Podcasts about child pugh

Drs. Shaalan Beg and Rachna Shroff discuss key abstracts on GI cancers that were featured at the 2024 ASCO Gastrointestinal Cancers Symposium, including SKYSCRAPER-08, EMERALD-1, and NEST-1 in esophageal squamous cell carcinoma, hepatocellular carcinoma, and colorectal cancer, respectively. TRANSCRIPT Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I'm an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. Today, we'll be discussing key abstracts and other exciting highlights from the 2024 ASCO Gastrointestinal Cancers Symposium. Joining me to discuss some key takeaways from the meeting is the chair of this year's Symposium, Dr. Rachna Shroff. Dr. Shroff is the division chief of Hematology Oncology and chief of GI Medical Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for clinical and translational research at the University of Arizona College of Medicine – Tucson. Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Dr. Shroff, welcome back to the ASCO Daily News Podcast, and congratulations on a great Symposium. The scientific advances and innovative, multidisciplinary approaches that were featured throughout the meeting were really inspiring and reflect the incredible strides we're making in GI cancer research. Dr. Rachna Shroff: Thank you so much for having me back. I am delighted to be here.  Dr. Shaalan Beg: Dr. Shroff, the theme of this year's symposium was "Taking Personalized Care to the Next Level." I'd love to hear your reflections on the sessions that you found most exciting and really resonated with the attendees.  Dr. Rachna Shroff: Yes, thank you. We were really excited about this theme because we really felt that “Taking Personalized Care to the Next Level” translated to thinking through personalized approaches to patient care, not just in the traditional ways that we think of with precision oncology and genomics driving our care, but also how we can think through multidisciplinary approaches and an individualized care plan. Thinking through how artificial intelligence and novel clinical trial designs can and should be implemented to meet the needs of our individual patients. And so we really highlighted that in what was a somewhat new reboot of a session called “Intersections,” which were every day and were really more cross-tumor; they were tumor agnostic but were thematic focused. As I mentioned, those themes were really based on feedback that we had from prior attendees, as well as from the program committee's feeling on what are really the questions that we are dealing with and that are burning in the clinic today and that includes the emerging role of artificial intelligence and machine learning and how we integrate that into our clinical care, approaches to oligometastatic disease, and it's not really just something that we think of in colorectal cancer but haven't fully used that paradigm to really apply it to other GI malignancies. And then the art and science of clinical trial design where, again, traditional randomized phase 3 trials might not be the best and most innovative and most expedient way of bringing novel therapeutics to our patients. And so, I thought that all of those sessions were really highlighting different important topics that we deal with day to day. Additionally, we had a really fantastic keynote lecture from Dr. Kimmie Ng of the Dana-Farber Cancer Institute. She is a world-renowned expert in the early-onset colorectal cancer space, and the timing of her keynote was perfect with the new cancer statistics that came out literally days before GI ASCO that demonstrated this just dramatic rise in early onset GI malignancies as a whole, not just colorectal. And she spoke really in a comprehensive manner not just on clinical approaches, screening approaches, and how to find these patients at an earlier stage, but also kind of gave us a call to action, if you will, in terms of public health initiatives, as well as like I said, clinical care and really thinking outside of the box for how to reach these patients.  And then, of course, we always have what I think is one of my favorite aspects of the meeting, which are the networking opportunities that include the Trainee and Early Career Networking Luncheon, the Women's Networking Reception, and the Meet the Experts Luncheon where, especially as junior career investigators, you have an opportunity to meet what we think of as the “big names” in GI cancer. Dr. Shaalan Beg: Absolutely, I remember my first couple of GI ASCO meetings and those were probably the most memorable sessions that I attended as junior faculty as well.   So let's take a deeper dive into some key abstracts from the meeting. I'd like to begin with Abstract 245. This is the SKYSCRAPER-08 study. It's first-line tiragolumab and atezolizumab with chemotherapy in an Asian patient population with esophageal squamous cell carcinoma. What are your key takeaways from this study?  Dr. Rachna Shroff: Yeah. This was an exciting study in my opinion in the sense that thinking through how we can build on immunotherapy backbones is obviously a pressing question across the GI cancer space. So this was a phase 3 randomized, double-blinded, placebo-controlled trial that looked specifically at patients with esophageal squamous cell carcinomas. And the study was enrolled fully with an Asian population. It looked at taking the traditional chemotherapy backbone and adding to it an anti-PD-L1 with atezolizumab and an anti-TIGIT with tiragolumab. Again, that proof of principle of using anti-TIGIT and PD-L1 has been looked at across a lot of different GI cancer spaces and we know that the esophageal squamous cell cancers tend to be very immunotherapy responsive. So this was a really important question.  This involved a number of patients, a little over 460 patients, who were randomized one-to-one to receive the tiragolumab with atezolizumab with the standard paclitaxel and cisplatin, that's used for esophageal squamous versus chemotherapy alone with placebo. And the primary endpoint was independent review of progression-free survival, and overall survival. And so, out of the 461 patients randomized, there was at the primary analysis, a median improvement in progression free survival, from 5.4 months in the control arm to 6.2 months with a tira-paclitaxel plus chemo arm with a hazard ratio of 0.56, highly statistically significant. Similarly the median overall survival was also improved from 11.1 months to 15.7 months again with a hazard ratio of 0.7 and some of the other key efficacy endpoints were also improved with the addition of the anti-TIGIT PD-L1 approach. And importantly, there was not really safety signals that jumped out at us.  And so, to me, what this means is that, in our patients with esophageal squamous cell carcinoma, we really should be thinking about chemotherapy with immunotherapy as a backbone and how we can build on it. And, you know, I would imagine that it's hard to argue with both the PFS and OS endpoint that adding anti-TIGIT won't necessarily be kind of the new approach to these patients. And importantly, I'll point out that it seems to be a benefit across the subgroups, including PD-1 status, which is always our big question here. I think the only thing to keep in mind is this was an all-Asian population and whether or not that kind of immune profile of the immune responsiveness is different in those patients, but regardless, a positive phase 3 trial. Dr. Shaalan Beg: It's really exciting to see immune checkpoint inhibitors or immunotherapy beyond PD-1 targeted, CTLA-4 targeted treatments making their way into GI Cancers.  Dr. Rachna Shroff: Absolutely. Dr. Shaalan Beg: Sticking with the immunotherapy theme, let's focus on hepatocellular carcinoma. So LBA432, the EMERALD-1 study of transarterial chemoembolization combined with durva with or without bevacizumab looked at people with unresectable hepatocellular carcinoma eligible for embolization. So really a highly anticipated study, I'm wondering what your thoughts are and whether it'll be practice-changing for this field.  Dr. Rachna Shroff: I was excited to see the press release when it showed that the study was positive, and I think it's because now that we're using immunotherapy in the advanced HCC space, our obvious question is, can we integrate it into multimodality approaches? There are a lot of smaller studies looking at neoadjuvant IO approaches, and in this intermediate stage, unresectable hepatocellular carcinoma patients. We wanted to know if there was a utility to liver directed therapy with immunotherapy.  So, this was a large study. It was a global study looking at unresectable HCC with preserved Child-Pugh function. But it was Child-Pugh A and up to B7, importantly. And there were 616 patients randomized in a 1:1:1 fashion, with the control arm being just TACE alone. But then, there was also an opportunity for durvalumab with TACE, as well as durvalumab plus bevacizumab with TACE. The patients would receive durvalumab during their TACE treatments and could receive up to four TACE treatments and then subsequently were either continued on durvalumab alone, durvalumab plus bevacizumab, or the placebo. The primary endpoint was progression-free survival, powered specifically to look at TACE versus durvalumab plus TACE. In this study, the primary endpoint was met with a significant improvement in PFS. Median PFS was 15 months versus 8.2 months, with a hazard ratio of 0.77. Most prespecified subgroups demonstrated this benefit.  Importantly, there was a secondary endpoint looking at durvalumab plus TACE versus TACE alone, and that actually did not show a statistically significant improvement in median PFS from 8.2 months in the control arm to 10.0 months. The overall response rates were slightly higher with the durvalumab plus bevacizumab approach at 43.6%. And importantly in these patients, who oftentimes have a higher burden of disease in the liver, median time to progression is a really important and clinically meaningful endpoint. That was 22 months with the durvalumab plus bevacizumab and TACE versus 10 months for TACE alone. I would just point out that the overall concern we always have with bevacizumab is the increased risk of bleeding and the treatment-related adverse event profile. Overall, there were no safety signals that emerged from this, with nothing that really, especially in that bleeding risk category, jumped out at us. Of course, we haven't seen the overall survival data yet because we have not seen enough follow-up to really see that number.  I do think that this is potentially practice-changing, and I think it just demonstrates that there's probably some synergy between anti-VEGF with anti-PD-1, and then the liver-directed treatments. The obvious question for us in the United States is that the vast majority of people are moving away from TACE and towards more radioembolization and what can we extrapolate from this? Does this really tell us much if people are using more of a Y90-based approach? I think those are a lot of the burning questions that most of us have.  Dr. Shaalan Beg: Yeah, and it's a very interesting direction that the HCC space is taking because we heard in previous meetings, the role of PD-1 inhibition as adjuvant therapy after resection. Now, we have data for local-regionally advanced disease over local-regional treatments. And of course, you already mentioned the data for more advanced disease. So it sounds like immunotherapy may be impacting the management of anyone diagnosed with hepatocellular carcinoma.  Let's talk about the MONET trial, Abstract 249, which compared thoracoscopic esophagectomy and open esophagectomy for thoracic esophageal cancer. Do you think this is a study which may influence the treatment of patients with thoracic esophageal cancer? Dr. Rachna Shroff: So, this was, again, I think, a really important question. It was a randomized, controlled phase 3 trial comparing a more minimally invasive approach with TE — thoracoscopic esophagectomy — versus an open approach. This had patients with clinical stage 1-3, excluding T4 thoracic esophageal squamous cell carcinomas. They were randomized 1:1 to the open versus the TE approach, with a primary endpoint of overall survival and an important secondary endpoint of relapse-free survival. 300 patients were randomized, and at the second planned interim analysis, the median follow-up was a little over two and a half years. The 3-year overall survival was 82% in the TE group versus 70.9% in the open group. The DSMC of this trial actually recommended early termination based on the non-inferiority, which is what they were specifically looking at. There was a very statistically significant one-sided p-value for non-inferiority.  Importantly, the 3-year recurrence-free survival was also markedly better in the TE group versus the open group, with no real notable differences in R0 resection, or a large percentage of patients who needed to be converted from a TE to an open approach, and really not any significant difference in overall postoperative morbidity. I think this just supports the concept that minimally invasive approaches for our patients with GI malignancies can and should be considered. Again, esophageal squamous because they tend to be seen a lot more in Asia, this study was conducted in Japan, but I think that being said, a lot of our surgeons in Europe and in the U.S. are also very amenable to minimally invasive approaches. And I think this just supports the fact that an open approach is not necessary. So, I would think again, that this is something that is implementable and I think will affect the field.  Dr. Shaalan Beg: Moving on to metastatic cholangiocarcinoma, there have been many FGFR inhibitors that have shown activity and promise and are approved for the management of cholangiocarcinoma with FGFR alteration. But at this ASCO GI, we heard the results of the safety and efficacy of an FGFR1, 2, and 3 inhibitor, tinengotinib, as monotherapy for advanced metastatic cholangiocarcinoma (Abstract 434). How do you see this fitting into the broad picture? Dr. Rachna Shroff: Yeah, so this was highly anticipated data, primarily because at this point, the FGFR space in cholangiocarcinoma is quite crowded. And so a lot of us were getting sick of the "me-too" drugs. What is really unique about tinengotinib is that, not only is it a selective multikinase inhibitor, but it also, in preclinical models as well as in early phase one trials, demonstrated potent inhibition of patients with FGFR2 fusions and rearrangements who had acquired resistance mutations. So, as we better understand the first generation of FGFR inhibitors and note the resistance mechanisms, these drugs are now being developed to try to circumvent or overcome those.  This study looked at 4 different cohorts: 1 cohort with FGFR2 fusion patients who had primary progression who never responded to FGFR inhibitors, a second cohort with FGFR2 fusion patients who had progression after primary response, so those with acquired resistance, and then there was non-fusion FGFR alterations because we do know that a number of cholangiocarcinoma patients have other FGFR alterations that are not fusions, and then those with FGFR wild-type. The primary endpoint was objective response rate, with a total of 48 patients enrolled across the four cohorts. And so the 40 patients who were evaluable in the group that had primary resistance, which was the first cohort, there was a response rate was 9.1% and that was partial response, and 31% had tumor reduction with tinengotinib. And similarly in those with acquired resistance, 37.5%, 3 out of 8 patients had a partial response and tumor reductions were noted with an overall disease control rate between those patients with FGFR2 fusions of 94.7%, between those with primary and secondary resistance.  In the patients who had FGFR alterations, there was 3 out of 9 patients with a partial response and again, tumor reductions were notable across the board and the disease control rate was 88.9%. The FGFR wild-type group, not surprisingly, did not see any partial responses, but interestingly, 75% of these patients had at least disease control, and the median progression-free survival was 5.26 months, again, kind of most notably impressive in the 2 cohorts that included FGFR2 fusions. The toxicity profiles are what we come to expect for FGFR inhibitors and we've gotten better at managing those and mitigating some of those so there was really nothing to jump out there. So there is now an ongoing randomized phase III trial specifically looking at tinengotinib versus physician's choice in patients with FGFR2-altered cholangiocarcinoma after having received prior FGFR inhibitors. So that's where I think it's in is for those of us who know that there are multiple drugs in the space, our big question is can we sequence through that? Can we offer multiple FGFR inhibitors in these patients? And I think we are all eagerly anticipating this data as well as the subsequent data to really justify the use of these novel second generation FGFR inhibitors.  Dr. Shaalan Beg: It's been fantastic to see the evolution of these compounds in precision medicine, or precision oncology at its finest, in terms of understanding mechanisms of resistance and treating refractory disease.   Let's focus on colorectal cancer. I'll tell you, there has been a lot of discussion, Dr. Shroff, on social media, on insurance companies sometimes rejecting one biologic or the other based on tumor sidedness. We have talked about tumor sidedness predicting response on this podcast based on data from previous studies. But this year in GI ASCO, Abstract 207 explored the role of tumor genomics and tumor sidedness and they said that it's tumor genomics, that tumor genomics better explains the differences on outcomes, and it explains it better than sidedness. What does this mean to the field? Because a lot of professional organizations have guidelines that are asking people to now incorporate sidedness. So how does that change based on these results? Dr. Rachna Shroff: I really commend these authors on leveraging real-world data, and I think we're getting better and better at recognizing that real world data actually informs our clinical decision making, possibly better than sometimes some of these studies that lead to the guidelines and algorithms that we develop. So this is a perfect example of a little bit cart before horse in trying to understand the way that sidedness and genomics may interplay.   So this was a study that basically leveraged both the Foundation Medicine and Flatiron Health clinical genomic database and looked at patients with microsatellite stable metastatic colorectal cancer. There were a total of 3,845 patients included in a kind of two-thirds one-third split between left sided and right-sided colorectal cancer. And they found the typical genomic alterations that historically have been thought of more with left-sided colorectal cancer like APC and then more of the RAS BRAF alterations in the right-sided patients. But I think what they really thought and what I think was remarkable is they really looked at the patients and how they received chemotherapy with anti-EGFR or bevacizumab therapies, and they did a multivariate analysis to really see what is driving outcomes. And like you mentioned, what they found was patients in the RAS pathway, those classified as having alterations in the RAS pathway, had less favorable outcomes, while those with APC altered group had more favorable outcomes. And that was regardless of treatment received and sidedness.  And so when they did an analysis of what was called a “likelihood ratio test,” they found that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction, but not when sidedness was added to genomics. Like you said, it kind of demonstrates, at least in this mining of real-world data from Flatiron that tumor genomics is probably a better driver and a more important driver in determining outcomes than sidedness.  I totally agree with you. I would push for us to really kind of bring a little bit of noise to this and to make insurance companies and other companies that are looking at this to think through this a little bit more and make sure that we're putting all of the data together in a comprehensive passion before making the treatment plans and determinations. Dr. Shaalan Beg: The last abstract I'd like to ask you about is Abstract 117, the NEST-1 trial. This study looked at neoadjuvant botensilimab and balstilimab for resectable mismatch repair proficient and deficient colorectal cancer, both MSS and MSI. What are your key takeaways from this study?  Dr. Rachna Shroff: This is another study that is demonstrating that there may potentially be a role for immunotherapy in microsatellite stable patients. I will make the caveat that this was a single-arm study that really was looking at feasibility safety, with efficacy as a secondary endpoint. The combination of bot-bal in the neoadjuvant space for colorectal cancer patients, they received one dose of boten and two fixed doses of bal two weeks apart and then were taken to surgery. They limited the number of patients and out of the 12 patients that were enrolled, they limited the number of mismatch repair deficient patients. So to your point, they allowed both, but they wanted to make sure it was not just MSI-high patients. What they basically found is that it was safe and did not delay surgery or increase risks of adverse events. But importantly, there was significant regression of tumor noted. And some interesting spatial biology analyses demonstrated potentially novel mechanisms of action, especially in the MSS population, and that ctDNA reductions correlated with pathologic response. There were a lot of different things that they were looking at, basically suggesting that bot-bal is safe and can be used in both mismatch repair–deficient and proficient patients with colorectal cancer. And now importantly, they've added some additional cohorts and expanding the study. As I mentioned, this is right now just 12 patients, but does definitely have a provocative result.  Dr. Shaalan Beg: Thanks so much, Dr. Shroff.  Finally, the role of cell-free DNA (cfDNA) in GI cancers has been an exciting and important development in our field. There's tremendous data that emerged at the GI meeting, and we have decided to do a separate ASCO Daily News Podcast dedicated to ctDNA. So listeners, please look out for our coverage of key studies on ctDNA in GI cancers very soon here on the ASCO Daily News Podcast.  Many thanks, Dr. Shroff, for sharing your insights with us today and for your great work in building a robust GI meeting this year. Thank you very much. Dr. Rachna Shroff: Thank you so much. Dr. Shaalan Beg: And thank you to all our listeners for your time today. You'll find links to the abstracts discussed on the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Our guests on this podcast express their own opinions, experiences, and conclusions. These statements do not necessarily reflect the views of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an endorsement by ASCO.   Find out more about today's speakers: Dr. Shaalan Beg @ShaalanBeg Dr. Rachna Shroff @rachnatshroff   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals   Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics

Accelerators co-host Dr. Matt Spraker hosts Radiation Oncologists Drs. Krish Jethwa, Neil Newman, and Jeff Ryckman for romp through the exciting world of radiotherapy for liver tumors! In the first of this two part episode, we Krish, Neil, and Jeff explore how liver tumors are treated in practice. We learn that Jeff can tell your Child-Pugh score by looking at your finger nails and other tips that can help with patient selection. Then we have a fantastic data-driven discussion on treatment planning. We also cover motion management and delivery. Toward the end, we approach the topic that inspired this episode, comparing SBRT with catheter-based therapies. Like Krish, we all want to know: will Neil "let it fly" on why SBRT should be the therapy of choice? Tune in next week to find out.Here are some things that were discussed doing the show:Dr. Newman's epic Twitter thread on TACE versus SBRT for HCCThe liver has a body - a Cook's tour by Adrien RubenDr. Zaorsky's Liver Anatomy Explained Using Your Right FistBujold et al., phase I and II studies of SBRT for HCCRitter et al., Application of Critical Volume-Dose Constraints for SBRT in NRG TrialsDawson et al., Individualized image guided iso-NTCP based liver cancer SBRTDawson et al., Partial Irradiation of the LiverPodcast art generously donated by Dr. Danielle Cunningham. Intro and Outro music by Emmy-award winning artist Lucas Cantor Santiago.The Accelerators Podcast is a Photon Media production. 

In this podcast episode from Clinical Care Options (CCO), Heinz-Josef Klumpen, MD, PhD, and Chris Verslype, MD, PhD, discuss challenges in selecting and sequencing therapy for patients with advanced hepatocellular carcinoma. Topics include:Factors to consider before selecting frontline immunotherapyRole of TKIs in the frontlineImpact of Child-Pugh status on the efficacy of immunotherapy/VEGF inhibitor combination therapyReal-world evidence on frontline immunotherapy/VEGF combination therapyFactors to consider when selecting second-line therapy including the role of TKIs and planning for multiple lines of therapyPresenters:Heinz-Josef Klumpen, MD, PhDStaff Specialist, Medical OncologistDepartment of Medical OncologyAmsterdam UMCAmsterdam, The NetherlandsChris Verslype, MD, PhDProfessorClinical Digestive OncologyKULeuvenHead of ClinicHepatologyDigestive OncologyU.Z. LeuvenLeuven, Belgium

Dr. Shaalan Beg, of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Science 37, discusses hot topics in GI oncology, including KRAS wild-type pancreatic cancer, the SURF-Cohort trial in hepatobiliary cancer, and key studies in gastric cancer featured at the 2022 ASCO Annual Meeting.  Transcript ASCO Daily News: Hello and welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Shaalan Beg, who is an adjunct associate professor and gastrointestinal (GI) medical oncologist at UT Southwestern Harold C. Simmons Comprehensive Cancer Center.  Dr. Beg also serves as vice president of oncology at Science 37. Dr. Beg will be telling us about key posters in GI oncology that will be featured at the 2022 ASCO Annual Meeting. His full disclosures are on our show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts.  Dr. Beg thanks for coming on the podcast today.  Dr. Shaalan Beg: Thank you so much for having me.  ASCO Daily News: Let's begin with “A multicenter, non-randomized, controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF-Cohort Trial): Analysis of overall survival.” That's Abstract 4095. This study evaluated the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma. So, what are your key takeaways from this study?  Dr. Shaalan Beg: This is a very interesting and timely clinical trial from our investigator colleagues in Japan, Dr. Yamashita, and colleagues, where they evaluated the effectiveness of radiofrequency ablation versus surgery for patients with small hepatocellular carcinomas who have a good liver function.  History is that the best most effective treatment option has always been surgery and we know that ablative techniques like radiofrequency ablation (RFA) or stereotactic radiation can do a good job in controlling the individual cancers, but we don't know what the long-term effects can be in terms of recurrence, free survival, and overall survival.  So, this trial looks to compare RFA or radiofrequency ablation versus surgery for groups of patients who have a good liver function, so a Child-Pugh score of 7 or less, and those who had no lesion greater than 3 centimeters and less than 3 hepatocellular carcinoma (HCC) nodules.  All the people were evaluated by surgeons and hepatologists, to confirm that they would be eligible for both procedures. And then the patients received either 1 of those treatments and they followed them in the long term and found that there was no significant difference between how people who are treated with surgery fared versus RFA.  This is really interesting and practical and timely because the results of these clinical trials can inform our clinical practice today. The median follow-up period was 6.8 years in the surgery group and 6.7 years in the RFA group and the overall survival was not different. Their 5-year overall survival for surgery was 79.7%. And very similar to what they were seeing in both groups.  ASCO Daily News: Excellent! Great to hear some promising developments for this patient population. Well, in Abstract 4026, investigators are suggesting that the choice of PD-L1 immunochemistry assay influences clinical eligibility for gastric cancer immunotherapy. What are your thoughts on this study?  Dr. Shaalan Beg: Yeah! Clinicians, clinical investigators, and even patients have been really confused by the definitions of PD-L1 expression. PD-L1 expression is 1 of our biomarkers for response to immunotherapy and immune checkpoint inhibitors. But the challenge in this field is that there are multiple assays that define various criteria for PD-L1 expression. And if you look at different clinical trials, they look at different definitions of positivity. So, a trial may have 1 plus. Some may have 5 plus percent. Some have 50 plus percent.  So, this group out of Singapore took 362 gastric cancer samples, and they evaluated its PD-L1 expression using the combined positive score or the combined positive score (CPS), the tumor proportion score (TPS), and immune cell expression, and they compared them to see how well all of these performed because what's important to remember is we don't know how interchangeable the different immunohistochemistry (IHC) assays are. We have the Dako 22C3, we have the Dako 28-8, and then the Ventana assays and different clinical trials have used different versions of these at different expression levels. And regulatory bodies haven't really defined how to do the testing.  So, different sites and different physicians, and different practice groups are using different assays and may be interpreting differently. What this trial is telling us is that if you use the Dako 28-8 assay, you identify a much higher proportion of people who are positive for PD-L1, whether you use the 1% cut off or the 5% cut off, or the 10% cut off. Listen to these numbers. 28-8 at CPS of greater than 1, 70% with 28-8, and 49% with 22C3.  If you use the 10% cut-off, it's 13% if you use a 28-8 assay, but 7% for the 22C3 assay. So, that kind of throws into question how these assays are being used in daily practice. Well, some people may be, but a lot of people are not thinking about the cut-offs that were used in those clinical trials, especially when that comes to finding treatment options for our patients. And if we use the 28-8 assay, we're bound to find more patients who are PD-L1 positive, but that may not be the assay that the trials used in their validation cohort.  So, we may end up treating the wrong patients. But at the same time, if we use the other assay, we may be missing out on people who are PD-L1 positive. So, I think this is a call. This is a call for the field to harmonize how PD-L1 expression is defined. We need more data on inter-assay concordance so we can find the right drug and the right biomarker for the right patients.  This is a call for better prospective data and a call for harmonization between different assays and between different trials because this is an issue that is plaguing clinical practice today.  ASCO Daily News: Thank you! So, let's talk about advances in pancreatic cancer and Abstract 4155. The authors of this study note that pancreatic adenocarcinoma is the fourth leading cause of cancer deaths, with an increased incidence among patients younger than 50 years old. This study is a comparative analysis of the targetable landscape in KRAS mutant and wild-type pancreatic adenocarcinoma. So, can you tell us about it?  Dr. Shaalan Beg: The pancreatic cancer field has really suffered from a lack of effective treatment options, especially targeted treatment options and lack of effectiveness of immunotherapy for this disease.  Most patients still receive chemotherapy and we only have a couple of different combination treatments to help treat this disease, which is increasing in terms of the number of new cases and cancer-related deaths, and by some estimates may be the third leading cause of cancer-related deaths in the U.S.  A big reason that the survival for this cancer has not improved is because we don't have a lot of actionable or targetable mutations for this disease. One of the biomarkers that does have a corresponding treatment option is people who have a BRCA mutation. PARP inhibitors like olaparib have been approved for that group of patients, but the effectiveness of that medicine is modest for this disease, and we still have to see how much it's incorporated into daily practice.  But outside of the BRCA mutations and other DNA damage repair alterations, KRAS is really the most common mutation and there are new drugs that are out there to target KRAS. 90 plus percent of pancreas cancers have KRAS and if you think about it the other way, a small proportion of patients with pancreas cancer don't have KRAS.  So, what this abstract is looking to study is what are the characteristics of patients with pancreas cancer who don't have a mutation in KRAS, and can be the absence of KRAS actually be a biomarker for other mutations and other treatment strategies for pancreas cancer.  And this was a fairly large study of about 5,000 patients with pancreas cancer that use a commercial NGS assay. The same commercial NGS assay, who performed gene analysis, as well as full transcriptome RNA-seq, were retrospectively reviewed. And they found that people who had a KRAS wild-type tumor meaning no mutation in KRAS were much more likely to have mutations in HRD and in BRAF compared to those that had mutations in KRAS.  And then when you look at fusions, there was a much higher rate of NRG fusions. At the 2021 ASCO Annual Meeting, we heard some data on some new agents that are primarily targeting tumors that have fusions in NRG. And what this abstract is telling us is that the absence of a KRAS mutation may indirectly prompt us to look for other mutations, particularly fusions that may have additional treatment options available. So, this indirectly may be a biomarker of other actionable mutations.  The overall proportion of KRAS wild-type in this cohort was 21%. So higher than what I would have expected, but it's 21% out of 5000 cases that they evaluated and they really set out to see if young-onset pancreas cancer folks have a different proportion of KRAS wild-type and the proportion of KRAS wild-type in both young and typical onset pancreas cancer was really the same.  So, I believe this prompts us to think about pancreas cancer in 2 buckets, the KRAS wild-type, and KRAS mutated pancreas cancer. If we ever come across someone who has no detectable KRAS mutation, we should make sure that they have full transcriptomic analysis so we can look and get better coverage on those fusion changes that may have more treatment options associated with them.  ASCO Daily News: I'd like to follow up with a question about Abstract 4130. Investigators analyzed the molecular profile and clinical outcome of a cohort of patients with KRAS wild-type pancreatic ductal adenocarcinoma, what does this study tell us about the treatment implications for these patients?  Dr. Shaalan Beg: Yeah, so this was an abstract by Dr. Aakash Desai from the Mayo Clinic, and they went back and retrospectively reviewed patients who were seen at their center. And they looked for similar questions as the other abstract had done, but this was from a single center, and it seems like people had had multiple different assays performed.  In this cohort, they found 240 patients. That's 8%, had KRAS wild-type disease. So, they found 19 patients who did not have a KRAS mutation. And they went to see if there were any hints of differences or specific mutations between the patients with wild-type and mutated. And they found that the landscape of KRAS wild-type in pancreas cancer was very heterogeneous, and it was difficult for them to generalize or make any statements on what that could suggest.  A couple of things to think about for this study. Well, first of all, I think it's important for us to acknowledge that this particular space, the KRAS wild-type space, is gaining a lot of attention and is being recognized as an independent entity. So, you have multiple abstracts that have looked to study this group of patients.  I think the second study is different from the prior one in that it's a single-center study. And from what I understand, they may have used multiple assays. So, there was less standardization on the actual mutation testing that was being performed. And that has relevance for this specific question because we know that we need deeper transcriptomic analysis in order to be able to perform RNA-seq and really understand the fusions that may be driving cancer, and it's hard to know what the coverage for the mutations that were evaluated in the second abstract, which mutations were really being covered.  But if we take a couple of steps back and look at this, with the lens of where the pancreas cancer field is headed, again, I want to emphasize that how I view these coming together is that KRAS wild-type, pancreas cancer is becoming recognized as its own identity.  ASCO Daily News: Excellent! Well, thank you Dr. Beg for sharing your valuable insights with us today on the ASCO Daily News podcast. It's certainly an exciting time in GI oncology.  Dr. Shaalan Beg: Absolutely! Thank you so much for having me.  ASCO Daily News: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you're enjoying the content on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.  Disclosures:   Dr. Muhammad Shaalan Beg:  Employment: Science 37  Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine  Research Funding (Inst): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals  Disclaimer:   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.     

This episode discusses the Child-Pugh scale to assess hepatic impairment. It also covers the FDA's position on the inclusion of drug metabolism data for various Child-Pugh stages and cirrhosis. Faculty: Jonathan Meyer, M.D. Hosts: Jessica Diaz, M.D.; Flavio Guzman, M.D. Learn more about Premium Membership here Earn 1 CME: Use of Psychotropics in Patients With Hepatic Issues The Importance of Child-Pugh Classification for Staging Hepatic Impairment

This episode discusses the Child-Pugh Rating Scale and how to interpret it, two clinical cases, and the use of paliperidone and lurasidone in patients with hepatic impairment (Child-Pugh C). Faculty: Jonathan Meyer, M.D. Hosts: Jessica Diaz, M.D.; Flavio Guzman, M.D. Learn more about Premium Membership here Earn 1 CME: Use of Psychotropics in Patients With Hepatic Issues Rating Scales for Hepatic Dysfunction: Child-Pugh

Oncotarget published this trending research paper on April 13, 2021, entitled, “Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib,” by researchers from the University of Texas MD Anderson Cancer Center, Massachusetts General Hospital, and Harvard Medical School. The majority of circulating insulin–like growth factor (IGF) is synthesized and secreted by the liver, and levels of IGF dramatically decrease in chronic liver disease and HCC. IGF can be a helpful tool to determine the prognosis of patients with advanced HCC while undergoing treatment with sorafenib. Researchers also use the Child-Turcotte-Pugh (CTP) qualitative scoring system to assess severity of liver cirrhosis, hepatic reserve, guide treatment decisions, and to stratify patients with HCC into three groups (A, B, and C). CTP class A has a better prognosis compared to classes B and C. “Assessing liver reserve in HCC is of a great value as a tool for stratification of patients in clinical trials as well as to predict HCC outcome and guide therapy decisions in routine practice.” In the researchers’ prospective study, 171 patients with HCC from the University of Texas MD Anderson Cancer Center were screened and included in this study. Of the patients, 116 were classified in CTP group A. Patient IGF/CTP scores were calculated and the researchers used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups. Based on CTP and the IGF/CTP scores, researchers reclassified group A patients into AA and AB risk groups, which differed significantly in terms of OS and PFS. The researchers followed up with all patients in the study until disease progression or death. Unfortunately, during the follow-up period, 100 patients passed away. “After IGF/CTP scoring, 87 of 116 CTP class A patients were reclassified as IGF/CTP-A (AA) and 29 patients were reclassified as IGF/CTP-B (AB).” Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27924 DOI - https://doi.org/10.18632/oncotarget.27924 Full text - https://www.oncotarget.com/article/27924/text/ Correspondence to - Ahmed O. Kaseb - akaseb@mdanderson.org Keywords - IGF-1, Child-Pugh, sorafenib, liver reserve, hepatocellular carcinoma About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

An interview with Dr. John D. Gordan from the University of California, San Francisco, and Dr. Michal G. Rose from Yale Cancer Center and VA Connecticut Healthcare System on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline." This guideline addresses first-line and subsequent systemic therapy options for patients with unresectable hepatocellular carcinoma that is not amenable to local therapies. Read the full guideline at www.asco.org/gastrointestinal-cancer-guidelines. Transcript ASCO: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network. A collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.asco.org My name is Brittany Harvey, and today I'm interviewing Dr. John D. Gordon from the University of California, San Francisco, and Dr. Michal G. Rose from Yale Cancer Center, and VA Connecticut Health Care System, co-chairs on "Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline." Thank you for being here Dr. Gordon and Dr. Rose. DR. MICHAL G. ROSE: Thank you. DR. JOHN D. GORDON: Thank you. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Gordon, do you have any relevant disclosures that are related to this guideline topic? DR. JOHN D. GORDON: I do not. BRITTANY HARVEY: Thank you. And Dr. Rose, do you have any relevant disclosures that are related to this guideline topic? DR. MICHAL G. ROSE: I do not, either. BRITTANY HARVEY: OK, then thank you. Then Dr. Rose, can you first explain the general purpose and the scope of this guideline? DR. MICHAL G. ROSE: Of course. Thank you for this opportunity. As people know, the incidence of liver cancer, hepatocellular carcinoma, is rising rapidly in the United States and worldwide. And although there are multiple local and potentially curable treatments for early stage disease, the medical oncologist does get involved when these fail or if the patient presents with metastatic disease. And over the last three years, or bit more than three years, we've gone from having only one agent for advanced disease, which is sorafenib, to having nine agents approved for either first or subsequent lines of treatment. So this has created a really good problem for medical oncologists, how to choose between these multiple options. So the purpose of our guideline is to help us select the best treatment for the individual patient based on the best current evidence. BRITTANY HARVEY: Great. Then this guideline covers both first line and subsequent systemic therapy options for patients with advanced hepatocellular carcinoma. Dr. Gordon, what are the key recommendations for first line therapy? DR. JOHN D. GORDON: Thanks, and it's also a great pleasure for me to be on this podcast and I appreciate the entire process of putting together this guideline. In the front line setting, a lot of what motivates the completion of this guideline is the approval of the first front line combination for advanced HCC, which is the combination of bevacizumab and atezolizumab. So this was approved based on a report in the New England Journal of Medicine back in May that specifically studied a first line population of patients with advanced HCC and relatively preserved liver function. And the key recommendation of this guideline is that the combination of atezolizumab and bevacizumab be adopted for patients that meet this description. Particular caution is recommended for patients who are at risk of specific side effects or adverse events with these agents. So for patients receiving bevacizumab, there is a particular risk of bleeding complications and MI or other ischemic complications. And so for patients with a recent MI or with uncontrolled esophageal varices, we recommend either management of these or not using this combination. Similarly, there are a range of contraindications to use of PD1, PDL1 inhibitors, such as atezolizumab, including history of various autoimmune diseases. And so we do not recommend this combination for patients with those co-morbidities. For patients with either more advanced liver failure or the specific risks that I just outlined, we're recommending continuation when safe and appropriate, of what was the previous standard of care. Which is front line treatment with either the oral TKI lenvatinib or the oral TKI sorafenib. BRITTANY HARVEY: Great. Thank you for that overview of the first line recommendations. And Dr. Rose, what are the recommendations for second line therapy? DR. MICHAL G. ROSE: So our team had a harder time with second line recommendations. And mainly because there's a lack, currently, of published data on treatment outcomes in patients who've received atezolizumab plus bevacizumab front line or lenvatinib front line. So we debated a lot in our group, which was a very multidisciplinary and collaborative group. And we did agree that patients who are well enough to receive second line therapy, that is their Child-Pugh was still A, and they had a good performance status, they should be considered for sorafenib, oral lenvatinib, if they had received atezolizumab plus bevacizumab in the front line setting. But of course other options for the second line would be cabozantinib or regorafinib, are reasonable in the evidence based options. In patients who received sorafenib oral lenvatinib front line, we also discussed that it was reasonable to treat them with atezo bev because we presume that these patients did not have access to that combination in the front line. Of course if they meet the criteria that John outlined in the discussion of front line treatment. In patients who received sorafenib or lenvatinib front line, of course that we have data on using other tyrosine kinase inhibitors, such as cabozantinib or regorafinib. We also have data on using ramucirumab in patients who have an alpha fetoprotein greater than 400. And those were the recommendations that we made. The other discussion that we had in these guidelines was the use of the immune checkpoint inhibitors second line. And we made the recommendation that they should be considered for patients who received sorafenib or lenvatinib in the front line setting, especially if they have contraindications to the use of further tyrosine kinase inhibitors. Or if they could not tolerate tyrosine kinase inhibitors. BRITTANY HARVEY: Got it. Thank you for reviewing those second line systemic therapy options. Then Dr. Gordon finally, what is the importance of this guideline and how will it impact clinical practice and affect patients with advanced hepatocellular carcinoma? DR. JOHN D. GORDON: Thanks. And so I think this very much follows on Michal's initial introduction about the purpose of this guideline, which was to address the dramatic proliferation of approved agents for advanced HCC. And what we were attempting to do, and I think achieved to the best that the evidence would support, was provide some degree of guidance on how providers could select both their first line agent and then later lines of therapy to the extent that patients are able to receive it. We think that the availability of these multiple agents for HCC, as Michal alluded to, is really an embarrassment of riches and now we need to think about how to use them wisely. And we hope that actually as these new combinations and just a greater set of options enter clinical practice, it will be possible to actually do some of the studies that would address the questions that right now remain unanswered around treatments sequencing and the like. I think that there remain some interesting questions in the management of HCC, both for patients with more impaired liver function and for patients at the threshold between localized HCC who are still candidates for local regional therapies such as TACE or selective internal radiotherapy, and requiring systemic therapy as the outcomes from systemic therapy are becoming more positive. But in aggregate we think that these guidelines now provide something of a sequence for the treatment of patients who do require systemic therapy and hopefully an outline for further development. BRITTANY HARVEY: Great. Thanks. It sounds like this will be important for both practitioners, and patients. So I want to thank you both for joining me on the podcast today and for your leadership on the development of these guidelines, Dr. Rose and Dr. Gordon. DR. MICHAL G. ROSE: Thank you. And thank you for the opportunity to discuss them. DR. JOHN D. GORDON: Yeah, thanks as well. And thanks to the amazing team at ASCO and to the entire expert panel, which put in quite a bit of time over the several years that we developed this guideline as more and more data became available. BRITTANY HARVEY: Great. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO guidelines app, available in iTunes or the Google Play store. If you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

Featuring a roundtable discussion with Drs Thomas A Abrams, Anthony El-Khoueiry and Robin K Kelley on the following topics: First-Line Systemic Therapy for Patients with Unresectable Hepatocellular Carcinoma (HCC) Recent advances in the management of HCC; the IMbrave150 trial and subsequent approval of atezolizumab with bevacizumab for unresectable HCC (0:00) Rationale for the use of atezolizumab with bevacizumab as first-line therapy; impact of COVID-19 on the management of HCC (1:48) Case: A woman in her mid-50s with advanced HCC receives atezolizumab/bevacizumab as first-line therapy — Thomas A Abrams, MD (7:06) Activity and tolerability of the combination of atezolizumab and bevacizumab (12:04) Ongoing investigation of pembrolizumab/lenvatinib and atezolizumab/cabozantinib for patients with HCC (16:33) Role of combination immunotherapy approaches versus locoregional therapies for the management of HCC (21:57) Case: A man in his mid-70s with moderately differentiated HCC experiences an improvement in pain with first-line atezolizumab/bevacizumab — Anthony El-Khoueiry, MD (28:35) Case: A man in his late 40s with chronic active hepatitis B is diagnosed with advanced HCC and receives first-line lenvatinib — Robin K Kelley, MD (33:46) Activity and tolerability of lenvatinib versus sorafenib as first-line therapy (36:29) Efficacy and side effects of nivolumab or pembrolizumab/lenvatinib as up-front therapy for HCC (39:50) Case: A man in his late 60s with hepatitis C and alcohol-related cirrhosis is diagnosed with HCC — Dr El-Khoueiry (44:17) Importance of Child-Pugh score in therapeutic decision-making (48:09) Selection of first-line therapy based on Child-Pugh score, symptoms and performance status (52:02) Clinical Decision-Making for Patients with Progressive Metastatic HCC  Choice of therapy for a patient with advanced HCC and disease progression after first-line sorafenib (1:00:54) Selection and sequencing of therapy for patients in the second- and later-line settings (1:06:13) Risks and benefits with cabozantinib or regorafenib for patients with progressive metastatic HCC (1:08:16) Case: A man in his early 70s who underwent a liver transplant for HBV-related cirrhosis receives regorafenib after experiencing disease progression on sorafenib — Dr Kelley (1:12:18) Side effects associated with immunotherapy in patients with HCC (1:16:24) Case: A man in his early 80s with recurrent HCC receives ramucirumab — Dr Abrams (1:19:18) Novel agents and strategies under investigation for the treatment of HCC (1:26:30) CME information and select publications

It’s your worst clinical nightmare: providing dosing recommendations for opioid and/or nonopioid pain medication treatment for a patient with renal or hepatic impairment. Even scarier, a patient with end-stage renal or hepatic disease! Put your panic aside and learn about the INs and OUT of managing opioid and/or nonopioid pain medications, and why some medications might need adjustment and others may not. From metabolism and metabolites to creatinine clearance and Child-Pugh score, you will leave this course feeling more confident in your ability to provide pain pharmacotherapy to patients with renal or hepatic impairment.

Episode 3: James Horowitz interviews Rachel Rosovsky on DOACs. Dr. Rosovsky is the Director of Thrombosis Research in the Division of Hematology at Mass General Hospital. She is also an Assistant Professor at Harvard and a member of the Board of Directors of the PERT Consortium.  Dr. Horowitz is the Director of the CCU at NYU Langone Health and the Co-Chair of the Interdisciplinary Resuscitation Committee. He is also an Assistant Professor or Medicine and a member of the Board of Directors of the PERT Consortium. Directly acting oral anticoagulants.   FDA approved DOACS: Xarelto (rivaroxaban), Eliquis (apixaban), Savasya (edoxaban), Pradaxa (dabigatran). All DOACs have similar efficacy in terms of VTE occurrence and better safety profile compared compared to Coumadin. MOA: Dabigatran: directthrombin inhibitor.   Rest of the DOACs: factor X inhibitors. DOACS usually do not need monitoring. Most common interaction noted with drugs like ketoconazole (CYP3A4). Dosing: Dabigatran and Edoxaban: Overlap with parenteral enoxaparin for 5 to 10 days is needed. Apixaban and Rivoraxaban: Need loading dose. For apixaban it is 10 mg 2 times a day for 7 days followed by 5 mg 2 times a day.  Rivaroxaban: 15 mg 2 times a day for 21 days followed by 20 mg once a day. (Xarelto need to be taken with food) Only 55% of the patients with Coumadin remain in therapeutic range. Drug reversal agents for DOACs Dabigatran reversal: Idarucizumab Xarelto and Eliquis reversal: Andexenat Alpha. Factors in deciding candidacy for DOACs: DOACs in patients with Child-Pugh score B/C cirrhosis should not be used. Renal failure with CrCl 120 kg, based on ISTH guidelines. (higher the BMI may have increased risk of bleeding with better efficacy, potentially due to absorption issues-- levels can fluctuate) Drug monitoring for DOACs: No standardized methods. Not routinely done. It should be considered in patients with extremes of weight and patients who have gone gastric/bariatric surgeries, because all DOACs are absorbed get into upper GI tract. Pregnancy and Venous thromboembolism: No DOACs in pregnancy. Enoxaparin is the treatment of choice -1 mg/kg every 12 hours up to week 36 followed by changing them to unfractionated heparin. (subcutaneous calculated dose). Patients who had prior DVTs/PEs and become pregnant may need prophylactic dose of enoxaparin (40 mg subcutaneous once a day) Cancer and VTE: VTE is a second leading cause of death in cancer patients. Drug of choice was enoxaparin over warfarin. Edoxaban Vs Enoxaparin: Edoxaban with less recurrent VTE, but worse bleeding profile (most bleeds in gastric cancer patients) Rivaroxaban Vs Enoxaparin: Rivaroxaban with less recurrent VTE, but worse bleeding profile (most bleeds in gastric cancer) Cancer patients who may not be good candidate: a) GI cancer b) needing many procedures c) liver/renal failure d)brain mets.  Provoked vs Unprovoked and extended a/c: Unprovoked PE: Two-year risk of recurrence 25% or higher. Provoked by surgery [mainly orthopedic surgery, pregnancy, long hospital stay]: risk of recurrence 1% at one year, 3% at 5 years. Flying is a weak risk factor to be considered as provoked. Amplify-Ext trial: 70% decrease risk of recurrence with low dose apixaban without an increased risk of bleeding in unprovoked VTE. Einstein Choice trial: 70% decrease risk of recurrence with low dose rivaroxaban without an increased risk of bleeding. 60% of patients had provoked VTE with ongoing risk factors. (i.e. Obese patients, patients who are immobile, and are still immobile). Cancer screening following PE: 5-10% of patients with VTE would be diagnosed with malignancy in next 5 years. Recommendation is to do age appropriate cancer screening. Valves and DOACS: (increase risk of ischemic events)   Reference: Rali P, Gangemi A Moores A et al. Direct-Acting Oral Anticoagulants in Critically Ill Patients. Chest. 2019 Sep;156(3):604-618.

Background and Aims: Patients with advanced liver cirrhosis who develop renal dysfunction have a poor prognosis. Elevated intrarenal resistance indices (RIs) due to renal vascular constriction have been described before in cirrhotic patients. In the current study, we prospectively investigated the course of intrarenal RIs and compared their prognostic impact with those of the Model for End-Stage Liver Disease (MELD) and the Child-Pugh scores. Methods: Sixty-three patients with liver cirrhosis underwent a baseline visit which included a sonographic examination and laboratory tests. Forty-four patients were prospectively monitored. The end points were death or survival at the day of the follow-up visit. Results: In 28 patients, a follow-up visit was performed after 22 8 months (group 1). Sixteen patients died during follow-up after 12 8 months (group 2). Group 2 patients showed a significantly higher baseline RI (0.76 +/- 0.05) than group 1 patients (RI = 0.72 +/- 0.06; p < 0.05). As shown by receiver operating characteristic analysis, the RI and the MELD score achieved similar sensitivity and specificity {[}area under the curve (AUC): 0.722; 95% confidence interval (95% CI): 0.575-0.873 vs. AUC: 0.724; 95% CI: 0.575-0.873, z = 0.029, n.s.] in predicting survival and were superior to the Child-Pugh score (AUC: 0.677; 96% Cl: 0.518-0.837). Conclusion: The RI is not inferior in sensitivity and specificity to the MELD score. Cirrhotic patients with elevated RIs have impaired short- and long-term survival. The RI may help identify high-risk patients that require special therapeutic care. Copyright (C) 2012 S. Karger AG, Basel

Background/Aims: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). Methods: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 +/- 0.7 with a mean size of 3.0 +/- 0.9 cm. Both local efficacy and patient survival were evaluated. Results: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. Conclusion: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC. Copyright (C) 2011 S. Karger AG, Basel

HCCUpdate.com – 67yo, unresectable Child-Pugh B HCC treated with sorafenib. Interviews conducted by Neil Love, MD. Produced by Research To Practice.

To assess the effect of prophylactic sclerotherapy on variceal hemorrhage and survival of patients with liver cirrhosis and esophageal varices, a randomized study had been carried out. We analysed the data from different points of view. The time-dependent Cox model and the linear counting process of Aalen are applied allowing for the time-dependent covariate ``variceal bleeding`` -- that switches up to three times -- in a multivariate analysis of the remaining life time. A model for the times to and between the recurrent events of bleeding including unobserved heterogeneity is estimated by a distribution-free and by a parametric method where the latter also admits time-dependent covariates such as repeated measurements of laboratory data. We find that high age, high Child-Pugh score and especially the first occurence of variceal bleeding have a statistically significant negative effect on survival whereas patients with fundic varices and/or alcoholic cirrhosis have a significant higher risk of bleeding. In both analyses, inclusion of time-dependent covariates does not change the estimation substantially. In particular, prophylactic sclerotherapy is not shown to reduce the risk of bleeding nor dying significantly.