should we think about doing with this guy now? So I say, I think like transplant work up. Yeah, I mean, he's all right. I mean, he's got a high total tumor volume. You'd be a very marginal transplant candidate. And I think the really concerning thing is serious. This is happening fast carry. You said this was a year and I think everybody would be very nervous that this is potentially a condition that just can't wait for transplant. Yeah. So I mean we do think about post resection recurrence. Should we think about a salvage transplant. And that's um definitely something I'm very aggressive about. You have to be really aggressive with local regional therapy. He's outside of Milan so he would have to be downstage with treatment. Um This is somebody also, we may even think about starting on systemic therapy while he's waiting for transplant although again we at scripts get again get very nervous as I said with immunotherapy around transplant. So we would not be using immunotherapy prior to transplant while we're waiting on more data for how that impacts the ability to have a transplant without horrible rejection after afterwards. But I agree that it would be something that I would want to think about as far as getting them to what's called a salvage transplant. Um So there was this really interesting study that actually looked at length Attentive or systemic therapy versus taste for HCC who are belong beyond up to seven criteria um where somebody like this for instance. And you know, we're one of the discussions in the systemic therapy world is how soon should we transition from LRT to systemic. And I think we've all been really used to local regional therapy. But now that we're getting so many systemic therapies out there, thinking about when to transition to systemic therapy is always a tough one. We have 20 seconds if you want to have a comment on that transition time because it's a toughie. Yeah, I mean I I agree with you. It's a difficult decision. And you know, I think this really begs the question too of combination therapy and what are the opportunities for combining therapy in these patients? And I know that this is not something we've done sort of prophylactically put people on T. K. I. S. Although this was done I think at the beginning of my career pretty commonly. So I think that's where my head goes. I see this data. Yeah. And there's a lot of studies actually going on right now with combination of systemic with local regional. In fact we just opened a study with Catnip and Embolism app in combination with tastes. And that may end up being a place that we go to as well for these difficult patients.