Chapters Transcript The Evolving Field of Hepato-Oncology Dr. Vivian Ortiz, MD provides and update on liver cancer and how liver transplant is used to treat these patients. Doctor Vivian Ortiz earned her medical degree at Mehari Medicine College in Nashville, Tennessee and did her residency in internal medicine at Yale New Haven Hospital in New Haven, Connecticut. She then completed her fellowship in gastroenterology at the University of Pennsylvania and Phil Philadelphia then went to the Mayo Clinic in Rochester, Minnesota to complete her fellowship in transplant hepatology. Doctor Ortiz is currently an assistant professor of medicine in the division of gastroenterology with washy physicians at Barnes Jewish Hospital. She sees patients at the Center for advanced medicine at Barnes Jewish Hospital and in South County for liver transplantation, acute or chronic liver disease including cirrhosis liver tumors, including car. Whoa, cool. I'm never gonna get it. Cholangiocarcinoma, cholangiocarcinoma, hepatitis, autoimmune liver disease, metabolic associated liver disease, alcoholic liver disease, vascular cardiac associated liver disease. So, thank you so much for speaking with us today and asking us on the field of he pato oncology. Great. Um Thank you for having me. Um It's my pleasure to um talk to you today about the evolving field that had oncology. Um An assistant professor and transplant hepatologist here at WASU I um have no disclosures. So, um so in a presentation, I wanna cover uh three types of tumors um that have really changed the landscape of HEPA oncology and more importantly, transplant oncology. Um These are three transplant, three transplant tumors that were three types of tumors that we're doing transplants for in these days. Um So first, let's get started with hepatocellular carcinoma or HCC. Um Just a little bit of history taking us back. Um Before the 19 nineties, it was actually referred to as hepatoma and it wasn't until 1994 that the internal um you know, working party defined it as HCC separating it from dysplastic tumors or dysplastic nodules at the time. Um and other benign lesions such as um hepatic adenoma in um 19 9, 1967 the first transplant for HC was actually done. Um and, and by the way, sorry Nicole, I just want to double check that you see the right view of on your screen. Mhm I'm assuming that the view is correct. Um So uh uh the so it was done we can see we can see your view or the correct view. OK. Thank you. Thank you. I appreciate that. Um So yeah, it was done in a 19 year old um um patient um who had HTC and it was done in Denver at that time. Um He actually ended up or this patient ended just over a year uh before he uh developed a tumor recurrence with meds in the abdomen. And lung. Um despite having received seven weeks of increasing post op in our um day and age and this is data collected from the 2020. Um the incidence of H CCS of uh 9.5 per 100,000 after standardizing for age alone. And this um and the incident is highest in Mongol in Mongolia with 85.6 cases per 100,000 a year uh followed by Egypt, Laos Cambodia. And just to put in perspective, the incidence rate in the US is a seven new cases per 100,000 um a year in terms of mortality, it follows a similar pattern with more than half of which happened in Eastern Asia. Um highest been in Mongolia again. And um just to, you know, put it incidence of HTC is also expected to increase by 2040 by um 55% uh especially in areas of uh developing with high developing index. But in terms of deaths, uh the it's expected to is expected to increase in areas of low human development index which is attributed or has been attributed to the growing aging population focusing on the um US population studies done from the year of 2000 to 2019, um showed that the age standardized mortality, uh cancer mortality rate has been particularly highest in the African Indian and Alaskan native population. But uh with a greater um with a greater rise in mortality in the Anglo Saxon population uh with a 50.2% increase compared to about 36% in native population. 35 in the black and 4% in Latinos. The, the Asian population has shown a steady decrease uh of 23%. But if we focus on 2019 alone and desert, the maps on the right liver cancer mortality rate um has been higher among minorities in the larger parts of the US which has been uh geographically focused um with. And this is compared to um why populations demonstrating significant disparities when it comes to this type of tumor. Um And this has been attributed to a delay in diagnosis for access to care, including of hepatitis C A rise in alcohol misuse, lack, lack of poor health insurance, lack or poor health insurance and financial burden. One of the tests that we do in many physicians to for HTC screening is a FP. Um The uh one of its components shown in the middle section was earlier shown to uh be elevated in patients with HCC compared to other liver diseases uh such as cirrhosis, but also frequently um elevated in those with thrombotic diseases. Um on warfarin therapy. Again, cautioning the interpretation of this test. Further studies um have shown and this is the graph on the on the table on the right has shown that A FP um um is um ha has been elevated in in um patients who are pregnant. Uh those who have um also um uh embryonic malignancies, cholangiocarcinoma, viral hepatitis. Um Again, cautioning uh the interpretation of this test about one third of patients don't have an elevation on IFP. Um So the lack of absence does not mean that you don't have um liver cancer. And then when we look at specific values um pointing to, to the graph on the right uh uh T 20 mill 20 nagra nanograms per milliliter has been uh suggested or given a suspicion for HTC. And those over 400 are, are the ones that are likely related to HTC. But again, um it has to be interpreted in the context of the patient. It has overall a poor sensitivity and specificity as you can see here. Um But uh the current recommendations of using it as um a dual AC C um uh screening modality has come from this mean doubling time um study on the left where you can see that the uh mean doubling time was shown to be between 93 and 204 days, which is again why we do it now every six months. So indeed, um A FP is employed as a screening tool um every six months in combination with ultrasonography. And when you done that correctly, the mortality has shown to be reduced by 37% compared to um those undergoing no primary screening method. And, and this was done in a population with chronic Hepatitis B in Shanghai, China. Um if P alone, again, as I, as I've, as I've mentioned, um has its limitations, but it has also been associated to be correlated to response to taste treatment. Um And again, owing to the limitations, some of the investigators have now looked into other um, tumor markers to um for HTC for HEC screening here are um the specificity and sensitivity of DC P uh compared to a FPAFPL three, and a combination of A FP plus DC P. Um And in this shows that A FP actually was superior to the other tests. Um But uh the other um A FP FP has been um approved to by the FDA to use stratification, not uh for HCC surveillance in the US. But what about combining this test? So this is what uh the galle score does, which is made up of gender age, the A FPL three A FP and DC P um And this has been uh tested in a large phase three biomarker study that showed a sensitivity of 63% and a specificity of 85% um compared to A F which is higher compared to um higher than a FP alone. This was validated in Asian and European cohorts as well. And um the sensitivity also increases if you combine it with ultrasound, which is shown in the, in the bottom um graphs, you can see the barcode and which you can access um the scoring system online. Uh uh Your own uh with your own patients. When it comes to imaging, we know that MRI and CT are better than ultrasound. Um But when comparing MRI to CT, MRI has demonstrated a higher sensitivity of 82% compared to 66% of the CT. And there was no significant difference in the specificity of the uh of comparing the two. But the nice thing about MRI is that it allows for the application of the lyre system, the lyre score. Um This was fir first proposed in 2011 and it relies on basically the arterial organization of the nodules that HCC has and behaves as it is subjected to um dynamic phases uh during the MRI testing classification. Um uh it's here, you can see the classification system where um LR four makes us suspicious for HTC. And LR five is by itself a diagnosis of HTC. And it's the, it's about the only um cancer that can be diagnosed by imaging alone. But again, let's not forget about LRN, which is suggestive of malignancy, not necessarily being HCC. And this is often one that we need to biopsy to get an accurate diagnosis. So having an LR five lesion based on lyre system can then allow uh for the application of exception points towards liver transplantation, which is useful in those patients who have low male scores as they bring them towards the top of the list. Um The main criteria that we use in liver transplantation is called the mong criteria, which is um a single lesion, uh less 5 m, five centimeters or less or up to three lesions of three centimeters. Um or of less. And earlier studies show that the um Malign criteria sh had a survival uh of 75 for those who exceeded uh size limits. More recently, the um U CS F criteria was proposed for larger tumors and this involved a single tumor, uh less than uh 6.5 centimeters or less, um or three nodules of less than 4.5 centimeters or less or a total uh tumor diameter of eight centimeters or less. And um in this study, they actually showed that the um two year survival was 88% actually better than the lung criteria. And so that's something that we also use. Um but it's not read that, but it's not what we, it's not the criteria that we use for transplant. It is one that we use for a downstage and then I'll go over that in a second. But um the tumor size, the presence of vascular invasion, applicability of Mulan or U CS F criteria, liver function and overall performance. That is what I look for treatment ST stratification. And this is beautifully summarized in this BC LC criteria proposed by the Barcelona Liver Unit. This algorithm, it breaks down the tumor into the different stages, um associates them with the treatment recommendations at each stage. Um And also um importantly, takes transplantation into account, not only when it is um applicable at evaluation, but also when it can be applicable after downs staging or treating the lesion to bring it down to Mulan criteria. So if we start with the early lesions, treatment constitutes basically ablation or surgery. But again, it's important to highlight however, that the there needs to be a careful assessment of the um liver function prior to surgery of a patient. And again, this is best done by measuring the venous hepatic portal gradient or the HVPG that those with clinically significant portal hypertension or an HVPG greater than 10 millimeters, mercury are at risk for decompensation, post surgery. So in those who um undergo resection, the five year survival has been shown to be between 80 90%. Um compared to those who had positive margins, additional nodules or microvascular invasion on pathology. And when comparing the radiofrequency ablation to surgery, um the study actually found no difference in the median recurrence free survival though, um the study suggested that radio frequencies of ablation has a superiority to surgery because of lower cost, lower hospital stay and um uh lower um adverse effects. And this is particularly important for those lesions that are less than two centimeters in size. But when not a candidate for surgery, then we think about this other local regional therapies. Um Here. So I on the right, I'm showing um the diagram of several of them the trans embolization or the tae, what it does is that it basically blocks your blood supply to the tumor inducing tumor ischemia, taste or trans arterial chemo embolization releases an anti tumor drugs like liberal um to the tumor. And then the drug eluding bead um carrying doc um or the depta um adds additional DOXOrubicin in, in those, in those beads when we use atrium nine D loaded micro fears and those are loaded into the tumor that is was called trans radio ambulation or commonly known as Y nine D. Um And so, here on the left is the meta analysis comparing Y nine D um showing a superiority with a 26% risk reduction in death, 39% reduction in tumor um in in time to progression and a shorter hospital estate hospital stay. And so these therapies are actually becoming more common and are growing because they're known to cause a recruitment of anti tumor immunologic response with a significant increase in CD four CD, eight T cells um express expression of grand and B and A tumor infiltrating lymphocytes. And this is especially higher in those receiving selective internal radiation um compared to taste. So you can imagine that this modality is especially useful if coupled with an immune checkpoint inhibitor um in taking when trying to take advantage of the increased inflammation recruitment to the tumor um to achieve a higher anti tumor response. The original therapies that I have gone over um uh reduce uh uh um what we use to reduce the tumor burden with the goal of achieving Milan criteria and demonstrating as long as they demonstrate a three month stability um of the tumor burden. So this is what we call the downs staging. So, on the top, this is the result of the legacy study um which is, which was a multi center single arm uh retrospective study conducted at three sites where um patients with an HTC of eight centimeters or less uh received Y nine D um and this was done between 2014 and 2017. So um in anticipation of transplant. So, the objective response here was 88% with uh 62 of them receive um uh exhibiting a duration of response of at least six months and a three year overall um survival of 86 of those undergoing um resection after the Y 90 compared to 93% of those undergoing transplantation after the Y 90. Here on the left is this um is a study that was done in open label. Monte Center randomized control trial at nine Italian uh tertiary centers of patients outside Milan criteria and uh who underwent liver transplantation after downs staging. And here you can see that the five year survival was 77% in the group that ended up um going through the transplant, meeting the lung criteria versus 32% of the control group that were treated with local regional therapy alone again, suggesting an overall um a survival advantage by the dual therapy. But when we're looking at the recurrence posttransplantation, um they, we have identified ac um progression analysis, 53 components A F that's that predict re uh recurrence post transplant. That is the A FP list um level at listing the tumor size. Um and the number of tumors on the X plan. So on the right, we're gonna be focusing on the, on the graph on the right. Um Low risk patients are defined as the um so low risk patients are the ones who are meet melan criteria and have an A FP level of less than 100. Whereas the high risk has been defined as those with um being outside melan criteria and high and having an A FP greater than 1000. So here you can see that survival decrease as the rate of uh recurrence increase over time posttransplant, which is not surprising. Um And, but it's actually worse in the high risk um group uh represented by the dash line. So that's when we're then. So then the goal would be to restrict or reduce the A FP level. And this is something that we show here on this um uh on the middle graph where um the reduction of A FP to less than 500 by local regional therapy um in leads to um improvement in post transplant outcomes. And this arrival actually is, is even better with lower A FP uh levels as seen on the graph on the left um where the um the survival improves even more, even more with a FP, less than 100. So, um in this cohort study, um of five centers in the US, five academic centers, the five year post transplant survival is up to 74% if they meet within Milan criteria, a little lower to 68% if they're downstaged and 53%. Um if they're beyond Malone crit in the recurrence um was observed in 10% of patients within Milan. Uh 16% of those who were downstaged and then um uh um and then, um and then basically, when comparing the median survival to um put, so when comparing the median survival of different modalities uh in patients, different treatment modalities of patients who had recurrence after transplant. Those who had uh surgery in those recurrences had a better outcome with 31.6 months compared to 17. Um in the, in the ones who were treated with local regional therapy and those who were, who were treated with systemic therapy had a median survival um of 12.5 months, much less if you were made um comfort care. Uh So this is why the retreat score was implemented and taken into account again, the last A FP prior to transplantation um and the X plan characteristics which involve the microvascular invasion, the number of viable tumors on the X plan and the size of the largest lesion, the calculator again is shown here on the um on the barcode. Um And it can give you a, a score of 0 to 5 where um the there's a higher risk of of recurrence with the higher retreat score as shown in the graphs. Um And this is accompanied by a rec by the score is accompanied by recommendations of how soon and how often you should be um monitoring and doing surveillance on this patient's post transplant moving on to systemic therapy um applicable to those uh of advanced uh tumors of BC LC grade C and above summarize here for the longest of time, we were only relying on Sainib as the only option for treatment. But it has really been since the I am brave 150 trial that has since changed the landscape of systemic therapy and HCC uh which is also composed by I mean and checkpoint inhibitor. And the ones on the red you can see are the ones that have been approved for first line treatment for HCC. The ones in the yellow and the blue are still undergoing trials um uh as second line treatments. The but I think the more provoking question is the combination of immunotherapy and local regional therapy. Again, to take advantage of that increased anti tumor response induced by uh local regional therapy, particularly why Nandi here as exhibited by this study um is being studied in HCC and those who have advanced HCC um in combination with systemic therapy. And this study has show that that there is a higher median overall mortality of 19.8 months compared to um 9.5 months if they were receiving immune therapy or systemic therapy alone. But then the question really remains, is immune therapy um safe for downstage in anticipation for liver transplant. And the data for that is um scars, scars. Um So more data to come here. I mentioned a few clinical trials that are ongoing. Um uh for example, standard um Tezo standard of care systemic therapy, which is a tezo bevacizumab uh with anti um antibody called tulum. Um There's also a study of combination local regional therapy Y 90 with stride um chemotherapy is stride systemic therapy. Uh Y 90 combination with Derval A and then um there's also a combination of Derval up SAB um as a potential systemic therapy. Um also not forget about car T cell therapy being um studied as a potential um therapeutic option for those with um HCC. So more possible therapies for HCC to come now switching gears to cholangiocarcinoma. Um It is a devastating malignancy of the biliary epithelium um characterized by dismal uh survival partially um owing to the to the fact that it's a very difficult, it's very difficult to diagnose. The different subtypes, depend on the location along the biliary tree with the distal beam in the common bile duct. Um the peri Hyler be between the cystic duct and the first order and the second order of bile ducts and then intra b. Um uh in this in being beyond the the ducts, male sex age, um older age, especially if it's over 70 has been found to be an associated risk factor. But also those with PSC, particularly for periyar cholangio and Corollas disease, particularly for intrahepatic cholangio has been associated with a risk to um developing cholangiocarcinoma. The mortality of um of combined all types of um subtypes of cholangiocarcinoma worldwide is the highest, it has been the highest in Thailand, China and South Korea. But again, notice that in the US, we're not immune to it and the mortality has increased over time with the latest b uh of 2.07 per 100,000. It's 22.2 0.05 in uh per 100,000. Um a year diagnosis as I told you is very difficult to diagnose. So, um here I sh so the MRI of a patient of mine who has very high um Choline and here you don't, again, you don't see a mass. Um Th this is somebody who has a um significant enhancement and thickening of his bile ducts um and work up for uh peri Haller. Um really, really relies on cytology and fish to help uh define a diagnosis. They're also um you can also do with a, obviously, those are things that you get through in, er CP. And here in the, er CP on the right, you can see this narrowing of the bile duct at the site of the malignancy. Um And again, so, cytology showing adenocarcinoma um is um helpful but also coupled with fish, uh showing polysome CN 99 is a biomarker for cholangiocarcinoma that has shown very variable sensitivity and specificity despite like different levels of CN 99 making this really not much of a reliable test. So again, one also needs to interpret in the context of the patient because it has also been found to be elevated in other conditions such as cholangitis, um other malignancies such as pancreatic cancer, pancreatitis, um and some uh post endoscopic procedures. So, again, needs to be taken into context and then understanding the limitations of cytology and fish um as well as the of CN 99. And knowing that about 20% of patients with malignant strictures um are having determinate findings because of sampling. Um it's not able to be done through the er CP. Um Some of the there's a study here um done um trying to see if a tri modality is better uh diagnosis or has a higher sensitivity and specificity in diagnosing cholangiocarcinoma. And, and you can see that the tri modality was better in the overall cohort. Um And the tri modality involves fish cytology and transpire biopsy. All of them obtained through er CP. But um notice that in the PSC group, there really wasn't a difference, a significant difference um between the um the dual modality of fish and cytology compared to the tri modality. Um So it increases it, it makes it better, but hasn't shown a significant difference in those with PSC. Not to mention that biopsy of the actual mass should not be done. And this is because as you can see on this table, it has been associated with um peritoneal seeding leading to metastasis at um that were found at staging procedures. So, um and this is regardless whether they were done E us guided or transferred to. And again, even if you were to find a bi uh even if you were to get a bi a biopsy, these tumors have um significant heterogeneity among uh patients. Um they're very fibrous. So, again, the diagnosis is not straightforward for these tumors. Liver transplantation was proposed by the male group um for the Peri Hydro Cholangio. Um And this was done in the early 19 nineties. Some of the first cases were done where they um whereby the tumor of two centimeters of less in diameter periyar um is subjected to neoadjuvant um chemo radiation. And um if they don't have evidence of local spread or extra hepatic disease at staging laparoscopy, they are then approved for liver transplantation. This is something that uh patients now get exceptions points for again, provided that they don't have um evidence of advanced disease here. Um I'm presenting the mayo experience um showing the 73.5 73 per uh 73% 5 year survival in those who underwent transplantation compared to 17% who underwent uh resection alone for intra diabetic um Cholangio carcinoma. Um Actually let le let me back off. So thi this actually prompted uh centers to um to try this themselves and apply their own version of the Mayo Protocol. Um And this is what has allowed a um international study to be done. Uh Looking at eight centers in North America, nine in Europe uh where they demonstrate that there is a significant higher five year survival uh of those who underwent live compared to those who underwent resection again after undergoing the male like protocol. Um And uh and also a five year disease free survival of 50% in the transplant group compared to 17% of those who underwent resection. So better outcomes and again, for intrahepatic cholangiocarcinoma, it has, it's, the data is a lot more, is a lot more difficult to gather. Um And much of the data comes from retrospective studies of incidentally transplanted Cholangio. But this study actually um was done in Italy uh performed prospectively. It was a case series of 21 patients who had locally unresectable endure hepatic cholangio. They underwent liver transplantation between 2010 and 2017 after having um a um neoadjuvant therapy of gene cabin based systemic therapy, second line treatment or local regional therapy. And that was at the discretion of the center. And so this shows, um and obviously, they had to show a stability of six months. So this graph shows that the three year overall um survival was 83% 83 and, and five year survival was 83%. Um And and this is um this is compared to those who did not undergo um transplantation again, suggesting that if patients are, are carefully selected, they uh may also um have successful liver transplantations for those who um are on res have unresectable tumors and are not amenable for transplantation. Systemic therapy is then the next step. Gyri cys Platin Andom A is the first line. Um Currently for um for cholangiocarcinoma is a two year overall survival of 54% compared to 47 in those who received inside Ave and Platin alone. And um they also have a higher uh progression free survival of seven months compared to 5.7 months um in the triple therapy compared to the dual therapy. Now, um Pembrolizumab is the list to be um is the last to be um approved and in combination with gemcitabine and CISplatin. Um This was approved in November of this past year, uh showing a higher median overall survival of 12 months compared to 10.9 months um alone. And then the other thing to note is that next generation sequencing allows us um is usually recommended because it allows us to find this unique mutations that tumors may have, which then we can apply targeted therapy to uh uh if patients have an I DH one mutation, we can um we can um treat them with vain or FGFR two. PIB or Infi gratin can be used for their cholangiocarcinoma. There is more studies that are underway. Um more biomarkers that are being studied particularly CT DNA or circular tumor, uh DNA for the purposes of early diagnosis um or, or I identification of targeted therapy, but studies are underway. So here I wanna actually highlight two studies um that are ongoing out of the many that are ongoing. Here is the I am brave only because it's sort of like a cousin. Uh The I am brave 150 for the HCC therapy. And um and this one, it basically uses the um the TE A applicable to HTC combined with GSIS, which was the previous backbone for um cholangiocarcinoma and um results so far um show that uh there is a better improvement in the progression free survival of 8.4 months compared to 7.9 months if they were only receiving uh GSIS with a TESOL alone. Um And then the, the safety profile is OK, it's manageable as they are reporting the immediate overall survival has, has not been breached yet. And the, the study is still ongoing to be able to report that. So that's underway. The other one that's also underway is the Tomalin study is currently enrolling. Um Basically, it's a, it's a phase three single arm open label multi center study. Basically looking at a combination of to follow up with gym Cyan based therapy. And here you can see the different permutations of it. Again, it is currently enrolling. So more, hopefully more therapies to come for cholangiocarcinoma last but not least. Um I wanna talk about metastatic colorectal cancer, which is the latest um tumor that we're doing transplantation for. Um and surely it's causing um a good amount of debate. We know that metastatic is that colorectal cancer in itself is the third leading cause of incidence in the world and the third leading um cause of mortality also in the world that it is more common in men over women. And it's also more common in developed countries. We can see here um ourselves where we put, we you were here towards the top and we know that liver are the most common sites of metastasis. And when it does happen, they have a two year old uh median overall survival that has been um reported to be of about 10%. So there's definitely a need for neurotherapy in patients with metastatic colorectal to the liver. So, until recently, um liver resection was considered the only curative treatment, had a five year overall survival of about 30 to 50%. And this is again, surgery to the liver metastasis. Um And, and then it obviously with this, a lot of the patients ended up needing palliative therapy as well. But um comparing um but what about doing surgery um uh with chemotherapy with preoperative chemo. And so this study showed that um there is really no difference, no difference in the overall survival undergoing surgery versus preoperative chemo. Um And then, um and, and this is the preoperative chemo was a fox based chemotherapy. OK. So the, the o the there was a little bit of a better advantage in the ones um of a preoperative uh of those who are going preoperative che chemo. But again, it was not significant. But what about if we use chemotherapy to downstage um the tumor prior to surgery, um sort of like what we use on Milan uh for ML criteria in HCC. And um here we can see that um that this, uh this study again showed no significant difference in the overall survival at three years. Um However, the progression free survival was higher in the group um that um had a pre uh that had neoadjuvant therapy with 53% of tumor free recurrence um at 34 months compared to 28 in the group that underwent primary resection. Ok. What about liver transplantation? Is that something that we should be doing? Um So here is uh this was a pilot study. It was published on um patients in Norway undergoing liver transplantation for unresectable colorectal um liver only metastasis, 21 of them had the liver transplantation. This is um um sorry, this is the data for the, for the, for the, for the downs of the chemo. And again, this is where we show that we show that there's no significance in the overall survival but the progression for survival. But here, um this is what I wanted to get at, which is the se um group compared to the Nordic group. The second group is the ones who underwent liver transplantation. Um unreceptable metastatic colorectal compared to the Nordic group, which was basically um a um is a phase three trial um of uh of uh flux based therapy um in different combinations um in the treatment arms but none of the arms showed a significant difference compared to each other. So, comparing the data of this Nordic study or this Nordic group with the SECA group, uh who underwent liver transplantation showed that there was a um significant um uh difference in the um overall median overall survival being 32 months in the second group compared to 21 months in the Nordic group. Um So when with this in mind, a higher number of transplant centers have a number of transplants have been done since then and have been enrolled uh within a basically demonstrating that um that there is a significant improvement in in survival if the tumor maximum tumor diameter is less than 5.5 centimeters if the ce a level is less than 80 if the time to transplantation is less than two years and there is no progression of disease. And this is what it amounts to the Oslo score that is stratified. Um Here on the right between zero and four, whereby the um median overall survival for um Oslo score of 0 to 2 is a 63% at five years compared to um compared to a um uh 8.3%. Uh if the score is 3 to 4, so, significantly better additional uh predictors um have been identified. And these are the um uh uh having partial response to undergoing therapy um or demonstrating stable disease. Also a diagnosis uh a time from diagnosis to liver transplantation of three years or more. Um a um a mean tumor Valium which is measured by pe T scan of being less than seven centimeters mercury and no more than or nine I. So, less than nine lesions in the liver have also been associated with better outcomes. It also um has been interested to show that the site of the primary cancer, whether it's left side colon or, or a um or right side of colon does um have a um suggestion of prognosis being that the right side of colonic tumors have a poor prognosis compared to the ones on the left. Also, the ones who um have M si high and RB patients have also been shown to be to bear poor prognosis. Um But again, even on this study, when comparing right sided tumors to left sided tumors, uh there, the, the response to systemic therapy was significantly better in those who had left sided tumors compared to the right side. And the in the US, the data is evolving, um There's a few specialized centers that are carrying transplantations for this disease. Um making about 1 to 2% of the yearly transplants that have been done so far. Um since so, looking at data from 2017 to 2022 about 64 transplants have been done in the US. Um of those 71 sorry, 12.5% were removed or those who underwent the evaluation, uh 12% were removed from the list. 10% is still um on the list uh at the time that this um analysis was done um uh a good amount underwent a living donor transplantation. Um The three year o overall survival was um 60% in those uh with. Um and uh and those who had a a um disease for survival also of um 50% at three years, which is comparable to the outcomes uh shown by a hepatic and hydro cholangiocarcinoma. Uh which is why now there is um a little bit of debate about these patients also receiving exception points. Um And there is a working group that is trying to um to make this possible nationally um uh for the for, for the liver review. But um so there is something important to mention is that again, like I said, there's no exception point. So how are the livers being obtained? And how are patients being transplanted? Uh They rely on donor um giving donors or discarded livers that prove their intact function when they're placed on nother machine perfusion and a large number of transplants are also done that way. But how can primary care help? Again, we know that the liver cancer burden in the world is growing currently being six and the most commonly diagnosed cancer there um being the most common cause of their death in, in over 40 countries. And um and again, it is expected to increase by 55% by 2040. So in the US, the most common ideology of those with HCC of liver disease in those with HTC is smash which is metabolic um associated dysfunction of um C hepatitis, formerly known as S NASH. This is expected to increase over time owing to the growing epidemic in obesity. Uh But important to note that those um F three fibrosis or more should be undergoing HCC screen every six months, just like the patient with cirrhosis because they have shown as it's shown in this graph that there are a particularly increase of developing HCC over time. I I wanna take the opportunity to also um talk about res meter or mention, Res Meron, it was just approved. This past Friday is the first medication approved for mass treatment which has shown to not only decrease um cytosis but has uh for the first time uh shown a decrease in fibrosis. So again, in the primary care uh setting, you know, addressing obesity and addressing MS is uh optimal and maybe with medications such as Rome Rosmarin being approved, the decrease in the incidence of uh sorry, the incidence of HC may decrease over time. Uh Primary care can also ensure that and surveillance is done in for hepatitis um in those with hepatitis B and have a uh surface antigen posi positivity and have cirrhosis or are Asian or African men age um greater uh of 40 above. Um those who are also um Asian females greater than um age of 50 have a first degree family member with a history of HTC or have a Hepatitis Delta co infection should undergo um regular HC uh HCC surveillance. Let's also let forget about hepatitis C, those with hepatitis C cirrhosis, regardless of their SVR status should undergo, um should continue to undergo um HTC screening. Um And you know, they're still questionable about doing HC screening those with F three fibrosis and hepatitis C. The data is mixed um has shown here, I can show you the latest one showing that the incidence of HC is not as high. Um that is not cost effective. But again, um there the the data is mixed and I still think that there needs to be more studies to further risk stratify those with advanced fibrosis um in hepatitis C because we do see um liver cancer in them as well as far as Cholangio carcinoma. Here, I'm showing the diagnostic approach algorithm for those with PSC as well. And this is on the guidelines and the AC LD guidelines. You can refer to uh where those with PSC should be going um surveillance with MRI MRCP yearly to screen for Cholangio. It's important again to remember to not biopsy. The lesion obtain cytology and fish at the time of the A RCP and then refer to a transplant center um whose experience in the transplantation for in the care of Cholangiocarcinoma, um the best mode of therapy for these patients. And I'll give this similar message uh when it comes to transplantation or when it comes to patients with metastatic colorectal carcinoma to the um to the liver. Um I have gone over the Oslo score here with you again. Um But, but, but it's not as simple as this. It does require multidisciplinary um care and expertise for this uh for this disease which is done at a handful of uh transplant centers in the US. Um And um uh for evaluation, I'll say that here, I was u we have um expertise in all the three tumors that we have. That I have discussed here. So if there's any um evaluation that you need, please feel free to refer to us. And again, um I really wanna thank you for having me here and um discussing this very important topic with you. Thank you. Thank you. Um It looks like recommended surveillance for PSC was one of the questions. Yeah. And um so here is uh let me see if I can go back. Um But um this is the algorithm and you can find it on the A SLD website. Um The, the, if they have PSC alone, the recommendation is to do um yearly MRI at least um depending if there's any lesions, you may choose to do it sooner. Um And obviously, if they have uh cirrhosis associated with it, then you also need to do HC screening um as well. And she actually said you already answered it. So it's just a reminder, refresher, sure anybody else have any other questions and if not um feel free to email me any questions and I'm happy to get those to Doctor Ortiz. So thank you so much for presenting all wonderful information. Thank you for having me. Created by Presenters Vivian Ortiz, MD, FACP Assistant Professor of Medicine, Gastroenterology View full profile
