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Featuring perspectives from Dr Yelena Janjigian, Prof Florian Lordick and Dr Zev Wainberg, moderated by Dr Samuel Klempner, including the following topics: • Optimizing the Selection of Therapy for Newly Diagnosed Advanced Gastric or Gastroesophageal Junction (GEJ) Cancer — Dr Klempner o Introduction (0:00) o Case: A man in his mid 50s with HER2-negative gastroesophageal adenocarcinoma (PD-L1 100%) — Victoria Giffi, MD (1:15) o Cases: A woman in her early 80s with a history of Stage 0 chronic lymphocytic leukemia, now with unresectable gastric adenocarcinoma, develops Coombs-positive hemolytic anemia after 2 cycles of FOLFOX and nivolumab and a man in his early 60s with localized adenocarcinoma of the GEJ receives the CROSS regimen but is found at surgery to have metastatic disease and tumor NGS demonstrates an ARID1A mutation — Matthew R Strickland, MD and Priya Rudolph, MD, PhD (8:05) o Faculty presentation: Dr Klempner (14:05) • Current Considerations in the Treatment of HER2-Positive Advanced Gastric/GEJ Adenocarcinoma — Dr Janjigian o Case: A woman in her early 30s with newly diagnosed metastatic HER2-amplified signet cell gastric adenocarcinoma — Farshid Dayyani, MD, PhD (22:36) o Cases: A man in his mid 80s with newly diagnosed HER2-positive gastroesophageal cancer metastatic to the liver and lung, tumor 3+ by IHC for HER2 with a PD-L1 of 10 and a woman in her mid 70s with HER2-positive esophageal adenocarcinoma and brain metastases after stereotactic radiosurgery — Warren S Brenner, MD and Dr Strickland (31:43) o Faculty presentation: Dr Janjigian • Selection and Sequencing of Therapy for Relapsed/Refractory Gastric/GEJ Cancer; Novel Investigational Approaches — Prof Lordick o Cases: A woman in her mid 70s with Lynch syndrome and a history of Stage III colon cancer presents with poorly differentiated GEJ carcinoma with liver and lung metastases and a man in his early 60s presents with a 70-lb weight loss and locally advanced high-grade neuroendocrine carcinoma of the distal esophagus — Namrata I Peswani, MD and Ranju Gupta, MD (46:19) o Case: A man in his early 60s with metastatic gastric adenocarcinoma (PD-L1 CPS 0) with clinical and radiographic progression of disease after 4 cycles of FOLFOX — Dr Strickland (52:31) o Faculty presentation: Prof Lordick (55:26) • Current Approaches to the Management of Esophageal Cancer — Dr Wainberg o Cases: A man in his late 50s with dysphagia, weight loss and a lower esophageal adenocarcinoma (T3N3) and a man in his mid 70s with dysphagia is found to have a lower esophageal adenocarcinoma with regional adenopathy and pulmonary nodules (CPS 40 by SP263) — Gurveen Kaur, MD and Liudmila N Schafer, MD (1:03:56) o Case: A woman in her early 60s with a known germline BRCA2 mutation and a history of Hodgkin lymphoma, breast and anaplastic thyroid cancers now has localized squamous cell esophageal cancer — Dr Brenner (1:11:56) o Faculty presentation: Dr Wainberg (1:17:49) CME information and select publications
(00:31) Could you provide a little bit about yourself and your background? (02:04) Could you provide an overview of the chromosomal microarray assay? (05:49) Why should the chromosomal microarray assay be used over other available assays, such as FISH? (08:56) Does the chromosomal microarray provide good benefits in terms of gain of 7 and loss of 10, and EGFR amplification? (12:03) What's the value of utilizing the test alongside a neuro-specific NGS panel, such as Mayo Clinic Laboratories' NONCP panel? (17:20) How are the results used in patient care? (19:41)Is there anything else you feel it's important to highlight?
We are in the depths of winter, and whatever the weather may - or may not - have in store for us in this traditionally chilly month, Head Gardeners Saul and Lucy turn their thoughts to the year ahead. Often mistaken for a quieter season, there are plenty of winter tasks to complete and projects to initiate. Winter pruning, leaf clearing, renovations and new plantings will all be discussed (we can't promise that conversations about biscuits and lists won't also appear...). Whatever the topic, the duo hope to prime us all for the unfolding gardening seasons.We've all enjoyed those visits to gardens where we've left with bellies full of cake and an imagination full of ideas, so why not become a significant part of that hugely rewarding process? Opening your garden for charity can feel like a daunting process, but inspired by the National Garden Scheme's recent 2023 media launch, Lucy and Saul discuss the many benefits it can bring. Talking to an NGS county organiser, and overcoming any hesitancies you might have, will help raise funds for brilliant causes and give your garden a motivational focus.Twitter links:Lucy @HeadGardenerLCSaul @GardeningSaulIntro and Outro music from https://filmmusic.io"Fireflies and Stardust" by Kevin MacLeod (https://incompetech.com)License: CC BY (http://creativecommons.org/licenses/by/4.0/) Support the show
(00:31) Could you provide our listeners with a little bit about yourself and your background?(01:48) Could you give an overview of the new neuro-oncology expanded gene panel by next generation sequencing? (03:43)Can you describe a little bit more about some examples of genes that were in the 2021 WHO classification that are now included in the NONCP panel? (06:50) Does this panel have high clinical utility in both in adult and pediatric cases? (08:05) Is picking up on copy numbers useful in both adult and pediatric cases? (09:12) Could you discuss a little bit more about how these results would be used in patient care? (10:27) Do you have anything else you would like to add about the enhanced neuro-oncology NGS panel?
Brought to you by LinkedIn Jobs recruitment platform with 800M+ users, FreshBooks cloud-based small business accounting software, and ButcherBox premium meats delivered to your door.Wade Davis (@wadedavisofficial, daviswade.com) is Professor of Anthropology and the BC Leadership Chair in Cultures and Ecosystems at Risk at the University of British Columbia. Between 2000 and 2013, he served as Explorer-in-Residence at the National Geographic Society. Named by the NGS as one of the Explorers for the Millennium, he has been described as “a rare combination of scientist, scholar, poet, and passionate defender of all of life's diversity.” An ethnographer, writer, photographer, and filmmaker, Wade holds degrees in anthropology and biology and a PhD in ethnobotany, all from Harvard University. Mostly through the Harvard Botanical Museum, he spent over three years in the Amazon and Andes as a plant explorer, living among 15 indigenous groups while making some 6000 botanical collections. His work later took him to Haiti to investigate folk preparations implicated in the creation of zombies, an assignment that led to his writing The Serpent and the Rainbow, an international bestseller, later released by Universal as a motion picture. In recent years, his work has taken him to East Africa, Borneo, Nepal, Peru, Polynesia, Tibet, Mali, Benin, Togo, New Guinea, Australia, Colombia, Vanuatu, Mongolia, and the high Arctic of Nunavut and Greenland. Wade is the author of 375 scientific and popular articles and 23 books including One River, The Wayfinders, Into the Silence, and Magdalena. His photographs have been widely exhibited and have appeared in 37 books and 130 magazines, including National Geographic, Time, Geo, People, Men's Journal, and Outside. He was curator of “The Lost Amazon: The Photographic Journey of Richard Evans Schultes,” first exhibited at the National Museum of Natural History, Smithsonian Institution. In 2012 he served as guest curator of “No Strangers: Ancient Wisdom in the Modern World,” at the Annenberg Space for Photography in Los Angeles. He was curator of “Everest: Ascent to Glory,” Bowers Museum, February 12–August 28, 2022. National Geographic has published two collections of his photography: Light at the Edge of the World (2001) and Wade Davis: Photographs (2018).His 40 film credits include Light at the Edge of the World, an eight-hour documentary series written and produced for National Geographic. His most recent film, El Sendero de la Anaconda, a 90-minute feature documentary shot in the Northwest Amazon, is available on Netflix.A professional speaker for 30 years, Wade has lectured at over 200 universities and 250 corporations and professional associations. In 2009 he delivered the CBC Massey Lectures. He has spoken from the main stage at TED five times, and his three posted talks have been viewed by 8 million. His books have appeared in 22 languages and sold approximately one million copies.Wade, one of 20 Honorary Members of the Explorers Club, is Honorary Vice President of the Royal Canadian Geographical Society and recipient of 12 honorary degrees. He has been awarded the 2009 Gold Medal from the Royal Canadian Geographical Society, the 2011 Explorers Medal, the 2012 David Fairchild Medal for botanical exploration, the 2015 Centennial Medal of Harvard University, the 2017 Roy Chapman Andrews Society's Distinguished Explorer Award, the 2017 Sir Christopher Ondaatje Medal for Exploration, and the 2018 Mungo Park Medal from the Royal Scottish Geographical Society. In 2016, he was made a Member of the Order of Canada. In 2018 he became an Honorary Citizen of Colombia.Please enjoy!*This episode is brought to you by LinkedIn Jobs. Whether you are looking to hire now for a critical role or thinking about needs that you may have in the future, LinkedIn Jobs can help. LinkedIn screens candidates for the hard and soft skills you're looking for and puts your job in front of candidates looking for job opportunities that match what you have to offer.Using LinkedIn's active community of more than 800 million professionals worldwide, LinkedIn Jobs can help you find and hire the right person faster. When your business is ready to make that next hire, find the right person with LinkedIn Jobs. And now, you can post a job for free. Just visit LinkedIn.com/Tim.*This episode is also brought to you by ButcherBox! ButcherBox makes it easy for you to get high-quality, humanely raised meat that you can trust. They deliver delicious, 100% grass-fed, grass-finished beef; free-range organic chicken; heritage-breed pork, and wild-caught seafood directly to your door.ButcherBox has a special offer running for you, my dear listeners. Use code TIM to get $20 off your first box. Sign up at ButcherBox.com/Tim and use code TIM to get $20 off.*This episode is also brought to you by FreshBooks. I've been talking about FreshBooks—an all-in-one invoicing + payments + accounting solution—for years now. Many entrepreneurs, as well as the contractors and freelancers that I work with, use it all the time.FreshBooks makes it super easy to track things like expenses, project time, and client info and then merge it all into great-looking invoices. And right now, there's a special offer just for my listeners. Head over to FreshBooks.com/Tim to get 90% off your FreshBooks subscription for 4 months. *[06:34] The Wayfinders.[17:01] The Earth's caretakers of Northern Colombia.[25:31] Coca and mambe.[34:17] Zombies, mysterious elixirs, and a sorcerer pimp.[49:35] The social implications of zombification and dangers of datura.[57:57] David Maybury-Lewis, Richard Evans Schultes, and living exploration.[1:02:13] Why helping young people is a top priority for Wade.[1:07:43] Pessimism is an indulgence. Choose optimism.[1:13:10] Rites of passage.[1:17:26] The night Wade had to light himself on fire.[1:20:37] The scar Wade doesn't regret.[1:23:41] Raising kids to be better citizens of the world.[1:31:02] Wade's own hero's journey.[1:34:19] Ayahuasca origin stories and uses alternative to healing.[1:47:34] The real tragedy of coca.[1:50:29] Dosed dogs, provocative gardens, and the cosmology of bitter manioc.[1:53:41] What psychedelics gave Wade earlier in life vs. later on.[2:06:34] How did Wade teach himself to write well?[2:18:50] Work points and outlining the course of a book.[2:28:26] Parting thoughts.*For show notes and past guests on The Tim Ferriss Show, please visit tim.blog/podcast.For deals from sponsors of The Tim Ferriss Show, please visit tim.blog/podcast-sponsorsSign up for Tim's email newsletter (5-Bullet Friday) at tim.blog/friday.For transcripts of episodes, go to tim.blog/transcripts.Discover Tim's books: tim.blog/books.Follow Tim:Twitter: twitter.com/tferriss Instagram: instagram.com/timferrissYouTube: youtube.com/timferrissFacebook: facebook.com/timferriss LinkedIn: linkedin.com/in/timferrissPast guests on The Tim Ferriss Show include Jerry Seinfeld, Hugh Jackman, Dr. Jane Goodall, LeBron James, Kevin Hart, Doris Kearns Goodwin, Jamie Foxx, Matthew McConaughey, Esther Perel, Elizabeth Gilbert, Terry Crews, Sia, Yuval Noah Harari, Malcolm Gladwell, Madeleine Albright, Cheryl Strayed, Jim Collins, Mary Karr, Maria Popova, Sam Harris, Michael Phelps, Bob Iger, Edward Norton, Arnold Schwarzenegger, Neil Strauss, Ken Burns, Maria Sharapova, Marc Andreessen, Neil Gaiman, Neil de Grasse Tyson, Jocko Willink, Daniel Ek, Kelly Slater, Dr. Peter Attia, Seth Godin, Howard Marks, Dr. Brené Brown, Eric Schmidt, Michael Lewis, Joe Gebbia, Michael Pollan, Dr. Jordan Peterson, Vince Vaughn, Brian Koppelman, Ramit Sethi, Dax Shepard, Tony Robbins, Jim Dethmer, Dan Harris, Ray Dalio, Naval Ravikant, Vitalik Buterin, Elizabeth Lesser, Amanda Palmer, Katie Haun, Sir Richard Branson, Chuck Palahniuk, Arianna Huffington, Reid Hoffman, Bill Burr, Whitney Cummings, Rick Rubin, Dr. Vivek Murthy, Darren Aronofsky, Margaret Atwood, Mark Zuckerberg, Peter Thiel, Dr. Gabor Maté, Anne Lamott, Sarah Silverman, Dr. Andrew Huberman, and many more.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.
Dr. Praveen Vikas, Dr. Tyler Johnson, and Dr. Russell Broaddus present the ASCO endorsement of the Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: Guideline From the College of American Pathologists in Collaboration With the Association for Molecular Pathology and Fight Colorectal Cancer. They discuss key evidence-based recommendations, focusing on the appropriate modality of testing (immunohistochemistry, polymerase chain reaction, or next generation sequencing) across multiple cancer types. Additionally, they cover the ASCO endorsement process, points of emphasis raised by the ASCO expert panel, and implications for clinicians and patients. Read the full guideline endorsement, Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of CAP Guideline at www.asco.org/molecular-testing-and-biomarkers-guidelines. TRANSCRIPT 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. Praveen Vikas from the University of Iowa, Dr. Tyler Johnson from Stanford University, and Dr. Russell Broaddus from the University of North Carolina; authors on, 'Mismatch Repair and Microsatellite Instability Testing for Immune Checkpoint Inhibitor Therapy: ASCO Endorsement of CAP Guideline'. Thank you for being here, Dr. Vikas, Dr. Johnson, and Dr. Broaddus. Dr. Praveen Vikas: Sure. Dr. Tyler Johnson: Thanks for having us. Dr. Russell Broaddus: Thank you. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of its guidelines, and ensuring that the ASCO Conflict of Interest policy is followed for each guideline product. The full conflict of interest information for this guideline endorsement panel is available online with the publication of the guideline endorsement in the Journal of Clinical Oncology. To start, Dr. Vikas, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Praveen Vikas: I don't. Brittany Harvey: And Dr. Johnson, do you have any relevant disclosures that are directly related to this guideline? Dr. Tyler Johnson: I do not. Brittany Harvey: And finally, Dr. Broaddus, do you have any relevant disclosures that are directly related to this guideline topic? Dr. Russell Broaddus: I do not. Brittany Harvey: Great. Thank you all for providing that information. So, starting us off on the content of this endorsement, Dr. Vikas, what is the scope of this guideline endorsement? Dr. Praveen Vikas: So, as you can see from the topic and headline, the guideline endorsement was focused on mismatch repair and microsatellite instability testing for immune checkpoint inhibitor therapy, and this is basically an endorsement by ASCO, of a guideline that was developed jointly by CAP, and others. Brittany Harvey: Great. And then you just mentioned that this is an endorsement of the guideline developed by CAP and other organizations. Can you provide us an overview of how this guideline endorsement process works? Dr. Praveen Vikas: ASCO definitely takes great pride in endorsing some of the guidelines that are relevant to our cancer community, and of course, mismatch repair and microsatellite instability testing has been one of those areas where there is a lack of clear guidance. So, when we were approached from CAP about endorsing this guideline, we definitely realized that there's not much published from most of our oncology community, so we were very excited about looking into this guideline and endorsing it. So, this was very much for a topic that we thought is very useful and very timely. Brittany Harvey: And that's great to hear. So then, Dr. Broaddus, as an author both on the guideline endorsement and as a member of the original guideline panel, what are the key recommendations of the CAP guideline? Dr. Russell Broaddus: So, there are six key recommendations from the College of American Pathologists guideline that ASCO recently endorsed. I like to think of the first four as being bundled together because they're interrelated - we dealt with these by cancer type for the first four. So, for colorectal cancer, there's by far the most published evidence on this type of testing, and the evidence-based guideline found that really did not matter so much whether you used immunohistochemistry, or PCR-based microsatellite instability analysis, or next-generation sequencing-based analysis to detect mismatch repair or microsatellite instability. The three different techniques are almost interchangeable in their metrics. Similarly, for gastroesophageal adenocarcinoma and small intestinal adenocarcinoma, immunohistochemistry and PCR-based MSI are very, very similar. There's not quite enough published evidence to equate next-generation sequencing. There were one or two very, very good papers with limited number of patients. The guideline committee felt like if there was maybe one or two more published papers in this space, that for gastroesophageal adenocarcinoma and small bowel adenocarcinoma, it would be similar to colorectal adenocarcinoma, whereas the three techniques were nearly interchangeable. After that, unfortunately, the published evidence really drops off in both quantity and quality for almost all other cancer types. So, endometrial cancer, there's quite a bit of literature. Most of it really points to the immunohistochemistry outperforms PCR-based MSI analysis and PCR-based next-generation sequencing analysis. Most likely, that's because these PCR-based approaches nearly always are optimized to detect mismatch repair defects in colorectal cancer, or other GI types of cancer. And there's actually very good published evidence that this detection of mismatch repair can be cancer-type specific. So, the recommendation is to use immunohistochemistry for endometrial cancer. Fourth recommendation for all other cancer types not encompassed by those first three recommendations, the committee recommends to choose a laboratory-based approach to detect mismatch repair or microsatellite instability defects, but there is no good published evidence to suggest which is the best approach. And again, like with endometrial cancer, there's evidence that the PCR-based approaches, which are usually optimized for colorectal cancer and GI-type cancers, may not be sufficient to work well with cancer types outside of the GI tract. So, almost by default, the recommendation is to choose immunohistochemistry. Fifth recommendation: Many people tend to equate microsatellite instability and high tumor mutation burden. For sure, in colorectal cancer and other GI tract cancers, these two entities, there is substantial overlap. But for cancer types outside of the GI tract, you can easily have a tumor that has a mismatch repair defect, or high levels of microsatellite instability and not have high tumor mutation burdens. So, the recommendation is to not equate those two entities. And finally, last recommendation is that for all of us to remember that these defects in DNA mismatch repair or microsatellite instability, are also hallmarks of hereditary cancer syndrome - Lynch syndrome, and that if you identify unexpectedly that a patient with an advanced cancer has one of these defects and DNA mismatch repair, to consider the possibility of Lynch syndrome, and to alert the appropriate care team, for those patients' family members can be screened as well. Brittany Harvey: Understood. Thank you for reviewing those evidence-based recommendations made by the CAP panel, and then endorsed by the ASCO panel. So, were there any additional points of discussion or emphasis raised by the ASCO endorsement panel? Dr. Russell Broaddus: Yes. And very appropriately, I believe. One-- and this is purely because of the issue of scope, and not to minimize the importance of these issues. One issue that the CAP guideline did not address was the important issue of pre-analytic variables and how they can impact diagnostic testing. A second issue, again, not considered by the CAP evidence-based guideline group, because of just tremendous scope problems, is how do these tests - immunohistochemistry, PCR-based MSI analysis, PCR-based next-generation sequencing analysis - how do we incorporate their use with PD-L1 immunohistochemistry, for example? Liquid biopsies, as a second example. Should we have a staged approach in assessing tumors with all these different testing modalities? And frankly, the answer is, we don't know right now. I think this represents an excellent area where oncologists and pathologists can actually work to provide the evidence in some specific cancer types on whether multiple modalities provide benefit compared to just one modality. Brittany Harvey: Definitely, those are key points perhaps for future research, and I appreciate you explaining what was in and out of scope of this guideline. So then following that, Dr. Johnson, in your view, what is the importance of this guideline endorsement, and how will it affect ASCO members? Dr. Tyler Johnson: I think to understand the importance of this particular endorsement, it's helpful to zoom the lens out to 30,000 feet for a minute. Pretty much, all oncologists, I think remember 10 or 12 years ago, the types of drugs that we now commonly use for immunotherapy, burst onto the scene with the treatment of melanoma. And those trials were quite remarkable because previous to that, not only did we not have a cure for metastatic melanoma, we hardly had a treatment for metastatic melanoma. We had really almost nothing to offer those patients. And then there was this, initially a small and then a larger, and then a much larger series of patients, who we now know with 10 or 12 years of follow up, that many patients who were treated with immunotherapy, who had metastatic melanoma were actually cured. Not just treated but cured. So, in the decade or so since then, there has been this understandable and appropriate stampede of trying to figure out, "Okay, how do we use similar drugs in all of the other many metastatic tumor types?" And I think to generalize a lot, and to make overly simple a very complicated picture, what has emerged from that is that unfortunately for many metastatic solid tumors, immunotherapy just doesn't do much. It's essentially inert, as best we can tell clinically. But there is a small percentage of patients, exactly what percentage depends on the tumor type and the genetic analysis as we're talking about here, but there's a small percentage, maybe 10-20% of patients, who derive this unbelievable benefit from immunotherapy in metastatic solid tumors, to the point that some of those patients, including in other solid tumors, not just melanoma, appear to be functionally cured by the administration of immunotherapy. And so, the question of course that has resulted from that, is if eight or nine patients are going to get no benefit and maybe even harm from administration of immunotherapy, but one or two patients out of 10 is going to get this really remarkable benefit, it would be so great if we could be much more specific in knowing which patients are going to derive benefit, and which patients are not going to derive any benefit and may even be harmed. And I think that that's the context within which we have to understand this guideline endorsement, is that this is getting us one step further to knowing which patients are likely to get benefit from immunotherapy in metastatic solid tumors. And the really nice thing, as Russell pointed out, is that one kind of shorthand takeaway from this is that it is almost never wrong to look at the question with immunohistochemistry. And that's a great answer, because it is also almost always the most readily available test. And so, if you have a patient who has a metastatic solid tumor and you order immunohistochemistry to look for microsatellite instability, that's almost regardless of the tumor type, it's probably going to give you a reliable answer. And if it shows that they're microsatellite unstable, then that means that that patient, regardless of the tumor type, really probably should get immunotherapy upfront or very close to upfront. And then there are more nuances sort of beyond that. But I think that's really the take home message, that this gives us one powerful tool for discerning who is likely to get benefit from these therapies. Brittany Harvey: Absolutely. That's a key thought that you just mentioned, that this is about delivering personalized medicine to individual patients. So then, you've already touched on this a bit in your last answer, but finally, to wrap us up, how will these recommendations impact patients with cancer being considered for immune checkpoint inhibitor therapy? Dr. Tyler Johnson: I think that many clinical oncologists have the experience that when you sit down to talk to a patient who has newly diagnosed metastatic cancer, what their treatment is going to be, almost all of them have heard about immunotherapy somewhere; in the newspaper, or from friends, or in a cancer support group or whatever. So, most of them want to know what part, if any, immunotherapy is going to play in the care of their cancer right upfront. And I think this gets us one step closer to being able to answer that question. Now, the one thing that-- and Russell touched on this a little bit, but I think it's just important to highlight, this gives us an important way to predict people who are going to respond, but that does not necessarily mean that people who this does not identify as likely responders are therefore not going to respond. And that gets into a much more complicated question that depending on the tumor type, you may have to look at PD-L1 expression, or other things. So, it's just to say that this is not a comprehensive, definitive answer, but it is one important part of the answer. I don't know if Russell or Praveen wants to add any more thoughts about that, but that's kind of how I would contextualize this. Dr. Russell Broaddus: I think where there's a lot of opportunity here for us to start developing the evidence on the utility or not, of such staged approaches that if-- say like, immunohistochemistry does not reveal a mismatch repair defect, should we, for some of these cancer types where we don't routinely assess PD-L1, should we next do PD-L1 immunohistochemistry? And if that doesn't show overexpression, should we next try next-generation sequencing approach? Because sometimes those don't overlap with immunohistochemistry. So, I think there's a lot of room for us to provide this evidence. Dr. Praveen Vikas: Yeah. And one point I would like to add, we had a lot of discussion among our ASCO endorsement panel, was that by recommending IHC or PCR over NGS in certain cancer, there would be scenarios where NGS will be needed, because NGS would tell us a lot more, like HER2 amplifications, and that was our point of discussion. We wanted to make sure that we send that message that even in cases where IHC and PCR is being done, that we may still have additional need for NGS testing. Dr. Tyler Johnson: Yeah. Thank you, Praveen, for that. I should qualify, just to make sure that it's clear, that when I said that IHC is a good go-to, I only meant in terms of testing for this specific thing. Part of the problem with next gen sequencing is that it often takes 4-6 weeks, and so I think the practical approach is, you should send the next-generation sequencing, but in the meantime, you can do the IHC to have an answer to that particular question, and usually in one or two days, depending on the lab, and then the next gen sequencing can come back whenever it comes back, and then you can use that for directing later lines of therapy. Brittany Harvey: Excellent. Well, I've really enjoyed this discussion today, and I want to thank you all for your work on this guideline endorsement, and thank you for your time today, Dr. Vikas, Dr. Johnson and Dr. Broaddus. Dr. Praveen Vikas: Thanks so much, Brittany. Dr. Russell Broaddus: Thank you. Dr. Tyler Johnson: Appreciate the time. Brittany Harvey: And 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/molecular-testing-and-biomarkers-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. If you have 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.
CME credits: 0.25 Valid until: 27-12-2023 Claim your CME credit at https://reachmd.com/programs/cme/expert-answers-to-common-questions-about-met-exon-14skipping-mutations-in-nsclc/14678/ Non-small cell lung cancer (NSCLC) is a highly heterogeneous disease, and research has evolved its diagnosis and treatment through the discovery of genetic alterations and molecular pathways, personalizing treatment based on tumor mutation(s). The molecular characterization of tumors using techniques such as next-generation sequencing (NGS) has expanded the understanding of actionable molecular alterations, and in tandem has accelerated the development of drugs to inhibit alterations with greater specificity, leading to the development of novel target-selected agents in NSCLC. The NCCN Guidelines strongly advise assessment of at least 8 targets for NSCLC by NGS, including MET exon 14–skipping mutations (METex14). The FDA has approved two MET inhibitors, capmatinib and tepotinib, for patients with METex14 metastatic NSCLC, and there is ongoing research for other targeted agents. Studies have established that treatment with MET-targeted therapies improves outcomes in patients with METex14, as opposed to patients receiving chemotherapy and/or immunotherapy, which generate a modest activity response. AXIS routinely collects and analyzes data gathered from participants in our live activities. These questions provide incredible insight regarding the persistent challenges that clinicians face when trying to optimize treatment and management of patients with cancer to verify where clinical practice gaps exist. That's why this activity will …
In this Podcast, Dr Malinda Itchins, Medical Oncologist at Royal North Shore Hospital, Co-Chair of the Advanced Non-Small Cell Lung Cancer Group for TOGA and the Lung Cancer Chair of COSA, is joined by Professor Stephen Fox, Director of Pathology and Head of the Molecular Pathology Laboratory at the Peter MacCallum Cancer Centre in Melbourne Victoria and Professor Michael Millward, Medical Oncologist and Cancer Council Professor of Clinical Cancer Research School of Medicine, University of Western Australia to discuss NGS panels in lung cancer. They discuss the logistics and other considerations behind choosing and implementing NGS panels and the potential future application of this technology in clinical management of NSCLC. Keen to hear more beyond this podcast? Save the date 19 July 2023 for a f2f workshop in Melbourne discussing the various technologies for molecular testing, considerations for implementation and downstream applications. Registration will be part of TOGA ASM 2023 registrations expected to open by April 2023.
This week we're joined by Tecan Associate Director of Product Management Ashesh Saraiya, Ph.D., to discuss Tecan's achievement in winning the New Product Award at SLAS Europe 2022. for their MagicPrep™ NGS system! Saraiya is the expert on the award-winning product as he played a vital role in getting the MagicPrep™ NGS system to market. Also, he shares a glimpse into what Tecan's plans are for the MagicPrep™ NGS system and how laboratories can use the award-winning device for better library preparation. Key Learning Points:What makes the MagicPrep™ NGS system new and innovative The inspiration behind this NGS library preparation deviceHow the MagicPrep™ NGS system compares to other NGS systemsLearn more about MagicPrep™ NGS system from Tecan by visiting: www.tecan.com/magic Our Sponsor for this EpisodeTheWell Bioscience – developer of VitroGel, a next-generation xeno-free 3D extracellular matrix (ECM), enables scientists to shift from 2D to 3D cell culture and help drive innovations for precision medicine, cell therapy and biomanufacturing by getting faster and more accurate data than animal-based systems.Learn more about TheWell Bioscience by visiting:www.thewellbio.comStay connected with SLASOnline at www.slas.orgFacebookTwitter @SLAS_OrgLinkedInInstagram @slas_orgYouTubeAbout SLASSLAS (Society for Laboratory Automation and Screening) is an international professional society of academic, industry and government life sciences researchers and the developers and providers of laboratory automation technology. The SLAS mission is to bring together researchers in academia, industry and government to advance life sciences discovery and technology via education, knowledge exchange and global community building. For more information about SLAS, visit www.slas.org.SLAS publishes two peer-reviewed and MEDLINE-indexed scientific journals, SLAS Discovery and SLAS Technology. For more information about SLAS and its jourUpcoming SLAS Events: SLAS2023 International Conference and Exhibition February 25 - March 1, 2023 San Diego, CA, USA SLAS 2023 Building Biology in 3D Symposium 20-21 April 2023 Cambridge, United Kingdom SLAS Europe 2023 Conference and Exhibition 23-26 May 2023 Brussels, Belgium
I detta avsnitt blir det lite aktuellt och en hel hög med rapporter. Bolagen är: Bahnhof (37:18), Catella (46:50), G5 (53:15), Harvia (66:10), Infracom (79:55), Kabe (88:22), NGS (96:25) och slutligen Raketech (110:15). Välkomna!Vår huvudsponsor hittar ni på: www.kavaljer.seFunderar ni på att bli Private Banking-kunder och kanske flytta era bostadslån till Nordnet så kan vi rekommendera denna länk: http://www.Nordnet.se/pbBörsdata hittar ni på: www.borsdata.se/terminal101 Tankar om aktier hittar ni här: https://sternersforlag.se/produkt/101-tankar-om-aktier-har-blivit-111/Röda korsets insamling för Ukraina hittar ni här: https://www.rodakorset.se/var-varld/har-arbetar-vi/ukraina/skank-pengar-till-vart-arbete-i-ukraina/ Hosted on Acast. See acast.com/privacy for more information.
A new research perspective was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Treasures from trash in cancer research.” Cancer research has significantly improved in recent years, primarily due to next-generation sequencing (NGS) technology. Consequently, an enormous amount of genomic and transcriptomic data has been generated. In most cases, the data needed for research goals are used, and unwanted reads are discarded. However, these eliminated data contain relevant information. Aiming to test this hypothesis, genomic and transcriptomic data were acquired from public datasets. In this new research perspective, researchers Fabiano Cordeiro Moreira, Dionison Pereira Sarquis, Jorge Estefano Santana de Souza, Daniel de Souza Avelar, Taíssa Maria Thomaz Araújo, André Salim Khayat, Sidney Emanuel Batista dos Santos, and Paulo Pimentel de Assumpção from Instituto Metrópole Digital at the Universidade Federal do Rio Grande do Norte and Núcleo de Pesquisas em Oncologia and Instituto de Ciências Biológicas at the Universidade Federal do Pará used metagenomic tools to explore genomic cancer data; additional annotations were used to explore differentially expressed ncRNAs from miRNA experiments, and variants in adjacent to tumor samples from RNA-seq experiments were also investigated. “Here, we demonstrate potential strategies to benefit from nontargeted information resulting from high-throughput cancer investigations.” In all analyses, new data were obtained: from DNA-seq data, microbiome taxonomies were characterized with a similar performance of dedicated metagenomic research; from miRNA-seq data, additional differentially expressed sncRNAs were found; and in tumor and adjacent to tumor tissue data, somatic variants were found. These findings indicate that unexplored data from NGS experiments could help elucidate carcinogenesis and discover putative biomarkers with clinical applications. Further investigations should be considered for experimental design, providing opportunities to optimize data, saving time and resources while granting access to multiple genomic perspectives from the same sample and experimental run. “Altogether, our results strengthen the hypothesis that abundant additional and potentially useful information can be extracted from NGS. Moreover, the integrated investigation of every available information should provide a broader and more robust interpretation of the molecular scenario from each experiment.” DOI: https://doi.org/10.18632/oncotarget.28308 Correspondence to: Paulo Pimentel de Assumpção - assumpcaopp@gmail.com Video: https://www.youtube.com/watch?v=etqlRWCdhI0 Keywords: cancer metagenomics, cancer sncRNA expression, RNA-Seq variant calling About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com
Global satellite internet access trends are the focus in this edition of the Business Day Spotlight. Our host Mudiwa Gavaza is joined by Sulaiman Al Ali, Yahsat's chief commercial officer at the recently held AfricaCom telecoms conference in Cape Town. Topics of discussion include: Yahsat's strategy and activities in Africa; the future of integrated satellite solutions; the use of satellite communications internet of things (IoT) or connected devices like cars and sensors; and updates on Thuraya 4 NGS, the group's latest satellite. Business Day Spotlight is a MultimediaLIVE Production.
To receive up to 2.0 CME/CE credit please complete the evaluation and request form here: https://www.ceconcepts.com/2022chest-podcast This dynamic live symposium, led by top experts in the field of pulmonary medicine and NSCLC, will take attendees on a deep dive into the sentinel role of the pulmonologist in the NSCLC management paradigm, exploring adaptive mechanisms to optimize collaborative strategies in a patient centric manner.Learning ObjectivesReview the sentinel placement of the pulmonologist in the management of NSCLC, including their principal role in diagnostics, disease staging, and molecular testing.Evaluate clinical and patient-value driven factors that may help inform nodule evaluation and diagnostic strategies for pulmonologists, thus ensuring “the right tissue in the right amount from the right place for the right patient.”Demonstrate knowledge of guideline recommendations and practical considerations for the use of EBUS-TNBA techniques by pulmonologists, emphasizing the fundamentals of safely and effectively obtaining adequate tissue for diagnosis and molecular characterization.Describe the evolving role of targeted therapy and immunotherapy in NSCLC and analyze currently FDA-approved therapeutics across the NSCLC disease continuum, highlighting the role of molecular testing for guiding treatment and individualizing patient care.Explore the established utility of next-generation sequencing (NGS) and discuss the potential for emerging “next-generation” biomarkers in the NSCLC management paradigm.Apply patient-centric, evidence-supported collaborative care strategies to real-world, case-based scenarios in order to elucidate the pivotal role of the pulmonologist on the multidisciplinary team across the NSCLC continuum of care.Presented by Creative Educational Concepts, LLC.Supported through an independent educational grant from AstraZeneca.
An die erzählerische Dichte und psychologische Tiefe ihrer ersten beiden Romane reicht Ngs neues Buch leider nicht heran.
Life Science Reagents Market Outlook 2031The global life science reagents market was valued at US$ 54.7 Bn in 2021The global market is projected to grow at a CAGR of 5.7% from 2022 to 2031The global life science reagents market is expected to reach more than US$ 100 Bn by the end of 2031Overview of Life Science Reagents MarketLife science reagents are substances or compounds used in a chemical reaction to observe and record changes. Medical researchers analyze this data to determine the cause of a disease. Life science and analytical reagents are used in chemical reactions to measure, detect, or examine other substances. Technological advancements in molecular biology, life sciences, and biotechnology have brought about significant changes in health care diagnostics, drug discovery, personalized medicines, forensic sciences, and clinical research & development. This has increased the demand for biotechnology media, sera and reagents, biotechnology reagents, etc. Growth of the life science industry and increase in incidence rate of chronic and infectious diseases are driving the global life science reagents market.Increase in Geriatric Population and Rise in Need for Disease Diagnosis Propel Global Life Science Reagents MarketAdvances in the health care industry and life sciences industry, improvement in public health measures, and decrease in life-threatening infectious diseases in developed countries are augmenting the life expectancy of the global geriatric population. According to the United Nations, the elderly population (aged 60+ years) is expected to double by 2050 and triple by 2100. The population is likely to rise from 962 million in 2017 to 2.1 billion in 2050 and 3.1 billion in 2100.Get Sample Copy of the Report @ https://www.transparencymarketresearch.com/sample/sample.php?flag=S&rep_id=1162Globally, the geriatric population is growing at a faster rate than the young population. The geriatric population in Asia Pacific and South America is estimated to increase by 300% in the next decade. As part of preventive health care, the geriatric population and people with chronic diseases such as diabetes, respiratory disorders, and cancer regularly require medical tests such as blood tests and urine tests. This is projected to augment the life science reagents market during the forecast period.Rise in Adoption of Advanced Products to Drive Global Life Science Reagents MarketDevelopment in the areas of enzyme-linked immune assay technology (ELISA), polymerase chain reaction (PCR) such as digital PCR, rtPCR, chromatography, single cell technology, next-generation sequencing (NGS), and flow cytometry techniques; and their application in the health care industry in disease diagnostics and treatment monitoring are propelling the life science reagents market. For instance, the chemiluminescence immunoassay (CLIA) technology provides enhanced sensitivity, specificity, improved precision, and reduced incubation. Together, these increase the efficiency of the technology to diagnose different types of genetic, chronic, acute, and infectious diseases.Technological advancements in point-of-care (POC) instruments for the diagnosis of various chronic and infectious diseases within a short period, development of high throughput aut
During this recorded 2022 ASCP Annual Meeting session, multidisciplinary faculty will discuss the science and latest evidence on emerging biomarkers, resistance mutations, immuno-oncology (I-O) resistance mechanisms, and I-O treatment options (e.g., combination therapy involving CTLA-4 inhibitors) in metastatic NSCLC. In addition, they will address how to integrate next generation sequencing (NGS) into your biomarker testing workflows and optimize its use for patients. Finally, they will share best practices in biomarker testing, reporting, and communication to help pathologists and laboratory professionals guide medical oncologists and other team members in the appropriate diagnosis, testing, and treatment for patients. The activity offers 1.0 CME/CMLE credit. The American Society for Clinical Pathology (ASCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education (CME) for physicians. Learning ObjectivesUpon completion of this activity, you should be able to:· Describe ongoing investigational efforts regarding emerging biomarkers in metastatic NSCLC · Utilize NGS to identify current and emerging biomarkers to predict response to personalized therapies for patients with metastatic NSCLC · Employ strategies for optimizing workflows and turnaround times for NGS · Discuss the science behind resistance mechanisms in patients with metastatic NSCLC · Recognize the use of emerging I-O combination therapies and potential biomarkers in patients with metastatic NSCLC · Develop ways to improve communication among pathologists, oncologists, and other members of the multidisciplinary lung cancer care team FacultyDiana N. Ionescu MD, FRCPC, FCAP Consultant Pathologist and Medical Lead Anatomical Pathology Medical Director BC Cervical Cancer Screening Laboratory Medical Director Clinical Trials, BC Cancer Laboratories Clinical Professor of Pathology, University of British Columbia Doru Paul, MD, PhDAttending Physician, Division of Hematology and Medical Oncology Weill Cornell and New York Presbyterian Hospital Faculty DisclosuresThe following Panel/Faculty members have relevant financial relationships to disclose: | Faculty Member | Ineligible Company | For what role? | Diana Ionescu, MD | AstraZeneca, Bayer, BMS, Merck, Pfizer, Roche | Consultant, Consultant, Consultant, Consultant, Consultant, Consultant Dr. Paul has no relevant financial relationships to disclose All of the relevant financial relationships listed for these individuals have been mitigated Commercial SupportFunded by an independent educational grant from AstraZeneca Pharmaceuticals
Episode Summary Dr. Devin Drown, associate professor of biology and faculty director of the Institute of Arctic Biology Genomics Core at the University of Alaska Fairbanks, discusses how soil disturbance gradients in the permafrost layer impact microbial communities. He also explains the larger impacts of his research on local plant, animal and human populations, and shares his experience surveilling SARS-CoV-2 variants in Alaska, where he and colleagues have observed a repeat pattern of founder events in the state. Ashley's Biggest Takeaways Permafrost is loosely defined as soil that has been frozen for 2 or more years in a row. Some permafrost can be quite young, but a lot of it is much older—1000s of years old. This frozen soil possesses large storage capacity for walking carbon and other kinds of nutrients that can be metabolized by microbes as well as other organisms living above the frozen ground. About 85% of the landmass in Alaska is underlined by permafrost. Some is continuous permafrost, while other areas of landmass are discontinuous permafrost—locations where both unfrozen soil and frozen soil are present. As this frozen resource is thawing as a result of climate change, it is releasing carbon and changing soil hydrology and nutrient composition, in the active layer in the soil surrounding it. Changes in the nutrients and availability of those nutrients are also likely changing the structure of the microbial communities. Drown and team are using a combination of traditional (amplicon sequencing) and 3rd generation (nanopore) next sequencing (NGS) techniques to characterize the microbes and genes that are in thawing permafrost soil. Featured Quotes: “Globally, we've seen temperatures increase here in the Arctic. Changes in global temperatures are rising even faster, 2-3 times, and I've heard recent estimates that are even higher than that.” “These large changes in temperatures are causing direct impacts on the thaw of the permafrost. But they're also generating changes in other patterns, like increases in wildfires. We just had a substantial wildfire season here in Alaska, and those wildfires certainly contribute to additional permafrost thaw by sometimes removing that insulating layer of soil that might keep that ground frozen, as well as directly adding heat to the to the soil.” “There are other changes that might be causing permafrost thaw, like anthropogenic changes, changes in land use patterns. As we build and develop roads into areas that haven't been touched by humans in a long time. We're seeing changes in disruption to permafrost.” “Some people are quite interested in what might be coming out of the permafrost. We might see nutrients, as well as microorganisms that are moving from this frozen bank of soil into the active layer.” “We're using next generation sequencing techniques to characterize not only who is in these soils, but also what they're doing.” “I started as a faculty member in 2015. As I moved up to Alaska, I got some really great advice from a postdoctoral mentor that said, make sure you choose something local. I'm fortunate enough that I have access to permafrost thaw gradient, that's effectively in the backyard of my office.” “Just a few miles from campus, we have access to a site that's managed by the Army Corps of Engineers. They have a cold regions group up here that runs a more famous permafrost tunnel. So they've dug a deep tunnel into the side of a hill that stretches back about 40,000 years into permafrost. They also have a great field site that has an artificially induced permafrost thaw gradient, and a majority of our published work has been generated by taking soil cores from that field site.” “Maintaining that cold chain, whether it's experimental reagents or experimental samples, is a challenge for everyone. We're collecting active layer soil—the soil directly beneath our feet—so that's not at terribly extreme temperatures. But we do put it in coolers immediately upon extracting from the from the environment. Then we can bring it back to our lab where we can freeze it if we're going to use it for later analysis, or we can keep it at appropriately cool temperatures, if we're going to be working with the microbial community directly.” “We were most interested in looking for microbes that might have impacts on the above ground. ecosystem. So when we were characterizing the microbial community, we were doing that because we also wanted to link it to above ground changes.” “Changes in vegetation that might be driven by changes in microorganisms would certainly have an impact on the wildlife that are that are present at the site. So, just as an example, if we see a decrease in berries that might be present, that might decrease the interest from animals that rely on that [food source]. And so we might see changes in who's there.” “Outside of my research, we've seen changes in the types of plants present across northern latitudes. So different willows, for instance, are moving farther north, and that is leading animals, like moose, to move farther north. And so we might see changes in those kinds of patterns directly as a result of the microorganisms as well.” “We're really working to expand our efforts to move to other kinds of disturbances. I mentioned wildfires before, these are an important source of disturbance for boreal forest ecosystems. We have a project here in the interior, looking at the impacts of wildfires on microbial communities and how [these disturbances] might be changing the functional potential of microbial communities.” Let us know what you thought about this episode by tweeting at us @ASMicrobiology or leaving a comment on facebook.com/asmfan.
Dr. Mark Hayden, MD discusses the benefit of gastrointestinal T cell immunity versus the mRNA gene therapy vax. What are T cells? T cells are key players in the adaptive immune system. When the body is invaded by a foreign substance like a virus or bacteria, the immune system rallies one of its earliest lines of defense, helper T cells. Helper T cells may call on their allies to kickstart antibody production to support the fight against the disease. Helper T cells also alert other types of T cells to the presence of foreign invaders to be targeted and destroyed. After the body has fought off an infection or disease, a small number of T cells remain in the blood. They are called memory T cells and their job is to remember how to ward off these invaders if they ever return. What is T-Detect COVID? T-Detect COVID is the first T cell test for COVID-19 available in the U.S. to those over age 18. It measures T cells instead of antibodies to detect recent or past SARS-CoV-2 infection (the virus that causes COVID-19). How does T-Detect COVID work? T cells are the first responders of the adaptive immune system and activate the antibody response. While antibodies to SARS-CoV-2 (the virus that causes COVID-19) naturally wane and are detectable in the shorter term, T cell responders can persist in the blood long after antibody responses wane. T-Detect COVID can detect T cells in the blood and recognize the SARS-CoV-2 virus for up to 10 months after symptoms appear with a 90% sensitivity. What does T-Detect COVID measure? T-Detect COVID can detect an immune response to SARS-CoV-2, the virus that causes COVID-19 disease, to assess recent or past infection. It is not intended for the diagnosis of active/current SARS-CoV-2 infection. The T-Detect® Assay – Blood test The T-Detect COVID Assay is intended for use as an aid in identifying individuals with an immune response to SARS-CoV-2, indicating recent or prior infection. The T-Detect COVID Assay uses next-generation sequencing (NGS) to assess the rearranged T-cell receptor beta (TCRβ) gene sequences present in genomic DNA isolated from human peripheral blood. This test is not intended for diagnosis of active SARS-CoV-2 infection. Tell your family, friends, and associates to listen to this important podcast by using this link: freedomfromaddiction.libsyn.com.
We strongly recommend you listen to our previous episodes metastatic lung cancer (Episodes 0032 and 0033) to better be able to follow along with this conversation. Key trials mentioned in this episode include:CHECKMATE 227KEYNOTE 024Q:Do you send molecular testing (PDL1 and NGS) on the biopsy, peripheral blood or both?* Yield is highest from the tissue sample* Peripheral blood (circulating DNA) samples are dependent on the burden of disease and so often the yield is lower ** One of the benefits is that it can be sent quickly and having a fast turn-around; Tissue samples are dependent on being able to schedule a biopsy* Dr. West says he definitely sends this on a non-smoker with non-squamous lung cancer, as they are more likely to have molecular targets* Dr. West has not personally adopted the idea of sending peripheral and tissue samples for NGS testing for everyoneQ: Do you ever use Ipi/Nivo in patients with PDL1
(00:32) Could you provide us some background about yourself?(01:34) Could you give us a brief overview of the new Mayo complete lung cancer assay?(03:31) Can you talk a little bit more about the specific genes and why they're important for patient care?(04:53) When would a clinician pathologist order a focused NGS panel, such as this new Mayo complete lung cancer panel, over a larger cancer panel? (07:27) What specimens are accepted for the Mayo complete lung cancer panel?(08:50) How are these molecular results used in patient care?
Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we begin to round out our NSCLC series with the first of two episodes where we interview Dr. Jack West from City of Hope!We strongly recommend you listen to our previous episodes on early stage lung cancer (Episodes 026 and 029) to follow along in this discussion. Key trials mentioned in this episode include:ADAURA Trial IMPOWER010CHECKMATE816Q: We've previously discussed that adjuvant cisplatin doublet chemotherapy is used for tumors > 4cm and/or nodal involvement. Given that PD-L1 status and EGFR status can also potentially change adjuvant therapy choices, how do you employ these tests in your practice?* Different approaches at every center/with different thoracic oncologists. * Dr. West does NOT recommend sending broad NGS testing on everyone if it is not going to change management. * It it may influence management, at the very least, PDL1 and EGFR should be performed because of implications on adjuvant treatment options (See Episode 026 for treatment discussions): ** ADAURA Trial: Adjuvant Osimertinib x3 years for EGFR+ patients** IMPOWER010: In patients with PDL1 >50%, patients did better with 1 year of immunotherapy (atezolizumab) after adjuvant therapy* In patients with higher risk disease, can consider sending broad NGS, particularly looking for ALK and other mutations; remember that EGFR and ALK+ patients do NOT respond to immunotherapy well. This is important because we don't want to give someone side effects that they would not otherwise had (these patients are getting treatment adjuvantly AKA after their disease is already resected!)Q: What are limitations of the ADUARA Trial? * The ADUARA suggested disease-free survival advantage with use of osimertinib, but we don't know final overall survival data yet.*Limitations:** Three years of therapy** Very expensive drug** More data presented at ESMO 2022 on efficacy; Dr. West stated that there appears to be drop off in survival after stopping drug. Overall survival data not yet available * Just because patients can get osimertinib does NOT mean that they are not eligible for chemotherapy**Adjuvant chemotherapy for patients provides long-term benefit** JBR.10 Trial: Older trial, but showed that patients who got adjuvant treatment (in this case vinorelbine plus cisplatin) had prolonged disease-free and overall survival in early-stage non–small-cell lung cancer.** Follow up study suggested that EGFR+ patients trended towards longer survival Q: What are your thoughts on Checkmate 816 with the use of neoadjuvant nivolumab in addition to the platinum doublet? Do you think pathologic CR was an appropriate surrogate endpoint for the trial?* Complete path CR is a new end-point, but it does correlate with PFS. We cannot always for traditional endpoints, such as overall survival data, to mature because doing so may result in us withholding therapy that may be very beneficial. * Biggest benefit to neoadjuvant treatment is that more patients are able to get the full regimen. Many have complications after surgery and never are able to then get/benefit from chemotherapy. Supported by data from NATCH trial Q: What are your thoughts on induction chemoradiation vs. chemotherapy alone?* Dr. West prefers to not use radiation pre-operatively, with some exception (for instance, pancoast tumor) Tune in next week for part 2 of this discussion!About our guest:Dr. Jack West is an internationally-renowned Thoracic Oncologist. Associate Professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center. He is also the Clinical Executive Director of AccessHope. He completed his medical education at Harvard Medical School, and then trained at Brigham and Women's Hospital before heading to Fred Hutchinson at the University of Washington. Twitter: @JackWestMD References:https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02098-5/fulltext - IMPOWER 010 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2027071- ADAURA Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032958/ - NATCH Trial https://www.nejm.org/doi/pdf/10.1056/NEJMoa043623 - JBR.10 Trialhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033998/ - Follow up to JBR.10 Trial looking at influence of EGFR status on chemotherapy responsehttps://www.nejm.org/doi/10.1056/NEJMoa2202170 - CHECKMATE 816 https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s - Episode 026https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s-6xae9-ws6nt-ntn8g - Episode 029Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google PodcastLove what you hear? 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A new research paper was published in Oncotarget's Volume 13 on September 14, 2022, entitled, “Site of analysis matters – Ongoing complete response to Nivolumab in a patient with HIV/HPV related metastatic anal cancer and MLH1 mutation.” Anal cancer is a rare disease with increasing incidence. In patients with locally recurrent or metastatic disease, which cannot be treated with chemoradiotherapy or salvage surgery, systemic first-line chemotherapy with carboplatin and paclitaxel is standard of care. For patients who progress after first-line therapy and are still eligible for second-line therapy, programmed cell death protein 1 (PD-1) antibodies are potential therapeutic options. However, prediction of response to immunotherapy is still challenging, including in patients with anal cancer. “Altogether, there is little data on PD-1 treatment in HIV infected patients.” In a new study, researchers Melanie Demes, Ursula Pession, Jan Jeroch, Falko Schulze, Katrin Eichler, Daniel Martin, Peter Wild, and Oliver Waidmann from Universitätsklinikum Frankfurt and Centrum für Hämatologie und Onkologie reported a case of an HIV infected patient with anal cancer, microsatellite instability (MSI) high status, a high mutation frequency regarding tumor mutational burden (TMB) and an ongoing response to Nivolumab. “We report here to our knowledge the first anal cancer case with microsatellite instability (MSI) due to MLH1 mutation and a deep and ongoing response to Nivolumab treatment.” Thorough analysis of the primary tumor as well as metastatic sites by next generation sequencing (NGS) revealed that MSI was formally only found in the metastatic sites but not in the primary tumor. Concomitantly, tumor mutational burden (TMB) was higher in the metastatic site than in the primary tumor. The researchers concluded that all anal cancer patients should be tested for MSI and whenever possible molecular analysis should be performed rather from metastatic sites than from the primary tumor. “According to our results, we propose to assess mutational status in tissue from metastasis rather than from the primary site when additional molecular analyses are performed for treatment decisions.” DOI: https://doi.org/10.18632/oncotarget.28274 Correspondence to: Oliver Waidmann – Emails: oliver.waidmann@kgu.de Keywords: anal cancer, microsatellite instability, immunotherapy, high-throughput nucleotide sequencing, nivolumab About Oncotarget Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/OncotargetYouTube LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
In this episode, Ryan D. Gentzler, MD, MS, and Jonathan Riess, MD, MS, answer audience questions on managing EGFR-mutated non-small-cell lung cancer (NSCLC) from a live meeting series. The episode includes expert insights on:• Identifying patients who may benefit the most from adjuvant osimertinib • Testing for EGFR mutations in early-stage NSCLC• Critical importance of getting molecular test results before starting immunotherapy• Monitoring cardiac toxicity in patients receiving osimertinib• Key ongoing trials in EGFR-mutated NSCLC for patients with newly diagnosed disease and following progression on osimertinibPresenters:Ryan D. Gentzler, MD, MSAssociate ProfessorDivision of Hematology/OncologyDepartment of MedicineUniversity of VirginiaThoracic Medical OncologistUniversity of Virginia Comprehensive Cancer CenterCharlottesville, VirginiaJonathan Riess, MD, MSAssociate ProfessorDepartment of Internal Medicine/Hematology-OncologyUniversity of California, DavisMedical Director, Thoracic OncologyUniversity of California, Davis Comprehensive Cancer CenterSacramento, CaliforniaLink to full program: https://bit.ly/3DZGzSO
“Nurses can bridge the information gap and help patients better understand that the information received from next-generation sequencing (NGS) can really help to determine which treatment they will respond best to, if there are therapies that won't be effective, or if there are clinical trials that are open to them based on the results,” Danielle Fournier, RN, MSN, APRN, AGPCNP-BC, AOCNP®, CORLN, advanced practice RN in the department of thoracic surgery at MD Anderson Cancer Center in Houston, TX, told Stephanie Jardine, BSN, RN, oncology clinical specialist at ONS. Fournier discussed the advancements being made in NGS technology and how it can be used to care for patients with cancer. This episode was produced by ONS and sponsored by Foundation Medicine. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Episode Notes NCPD contact hours are not available for this episode. ONS Next-Generation Sequencing Toolkit, Sample Report, and Discussion Tool ONS Biomarker Database Oncology Nursing Podcast episodes: Episode 169: How Biomarker Testing Drives the Use of Targeted Therapies Episode 172: Address Knowledge Gaps in Evidence-Based Precision Medicine Care Episode 180: Learn How Nurse Practitioners Use Biomarker Testing in Cancer Care ONS Voice articles: Oncology Nurses' Role in Translating Biomarker Testing Results Advocate for Equal Access for Next Generation Sequencing and Clinical Trials Help Patients Understand Genomic Variants of Unknown Significance How DNA Sequencing Technologies Are Used in Cancer Care, Now and in the Future ONS clinical practice resources: Biomarker Testing Quick Guide Biomarker Testing for Genomics Variants: What to Know From the Laboratory Performing the Test Paired Somatic and Germline Testing Resource The Oncology Nurse's Role in Somatic Biomarker Testing Biomarker Testing Nursing Process Understanding Genetic Variants Discussion Tool ONS Genomics Taxonomy ONS Genomics and Precision Oncology Learning Library International Society of Nurses in Genetics Position statement on informed consent National Comprehensive Cancer Network Guidelines National Comprehensive Cancer Network Biomarkers Compendium Information on Sanger sequencing Information on the Genetic Information Nondiscrimination Act Video series: Seq It Out To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From Today's Episode “With next-generation sequencing (NGS), multiple biomarkers can be evaluated using one test. So, in cancer care, we're learning that any given tumor may harbor a variety of variants. So, if we're considering using in situ hybridization (ISH) or fluorescence in situ hybridization (FISH) to identify biomarkers, multiple assays may be needed and may need to be performed in order to test for multiple variants.” Timestamp (TS) 10:21 “There are multiple testing strategies that can be used with NGS technology, which is kind of what makes it so versatile. What type of testing is most appropriate really depends on the patient's risk factors, their diagnosis, their cancer stage, what testing has previously been completed, and what tissue is available for analysis.” TS 12:00 “Within oncology care, there is a role for NGS in the identification and management of both solid tumors and hematologic cancers, and this role is likely just going to continue to expand. So, really there's been an increased focus on genomic pharmacotherapy and targeted therapy, and this is playing an ever-greater role in the treatment of cancer. So, NGS will really continue to serve as a means to take a closer look at a patient's cancer at the molecular level and hopefully match patients with treatments that will be most effective at treating their cancer.” TS 20:54 “In reality, there's an expanding role for NGS testing in the diagnosis of many complex diseases. So, I think more than likely what we're going to see is that the indications and utility of NGS is only going to continue to grow in both the oncology setting as well as the non-oncology setting.” TS 23:08 “The oncology nurse really plays a key role in several important steps along the way. The first place they may be involved is in the informed consent process. Many—but not all—hospitals require patients to sign consent for genetic and genomic testing and this is just acknowledging that the patient is making an informed and autonomous decision related to their health care. Nurses may also play a role in the collection of a tissue sample or blood sample. And once testing has been completed, nurses may play a role in discussing the NGS results with patients.” TS 24:03 “Nurses really can help to somewhat bridge this information gap and help patients better understand that the information received from NGS can really help to determine which treatment they will respond best to, if there are therapies that won't be effective, or if there are clinical trials that are open to them based on the results. And these are all really important considerations for cancer treatment.” TS 36:21
Learn about a genetic disorder called duchenne muscular dystrophy! We explore the genetics of DMD and treatments available with two experts in the field.We're joined by genetic counselor, Ann Martin, who serves as the VP of Community Research and Genetic Services at Parent Project Muscular Dystrophy. Our other guest is world-renowned geneticist Dr. Madhuri Hegde from PerkinElmer Genomics. She is the Senior Vice President and Chief Scientific Officer of Global Lab Services at PerkinElmer. You may remember her from Episode 177 of DNA Today, which was a really fun episode where we geeked out on the power of whole genome sequencing!Sick of Zoom conferences? The Connecticut Genetic Counselors Association's first conference is in person! Jackson Laboratory is hosting us on Friday, October 14th in Farmington, CT. Our host, Kira Dineen, will be the moderator for Roe v. Wade Panel where we will be discussing the implications for practicing in a safe harbor state. Other presentation topics include polygenic risk scores, inclusive practice for LGBTQIA+ patients, and billing/credentials. We also built in networking time so we can all chat and get to know each other. Register here!On This Episode We Discuss:DMD average age of onset, symptoms, and symptom progressionDMD prevalence and inheritanceWhy it's important for people to be offered carrier screening before they are trying to conceiveReproductive options for people who are carriers of DMDWhat symptoms carriers of DMD are at risk forGetting the right testing for DMDCurrent treatment approaches for DMD (EMFLAZA)Ongoing clinical trialsPPMD's guides for caregivers of newly diagnosed peoplePerkinElmer Genomics' free testing program, DeCode Duchenne If you're interested in learning more about Decode Duchenne, the free genetic testing, counseling, and education program offered through a joint partnership between PerkinElmer Genomics and Parent Project Muscular Dystrophy, visit their website.We'd also like to feature a paper authored by one of our guests, Dr. Madhuri Hegde, about a single NGS-based assay that is highly sensitive for diagnostic testing for DMD and is also suitable for confirmatory testing for newborn screening for DMD.Keep up with our guests on social media! Follow Parent Project MD on Twitter, Facebook, and Instagram, Dr. Maduri Hegde on Twitter, and PerkinElmer Genomics on Twitter and Facebook. If you found today's episode topic interesting and you want to learn more about DMD, we also chatted with Rich Horgan of Cure Rare Diseases whose brother has DMD in Episode 156!Stay tuned for the next new episode of DNA Today on September 16th 2022, where we'll be joined by Effie Parks of Once Upon A Gene Podcast to discuss CTNNB1 Syndrome! New episodes are released on Fridays. In the meantime, you can binge over 200 other episodes on Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Today”. Episodes since 2021 are also recorded with video which you can watch on our YouTube channel. DNA Today is hosted and produced by Kira Dineen. Our social media lead is Corinne Merlino. Our video lead is Amanda Andreoli. See what else we are up to on Twitter, Instagram, Facebook, YouTube and our website, DNApodcast.com. Questions/inquiries can be sent to info@DNApodcast.com. Support for DNA Today comes from the People for The Ethical Treatment of Animals (also known as PETA), whose scientists have developed the research modernization deal, a strategy to phase out ineffective experiments on animals with high-tech, state-of-the-art research. PETA has collected an abundance of evidence demonstrating that the use of animals in biomedical research hinders scientific progress and puts patients at risk. Learn more at PETA.ord/NewDeal.TrakGene has designed a genetics electronic health record. Here's what it features: pedigrees, demographic data, genetics information, risk tools, and sophisticated reporting, all within a clinician designed workflow. It integrates with other clinical genetic software, databases, and hospital information systems to maintain accurate patient records.Go check it out at TrakGene.com. And keep your eye out for our full episode interviews with TrakGene coming soon to DNA Today.
It is often said that surveyors don't know how to retire and that they go on to do bigger and better things. This week's episode of “Surveyor Says!” The NSPS Podcast proves exactly that as we catch up with Steve Martin, a recently retired surveyor formerly with the East Bay Municipal Utility District (EBMUD). He is a long serving CLSA member (2011 Member of the Year recipient) and dedicated steward to the “GPS on Benchmarks” initiative through NGS (for more information, listen to Episode 111 w/ Galen Scott). Steve recent chatted with Tim Burch about his efforts to recover and submit data for the initiative, thoughts on mentoring, and the future of the profession. Check out Steve's efforts through his posts on LinkedIn and let him know that his work is appreciated! Thanks for listening to “Surveyor Says!” The NSPS Podcast and subscribe wherever you listen to your audio selections. For more information about “GPS on Benchmarks,” visit the NGS website at: https://geodesy.noaa.gov/web/science_edu/webinar_series/gpsonbm-nsrs-campaign-continues.shtml https://geodesy.noaa.gov/GPSonBM/
https://www.patreon.com/datameshradio (Data Mesh Radio Patreon) - get access to interviews well before they are released Episode list and links to all available episode transcripts (most interviews from #32 on) https://docs.google.com/spreadsheets/d/1ZmCIinVgIm0xjIVFpL9jMtCiOlBQ7LbvLmtmb0FKcQc/edit?usp=sharing (here) Provided as a free resource by DataStax https://www.datastax.com/products/datastax-astra?utm_source=DataMeshRadio (AstraDB); George Trujillo's contact info: email (george.trujillo@datastax.com) and https://www.linkedin.com/in/georgetrujillo/ (LinkedIn) Transcript for this episode (https://docs.google.com/document/d/15QaPbgVvALLawq19qe62-CRxVFbawjo1BGOrvt9rX3g/edit?usp=sharing (link)) provided by Starburst. See their Data Mesh Summit recordings https://www.starburst.io/learn/events-webinars/datanova-on-demand/?datameshradio (here) and their great data mesh resource center https://www.starburst.io/info/distributed-data-mesh-resource-center/?datameshradio (here) In this episode, Scott interviewed Gretchen Moran, the Senior Director, Data Products at the National Geographic Society (NGS; the non-profit arm of National Geographic). Some key takeaways/thoughts from Gretchen's point of view: NGS is a bit unique in that they don't have a widely deployed data architecture so they do not have a lot of habits to unlearn. Starting with a greenfield means likely more training and learning/experimenting will be required but at least no institutional unlearning. To move forward with data mesh, organizations must be able to embrace change - and the pain that it will inevitably bring - and embrace ambiguity. You need to move forward and figure it out together but also be okay with failure as a learning experience as you test what works for your organization. To win the hearts and minds of data producers, show them what high-quality data can mean for the organization and their domain/role. Work closely with them, understand their context, hold their hand to bring them along and align them to the vision of data mesh. It's easier to drive buy-in widely if you find the organizational influencers and win them over. It is the domino effect in practice. Partner closely with the influencers early on to drive your initiative forward. For NGS, they are working with a single initial data producing team for their proof of value. The data mesh world seems to be split a bit between working with one or two to three teams in the initial proof of value stage. "Any technology effort is still a people effort." We have yet to learn how to leverage the knowledge and context of people without data knowledge in general in the data and analytics space. This is what data mesh tries to unlock but we are still figuring out how to do it well. It's very easy to intimidate people with data. We need to make tech and especially data much less intimidating to push broader adoption. The business context of those who aren't yet data literate can be extremely valuable. We need to lower the actual bar to leveraging data but also lower the perceived bar to leveraging data. "Metrics + outcomes = value" - without outcomes attached, metrics have no value. Automation is going to be key to many aspects of data mesh. Upskilling people to leverage data will only really pay off if it doesn't mean a large increase in the amount of work to leverage data. User experience is crucial to getting the most value out of your data. Think about your data user experience (DUX) and bring in designers to help optimize the experience and really focus on data as a product thinking. NGS is still trying to find who should own generating and sharing insights on data combined from multiple domains. Is that a centralized insights team? Does that push us too far back towards centralization? It's still early days but those insights are crucial to driving value from data. We will see where new insights come from in data mesh. Will it be more insights from data consumers as they...
Featuring perspectives from Prof Ghassan Abou-Alfa, including the following topics: Introduction (0:00) Case: A woman in her early 50s with metastatic hepatoid carcinoma of the ovary with an FGFR fusion — Syed M Ahmed, MD, PhD (2:56) Key recent data sets (5:59) Case: A man in his mid 60s with a history of Child-Pugh B cirrhosis and Grade 1 esophageal varices who is receiving atezolizumab/bevacizumab for multifocal HCC — Raji Shameem, MD (22:28) Case: A man in his late 60s with previously treated HCC cirrhosis who is now diagnosed with potentially resectable HCC — Syed F Zafar, MD (29:30) Case: A woman in her late 70s receiving adjuvant anastrozole for Stage I breast cancer who is now receiving atezolizumab/bevacizumab for metastatic HCC — Sunil Gandhi, MD (33:41) Case: A man in his late 70s with metastatic HCC and portal vein thrombosis receiving atezolizumab/bevacizumab (NGS [next-generation sequencing] with PIK3CA mutation, PD-L1 50%) — Susmitha Apuri, MD (35:47) Management of Biliary Tract Cancers (40:18) Case: A man in his late 50s with resected Stage IIB gallbladder cancer s/p adjuvant capecitabine who now has metastatic disease (HER2-positive; MSS, PD-L10) — Nasfat Shehadeh, MD (44:01) Case: A woman in her early 40s with a history of ductal carcinoma in situ and family history of breast cancer, now with metastatic cholangiocarcinoma (NGS with IDH2 mutation) — Joanna Metzner-Sadurski, MD (53:41) CME information and select publications
In this episode of the Epigenetics Podcast, we caught up with Active Motif's own Yuan Xue to talk about some of the challenges of performing ATAC-Seq. ATAC-Seq stands for Assay for Transposase-Accessible Chromatin with high-throughput sequencing and was initially described by Jason Buenrostro in 2013. The ATAC-Seq method relies on next-generation sequencing (NGS) library construction using the hyperactive transposase Tn5. NGS adapters are loaded onto the transposase, which allows simultaneous fragmentation of chromatin and integration of those adapters into open chromatin regions. ATAC-Seq is an attractive method to start your epigenetic journey. Whether you want to analyze the state of the chromatin in your sample or compare the chromatin state before and after a special treatment, ATAC-Seq allows you to investigate genome-wide chromatin changes and can offer guidelines about which epigenetic modification or transcription factor should be studied next in the follow-up experiments and which method should be used to study them. In this Episode we go through the Protocol in detail and discuss potential challenges and points to pay attention to when starting your first ATAC-Seq experiment. References ATAC-Seq Resource Center Complete Guide to Understanding and Using ATAC-Seq Beginner's Guide to Understanding Single-Cell ATAC-Seq Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y., & Greenleaf, W. J. (2013). Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nature methods, 10(12), 1213–1218. https://doi.org/10.1038/nmeth.2688 Buenrostro, J. D., Wu, B., Litzenburger, U. M., Ruff, D., Gonzales, M. L., Snyder, M. P., Chang, H. Y., & Greenleaf, W. J. (2015). Single-cell chromatin accessibility reveals principles of regulatory variation. Nature, 523(7561), 486–490. https://doi.org/10.1038/nature14590 Cusanovich, D. A., Daza, R., Adey, A., Pliner, H. A., Christiansen, L., Gunderson, K. L., Steemers, F. J., Trapnell, C., & Shendure, J. (2015). Multiplex single cell profiling of chromatin accessibility by combinatorial cellular indexing. Science (New York, N.Y.), 348(6237), 910–914. https://doi.org/10.1126/science.aab1601 Podcast: ATAC-Seq, scATAC-Seq and Chromatin Dynamics in Single-Cells (Jason Buenrostro) Contact Active Motif on Twitter Epigenetics Podcast on Twitter Active Motif on LinkedIn Active Motif on Facebook Email: podcast@activemotif.com
This episode is sponsored by the Osteosarcoma Institute (OSI), a nonprofit organization led by osteosarcoma experts from top U.S. cancer centers who, together, are concentrating on the cure ® for osteosarcoma. The mission of the OSI is to dramatically increase treatment options and survival rates in osteosarcoma patients through identifying and funding the most promising and breakthrough osteosarcoma clinical trials and science. In addition to advancing research, OSI also provides a free resource called OSI Connect for osteosarcoma patients. Our osteosarcoma experts can discuss available treatments, possible side effects, and provide helpful advice for getting the most out of your visits with your treating physician. This resource is available in English and Spanish and aims to help patients and families find answers to their questions. Join us for OsteoBites with Dr. Alanna Church from Boston Children's Hospital. She will discuss the study recently published in Nature Medicine with Dr. Katie Janeway and many other collaborators, demonstrating the clinical utility of molecular tumor profiling for children with cancer. This cohort includes 345 children and AYA cancer patients from 12 institutions who had molecular tumor profiling using targeted NGS panels, including 64 patients with osteosarcoma. Molecular alterations with potential impact on the diagnosis, prognosis or treatment were identified in 86% of patients. She hopes these results will help to advocate for molecular profiling for all children with cancer. Read the paper here: https://rdcu.be/cQgmj Reminder that this July for Sarcoma Awareness month, join us for our Virtual OutRunning OsteoSarcoma event! When you run/walk/cycle with us, you can help Cause A Cure. With MIB, no one walks through Osteosarcoma alone - let's go OutRunning together! Register at: https://mibagents.swoogo.com/OutRunning Also to commemorate Sarcoma Awareness Month, MIB is partnering with Kendra Scott for a Multi-City give back event taking place the weekend July 15-17! By making a purchase during this weekend, you are helping raise funds and awareness for Osteosarcoma. This September, we encourage you to Be Bold and Go Gold for Childhood Cancer Awareness Month! Make & Sell Bows in your community OR Make a donation this summer and get a bow that shows you care. Contact anita@mibagents.org to volunteer today!
In this podcast, our Medical Director, Brad Lewis, continues his conversation with Jamey Kain, Vice President of Genetic Innovation here at Machaon. Brad and Jamey discuss what next-generation sequencing (NGS) is, why it's important and some of the issues we face with NGS.Don't forget, Machaon offers genetic testing STAT results in 48 hours!
This episode is brought to you by Gut Food, Cozy Earth, InsideTracker, and Rupa Health.Many of us are feeling a crisis of meaning; feeling we've lost our way amongst the stressors and distractions of modern life. We are more isolated, divided, and sick than ever before. Personally, I always turn to nature when I'm feeling lost. And in traveling, talking to interesting people, and learning about the world, I've found that ancient cultures and their relationships to nature can teach us volumes when it comes to rediscovering connection, health, and meaning. Today, I'm excited to share a conversation I had with Wade Davis, all about culture, the depth of the natural world, belief systems, ethnobotany, psychedelics, and more. Wade Davis is a writer, photographer, and filmmaker. Explorer-in-Residence at the National Geographic Society from 2000 to 2013, he is currently Professor of Anthropology and the BC Leadership Chair in Cultures and Ecosystems at Risk at the University of British Columbia. He is the author of 23 books, including One River, The Wayfinders, and Into the Silence, and he was the winner of the 2012 Samuel Johnson prize, the top nonfiction prize in the English language. His latest book is Magdalena: River of Dreams. Wade's many film credits include Light at the Edge of the World, an eight-hour documentary series written and produced for the NGS. This episode is brought to you by Gut Food, Cozy Earth, InsideTracker, and Rupa Health.Check out Gut Food at gutfood.com.Right now, get 40% off your Cozy Earth sheets. Just head over to cozyearth.com and use code MARK40.Right now, InsideTracker is offering my community 20% off at insidetracker.com/drhyman.Rupa Health is a place where Functional Medicine practitioners can access more than 2,000 specialty lab tests. You can check out a free, live demo with a Q&A or create an account at RupaHealth.com.Here are more details from our interview (audio version / Apple Subscriber version): Wade's early experiences that first got him interested in anthropology (5:56 / 3:24)Why western culture is actually an anomaly, not the norm (7:57 / 5:23)Our misguided understanding of the purpose of culture (18:00 / 15:50) Why ancient wisdom matters in the modern world (20:40 / 18:57) The nature of life (22:48 / 20:50)Human commonalities among all cultural expressions (27:30 / 23:08)The value of language and storytelling (29:36 / 24:28) Why biologically, the concept of race is utter fiction (31:27 / 27:06) Psychedelics and our relationship to nature and plant medicines (37:27 / 33:20) Communicating with plants (1:01:22 / 39:35) Learn more about Wade Davis at daviswade.com. See acast.com/privacy for privacy and opt-out information.
ASCO: You're listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the voice of the world's oncology professionals. 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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, members of the Cancer.Net Editorial Board discuss new research in molecular testing, also known as biomarker testing or tumor marker testing, to help guide treatment for people with early-stage non-small cell lung cancer. This podcast is led by Dr. Ryan Gentzler, Dr. Xiuning Le, Dr. Brendan Stiles, and Dr. Vamsidhar Velcheti. Dr. Gentzler is the director of the Thoracic Oncology Clinical Research Program at the University of Virginia (UVA) and chairs the UVA Cancer Center's Lung Cancer Translational Research Team. Dr. Le is an assistant professor in the Department of Thoracic/Head and Neck Medical Oncology in the Division of Internal Medicine at The University of Texas MD Anderson Cancer Center. Dr. Stiles is chief of thoracic surgery and surgical oncology at Montefiore and Albert Einstein College of Medicine. Dr. Velcheti is the director of thoracic medical oncology at New York University Langone's Perlmutter Cancer Center. View disclosures for Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti on Cancer.Net. Dr. Gentzler: Thank you, everyone, for joining us. We've got a great group here today, and we're really going to focus on talking about molecular testing in lung cancer. This is a very hot topic. My name is Ryan Gentzler from the University of Virginia. I'm a thoracic medical oncologist. We have Drs. Le, Stiles, and Velcheti with us today. I'd like them to go ahead and introduce themselves, starting with Dr. Le. Dr. Le: My name is Xiuning Le. I'm an assistant professor. I'm at the MD Anderson Cancer Center here in Houston, Texas. I'm also a medical oncologist. Thank you, Ryan, for inviting us today. Dr. Stiles: Hey, everybody. I'm Brendan Stiles. I'm a thoracic surgeon. I'm chief of thoracic surgery at Albert Einstein College of Medicine in Montefiore Health System here in the Bronx in New York. Dr. Gentzler: All right, thanks for joining us. And Dr. Velcheti. Dr. Velcheti: Thank you, Ryan. I'm Vamsidhar Velcheti. I'm the director of the thoracic oncology program at NYU. Dr. Gentzler: All right, great. We hear a lot of terms thrown around about molecular testing, genomic testing, biomarkers, oncogenic drivers, and I thought it would be good to just define what exactly is molecular testing, so all of our listeners are aware of what we're talking about. Dr. Le, do you want to take this question? Dr. Le: Yeah. So we have many terms, as you described. In my eyes, there are 2 sets of testing, and then some of them also classify into actionable versus not actionable. So for clinical use, we usually ask the tumor to be tested for both the mutations as well as the immune marker. Usually, the panel of mutational testing is more than a field. Usually, it's depending on the platform we're using, oftentimes in the hundreds of things. And then the immune markers, usually, we refer to PD-L1 and the tumor mutational burden. Those are the 2 commonly used markers now in the clinic. Some of those markers, especially the hundreds in gene testing, not all of them can lead to a clinical decision because we're still in the phase of understanding the interactions of different genes. However, there is a subgroup of those mutations. Nowadays, we have targeted therapy for, we call those actionable mutations. So in the clinic, we push for testing for a panel of mutations as well as immune markers, hoping to look at the tumor comprehensively so that we can recommend a good treatment regimen precise to that particular tumor, precise to that particular patient. Dr. Gentzler: Yeah. Wonderful. This has also been termed precision medicine, where we really match a therapy to a specific genomic abnormality identified on these tests and maybe, Dr. Velcheti, if you could maybe elaborate on some of the different ways that these tests are performed and how we're using these in clinic today? Dr. Velcheti: Yeah, definitely. I think our understanding of the biology of lung cancer has evolved quite dramatically over the past several years and obviously it's led to a lot of advancements in terms of treatment opportunities for patients. Broadly, the way I look at biomarkers in lung cancer or, for that matter, any cancer, it's like you have biomarkers that actually kind of give us very deep insights into the biology of the cancer and giving us insights into how aggressive somebody's cancer is. Those are called prognostic biomarkers, kind of predicting outcome. And there are predictive biomarkers where there are certain biomarkers. If you do have some of these biomarkers in the tumor, then you could potentially use certain treatments that might work better for patients who have those biomarkers. So now we have a lot of different approaches in terms of how we kind of test for these biomarkers. Especially in lung cancer, now we have a lot of new therapeutics for certain genomically categorized types of lung cancer. And the challenge now is that we have so many different mutations we absolutely need that information to decide on treatment. So how do we test that? Until a few years ago, we've been doing a single gene testing. The problem with those approaches is that we have so many different genes we need to test and we kind of do sequential gene testing, a single gene testing, we won't get all the information we need to make the right decision for our patients. So the standard approach in most oncology practices, especially larger cancer centers and academic medical centers, is do comprehensive genomic profiling, and that's being widely accepted as a standard approach right now. Dr. Gentzler: Wonderful. And this has really been something that has fallen on the laps of thoracic medical oncologists as we've treated patients with advanced stage or stage 4 disease. And this is starting to become more and more important and relevant for surgeons. And Dr. Stiles, I just wanted to bring you into the conversation and see if this is something that, prior to some of the more recent data, which we'll discuss in a minute, is this something that as a surgeon, you've kept up with and think it's important in a surgical practice? Dr. Stiles: Yeah, definitely, Ryan. And I think now is probably the most exciting time for that, right? We used to just be sort of in the prognostic side, like Vamsi said, but now we really are in the predictive side in the early-stage disease. And I think that's why everybody is so excited. But that's why there's now this pressure about the timing of biomarker testing. What do you get? Do you get a whole panel? As we'll talk about some of the trials that have made their way into earlier stage disease, but it becomes inherent upon surgeons to really think about this and understand this, from the first time that they meet the patient I think, as we increasingly get better therapies in earlier stage disease. Dr. Gentzler: So as this has moved into earlier stage disease, a lot of this has been driven by some new data from clinical trials, and Dr. Velcheti, I thought maybe you could comment on the IMpower010 trial and its relevance and why molecular testing is important in the context of that trial. Dr. Velcheti: Yes, absolutely. I think the IMpower010 Trial is certainly a new shift in our approach to treating stage I, II curable non-small cell lung cancers. So we haven't had an approval in the adjuvant setting in a while. I mean, of course, we had approval with the osimertinib result of the ADAURA trial, but that's only for EGFR patients. Now we have approval for using immunotherapy in the postoperative adjuvant setting for patients with any level of PD-L1 expression. So this is a large randomized study looking at the role of adjuvant atezolizumab, which is a PD-L1 inhibitor in patients who have PD-L1 expression greater than 1%. Patients were randomized getting platinum doublet alone, which is a standard-of-care adjuvant assistant therapy for patients at stage I, II lung cancer. It is atezolizumab at a dose of 1,200 milligrams given every 3 weeks. Patients who received atezolizumab had significantly improved outcomes in disease-free survival. And the benefit was actually really striking for patients who had high PD-L1, patients with PD-L1 testing TPS score of greater than 50%. They had a really remarkable increase in terms of disease-free survival for those patients. So this is certainly very encouraging. And of course, we know it's now approved. We are still awaiting some overall survival results to mature. But given the extent of the benefits we're seeing with the disease-free survival, I think it's a very promising approach. Dr. Gentzler: Yeah, so obviously, immune therapy has had a tremendous benefit in the adjuvant setting from this trial and still some longer-term follow-up that's needed. But I think the important point here is that molecular testing may identify certain mutations that may make patients less likely to benefit or respond, or perhaps there's more appropriate treatments than immunotherapy within this group. And that brings us to the next trial that I think really shifted this discussion stage with the ADAURA trial. Maybe Dr. Le, if you could summarize this trial and give us your thoughts on why molecular testing is so important in the era of ADAURA. Dr. Le: Yeah. So ADAURA trial is also an adjuvant trial, meaning that the patient received additional treatment after the completion of surgery. So ADAURA trial looked at patients who have EGFR mutations. So it's a different biomarker. It's a gene biomarker, not the immune biomarker. So this is a large international trial, enrolled almost 700 patients and then randomized the patients after surgery, after standard chemo, the patient can go on to either receive 3 years of osimertinib, which is the standard-of-care therapy for EGFR mutant patients for metastatic setting, or the control group if the patient just received standard of care, which is to continue the monitoring. The trial actually showed that for people who had osimertinib before that prolonged time of 3 years, the risk of the disease coming back is almost 5 times lower than the patient who did not receive therapy. So based on that really striking benefit of after surgery, after chemotherapy, continue osimertinib in EGFR patients, FDA approved after the surgical resection and all the standard care patient can go on for osimertinib for a prolonged time, which we think currently the data is saying the disease is more likely not to come back. And hopefully, in the future, that result will translate into overall survival benefit. Dr. Gentzler: Okay, wonderful. And I think both of these trials, both the ADAURA and the IMpower010, are adjuvant trials. So these are trials that allow us adequate time to do molecular testing on a large surgical specimen, formulate our plans, and implement those plans up to a month or longer after surgery. Obviously, there's some new data that we've seen in a press release from the CheckMate 816 trial. This is a neoadjuvant trial of chemotherapy plus nivolumab. We've seen previous data from this trial showing some results, but this moves the conversation into the neoadjuvant space, and Dr. Stiles, I wonder if you could give us a summary of your thoughts on the CheckMate 816 and the relevance for molecular testing in that context of neoadjuvant therapy. Dr. Stiles: Yeah. Thanks, Ryan. I think, first of all, those are incredibly important adjuvant trials. I saw 2 patients each this week on adjuvant osimertinib and adjuvant atezo [atezolizumab], so it's real-life practice. Every day, it's going to benefit patients. But I think that's easy, like you said, these are big specimens that are taken out. You've got time to decide while the patient gets better. Now, we have to shift all this even earlier because CheckMate 816 really has some pretty impressive results. We, unfortunately, don't have the paper yet. I'm told it's going to be coming out soon, but the primary endpoint pathologic complete response 24% versus 2.2%. That's with chemo-nivo versus chemo alone. Obviously, people are questioning, does pathologic complete response correlate with outcomes? Certainly, we got a signal on a press release that the event-free survival is going to be the hazard ratio is 0.63, so it sounds like it does, and I think we'll see more data on that in the next couple of months. A difference in median event-free survival of 32 months versus 21 months in the report. So everybody is excited to see this. And I think it has some advantages over the adjuvant strategy. First of all, more patients are able to tolerate it. It's just 3 cycles, and so it's not given indeterminately for a year. And it worked across different subgroups. And we can talk about some of the nuances, but as where atezo [atezolizumab] was only looking good in the PD-L1-high. This sort of worked across different groups. The caveat to that is we don't really know what happens with these EGFR patients who are eligible and sort of, how do we then move that test? And all of a sudden, we've got to make a decision on neoadjuvant therapy. Now we need to know. It helps to know the PD-L1 maybe preoperatively, with the high PD-L1, maybe you could wait until adjuvant therapy, with the low to sort of medium PD-L1, maybe you want to give them their shot in the neoadjuvant space. But if they have an EGFR mutation, it's probably not the right thing. We don't really know the data on that and CheckMate 816 yet, but certainly, I'd be sort of hesitant to give them neoadjuvant chemoimmunotherapy. So then you have to teach surgeons all this too, and teach them to think about this and teach them to hold their horses on taking patients to the operating room while they wait for molecular testing. But that probably means we need to speed up the process somewhat either with sort of more rapid turnaround test, with consideration of liquid tests in some instances. It's just an incredibly fast-changing place that here we are speaking about a trial that hasn't even been published yet, so that tells you how fast things are happening. Dr. Gentzler: One last question. How can the results of these tests guide therapy after surgery? Do we incorporate a full NGS [next-generation sequencing] panel at the time of surgery? And we don't have data on adjuvant therapy for ALK or ROS1, or RET. Do we factor that into how we think about adjuvant chemotherapy, adjuvant immunotherapy, do we employ targeted therapies for some of these mutations? Any thoughts on that? Dr. Le: Ryan, I think you bring an important point in that EGFR is 1 of the 8 actionable mutations we have nowadays based on FDA and NCCN. The tumor biology between EGFR and ALK-fusion oncogenesis and potential response and benefits probably share some similarities. So we look forward to seeing trials reporting out the adjuvant setting with ALK inhibitors with ROS1. And the smaller target might require a multi-institutional or co-op group effort to really achieve the sample size for us to see. But as of now, we don't have the approval. We try to enroll patients to the oncogene trials, but I think currently we're practicing based on EGFR and PD-L1. Dr. Stiles: Yes, and I agree. I'm excited to see what comes out of some of those trials. They're slow to grow, but we'll eventually get some readouts. I think an interesting question sometimes is PD-L1. And we had an example recently where in the pre-op biopsy, the patient had a low PD-L1, and so not particularly enthusiastic. And the question sometimes arises, do you test that whole tumor to consider them as kind of an adjuvant to atezo [atezolizumab]and then the fully resected tumor, the PD-L1 was greater than 50%. And so I would sort of sound a caution that the small biopsy sample, they're incredibly helpful for many things, incredibly helpful for moleculars. It may not always be totally representative of the PD-L1 staining. Dr. Gentzler: And I think that's a good point. Even for molecular testing, sometimes if you have smaller biopsies, you may get a result that's negative, but it could be low levels of DNA and not sufficient to complete the full panel with high quality. So you really have to pay attention to the report and make sure that there's some confidence in the amount of DNA in some of these results. Well, I think that's all the time we have here, so I appreciate everyone's participation, and hopefully we're able to learn a little bit about genomic testing today. ASCO: Thank you, Dr. Gentzler, Dr. Le, Dr. Stiles, and Dr. Velcheti. Learn more about treating lung cancer at www.cancer.net/lung. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care. And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology. Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate.
Mr.GQ and DJ Micah B introduce a new mini segment called the words of Mr. Noble inspired by a close friend of Mr.GQ. They also get into some upcoming NBA FA questions, and they wrap up part 3 with the NFL top 10 NGS explosive runners of 2021! Tune in and enjoy the show. --- Send in a voice message: https://anchor.fm/gentlemans-talk/message
In this episode, supported by Zymo Research, guest host Georgia Bickerton explores NGS data and how bioinformatic pipelines and workflows can be optimized to make NGS data more accessible. To do this she speaks with Jeffrey Bhasin, Director of Informatics at Zymo Research, who discusses the key issues of reproducibility in bioinformatics, the selection of methods available to analyze different datasets and to investigate different aspects of these data. Listen today to discover the techniques available to help increase the portability and reproducibility of fine-tuned bioinformatics workflows and to streamline the application of these workflows. Bhasin also reveals how these 'workflow management' technologies can enable more global, collaborative approaches to bioinformatics workflow construction and begin to increase the automation and accessibility of bioinformatics workflows. Contents: Introduction: 00:00-00:55 How the rise of NGS has impacted the field of bioinformatics: 00:55-01:35 Issues of reproducibility in bioinformatics: 01:35-03:50 Using bioinformatics for different data types and different applications: 03:50-06:10 The impact of bioinformatics workflow management: 06:10-08:50 The future of NGS data analysis: 08:50-12:05 Busting overreliance on bioinformatics experts? 12:05-15:05 Closing remarks: 15:05-15:50
In this episode of LPM's “And This Is Why…” podcast series, Kevin McMenimen interviews Brian Wedoff, the senior director of loss prevention operations for Ulta Beauty. They discuss how NGS helped them through the challenges of the past few years, and keeping the safety of guests and staff as the number one priority.
NGS is more than a glass contractor—they're the biggest installer of window films and graphics in America. They consider themselves more of a solution provider, and have grown with a number of acquisitions in recent years. Retail is the first market segment they really focused on when the company started in 2009, but much has changed since then.Here, NGS CEO James Beale describes the evolution of NGS, and what they can offer retailers now.
Dr. Shaalan Beg, of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Science 37, discusses hot topics in GI oncology, including KRAS wild-type pancreatic cancer, the SURF-Cohort trial in hepatobiliary cancer, and key studies in gastric cancer featured at the 2022 ASCO Annual Meeting. Transcript ASCO Daily News: Hello and welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Shaalan Beg, who is an adjunct associate professor and gastrointestinal (GI) medical oncologist at UT Southwestern Harold C. Simmons Comprehensive Cancer Center. Dr. Beg also serves as vice president of oncology at Science 37. Dr. Beg will be telling us about key posters in GI oncology that will be featured at the 2022 ASCO Annual Meeting. His full disclosures are on our show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Beg thanks for coming on the podcast today. Dr. Shaalan Beg: Thank you so much for having me. ASCO Daily News: Let's begin with “A multicenter, non-randomized, controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF-Cohort Trial): Analysis of overall survival.” That's Abstract 4095. This study evaluated the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma. So, what are your key takeaways from this study? Dr. Shaalan Beg: This is a very interesting and timely clinical trial from our investigator colleagues in Japan, Dr. Yamashita, and colleagues, where they evaluated the effectiveness of radiofrequency ablation versus surgery for patients with small hepatocellular carcinomas who have a good liver function. History is that the best most effective treatment option has always been surgery and we know that ablative techniques like radiofrequency ablation (RFA) or stereotactic radiation can do a good job in controlling the individual cancers, but we don't know what the long-term effects can be in terms of recurrence, free survival, and overall survival. So, this trial looks to compare RFA or radiofrequency ablation versus surgery for groups of patients who have a good liver function, so a Child-Pugh score of 7 or less, and those who had no lesion greater than 3 centimeters and less than 3 hepatocellular carcinoma (HCC) nodules. All the people were evaluated by surgeons and hepatologists, to confirm that they would be eligible for both procedures. And then the patients received either 1 of those treatments and they followed them in the long term and found that there was no significant difference between how people who are treated with surgery fared versus RFA. This is really interesting and practical and timely because the results of these clinical trials can inform our clinical practice today. The median follow-up period was 6.8 years in the surgery group and 6.7 years in the RFA group and the overall survival was not different. Their 5-year overall survival for surgery was 79.7%. And very similar to what they were seeing in both groups. ASCO Daily News: Excellent! Great to hear some promising developments for this patient population. Well, in Abstract 4026, investigators are suggesting that the choice of PD-L1 immunochemistry assay influences clinical eligibility for gastric cancer immunotherapy. What are your thoughts on this study? Dr. Shaalan Beg: Yeah! Clinicians, clinical investigators, and even patients have been really confused by the definitions of PD-L1 expression. PD-L1 expression is 1 of our biomarkers for response to immunotherapy and immune checkpoint inhibitors. But the challenge in this field is that there are multiple assays that define various criteria for PD-L1 expression. And if you look at different clinical trials, they look at different definitions of positivity. So, a trial may have 1 plus. Some may have 5 plus percent. Some have 50 plus percent. So, this group out of Singapore took 362 gastric cancer samples, and they evaluated its PD-L1 expression using the combined positive score or the combined positive score (CPS), the tumor proportion score (TPS), and immune cell expression, and they compared them to see how well all of these performed because what's important to remember is we don't know how interchangeable the different immunohistochemistry (IHC) assays are. We have the Dako 22C3, we have the Dako 28-8, and then the Ventana assays and different clinical trials have used different versions of these at different expression levels. And regulatory bodies haven't really defined how to do the testing. So, different sites and different physicians, and different practice groups are using different assays and may be interpreting differently. What this trial is telling us is that if you use the Dako 28-8 assay, you identify a much higher proportion of people who are positive for PD-L1, whether you use the 1% cut off or the 5% cut off, or the 10% cut off. Listen to these numbers. 28-8 at CPS of greater than 1, 70% with 28-8, and 49% with 22C3. If you use the 10% cut-off, it's 13% if you use a 28-8 assay, but 7% for the 22C3 assay. So, that kind of throws into question how these assays are being used in daily practice. Well, some people may be, but a lot of people are not thinking about the cut-offs that were used in those clinical trials, especially when that comes to finding treatment options for our patients. And if we use the 28-8 assay, we're bound to find more patients who are PD-L1 positive, but that may not be the assay that the trials used in their validation cohort. So, we may end up treating the wrong patients. But at the same time, if we use the other assay, we may be missing out on people who are PD-L1 positive. So, I think this is a call. This is a call for the field to harmonize how PD-L1 expression is defined. We need more data on inter-assay concordance so we can find the right drug and the right biomarker for the right patients. This is a call for better prospective data and a call for harmonization between different assays and between different trials because this is an issue that is plaguing clinical practice today. ASCO Daily News: Thank you! So, let's talk about advances in pancreatic cancer and Abstract 4155. The authors of this study note that pancreatic adenocarcinoma is the fourth leading cause of cancer deaths, with an increased incidence among patients younger than 50 years old. This study is a comparative analysis of the targetable landscape in KRAS mutant and wild-type pancreatic adenocarcinoma. So, can you tell us about it? Dr. Shaalan Beg: The pancreatic cancer field has really suffered from a lack of effective treatment options, especially targeted treatment options and lack of effectiveness of immunotherapy for this disease. Most patients still receive chemotherapy and we only have a couple of different combination treatments to help treat this disease, which is increasing in terms of the number of new cases and cancer-related deaths, and by some estimates may be the third leading cause of cancer-related deaths in the U.S. A big reason that the survival for this cancer has not improved is because we don't have a lot of actionable or targetable mutations for this disease. One of the biomarkers that does have a corresponding treatment option is people who have a BRCA mutation. PARP inhibitors like olaparib have been approved for that group of patients, but the effectiveness of that medicine is modest for this disease, and we still have to see how much it's incorporated into daily practice. But outside of the BRCA mutations and other DNA damage repair alterations, KRAS is really the most common mutation and there are new drugs that are out there to target KRAS. 90 plus percent of pancreas cancers have KRAS and if you think about it the other way, a small proportion of patients with pancreas cancer don't have KRAS. So, what this abstract is looking to study is what are the characteristics of patients with pancreas cancer who don't have a mutation in KRAS, and can be the absence of KRAS actually be a biomarker for other mutations and other treatment strategies for pancreas cancer. And this was a fairly large study of about 5,000 patients with pancreas cancer that use a commercial NGS assay. The same commercial NGS assay, who performed gene analysis, as well as full transcriptome RNA-seq, were retrospectively reviewed. And they found that people who had a KRAS wild-type tumor meaning no mutation in KRAS were much more likely to have mutations in HRD and in BRAF compared to those that had mutations in KRAS. And then when you look at fusions, there was a much higher rate of NRG fusions. At the 2021 ASCO Annual Meeting, we heard some data on some new agents that are primarily targeting tumors that have fusions in NRG. And what this abstract is telling us is that the absence of a KRAS mutation may indirectly prompt us to look for other mutations, particularly fusions that may have additional treatment options available. So, this indirectly may be a biomarker of other actionable mutations. The overall proportion of KRAS wild-type in this cohort was 21%. So higher than what I would have expected, but it's 21% out of 5000 cases that they evaluated and they really set out to see if young-onset pancreas cancer folks have a different proportion of KRAS wild-type and the proportion of KRAS wild-type in both young and typical onset pancreas cancer was really the same. So, I believe this prompts us to think about pancreas cancer in 2 buckets, the KRAS wild-type, and KRAS mutated pancreas cancer. If we ever come across someone who has no detectable KRAS mutation, we should make sure that they have full transcriptomic analysis so we can look and get better coverage on those fusion changes that may have more treatment options associated with them. ASCO Daily News: I'd like to follow up with a question about Abstract 4130. Investigators analyzed the molecular profile and clinical outcome of a cohort of patients with KRAS wild-type pancreatic ductal adenocarcinoma, what does this study tell us about the treatment implications for these patients? Dr. Shaalan Beg: Yeah, so this was an abstract by Dr. Aakash Desai from the Mayo Clinic, and they went back and retrospectively reviewed patients who were seen at their center. And they looked for similar questions as the other abstract had done, but this was from a single center, and it seems like people had had multiple different assays performed. In this cohort, they found 240 patients. That's 8%, had KRAS wild-type disease. So, they found 19 patients who did not have a KRAS mutation. And they went to see if there were any hints of differences or specific mutations between the patients with wild-type and mutated. And they found that the landscape of KRAS wild-type in pancreas cancer was very heterogeneous, and it was difficult for them to generalize or make any statements on what that could suggest. A couple of things to think about for this study. Well, first of all, I think it's important for us to acknowledge that this particular space, the KRAS wild-type space, is gaining a lot of attention and is being recognized as an independent entity. So, you have multiple abstracts that have looked to study this group of patients. I think the second study is different from the prior one in that it's a single-center study. And from what I understand, they may have used multiple assays. So, there was less standardization on the actual mutation testing that was being performed. And that has relevance for this specific question because we know that we need deeper transcriptomic analysis in order to be able to perform RNA-seq and really understand the fusions that may be driving cancer, and it's hard to know what the coverage for the mutations that were evaluated in the second abstract, which mutations were really being covered. But if we take a couple of steps back and look at this, with the lens of where the pancreas cancer field is headed, again, I want to emphasize that how I view these coming together is that KRAS wild-type, pancreas cancer is becoming recognized as its own identity. ASCO Daily News: Excellent! Well, thank you Dr. Beg for sharing your valuable insights with us today on the ASCO Daily News podcast. It's certainly an exciting time in GI oncology. Dr. Shaalan Beg: Absolutely! Thank you so much for having me. ASCO Daily News: And thank you to our listeners for your time today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you're enjoying the content on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Disclosures: Dr. Muhammad Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
This week on the Life Science Success podcast I am interviewed Mike Klein the CEO of Genomenon. Mike is an accomplished CEO with over 25 years of experience developing, building and growing high tech, software and IT companies. As a seasoned CEO, he draws upon a unique blend of vision, strategic thinking, communication and execution skills to help turn around and put companies on the high growth track. He has the technical and financial background to guide businesses to meet their objectives and extensive experience in raising capital, acquisitions and delivering successful investor exits. Notes: 3:00 What does Genomenon Do? 4:00 What made Mike want to be in Life Sciences? 7:30 What are some of the lessons learned in his previous startups that he brought to Genomenon? 11:00 The importance of culture & core values 12:55 The impact Genomenon will have on the world 18:30 Advice Mike would give a new entrepreneur 20:00 Advice to someone outside of life sciences 22:50 Proudest Moment 26:32 Biggest Challenges 28:00 Three Questions What inspires you? What concerns you? What excites you?
With a ton of noise coming out of Detroit, Josh and Dan dig into the free speech issues between Detroit City FC, NGS, USL, and USSF. Can this be solved amicably or do things have to get crazy? Plus, women's soccer is about to kick off big time, let's take a look at the leagues set to kick off this week!
With the prevalence of Leaf Roll Three, Red Blotch, and other viruses, accurate and timely detection of viruses in grapevines has never been more imperative. Alan Wei, Owner and Lab Manager at Agri-Analysis LLC in Davis California explains how his lab is using next generation sequencing (NGS) to find new viruses. Currently, polymerase chain reaction (PCR) is the widely accepted method for testing for viruses. This process tests for one gene at time. Next generation sequencing allows labs to test multiple genes at a time and get results much faster. References: 20: Dr. Mark Fuchs | Red Blotch Virus in Grapevines 49: Stopping the Spread of Red Leaf Viruses 71: New Techniques to Detect Grapevine Leafroll Disease Agri-analysis LLC Donate: Juan Nevarez Memorial Scholarship Grape Program at Foundation Plant Services Leafroll 3 Virus (GLRaV3) AKA Grapevine Leafroll Disease in Washington Next Generation Sequencing (Deep Sequencing) PCR (Polymerase Chain Reaction) Testing Red Blotch Virus SIP Certified Sustainable Ag Expo November 14-16, 2022 Get More Subscribe wherever you listen so you never miss an episode on the latest science and research with the Sustainable Winegrowing Podcast. Since 1994, Vineyard Team has been your resource for workshops and field demonstrations, research, and events dedicated to the stewardship of our natural resources. Learn more at www.vineyardteam.org. Transcript Craig Macmillan 0:00 My guest today is Alan Wei, who's owner and lab manager of Agri Analysis LLC in Davis, California. Alan, thanks for being on the show. Alan Wei 0:10 Thank you very much, Craig, for hosting me. And I'm very delighted to be here. And I want to use this opportunity to say hello to listeners as well. Craig Macmillan 0:19 So Alan, I want to have you on the show, because I want