Podcasts about IHC

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Guest: Fernando López-Ríos, MD, PhD Guest: Christian Rolfo, MD, PhD Guest: Charlie Gourley, MD, PhD In this on-demand replay of a recent interactive webinar, renowned experts Prof. Fernando López-Ríos, Prof. Christian Rolfo, and Prof. Charlie Gourley review the latest data, guidelines, and patient cases as they explore best practices for HER2 testing and the evolving role of IHC in lung and ovarian cancers. Topics of conversation include the following: An overview of challenges related to HER2 immunohistochemistry, guidance, and interpretation of the results Targeting HER2 in lung cancer: where does IHC testing fit in? Ovarian cancer: challenges and considerations for HER2 IHC testing Watch the on-demand video to gain expert insights on optimising IHC HER2 testing and interpreting results in lung and ovarian cancer. The full programme is also featured on the COR2ED website, here: HER2 Testing: The Evolving Role of Immunohistochemistry (IHC)

Guest: Fernando López-Ríos, MD, PhD Guest: Christian Rolfo, MD, PhD Guest: Prof. Charlie Gourley In this on-demand replay of a recent interactive webinar, renowned experts Prof. Fernando López-Ríos, Prof. Christian Rolfo, and Prof. Charlie Gourley review the latest data, guidelines, and patient cases as they explore best practices for HER2 testing and the evolving role of IHC in lung and ovarian cancers. Topics of conversation include the following: An overview of challenges related to HER2 immunohistochemistry, guidance, and interpretation of the results Targeting HER2 in lung cancer: where does IHC testing fit in? Ovarian cancer: challenges and considerations for HER2 IHC testing Watch the on-demand video to gain expert insights on optimising IHC HER2 testing and interpreting results in lung and ovarian cancer. The full programme is also featured on the COR2ED website, here: INSERT LINK

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

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JCO PO authors Dr. Philippe Bedard (Staff Medical Oncologist at Princess Margaret Cancer Centre and Professor of Medicine at University of Toronto) and Dr. Alberto Hernando Calvo (Medical Oncologist at Vall d´Hebron University Hospital) share insights into their JCO PO article, “Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab,” one of the top downloaded articles of 2024. Host Dr. Rafeh Naqash and Drs. Bedard and Hernando Calvo discuss how combined transcriptome and ctDNA longitudinal analysis associates with pembrolizumab outcomes. TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations where we bring you engaging conversations with authors of clinically relevant and highly significant JCO PO articles. I'm your host, Dr. Rafeh Naqash, podcast editor for JCO Precision Oncology and Assistant Professor at the OU Health Stephenson Cancer Center at the University of Oklahoma.  Today we are excited to be joined by Dr. Philippe Bedard, Staff Medical Oncologist at the Princess Margaret Cancer Center and Professor of Medicine at the University of Toronto, as well as by Dr. Alberto Hernando-Calvo, Medical Oncologist at the Vall d'Hebron University Hospital, both authors of the JCO Precision Oncology article titled, “Combined Transcriptome and Circulating Tumor DNA Longitudinal Biomarker Analysis Associates With Clinical Outcomes in Advanced Solid Tumors Treated With Pembrolizumab.”  Thank you for joining us today. Phil and Alberto. Dr. Alberto Hernando-Calvo: Thank you. Dr. Philippe Bedard: Great to be with you. Thanks for having us.  Dr. Rafeh Naqash: One of the reasons we do this podcast, as some of the listeners who listen to this podcast regularly may know, is to bring in novel approaches and try to understand how the field is moving towards a space where we are understanding biomarkers better. So your manuscript that was published in JCO Precision Oncology fulfills many of those criteria. And interestingly enough, I was at a conference at the Society for Immunotherapy of Cancer last month earlier in November and a lot of excitement at SITC was revolving around novel transcriptomic biomarkers, proteomic biomarkers or imaging based biomarkers. So could you tell us a little bit about why you started looking at biomarkers? This is an extremely competitive field. Why did you think that looking at the transcriptome is somewhat different from or more interesting from tumor mutational burden PDL-1 than other biomarkers that we currently use? And that question is for you Alberto to start off.  Dr. Alberto Hernando-Calvo: So I think gene expression profiles may have a predictive performance as compared to already existing biomarkers and this was one of the points that we describe in our manuscript. The gene expression signature that we developed back in 2019 at Vall d'Hebron Institute of Oncology was initially developed based on over 45 different tumor types and tested in over 1000 patients treated with antiPD-1 and anti PDL-1. And back then and in this manuscript, we proved that for instance the gene expression signature VIGex that we developed has a potential complementary role to other predictive biomarkers. In this case, we observe this predictive power with ctDNA dynamics and we then see a correlation with other existing biomarkers such as tumor mutational burden. So I don't think we need to use one or the other, but rather they may have additive predictive power. So we need to better individualize predictive biomarkers based on tumor types and select the best combination possible to improve the performance.  Dr. Rafeh Naqash: I completely agree that one size does not fit all, especially in the landscape of immunotherapy. From your perspective, when you developed the original signature, how did you choose what genes to look at? I looked at the manuscript, on the methodology side, some of the signatures are pro-inflammatory STING interferon gamma based, so how did you try to identify that these are the 7 to 10 or whatever number of signatures on the transcriptome side? And then why did you try to combine it with ctDNA based changes?  Dr. Alberto Hernando-Calvo: Back in our initial manuscript, published in Med from Cell Press, we developed the VIGex gene expression signature, as I mentioned, with taking into consideration over 1000 tumor samples from FFPE that we can consider real world samples because they are from real patients coming from the clinic notes as part of real investigational protocol doing or performing biopsies on patients. We did observe after doing a VIGex research and doing different tests, we eventually collected these 12 different genes. Because there is a combination of both genes involved in the interferon gamma pathway, we have genes associated with Tregs as well as T cell memory cells. So it's not only looking at genes that are associated with T cell activation or CD8+ T cell infiltration, but also looking at genes that may be overactivated, overexpressed, an immunosuppressive tumor microenvironment. So it was both selecting genes, the minimum number of genes to do it more scalable and having the minimum dataset of genes and including in the signature genes that are already at targets for immune sequent inhibitors or are being tested in immunotherapy combinations.  Dr. Rafeh Naqash: Thank you. And Phil, for the sake of our listeners, could you elaborate upon this aspect of using ctDNA? So this was tumor-informed ctDNA from what I understood in the manuscript. You guys basically try to use it to understand changes in the ctDNA with treatment and then try to combine it with the transcriptome signature. How did the idea come up initially and how did you plan on combining this with an RNA-based signature? Because I have seen manuscripts and other data where people are either using one or the other, but not necessarily both together. So how did you guys come up with that idea? Dr. Philippe Bedard: Well, we thought that this was a great opportunity to look at the combination of the transcriptome as well as the ctDNA dynamics because we had run an investigator-initiated phase 2 clinical trial called INSPIRE at our institution at Princess Margaret from 2016 to 2018, where patients across five different tumor groups received single agent pembrolizumab. And we really did a deep dive on these patients where there were tumor biopsies before and while on treatment. We did exome sequencing, we did RNA sequencing to capture the transcriptome. And in a prior analysis, we had partnered with Natera to look at their Signatera assay, which is a bespoke ctDNA assay, to look at ctDNA dynamics using this test and the association with response outcomes as well as survival outcomes. So we thought that this was a really unique data set to try and address the question of whether or not there was complementarity in terms of looking at the transcriptome and transcriptome signatures of IO benefit together with the ctDNA dynamics. Dr. Rafeh Naqash: From a patient treatment standpoint, it sounded like you mostly tried to include individuals who were treated with pembrolizumab. Did this not include individuals who were treated with chemoimmunotherapy or chemotherapy with pembrolizumab? Just pembrolizumab alone? And if that's the case, some of the tumor types there included, from what I remember, ovarian cancer and some other unusual cancers that don't necessarily have approvals for single agent pembrolizumab, but perhaps in the TMB-high setting. So can you elaborate on the patient selection there for the study?  Dr. Philippe Bedard: Yeah, that's a great question. So at the time that the study was designed in 2015, this was really the early days of immune checkpoint inhibitor therapy, so we didn't have the approvals that we have now in specific tumor types for immunotherapy and chemotherapy combinations. So when the study was designed as an investigator initiated clinical trial, the idea was really to capture patients across different tumor types - so head and neck squamous cell carcinoma, malignant melanoma, ovarian cancer, triple negative breast cancer, and a kind of mixed histology solid tumor cohort, where we knew that there were some patients who were going to be immunotherapy responsive, where there was already approvals or evidence of single agent activity, and others where the responses were more anecdotal, to try and understand in a phase 2 clinical trial with kind of a deep dive, which patients benefited from treatment and which didn't. Dr. Rafeh Naqash: Interesting approach. Going to the results, Alberto, could you help us understand some of the important findings from these data? Because there's different sections of how you tried to look at the response rates, the survival, looking at the immune deconvolution, if you could explain that. Dr. Alberto Hernando-Calvo: So the first thing that we tried was to further confirm the external validation of this immune gene expression signature, VIGex in the INSPIRE asset. So what we observed at VIGex-Hot, the category defined by VIGex-Hot tumor microenvironment, was associated with better progression free survival. After including that in a multivariable analysis adjusted by other biomarkers such as TMB, PDL-1 or tumor type, this was also confirmed for overall survival. So then the next step was to really try to hypothesize if the addition of ctDNA dynamics, taking into consideration the ctDNA quantification at baseline as compared to cycle three, if those dynamics could further improve the predictive performance of VIGex categories taken in the baseline samples. What we did observe was that, for instance, VIGex-Hot tumors in baseline tumor samples that were having a ctDNA decrease, as I mentioned before on cycle three assessment as compared to baseline, were having both better progression free survival and better prognosis overall. Another important finding was the evaluation of response rate across tumor types considering both biomarkers. I would say the most important finding is that when we were considering a cold tumor microenvironment in baseline samples before pembrolizumab initiation plus an increase in ctDNA values, what we observed is that those patients were having a 0% response rate. So this may help as a future strategy either for intensification of immunotherapy regimens in a more individualized way or for an early stop to immunotherapy and try to avoid financial toxicities as well as toxicities for our patients. Dr. Rafeh Naqash: From the data that you showed, it seems that there was a strong correlation, as you sort of mentioned, between individuals that had ctDNA clearance and baseline immune pro-inflammatory signatures. So do you really need the transcriptome signature or could the ctDNA just serve as an easy quick surrogate? Because from a cost standpoint, doing whole transcriptome sequencing or more RNA sequencing or tissue standpoint, where tissue is often limited, can become a big issue. So do you think that validation of this may perhaps more revolve around using ctDNA as an easier metric or surrogate? Or am I overestimating the utility of ctDNA? Dr. Philippe Bedard: I think it's a really good question. In our data set which was relatively small, there were 10 patients who had ctDNA clearance, meaning ctDNA that was positive at baseline was not detected. And so 9 out of those 10 patients, as you alluded to, were VIGex-Hot. So the question is a good one, could you do the same with just ctDNA clearance alone, particularly in identifying these patients who really do well, who have long term disease control on immunotherapy? I think it's a tough question to answer because the field is also changing in terms of sensitivity of detection of ctDNA tests. So we know now that there are newer generations of tests which can detect even at logs down in terms of allele variants in the circulation. So I think we need more data to address the question. I think it is important as to what is the best test, what is the endpoint that we should be using from a drug development point of view in terms of really trying to push and understand which treatment regimens are the most effective and have early readouts in terms of activity. Because we all recognize in the clinic that radiographic response doesn't tell the whole story, especially early radiographic assessments using RECIST or other criteria that we apply in clinical trials. Dr. Rafeh Naqash: From a clinical trial standpoint, we often talk about validation of these studies. You may have heard of other tests where, for example, the NCI iMatch, which is incorporating transcriptome sequencing based approach to stratify patients as an integral biomarker for treatment stratification. Is that something that you guys are thinking of using, this approach where individuals who are signature highly inflamed perhaps get lesser therapies or there's a de-intensification of some sort similar to what people are trying to do with ctDNA-based approaches? Dr. Philippe Bedard: I think that's a great question. I think it makes a lot of sense. And certainly, with the new wave antibody drug conjugates in terms of identifying patients who have expression of targets for antibody drug conjugates, that's very attractive as an approach because we don't necessarily have IHC markers for all of the different targets of antibody drug conjugates. We don't necessarily have IHC markers to completely understand different contributions to the tumor microenvironment and whether or not tumors are inflamed. But it's also a challenging approach too because RNA-seq currently is not a routine clinical test. Sometimes there are issues, particularly in patients who have stored specimens that are formalin-fixed and paraffin-embedded in terms of the quality of the RNA for RNA sequencing. And it's not always feasible to get pre-treatment biopsies and turn them around in an approach. So I think it is an attractive approach for clinical trials, but it's a hypothesis that needs to be tested. It's not something that is ready for clinical prime time today in 2024. Dr. Rafeh Naqash: One of the other interesting observations that I came across in your manuscript was that tumor mutational burden, interestingly, did not correlate with signature high tumors. What is the explanation for that? Because generally you would expect a TMB high to perhaps also have an immune gene high signature. Could it have something to do with the tumor types because there was a heterogeneous mixture of tumor type? Or I'm not sure. What else could you possibly think of that you didn't see those correlations or just sample size limitations? Dr. Alberto Hernando-Calvo: Yes. So our findings are consistent with prior data suggesting for instance T cell inflamed gene expression profile was also not correlated with tumor mutational burden and both biomarkers in a prior publication. So to have additive predictive performance for identifying patients most likely to benefit from anti PD-1 regimen, so we somehow were expecting this observation, the fact that both biomarkers are not very correlated. Dr. Rafeh Naqash: So given the proof of concept findings from your study, Phil, what is the next interesting step that you guys are thinking of to expand this? Would you think that a nivolumab-ipilimumab treated cohort would have similar findings? Or is this a treatment specific single agent immunotherapy specific correlation that you found versus something else that you may find in a nivo-ipi cohort or a doublet immune checkpoint cohort?  Dr. Philippe Bedard: The findings are really hypothesis generating. They require additional validation. And you're quite right, there may be nuances in terms of specific tumor types, combinations with other immunotherapy or combinations with chemotherapy or other agents. So I think it would be great if there are other data sets that are collecting this type of information that have ctDNA dynamics and also have transcriptome and potentially exome or genome analysis to look at these types of questions because the field is moving quickly and we really need more data sets in order to understand some of the nuances and greater numbers to validate the signals that we see. Dr. Rafeh Naqash: And one thing, as you said, the field is definitely moving very quickly. I was meeting with a company an hour back and they have an imaging-based approach using fresh tissue to look at pharmacodynamic biomarkers. And I used to work in the NCI with a group that was very interested and they developed an immuno-oncology pharmacodynamic panel that has been used and published in a few clinical trials where they did phosphorylation status. So the final theme that comes out of most of these research based studies that are being done is that one size does not fit all. But the question that comes to my mind is how many things do you necessarily need to combine to get to a predictive biomarker that is useful, that is patient centric, and that perhaps is able to identify the right therapy for the right patient. What is your take on that, Phil?  Dr. Philippe Bedard: Yeah, that's a great question too. The challenge is it depends on the context in terms of what degree of positive predictive value do you need as well as the negative predictive value to drive clinical decisions. So I think in certain situations where you don't have other approved treatment options and with a therapy that is potentially low toxicity and low financial toxicity, then I think the bar is very high in terms of being able to really confidently identify that patients aren't going to benefit. I think the nuance and the challenge becomes when you move into earlier lines of therapy, or when you talk about combinations of agents, or trying to understand within the context of other available options, particularly with treatments that have significant side effect profiles as well as financial risks, then it becomes a much more nuanced question and you really need comparative studies to understand how it fits versus the existing treatment paradigm. So I'm not really answering your question with a specific number because I think it's hard to give you a number. Some of that we also need input from patients in terms of what kind of level of validation do you need and what kind of level of discrimination do you need in order to drive decisions that are meaningful for them. Dr. Rafeh Naqash: Definitely early days, as you pointed out. More and more work in this field will hopefully lead us in the direction that we all want to go in.  Now, going to a different aspect of this podcast, which is trying to understand the trajectories for both of you, Phil and Alberto. And as you mentioned, this project seemed to have started in 2015. So I'm guessing there's a history there between Princess Margaret and Vall d'Hebron. Could you highlight that a little bit? And then perhaps, Alberto, after that you could tell us a little bit about your career when you worked at Princess Margaret as a fellow and then now back at Vall d'Hebron. Phil, you as well. Dr. Philippe Bedard: So absolutely. We have a long history of collaborating with Vall d'Hebron in Barcelona. It's really a great cancer institution with a lot of like minded individuals. We have a formal partnership and we have a lot of informal links in terms of scientists and clinicians who we work with and who we collaborate with on early phase clinical trials, as well as through different investigator networks and other translational projects. So this was really how this collaboration came about and we were fortunate to have Alberto, who came to work with us for two years and brought this great idea of looking at this signature they had developed at Vall d'Hebron in their phase one group and applying it to a data set that we had through the INSPIRE clinical trial.  Dr. Rafeh Naqash: Sounds like a very successful academia-academic collaboration, which is very nice to see. So, Alberto, could you tell us a little bit about your career trajectory and how you ended up at Princess Margaret and then back at Vall d'Hebron and what you do currently? Dr. Alberto Hernando-Calvo: Yes. So I did my oncology residency at Vall d'Hebron in Barcelona, Spain. Then I decided to further specialize in early drug development as well as head and neck cancer oncology. So I decided to pursue a clinical research fellowship under the supervision of Phil Bedard, among others. And so we decided to further validate the signature that we had developed both in the cancer genomic lab at Vall d'Hebron Institute of Oncology and the phase one unit at Vall d'Hebron, and apply the signature that have been originally tested in patients receiving anti PD-1 or anti PDL-1 combinations in early phase clinical trials. In the phase 2 clinical trial of INSPIRE, where we also had ctDNA dynamics and allowed us to test both biomarkers and see that additive predictive power when we were using both. That was one of my research topics under the mentorship of Dr. Bedard and my fellowship at Princess Margaret. And this was one of the manuscripts describing all the findings of this collaboration between Vall d'Hebron and Princess Margaret Cancer Center. Dr. Rafeh Naqash: And then, Phil, if you could highlight some of the things that you've done over the course of your career and perhaps some advice for early career junior investigators and trainees.  Dr. Philippe Bedard: I finished my oncology, medical oncology training at the University of Toronto in 2008. And then I did a breast cancer fellowship in Brussels at Breast International Group. At the time, I was really intrigued because it was really kind of the early days of microarray and RNA signatures in terms of expressing signatures were being used as part of a clinical trial that BIG was running called the MINDACT Study. And so when I finished my fellowship, I came back to Princess Margaret, started on staff. I've been here now for 15 years. I was fortunate to work with the phase 1 group and kind of my career has sort of morphed in terms of early drug development as well as genomics. I've been involved with the American Association for Cancer Research project GENIE, where I'm the current chair. This is really an international data sharing project with panel based sequencing, which both Princess Margaret and Vall d'Hebron have contributed to. And I've been fortunate to work with a number of really talented early career investigators like Alberto, who spend time with us in our drug development program and launched transitional research projects that leverage some existing data sets at their own institutions and also bring together with different research groups at our institution to lead to publications like this one. Dr. Rafeh Naqash: Thank you so much. This was very exciting. Phil and Albert, thanks for joining us today and thank you for allowing us to discuss your interesting manuscript and hopefully we'll see more of this biomarker work from you guys in the near future, perhaps published in JCO Precision Oncology.   And thank you for listening to JCO Precision Oncology Conversations. Don't forget to give us a rating or review and be sure to subscribe so you never miss an episode. You can find all ASCO shows at asco.org/podcasts.     The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

The Use of Immunohistochemistry vs. qPCR to Detect BRAFV600E in Thyroid Cancer- Kannitha Chek HTL (ASCP), Nicholas Hoo-Fatt, MS, HTL (ASCP), DP, Samantha Diamond, M.D., Haresh Mani, M.D., Myong Ho “Lucy” Nam, M.D. Introduction: This study aimed to validate the effectiveness of the Ventana anti-BRAFV600E antibody in detecting the BRAFV600E mutation in thyroid cancer using immunohistochemistry (IHC) as an initial screening test. The BRAFV600E mutation is a common genetic alteration in thyroid cancer, particularly papillary thyroid carcinoma (PTC), and detection is crucial for prognosis and treatment decisions. Methods: The research examined 12 thyroid cancer cases (11 PTC and 1 anaplastic thyroid carcinoma) and 12 non-cancerous thyroid cases. This study was conducted by using both the IHC BRAFV600E antibody as well as genetic testing methods including Next-Generation Sequencing (NGS) and the Biocartis Idylla rapid qPCR module for BRAF mutation. Results: The antibody successfully identified the BRAFV600E mutation in all cancer cases, aligning with results from other genetic testing methods, and as expected, non-cancerous cases showed no mutation-specific staining. The study highlighted important considerations in interpreting IHC results, such as the presence of non-specific brown staining due to colloid containing brown pigments in negative cases. It also emphasized the importance of proper tissue representation, as demonstrated by one case that initially lacked staining. While the research provides strong evidence for the accuracy of the Ventana anti-BRAFV600E antibody, it also identified limitations. The study lacked PTC cases negative for the BRAFV600E mutation, which would have provided a more comprehensive validation. Conclusion: The researchers suggest further investigation with a broader range of samples, including more anaplastic thyroid carcinoma cases and follicular variant of PTC, to explore potential correlations between tumor heterogeneity and staining intensity. This validation study contributes to improving thyroid cancer diagnosis and treatment by authenticating the reliability IHC methods in detecting a key genetic mutation. It also highlights the importance of continued research to optimize diagnostic methods in thyroid cancer.

Assessing Adhesion Slide Performance Across Histology Applications -Colin Brewer, CellPath, Newtown, Wales; Rachel Finn, HTL, StatLab, McKinney, TX; Neil Haine, PhD, CellPath, Newtown, Wales; Arielle Hobson, StatLab, McKinney, TX; Moritz Kamphenkel, Knittel Glass, Braunschweig, Germany; Ronja-Melinda Komoll, Ph.D, Knittel Glass, Braunschweig, Germany; Racheal Moore, HT, StatLab, McKinney, TX; Nicole Romer, Knittel Glass, Braunschweig, Germany; Edeltraud Schikora, Knittel Glass, Braunschweig, Germany; Stefan Welsch, Knittel Glass, Braunschweig, Germany; Susan Willis, CellPath, Newtown, Wales Adhesion slides are widely preferred for IHC to aid in securing tissue sections to the slide and prevent reworks that could potentially postpone a patient diagnosis and drive-up costs in the lab. The cost of reworking a failed IHC slide due to poor tissue adhesion is estimated to be ~$80 per slide, considering the reagent cost and workload administration.1 Adhesion slides reinforce tissue adherence and integrity, minimizing the need to recut and restain the sample to ensure proper tissue morphological characteristics. Adhesion slides may also be used for H&E stains and special stains for added adhesion, but could retain excess reagent, or background staining, on the slide. In this study the differences in contact angle and in tissue adherence during microtomy were analyzed,  investigation was done on whether different adhesion slides exhibit similar levels of background staining during histological staining procedures, and evaluation and comparison of the tissue adhesion properties of adhesion slide brands across different tissue types and applications was performed.  After wide-ranging testing of adhesion slide characteristics, this study exhibited that not all adhesion slides are created equal. While water bath behavior showed to not be a relevant factor, there was considerable variation in background staining and tissue adhesion between slides. The results of this study suggested that it is important to determine what the needs are for your laboratory based on the types of staining done and tissue types used. It is also important to test adhesion slides to find the right slide or slides for your laboratory applications.

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

Research Requires Flexibility: Protease-Free Permeabilization Expands FISH Tissue Applications.-Andrelie Branicky, Shared Laboratory Resources, Lerner Research Institute, Cleveland Clinic, Cleveland, OH Fluorescence in situ hybridization (FISH) visualizes the presence of a specific DNA or RNA sequence in a tissue sample or cell. This method, particularly the mRNA version, detects gene expression when protein might not be present or IHC is impossible. FISH combined with immunohistochemistry enables spatial transcriptomics, which provides significantly more information about the tissue microenvironment. Formalin-fixed paraffin-embedded (FFPE) tissues are the standard for tissue preservation in the clinical world. Most commercial mRNA probe and amplification systems are built around the model of FFPE tissue that can withstand harsh protease permeabilization. In the research world, tissues are fixed in different fixatives for varying times; all at the discretion of the investigator instead of an organization like the CLIA.  Given the wide range of tissue preparations, the HCR automated FISH-ISH protease-free program provides the flexibility to combine  FISH and fluorescent immunohistochemistry on tissue fixed in a variety of ways such as: 10% NBF, Histochoice (a glyoxal-based fixative), and methanol/acetic acid, with only minor changes to the basic protocol. Additionally, the lack of harsh protease pre-treatment maintains tissue integrity and morphology for staining and imaging. 

Cellular localization of the pink bollworm Cry1Ac Bt protein receptor PgCad1 in cultured insect cells Authors: Melanie Miranda (BS, HTL- ASCP, University of Arizona-Comparative Pathology Core Laboratory, Tucson, AZ) Jeff Fabrick (PhD, United States Department of Agriculture, Phoenix, AZ) Transgenic cotton genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) are used to manage insect pests, including the pink bollworm (Pectinophora gossypiella), a globally invasive pest of cotton. However, the evolution of resistance to Bt Cry proteins (Cry1Ac and Cry2Ab) by the pink bollworm in parts of Asia has reduced the effectiveness of Bt cotton. Several mutations in the midgut cadherin gene PgCad1 are genetically linked with the resistance of the Cry1Ac Bt toxin, which can result in disrupted cellular trafficking of the cadherin receptor to the surface of the midgut membrane and decrease toxin binding. Here, we established specialized insect histology and immunohistochemistry (IHC) protocols for reliable localization the PgCad1 receptor in cultured Tni insect cell lines. Such protocols may be useful for in situ localization of wild type PgCad1 and mutant variants in midgut cells of the pink bollworm.    

 Taranaki features twice on today's show. We find PGG Wrightson Livestock's regional manager Andrew Gibson at a buoyant Inglewood sale where 200 IHC calves are up for auction.See omnystudio.com/listener for privacy information.

Hurling Chat sees Andy Coen, Cyril Farrell, Niall Canavan and Sean Walsh look back at the big Hurling weekend.  St Thomas gets the job done again as Turloughmore, Sarsfields, Tommie Larkins and Castlegar crash out at the quarter final stage. Athenry and Portumna qualify for the B Final. Tynagh Abbey Duniry, Kinvara and Meelick Eyrecourt reach the IHC semis. Meanwhile, Mullagh, Beagh, and Kiltormer get relegated.

When working with patients, it is essential for palliative care providers to have goal-oriented conversations. Without them, caregivers may not efficiently and collaboratively meet the patients' needs and goals for their own care. How can new technologies enhance these conversations, both from a productivity and a human relationship standpoint?Matthew Gonzales, MD, of the Institute for Human Caring at Providence, joins the conversation to discuss IHC, the center's successes, and its use of generative artificial intelligence. Gonzales lays out how “EmpathyAI” can enhance caregiver-to-patient interactions and lead to better outcomes for patients in a goal-aligned care model.ResourcesVisit the IHC's official website to learn more about its work

Our food choices are directly impacting our health and well-being. It's time to make a change… Join us as we expose the shocking truth about our food system. Kelly Ryerson, MBA, IHC, a nutrition expert and regenerative agriculture advocate, reveals the hidden dangers lurking in our grocery stores. From GMOs to gluten, glyphosates to glycocins, we're uncovering the dirty secrets that are making us sick.  Get ready to rethink everything you thought you knew about organic, and discover the transformative power of eating clean! Topics discussed include: What are glycocins and why do we care? The government subsidizing chemical agriculture Suffering chronic illness due to your GMO intake The connection between autoimmunity and gluten Organic can still be detrimental to your health Food Regulations in the U.S. vs Food Regulations Elsewhere Regenerative agriculture and its benefits Why are seed oils bad and why do you need to avoid them? Greenwash companies that are highly recommended. Connect with Kelly: Follow Kelly on her Website: https://glyphosatefacts.com/about/ Follow Kelly on Instagram: https://www.instagram.com/glyphosategirl Connect with Kacie & Gianna: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.motheruppod.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.instagram.com/motheruppod⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.youtube.com/@motheruppod⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ View full show notes at ⁠⁠⁠⁠⁠⁠www.motheruppod.com⁠⁠⁠⁠⁠⁠⁠ The Go Diaper Free Podcast, hosted by Andrea Olson and Nicole Cheever, delves into elimination communication—a unique approach to infant potty training that begins from birth. As the world's first podcast dedicated to this topic, it offers everything you need to know, whether you're new to the concept or already familiar. To learn more, visit Go Diaper Free Podcast. We are BIG BELIEVERS in therapy here at Mother Up. Let our sponsor BetterHelp connect you to a therapist who can support you - all from the comfort of your own home. Visit ⁠⁠⁠⁠⁠https://betterhelp.com/motherup⁠⁠⁠⁠⁠ and enjoy a special discount on your first month. If you have any questions about the brand relating to how the therapists are licensed, their privacy policy, or therapist compensation model, check out this FAQ: ⁠⁠⁠⁠⁠https://www.betterhelp.com/your-questions-answered/

HURLING: Turloughmore 1-24 Kiltormer 3-10 (IHC match report with Galway Bay FM's Sean Walsh)

HURLING: Sylane 2-11 Annaghdown 1-11 (IHC match report with Galway Bay FM's PJ Lynch)

HURLING: Sylane manager Ronan Higgins with Galway Bay FM's PJ Lynch after their IHC victory over Annaghdown

HURLING: Tynagh/Abbey-Duniry manager Mattie Kenny with Galway Bay FM's Gordon Duane after their IHC victory over Kilbeacanty

HURLING: Kinvara joint manager Mike Helebert with Galway Bay FM's Ollie Turner after their IHC victory over Killimor

HURLING: Kinvara 1-24 Killimor 1-17 (IHC match report with Galway Bay FM's Ollie Turner)

Dr. Allison Zibelli and Dr. Erika Hamilton discuss the results of the DESTINY-Breast06 trial in HR+, HER2-low and HER2-ultralow metastatic breast cancer and the A-BRAVE trial in early triple-negative breast cancer, the results of which were both presented at the 2024 ASCO Annual Meeting. TRANSCRIPT Dr. Allison Zibelli: Hello, I'm Dr. Allison Zibelli, your guest host of the ASCO Daily News Podcast. I'm an associate professor of medicine and breast medical oncologist at the Sidney Kimmel Cancer Center of Jefferson Health in Philadelphia. My guest today is Dr. Erika Hamilton, a medical oncologist and director of breast cancer research at the Sarah Cannon Research Institute. We'll be discussing the DESTINY-Breast06 trial, which showed a progression-free advantage with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) compared to chemotherapy in hormone receptor-positive HER2-low or HER2-ultralow metastatic breast cancer. We'll address the implications of this study for the community, including the importance of expanding pathology assessments to include all established subgroups with HER2 expression, and the promise of expanding eligibility for antibody-drug conjugates. We'll also highlight advances in triple-negative breast cancer, focusing on the A-BRAVE trial, the first study reporting data on an immune checkpoint inhibitor avelumab in patients with triple-negative breast cancer with invasive residual disease after neoadjuvant chemotherapy.  Our full disclosures are available in the transcript of this episode.  Erika, it's great to have you on the podcast today. Dr. Erika Hamilton: Thanks so much, Allison. Happy to join. Dr. Allison Zibelli: Antibody-drug conjugates are rapidly changing the treatment landscape in breast cancer. The data from the DESTINY-Breast06 trial suggests that trastuzumab deruxtecan may become a preferred first-line treatment option for most patients with HER2-low or HER2-ultralow metastatic breast cancer after progression on endocrine therapy. First, could you remind our listeners, what's the definition of HER2-ultralow and what were the findings of this trial? Dr. Erika Hamilton: Yeah, those are fantastic questions. Ultralow really has never been talked about before. Ultralow is part of a subset of the IHC zeros. So it's those patients that have HER2-tumor staining that's less than 10% and incomplete but isn't absolutely zero. It's even below that +1 or +2 IHC that we have classified as HER2-low. Now, I think what's important to remember about D-B06, if you recall, D-B04 (DESTINY-Breast04) was our trial looking at HER2-low, is that D-B06 now included HER2-low as well as this HER2-ultralow category that you asked about. And it also moved trastuzumab deruxtecan up into the frontline. If you recall, D-B04 was after 1 line of cytotoxic therapy. So now this is really after exhausting endocrine therapy before patients have received other chemotherapy. And what we saw was an improvement in progression-free survival that was pretty significant: 13.2 months versus 8.1 months, it was a hazard ratio of 0.62. And you can ask yourself, “well, was it mainly those HER2-low patients that kind of drove that benefit? What about the ultralow category?” And when we look at ultralow, it was no different: 13.2 months versus 8.3 months, hazard ratio, again, highly significant. So I think it's really encouraging data and gives us some information about using this drug earlier for our patients with hormone receptor-positive but HER2-negative disease.  Dr. Allison Zibelli: I thought this study was really interesting because it's a patient population that I find very difficult to treat, the hormone receptor-positive metastatic patient that's not responding to endocrine therapy anymore. But it's important to mention that T-DXd resulted in more serious toxicities compared to traditional chemotherapy in this study. So how do you choose which patients to offer this to? Dr. Erika Hamilton: Yeah, those are both great points. So you're right, this is after endocrine therapy. And in fact, about 85% of these patients had received at least 2 prior lines of endocrine therapy. So I have some people kind of asking, “Well, if endocrine therapy really isn't benefiting everyone in the second-line setting post-CDK, should we just move to the ADCs?” And, no, probably we should really make sure that we're exhausting endocrine therapies for those patients that are going to benefit. And once we determine somebody has endocrine-resistant disease, that's when we would think about switching. In terms of the side effects, I think you're right. It's mainly ILD that's probably the more serious side effect that we worry about a little bit with trastuzumab deruxtecan. The good news is, through multiple trials, we've gotten a little bit better at managing this. We've pretty much all but eliminated any fatal cases of ILD, definitely less than 1% now. ILD rates, depending on what study you look for, kind of ranges in that 10% to 15% range. Any grade ILD on D-B06 was 11.3%. So really kind of making sure that we look for ILD at scans, making sure that patients are educated to tell us about any new pulmonary symptoms: cough, exertional dyspnea, shortness of breath at rest, etc. But I think the most common side effects that we really deal with on a daily basis with trastuzumab deruxtecan, luckily, is nausea, which we've gotten better at managing with the 2- or 3-drug antiemetic regimen, and probably a little bit of fatigue as well. Dr. Allison Zibelli: Thank you. So, I think for most people in the community, the sticking point here will be expanding pathology assessments to include all of the subgroups, including the ultralow. Most patients in the community are not testing for HER2-low and HER2-ultralow now. Dr. Erika Hamilton: Historically, we kind of all did HER2 IHC, right? And then as FISH became available, there were a lot of institutions that moved to FISH and maybe didn't have IHC anymore. And now, at least in my institution, we do both. But I think it's a very important point that you made that IHC was really designed to pick out those patients that have HER2-high, the 3 pluses or the FISH amplified cases. It was not to tell the difference between a 1+ or a 2+ or a 0 that's not quite a 0 and a 1+. So I think you're right. I think this is tough. I probably have a little bit more of an interesting take on this than some people will. But data from ASCO, not this year but in 2023, there was actually a pretty eloquent study presented where they looked at serial biopsies in patients, and essentially, if you got up to 4 or 5 biopsies, you were guaranteed to have a HER2-low result. Now, this didn't even include ultralow, which is even easier. If we know we include ultralow, we're really talking about probably 85% to 90% of our patients now that have some HER2 expression. But if we biopsy enough, we're guaranteed to get a HER2 low.  And so I think the question really is, if we know IHC wasn't really designed to pick out these ultralows, and we know kind of greater than 90% of patients are going to have some expression, did we kind of develop this drug a little bit backwards? Because we thought we understood HER2, and the reality is this drug is a little bit more like a sacituzumab govitecan, where we don't test for the TROP2. Should we really be kind of serial biopsying these patients or should maybe most patients have access to at least trying this drug?  Dr. Allison Zibelli: So I don't think that most of my patients will really be happy to sign up for serial biopsies. Dr. Erika Hamilton: Agreed. Dr. Allison Zibelli: Do we have any emerging technologies for detecting low levels of HER2? You talked about how the IHC test isn't really designed to detect low levels of HER2. Do you think newer detection techniques such as immunofluorescence will make a difference, or will we have liquid biopsy testing for this? Dr. Erika Hamilton: Yeah, I think liquid biopsy may be a little bit hard, just because some of those circulating tumor cells are more of a mesenchymal-type phenotype and don't necessarily express all of the same receptors. Normally, if they're cytokeratin-positive, they do, but certainly there is a lot out there looking at more sensitive measures. You mentioned immunofluorescence, there are some even more quantitative measures looking at lower levels of HER2. I definitely think there will be. I guess, ultimately, with even the IHC zeros that are the less than 10% incomplete staining, having a PFS that was absolutely no different than the HER2 low, I guess the question is, how low can we really go? We know that even the IHC zeros doesn't mean that there's no HER2 expression on the cell surface. It just means that maybe there's a couple of thousand as opposed to 10,000 or 100,000 copies of HER2. And so it really appears that perhaps this drug really is wedded to having a lot of HER2 expression. So ultimately, I wonder how much we're going to have to use those tests, especially with what we know about tumor heterogeneity. We know that if we biopsy 1 lesion in the liver, biopsy a lymph node, or even another lesion in the liver, that the HER2 results can have some heterogeneity. And so ultimately, my guess is that most people have some HER2 expression on their breast cancer cells. Dr. Allison Zibelli: So maybe we're going to be using this for everybody in the future. Dr. Erika Hamilton: It certainly seems like we keep peeling back the onion and including more and more patients into the category that are eligible to receive this. I agree. Dr. Allison Zibelli: Let's move on to triple-negative breast cancer, namely the A-BRAVE trial. This was an interesting trial for patients that did not get neoadjuvant immunotherapy and testing 2 groups. The first group was those with residual disease after neoadjuvant conventional chemotherapy. The second group was people with high-risk disease identified upfront that had upfront surgery. The study found that adjuvant avelumab did not improve disease-free survival versus observation, which was the study's primary endpoint. But interestingly, there was a significant improvement in 3-year overall survival and distant disease-free survival. Can you give us your thoughts on that? Dr. Erika Hamilton: Yeah, I think this study was really interesting. Right now, the standard for our patients with larger or node-positive triple-negative cancers is KEYNOTE-522. It's a pretty tough regimen. It's kind of 2 sequential uses of 2 chemotherapies, so 4 chemotherapy agents total with pembrolizumab. But you're right, this study looked at those that had residual disease after neoadjuvant that didn't include immunotherapy, or those patients that didn't get neoadjuvant therapy, went to surgery, and then were receiving chemotherapy on the back end. I'm going to give you the numbers, because you're right. The 3-year disease-free survival rates were not statistically significant. It was 68.3% among those that had avelumab, 63.2% with those that had observation only. So the difference was 5.1% in favor of avelumab, but it wasn't statistically significant. A p value of 0.1, essentially. But when we looked at the 3-year overall survival rates, we saw the same pattern, those patients with the avelumab doing better, but it was 84.8% overall survival and not, unfortunately, dying, versus 76.3%. So the magnitude of benefit there was 8.5%, so about 3% higher than we saw for disease-free survival, and this was statistically significant.  So is this going to change practice for most patients? I probably don't think so. I think for our patients that have larger tumors that's recognized upfront or have node positivity, we're probably going to want to use neoadjuvant chemo. Being able to get a PCR is very prognostic for our patients and enables us to offer things on the back end, such as PARP inhibitors or further chemotherapy of a different type of chemotherapy. But for our patients that go to surgery and maybe the extent of their disease just isn't recognized initially, this could be an option. Dr. Allison Zibelli: I agree. I think this will be a really useful regimen for patients where we get the surprise lymph node that we weren't expecting, or somebody who comes to us, maybe without seeing the medical oncologist, who got upfront surgery. So I thought this was really interesting. What kind of translational studies do you think we're going to do to try and understand which patients would benefit from avelumab? Dr. Erika Hamilton: Yeah, I think that's a great question, and honestly, it's a question that we haven't really answered in the neoadjuvant setting either. Immunotherapy in breast cancer is just a little bit different than it is in some other diseases. We have a benefit for those patients that are PD-L1 positive in the first line. We really haven't seen benefit for metastatic outside of first line. And then in neoadjuvant, it was among all comers. We don't have to test for PD-L1. And now we have this avelumab data from A-BRAVE. I think the question is, is there's probably a subset of patients that are really getting benefit and a subset that aren't. And I don't know that PD-L1 testing is the right test. We know a lot of people are looking at TILs, so kind of lymphocytes that are infiltrating the tumor, a variety of other kind of immunologic markers. But my guess is that eventually we're going to get smart enough to tease out who actually needs the immunotherapy versus who isn't going to benefit. But we're not quite there yet. Dr. Allison Zibelli: Thank you, Erika, for sharing your valuable insights with us on the ASCO Daily News Podcast today. Dr. Erika Hamilton: Thanks so much for having me.  Dr. Allison Zibelli: And thank you to our listeners for joining us. You'll find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you like this podcast and you value our insights, please take a moment to rate, review, and subscribe wherever you get your podcasts. It really helps other people to find us. So thank you very much for listening today.   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.    Find out more about today's speakers:  Dr. Allison Zibelli Dr. Erika Hamilton @ErikaHamilton9   Follow ASCO on social media:  @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures: Dr. Allison Zibelli:  None Disclosed   Dr. Erika Hamilton: Consulting or Advisory Role (Inst): Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Hosun Pharma, Zentalis Pharmaceuticals, Jefferies, Tempus Labs, Arvinas, Circle Pharma, Janssen, Johnson and Johnson   Research Funding (Inst): AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millenium, TapImmune, Inc., Lilly, Pfizer, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceuticals, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Zenith Epigentics, Arvinas, Harpoon, Black Diamond, Orinove, Molecular Templates, Seattle Genetics, Compugen, GI Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akesobio Australia, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repetoire Immune Medicines, Treadwell Therapeutics, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Cullinan Oncology, Bristol-Myers Squib, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics

Bioconjugation of antibodies to drugs via chemical linkers is how antibody drug conjugates (ADCs) are made. We're joined by Matt Giese, Senior Scientist at Vector Laboratories, who talks us through the complex chemistry options and biodesign considerations that have to be considered and balanced when making a successful ADC.How does one build the skillset to work in biodesign of ADCs you might ask? Well, Matt's career path might not provide a clearcut roadmap like you might hope. That's because Matt started his career as an auto mechanic, moved into art, went back to auto mechanics, worked as baggage handler and as a construction worker, all before ever finding chemistry. If you think that's a convoluted path, just wait to hear about his academic and professional work journeys.  You'll revel in following this journey, and in the lessons and diverse skills learned along the way. Join us to hear it yourself, from who might just be the most interesting man in chemistry!Related episodes:Season 5, Ep.7: The life-altering impact of one chemist's sabbaticalSeason 2, Ep.1: Chemistry: a modern American dreamSeason 3, Ep.5: On the COVID pill and other process chemistry tales Bonus content!Access bonus content curated by this episode's guest by visiting www.thermofisher.com/chemistry-podcast for links to recent publications, podcasts, books, videos and more.View the video of this episode on www.thermofisher.com/chemistry-podcast. A free thank you gift for our listeners! Request your free Bringing Chemistry to Life t-shirt on our episode website.Use Podcast Code: LabRatsRul3 in July or OchemRcks in August. We read every email so please share your questions and feedback with us! Email helloBCTL@thermofisher.com

BUFFALO, NY- July 16, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on June 20, 2024, entitled, “HER2-low and HER2-zero in breast cancer between prognosis, prediction and entity.” In this new editorial, researchers Marcus Schmidt, Hans-Anton Lehr, and Katrin Almstedt from the University Medical Center of Johannes Gutenberg University discuss HER2 in breast cancer. HER2 is a well-established prognostic and predictive factor in breast cancer, which is associated with a poor prognosis but also offers the chance of improved survival when treated with targeted therapies based on the monoclonal antibody trastuzumab, both in advanced (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71 to 0.94, P = 0.004) and in early (HR 0.66, 95% CI 0.57 to 0.77, P < 0.00001) stages. The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) defines HER2-positivity as either 3+ by immunohistochemistry (IHC) or 2+ with amplification by in situ hybridization (ISH). Yet, the vast majority of breast tumors are considered HER2- negative (IHC 0 or 1+ or 2+ without amplification) by these criteria, and it has until recently been accepted that HER2-negative tumors do not benefit from trastuzumab based therapy. “Now, results of randomized trials with trastuzumab-based antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) have fundamentally challenged this long-held view.” DOI - https://doi.org/10.18632/oncotarget.28598 Correspondence to - Marcus Schmidt - marcus.schmidt@unimedizin-mainz.de Video short - https://www.youtube.com/watch?v=4ROlLZo82uY Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28598 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, breast cancer, HER2, HER2-low, prognostic, predictive 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. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Join us for an episode of BioTalk with Rich Bendis featuring Dr. Bradley Maron, Senior Associate Dean for Precision Medicine and Executive Co-Director of the University of Maryland-Institute for Health Computing at the University of Maryland School of Medicine. With his extensive background in cardiovascular research and precision medicine, Dr. Maron offers a wealth of knowledge and innovative perspectives.   In this episode, Dr. Maron shares his professional journey, discussing his various roles at the University of Maryland and what drew him to the region. He provides a comparative analysis of the ecosystems in Boston/Harvard and Maryland/University of Maryland, highlighting the unique attributes and opportunities within each.   Dr. Maron introduces the Institute for Health Computing (IHC), explaining its creation, mission, and strategic partnerships with the University System of Maryland and Montgomery County. He outlines the significance of data science in improving health and wellness, addressing its increasing role and challenges.   We learn about the IHC's approach to bringing learning and healthcare directly to communities, illustrated by an example of their methodology: analyze, innovate, prevent, treat, and adapt. Dr. Maron discusses how the IHC aims to become an economic driver for the University System of Maryland, the state, the BioHealth Capital Region, and the nation, fostering startups, spinouts, commercialization efforts, and entrepreneurial activities.   Dr. Maron outlines the Institute's ambitious goals for the first five years and the range of services to be provided. He also details the decision to establish the IHC in Montgomery County, describing its new facilities and the county's supportive role.   Tune in to BioTalk for an informative discussion with Dr. Bradley Maron as we explore the future of precision medicine and the impactful work of the Institute for Health Computing.  

Drs. John Sweetenham and Angela DeMichele discuss potentially ground-breaking abstracts in breast and lung cancer as well as notable research on artificial intelligence and its impact on cancer care, all of which were featured at the 2024 ASCO Annual Meeting.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast. My guest today is Dr. Angela DeMichele, the Marianne and Robert McDonald Professor in Breast Cancer Research and co-leader of the Breast Cancer Program at the University of Pennsylvania's Abramson Cancer Center. Dr. DeMichele also served as the chair of the 2024 ASCO Annual Meeting Scientific Program. Today, she'll be sharing her reflections on the Annual Meeting and we'll be highlighting some advances and innovations that are addressing unmet needs and accelerating progress in oncology.  Our full disclosures are available in the transcript of this episode.  Dr. DeMichele, congratulations on a very robust and highly successful program at ASCO24, and thanks for joining us on the podcast today. Dr. Angela DeMichele: Well, thanks so much for having me, Dr. Sweetenham. It's a pleasure to be here.  Dr. John Sweetenham: The presidential theme of the Annual Meeting this year was the "The Art and Science of Cancer Care: From Comfort to Cure." And this was certainly reflected throughout the meeting in Chicago that welcomed more than 40,000 attendees from across the globe. I know our listeners will be interested to hear some of your own reflections from the meeting now that we're on the other side of it, so to spea  Dr. Angela DeMichele: Yes. Well, I will say that playing this role in the annual meeting really was a highlight of my career, and I feel so fortunate to have had the opportunity to do it. We had over 200 sessions, and in many, if not all of these sessions, we really tried to make sure that there was a case that really sort of grounded the session to really help people understand: you're going to hear about science, but how are you going to apply that? Who is the patient for whom this science really is important?  We had over 7,000 abstracts submitted, and our 25 tracks and their chairs really pulled through to find really the best science that we could present this year. I think what you saw really was a representation of that across the board: incredible advances in lung cancer, breast cancer, melanoma, GI cancers; also really cutting-edge technologies: AI, as we'll talk about in a little while circulating markers like ctDNA, new drug development, new classes of drugs. So it was really an exciting meeting. I mean, some highlights for me, I would say, were certainly the Plenary, and we can talk a little bit about that. Also, we had a fantastic ASCO/AACR Joint Session on “Drugging the “Undruggable Target: Successes, Challenges, and the Road Ahead.” And, if any of the listeners have not had a chance to hear this, it's really worth going in and watching this because it really brought together three amazing speakers who talked about the successes in KRAS, and then really, how are we using that success in learning how to target KRAS to now targeting a variety of other previously thought to be undruggable targets. I learned so much. And there's really both the academic and the pharma perspective there. So I'd really encourage watching this session. The other session that I really thought was terrific was one that I was honored to chair, which was a fireside chat (“How and Where Will Public Investment Accelerate Progress in Oncology? A Discussion with the NIH and NCI Directors”) with both Dr. Monica Bertagnolli, who is the director of the NIH, and Dr. Kim Rathmell, who's now the director of the NCI. And boy, I'll tell you, these two incredibly smart, thoughtful, insightful women; it was a great conversation. They were really understanding of the challenges we face conducting research, practicing medicine. And maybe different from leadership at the NIH in the past, they've really taken the approach to say that everything they do is focused on the patient, and they don't limit themselves to just research or just science, that everything that the NIH does, and particularly the NCI does, really has to be focused on making sure we can give patients the best possible care. And I think they're being very thoughtful about building important infrastructure that's going to take us into the future, incorporating AI, incorporating new clinical trial approaches that are going to make it faster and easier to conduct clinical trials and to get the results that we need sooner. So just a few of the highlights, I think, from some really interesting sessions. Dr. John Sweetenham: It certainly was an extremely enriching and impactful ASCO24. And I think that the overall theme of the meeting was extremely well reflected in the content with this amazing mix of really, truly impactful science, along with a great deal of patient-centered healthcare delivery science to accompany it. So, I completely agree with you about that. There was a lot, of course, to take in over the five days of the meeting, but I'm sure that our listeners would be very interested to hear about one or two abstracts that really stood out for you this year.  Dr. Angela DeMichele: Sure. I'm a breast cancer specialist, so I can't help but feel that the late breaking abstract, the DESTINY-Breast06 trial, was really important for the field of breast cancer. So just briefly, this is a study of the antibody drug conjugate T-DxD, trastuzumab deruxtecan. This is a drug that is actually now approved in metastatic breast cancer, really effective in HER2-positive disease. But the question that this trial was trying to answer is, can this drug, which is built with the herceptin antibody against HER2, then linked to a chemotherapeutic molecule, can this work even in the setting of very, very low HER2 expression on a tumor? I think this is an incredibly important question in the field of antibody drug conjugates, of which there are now many across diseases, is how much of the target do you really need to have on the surface of the tumor?  We had seen previously HER2 overexpressing tumors respond really well to this drug. HER2 tumors that have an intermediate level of expression were tested in the DP04 trial, and we saw that even those 2+ intermediate tumors responded well to this drug. The DP06 trial that was presented at ASCO was looking at this group of patients that have even less HER2 on the surface. So we typically measure HER2 by immunohistochemistry as 0, 1+, 2+, or 3+. And this was looking at patients whose tumors were over 0, but were at 1+ or below, so low and ultra-low. And it turned out that compared to treatment of physician's choice, the drug really had quite a lot of activity, even in these patients who have very little HER2 on their tumors, really showing progression-free survival benefits in the HER2-low and HER2-ultra-low groups that were appreciable on the order of about 5 months, additional progression free survival hazard ratios around 0.6, so really demonstrating that utilizing an antibody drug conjugate, where you've got very little target, can still be a way to get that drug to a tumor.   And I think it'll remain to be seen whether other ADCs can have activity at very low levels of IHC expression of whatever target they're designed against. I think one of the tricky things here for implementing this in breast cancer will be how do pathologists actually identify the tumors that are ultra-low because it's not something that we typically do. And so we'll go through a period, I think, of adjustment here of really trying to understand how to measure this. And there are a bunch of new technologies that I think will do a better job of detecting low levels of the protein on the surface of the tumor because the current IHC test really isn't designed to do that. It was only designed to be focused on finding the tumors that had high levels. So we have some newer technologies with immunofluorescence, for example, that can really get down to very low levels. And I think this is going to be a whole new area of ADCs, target detection – how low can you go to still see activity? So I thought that this was an important abstract for many reasons.  I will just say the second area that I was really particularly impressed with and had a big impact on me were the two lung cancer abstracts that were presented in the Plenary, the LAURA trial (LBA4) and the ADRIATIC trial (LBA5). And I think, I've been in the field of oncology for 30 years now, and when I started in the late ‘90s, lung cancer was a disease for which we had very few treatments. If we didn't catch it early and surgery wasn't possible for non-small cell lung cancer, really, it was a horrible prognosis. So we knew this year was the 20th anniversary of the discovery of EGFR as a subtype of lung cancer. That was really, I think, a turning point in the field of non-small cell lung cancer – finding a target. And now seeing the LAURA trial show that osimertinib really had such an enormous impact on progression-free survival amongst these patients who had EGFR-positive non-small cell lung cancer, progression-free survival hazard ratio of 0.16; there was a standing ovation.  And one of the really big privileges of being the Scientific Program Chair is getting to moderate the Plenary Session, and it's a really amazing experience to be standing up there or sitting there while the presenter is getting a standing ovation. But this was well deserved because of the impact this is having on patients with EGFR positive lung cancer. And it was similar with the ADRIATIC trial, which looked at the benefits of adding immunotherapy in limited-stage small-cell lung cancer. Again, a disease that treatment has not changed in 30 years, and so the addition of durvalumab to the standard backbone of chemotherapy for small cell lung cancer had its survival advantage. These patients are living longer and it was really an impressive improvement. And I think it really underscores just the revolution that has happened in lung cancer between targeted therapy and immunotherapy has completely changed the prognosis for patients with this disease. So to me, these were really landmark reports that came out at ASCO that really showed us how far we've come in oncology. Dr. John Sweetenham: Yeah, absolutely. I think that, as you mentioned, those results are truly remarkable, and they reflect extraordinary advances in science. I think we see that both in terms of the therapeutic arena, but also, I think we've started to see it in other areas as well, like symptom control, remote patient monitoring, and so on and so forth, where some of the newer virtual technologies are really having major impacts as well. Dr. Angela DeMichele: Yes, we really wanted to have a focus on artificial intelligence in this meeting, because it's having such an enormous impact on our field in everything from care delivery to diagnostics. I'd love to hear what you thought was the most interesting, because there really was just new data across the board presented. Dr. John Sweetenham: I've actually chosen 3 abstracts which I thought were particularly interesting for a couple of reasons, really. They're all based on virtual health interventions, and I think they're interesting in really reflecting the theme of the meeting, in that they are extremely advanced technology involved in the virtual platforms, a couple of which are artificial intelligence, but very impactful to patients at the same time in terms of remote symptom control, in terms of addressing disparities, and in one case, even influencing survival. So I thought these were three really interesting abstracts that I'll walk the listeners through very quickly.  The first of these was a study, Abstract 1500 (“National implementation of an AI-based virtual dietician for patients with cancer”) which looked at an artificial intelligence-based virtual dietitian for patients with cancer. This is based on the fact that we know nutritional status to be a key driver of patient experience and of cancer outcomes. And as the authors of the presentation noted, 80% of patients look for nutritional support, but many of them don't get it. And that's primarily a workforce issue. And I think that's an important thematic point as well, that these new technologies can help us to address some of the workforce issues we have in oncology. So this was an AI-based platform developed by experts in nutrition and cancer patients, based on peer reviewed literature, and a major effort in terms of getting all of these data up together. And they developed an artificial intelligence platform, which was predominantly text message based. And this platform was called INA. And as this is developing as a platform, there's a machine learning component to it as well. So in theory, it's going to get better and better and better over time.  And what they did in their study was they looked at little over 3,000 patients across the entire country who were suffering from various types of cancer, GU, breast, gynecological malignancy, GI and lung. And most of them had advanced-stage disease, and many of them had nutritional challenges. For example, almost 60% of them were either overweight or obese by BMI. And the patients were entered into a text exchange with the AI platform, which would give them advice on what they should eat, what they shouldn't eat. It would push various guidance and tips to them, it would develop personalized recipes for them, and it would even develop menu plans for the patients. And what's really interesting about this is that the level of engagement from the patients was very high, with almost 70% of patients actually texting questions to this platform. About 80% of the patients completed all of the surveys, and the average time that patients interacted with the platform was almost nine months, so this was remarkable levels of engagement, high levels of patient satisfaction. And although at this point, I think it's very early and somewhat subjective, there was certainly a very positive kind of vibe from patients. Nearly 50% have used the recommended recipes. More than 80% of them thought that their symptoms improved while they were using this platform. So I think as a kind of an assistant for remote management of patients, it's really remarkable. And the fact that the level of engagement was so high also means that for those patients, it's been very impactful.   The second one, this was Abstract 100 (“AI virtual patient navigation to promote re-engagement of U.S. inner city patients nonadherent with colonoscopy appointments: A quality improvement initiative”) looked again at an AI-based platform, which in this case was used in an underserved population to address healthcare disparities. This is a study from New York which was looking at colorectal cancer screening disparities amongst an underserved population, where historically they've used skilled patient navigators to address compliance with screening programs, in this case specifically for colorectal cancer. And they noticed in the background to this study that in their previous experience in 2022, almost 60% of patients either canceled or no-showed for colonoscopy appointments. And because of this and because of the high burden of patients that this group has, they decided to take an AI-based virtual patient navigator called MyEleanor and introduce this into their colorectal cancer screening quality improvement.  And so they introduced this platform in April of 2023 through to the end of the year, and their plan was to target reengagements of around 2,500 patients who had been non adherent with colonoscopy appointments in a previous year. And so the platform MyEleanor would call the patients to discuss rescheduling, it would assess their barriers to uptake, it would offer live transfer to somebody to schedule for them, and then it would go on closer to the point of the colonoscopy to call the patients and give them advice about their prep. And it was very nuanced. The platform would speak in both English and Spanish versions. It could detect nuances in the patient's voice, which might then trigger it to refer the patient to a live agent rather than the AI platform. So, very sophisticated technology. And what was most interesting about this, I think, was that over the eight months of the study, around 60% of patients actually engaged with this platform, with almost 60% of that group, or 33% overall, accepting a live transfer and then going on to scheduling, so that the completion rate for the no show patients went from 10% prior to the introduction of this platform to 19% after it was introduced. So [this is] another example, I think, of something which addresses a workforce problem and also addresses a major disparity within cancer care at the moment by harnessing these new technologies. And I think, again, a great interaction of very, very high-level science with things that make a real difference to our patients.  So, Dr. DeMichele, those are a couple of examples, I think, of early data which really are beginning to show us the potential and signal the impact that artificial intelligence is going to have for our patients in oncology. I wonder, do you have any thoughts right now of where you see the biggest impact of artificial intelligence; let's say not in 20 years from now, but maybe in the next year or two?  Dr. Angela DeMichele: Well, I think that those were two excellent examples. A really important feature of AI is really easing the workload on physicians. And what I hope will happen is that we'll be able to use AI in the very near future as a partner to really offload some of the quite time-consuming tasks, like charting, documentation, that really take us away from face-to-face interaction with patients. I think this has been a very difficult period where we move to electronic medical records, which are great for many reasons, but have really added to the burden to physicians in all of the extra documentation. So that's one way, I think, that we will hope to really be able to harness this. I think the other thing these abstracts indicate is that patients are very willing to interact with these AI chatbots in a way that I think, as you pointed out, the engagement was so high. I think that's because they trust us to make sure that what we're doing is still going to be overseen by physicians, that the information is going to get to us, and that they're going to be guided. And so I think that in areas where we can do outreach to patients, reminders, this is already happening with mammograms and other sorts of screening, where it's automated to make sure you're giving reminders to patients about things that they need to do for some of their basic health maintenance. But here, really providing important information – counseling that can be done by one of these chatbots in a way that is compassionate, informative and does not feel robotic to patients.   And then I was really impressed with, in the abstract on the screening colonoscopy, the ability of the AI instrument to really hear nuances in the patient's responses that could direct them directly to a care provider, to a clinician, if they thought that there might be some problem the patient was experiencing. So again, this could be something that could be useful in triaging phone calls that are coming in from patients or our portals that just feel like they are full of messages, no matter how hard you try to clear them all out, to get to them all. Could we begin to use AI to triage some of the more mundane questions that don't require a clinician to answer so that we can really focus on the things that are important, the things that are life threatening or severe, and make sure that we're getting to patients sooner? So there's just a few ways I really hope it'll help us. Dr. John Sweetenham: Yeah, absolutely. I think we're just scratching the surface. And interestingly enough, in my newsfeed this morning through email, I have an email that reads, “Should AI pick immunotherapy combinations?” So we'll see where that goes, and maybe one day it will. Who knows? Dr. Angela DeMichele There was a great study presented at ASCO about that very thing, and I think that is still early, but I could envision a situation where I could ask an AI instrument to tell me all of the data around something that I want to know about for a patient that could deliver all of the data to me in real time in the clinic to be able to help me make decisions, help me quote data to patients. I think in that way it could be very, very helpful. But it'll still need the physicians to be putting the data into context and thinking about how to apply it to the individual person. Dr. John Sweetenham: Absolutely, yes. And so just to round off, the final abstract that caught my eye, which I think kind of expands on a theme that we saw at an ASCO meeting two or three years ago around the impact of [oncology] care at home, and this was Abstract 1503 (“Acute care and overall survival results of a randomized trial of a virtual health intervention during routine cancer treatment”). So, a virtual platform but not AI in this case. And this was a study that looked at the use of an Integrative Medicine at Home virtual mind-body fitness program. And this was a platform that was used to look at hospital admission and acute care of patients who used it, and also looked at survival, interestingly enough. So what was done in this study was a small, randomized study which looked at the use of virtual live mind, body and fitness classes, and compared this in a randomized fashion to what they called enhanced usual care, which essentially consisted of giving the patients, making available to the patients, some pre-recorded online meditation resources that they could use. And this was applied to a number of patients with various malignancies, including melanoma, lung, gynecologic, head and neck cancers, all of whom were on systemic therapy and all of whom were reporting significant fatigue.  This was a small study; 128 patients were randomized in this study. And what was very interesting, to cut to the chase here, is that the patients who had the virtual mind-body program, compared with the control group, actually were less likely to be hospitalized, the difference there being 6.3% versus 19.1%, respectively. They spent fewer days in the hospital. And remarkably, the overall survival was 24.3 months median for patients in the usual care arm and wasn't reached in those patients who were on the virtual mind-body fitness class platform. So very preliminary data, certainly are going to need more confirmation, but another example of how it appears that many of these non-pharmacological interventions have the potential to improve meaningful endpoints, including hospital stays and, remarkably, even survival. So again, I think that that is very consistent with the theme of this year's meeting, and I found that particularly interesting, too.  I think our time is up, so I want to thank you, Dr. DeMichele, for sharing your insights with us today on the ASCO Daily News Podcast. We really appreciate it. And once again, I want to congratulate you on what was really a truly remarkable ASCO this year.  Dr. Angela DeMichele: Well, thanks so much for having me. It's been a tremendous pleasure to be with you today. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in a transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and 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.   Follow ASCO on social media:    @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:   Dr. John Sweetenham:   Consulting or Advisory Role: EMA Wellness  Dr. Angela DeMichele: Consulting or Advisory Role (an immediate family member): Pfizer Research Funding (Inst.): Pfizer, Genentech, Novartis, Inviata/NeoGenomics  

Featuring perspectives from Dr William J Gradishar, Dr Virginia Kaklamani, Dr Erica Mayer and Dr Seth Wander, including the following topics: Introduction (0:00) Addition of Ovarian Function Suppression (OFS) to Adjuvant Endocrine Therapy for Premenopausal Patients with Hormone Receptor (HR)-Positive Breast Cancer — Dr Gradishar (4:49) Case: A woman in her mid 20s with HR-positive, HER2-positive intraductal carcinoma (IDC) who received ovarian suppression with TAC chemotherapy and concurrent trastuzumab/pertuzumab followed by tamoxifen (30:48) Case: A woman in her late 30s with HR-positive, HER2-negative IDC and no nodal involvement who received postoperative chemoradiation therapy followed by tamoxifen and is considering ovarian suppression (39:31) Role of OFS in Preserving Fertility and/or Ovarian Function in Premenopausal Patients – Dr Mayer (44:55) Case: A woman in her early 30s with HR-positive, HER2-positive (IHC 3+) IDC recommended to receive perioperative TCHP who is interested in fertility preservation (1:11:15) Case: A woman in her mid 30s presenting with ER-positive, HER2-negative breast cancer during early pregnancy who received preoperative TAC and had pathologic complete response at surgery (1:14:18) Tolerability and Toxicity of OFS – Dr Kaklamani (1:21:21) Case: A woman in her mid 30s, uninterested in fertility preservation, who received chemotherapy and TAC followed by tamoxifen and abemaciclib for ER-positive, HER2-negative breast cancer (1:39:42) Case: A premenopausal woman in her late 40s with a 3.6-cm breast tumor and a Recurrence Score (RS) of 26 who becomes amenorrheic with chemotherapy and TC (1:43:32) Other Practical Considerations in the Application of OFS – Dr Wander (1:46:29) Case: A woman in her early 50s with HR-positive, HER2 IHC 2+ invasive lobular carcinoma and a RS of 15 who declined chemotherapy and opted to stop adjuvant leuprolide after 1 year (1:59:56) Case: A woman in her early 40s with HR-positive, HER2 IHC 1+ breast cancer who has no interest in fertility preservation and significant residual disease at surgery (2:14:06) CME information and select publications

In this episode, Uzair talks to Abdul Moiz Jaferii about the ongoing cases in Pakistan's superior judiciary. We focused on the wiretapping case being heard by Justice Babar Sattar, cases related to Imran Khan, and the broader implications of the supposed standoff between the establishment and the judiciary. We also focused on the political ramifications of these cases through the summer and whether Imran Khan will be out of jail in the next few months. Abdul Moiz Jaferii is a lawyer and tweets @jaferii Chapters: 0:00 Introduction 1:30 The latest at the courts 7:30 IHC's letter to Justice Isa 15:00 Illegal wiretapping case 33:30 Political ramifications 39:00 Will Khan be out soon?

Featuring perspectives from Dr Adam M Brufsky, including the following topics: Review of Local Therapy (0:00) Treatment Advances for HER2 Positive Early-Stage Breast Cancer (18:34) Case: A woman in her early 60s with ER-positive, HER2-positive (IHC 3+) with infiltrating ductal carcinoma who received T-DM1 with an aromatase inhibitor (19:37) Case: A woman in her early 50s with ER-positive, HER2-positive (IHC 3+) who received TCHP followed by a mastectomy (56:36) Beyond the Guidelines Survey and HERRISK (1:02:33) Trials in Progress (1:14:24) CME information and select publications