Podcasts about IHC

Dr. Deb Muth 00:02What if I told you that before a single drop of chemotherapy goes into a cancer patient’s body, we can take a blood sample, grow their actual living cancer cells in a lab, and test 70 different drugs against those cells, all outside the patient’s body, to find out which ones actually work. And what if I told you that the conventional oncology doesn’t routinely use this test? Well, today we’re going to talk about why that matters and we’re going to go through and I’m going to share a story that is very personal to me. It’s about a 38 year old man with a rare complex cancer diagnosis and the precision testing that is helping to keep that cancer from progressing. Stay with me. This is one that is going to change how you think about cancer treatment. Dr. Deb Muth 01:05You guys can put a little ad right in here before we start the next segment here. Hey everybody, welcome back to Let’s Talk Wellness Now. I’m Dr. Deb and today we’re going deep. I mean really deep. It’s some of the most cutting edge cancer testing I have ever seen in clinical practice. Now, normally I don’t talk about cancer. And I would not be sharing this story if it was anyone other than my own family. I do have permission to share and talk about this publicly. So I want to do this. I want to make sure that I share this message. And he is giving his blessing to share this story because we both believe that it can save lives. So his name is Cameron. He’s 38 years old. And he is my son-in-law. And two years ago, he came to me with a small lymph node underneath his arm and a bullseye rash. So of course, being the lime literate person that I am, my first inclination was to say, yeah, this makes sense. You have an enlarged lymph node because you have this bullseye rash. You got bit by the tick. Let’s keep an eye on it. If it doesn’t go away, let me know. So Fast forward a year and a half later, he comes to me and says, mom, what do you think about this? This thing is getting a little bit larger. And I said, yeah, it’s a little larger. Not sure. Let’s keep an eye on it. He wasn’t feeling anything. All his labs looked okay. And then one day he was out chopping wood and he started getting numbness in that arm and he felt it again. And it had exploded in size. And so after some evaluation with my daughter and him, we decided to do a ultrasound. And we thought what was going to come back was a fatty tumor. It felt like one looks like one responded to one. He’s 38 years old. He’s healthy. There’s nothing in our mind that’s ever thinking the result that we’re going to get back. Dr. Deb Muth 03:28Is a possible lymphoma. Needless to say, we were shocked by that ultrasound result. And we go fast forward, we have the biopsy. I requested a total excisional biopsy. I was told by the oncologist that that was old school. They don’t do that that way anymore. And I need to stay out of this. I need to let the experts take care of this because that’s what they do best. And this came from a breast surgeon here in Wisconsin. And so I stepped back for a moment. I let him do his biopsy and what came back was adenocarcinoma of an unknown origin. Had we excised the entire lymph node, we would have had more tissue to work with. I think we could have gotten a better diagnosis. So over the course of the next two and a half, three months, we have some more imaging done. We have some more testing done. They send a pathology out to Mayo Clinic. And what continues to come back is this incongruent test results. If anybody’s ever had this, it’s extremely frustrating. One test shows lymphoma. Now it shows breast cancer. Then the next week it shows estrogen receptor HER2 positive breast cancer. Two weeks later, another test comes back and it says, no, it’s not HER2, it’s triple negative breast cancer. And now it looks like it’s out of the lymph nodes. Now it looks like it’s in the lymph nodes. And we do a PET scan and they can’t find cancer anywhere except in this axilla area. But now we find a lymph node on the right side. So it must have spread.Let’s go ahead and do a biopsy on that. And so they biopsy the right side and the right side comes back with nothing other than tattoo ink. Now, all of this is kind of crazy. I am not a cancer specialist. I want to start by saying that I am not a cancer specialist. What I am sharing today is from a mother-in-law’s perspective, from a medical detective’s perspective, I do know how to do research. I do know how to find answers. And so what I’m going to share with you Dr. Deb Muth 05:54Is totally my opinion and totally my experience. And I’m not telling anybody to do anything different than what their doctors are telling them to do. But I am telling you to ask questions. So I go deep down the rabbit hole and find out that Tattoo Ink can appear like metastatic cancer on a PET scan. And we all know everybody gets tattoos today. They’re all over everyone. And yet we’re not thinking about how this tattoo ink can cause problems for us down the road, not to mention that there are heavy metals in them and it’s a toxin and it’s creating an inflammatory process in your body that your body’s constantly trying to get rid of. So the surgeon says to us, well, yes, that’s normal that that lymph nodes inflamed. It’s normal that there’s tattoo ink in it. The body’s doing what it’s supposed to do. It’s trying to get rid of a toxin. Okay. I will agree with that, but My son-in-law is covered with tattoos everywhere. And why didn’t we mention the tattoo ink that was found in the left axilla? We are only mentioning it in the right axilla. So there’s a lot of controversy, a lot of confusion. Many of you would never know any of this because A, you either don’t look at your lab results. And if you do, you don’t understand what you’re looking at. And that creates a problem for us, right? You don’t know what questions to ask. So we go into the doctor and the doctor tells us you have cancer and we’re going to swoop you in. And in the next two weeks, you’re going to be doing chemotherapy and radiation. And six months from now, we’re going to be doing surgery and there’s no time for questions and you’re scared shitless and you’re just doing what you can to survive. And I get that. And I totally understand that. And I appreciate that. But I’m telling you that If that is your choice, that is your choice. But as you’re doing that, take the time to ask the right questions. When this happened to us, there was a lot of challenging things with the oncology team. Nobody bothered to allow them to be a partner in their care. They dictated their care, but didn’t allow them to be a partner. So, Dr. Deb Muth 08:17Here’s what most oncologists do when patients get a cancer diagnosis. They look at the tumor type, they look at the stage, they look up the NCC guidelines, the National Comprehensive Cancer Network, and they follow the algorithm. Now, I have an enormous respect for conventional oncology. I really do. Working with cancer is probably one of the hardest things in medicine that anyone can do. The advances in this field over the last 10 years have been remarkable. But here’s my issue. Standard treatment assumes your cancer is the same as the cancer in the clinical trial that created the guidelines. It’s assuming that you and your cancer are the exact same as everyone else. You are the unique fingerprint, not the cancer. And this is the problem because your cancer is unique, just as unique as if you had your fingerprint taken, the mutations driving your tumor, the drugs your cancer cells are sensitive to, the metabolic vulnerabilities of your cancer. These are all different from the person sitting next to you in the chemo suite that has the same triple negative breast cancer or HER2 positive breast cancer or prostate cancer or colon cancer that you have. So what do do about that? Well, in my world, in the integrative medicine world, we test precisely, intelligently with the tools that most oncologists have never heard of. Or if they have, they haven’t incorporated it into their treatment modality for a variety of reasons. Either it’s not acceptable by the organization that they work for, they don’t understand it, They’re not going to be able to change their protocol anyway because they have to follow the NCCN protocol. So they don’t do it or they use a portion of it and they don’t do anything outside the protocol. So today I want to cover three things with you, three tools that we used that I think every cancer patient should be asking for when they start treatment or wherever you are in treatment at this point. Dr. Deb Muth 10:44you need to have these tests done. I don’t have any affiliation with any of these companies. I don’t get paid to tell you any of this. So let me just start by saying that I understand the chemistry behind these and how important it is to give you precision cancer treatment. And that’s why I’m talking about them today. The first one we’re going to talk about is the North Star response. This is your cancer surveillance score in the blood. How much cancer is circulating in the blood. The North Star Select, your cancer’s genomic blueprint from a blood draw. And the Datar Cancer Genetic Chemoscale, the live cell drug sensitivity test that tells us which drugs actually kill your cancer. So let’s go. Let’s dive into this. Let me just take a drink here. I’m going to cough a little bit. I apologize. I have this horrible tickle. It just never seems to go away, but that is not for today to discuss. So what is all of this? OK, the North Star response is a test that was developed by a company called Billion to One. And yes, that name is intentional because of the precision involved. It’s a next generation sequencing test, meaning it reads DNA at an incredibly detailed level. And it looks at something called methylated circulating tumor DNA or methylated CT DNA. Now let me break this down in plain English for you, because this can get a little overwhelming. When the cancer cells die or shed, they release tiny fragments of DNA into your bloodstream. We call this cell-free DNA or CFDNA, and it’s hidden within that cell-free DNA. And there are fragments that come from tumor cells. We call those CT DNA or circulating tumor DNA. Here’s what makes North Star’s response different. Rather than just looking for mutations in that tumor DNA, which is what most liquid biopsies do, and a liquid biopsy is just a blood test, Dr. Deb Muth 13:03This test looks at something called methylation patterns. Think of methylation like a dimmer switch on a gene. In healthy cells, certain genes are switched on and off in a very predictable way. In cancer cells, those dimmer switches go haywire. And cancer DNA has a characteristic hypermethylation, meaning switches are turning on and should be off or off and they should be on. And these patterns are essentially a cancer fingerprint in the blood. Now the North Star response scans more than 2000 locations in the genome for these cancer specific methylation patterns. And then it adds them all up into a single number called the tumor methylation score or TMS. So for Cameron, Cameron’s blood which was drawn on April 20th, 2026, his baseline tumor methylation score came back at 13. Now here’s the critical thing, to understand this was his baseline test, his starting point. And the real power of this test is in serial monitoring, meaning we run it again and again and again over time. And if that number goes up, the cancer activity is likely increasing. If it goes down, we’re likely suppressing the tumor activity. And if it stays flat or falls, that’s telling us that the disease is responding. So this is now in the blood. We have an actual fingerprint and every test from here forward will be compared to this number. Now let’s talk a little bit about this because I was not familiar with this test at all. I wasn’t sure what to expect. I wasn’t sure what to do with it. I did not order this test. He’s working with Inveda Medical and they are fabulous over there. I will tell you that from the beginning. This is coming from a practitioner and from a mother-in-law. They were absolutely wonderful to us. So when I saw this North Star, I didn’t know, should it be zero? Should it be a hundred? And when I talked to the doctor, he said, Dr. Deb Muth 15:29This number is actually really good. An average person walking around who’s never been diagnosed with cancer, who doesn’t have cancer, their number will be between 75 and 100. Cameron’s was 13. I think that’s fantastic. But what was the first question that went through my head? It’s probably the same question that you guys are doing. How can he have cancer with a number of 13 when it’s less than the normal average? And if we’re supposed to use this to track what’s happening with his cancer, how are we going to do that once we remove the cancer? Is this number going to go to zero? And it could possibly do that. And we may not be able to use this to track whether or not the disease is actually gone. But what we can do is use this to track over the course of his lifetime to see if the cancer cells are coming back long before we detect them on imaging. And that’s the huge part of this.So this is not a test that just anybody should go out and get because you’re worried about cancer. It is a test that should be done in somebody that is already diagnosed with cancer. So let’s start by making sure we explain that, okay? So imagine if every time your cancer cells are active and they’re shedding and they’re multiplying and they’re fighting back, they’re leaving a signature in your blood not just any signature, but a specific chemical tag that says, cancer’s here. That’s what the North Star Response Test reads. Those tags across thousands of locations and gives us a single score. So we track that score over time like a thermometer for your tumor. If it goes up, we get concerned. If it stays stable or goes down, we celebrate. And we can catch a change in the blood often months before it will show up on a scan. Pretty important when we’re talking about surveilling somebody for cancer returning, when we’re worried about it, and everybody knows the cancer patient is always worried after they get that clean bill health that something’s gonna come back, and most of the time they’re told that there is no way for them to determine that or know that from a blood test. And here is the blood test that can tell us, yes, it can. Dr. Deb Muth 17:51So I would really encourage you guys to talk to your oncologist about this. If you can’t find an oncologist that will do this, talk to an integrative cancer doctor. They will most likely be familiar with it. If not, ask them to find it for you and order it for you. So next, let’s talk about that genetic blueprint because North Star Select is a different test also by billion to one run on the same blood draw, but this one is doing something completely different. This is a comprehensive genomic liquid biopsy. Liquid biopsy just means blood tusks, meaning it’s looking for specific mutations in 84 cancer related genes, all from a blood sample, no biopsy needle, no surgery, just a blood draw. It looks for CNVS, single nucleotide variants, tiny one-letter typos in the DNA code. It looks for indels, small insertions or deletions in the DNA. It looks for copy number changes, the sections of the genomes that are duplicated or deleted. It looks at fusions. So when two genes incorrectly link together to create a dangerous hybrid, MSI status, micro satellite instability, which tells us whether immunotherapy is likely to work. And it has extraordinary sensitivity. It can detect a mutation that represents as little as 0.15 % of cell free DNA in the bloodstream. That is an almost impossibly small signal in the ocean of genetic noise. So what did this show for Cameron? This is where Cameron’s case gets clinically fascinating and where it tells the story of how his cancer is being held in check. Two major mutations were identified as actionable. One was called CRAS G12C. Dr. Deb Muth 20:11And it’s a variant-ELI fraction at 0.1%. Now, CRAS, if you’ve spent any time in integrative oncology, you’ve heard this name. CRAS is one of the most well-known oncogenes in cancer biology. Think of it like an accelerator pedal in the car. In a healthy cell, CRAS pushes the cell to grow when it receives the signal to do so. And then it stops. In cancer, crass gets stuck in the go position, like on the accelerator, foot on the accelerator, to the floor, going as fast as you can around that track, right? But it’s stuck there permanently. It doesn’t turn off and it’s supposed to be turning off. The G12C variant specifically is a mutation at a very precise location. Position 12 of the CRAS protein, where a glycine is replaced by cysteine. And this matters because CRAS G12C is now a drugable target. There are FDA approved drugs specifically designed to lock this mutation into its inactive state, essentially putting a foot on the brake. Now those are drugs like, and I’m gonna slaughter these names, Sordisib, a brand name is Lumacras, and Atacras, the brand name is Crastol. Neither is yet FDA approved for breast cancer, but they are approved for lung and colorectal cancer with CrasG2C. And Cameron’s tests identified 10 active clinical trials within a region that he could potentially qualify for with this mutation. The fact that his CRAS G12C is circulating at only 0.1%. That is a very low fraction. We call that a VAF, V-A-F, very low fraction. And it tells us something important. It means that this mutation is present in a small subclone of the tumor. It’s not the overall tumor burden. So either way, when we identify, we know it’s there. Dr. Deb Muth 22:37We can catch it and we can watch it. Now, here’s another interesting thing that we saw. His TP53 was at 0.23%. This is a tumor suppressor gene, the guardian of genome. And this gene is responsible for telling damaged cells to either repair themselves or self-destruct. And when it mutates as it is here in the position R196Q, that guardian goes off duty. The cell no longer has a reliable mechanism to prevent uncontrolled growth. So TP53 mutations are present in roughly 50 % of all human cancers. And there’s currently no FDA approved drug directly targeting the TP53 but there are clinical implications. TP53 mutant tumors may respond differently to chemotherapy and several investigational approaches, including TP53 vaccines and aurora kinase inhibitors are under active investigation. So we are seeing things happen in this part of cancer right now. Now there’s something called the VUS list and we are watching This is what we’re watching. beyond those two actionable mutations, NORSTAR Select identified what we call variants of an unknown significance, VUS, adenocarcinoma of an unknown significance, ACUP. These are mutations where we don’t yet have enough clinical evidence to determine whether they’re driving cancer or not, but we watch them. So on our mutation list was CDH1, a gene linked to hereditary gastric and lobular breast cancer, CDKN2A, a tumor suppressor cell cycle regulator, CDK12, involved in DNA repair, EGFR, ERBB, this is HER2 receptor, tyrosine kinases. Dr. Deb Muth 24:55I thought this one was pretty interesting since he had an IHC that showed a three plus HER2, but then when we confirmed it with FISH, FISH showed that was negative, but now we’re actually seeing genes expressing this HER2. So is there a HER2? Is there not a HER2? This is really important because if we don’t get these diagnoses right in cancer the first time, people will spend months and years treating the wrong type of cancer with the wrong type of medication. And this may be in part why some people do better than others. If we get it right out of the gate, they do good. If we don’t get it right out of the gate, they don’t do so good. Very important to have the actual genetic makeup of the tumor that’s growing in somebody. Now last, we have something called Notch C1, NRAS and RAF1. These are key pathway components. Now all of these were at very low baffs under 0.5%. These are just whispers, not shouts, but whispers that this cancer is excreting, but your body is listening. We have to be listening. We have to be able to watch these things and monitor these. Now here’s another note of clinical interest. It was an androgen receptor positive cancer. So also detected as a VUS.We know from tissue pathology that Cameron’s tumor was androgen receptor positive. So seeing this in circulation confirms that this AR expression of the cells are present in the bloodstream and that an anti-androgen approach remains worth considering. What that means is suppressing the testosterone. What all of you know I’m about ready to say is that I hate ever suppressing hormones, especially in a 38 year old male. That is not necessarily a good thing. So before we go suppressing hormones willy-nilly, we have to know that it’s the right thing to do. And we have to be able to combat all of the complications that are going to result of that. A 38-year-old male with no testosterone could lead to heart disease down the road, could lead to bone loss, could lead to dementia, Alzheimer’s. Not to mention the sexual side effects that are going to be present. And in a man that is very, very Dr. Deb Muth 27:20Difficult for someone to manage. So you have to be very specific and you want to be very, very diligent about what you’re doing in these cases like this. Now the MSI status was not detected. This tells us that cancer is not a microsatellite instability high, meaning that standard monotherapy may have a lower baseline response of probability and the strategic integration that we’re working with with in Vita could create an immunogenesis genicity becomes even more critical. So immunotherapy is going to be very critical in a cancer case like this and working with somebody that understands that and can carefully navigate that, especially if you have an autoimmune disease like Hashimoto’s or lupus, this is all very, very pristine and has to be looked at very carefully and done very diligently in order for somebody to do this without overstimulating that immune system and causing more problems. So when we looked at the blood and found this DNA fingerprint of the cancer cells circulating in the body, from that, what we see exactly is the genetic switches that are stuck on. They’re stuck on in the wrong position. This tells us which drugs were designed to fix exactly that problem. And it opens the door to clinical trials built for these specific mutations. It also gives us a list of things to watch for over time. And if one of those tiny little signals starts to grow, we know that cancer is gaining a ground in that area. And if it shrinks or disappears, we know we’re winning. This is like, I cannot tell you how exciting this is in the cancer world and the medical world because this is really pristine cancer therapy that we’re dealing with here. And to be able to have this is just so important to life saving events in treating cancer. So. Dr. Deb Muth 29:41Let’s talk about something called the Dittar Chemoscale. This is the battle before the battle. Okay, so I’ve saved the most remarkable test for last, and this is one from a company called Dittar Cancer Genetics. They’re based out of the UK. They are CAP and CLIA certified, which means it meets the rigorous standards required for clinical laboratory testing in the US. And this test is called the ChemoScale. And it is a live cell chemosensitivity assay. So let me explain exactly what that means because it sounds complex, but the concept is actually quite elegant. When we drew the blood from Cameron, the Dittar’s laboratory isolated what are called circulating tumor associated cells or CTACs. And these are actually living cancer cells and they’re associated cells that are traveling through his bloodstream. Excuse me. So let’s think about that for a moment. Real live cancer cells isolated from a blood draw. Those living cancer cells were placed into a lab environment and exposed to over 70 different drugs, both conventional chemotherapy agents and what we call repurposed drugs. I’ll talk more about those in a minute. The lab then measured how many of those cancer cells were killed by each drug expressed as a percentage of cell death. So the scale runs from zero to a hundred and below 25%, that drug doesn’t work well against any type of cancer in that person. Might work great in somebody else, but in that particular person’s cancer that they have, it’s not gonna work so great. Anything that’s 25 to 50 % is intermediate and above 50 % is a high response. And that’s really where Dr. Deb Muth 31:43we want to be. We want to see anything higher than 50 % because that’s a great medication that can be used to kill the cancer. This is not a theoretical test. This is not based on tumor’s genetic sequence and the computer algorithm that predicts the drug response. This is a HIS actual tumor cell being killed or not being killed in real time. That is the difference. So in traditional chemotherapy, we have our protocols. If you have triple negative breast cancer, if you have HER2 positive breast cancer, if you have prostate cancer, if you have colon cancer, here’s the protocol that you’re going to use because that’s the type of cancer you have. That’s what’s been studied. Now, the problem is most of these cancers have mutated over time, especially depending on how long they’ve been in your body, because that’s what they do to try to survive. They have to change so they can survive because your immune system’s constantly trying to kill them. And so this is a really important thing. And if we don’t take an individual into response or into our thought process when we’re creating these protocols, we may give a drug that doesn’t work at all towards that cancer and you just wasted seven cycles of chemotherapy with a drug that never would have worked in the first place or had such low resistance to it that it’s now just created side effects for you but did nothing to the cancer. And then we pull out another drug and we try that. And then we pull out another drug and we try that. Instead of us knowing precisely what we can use and what we can do. And this goes for both the conventional world and the alternative world. In the alternative world of cancer, we use things like IV vitamin C and tumeric and lately ivermectin and fenbendazole and mendendazole and all kinds of other things. And if we are not truly aware that this is going to do anything, we could be wasting somebody’s time and money. So I love that this test is available. I want to walk you through a little bit about what Dr. Deb Muth 34:01we are what we saw in our case, because I think this can make a big impact on people to ask the right questions. So this particular blood test looked at several different drugs. Cameron had sensitivity from 44 % up to 61 % on different medications. Now he was really lucky. The three main drugs that they would use to treat his cancer he had greater than a 50 % response to. So that was great. However, the drugs that were recommended for him to use out of the gate had less than 50 % activity. So he would have had one drug that was really good, one drug that was not so good. And we don’t know what the outcome would have been, right? So I think this is such an incredible, incredible test to have done. This is critical friends. I’m telling you if his oncologist had chosen the two drugs based on the general guidelines for his tumor, his cells would have largely not survived. But because we ran this test, we know. So we know to avoid the drugs that won’t work and we focus on the firepower where it really counts. So I want to also talk about this repurposed drug result because this is where it gets integrated for us. Now, this section is what I want everyone in our community, our Let’s Talk Wellness community, our members to understand. This is where conventional medicine and integrative medicine intersect in a peer-reviewed clinical validated way. So the Dittar test looks at live cancer cells against what they call repurposed drugs, meaning pharmaceuticals and natural compounds that were developed for the purposes, for other purposes, like it could be an antibiotic, it could be an herbal medicine, it could be all kinds of things, vitamins, whatever. But they have demonstrated anti-cancer activity in research. And when we’re talking about integrative medicine, this is a lot of where we get Dr. Deb Muth 36:26The integrative protocols from because these particular drug compounds are known for having anti-cancer benefits. And so that’s how integrative protocols get developed. But again, it could be just like medication, like cancer drugs. If your body doesn’t have a susceptibility to it, then you’re using a product that’s not necessarily going to work. And we all know we cannot take everything that somebody recommends just simply because it has an anti-benefit to whatever it is we’re treating. There’s only so many supplements you can take. There’s only so many things you can do before you get burnt out on taking it. We call it supplement fatigue. And so we want to be very precise with what we’re doing and target this very specific area. So one of the things that showed up really, really well for our case was artemisium, sweet wormwood. It’s an anti-malarial drug that has very potent anti-cancer effects. Now I found this extremely interesting in Cameron’s case because he does have a positive tick-borne illness called Babesia. And this is one of the things that we use to treat Babesia. The other thing I think is very interesting in this case is we are studying how parasites affect cancer these days. And that’s how Ivermectin, Fenbendazole, and Menbendazole have all gotten thrown into the treatment of cancer. And so for this drug or this herb to be sensitive to this type of cancer is really intriguing to me in the world of parasites and how parasites are truly decreasing the body’s immune system and causing cancer to grow. Another thing that worked, showed up really well for him was Valprolac acid. It’s an anti-seizure drug with HDAC inhibitor properties, and this disrupts cancer cell gene expression. There was a soy formula that showed up really well. Naltrexone, you guys have heard me talk about low dose naltrexone, LDN. This actually stimulates an endogenous opioid immune response feeling, and this drug actually showed up really well. Dr. Deb Muth 38:49Something as simple as quercetin. It’s an anti-inflammatory. This is a crass inhibitor in some studies. So this is really important. I’m sure most of you have heard about the benefits of green tea and green tea also actually has anti-angiogenic or anti-cancer benefits to it. Hydroxychloroquine, very popular drug. It’s another anti-malarial drug. So again, now we have two anti-malarial drugs that are susceptible to this type of cancer. And on top of it, he has a positive babesia test. So just saying, you got to connect the dots sometimes. You got to think outside the box sometimes. Metformin is very well known as a anti-proliferative in cancer. We use it to suppress the sugar because sugar feeds cancer. Nobody should be eating sugar if they have cancer. So this one showed up as well. And then CBD, we all know of the benefits of THC, the Rick Simpson oil, and CBD can be tested to see if that is beneficial to a particular cancer cell. This is different than THC. THC works very differently in cancer. CBD is your healthy component of it. It’s the part of the marijuana plant that does not make you high. So very important here. So now let me be very clear, because I always try to be very clear. This is not FDA approved. I’m going to repeat that. This is not FDA approved. This test is a laboratory developed test, not FDA cleared. These results represent in vitro testing, meaning in a lab, not inside the human body. And the results can differ in what we call in vivo, inside the body. And this is why I always say work with a qualified clinician who can interpret these results in full clinical context. But here’s why this matters. We now have evidence, live evidence of a cancer cell that shows sensitivities to compounds that are accessible, relatively safe, and some of which he may already be using, which some of them we were. Dr. Deb Muth 41:13We were already using some of them, which made us sit back and say, this cancer has been in there for two years. If it’s a triple negative breast cancer, it’s supposed to be an aggressive breast cancer that should have spread to a different organ already after two years. It is not, it has stayed in one spot. Also interesting in this case is that there is no breast tumor that they could find anywhere. This was all confined to the axilla into the lymph node. So to have this growing for this period of time with such a small tumor marker number, that 13 that we talked about in the North Star test originally, and to see some mutations, there’s a lot of questions to this particular case. And there are lots of questions to everybody’s cancer case. They are not all straightforward cancer cases. So this is what’s important to understand this fingerprint of these cancer cells so that you can identify exactly, exactly what’s going on and treat it exactly the correct way. Super important. So this kind of information gives us the direction in an integrative protocol. It’s not guessing. This is not eat more tumor, I can hope for the best. This is personalized tumor specific precision guided integrative oncology. It is very precise. There are several countries, several clinics like this around the country that offer this type of therapy. If it’s something that you’re interested in doing, I would encourage you to look at in Vita Medical. Hope for Cancer is another great facility. There are several great facilities around the country. Like I said, that could put together an integrative approach for you if this is something that you are thinking about doing. If you’re looking for answers, if you’re in stage four or stage three and you are not getting the results that you want to get, you want to look at a different approach. You want to do a combo approach of integrative medicine and traditional medicine and alternative medicine. Dr. Deb Muth 43:37I think this is so important to look at and have experts on your team. You know, in our case, Cameron’s cancer is very complex. It’s genomically aggressive in its presentation, yet it’s not progressing to distant areas, which is so wonderful. And I want to be careful here. I can’t tell you with certainty that this is any one thing. Biology is complex. Cancer is adaptive. It’s trying to survive. That’s what it is supposed to do. It is changing its shape. It’s changing its genetic structure. It’s changing everything to try to survive and try to hide against your immune system. Now we are not even close to the finish line in our journey, but what I can tell you is that what the integrative precision approach has done that standard care alone might not do. I can tell you that today and I will share our journey along the way for any of you that are going through this that want to look at a different approach as well because I think it’s important to have this information. So first of all, we know the tumor’s fingerprint. North Star response gives us that TMS score. so we can track it over time. And if the cancer tries to gain ground, we’ll see it in the blood before a scan, we’ll show it. We know the cancer’s genetic vulnerability. We know how to handle the DNA now. We know the watch list of things to look for. And when those signals start to grow, we have a roadmap of how to address it next, how to change it. We know which drugs will automatically work against the tumor cells. We’re not guessing based on a tumor type. We tested the cells. We know how many drugs in the commercial world and in the repurposed world will and will not work. And this is going to guide the treatment protocol that we walk forward with. So we’re not giving him drugs that won’t work or have a low response. Dr. Deb Muth 45:55We’re avoiding them completely and that matters because every ineffective drug is a dose of toxicity with no benefit. There is no lie to this. Chemotherapeutic drugs are toxic. That’s how they kill the cells, but they kill the good cells and the bad cells. And if we can avoid using a drug that’s not going to work, that is so important. And then we’re layering in those repurposed and natural compounds with proven activity against specific cells. This is not complementary fluff. This is biologically active tumor tested precision medicine. Very, very important. So here is what I need you all to know and what I want you to walk away with today. If you or someone you love is facing a cancer diagnosis before treatment starts, before the first infusion goes in, I want you to ask these questions so quick. Go grab something to write with. Pause this if you need to, because this is really, really important for you to do that. And we’re going to take a break for just a second while you guys go and do that. We’re going to give you a word from our sponsor, and then we’re going to come back. And I’m going to give you the four questions that I want you to ask specifically of your medical team so that you have the answers and the ammunition that you need to work with. So we’ll be right back. Dr. Deb Muth 47:29All right, everybody, welcome back. I hope you got your pencil, your paper, your pen, your phone, whatever you’re going to take notes with because this is important. So I’m to give you four questions that I want you to ask your medical team before you get started. Question one, can we do a chemo sensitivity test before we choose a chemotherapy regime? Ask specifically about DATAR, D-A-T-A-R. cancer genetics, Oncostat Plus, or a similar functional chemosensitivity platform. Very, very important to ask those specific things. All right, question two. Can we do a comprehensive liquid biopsy to identify actionable mutations and monitor tumor burden? Ask about North Star Select, Billion to One, Guardian 360, or Foundation One Liquid CDX? I’m gonna say those for you one more time, because I said them kind of fast. North Star Select by Billion to One, Guardian 360 or Foundation One Liquid CDX? Okay, question three. Can we establish a baseline tumor methylation score, TMS, so we have a surveillance marker to track over time? and ask specifically about the North Star Response Test. All right, question four. Is there an integrative oncology center that can layer precision guided natural compounds alongside conventional treatment? Research institutes like Inveda Medical Center, CTA CA Integrative Medicine, or Hope for Cancer, these people are doing integrative medical miracles. Let me tell you, I have researched every one of them. I have spoken to each of them individually before we made our decision of who we were going to work with. They are all fantastic. You want to work with an integrative nurse practitioner who understands oncology. And if you’re working with an integrative practitioner, you want to ask them these same questions about this test so that you can get the best outcome. Dr. Deb Muth 49:56For what you’re dealing with. You are allowed to ask these questions. You are allowed to want more information from that protocol that was designed for the average patient. You’re not average and your cancer is not average either. And your care doesn’t have to be. You do not have to settle for the same thing that the person sitting next to you in the IV suite is dealing with when you both have different cancers excreting different genetic material. This is so incredibly important. want to make sure you understand precision medicine is what changes the lives for people every single day, every single day. So I started this episode by telling you about a 38 year old man with a cancer that baffled conventional medicine and integrative medicine, an occult primary that was not found complex genetic genomic profile, a presentation that in many hands might have resulted in a one size fits all treatment protocol and a prayer. And instead we ran the tests, we mapped the fingerprint, we watched the cells, we guided the protocol, and we are still fighting with precision, with data, with intelligence. This is what Let’s Talk Wellness is all about not giving up. This is what not accepting we don’t know as a final answer and demanding the level of scrutiny and personalization that every cancer patient deserves. So if this episode resonates with you, please share it because somewhere out there, there is a person who is about to get the wrong chemotherapy because no one ran the right test. And maybe, just maybe, that This episode will be the reason someone asks the right question at the right moment. If you’re going through something like this, you need a group, you need somebody to connect with, please join our free Facebook group called Seen At Last. It is where we support one another, we share this information, we share knowledge, and we help people for free support and ask the right questions. Dr. Deb Muth 52:23And if you’re inclined in your heart to pray, pray for Cameron, we could use every ounce of prayer. If you are in a position where you can help support this journey financially, we do have a fund going in free funder. I can post the link below. Every little bit helps. If you have $5, $500, it doesn’t matter. We’re raising money for this treatment. And along the way, I am documenting every step of what we’re going through so I can provide more episodes like this for you guys to share the outcome and share what our journey is like so that it can help the next person along. I really always believe that whatever happens to us happens to us because we’re meant to share it. That’s why I’ve shared my personal journey. I’m sharing his personal journey and we want to help other people. So until next time, I’m Dr. Deb. Keep asking questions, keep advocating, and never ever accept being unseen.The post Episode 274 – Stop Guessing on Chemotherapy: The Live Cell Test Most Doctors Miss first appeared on Let's Talk Wellness Now.

HEADLINES:• Former Sky News Arabia boss slams Guardian reporting on Sky UAE exit• Alabbar and IHC show interest in debt-hit IFFCO• e& sells 12.5% Careem stake to Uber in $100 million dealNewsletter: https://aug.us/4jqModrWhatsApp: https://aug.us/40FdYLUInstagram: https://aug.us/4ihltzQTiktok: https://aug.us/4lnV0D8Smashi Business Show (Mon-Friday): https://aug.us/3BTU2MY

CME credits: 0.25 Valid until: 01-06-2027 Claim your CME credit at https://reachmd.com/programs/cme/chairpersons-perspective-her2-in-solid-tumors-from-pathology-to-personalized-treatment-plans/54582/ Dr. Kathleen Moore reviews the clinical significance of HER2 expression across diverse solid tumors and its role in guiding treatment decisions. She outlines HER2 testing methodologies, including immunohistochemistry (IHC), to identify patients with advanced solid tumors who may benefit from HER2-targeted antibody–drug conjugates (ADCs). Dr. Moore summarizes key data from trials such as DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02 that supported tumor-agnostic approval of trastuzumab deruxtecan (T-DXd) for previously treated metastatic HER2-positive (IHC 3+) solid tumors, along with strategies for proactive monitoring and management of ADC-associated adverse events.=

In today's episode, we spoke with Anthony Chi, MD, a staff pathologist; Monica Peravali, MD, a medical oncologist; and Archana Jadhav, MD, a medical oncologist, all faculty at the Mid-Atlantic Permanente Medical Group in Maryland. In our exclusive interview, Drs Chi, Peravali, and Jadhav discussed the practical advantages and clinical implications of implementing in-house next-generation sequencing (NGS) testing for patients with non–small cell lung cancer (NSCLC). The conversation focused on how internal molecular testing platforms can improve turnaround times, optimize tissue stewardship, reduce costs, and enhance quality control across the diagnostic and treatment continuums.Chi explained that performing NGS internally eliminates delays associated with specimen transportation and external laboratory accessioning, significantly shortening turnaround times. He also highlighted Kaiser Permanente's decision to implement a molecular platform distinct from those commonly used by outside vendors, allowing for reduced tissue input requirements and faster processing times. According to Chi, internal testing also gives pathology teams greater oversight of specimen use, enabling more strategic tissue conservation for future immunohistochemical (IHC) staining, repeat molecular analyses, or additional biomarker testing.The panel emphasized the importance of close coordination between pathology and oncology teams in maximizing tissue adequacy, particularly in small biopsies and cytology specimens. Chi described educational initiatives implemented within pathology departments to encourage judicious use of IHC stains and preserve tissue for downstream molecular testing. He also outlined specimen-handling workflows in which tissue is divided into separate cassettes to prioritize molecular analysis and still supporting diagnostic evaluation.Jadhav discussed the oncologist's role in ensuring adequate tissue acquisition, emphasizing proactive communication with pathologists and interventional radiologists. She noted that when clinicians anticipate limited tissue yield, such as in pleural fluid cytology specimens, they often promptly arrange additional biopsies to avoid delays in treatment initiation and ensure comprehensive genomic profiling can be completed efficiently.The discussion also addressed optimal timing for comprehensive genomic profiling in NSCLC. Peravali explained that Kaiser Permanente routinely performs NGS across all disease stages, including early-stage disease, due to increasing use of neoadjuvant chemoimmunotherapy approaches and the need to identify actionable biomarkers that may influence treatment selection. Although in-house testing serves as the primary platform, she noted that send-out testing remains important in select situations, including cancers of unknown primary origin, clinical trial enrollment, and discordant or clinically suspicious cases requiring additional confirmation.As molecular reports become increasingly complex, the panel highlighted the importance of interpreting co-mutations, variants of unknown significance, and emerging biomarkers within a broader clinical context. Peravali explained that although variants without current therapeutic relevance may not immediately affect treatment decisions, repeat biopsies and serial NGS at disease progression can reveal newly actionable alterations as therapeutic options evolve.Chi further emphasized the growing importance of newly approved biomarkers, including HER2 and c-MET alterations, in NSCLC. He described how pathology teams actively monitor FDA approvals and National Comprehensive Cancer Network (NCCN) guideline updates to identify new therapeutic opportunities for previously profiled patients. In some cases, archived tumor specimens are revisited for additional IHC testing when emerging therapies become clinically relevant.The conversation also highlighted the value of multidisciplinary collaboration and tumor board discussions in complex diagnostic scenarios. The speakers described how integrated molecular analysis can help distinguish separate primary lung tumors from metastatic disease, resolve diagnostically challenging cases involving uncommon metastatic presentations, and support more confident staging and treatment decisions.Finally, the panel underscored that successful implementation of precision oncology workflows depends on seamless collaboration among pulmonologists, pathologists, oncologists, interventional radiologists, and molecular laboratories. Early test ordering, centralized communication systems, and multidisciplinary case review were identified as key components of efficient, patient-centered care that can accelerate diagnosis and improve treatment planning for patients with lung cancer.

Send us Fan MailDo you really need a scanner, whole slide images, and AI infrastructure before you can start in digital pathology?In this episode, I argue that you do not.I'm Dr. Aleksandra Zuraw, veterinary pathologist and digital pathology educator, and this talk is about a belief I hear all the time: I don't have the tools yet, so there is no point learning digital pathology. I used to think that too. When I was training in Berlin, there was one Leica 6-slide scanner, and it felt like digital pathology was only for a small group of chosen people. That experience made the field feel distant, exclusive, and not really available to beginners. What changed for me was not a new scanner. It was a small project.I needed a more consistent way to quantify a senescence marker in archived skin samples, so I used a microscope camera, captured images, opened them in Microsoft Paint, and manually marked cells with colored dots. It was scrappy. Very low tech. But it was also digital, consistent, and verifiable. That project became my first real step into digital pathology and helped me get my first job in the field, where I worked between pathologists and image analysis scientists on biomarker quantification and patient stratification problems. That is the core point of this episode: knowledge unlocks technology.Scanners matter. AI tools matter. But the deeper bottleneck is whether enough people understand how to use these tools, ask good questions, and connect pathology expertise with digital workflows. That is why this episode is really about readiness. Not readiness of the hardware. Readiness of the people.I also talk about Dr. Taladzer from Pakistan, whose story makes this point even more clearly. At the time, Pakistan had around 220 million people, about 500 pathologists, and zero scanners. She still started learning digital pathology during COVID using a microscope and camera, joined the Digital Pathology Association, taught herself from papers and online resources, and kept going even after multiple AI vendors rejected her because she did not have whole slide images. Eventually, she found a DIY image analysis platform, learned to annotate and train models on static images, completed projects quickly, and went on to publish more than 10 digital pathology papers without ever using WSI.Why should you listen?Because this episode is for pathologists and lab leaders who are interested in digital pathology but still feel stuck at the beginning. It is for people waiting for permission, perfect infrastructure, or a formal roadmap. And it is for trailblazers who came back from a meeting or conference energized, but need a practical way to turn that energy into action before it fades.I also address an important AI question near the end: How do we know an AI model is good enough for pathology? I talk about why models are only as good as the pathologist annotations used to train them, why concordance between pathologists matters, how orthogonal labels like IHC can improve model quality, and why pathologists still need to stay in the loop as these systems develop and get deployed.If you are trying to figure out where to start, this episode gives you a practical answer: start where you are. Start with what you have. Start learning now.Episode Highlights00:00 – Why the real barrier to digital pathology is usually not the hardware 00:33 – What it feels like to be at the beginning of the digital pathology journey 02:50 – My first practical digital pathology project using a microscope camera and Microsoft Paint 05:37 – How that low-tech project led to my first digital pathology job 08:52 – Why knowledge, not infrastructure, is the real unlock 09:57 – Dr. Taladzer's story: starting digital pathology in Pakistan with zero scanners 12:03 – What happened after repeated vendor rejection and why persistence mattered 14:39 – The “forgetting loop” vs the “commitment loop” after conferences 16:48 – Practical next steps: book, PubMed alerts, journal clubs, webinars, vendor resources 18:52 – Why I believe digital pathology is the gateway to faster diagnosis 20:00 – How to think about whether an AI model is really ready for pathologyResources MentionedDigital Pathology 101 – free book recommended as a starting point for learning digital pathology. Digital Pathology Association – mentioned as a learning resource and professional community. PubMed alerts for AI and digital pathology. Journal clubs – mentioned as one way to keep learning consistently. Webinars and vendor resources – suggested as practical ways to keep building knowledge. A4A – the DIY image analysis platform that supported Dr. Taladzer's early work with static image annotation and model training. Support the showGet the "Digital Pathology 101" FREE E-book and join us!

Send us Fan MailWhy are pathology vendors still speaking different image languages when radiology solved that problem decades ago?In this episode of DigiPath Digest #46, I talk through four papers that all point to a bigger issue in digital pathology: we are not only dealing with better algorithms. We are dealing with interoperability, workflow design, explainability, and whether the field is actually ready to use these tools well.I start with DICOM in digital pathology, because I think this is still one of the most important infrastructure questions in the field. Digital pathology has clear value for consultation, image analysis, archival, and workflow, but vendor-specific whole slide image formats still create silos. In the episode, I explain why DICOM matters, why adoption is still low, how the multi-resolution pyramid works, and why this is really about enterprise imaging and future-proofing, not just file conversion. Then I move into kidney transplant rejection, where the paper makes a strong case for multimodal precision diagnostics. Creatinine is late. Antibody testing can miss important biology. Biopsies can miss the area that matters. So the opportunity is not to replace pathology, but to combine biomarkers, biopsy, and machine learning in a way that is more useful than any one signal alone. I also talk about explainability here, because if a model gives a risk score, we need to know what contributed to it. The third paper focuses on perineural invasion in solid tumors, and I liked this one a lot because it shows how AI can help standardize something that is clinically important but still inconsistently detected and reported. Perineural invasion is not just a passive pathway of spread. The biology is more active than that, and the quantification can go far beyond a simple yes-or-no answer. This is a good example of where digital pathology can do something humans cannot realistically do by eye at scale. The last paper is on gastric cancer immunohistochemistry biomarkers and advanced quantification, including HER2, PD-L1, mismatch repair, and CLDN18.2. This section is really about complexity. We are now asking pathologists to visually score biology that is getting harder and harder to summarize consistently, especially when markers, spatial context, and multiplexing all start to matter at once. I make the case that computational pathology is becoming necessary here, not because pathologists are failing, but because the biology is outgrowing purely visual workflows. What ties these four papers together is simple: digital pathology is not only about remote reading anymore. It is about interoperability, quantification, explainable AI, and making pathology more precise in places where the old workflow is reaching its limit. If you are a pathologist, lab leader, or digital pathology trailblazer trying to figure out what actually matters right now, this episode will help you connect the dots.Episode Highlights 07:41 – Why DICOM still matters if we want digital pathology systems to work together. 14:39 – Current adoption of SVS, MRXS, and DICOM, and why DICOM is still lagging. 16:44 – How the DICOM whole slide image pyramid works and why it matters for workflow. 24:29 – Why kidney transplant rejection is still difficult to diagnose with any single marker. 29:18 – Why perineural invasion is clinically important and still inconsistently reported. 34:44 – How AI can quantify tumor-nerve relationships more consistently than visual review alone. 46:39 – Why gastric cancer biomarker scoring is getting too complex for purely visual workflows. 54:55 – Multiplexing, spatial biology, and why explainable AI matters in biomarker interpretation. 01:04:01 – What is really blocking digital pathology adoption: cost, workflow, regulation, or mindset? Resources mentionedDICOM / digital pathology interoperability paper https://pubmed.ncbi.nlm.nih.gov/42093730/Kidney transplant rejection, biomarkers, and artificial intelligence https://pubmed.ncbi.nlm.nih.gov/42073482/Perineural invasion in solid tumors with AI and machine learning applications https://pubmed.ncbi.nlm.nih.gov/42100436/Gastric cancer IHC biomarkers, advanced detection methods, and perspectives https://pubmed.ncbi.nlm.nih.gov/42075555/Digital Pathology Place https://digitalpathologyplace.comDigital Pathology 101 Free PDF book mentioned at the end of the episode through Digital Pathology Place.Support the showGet the "Digital Pathology 101" FREE E-book and join us!

In this episode, we cover the billion-pound acquisition by IHC's Diafa of the iconic British hospitality empire "The Ivy." We also break down the stalemate in U.S.-Iran talks over the nuclear file and the Strait of Hormuz. Finally, we highlight the powerful display of national unity as global giants like Microsoft and ADNOC join the UAE community in raising the national flag.

Send us Fan MailYou don't need a fancy scanner, a huge budget, or a computational background to get started in digital pathology. That's what I told the ACVP podcast — and I meant it. In this episode, I share my full digital pathology journey: from being completely intimidated by scanners during residency, to building a career that combines toxicologic pathology, image analysis, and remote work at a global CRO.If you're a resident, a trainee, or even a seasoned pathologist who hasn't fully stepped into the digital space yet — this one's for you.We talked about practical ways to get started, what foundation models actually mean for our daily work, how to build a team when implementing digital pathology at your institution, and why change management might be the most underestimated skill in this whole process.What we cover:[00:00] My background — from veterinary school in Poland to digital pathology[03:22] Why I chose industry over academia, and what that transition looked like[05:02] How a simple IHC side project became my entry point into digital pathology[07:11] How digital slides helped me pass my boards — and fall back in love with histopathology[10:24] My first job at a digital pathology image analysis company[12:00] What my current role at Charles River Laboratories looks like day-to-day[13:53] The best free resources for trainees to start exploring digital slides RIGHT NOW[15:26] Why pathologists need to understand image analysis principles — segmentation, classification, object detection[19:31] Foundation models, transformer architecture, and why annotation bottlenecks may soon be a thing of the past[24:13] Practical advice for institutions implementing digital pathology — equipment, teams, and managing resistance to change[27:30] How I unplug: trail running, weight training, and pathology-themed earringsResources & Links:Joint Pathology Center (JPC) digital slides: https://www.jpc.orgDavis Thompson Foundation — Noah Slidebox: https://www.davisthomasonfoundation.orgQuPath (free, open-source image analysis): https://qupath.github.ioDigital Pathology Place: https://www.digitalpathologyplace.comWatch the full conversation on YouTube: https://youtu.be/wTDdlxJzq-A?si=xkz5YNljrUX5SnhdSupport the showGet the "Digital Pathology 101" FREE E-book and join us!

In this episode of the Oncology Brothers podcast, we dived deep into the complexities of Cancer of Unknown Primary (CUP). Joined by Dr. Harry Fuentes Bayne and Dr. Thor Halfdanarson from the Mayo Clinic, they discussed the current standard of care, diagnostic workup, and treatment options for this challenging condition. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Apple Podcast: https://podcasts.apple.com/us/podcast/oncology-brothers-practice-changing-cancer-discussions/id1653340966 Follow us on social media: ⁠X/Twitter: https://twitter.com/oncbrothers Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Key topics included: Initial diagnostic approaches for CUP, including imaging and tissue sampling The role of immunohistochemistry (IHC) and tumor markers in guiding treatment The use of next-generation sequencing (NGS) and tools like Cancer Type ID Treatment strategies, including chemotherapy regimens and the potential for immunotherapy The importance of thorough workup and palliative care in managing CUP Whether you're a healthcare professional or simply interested in oncology, this episode provides valuable insights into the latest approaches for diagnosing and treating cancer of unknown primary origin. Don't forget to like, subscribe, and check out our other episodes for more discussions on treatment algorithms, conference highlights, and FDA approvals. Join us on this journey through the world of oncology! #CancerOfUnknownPrimary, #CUP, #NGS, #Immunohistochemistry, #OncologyBrothers

#stockmarketnews #investing #finance #nasdaq #crudeoil #indiagdp #hdfcbank #pbfintech #sammaancapital #nifty50 #bse #wallstreet #economy #businessnews #geopolitics Get the latest market updates! Today we discuss Wall Street's 2% surge amid Iran de-escalation hopes and rising oil risks from Houthi threats. We also cover EY's warning on India's FY27 GDP taking a hit from the conflict. In corporate news, Abu Dhabi's IHC invests ₹8,850Cr in Sammaan Capital, HDFC Bank's CEO is likely to get an extension, and PB Fintech expands to the UAE.https://shorturl.at/gM97lHow to Use Artificial Intelligence for Investing - Combo of 5 ebooks00:00 Nasdaq Soars on Iran Hopes03:20 Oil Risks Rise on Houthi Threats05:25 EY Warns of India GDP Hit08:11 IHC Acquires Stake in Sammaan10:36 HDFC Bank CEO Likely to Stay12:00 PB Fintech Invests in UAE13:12 Believe it or not section

In this episode of the Oncology Brothers podcast, we were joined by two international experts — Professor Gary Tse, a pathologist from the Chinese University of Hong Kong, and Dr. Carlos Barrios, a medical oncologist from Brazil — to unpack the evolving landscape of HER2 testing in breast cancer. What was once a binary positive or negative classification has now expanded to include HER2-low and HER2-ultra-low, opening the door to new treatment options for the majority of breast cancer patients. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o   Follow us on social media: X/Twitter: https://twitter.com/oncbrothers ⁠Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Key topics discussed included: How HER2 classification has evolved from a binary result to a continuous spectrum including HER2-low and HER2-ultra-low, driven by the efficacy of antibody drug conjugates like T-DXd Pre-analytical challenges in metastatic settings including tumor heterogeneity The role of IHC, ISH, NGS, and liquid biopsy in HER2 assessment, and how each tool fits into clinical practice. The importance of multidisciplinary collaboration between pathologists and oncologists to ensure accurate interpretation and optimal treatment selection. Join us for this expert discussion on one of the most clinically impactful topics in breast oncology today. Don't forget to like, subscribe, and check out our other episodes for more insights on oncology! #HER2, #BreastCancer, #BiomarkerTesting, #PrecisionOncology, #OncologyBrothers

Send us a textThis session is a practical walkthrough of where digital pathology and AI truly stand in early 2026—based on five recent PubMed papers and real-world implementation experience.In this episode, I review new clinical adoption guidelines, AI applications in liver cancer imaging and pathology, AI-ready metadata for whole slide images, non-destructive tissue quality control from H&E slides, and machine learning–assisted IHC scoring in precision oncology.This conversation is not about hype. It's about standards, validation, data integrity, and clinical translation—the factors that decide whether AI tools stay in research or reach patient care.Episode Highlights01:21 – Practical digital pathology adoption guidelines (Polish Society of Pathologists)08:05 – AI in liver cancer imaging & pathology, and why framework alignment matters18:10 – AI-generated tissue maps as metadata for WSI archives23:01 – PathQC: predicting RNA integrity and autolysis from H&E slides32:14 – ML-assisted IHC scoring in genitourinary cancers29:42 – Digital Pathology 101 book + community updatesKey TakeawaysDigital pathology adoption still requires clear standards and validation workflowsAI performs best when aligned with existing diagnostic frameworks (e.g., LI-RADS)Metadata extraction is a low-effort, high-impact AI use caseSlide-based quality control can support biobanking and biomarker researchAutomated IHC scoring improves consistency—but adoption remains uneven globallyResources Mentioned Digital Pathology 101 (free PDF & audiobook)Publication Links:  a. https://pubmed.ncbi.nlm.nih.gov/41618426/                                                                 b. https://pubmed.ncbi.nlm.nih.gov/41616271/                                                                   c. https://pubmed.ncbi.nlm.nih.gov/41610818/                                                                 d. https://pubmed.ncbi.nlm.nih.gov/41595938/                                                                 e. https://pubmed.ncbi.nlm.nih.gov/41590351/ Support the showGet the "Digital Pathology 101" FREE E-book and join us!

Dr. Sonam Puri discusses the full update to the living guideline on stage IV NSCLC with driver alterations. She shares a new overarching recommendation on biomarking testing and explains the new recommendations and the supporting evidence for first-line and subsequent therapies for patients with stage IV NSCLC and driver alterations including EGFR, MET, ROS1, and HER2. Dr. Puri talks about the importance of this guideline and rapidly evolving areas of research that will impact future updates. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.0" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  https://ascopubs.org/doi/10.1200/JCO-25-02822    Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Sonam Puri from Moffitt Cancer Center, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It's great to have you here today, Dr. Puri. Dr. Sonam Puri: Thanks, Brittany. Brittany Harvey: And then just before we discuss this guideline, 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 disclosures of potential conflicts of interest for the guideline panel, including Dr. Puri, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content that we're here today to talk about, Dr. Puri, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer with driver alterations is updated on an ongoing basis. So, what data prompted this latest update to the recommendations? Dr. Sonam Puri: So Brittany, non-small cell lung cancer is one of the fastest-moving areas in oncology right now, particularly when it comes to targeted therapy for driver alterations. New data are emerging continuously from clinical trials, regulatory approvals, real-world experience, which is exactly why these are living guidelines. The goal is to rapidly integrate important advances as they happen, rather than waiting for years for a traditional update. Since the last full update of the ASCO Stage IV Non-small Cell Lung Cancer Guideline with Driver Alterations published in 2024, there have been seven new regulatory approvals and changes in first-line therapy for some driver alterations. [This version] of the "Stage IV Non-small Cell Lung Cancer Guidelines with Driver Alterations" represents a full update, which means that the panel reviewed and refreshed every applicable section of the guideline to reflect the most current evidence across therapies including sequencing and clinical decision-making. This is to ensure that clinicians have up-to-date practical guidelines that keep pace with how quickly the field is evolving. Brittany Harvey: Absolutely. As you mentioned, this is a very fast-moving space and this full update helps condense all of those versions that the panel reviewed before into one document, along with additional approvals and new trials that you reviewed during this time period. So then, the first aspect of the guideline is there's a new overarching recommendation on biomarker testing. Could you speak a little bit to that updated recommendation? Dr. Sonam Puri: Yeah, definitely. So the panel has discussed and provided recommendations on comprehensive biomarker testing and its importance in all patients diagnosed with non-small cell lung cancer. Ideally, biomarker testing should include a broad-based next-generation sequencing panel, rather than single-gene tests, along with immunohistochemistry for important markers such as PD-L1, HER2, and MET. These results really drive treatment decisions, both in frontline settings for all patients diagnosed with non-small cell lung cancer and in subsequent line settings for patients with non-small cell lung cancer harboring certain targetable alterations. Specifically in the frontline setting, it helps determine whether a patient should receive upfront targeted therapy or immunotherapy-based approach. We now have strong data that shows that complete molecular profiling results before starting first-line therapy is associated with better overall survival and actually more cost-effective care. Using both tissue and blood-based testing can improve likelihood of getting actionable results in a timely way, and we've also provided guidance on platforms that include RNA sequencing, which are specifically helpful for identifying gene fusions that might be otherwise missed with other platforms. On the flip side, outside of a truly resource-limited setting, single-gene PCR testing really should not be routine anymore. This is what the panel recommends. It's less sensitive and inefficient and increases the risk of missing important actionable alterations. Brittany Harvey: Understood. I appreciate you reviewing that recommendation. It really helps identify critical individual factors to match the best treatment option to each individual patient. So then, following that recommendation, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer with a driver alteration? Dr. Sonam Puri: Since the last full update in 2024, there have been four additional interim updates which were published across 2024 and 2025. Compared to the last version, there have been several updates which have been included in this full update. One of the most important shifts has been in first-line treatment of patients with non-small cell lung cancer harboring the classical, or what we call as typical, EGFR mutation. The current version of the recommendation is based on the updated survival data from the phase III FLAURA2 and MARIPOSA studies, based on which the panel recommended to offer either osimertinib combined with platinum-pemetrexed chemotherapy or the combination of amivantamab plus lazertinib in the first-line treatment of classical EGFR mutations. And these recommendations, as I mentioned, are grounded in the results of the FLAURA2 and MARIPOSA trials, both of which demonstrated improvement in progression-free survival and overall survival compared to osimertinib alone in patients with common EGFR mutations. That being said, the panel actually spent significant time discussing the toxicities associated with these treatments as well. These combination approaches come with higher toxicity, longer infusion time, increased treatment frequency. So while combination therapy is now recommended as preferred, the panel has recommended that osimertinib monotherapy remains a reasonable option, particularly for patients with poor performance status and for those who are not interested in treatment intensification after knowing the risks and benefits. Brittany Harvey: Absolutely. It's important to consider both those benefits and risks of those adverse events that you mentioned to match appropriately individualized patient care. So then, beyond those recommendations for first-line therapy, what is new for second-line and subsequent therapies? Dr. Sonam Puri: So this is a section that saw several major updates, particularly again in the EGFR space. The first was an update on treatment after progression on osimertinib for patients with classical EGFR mutation. Here the panel recommends the combination of amivantamab plus chemotherapy, and this recommendation was based on the phase III MARIPOSA-2 trial, which compared amivantamab plus chemotherapy with chemotherapy alone with progression-free survival as the primary endpoint. The study met its primary endpoint, showing an improvement in median PFS with the combination of amivantamab plus chemotherapy compared to chemotherapy alone. And as expected, the combination was associated with higher toxicity. So, although the panel recommends this regimen, the panel emphasizes that patients should be counseled on the side effects which may be moderate to severe with the combination therapy approach. In addition, a new recommendation was added for patients who are not candidates for amivantamab plus chemotherapy. In those cases, platinum-based chemotherapy with or without continuation of osimertinib may be offered, and the option of continuing osimertinib with chemotherapy was recommended and supported by data from a recently presented phase III COMPEL study, which randomized 98 patients with EGFR exon 19 deletion or L858R-mutated advanced non-small cell lung cancer who had experienced no CNS progression on first-line osimertinib, and these patients were randomized to receive platinum-pemetrexed chemotherapy with osimertinib or placebo. Although this study was small, it demonstrated a PFS benefit with continuation of osimertinib with chemotherapy, and this approach may be appropriate for patients without CNS progression who prefer or require alternatives to more intensive treatment strategies. Next was an update on options for patients with EGFR-mutated lung cancer after progression on osimertinib and platinum-based chemotherapy. Here the panel recommended that for patients whose disease has progressed after both osimertinib and platinum-based chemotherapy, a new drug known as datopotamab deruxtecan can be offered as a treatment option. And this treatment recommendation was based on evaluation of pooled data from the TROPION-Lung01 and TROPION-Lung05 study, in which in the pooled analysis about 114 patients with EGFR-mutant non-small cell lung cancer were treated with Dato-DXd, 57% of whom had received three or more prior lines of treatment, and what was observed was an overall response rate of 45% with a median duration of response of 6.5 months. So definitely promising results. Next, we focused on updates to subsequent therapy options for patients with another type of EGFR mutation known as EGFR exon 20 insertion mutations. In this section, the panel added sunvozertinib as a subsequent line option after progression on platinum-based chemotherapy with or without amivantamab. Sunvozertinib is an oral, irreversible, and selective EGFR tyrosine kinase inhibitor with efficacy demonstrated in the phase II WU-KONG6 study conducted in Chinese patient population. In this study, amongst 104 patients with platinum-pretreated EGFR exon 20 mutated non-small cell lung cancer, the observed response rate was 61%. Staying in the EGFR space, the panel added a recommendation for patients with acquired MET amplification following progression on EGFR TKI therapy. In these situations, the panel recommended that treatment may be offered with osimertinib in combination with either tepotinib or savolitinib. As our listeners may know, MET amplification occurs in approximately 10% to 15% of patients with EGFR-mutated non-small cell lung cancer when they progress on third-generation EGFR TKIs, and detection of MET amplification is done with various methods, such as tissue-based methods like FISH, NGS, and IHC, as well as ctDNA-based NGS with variable cut-offs. Over the last few years, several studies have informed this recommendation. I'm going to be discussing some of them. In the phase II ORCHARD trial, 32 patients with MET-amplified non-small cell lung cancer after progression on first-line osimertinib were evaluated, where the combination of osimertinib plus savolitinib achieved an overall response rate of 47% with a duration of response of 14.5 months. More recently, the phase II SAVANNAH trial reported outcomes in 80 patients with MET-amplified tumors after progression on osimertinib, and in this patient population, the combination of savolitinib and osimertinib achieved an overall response rate of 56% with a median PFS of 7.4 months. And lastly, the phase II single-arm INSIGHT 2 trial assessed the efficacy of osimertinib plus tepotinib in patients with advanced EGFR-mutant non-small cell lung cancer who had disease progression following first-line osimertinib therapy. And in this study, in a cohort of 98 patients with MET-amplified tumors confirmed by central testing, the overall response rate with the combination was 50% with a duration of response of 8.5 months. So definitely informing this guideline recommendation. Next, we had an update on recommendation in patients with ROS1-rearranged non-small cell lung cancer. For patients with ROS1-rearranged non-small cell lung cancer, the panel recommended specifically for patients who progressed after first-line ROS1 TKIs, the addition of taletrectinib as a new option alongside repotrectinib. And this recommendation was based on analysis of the results of the TRUST-I and TRUST-II studies, which showed that amongst 113 tyrosine kinase inhibitor-pretreated patients, taletrectinib achieved a confirmed overall response rate of 55.8% with a median duration of response of 16.6 months and a median PFS of 9.7 months, a very promising agent. Finally, for patients with HER2 exon 20 mutated non-small cell lung cancer, the panel added two new oral HER2 tyrosine kinase inhibitors, zongertinib and sevabertinib, as options in addition to T-DXd and after exposure to T-DXd. These recommendations are based on early phase data from two trials: the phase I Beamion LUNG-01 study, which evaluated zongertinib, and the phase I/II SOHO-01 study that evaluated sevabertinib. In this study, zongertinib demonstrated an overall response rate of 71% in previously treated patients, with an overall response rate of 48% amongst patients who had received prior HER2-directed ADCs including T-DXd. Sevabertinib in its early phase study showed an overall response rate of 64% in previously treated but HER2 therapy-naive patients, and an overall response rate of 38% in patients previously exposed to HER2-directed therapy. The panel believes that both agents had manageable toxicity profile and represent meaningful new options for this patient population. Brittany Harvey: Certainly, it's an active space of research, and I appreciate you reviewing the evidence underpinning all of these recommendations for our listeners. So, it's great to have these new options for patients in the later-line settings. And given all of these updates in both the first and the later-line settings, what should clinicians know as they implement this latest living guideline update, and how do these changes impact patients with non-small cell lung cancer? Dr. Sonam Puri: Some great questions, Brittany. I think for clinicians when implementing this update, I think about two practical steps. First is reiterating the importance of comprehensive biomarker testing. That is the only way to identify key drivers and resistance mechanisms that we are now targeting. And second, picking a first-line strategy that balances efficacy and toxicity and patient preference for your specific patient. I think informed decision-making, shared decision-making is more important than any time right now. It has always been important, but definitely very important now. For patients, this guideline brings recommendations on more personalized treatment options for both first-line and post-progression settings, which potentially means better outcomes. But it is also very important for our patients to continue to have informed conversations about side effects, time commitment, and what matters most to them with their providers. The panel in this version of the guideline specifically acknowledges the real-world barriers that prevent patients from receiving guideline-concordant therapy, including challenges with access to comprehensive molecular testing and treatment availability, and the panel emphasizes on the importance of shared decision-making, and we provide practical discussion points to help clinicians navigate these conversations with the patient. In addition, the panel has also addressed common real-world clinical complexities, such as treating elderly or frail patients, managing multiple chronic conditions, considerations around pregnancy and fertility, and certain disease scenarios such as oligoprogression or oligometastatic disease. And where available, the guideline summarizes this existing data to support informed individual decision-making in these complex situations. Brittany Harvey: Shared decision-making is really paramount, especially with all of the options and weighing the risks and benefits and considering the individual circumstances of each patient that comes before a clinician. We've talked a lot about all of the new studies that the panel has reviewed, but what other studies or areas of research is the panel examining for future updates to this living guideline as it continues to be updated on an ongoing basis? Dr. Sonam Puri: Yes, definitely, so much to look forward to, right? Looking ahead, the panel is closely monitoring several rapidly evolving areas that are likely to shape future updates of the guideline. This includes emerging data from ongoing later-phase studies, particularly the studies that are evaluating these new targeted agents moving to earlier lines of therapy, alongside studies evaluating additional combination strategies or more refined approaches to treatment sequencing. We're also closely watching advances in biomarker testing, the evolving understanding of resistance mechanisms, development of new targets, and promising therapeutic agents. I think ultimately the living guideline exists to help clinicians and patients navigate this rapidly evolving field, and we would like to ensure that scientific advances are rapidly translated into better, more personalized patient care. Brittany Harvey: Definitely. We'll look forward to those updates from those ongoing trials and future areas of research that you mentioned to provide better options for patients with non-small cell lung cancer and a driver alteration. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Puri. Dr. Sonam Puri: Thanks so much. Thanks so much for the opportunity. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. There's also a companion episode with Dr. Reuss on the related living guideline on stage IV non-small cell lung cancer without driver alterations that listeners can find in their feeds as well. And 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. 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.  

Featuring perspectives from Dr Angela DeMichele, Dr Komal Jhaveri, Dr Erica Mayer, Dr Hope S Rugo and Dr Seth Wander, including the following topics:  Introduction (0:00) 1985 NCI Consensus Conference on Early Breast Cancer: Sir Richard Peto, FRS (2:01) Current Role of Genomic Assays in Treatment Decision-Making for Localized Hormone Receptor (HR)-Positive Breast Cancer — Dr DeMichele (5:13) Case: A premenopausal woman in her mid 40s with an ER-positive, HER2-negative, node-negative infiltrating ductal carcinoma (IDC) after partial mastectomy/radiation therapy who enrolls in the prospective, observational FLEX study: MammaPrint® low risk — Laurie Matt-Amaral, MD, MPH (15:30) Case: A premenopausal woman in her mid 40s after modified radical mastectomy for T2N0 ER-positive, HER2-negative IDC with an Oncotype DX® Recurrence Score (RS®) of 19 — Swati Vishwanathan, MD Case: A woman in her mid 60s with locally advanced (19 cm) ER-positive, HER2-low (IHC 1+) Stage IIIB mucinous carcinoma breast cancer and an RS of 18 — Alan B Astrow, MD (22:40) Role of CDK4/6 Inhibitors and Other Novel Strategies in Therapy for HR-Positive, HER2-Negative Localized Breast Cancer — Dr Jhaveri (30:18) Case: A woman in her mid 50s with ER-positive, HER2-negative Stage IIB, T2N1 IDC after neoadjuvant dose-dense AC-T, lumpectomy and adjuvant radiation therapy — Eleonora Teplinsky, MD (42:14) Case: A woman in her mid 60s with ER-positive, HER2-negative breast cancer with a surgically removed solitary lung metastasis after 4 years of adjuvant letrozole — Eric Fox, DO (46:32) Evolving Up-Front Treatment Paradigm for HR-Positive, HER2-Negative Metastatic Breast Cancer (mBC) — Dr Rugo (49:45) Case: A woman in her early 80s with Type 2 diabetes, well controlled hypertension and recurrent ER-positive, HER2-negative mBC after 4 years of adjuvant letrozole — Sunil Gandhi, MD (1:02:30) Clinical Utility of Agents Targeting the PI3K/AKT/mTOR Pathway for Patients with Progressive HR-Positive mBC — Dr Mayer (1:06:37) Case: A woman in her late 60s with ER-positive, HER2-low (IHC 1+), PIK3CA-mutant mBC with disease progression after 2 years of adjuvant letrozole — Laila Agrawal, MD (1:20:22) Case: A woman in her early 60s with ER-positive, HER2-low PIK3CA-mutant mBC and disease progression on first-line palbociclib/fulvestrant — Dr Teplinsky (1:26:36) Results from the Global Phase III lidERA Breast Cancer Trial of Giredestrant versus Standard Endocrine Therapy as Adjuvant Treatment for ER-Positive, HER2-Negative Localized Breast Cancer (1:31:48) Current and Future Role of Oral Selective Estrogen Receptor Degraders for Progressive HR-Positive mBC — Dr Wander (1:42:30) Case: A woman in her early 100s with locally advanced ER-positive, HER2-negative breast cancer with disease progression on letrozole, now with an ESR1 mutation — Dr Astrow (1:57:51) CME information and select publications

العناوين:• IHC تتعاون مع الذراع الاستثمارية الأمريكية في صفقة تتماشى مع السياسة الخارجية الأمريكية• PwC تعين لورا هينتون كبير شركاء الشرق الأوسط بعد حظر الاستشارات السعودي• HSBC وPresight توقعان شراكة استراتيجية في الذكاء الاصطناعي Newsletter: https://aug.us/4jqModrWhatsApp: https://aug.us/40FdYLUInstagram: https://aug.us/4ihltzQTiktok: https://aug.us/4lnV0D8Smashi Business Show (Mon-Friday): https://aug.us/3BTU2MY

The current landscape of testing for NSCLC is complex, with many new biomarkers emerging rapidly, more points during which testing is possible, and precision drug treatments available on the basis of findings from biomarker testing. While promising for patients, the result of this rapidly changing landscape is confusion from interdisciplinary care teams as to what testing is necessary and when, who in multidisciplinary care teams should be ordering new tests and when, and what workflows are necessary for labs. Host David Ritter, MA is joined by Dr. Ying-Chun Lo and Dr. Mamatha Chivuluka to discuss what things pathologists and lab professionals need to know about emerging biomarkers for NSCLC. In this conversation, the panel reflects on how NSCLC biomarker testing has evolved over the past decade, highlighting the shift from limited, sequential testing to guideline-recommended broad molecular profiling. Drs. Lo and Chivuluka explore the clinical relevance of emerging biomarkers such as HER2, TROP2, and HER3, and discuss how new targeted therapies are influencing testing strategies in real-world practice. They also examine practical considerations for laboratories, including platform selection across IHC, PCR, and NGS, approaches to tissue stewardship in small lung biopsies, and the growing leadership role of pathologists in multidisciplinary teams to ensure timely, guideline-concordant, and equitable access to biomarker testing for patients with NSCLC. 

Featuring perspectives from Dr Javier Cortés, Dr Rita Nanda, Prof Peter Schmid and Dr Priyanka Sharma, including the following topics:  Introduction (0:00) Case: A woman in her early 80s with multiple comorbidities and triple-negative breast cancer (TNBC) develops bone-only metastases 4 months after declining capecitabine for post-neoadjuvant residual disease — Justin Favaro, MD, PhD (1:50) Case: A woman in her mid 70s with ER-negative, HER2-low (IHC 1+), PIK3CA-mutated, PD-L1-positive metastatic breast cancer (mBC) after receiving 3 cycles of neoadjuvant paclitaxel/carboplatin/pembrolizumab, which was discontinued — Alan Astrow, MD (6:47) Previously Untreated Metastatic TNBC (mTNBC) — Prof Schmid (10:47)  Case: A woman in her early 80s with multiregimen-recurrent ER-positive, HER2-low (IHC 1+) ESR1-mutant mBC receives sacituzumab govitecan — Jennifer Yannucci, MD (27:19) Case: The role of datopotamab deruxtecan (Dato-DXd) for patients with ER-positive, HER2-low mBC who experienced disease progression on prior trastuzumab deruxtecan (T-DXd) — Ranju Gupta, MD; Case: A woman in her late 70s with bilateral recurrence in the lungs of ER-negative, HER2-low (IHC 1+) breast cancer (PD-L1 TPS 20%) receives Dato-DXd with durvalumab on protocol — Yanjun Ma, MD, PhD (31:35) Integrating Antibody-Drug Conjugates (ADCs) into the Management of Endocrine-Resistant Hormone Receptor-Positive mBC — Dr Sharma (36:31) Case: A woman in her early 70s with recurrent ER-negative, HER2-low (IHC 2+) mBC receives sacituzumab govitecan and achieves complete remission — Dr Gupta; Case: Management of neutropenia associated with sacituzumab govitecan — Gigi Chen, MD (50:30) Case: A woman in her late 60s with recurrent ER-negative, HER2-low (IHC 1+) mBC (HER2 V69L mutation) receives T-DXd and achieves a complete response but develops Grade 1 interstitial lung disease — Dr Gupta; Case: Management of T-DXd-related side effects — Laila Agrawal, MD (54:10) Selection and Sequencing of Therapy for Relapsed/Refractory mTNBC — Dr Nanda (58:59) Case: A woman in her early 40s with multiregimen-recurrent ER-positive, HER2-low mBC who has experienced severe nausea with past treatments is about to initiate T-DXd — Atif M Hussein, MD, MMM (1:12:40) Tolerability and Other Practical Considerations with ADCs and Other Cytotoxic Agents for mBC — Dr Cortés (1:18:10) CME information and select publications

Featuring perspectives from Dr Lisa A Carey and Dr Rita Nanda, including the following topics:  Overview: Molecular basis of antibody-drug conjugate (ADC) toxicities — Sequencing of ADCs and mechanisms of resistance (0:00) Case: A woman in her late 60s with localized triple-negative breast cancer develops myocarditis during neoadjuvant therapy with chemotherapy/pembrolizumab — Richard Zelkowitz, MD (8:22) Case: A woman in her mid 70s with recurrent ER-negative, HER2-low, PD-L1-positive metastatic breast cancer (mBC) who experiences disease progression on nab paclitaxel/atezolizumab responds to sacituzumab govitecan — Ranju Gupta, MD (26:43) Case: A woman in her early 80s with recurrent ER-positive, HER2-low (IHC 1+) mBC experiences disease progression on trastuzumab deruxtecan (T-DXd), then receives datopotamab deruxtecan and develops pulmonary symptoms — Laila Agrawal, MD (32:11) Data Review: T-DXd (37:51) Case: A woman in her early 70s with recurrent ER-positive, HER2-low (IHC 1+) mBC, including bladder metastases, experiences disease progression after palbociclib/letrozole, then capivasertib/fulvestrant, then nab paclitaxel — Justin Favaro, MD, PhD (44:02) Case: A woman in her late 70s with ER-positive, HER2-low mBC who experiences disease progression after 1 year of ribociclib/letrozole receives sacituzumab govitecan — Erik Rupard, MD (55:19) CME information and select publications

في حلقة اليوم من سماشي بزنس، نناقش تقارير عن نية ولي العهد السعودي تقديم عرض بقيمة 10 مليارات يورو للاستحواذ على نادي برشلونة، ونستعرض انهيار مشروع ترامب تاور بلغراد الذي جمع جاريد كوشنر ومحمد العبار، إضافة إلى خطوة شركة IHC في أبوظبي لتعزيز استثماراتها في تجارة السلع عبر إنفكتس. من الرياضة العالمية إلى العقارات والأمن الغذائي، هذه أبرز تحركات اليوم في عالم الأعمال.

Featuring perspectives from Dr Manish A Shah, moderated by Dr Stephen "Fred" Divers, including the following topics:  Highlights and Principles of Management of Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma — Dr Shah (0:00) Case: A man in his early 50s with microsatellite instability-high localized esophageal adenocarcinoma — Dr Mulherin (15:24) Case: A woman in her late 60s with HER2-positive (IHC 3+) and HER2 TKD-mutant metastatic esophageal adenocarcinoma — Dr Warsch (25:34) Case: A woman in her early 70s with HER2-positive (IHC 3+), PD-L1-negative, CLDN18.2-negative metastatic gastric cancer — Dr Mulherin (28:15) Case: A woman in her early 70s with metastatic gastroesophageal junction adenocarcinoma (PD-L1 CPS 15) who begins treatment with FOLFOX/nivolumab and subsequently is found to have CLDN18.2 overexpression — Dr Lamar (35:23) Case: A man in his mid 40s with CLDN18.2-positive metastatic esophageal adenocarcinoma (PD-L1 10%) who receives mFOLFOX6 and zolbetuximab — Dr Yannucci (42:54) CE information and select publications

On this weeks show We focus on previewing the Munster Club SHC & IHC finals, and we have Greyhound Focus too

Authors Drs. Jessica Ross and Alissa Cooper share insights into their JCO PO article, "Clinical and Pathologic Landscapes of Delta-Like Ligand 3 and Seizure-Related Homolog Protein 6 Expression in Neuroendocrine Carcinomas"  Host Dr. Rafeh Naqash and Drs. Ross and Cooper discuss the landscape of Delta-like ligand 3 (DLL3) and seizure-related homolog protein 6 (SEZ6) across NECs from eight different primary sites. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO PO and an Associate Professor at the OU Health Stephenson Cancer Center. Today, I'm excited to be joined by Dr. Jessica Ross, third-year medical oncology fellow at the Memorial Sloan Kettering Cancer Center, as well as Dr. Alissa Cooper, thoracic medical oncologist at the Dana-Farber Cancer Institute and instructor in medicine at Harvard Medical School. Both are first and last authors of the JCO Precision Oncology article entitled "Clinical and Pathologic Landscapes of Delta-like Ligand 3 and Seizure-Related Homolog Protein 6 or SEZ6 Protein Expression in Neuroendocrine Carcinomas." At the time of this recording, our guest disclosures will be linked in the transcript. Jessica and Alissa, welcome to our podcast, and thank you for joining us today. Dr. Jessica Ross: Thanks very much for having us. Dr. Alissa Cooper: Thank you. Excited to be here. Dr. Rafeh Naqash: It's interesting, a couple of days before I decided to choose this article, one of my GI oncology colleagues actually asked me two questions. He said, "Rafeh, do you know how you define DLL3 positivity? And what is the status of DLL3 positivity in GI cancers, GI neuroendocrine carcinomas?" The first thing I looked up was this JCO article from Martin Wermke. You might have seen it as well, on obrixtamig, a phase 1 study, a DLL3 bi-specific T-cell engager. And they had some definitions there, and then this article came along, and I was really excited that it kind of fell right in place of trying to understand the IHC landscape of two very interesting targets. Since we have a very broad and diverse audience, especially community oncologists, trainees, and of course academic clinicians and some people who are very interested in genomics, we'll try to make things easy to understand. So my first question for you, Jessica, is: what is DLL3 and SEZ6 and why are they important in neuroendocrine carcinomas? Dr. Jessica Ross: Yeah, good question. So, DLL3, or delta-like ligand 3, is a protein that is expressed preferentially on the tumor cell surface of neuroendocrine carcinomas as opposed to normal tissue. It is a downstream target of ASCL1, and it's involved in neuroendocrine differentiation, and it's an appealing drug target because it is preferentially expressed on tumor cell surfaces. And so, it's a protein, and there are several drugs in development targeting this protein, and then Tarlatamab is an approved bi-specific T-cell engager for the treatment of extensive-stage small cell lung cancer in the second line. SEZ6, or seizure-like homolog protein 6, is a protein also expressed on neuroendocrine carcinoma cell surface. Interestingly, so it's expressed on neuronal cells, but its exact role in neuroendocrine carcinomas and oncogenesis is actually pretty poorly understood, but it was identified as an appealing drug target because, similarly to DLL3, it's preferentially expressed on the tumor cell surface. And so this has also emerged as an appealing drug target, and there are drugs in development, including antibody-drug conjugates, targeting this protein for that reason. Dr. Alissa Cooper: Over the last 10 to 15 years or so, there's been an increasing focus on precision oncology, finding specific targets that actually drive the cancer to grow, not just within lung cancer but in multiple other primary cancers. But specifically, at least speaking from a thoracic oncology perspective, the field of non-small cell lung cancer has completely exploded over the past 15 years with the discovery of driver oncogenes and then matched targeted therapies. Within the field of neuroendocrine carcinomas, including small cell lung cancer but also other high-grade neuroendocrine carcinomas, there has not been the same sort of progress in terms of identifying targets with matched therapies. And up until recently, we've sort of been treating these neuroendocrine malignancies kind of as a monolithic disease process. And so recently, there's been sort of an explosion of research across the country and multiple laboratories, multiple people converging on the same open questions about why might patients with specific tumor biologies have different kind of responses to different therapies. And so first this came from, you know, why some patients might have a good response to chemo and immunotherapy, which is the first-line approved therapy for small cell lung cancer, and we also sort of extrapolate that to other high-grade neuroendocrine carcinomas. What's the characteristic of that tumor biology? And at the same time, what are other targets that might be identifiable? Just as Jesse was saying, they're expressed on the cell surface, they're not necessarily expressed in normal tissue. Might this be a strategy to sort of move forward and create smarter therapies for our patients and therefore move really into a personalized era for treatment for each patient? And that's really driving, I think, a lot of the synthesis of this work of not only the development of multiple new therapies, but really understanding which tumor might be the best fit for which therapy. Dr. Rafeh Naqash: Thank you for that explanation, Alissa. And as you mentioned, these are emerging targets, some more further along in the process with approved drugs, especially Tarlatamab. And obviously, DLL3 was something identified several years back, but drug development does take time, and readout for clinical trials takes time. Could you, for the sake of our audience, try to talk briefly about the excitement around Tarlatamab in small cell lung cancer, especially data that has led to the FDA approval in the last year, year and a half? Dr. Alissa Cooper: Sure. Yeah, it's really been an explosion of excitement over, as you're saying, the last couple of years, and work really led by our mentor, Charlie Rudin, had identified DLL3 as an exciting target for small cell lung cancer specifically but also potentially other high-grade neuroendocrine malignancies. Tarlatamab is a DLL3-targeting bi-specific T-cell engager, which targets DLL3 on the small cell lung cancer cells as well as CD3 on T cells. And the idea is to sort of introduce the cancer to the immune system, circumventing the need for MHC class antigen presentation, which that machinery is typically not functional in small cell lung cancer, and so really allowing for an immunomodulatory response, which had not really been possible for most patients with small cell lung cancer prior to this. Tarlatamab was tested in a phase 2 registrational trial of about 100 patients and demonstrated a response rate of 40%, which was very exciting, especially compared with other standard therapies which were available for small cell lung cancer, which are typically cytotoxic therapies. But most excitingly, more than even the response rate, I think, in our minds was the durability of response. So patients whose disease did have a response to Tarlatamab could potentially have a durable response lasting a number of months or even over a year, which had previously not ever been seen in this in the relapsed/refractory setting for these patients. I think the challenge with small cell lung cancer and other high-grade neuroendocrine malignancies is that a response to therapy might be a bit easier to achieve, but it's that durability. The patient's tumors really come roaring back quite aggressively pretty quickly. And so this was sort of the most exciting prospect is that durability of response, that long potential overall survival tail of the curve really being lifted up. And then most recently at ASCO this year, Dr. Rudin presented the phase 3 randomized controlled trial which compared Tarlatamab to physician's choice of chemotherapy in a global study. And the choice of chemotherapy did vary depending on the part of the world that the patients were enrolled in, but in general, it was a really markedly positive study for response rate, for progression-free survival, and for overall survival. Really exciting results which really cemented Tarlatamab's place as the standard second-line therapy for patients with small cell lung cancer whose disease has progressed on first-line chemo-immunotherapy. So that has been very exciting. This drug was FDA approved in May of 2024, and so has been used extensively since then. I think the adoption has been pretty widespread, at least in the US, but now in this global trial that was just presented, and there was a corresponding New England Journal paper, I think really confirms that this is something we really hopefully can offer to most of our patients. And I think, as we all know, that this therapy or other therapies like it are also being tested potentially in the first-line setting. So there was data presented with Tarlatamab incorporated into the maintenance setting, which also showed exciting results, albeit in a phase 1 trial, but longer overall survival than we're used to seeing in this patient population. And we await results of the study that is incorporating Tarlatamab into the induction phase with chemotherapy as well. So all of this is extraordinarily exciting for our patients to sort of move the needle of how many patients we can keep alive, feeling functional, feeling well, for as long as possible. Dr. Rafeh Naqash: Very exciting session at ASCO. I was luckily one of the co-chairs for the session that Dr. Rudin presented it, and I remember somebody mentioning there was more progress seen in that session for small cell lung cancer than the last 30, 35 years for small cell, very exciting space and time to be in as far as small cell lung cancer. Now going to this project, Jessica, since you're the first author and Alissa's the last, I'm assuming there was a background conversation that you had with Alissa before you embarked on this project as an idea. So could you, again, for other trainees who are interested in doing research, and it's never easy to do research as a resident and a fellow when you have certain added responsibilities. Could you give us a little bit of a background on how this started and why you wanted to look at this question? Dr. Jessica Ross: Yeah, sure. So, as with many exciting research concepts, I think a lot of them are derived from the clinic. And so I think Alissa and I both see a good number of patients with small cell, large cell lung cancer, and then high-grade neuroendocrine carcinomas. And so I think this was really born out of a basic conversation of we have these drugs in development targeting these two proteins, DLL3 and SEZ6, but really what is the landscape of cancers that express these proteins and who are the patients that really might benefit from these exciting new therapies. And of course, there was some data out there, but sort of less than one would imagine in terms of, you know, neuroendocrine carcinomas can really come from anywhere in the body. And so when you're seeing a patient with small cell of the cervix, for example, like what are the chances that their cancer expresses DLL3 or expresses SEZ6? So it was really derived from this pragmatic, clinically oriented question that we had both found ourselves thinking about, and we were lucky enough at MSK, we had started systematically staining patients' tumors for DLL3, tumors that are high-grade neuroendocrine carcinomas, and then we had also more recently started staining for SEZ6 as well. And so we had this nice prospectively collected dataset with which to answer this question. Dr. Rafeh Naqash: Excellent. And Alissa, could you try to go into some of the details around which patients you chose, how many patients, what was the approach that you selected to collect the data for this project? Dr. Alissa Cooper: This is perhaps a strength but also maybe a limitation of this dataset is, as Jesse alluded to, our pathology colleagues are really the stars of this paper here because we were lucky enough at MSK that they were really forethinking. They are absolute experts in the field and really forward-thinking people in terms of what information might be needed in the future to drive treatment decision-making. And so, as Jesse had said, small cell lung cancer tumor samples reflexively are stained for DLL3 and SEZ6 at MSK if there's enough tumor tissue. The other high-grade neuroendocrine carcinomas, those stains are performed upon physician request. And so that is a bit of a mixed bag in terms of the tumor samples we were able to include in this dataset because, you know, upon physician request depends on a number of factors, but actually at MSK, a number of physicians were requesting these stains to be done on their patients with high-grade neuroendocrine cancers of of other histologies. So we looked at all tumor samples with a diagnosis of high-grade neuroendocrine carcinoma of any histology that were stained for these two stains of interest. You know, I can let Jesse talk a bit more about the methodology. She was really the driver of this project. Dr. Jessica Ross: Yeah, sure. So we had 124 tumor samples total. All of those were stained for DLL3, and then a little less than half, 53, were stained for SEZ6. As Alissa said, they were from any primary site. So about half of them were of lung origin, that was the most common primary site, but we included GI tract, head and neck, GU, GYN, even a few tumors of unknown origin. And again, that's because I think a lot of these trials are basket trials that are including different high-grade neuroendocrine carcinomas no matter the primary site. And so we really felt like it was important to be more comprehensive and inclusive in this study. And then, methodologically, we also defined positivity in terms of staining of these two proteins as anything greater than or equal to 1% staining. There's really not a defined consensus of positivity when it comes to these two novel targets and staining for these two proteins. But in the Tarlatamab trials, for some of the correlative work that's been done, they use that 1% cutoff, and we just felt like being consistent with that and also using a sort of more pragmatic yes/no cutoff would be more helpful for this analysis. Dr. Alissa Cooper: And that was a point of discussion, actually. We had contemplated multiple different schemas, actually, for how to define thresholds of positivity. And I know you brought up that question before, what does it mean to be DLL3 positive or DLL3 high? I think you were alluding to prior that there was a presentation of obrixtamig looking at extra-pulmonary neuroendocrine carcinomas, and they actually divvied up the results between DLL3 50% or greater versus DLL3 low under 50%. And they actually did demonstrate differential efficacy certainly, but also some differential safety as well, which is very provocative and that kind of analysis has not been presented for other novel therapies as far as I'm aware. I could be wrong, but as far as I'm aware, that was sort of the first time that we saw a systematic presentation of considering patients to be, quote unquote, "high" or "low" in these sort of novel targets. I think it is important because the label for Tarlatamab does not require any DLL3 expression at all, actually. So it's not hinging upon DLL3 expression. They depend on the fact that the vast majority of small cell lung cancer tumors do express DLL3, 85% to 90% is what's been demonstrated in a few studies. And so, there's not prerequisite testing needed in that regard, but maybe for these extra-pulmonary, other histology neuroendocrine carcinomas, maybe it does matter to some degree. Dr. Rafeh Naqash: Definitely agree that this evolving landscape of trying to understand whether an expression for something actually really does correlate with, whether it's an immune cell engager or an antibody-drug conjugate is a very evolving and dynamically moving space. And one of the questions that I was discussing with one of my friends was whether IHC positivity and the level of IHC positivity, as you've shown in one of those plots where you have double positive here on the right upper corner, you have the double negative towards the left lower, whether that somehow determines mRNA expression for DLL3. Obviously, that was not the question here that you were looking at, but it does kind of bring into question certain other aspects of correlations, expression versus IHC. Now going to the figures in this manuscript, very nicely done figures, very easy to understand because I've done the podcast for quite a bit now, and usually what I try to do first is go through the figures before I read the text, and and a lot of times it's hard to understand the figures without reading the text, but in your case, specifically the figures were very, very well done. Could you give us an overview, a quick overview of some of the important results, Jessica, as far as what you've highlighted in the manuscript? Dr. Jessica Ross: Sure. So I think the key takeaway is that, of the tumors in our cohort, the majority were positive for DLL3 and positive for SEZ6. So about 80% of them were positive for DLL3 and 80% were positive for SEZ6. About half of the tumors were stained for both proteins, and about 65% of those were positive as well. So I think if there's sort of one major takeaway, it's that when you're seeing a patient with a high-grade neuroendocrine carcinoma, the odds are that their tumor will express both of these proteins. And so that can sort of get your head thinking about what therapies they might be eligible for. And then we also did an analysis of some populations of interest. So for example, we know that non-neuroendocrine pathologies can transform into neuroendocrine tumors. And so we specifically looked at that subset of patients with transformed tumors, and those were also- the majority of them were positive, about three-quarters of them were positive for both of these two proteins. We looked at patients with brain met samples, again, about 70% were positive. And then I'd say the last sort of population of interest was we had a subset of 10 patients who had serial biopsies stained for either DLL3 or SEZ6 or both. In between the two samples, these patients were treated with chemotherapy. They were not treated with targeted therapy, but interestingly, in the majority of cases, the testing results were concordant, meaning if it was DLL3 positive to begin with, it tended to remain DLL3 positive after treatment. And so I think that's important as well as we think about, you know, a patient who maybe had DLL3 testing done before they received their induction chemo-IO, we can somewhat confidently say that they're probably still DLL3 positive after that treatment. And then finally, we did do a survival analysis among specifically the patients with lung neuroendocrine carcinomas. We looked at whether DLL3 expression affected progression-free survival on first-line platinum-etoposide, and then we looked at did it affect overall survival. And we found that it did not have an impact or the median progression-free survival was similar whether you were DLL3 positive or negative. But interestingly, with overall survival, we found that DLL3 positivity actually correlated with slightly improved overall survival. These were small numbers, and so, you know, I think we have to interpret this with caution, for sure, but it is interesting. I think there may be something to the fact that five of the patients who were DLL3 positive were treated with DLL3-targeting treatments. And so this made me think of, like in the breast cancer world, for example, if you have a patient with HER2-positive disease, it initially portended worse prognosis, more aggressive disease biology, but on the other hand, it opens the door for targeted treatments that actually now, at least with HER2-positive breast cancer, are associated with improved outcomes. And so I think that's one finding of interest as well. Dr. Rafeh Naqash: Definitely proof-of-concept findings here that you guys have in the manuscript. Alissa, if I may ask you, what is the next important step for a project like this in your mind? Dr. Alissa Cooper: Jesse has highlighted a couple of key findings that we hope to move forward with future investigative studies, not necessarily in a real-world setting, but maybe even in clinical trial settings or in collaboration with sponsors. Are these biomarkers predictive? Are they prognostic? You know, those are still- we have some nascent data, data has been brewing, but I think that we we still don't have the answers to those open questions, which I think are critically important for determining not only clinical treatment decision-making, but also our ability to understand sequencing of therapies, prioritization of therapies. I think a prospective, forward-looking project, piggybacking on that paired biopsy, you know, we had a very small subset of patients with paired biopsies, but a larger subset or cohort looking at paired biopsies where we can see is there evolution of these IHC expression, even mRNA expression, as you're saying, is there differential there? Are there selection pressures to targeted therapies? Is there upregulation or downregulation of targets in response not just to chemotherapy, but for example, for other sort of ADCs or bi-specific T-cell engagers? I think those are going to be critically important future studies which are going to be a bit challenging to do, but really important to figure out this key clinical question of sequencing, which we're all contemplating in our clinics day in and day out. If you have a patient, and these patients often can be sick quite quickly, they might have one shot of what's the next treatment that you're going to pick. We can't guarantee that every patient is going to get to see every therapy. How can you help to sort of answer the question of like what should you offer? So I think that's the key question sort of underlying any future work is how predictive or prognostic are these biomarkers? What translational or correlative studies can we do on the tissue to understand clinical treatment decision-making? I think those are the key things that will unfold in the next couple of years. Dr. Rafeh Naqash: The last question for you, Alissa, that I have is, you are fairly early in your career, and you've accomplished quite a lot. One of the most important things that comes out from this manuscript is your mentorship for somebody who is a fellow and who led this project. For other junior investigators, early-career investigators, how did you do this? How did you manage to do this, and how did you mentor Jessica on this project with some of the lessons that you learned along the way, the good and other things that would perhaps help other listeners as they try to mentor residents, trainees, which is one of the important things of what we do in our daily routine? Dr. Alissa Cooper: I appreciate you calling me accomplished. Um, I'm not sure how true that is, but I appreciate that. I didn't have to do a whole lot with this project because Jesse is an extraordinarily smart, driven, talented fellow who came up with a lot of the clinical questions and a lot of the research questions as well. And so this project was definitely a collaborative project on both of our ends. But I think what was helpful from both of our perspectives is from my perspective, I could kind of see that this was a gap in the literature that really, I think, from my work leading clinical trials and from treating patients with these kinds of cancers that I really hoped to answer. And so when I came to Jessica with this idea as sort of a project to complete, she was very eager to take it and run with it and also make it her own. You know, in terms of early mentorship, I have to admit this was the first project that I mentored, so it was a great learning experience for me as well because as an early-career clinician and researcher, you're used to having someone else looking over your shoulder to tell you, "Yes, this is a good journal target, here's what we can anticipate reviewers are going to say, here are other key collaborators we should include." Those kind of things about a project that don't always occur to you as you're sort of first starting out. And so all of that experience for me to be identifying those more upper-level management sort of questions was a really good learning experience for me. And of course, I was fantastically lucky to have a partner in Jesse, who is just a rising star. Dr. Jessica Ross: Thank you. Dr. Rafeh Naqash: Well, excellent. It sounds like the first of many other mentorship opportunities to come for you, Alissa. And Jessica, congratulations on your next step of joining and being faculty, hopefully, where you're training. Thank you again, both of you. This was very insightful. I definitely learned a lot after I reviewed the manuscript and read the manuscript. Hopefully, our listeners will feel the same. Perhaps we'll have more of your work being published in JCO PO subsequently. Dr. Alissa Cooper: Hope so. Thank you very much for the opportunity to chat today. Dr. Jessica Ross: Yes, thank you. This was great. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so as you never miss an episode. You can find all ASCO shows at asco.org/podcasts. 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. Disclosures: Dr. Alissa Jamie Cooper Honoraria Company: MJH Life Scienes, Ideology Health, Intellisphere LLC, MedStar Health, Physician's Education Resource, LLC,  Gilead Sciences, Regeneron, Daiichi Sankyo/Astra Zeneca, Novartis,  Research Funding: Merck, Roche, Monte Rosa Therapeutics, Abbvie, Amgen, Daiichi Sankyo/Astra Zeneca Travel, Accommodations, Expenses: Gilead Sciences

Send us a textIs your lab truly digitally ready—or just scanning slides?That's the question I unpack in this live discussion from Day 2 of SITC's 40th Anniversary Meeting, joined by David Anderson (Biocare Medical) and Don Ariyakumar (Hamamatsu Photonics). Together, we explore what digital readiness really means for multiplex immunofluorescence (mIF) and how to build reliable, reproducible workflows that scale from research to clinical settings.What We DiscussThe Discovery Funnel I open by situating mIF within the broader discovery funnel: researchers begin with hundreds of biomarkers, narrowing down to focused 4–10 marker panels where true clinical utility begins. But this only works if the lab is digitally prepared from the start—from slide prep to data capture.Defining Digital Readiness David Anderson reframes digital readiness as everything that happens before the scanner turns on:Reagent consistencyAntibody optimizationAutomationStandardized protocols All these elements ensure that downstream AI and image analysis tools work on clean, reproducible data instead of “fixing” noise later.The Pre-Analytical Foundation Don Ariyakumar emphasizes that scanning can't fix variability. If staining or section quality isn't standardized, digitization simply amplifies inconsistencies. True readiness starts at the bench, not the monitor.Integration Across Vendors We also talk about how interoperability between stainers, scanners, and spatial biology software is becoming essential. A disconnected workflow—mixing manual, unaligned steps—adds variables that no algorithm can fully normalize.Lessons from IHC's Evolution The team draws parallels between multiplex IF today and IHC's early days: once complex, now routine. Multiplex IF promises even richer tumor microenvironment insights, but only if standardization and automation catch up to the technology.Beyond the Funnel I revisit the “funnel” metaphor in a new light—arguing that as precision medicine grows, the bottom of the funnel broadens, not narrows. That means more tailored, smaller panels rather than one-size-fits-all assays, and a growing need for efficient, reproducible digital workflows.Key Takeaways“Digital readiness” starts before scanning — with chemistry, automation, and process control.Consistent pre-analytical quality = reproducible, AI-ready data.Interoperability between systems (like Biocare's ONCORE Pro X and Hamamatsu's MoxiePlex) accelerates workflow standardization.Multiplex IF is maturing quickly, just as IHC once did—on its way to becoming a cornerstone of precision pathology.Resources Mentioned

Send us a textCan spatial biology and multiplex immunofluorescence truly transform how we understand cancer?I went live from the Society for Immunotherapy of Cancer (SITC) 2025 — the 40th Anniversary Meeting to explore how spatial biology, multiplex IF, and digital pathology are coming together to redefine cancer diagnostics, research, and precision medicine.This session kicked off a weekend of cutting-edge discussions with leaders from Hamamatsu (Booth 415) and Biocare Medical (Booth 717) — two companies helping laboratories around the world embrace digital transformation and spatial imaging in oncology.

JCO PO author Dr. Asaf Maoz at Dana-Farber Cancer Institute shares insights into article, “Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era.” Host Dr. Rafeh Naqash and Dr. Maoz discuss the causes of death in individuals with LS and the evolving role of immunotherapy. TRANSCRIPT Dr. Rafeh Naqash: Hello, and welcome to JCO Precision Oncology Conversations, where we bring you engaging conversations with authors of clinically relevant and highly significant JCOPO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Associate Professor Medicine, at the OU Health Stephenson Cancer Center. Today, I'm super thrilled to be joined by Dr. Asaf Maoz, Medical Oncologist at Dana-Farber Cancer Institute, Brigham and Women's Hospital, and faculty at the Harvard Medical School, and also lead author on the JCO Precision Oncology article entitled "Causes of Death Among Individuals with Lynch Syndrome in the Immunotherapy Era." This publication will be a concurrent publication with an oral presentation at the annual CGA meeting. At the time of this recording, our guest's disclosures will be linked in the transcript. Asaf, I'm excited to welcome you on this podcast. Thank you for joining us today. Dr. Asaf Maoz: Thank you so much for highlighting our paper. Dr. Rafeh Naqash: Absolutely. And I was just talking to you that we met several years back when you were a trainee, and it looks like you've worked a lot in this field now, and it's very exciting to see that you consider JCOPO as a relevant home for some of your work. And the topic that you have published on is of significant interest to trainees from a precision medicine standpoint, to oncologists in general, covers a lot of aspects of immunotherapy. So, I'm really excited to talk to you about all of this. Dr. Asaf Maoz: Me too, me too. And yeah, I think JCOPO has great content in the area of cancer genetics and has done a lot to disseminate the knowledge in that area. Dr. Rafeh Naqash: Wonderful. So, let's get started and start off, given that we have hosts of different kinds of individuals who listen to this podcast, especially when driving from home to work or back, for the sake of making everything simple, can we start by asking you what is Lynch syndrome? How is it diagnosed? What are some of the main things to consider when you're trying to talk an individual where you suspect Lynch syndrome? Dr. Asaf Maoz: Lynch syndrome is an inherited predisposition to cancer, and it is common. So, we used to think that, or there's a general notion in the medical community that it is a rare condition, but we actually know now from multiple studies, including studies that look at the general population and do genetic testing regardless of any clinical phenotype, that Lynch syndrome is found in about 1 in 300 people in the general population. If you think about it in the United States, that means that there are over a million people living with Lynch syndrome in the United States. Unfortunately, most individuals with Lynch syndrome don't know they have Lynch syndrome at the current time, and that's where a lot of the efforts in the community are being made to help detect more individuals who have Lynch syndrome. Lynch syndrome is caused by pathogenic germline variants in mismatch repair genes, MLH1, MSH2, MSH6, or PMS2, or as a result of pathogenic variants in EPCAM that cause silencing of the MSH2 gene. Dr. Rafeh Naqash: Excellent. Thank you for that explanation. Now, one of the other things I also realized, similar to BRCA germline mutations, where you require a second hit for individuals with Lynch syndrome to have mismatch repair deficient cancers, you also require a second hit to have that second hit result in an MSI-high cancer. Could you help us understand the difference of these two concepts where generally Lynch syndrome is thought of to be cancers that are mismatch repair deficient, but that's not necessarily true for all cases as we see in your paper. Can you tease this out for us a little bit more? Dr. Asaf Maoz: Of course, of course. So, the germline defect is in one of the mismatch repair genes, and these genes are responsible for DNA mismatch repair, as their name implies. Now, in a normal cell, we think that one working copy is generally enough to maintain the mismatch repair machinery intact. What happens in tumors, as you alluded to, is that there is a second hit in the same mismatch repair gene that has the pathogenic germline variant, and that causes the mismatch repair machinery not to work anymore. And so what happens is that there is formation of mutations in the cancer cell that are not present in other cells in the body. And we know that there are specific types of mutations that are associated with defects in mismatch repair mechanisms, and those are associated a lot of times with frameshift mutations. And we have termed them ‘microsatellites'. So there are areas in the genome that have repeats, for example, you know, if you have AAAA or GAGA, and those areas are particularly susceptible to mutations when the mismatch repair machinery is not working. And so we can measure that with DNA microsatellite instability testing. But we can also get a sense of whether the mismatch repair machinery is functioning by looking at protein expression on the surface of cancer cells and by doing immunohistochemistry. More recently, we're also able to infer whether the mismatch repair machinery is working by doing next-generation sequencing and looking at many, many microsatellites and whether they have this DNA instability in the microsatellites. Dr. Rafeh Naqash: Excellent explanation. As a segue to what you just mentioned, and this reminds me of some work that one of my good friends, collaborators, Amin Nassar, whom you also know, I believe, had done a year and a half back, was published in Cancer Cell as a brief report, I believe, where the concept was that when you look at these mismatch repair deficient cancers, there is a difference between NGS testing, IHC testing, and maybe to some extent, PCR testing, where you can have discordances. Have you seen that in your clinical experience? What are some of your thoughts there? And if a trainee were to ask, what would be the gold standard to test individuals where you suspect mismatch repair deficient-related Lynch syndrome cancers? How would you test those individuals? Dr. Asaf Maoz: We do sometimes see discordance, you know, from large series, the concordance rate is very high, and in most series it's over 95%. And so from a practical perspective, if we're thinking about the recommendation to screen all colorectal cancer and all endometrial cancer for mismatch repair deficiency, I think either PCR-based testing or immunohistochemistry is acceptable because the concordance rate is very high. There are rare cases where it is not concordant, doing multiple of the tests makes sense at that time. If you think about the difference between the tests, the immunohistochemistry looks at protein expression, which is a surrogate for whether there is mismatch repair deficiency or not, right? Because ultimately, the mismatch repair deficiency is manifested in the mutations. So if the PCR does not show microsatellite instability and now NGS does not show microsatellite instability, the IHC may be a false positive. At the end of the day, the functional analysis of whether there are actually unstable microsatellites either by PCR or by NGS is what I would consider more informative. But IHC again is an excellent test and concordant with those results in over 95% of cases. Now there is also an issue of sampling. It's possible that there's heterogeneity within the tumor. We published a case in JCOPO about heterogeneity of the mismatch repair status, and that was both by immunohistochemistry, but also by PCR. So there are some caveats and interpreting these tests does require some expertise, and I'm always happy to chat with trainees or whoever has an interesting or challenging case. Dr. Rafeh Naqash: Thanks again for that very easy to understand explanation. Now going to management strategies, could you elaborate a little bit upon the neo-adjuvant data currently, or the metastatic data which I think more people are familiar with for immunotherapy in individuals with MSI-high cancers? Dr. Asaf Maoz: Yeah, that's an excellent question and obviously a very broad topic. Individuals with Lynch syndrome typically develop tumors that are mismatch repair deficient or microsatellite unstable. And we have seen over the last 15 years or so that these tumors, because they have a lot of mutations and because these mutations are very immunogenic, we have seen that they respond very well to immunotherapy. And this has been shown across disease sites and has been shown across disease settings. And for that reason, immunotherapy was approved for MSI-high or mismatch repair deficient cancer regardless of the anatomic site. It was the first tissue-agnostic approval by the FDA in 2017. And so there are exciting studies both in the metastatic setting where we see individuals who respond to immunotherapy for many years, and one could wonder whether their cancer is going to come back or not. And also in the earlier setting, for example, the Cercek et al. study in the New England Journal from Sloan Kettering, where they showed that neoadjuvant immunotherapy can cause durable responses for rectal cancer that is mismatch repair deficient. And in that series, the patients did not require surgery or radiation, which is standard of care for rectal cancer otherwise. And there's also exciting data in the adjuvant space, as was presented in ASCO by Dr. Sinicrope, the ATOMIC study, and many more efforts to bring immunotherapy into the treatment landscape for individuals with MSI-high cancer, including individuals with Lynch syndrome. Dr. Rafeh Naqash: A lot of activity, especially in the neo-adjuvant and adjuvant space over the last two years or so. Now going to the actual reason why we are here is your study. Could you tell us why you looked at this idea of patients who had Lynch syndrome and died, and the reasons for their death? What was the thought that triggered this project? Dr. Asaf Maoz: As we were talking about, we now know that immunotherapy really has changed the treatment landscape for individuals with Lynch syndrome, and that most cancers that individuals with Lynch syndrome do have this mismatch repair deficiency. But we also know that individuals with Lynch syndrome can develop tumors that do not have mismatch repair deficiency, and we call them mismatch repair proficient or microsatellite stable. And there was a series from Memorial Sloan Kettering showing that in colorectal cancer, about 10% of the tumors that individuals with Lynch syndrome developed did not have mismatch repair deficiency. In addition to that, we anecdotally saw that some of our patients with Lynch syndrome died of causes that were not mismatch repair deficient tumors. We wanted to see how that has changed since immunotherapy was approved in a tissue-agnostic manner, meaning that we could look at this regardless of where the cancer started, because we would anticipate that if the tumor was mismatch repair deficient, the patient would be able to access immunotherapy as standard of care. Dr. Rafeh Naqash: Thank you. And then you looked at different aspects of correlations with regards to individuals that had an MSI-high cancer with Lynch syndrome or an MSS cancer with Lynch syndrome. Could you elaborate on some of the important findings that you identified as well as some of the unusual findings that perhaps we did not know about, even though the sample size is limited, but what were some of the unique things that you did identify through this project? Dr. Asaf Maoz: The first question was what cause is leading to death in individuals with Lynch syndrome? And we had 54 patients that we identified that had died since the approval of immunotherapy in 2017, 44 of which died of cancer-related causes. And when we looked at cancer-related causes of death, we wanted to know how many of those were due to mismatch repair deficient tumors versus mismatch repair proficient tumors or MS-stable tumors. And we found, somewhat surprisingly, that 43% of patients in our cohort actually died of tumors that were microsatellite stable or mismatch repair proficient, meaning of tumors that are not typically associated with Lynch syndrome. This is not entirely surprising as a cause of death because we know that immunotherapy does not typically work for tumors that are microsatellite stable. And so in the metastatic setting, there are much less cases of durable remissions with treatment. But it was helpful to have that figure as an important benchmark. There are previous studies about causes of death in Lynch syndrome, and particularly from the Prospective Lynch Syndrome Database in Europe. Those have provided really important information about cause of death by cancer site, but they typically don't have mismatch repair status and are more difficult to interpret in that regard. They also don't include a large number of individuals who have PMS2 Lynch syndrome, which is the most common, but least penetrant form of Lynch syndrome. Dr. Rafeh Naqash: As far as the subtype of pathogenic germline variants is concerned, did you notice anything unusual? And I've always had this question, and you may know more about this data, is: In the bigger context of immunotherapy, does the type of the pathogenic germline variant for Lynch syndrome associated MSI-high cancers, does that impact or have an association with the kind of outcomes, how soon a cancer progresses or how many exceptional responders perhaps with MSI-high cancers actually have a certain specific pathogenic germline variant? Dr. Asaf Maoz: That's an excellent question, and certainly we need more data in that space. We know that the type of germline mutation, or the gene in which there is a germline pathogenic variant, determines to a large degree the cancer risk, right? So we know that individuals who have germline pathogenic variants in MLH1 or MSH2 have a much higher colorectal cancer risk than, for example, PMS2. We know that for PMS2, the risks are more limited to colorectal and endometrial, and may be lower risk of other cancers. We also know that, you know, the spectrum of disease may change based on the pathogenic germline variants. For example, individuals who have MSH2 associated Lynch syndrome have more risk of additional cancers in other organs like the urinary tract and other less common Lynch-associated tumors. The question about response to therapy is one where we have much less information. There are studies that are trying to assess this, but I don't think the answer is there yet. Some of the non-clinical data looks at how many mutations there are based on the pathogenic variant and what the nature of those mutations are, whether they're more frameshift or others. But I think we still need more clinical data to understand whether the response to immunotherapy differs. It's also complicated by the fact that the immunotherapy landscape is changing, especially in the metastatic setting, now with the approval of combination ipilimumab and nivolumab for first-line treatment of colorectal cancer that is microsatellite unstable. But in our study, we did find that, as you would expect, there is an enrichment in MS-stable cancers among those with PMS2 Lynch syndrome. Again, our denominator is those who died, right? So this is not the best way to look at the question whether this is overall true, that is more addressed by the study that Sloan Kettering published. But we do see, as we would anticipate, that there are more microsatellite stable cancers among those with PMS2 Lynch syndrome that died. Dr. Rafeh Naqash: A lot to uncover there for sure. This study and perhaps some of the other work that you're doing is slowly advancing our understanding of some of these concepts. So I'd like to shift gears to a couple of provocative questions that I generally like to ask. The first is, in your opinion, and you may or may not have data to back this up, which is okay, and that's why we're having a conversation about it. In your opinion, do you think the type or the quality of the neoantigen is different based on the pathogenic germline variant and a Lynch syndrome associated MSI-high cancer? Dr. Asaf Maoz: I think there are some data out there that, you know, I can't cite off the top of my mind, but there are some data out there that suggest that that may be the case. I think the key question is the quality, right? I think that whether these differences that are found on a molecular level also translate to a clinical difference in response is something that is unknown at this moment. Some people hypothesize that if the tumor has less neoantigens, there's less of a response to immunotherapy. But I think we really need to be careful before making those assertions on a clinical level. I do think it's a really important question that needs to be answered, among others because, you know, in the colorectal space, for example, where we have both the option of doing ipilimumab with nivolumab and the option of doing pembrolizumab, we don't really know which patients need the CTLA-4 blockade versus which patients can receive PD-1 blockade alone and avoid the potential excess toxicity of the CTLA-4 blockade. There are a lot of interesting questions there that still need to be answered. And of course, individuals with Lynch syndrome are just a fraction of those individuals who have MSI-high cancer. So there's also the question about whether non-Lynch syndrome associated MSI-high cancer responds differently to immunotherapy than Lynch syndrome associated MSI-high cancer. A lot of very interesting questions in the field for sure. Dr. Rafeh Naqash: Absolutely. My second question is more about trying to understand the role of ctDNA, MRD monitoring in individuals with Lynch syndrome. If somebody has a germline, you know, Lynch syndrome MSI-high cancer, when you do a tumor-informed ctDNA assessment, what do you capture generally there? Because, and this question stems from a discussion I've had with somebody regarding EGFR lung cancer, since I treat individuals with lung cancer, and the concept generally is that even if the tissue showed EGFR, but for MRD monitoring, when you do a barcoded sequence of different tumor specific mutations, it's not actually the EGFR that they track in the blood when they do ctDNA assessment. But from a Lynch syndrome standpoint, if you have a germline, right, which is the first hit, and then you have the somatic in the tumor, which is the second hit, are you aware or have you tried to look into this where what is exactly being followed if one had to follow MRD in a Lynch syndrome MSI-high colorectal cancer? Dr. Asaf Maoz: I think a lot of the MRD assays are proprietary, and so we don't receive information about what the mutations that are being tracked are. In general, the idea is to track mutations that we would not expect to disappear as part of resistant mechanisms. We want these to be truncal mutations. We want these to be mutations in which resistance is not expected to result in reversion mutations. But what specifically is being tracked is something that I don't know because these assays, the tumor-informed ones, are proprietary, and we don't get the results regarding specific mutations. When it's circulating tumor DNA that is not necessarily tumor-informed, we do get those results, but that is less so about the specific selection of mutations. Dr. Rafeh Naqash: Thank you for clarifying that question to some extent, of course, as you said, we don't know a lot, and we don't know what we don't know. That's the most important thing that I've learned in the process of understanding precision medicine and genomics, and it's a very fast-paced evolving field. Last question related to your project, what is the next step? Are you planning any next steps as a bigger multicenter study or validation of some sort? Dr. Asaf Maoz: There are two big questions that this study raises. One, is this true across multiple other sites, right? Because this is a single center study, and we really need additional centers to look at their data and validate whether they are also seeing that a substantial portion of deaths in individuals with Lynch syndrome are attributable to mismatch repair proficient cancer. The other question is whether we can look at specifically MSI-high cancer versus MS-stable cancer and understand what the mortality rate for each of those are. From a clinical perspective, it's important to counsel individuals with Lynch syndrome about general cancer screening outside of mismatch repair deficient tumors and to understand that there is also a risk of mismatch repair proficient tumors and that treatment for those tumors would be different. There's a lot of work to be done in the future. Another major area of need is to see whether tumors that are microsatellite stable can be sensitized to immunotherapy, and that is beyond the Lynch syndrome field, but that is something that certainly would benefit these individuals with Lynch syndrome who develop mismatch repair proficient cancer. Dr. Rafeh Naqash: That's very interesting to hear, and we'll look forward to seeing some of those developments shape in the next few years. Now, I'd like to spend a minute, minute and a half on you specifically as a researcher, clinician, scientist. Could you briefly highlight - because I remember meeting you several years back as a trainee, with your interest in genomics, computational research - could you briefly tell us what led you to hereditary cancer syndromes based on your research and work? What are some of the things that you learned along the way that other early career investigators can perhaps take lessons from? Dr. Asaf Maoz: Big questions there, thanks for asking. I got interested in the field of hereditary cancer syndromes when I came to the United States and started doing lab research in Stephen Gruber's lab at the time at USC. He's now at City of Hope. And my interest was originally looking at immunotherapy and immunology, but I went to the case conferences where we were learning about individuals with hereditary cancer, and those were kind of earlier days where we were still trying to figure out how to test and what the implications for these individuals would be. And through fellowship, I was also very interested in that, and I did my senior fellowship years with Dr. Yurgelun here at Dana-Farber, who is the director of the Lynch Syndrome Center. And I I think it's the combination between being able to treat individuals based on precision medicine and what the germline mutation is, but also the ability to prevent cancer and to develop strategies to intercept cancer early that is really appealing to me in this field. It's also a great field to be in because it's a small field. If you come to the CGA-IGC meeting, you'll be able to interact with everyone. Everyone is super collaborative, super nice, and I really recommend it to trainees. The CGA-IGC annual meeting is really a great opportunity to learn more and experience some of the advancement specifically in the GI hereditary space. Lessons for trainees. I think there are a lot of lessons that I could think about, but I think finding strong and supportive mentors is one of the things that has helped me most. I think that just having close relationship with your mentor, having frequent discussions and honest discussions about what is feasible, what is going to make a difference for your patients and your research and what you want to focus on is really important. And so I think if I had to choose one thing, I would say choose a mentor that you trust, that you feel you have a good relationship with, and that has the availability to support you. Dr. Rafeh Naqash: Thank you so much for those insightful comments, and thank you for sharing with us your journey, your project, and some of your interesting thoughts on this concept of hereditary cancers. Hopefully, we'll see more of this work being published in JCOPO through your lab or work from others. Dr. Asaf Maoz: Thank you so much. I appreciate the opportunity to be here. Dr. Rafeh Naqash: Thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at ASCO.org/podcasts. 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.

Abu Dhabi's IHC to buy a 41.3% stake in Sammaan Capital, but even as FDIs look promising, FPIs have been exiting despite the government's efforts to revive demand. Domestic institutional investors have cushioned the blow. Also find: our analysis of IPO performances so far, how gamers can retrieve their deposits and a dissection of the RSS chief's Vijayadashami speech.

Hurling Chat this week looks back on the weekend knockout hurling action with Andy Coen joining Niall and Sean. They look at: - Wins for Loughrea, Tommy Larkins, Turloughmore and Sarsfields in Senior - ⁠Liam Mellows & Ballindereen progress to Senior B semis - ⁠Rahoon Newcastle, Sylane, Meelick Eyrecourt & Kinvara reach the IHC quarters - ⁠While Gort and Cappataggle force Ardrahan & Kilconerion into the Senior relegation final

Send us a textWhat if up to 35% of the diagnostic color data on your pathology slides never reaches your eyes—just because of your monitor? In this episode, sponsored by Barco, I sit down with Dr. Monika Lamba Saini (ADC Therapeutics) and Tom Kimpe (Barco) to uncover why color calibration in digital pathology isn't optional anymore—it's critical for diagnosis, efficiency, and AI readiness.Highlights:[00:03:42] Monika's path from CROs to biopharma and why color consistency matters in clinical trials.[00:09:22] What “color science” means in pathology and why color is one-third of diagnosis.[00:12:40] When the same tissue looks different across labs and scanners—and how this causes diagnostic conflicts.[00:16:19] Why HER2 scoring and IHC rely on color intensity—and how poor color fidelity lowers diagnostic confidence.[00:18:34] Research showing up to 35% of H&E slide colors fall outside of the sRGB color space—meaning you never see them on a standard monitor.[00:22:23] Where the biggest sources of color variability occur across the imaging chain come from.[00:26:26] Calibrated displays and pathologist speed—why confidence = faster reads.[00:35:19] How monitors degrade over time and why calibration is essential.[00:41:27] Why choosing a monitor based on price is short-sighted—and the real ROI of medical-grade displays.[00:43:45] ICC profiles explained: the missing piece in end-to-end color consistency.[00:52:48] Training pathologists on color literacy and internal calibration strategies.[01:00:10] How color variability affects AI algorithm accuracy—up to a 30% drop if scanners differ.[01:14:57] The role of professional societies in building color literacy and regulatory guidance.[01:22:30] Final takeaways: if you're skeptical about calibration, here's why you should care.Resources from this EpisodeFDA Research by Cheng – H&E slide colors beyond sRGB Reproducible Color Gamut of Hematoxylin and Eosin Stained Images in Standard Color Space. Barco White Paper – The Importance of Color in Modern Pathology.Barco eBook – Digital Pathology: What Are The BenefitsBarco MDPC-8127 Monitor – Medical-grade display optimized for pathology.Digital Pathology 101 (by me, Dr. Aleksandra Zuraw) – Free PDF & Amazon print edition.Support the showGet the "Digital Pathology 101" FREE E-book and join us!

Klaus Schwab is OUT — and Larry Fink has stepped into the spotlight at the World Economic Forum. What does this power shift mean for the future of the WEF and its global agenda? In this video, we break down the truth behind Schwab's exit, the rise of Larry Fink, and why it matters for everyone watching the moves of global elites. From stakeholder capitalism to the WEF's vision for the future, Larry Fink's influence as the head of BlackRock and now as one of the new leaders of the World Economic Forum reveals just how deep this shift goes. Is this the start of a new era for the WEF — or just the next phase of the same globalist plan? Visit https://ao.gold/ihc/ — where Alpha Omega Gold is giving IHC viewers a free Precious Metals Navigation Guide to help you safeguard and grow your wealth!

The danger of “question everything” is that it often leads to believing nothing. In this episode of Ideas Have Consequences, Larry Alex Taunton explores how influencers today encourage a skepticism that can slide into denialism — from rewriting WWII history to reshaping the definitions of fascism and Marxism. Larry exposes why the common belief that fascism and Marxism are opposites is misleading — and how both are being repackaged in modern globalist agendas. He also discusses the misuse of AI in research, and reflects on his time in Berlin, drawing comparisons between its turbulent history and the political climate we see now. Visit https://ao.gold/ihc/ — where Alpha Omega Gold is giving IHC viewers a free Precious Metals Navigation Guide to help you safeguard and grow your wealth! ✉️ Get all the content I can't share publicly directly in your inbox… https://join.larrytaunton.com/

“She's triple negative and has a very, very aggressive tumor. Instead of going on spring break that year, she sat in our chemo room and got chemo. Her friends from college are good to try to keep her involved and try to surround her and encourage her, but they're right now in very, very different spots in their lives. She's fighting for her life; her friends are fighting for the grade they get in a class—and that's different,” ONS member Kristi Orbaugh, MSN, NP, AOCN®, AOCNP®, nurse practitioner at Community Hospital North Cancer Center in Indianapolis, IN, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about metastatic breast cancer in adolescent and young adult patients. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  This podcast is sponsored by Lilly and is not eligible for NCPD contact hours. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. Episode Notes This episode is not eligible for NCPD. ONS Podcast™ episodes: Episode 368: Best Practices for Challenging Patient Conversations in Metastatic Breast Cancer Episode 354: Breast Cancer Survivorship Considerations for Nurses Episode 350: Breast Cancer Treatment Considerations for Nurses Episode 345: Breast Cancer Screening, Detection, and Disparities Episode 307: AYAs With Cancer: Financial Toxicity Episode 300: AYAs With Cancer: End-of-Life Care Planning ONS Voice articles: ‘Cancer Ghosting' May Add Another Layer of Emotional Burden for Patients Discoveries in Race-Related Breast Cancer Biomarkers May Improve Precision Treatments What Is HER-2-Low Breast Cancer? What Oncology Nurses Need to Know About Supporting AYAs With Cancer ONS books: Guide to Breast Cancer for Oncology Nurses Oncology Nursing Forum articles: An Integrative Review of the Role of Nurses in Fertility Preservation for Adolescents and Young Adults With Cancer Impact of Race and Area Deprivation on Triple-Negative Metastatic Breast Cancer Outcomes Relations of Mindfulness and Illness Acceptance With Psychosocial Functioning in Patients With Metastatic Breast Cancer and Caregivers ONS huddle cards: Altered Body Image Fertility Preservation Sexuality Other ONS resources: Breast Cancer Learning Library Fertility Preservation in Individuals With Cancer ONS Biomarker Database American Cancer Society's breast cancer resources American Society of Clinical Oncology continuing education resources Elephants and Tea Life, Interrupted Livestrong National Cancer Institute's breast cancer resources Stupid Cancer Young Survival Coalition To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “When we use ‘adolescent and young adult,' we're really talking about age 19–35. Some groups will say 15–39, but right around that age. When we think about that age, think about what all could be going on during those ages. Late teenagers, they may be going off to college, they may be graduating high school, trying to set up their own life, trying to become independent from mom and dad. If you're talking about early to mid 30s, you could be talking about young parents, young career folks. So, just setting that into place makes you realize this can be a very tumultuous time for folks.” TS 2:06 “Unfortunately, this group tends to have more aggressive subtypes. We see more triple-negative in this group. We see more hormone-negative, HER2-positive in this group. Normal breast cancer cells should be stimulated by hormone. They are stimulated by hormones. So when you have a breast cancer cell that is not driven by hormones, it's much more difficult to treat. We tend to see more aggressiveness in these tumors. We also see a higher incidence in non-Caucasian folks in this age group compared to the older age groups.” TS 4:53 “I think we have gotten much better about understanding the importance of fertility preservation and getting reproductive endocrinologists in, sooner rather than later. If we have earlier-stage cancers and we have patients that want to try to preserve eggs, preserve fertility, sperm banking. … If you have that time to talk to them—maybe a 21-year-old—the primary thing on her mind is not how many children she wants to have one day. Maybe she's not even thought about having kids yet. It's still a question you need to [ask]. Do you want to try to preserve fertility? Do you want to try to harvest some eggs? That's a conversation that needs to be had and is very, very important for that age group.” TS 10:35 “One thing that helps is if you can get them [into] reputable support groups with people their own age that are going through what they're going through. Someone else that doesn't have hair, someone else that isn't going to make it to the big board meeting or isn't going to get the promotion this year because they've had to take a medical leave. Someone else that understands it differently.” TS 16:47 “In breast cancer, many of those biomarkers just get reflexed. And what I mean by reflexed is a breast cancer pathology comes through, or a breast cancer specimen comes through, and it just automatically gets tested for X, Y, Z. HER2 and of course ER/PR. Now we understand that we don't just need to know whether they're HER2 positive or HER2 negative. We need to know: What is the IHC score? And even if the IHC score is zero, is there any membrane staining? And then we need to know what's their ESR1, their PTEN, their AKT, their PIK3CA. Those are so important to know.” TS 18:11 “I think it's important to try to remember what our priorities were when we were in our 20s—what our priorities were when we were starting out as young mothers or starting out our career. Because that's where these folks are. … I can't imagine in the midst of college, when I'm trying to be independent, to suddenly have to be at home and rely on my mom to take me to my chemo appointment. … So I think one really important bias is to remember where they are in the developmental stages of life. They're not 40-something. They haven't lived X amount of life, and we need to take a step back and try to remember when we were their age, what was important to us? Where were our priorities at that point? And then hear them when they're telling us what's important to them.” TS 29:22 “From a female standpoint … we frequently throw these patients into menopause or have early menopausal symptoms, and I think we forget how devastating that can be. … They now are at higher risk for osteopenia or osteoporosis. … And then we tell people, ‘Be as normal as possible, get back and do those normal things.' Well, they're in a relationship, and they want to be intimate [but] suddenly having sexual intercourse is incredibly painful. Or if it's not painful, sometimes they've just lost pure interest in that. They don't feel confident about their body. All of those things need to be addressed because patients are trying to live each day as normally as possible.” TS 31:55 

Send us a textWhat if AI could predict cancer outcomes better than traditional methods—and at a fraction of the cost? In this episode, I explore how multimodal AI is reshaping lung and prostate cancer predictions and why integration challenges still stand in the way.Episode Highlights with Timestamps:[00:02:57] Agentic AI in toxicologic pathology – what it is and how it could orchestrate workflows.[00:05:40] Grandium desktop scanners – making histology studies more accessible and efficient.[00:08:03] Clover framework – a cost-effective multimodal model combining vision + language for pathology.[00:13:40] NSCLC study (Beijing Chest Hospital) – AI predicts progression-free and overall survival with high accuracy.[00:17:58] Prostate cancer prognostic model (Cleveland Clinic & US partners) – validating AI-enabled Pathomic PRA test.[00:23:35] Thyroid neoplasm classification – challenges for AI in distinguishing overlapping histopathological features.[00:34:49] Real-world Belgium case study – AI integration into prostate biopsy workflow reduced IHC testing and turnaround time.[00:41:03] Lessons learned – adoption hurdles, system integration, and why change management is essential for successful digital transformation.Resources from this EpisodeWorld Tumor Registry – A global open-access repository for histopathology images: World Tumor RegistryBeijing Chest Hospital NSCLC AI Prognostic Study – Prognosis prediction using multimodal models.Cleveland Clinic Pathomic PRA Study – Independent validation of AI-enabled prostate cancer risk assessment.Grandium Scanners – Compact desktop scanners for histology slides: Grandium.aiSupport the showBecome a Digital Pathology Trailblazer get the "Digital Pathology 101" FREE E-book and join us!

IHC’s national fundraising manager welcomes a new sponsor, Alltech, to join PGG Wrightson and Allflex. Last year, the Calf and Rural Scheme returned to pre-covid income of $1.2 million, and the number of pledges has just gone over 3000. While this is ahead of last year, some canvassers are still phoning farmers they haven’t got to.See omnystudio.com/listener for privacy information.

In this episode of Ideas Have Consequences, Larry Alex Taunton calls out Tucker Carlson's troubling decision to give a platform to controversial figures like Nazi apologist David Collum. Taunton warns of the moral cost of chasing clicks at the expense of truth and highlights the responsibility of leaders to maintain intellectual and moral integrity. Visit www.ao.gold — where Alpha Omega Gold is giving IHC viewers a free Precious Metals Navigation Guide to help you safeguard and grow your wealth! ✉️ Get all the content I can't share publicly directly in your inbox https://join.larrytaunton.com/

Send us a textAI Pathology & Genomics: A New Benchmark for Predicting Gene MutationsIf you still think visual quantification is “good enough” in pathology, think again. In this 27th episode of DigiPath Digest, I break down four transformative abstracts that show how AI is shifting our diagnostic landscape—from breast cancer segmentation to fibrosis assessment, and all the way to spatial immunology and the evolving immunoscore.If you're still relying on manual scoring, static staging systems, or single-marker immunohistochemistry, this episode will challenge you to look deeper—literally and algorithmically.

In today's episode, supported by Daiichi-Sankyo, we spoke with Ronan J. Kelly, MD, MBA, FASCO; and Michelle Shiller, DO, AP/CP, MGP, about HER2 immunohistochemistry (IHC) testing in non–small cell lung cancer (NSCLC). Kelly is director of the Charles A. Sammons Cancer Center and chief science officer at Baylor University Medical Center in Dallas, Texas; the W.W. Caruth Jr. Endowed Chair of Immunology at Baylor University Medical Center; chief of Oncology at Baylor Scott & White Health System; founder and medical director of the Texas Cancer Interception Institute; a clinical professor at the Texas A&M University College of Medicine; an adjunct associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, Maryland; and a professor in the Clinical Sciences Division at the Translational Genomics Research Institute in Phoenix, Arizona. Shiller is a molecular genetic pathologist at Baylor University Medical Center.  In our conversation, Drs Kelly and Shiller discussed the importance of performing IHC testing for HER2 in NSCLC, how IHC results may influence treatment decision-making beyond the scope of next-generation sequencing results, and recommendations for more efficient and collaborative IHC testing implementation in clinical practice. 

Send us a textIf our visual scoring is still based on gut feeling, how do we scale precision? In this week's DigiPath Digest, I explored four new AI-focused papers that could reshape how we diagnose prostate, bladder, gastroesophageal, and endocrine cancers.From automated IHC scoring to predicting urethral recurrence post-cystectomy, these studies highlight the growing value—and responsibility—of integrating AI into our pathology workflows.And yes, I also reveal where to get my histology-inspired earrings

Kilbeacanty's Brendan Burke, Beagh captain Joe Gantley, Rahoon Newcastle's Tony Og Regan and Turloughmore intermediate manager Nigel O'Kane join Paul to preview group group 4 in the IHC

In today's episode, we had the pleasure of speaking with Martin F. Dietrich, MD, PhD, about updates and best practices for HER2 and MET immunohistochemistry (IHC) testing for patients with non–small cell lung cancer (NSCLC). Dr Dietrich is a medical oncologist at Cancer Care Centers of Brevard in Rockledge, Florida; as well as an assistant professor of internal medicine at the University of Central Florida in Orlando.  In our exclusive interview, Dr Dietrich discussed the rationale for testing for these mutations in patients with NSCLC, standard practices for implementing these tests in the clinic, and when testing may be appropriate at disease progression. 

“Colorectal cancer treatment is not just about eliminating a disease. It's about preserving life quality and empowering patients through every phase. So I think nurses are really at the forefront that we can do that in the oncology nursing space. So from early detection to survivorship, the journey is deeply personal. Precision medicine, compassionate care, and informed decision-making are reshaping outcomes. Treatment's just not about protocols. It's about people,” ONS member Kris Mathey, DNP, APRN-CNP, AOCNP®, gastrointestinal medical oncology nurse practitioner at The James Cancer Hospital of The Ohio State University Wexner Medical Center in Columbus, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about colorectal cancer treatment.  Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0  Earn 1.0 contact hour of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by August 1, 2026. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. Learning outcome: Learner will report an increase in knowledge related to the treatment of colorectal cancer. Episode Notes  Complete this evaluation for free NCPD. ONS Podcast™ episodes: Episode 370: Colorectal Cancer Screening, Early Detection, and Disparities Episode 153: Metastatic Colorectal Cancer Has More Treatment Options Than Ever Before ONS Voice articles: Colorectal Cancer Prevention, Screening, Treatment, and Survivorship Recommendations Genetic Disorder Reference Sheet: Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) How Liquid Biopsies Are Used in Cancer Treatment Selection Oncology Drug Reference Sheet: 5-Fluorouracil Oncology Drug Reference Sheet: Oxaliplatin What Is a Liquid Biopsy? Clinical Journal of Oncology Nursing article: Colorectal Cancer in Young Adults: Considerations for Oncology Nurses Oncology Nursing Forum article: Neurotoxic Side Effects Early in the Oxaliplatin Treatment Period in Patients With Colorectal Cancer ONS Colorectal Cancer Learning Library ONS Biomarker Database (filtered by colorectal cancer) ONS Peripheral Neuropathy Symptom Interventions American Cancer Society colorectal cancer resources CancerCare Colorectal Cancer Alliance Colorectal Cancer Resource and Action Network Fight Colorectal Cancer National Comprehensive Cancer Network To discuss the information in this episode with other oncology nurses, visit the ONS Communities.  To find resources for creating an ONS Podcast club in your chapter or nursing community, visit the ONS Podcast Library. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From This Episode “Colorectal cancer has several different types, but there is one that dominates the landscape, and that is adenocarcinoma. So I think most of us have heard that. It's fairly common, and it accounts for about 95% of all colorectal cancers. It begins in the glandular cells lining the colon or rectum and often develops from polyps, in particular adenomatous polyps.” TS 1:41 “One of the biomarkers that we'll most commonly hear about is KRAS or NRAS mutations. This indicates tumor genetics, and these mutations suggest resistance to our EGFR inhibitors such as cetuximab. BRAF mutation or V600E is a more aggressive tumor subtype, and those may respond to our BRAF targeted therapy. … And then our MSI-high or MMR-deficient—microsatellite instability or mismatch repair deficiency—that really predicts an immunotherapy response and may indicate Lynch syndrome, which is a huge genetic component that takes a whole other level of counseling and genetic testing with our patients as well.” TS 6:02 “Polypectomy or a local excision—that removes our small tumors or polyps during that colonoscopy. And that's what's used for those stage 0 or early stage I cancers. A colectomy removes part or all of the colon. This may be open or laparoscopic. It can include a hemicolectomy, a segmental resection, or a total colectomy, so where you take out the entire part of the colon. A proctectomy removes part or all of the rectum. This may include a low anterior resection, also known as an LAR … or an abdominal perineal resection, which is an APR. … Colostomy or ileostomy—that diverts the stool to an external bag via stoma. Sometimes this is temporary or permanent depending on the type of surgery.” TS 14:11 “We'll have our patients say, ‘Hey, I want immunotherapy therapy. I see commercials on it that it works so well.' We have to make sure that these patients are good candidates for it, also that we're treating them adequately. We need to make sure that they have those biomarkers, so as I mentioned, the MSI-high or MMR tumors. Our MSS-stable tumors—they may benefit from newer combinations or clinical trials. Metastatic disease—immunotherapy may be used alone or with other treatments. And then in the neoadjuvant setting, some trials are really showing promising results using immunotherapy prior to surgery.” TS 25:38 “Antibody-drug conjugates are really an exciting frontier in all cancer treatments as well as colorectal cancer treatment. This is used mainly for patients with advanced or treatment-resistant disease, and these therapies combine the targeted power of monoclonal antibodies with the cell-killing ability of potent chemotherapy agents. They're still on the horizon for the most part in colorectal cancer. However, there is only one approved antibody-drug conjugate, or ADC, at this time, and that's trastuzumab deruxtecan, or Enhertu. That's approved for any solid tumor, such as colorectal cancer with HER2 IHC 3+. So again, looking back at that pathology in those markers, making sure that you have that HER2 mutation and that IHC.” TS 35:00 “There are a few myths going around about colorectal cancer treatment that can lead to confusion or even delayed care. One myth is only older men get colorectal cancer. As you heard me talk in my previous podcast on screening, unfortunately, this isn't necessarily true. Colorectal cancer affects both men and women and our cases in the younger population are rising. So our screening guidelines have changed to age 45 because we are seeing it in the younger population.” TS 45:54

The beer industry looks a lot different than it did a few years ago, and packaging strategies are evolving right alongside it. In this conversation, we'll talk with Brian Casse from Iron Heart Canning about how mobile canning has adapted to meet the needs of today's breweries.We'll cover what's changed in the market, what breweries should consider before investing in their own equipment, and where mobile canning fits into a smart, flexible business model. Brian will also share lessons from more than a decade in the field and what he sees ahead for both packaging and the industry as a whole.Brian Casse is the second ever Iron Heart Canning employee and has done everything from warehouse work, to working the back end of the canning line, leading into being a sales manager, helping grow the business in the North East before expanding the South and Midwest. He is now the Head of Sales, managing the sales team and continuing to help IHC grow. You can find him on instagram @idrinkgoodbeer as well as listen to the podcast he helps manage called Steal This Beer with his friends Justin Kennedy, John Holl from All About Beer Magazine and Augie Carton of Carton Brewing.Stay up to date with CBP: http://update.craftbeerprofessionals.org

Leo McGough joinus us this week for a superb discussion on Carlow hurling.We thrash out the inter county season and where Carlow may have missed a trick outside of the Joe McDonagh Cup also.We look at Kildare and weigh up who is currently better placed to make a push.We chat about what a future All Ireland Championship may look like.We discuss how dead rubbers could be reduced in Carlow club formats.The continued love for this years IHC.Setanta's landmark with in the JHC.Bennekerry/Tinryland see off Old Leighlin in Ladies SFCIntermediate Camogie Championship novelty.Some funny stories near the end of the pod also!Thanks to Brendan Kavanagh Furniture and Property Partners Buggy PortlaoiseIf you like what you're hearing you can help us fuel the podcast for the price of a coffee - https://buymeacoffee.com/leftwingback

After a little sabbatical Kev & Stevie are back to take you through the Carlow Club Hurling Championships!- All Ireland Hurling Final conversation- The story of the adult grades so far- Parish Derby to whet the appetite- First teams to the fore in IHC

In today's episode, we had the pleasure of speaking with Jonathan M. Gerber, MD; and Shyam A. Patel, MD, PhD, about a study they conducted investigating the use of immunohistochemistry (IHC) as a biomarker for early TP53 mutation identification in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Dr Gerber is a member of the faculty in the Department of Medicine at New York University (NYU) Grossman School of Medicine; as well as the chief clinical officer of the NYU Perlmutter Cancer Center. Dr Patel is an associate professor at the University of Massachusetts Chan Medical School; as well as a hematologist and oncologist at the UMass Memorial Medical Center in Worcester.  In our exclusive interview, Drs Gerber and Patel discussed the evaluation of p53 IHC as a surrogate biomarker for TP53-mutant MDS and AML. They shared how the presence of TP53 mutations in these diseases significantly worsens prognosis, necessitating urgent treatment. They also highlighted how IHC results are available within 48 to 72 hours. Gerber and Patel explained this study's design and patient population, as well as how IHC's inverse correlation with overall survival highlights its potential as an early biomarker, though it has lower sensitivity for certain mutations.

Next Tuesday the IHC - which advocates for the rights, inclusion and welfare of people with intellectual disabilities will offiicially launch its new report entitled The Cost of Exclusion.

Welcome to another episode of the Oncology Brothers podcast! In this episode, Drs. Rohit and Rahul Gosain, both practicing community medical oncologists, continue their discussion on HER2-positive biliary tract cancer. They are joined by Dr. Shubham Pant from MD Anderson, who shares his expertise on this rapidly evolving field. In this episode, we cover: •⁠  ⁠The importance of HER2 testing in biliary tract cancers, including intrahepatic and extrahepatic cholangiocarcinomas and gallbladder cancers. •⁠  ⁠Who should be tested for HER2 positivity and how to classify HER2-positive disease. •⁠  ⁠The role of next-generation sequencing (NGS) and immunohistochemistry (IHC) in determining HER2 status. •⁠  ⁠Current treatment options for HER2-positive biliary tract cancer, including the latest clinical trials and approved therapies like trastuzumab deruxtecan and zanidatamab. •⁠  ⁠The significance of patient-centered decision-making and managing side effects associated with these treatments. •⁠  ⁠Insights into the potential for brain metastases in biliary tract cancer and the importance of ongoing surveillance. Join us as we delve into the latest data and strategies for managing HER2-positive biliary tract cancer, and stay tuned for our next episode where we will discuss side effects and management of these therapies. Accreditation/Credit Designation Physicians' Education Resource®, LLC is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Physicians' Education Resource®, LLC designates this enduring material for a maximum of 0.25 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Acknowledgment of Commercial Support This activity is supported by an educational grant from Jazz Pharmaceuticals, Inc. Link to gain CME credits from this activity: https://www.gotoper.com/courses/from-bench-to-bedside-paradigm-shifts-in-her2-metastatic-btc-treatment Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates from the Oncology Brothers!

Join us for an insightful episode of the Oncology Brothers podcast as we dive into the fast-evolving landscape of HER2-positive non-small cell lung cancer (NSCLC). In this first part of the two-part series, Drs. Rahul and Rohit Gosain were joined by Dr. Devika Das, a thoracic medical oncologist, and Dr. Fernando Lopez-Rios, a pathologist, to discuss the critical importance of testing and identifying HER2 alterations in lung cancer patients. In this episode, we covered: •⁠  ⁠The significance of HER2 alterations in NSCLC and how they differ from breast and gastric cancers. •⁠  ⁠The complexities of biomarker testing, including NGS, IHC, and FISH amplification. •⁠  ⁠Patient characteristics and phenotypes associated with HER2-positive disease. •⁠  ⁠The current testing workflows in clinical practice and the role of liquid biopsies. •⁠  ⁠Insights into the treatment landscape for HER2-positive NSCLC, including recent FDA approvals and ongoing clinical trials. Whether you're a healthcare professional or simply interested in the latest advancements in oncology, this episode provides valuable information on the integration of precision medicine in lung cancer treatment. YouTube: https://youtu.be/gMi-sflQyQo Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to subscribe for the next episode, where we will explore treatment options for HER2-positive non-small cell lung cancer in greater detail!

“Now, what we found is that epigenetics is actually heritable and it's actually reversible. And we can now manipulate these principles with pharmacotherapy drugs,” Eric Zack, RN, OCN®, BMTCN®, clinical assistant professor at Loyola College Chicago Marcella Niehoff School of Nursing in Chicago, IL, and RN3 at Rush University Medical Center in Chicago, told Jaime Weimer, MSN, RN, AGCNS-BS, AOCNS®, manager of oncology nursing practice at ONS, during a conversation about the epigenetics drug class.  Music Credit: “Fireflies and Stardust” by Kevin MacLeod  Licensed under Creative Commons by Attribution 3.0   Earn 0.75 contact hours (including 40 minutes of pharmacotherapeutic content) of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at courses.ons.org by February 28, 2027. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation.  Learning outcome: Learners will report an increase in knowledge related to the epigenetics drug class.  Episode Notes   Complete this evaluation for free NCPD.  ONS Podcast™ Pharmacology 101 series ONS Voice articles: Financial Navigation During Hematologic Cancer Saves Patients and Caregivers $2,500 Oncology Drug Reference Sheets What Is MCED Testing? ONS book: Clinical Guide to Antineoplastic Therapy: A Chemotherapy Handbook (Fourth Edition) ONS Biomarker Database ONS course: Genomic Foundations for Precision Oncology ONS Huddle Card: Financial Toxicity  ONS Learning Libraries: Genomics and Precision Oncology Oral Anticancer Medication American Cancer Society: Patient Programs and Services Centers for Disease Control and Prevention: Epigenetics, Health, and Disease Leukemia & Lymphoma Society: Financial Support National Institutes of Health: Epigenetics University of Pennsylvania: Epigenetics Institute University of Utah: Genetic Science Learning Center To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library.  To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.  Highlights From This Episode  “Epigenetics is influenced by several factors. Right now, there's about seven of them that we've identified, and we can only manipulate right now about two of those seven. So the first one is DNA methylation. When you methylate DNA, that's adding or subtracting a methyl group, which is CH3, chemically. The addition of methyl to DNA tightens the DNA around the chromatin, which then can block some genes from being expressed.” TS 7:21  “Histones basically package DNA into the chromatin, which is a mixture of DNA and proteins, and they spool around this structure like the DNA is coiled around that. And again, it has to do with how tight or loose that is coiled. That determines if the genes are expressed or not. And again, we found that histones also play a role in DNA repair as well as regulating the cell cycle.” TS 8:21  “When we're dealing with the azacitidine and decitabine, these drugs cause pancytopenia. Pancytopenia is neutropenia, thrombocytopenia, and anemia. So it affects the complete blood count. We see GI toxicity, nausea, vomiting, diarrhea, constipation, sometimes mouth sores, and urticaria—hives.” TS 15:34  “It's really, really important to take these drugs exactly as they are prescribed. They have to follow the doctor's orders carefully, which requires taking them properly, doing the proper follow up. There's a lot of blood tests and appointments that we have to do to make sure that everything is okay. And again, because we know when there is nonadherence, the disease progresses and becomes resistant, so that's a really, really important teaching point. We have to monitor the patient for expected side effects and unexpected side effects.” TS 23:58  “Now, we expect the landscape to change dramatically over the next few years. And again, it's just an explosion of science information. As we learn more about the science, it's going to translate into practice. We're always identifying new biomarkers. These biomarkers are essentially DNA mutations or variations. There's so many variants of unknown significance.” TS 30:02  “Every patient deserves biomarker testing. Very important, whether it's through IHC, polymerase chain reactions, or the most common next-gen sequencing. Again, there's several companies out there that have standard kits available.” TS 31:33  “This is a precision medicine. This is what we've always dreamed about—tailoring the treatment to the specific patient. We've gone away from treating standard diseases, like lung cancer and breast cancer, the way they're supposed to be treated to now looking at these biomarkers and using epigenetic drugs and other medications tailored to those variants that that patient is having, not necessarily based on their disease type.” TS 33:59   

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The Development of a Cocktail of Microglia and GFAP For Easy Diagnosis - Anisha Bhasin B.S, Sarah Holguin, MBA. B.S, Joe Vargas, M.S Microglia and GFAP are distinct neural markers, typically used separately to diagnose the degree of neurological infection and injury. Microglia, a glial cell, is used in the immune response of the central nervous system. GFAP is an astrocyte marker; astrocytes provide structural support and make up the blood-brain barrier. Using the two in conjugation with one another would prove to be an efficient diagnostic tool. A cocktail was constructed with optimal titration to observe the two markers in unison. In clinical usage, it will provide an efficient diagnosis of chronic inflammatory conditions of the central nervous system. The staining was conducted in IHC and fluorescence to compare morphology and count. Due to anatomical similarities, there tends to be morphological confusion between microglia and GFAP. However, when stained in conjunction with one another, notable differences can allow for easy distinction. This is why a cocktail run with a dual staining technique would be a superior diagnostic tool in comparison to testing the two markers independently.