Intermediate Hepatocellular Carcinoma (HCC) – Treatment Options & Strategies

Intro This podcast is for healthcare professionals only and is supported by an independent educational grant from Bayer. Speaker 2 Welcome back to another episode of Oncology Brothers podcast. I'm Rohed Ghosain alongside with my brother and Co host Rahul Ghosain. We are on this journey of four part series of hepatocellular Carcinoma 8 CC. Today we will be focusing out of the two discussions, The first discussion on intermediate hepatocellular carcinoma and last two discussions we have focused on advanced ACC where we covered first line treatment options with Doctor Rachna Shroff and the second line treatment options with Doctor Ramassa and Doctor Vogel. Speaker 3 Today particularly our focus is on intermediate ACC with an emphasis on multi modality treatment strategies. In this space, we're excited to have two experts with us, Doctor Maria Rage, a hepatologist who's leading efforts for BCLC from Barcelona and Doctor Emil Cohen, Interventional Radiology with MedStar Georgetown. Maria and Emil welcome. Speaker 2 Hello, thanks for having us. Let's kick this off. So intermediate hepatocellular carcinoma is tricky, multidisciplinary rather is the key here. What is the Barcelona Clinical Liver Cancer Staging System (BCLC) and how does it work for intermediate stage hepatocellular carcinoma? Maria, we'll start off with you first. Given the background and leading efforts with Barcelona clinical liver cancer staging system, which is the BCLC. If you don't mind briefly touching on what BCLC staging system is and how do you exactly go about intermediate stage here? Intermediate ATC is the best example of the need of multisimillionaire team because we have all the tumor inside the liver, but the amount of tumor that we have could be completely a transient. That's why in the last version of the BCLC, we consider the liver function the performance that was 0, but also what is the amount of tumor that we have. If you remember in the past, BBCLCB have only taste, now have some group of patient that could benefit for liver transplantation. Everybody knows that the criteria for liver transplantations are not homogeneous around the world, but we have a specific population that we consider that. Then in the other side, we have patient who have two more inside the liver, but it's diffuse or is not feasible to do a local original treatment. In this case, we think about systemic therapy, but the main group of patients is still receive the local original treatment. Then we can discuss if we believe in local original treatment taste or or rather embolization. The evidence based today is taste. So if I have to breathe, intermediate ATC is 2 more inside the liver without symptoms and the liver function is not any more an issue. Because if we fit the criteria for the implementation, you can consider this option. I believe that now is one of the areas that we really have a lot of things to to do see more. How would you like to add anything to this ATC and staging system, particularly from BCLC standpoint? Speaker 4 Well, as usual, I think the oncologists are very more well refined in their definitions. In IR we try to keep things simple obviously like the patients are going to go under go transplants depending on the institution's criteria are easier to handle. And once we have those two other groups subgroups, I should mention of BCLCB it. Speaker 5 Gets a little. Speaker 4 Bit harder and a heated discussion about how to treat them. So it's this is good that we're having this discussion to discuss this issue. Speaker 3 Thank you for touching on that. And it's important to address that. BCLC though is widely used system. Of course, there are other staging modalities, be it TNM. We also have clip staging. So as a community medical oncologist, this can often get complicated. The key here is having these discussions with our radiation oncologist or be it with interventional radiologist. OK, now that we have this foundation, let's take a little deeper dive and few treatment options for intermediate ACC. Treatment options for intermediate-stage ACC Maria, you alluded to this, but Mel, coming back to you, multiple local, regional treatments, be it SBRT, taste tear Y-90 or are we bridging for a transplant? Can you please walk us through some of these available options here? Speaker 4 So the options that we have for local, regional options are chemoembolization, which is the old school thing that's been around for like 50 plus years. We have modifications of that radioembolization which is radioactive beads as you well know that's been around for about 20 plus years and we have microwave ablation, but in this. Speaker 5 Category It's a little bit harder to apply. Speaker 4 And then you also mentioned the external beam radiation therapy, which based again, I'm not a radiation oncologist, but based on the guidelines that I've looked up, it seems like it's mostly confined to cases where we cannot use other curative options. It can be first line treatment confined for ACC, confined to the liver if other therapies are not. Speaker 5 Available or if a consolidated therapy if the. Speaker 4 Patients have an incomplete response to liver. Speaker 5 Directed therapies. Speaker 4 And salvage. Speaker 5 Therapy as well. That's what I basically gathered. Speaker 3 Can I push you a little more on this? And what scenarios would you use Y-90 versus taste today? If you have a patient in front of you, how are you making that decision based on these 3 modalities? Speaker 4 There has been a lot of evidence coming to the forefront that maybe radio ambolization is not only easier for the patients because it's an outpatient procedure for most parts, but also because it's been on X plan studies and follow up studies showing much more progression free survival or necro tumor necrosis, especially with the personal symmetry options that we have now. So there's been a trend not just in my practice, but I think most people's practice to move away from chemo embolization and move more towards radio embolization because not only of the side effect profile, you get an advantage there, but also because of the fact that we see better tumor response to it. So we've been moving more and more towards radio embolization for patients. Speaker 5 For liver directive therapy. Liver Directive Therapy Can I make a comment here? Because I believe that nowadays we need to understand and the audience maybe needs also to to hear our discussion about that. There's not white and black now, it's more Gray and there are more and more discussion because the evidence level is different, but also the patient characteristics. So I agree with the previous comment and I will also add to the audience that we need to consider many factors that are completely beyond the liver function and the tumor burden and it's more related where we are working on and other things where are the specialists that are in the centre and also the reimbursement. So all of the things now is also part of the discussion on selecting the treatment truly. So because sometimes we are limited with the hospital support or one only have taste available, patients don't want to travel. So there are much more complications that are tied in with just administering the treatment and sometimes how close the tumor is with the vessel and all that sort of stuff ties in as well with the anatomy aspect of it. Now while we know that this in general apatocellular carcinoma is associated with poor prognosis. Systemic therapies in early stage liver cancer As a result, systemic therapies which have been doing well, at least in metastatic setting are being put out or brought in earlier stages. We have seen that whether that's standalone or combined with local regional therapies. We've seen that with replace data with rigrafinib plus pembrolizumab versus taste or tear Emerald with durvalumab with taste. Maria, we'll start you off with here. How are you interpreting that and how are you sort of talking about the data here? And this is also a challenge because what today we're talking about intermediate ATC. But when you go to the clinical trials, the population that were included are patient candidate for taste. That means for example, the replace trial and also the ABC trial include patient with personal status 01 and both of them include patient with all the tumor inside the liver. But for example, replace, Grego plus pembro have patients who are beyond the up to seven criteria. In the ABC trial, we have patients who are beyond the Milan criteria. So the key thing here is the stratification factors, but also consider the primary endpoint. The primary endpoint is also different. In one, the ABC is treatment failure, in the other, in the replace is the progression for survival. How do we interpret all of these data? Maybe we could have another session for that, but to be simple, the key thing is identify the patient that were included and also the result that we expect to have result in the next year to know where we are. Maybe we can discuss later on the other data. But Sharon is speaking, I'm happy to say that we expect new data and new information related treatment failure for example, and understand better what does mean progression for survival. Speaker 4 Right. I think that's a very good point. I think these therapies, systemic therapies are showing great promise, especially with combination. And I think one more thing to add here. Every time I look at a new study, I'm sure you guys all do this too, because oncology is much more versed in this. It has to apply to our patient population. And as you mentioned, like you know where I am, I'm seeing alcohol mash and Hep C I'm sure Maria sees a different patient population and also patient use. Our listeners in Asia probably see a different patient publishing from hepatitis B. Speaker 5 Etcetera, So. Speaker 4 That's always AI know it's probably free base of the oncologist listening to this, but I'm just good for my radiation International radiology friends. Speaker 2 And just to actually harp on some of that stuff that you were talking about where Tear is better than TASE itself and TASE has fallen out of favour while Emerald itself has been utilizing Tase. The use of Tear vs TASE in cancer therapy We are waiting on Emerald Tear which is rather more tear focus if this was to get approved or are you going to be relying more on Tear aspect of it versus TASE in this case? Speaker 4 My practice has shifted a lot from tase to tear in the past 5-10 years. I do still do taste occasionally, but to be completely frank, it's usually when terror has not worked or if I think there's very unique situation. So this is where has been and I think most of my partners are doing the same thing. But going by guidelines, if we're just doing bridge to transplant etcetera, it taste is perfectly. Speaker 5 Viable. Speaker 4 Still in those situations occasionally. Speaker 2 To add to this comment, we also need to remember that at the beginning that the embolization would focus in patient with more and to more burden now. So they are moving more for local, local asset tumor and it is not data to support that one is better to the other due to the patient population. So again, I believe that we can consider as an alternative option for those who are not candidate for test. But if you're in a centre at the antialiologist, use this technique, we know that is safe and have response. So that's why the discussion is, is beyond what is the priority for the physicians and the patient for sure. Speaker 3 And again, Maria and all you've touched on this, it's not black and white because the real world patient in front of us looks very different than what they usually go in clinical trials. And by the time something is approved, we're looking forward to something else already. One thing in the clinic settings that we often run into is if you're having side effects, is it more so from the TKI that we're giving? Side effects of TKIs and local regional therapy Is it more so from the immunotherapy or the local regional therapy that we're getting? Maria, can you touch on this a little more? How do you often dissect as more and more of these therapies are moving early on and now focusing on intermediate ACC? Speaker 2 Yeah, sure. For combination local original treatment plus immunotherapy or tiki eyes, we have experience in the clinical trials and we need to follow the rules for the clinical trials and then you translate to clinical practice for sure. Systemic therapy depends on the profile of the adverse events you can induce to think that is more related to one treatment to the other. Frankly speaking, complication after kidney embolization rather embolization are really, really rare if the patient if compensate cirrhosis and and so on. So generally speaking, we focus in the profile of adverse events and depends on that we discontinue or not. If the patient have a severe adverse events, the travelers of the origin, you have to resolve the complication and then you can decide if we're linked for one or the other. From a clinical point of view, I believe that the most important thing is identify the profile of adverse event that we're talking about. All this data is convincing, but the real world is, of course, a lot different because there are a lot of factors that are tying in as we were talking about it earlier, whether that's different practice patterns or different patient profiles, center of capabilities or regional differences, whether one is practicing in Europe versus North America. Real-life practice Maria, let's start off with you here in real practice outside of clinical trials, how are you putting all this together and treating patients with intermediate hepatocellular carcinoma in Barcelona? We treat according to the guidelines and we deal with taste. Having said that, if the patient is failure to the taste or is not candidate for taste, we could consider radiomatization or systemic therapy. But if you go to the evolution, there are some patient that will also be benefit for SBRT. That's means depends on the characteristics of the patient. We go through different option, depends on the data that we have in terms of evidence for our group evidence base is over survival, but we know that in clinical practice some patients are not candidate for that. The only thing that we're not doing, at least up to now, is giving combination therapy, systemic therapy plus hemobilization or radi embolization outside the clinical trials because the data we can discuss later on is not mature enough. Speaker 3 We all are eagerly waiting on overall survival and all you had touched on that as well. This is all exciting, but we eagerly await overall survival before all of us jump on that bandwagon and we're coming back to you for local regional control here. Pearls around sequencing Any pearls around sequencing? Maria touched on this, that if someone got taste, maybe you can still use SPRT, some of these modalities that you have in hand, be it with IR or radiation colleagues, how are you sequencing that? Speaker 4 So let me just back step back for one second to address that. I think in the United States we're have been trending towards radio embolization a lot more and there is actually data already in our journals that's showing the unexplanted livers you're getting much more complete response a tumor necrosis from radio embolization. But of course those are people who are transplant candidate and we're discussing patients who have more than one or two diseases. So it's a little bit different because you can give higher doses. Putting that aside, we're talking about we usually generally start out with radio embolization if we can do it again because it's more better tolerated for the patients. I should say the side effect profile is better and we've seen that and you can do taste more gently, but if you do it, you're going to get less of a response. So I always tell patients that who are feeling not so great after a procedural or at least you know the treatment is affecting something in your body, right. But if you don't get any side effects on that could also be a bad sign that maybe we didn't treat you more aggress as aggressively as we should have having because there's not just like anyone method to do this. I think between my four or five partners at Georgetown, we have like 5 different ways of doing things and we've fortunately discussed this once we see one. Therapy doesn't work. For instance, if you're the patient hasn't gotten a good response, move to something else. For instance, like you mentioned external beam radiation. Speaker 5 Therapy. Speaker 4 Just like their guidelines, if we see that our tumors aren't responding and there's peripheral residual tumor, we might ask our colleagues in radiation therapy to treat them because frequently there's accessory blood vessels that maybe we can't treat through like phrenic arteries, internal mammary arteries and maybe residual tumor and edge of a tumor. And we ask them for their help to addressed as issues. Speaker 2 I think this complicated conversation only tends to reiterate that we need to have radiation oncologist, IR surgeon, pathologist, radiologist and medical oncologist sitting on the same table when making decisions, especially when intermediate ACC. As we wrap up, Maria, any important studies that are on your radar for intermediate HCC which you're looking forward to and importantly clinical takeaways from today? Key Takeaways Sure. In intermediate ATC, we have to talk about the Imran Guan trial, the 3rd that improved progression fee survival. But I would like to emphasize the the fairpoint that we discussed at the beginning, 57% of these patients were intermediate ATC, the other 16 BCC. So advanced stage or early stage in your clinical practice with the presence of positive data based on EMERALD 1 and LIPO 1-2 that is combination of local regional therapy with immunotherapy. Are you utilizing these practices currently in your practice at all or rather waiting for the approval itself? Our clinical practice have different factors. One is the evidence. We have data, but it's not mature enough. We have chance to think about new options, but we still need to know exactly what is the impact in clinical practice. Speaker 4 If I can make one comment, I think Maria alluded to this, I think it would be really nice if you could get recruit more of these patients for trials to get a more definitive answer. Speaker 2 Long term data and recruitment plays a huge role, especially that's where community oncologist comes in as well to help with the accrual process. But again, involving turf free care Centers for multidisciplinary approach is extremely important. MO, any final thoughts or key takeaways from you, Sir? Speaker 4 I think you summed it up very nicely. I given the fact that we don't have a flow chart for these category of patients. But if you can reach out to, and I, as I do to my even colleagues sometimes in more difficult cases to other institutions to try to get an answer in a difficult patient, It's very useful and working as a team like you mentioned is extremely important. Speaker 3 Doctor Rage and Doctor Cohen, thank you so much both for your time and insights on this rapidly involving but complex space of intermediate ACC. For our listeners, let us go over a quick recap. In today's discussion with Doctors Maria Rage and Emil Cohen, we focus on treatment strategies for intermediate ACC from local regional options like Taste, Tear, Y-90, SBRT to systemic approaches and combination strategies. Speaker 2 We also discussed the clinical importance of multi modality approach and the need to personalize treatment based on the patient specific profile and disease progression. Thanks for joining us. Make sure to check out our other discussions in the ACC series and stay tuned for the final episode on a pad of cellular carcinoma. We are the oncology brothers. Speaker 1 For more details on all the trials mentioned in this podcast, please visit the Cortuet website for a complete list with links. If you enjoyed this podcast and want to find out more than please look for the Oncology Medical Conversation podcast under the account of Core to add medical education. Also, don't forget to rate this podcast, subscribe to our channel and share it with your colleagues. Thank you for listening and see you next time. This podcast is an initiative of Core to Add and developed by HCC Connect, a group of international experts working in the field of oncology. The views expressed are the personal opinions of the experts and they do not necessarily represent the views of the experts, organizations or the rest of the HCC Connect group. For expert disclosures on any conflict of interest, please visit the Core to Add website.