Podcasts about tils

So viel Stumpfsinn, wie ihn nur die Insel hervorbringt! André und Alex haben sich zusammengetan, um gemeinsam wieder einmal zu schauen, welche verrückten Nachrichten die Welt hervorgebracht hat – und sie wurden nicht enttäuscht! In dieser Ausgabe ging es unter anderem um schweigende Tils, Bienen mit Mitspracherecht, gestohlene Dixi-Klos, duschende Altrocker, Proktologen-Zwillinge und nach Adressen suchende Königskinder. Außerdem kramen die beiden Inselbegabten in ihrer Kindheit herum und holen den einen oder anderen verdrängten Werbeschatz der 90er Jahre zurück in die Gegenwart, um die Top-3-Liste des Monats zu füllen. Die Insel – weil wir es uns wert sind! Diese Folge gibt es auch als Video-Podcast auf Patreon Unser Twitch Kanal Folge direkt herunterladen

Welcome to another episode of the VJ Oncology Podcast, where we bring you the forefront of cancer research and clinical... The post Expanding Cell Therapy – TILs, TCRs & CARs in Lung Cancer and Melanoma appeared first on VJOncology.

The Herald Sun is back and so is Remco. Did Tadej lose because of his sunglasses? Unlike Gicconi, Amstel Gold brings more questions than answers and surprise winners all round. Hollywood, Tils and Marko are back for a quick-fire round. Happy Easter!Shop Black Sheep Cycling 20% off with the code: domestiques

Brought to you by Black Sheep Cycling. Use code "domestiques" new range live now, and yes, there's 20% OFF for all the domestiques out there. The most feared weekend for riders, the most loved by fans Paris-Roubaix delivered again. This week, we break down the madness with Hollywood Elvis Turner, Mark'O and Tils. We're talking Pauline Ferrand-Prévot's historic first for France, SD Worx misfire, and Vos's selflessness. On the men's side, Van der Poel was untouchable except for a water bottle on his way to a golden cobble hat trick, Tadej bonks, Mads breaks hearts, Wout diesels and sprinting at 140km to go.

Use the code domestiques for 20% off ⁠Black Sheep⁠Another huge episode of The Domestiques as we dissect the world's most beautiful sport in what is truly the golden era of cycling. With the dust (and beer) still settling after the Ronde van Vlaanderen, Tils, Hollywood and Marko break down every attack, and cobble that made this year's edition one to remember.

When I found out that Django developer and Python Software Foundation chair Dawn Wages has a chapter in her upcoming Domain-Driven Django book called “Just Use Postgres”, I knew we had to get her on the show. In this episode of Talking Postgres with Claire Giordano, Dawn breaks down why so many Python and Django developers have such an affinity for Postgres. And we dive into the Djangonaut Space mentoring program (where contributors launch), learn why “free as in puppies” beats “free as in cake” for open source vibes, and dig into why Python is the second-best language for everything.Links mentioned in this episode:Project page: psycopgDocumentation: Psycopg 3 – PostgreSQL database adapter for PythonProject page: PostgreSQL open source projectGit repo: code for PostgreSQL.org websiteConference: PyCon US 2025, happening May 14-22 in PittsburghConference: PGConf.dev 2025 Schedule, happening May 13-16 in Montreal CanadaConference: Prague PostgreSQL Developer Day 2025 (P2D2) Schedule, which took place Jan 28-29Wikipedia page: Model-view-controller software design patternBook: Professional ASP.NET MVC 1.0, affectionately called “the four heads book”Podcast episode: Working in Public with Simon Willison & Marco SlotBlog: Simon Willison's TILs, aka Things I've learnedSimon Willison's Weblog: Here's how I use LLMs to help me write codeSimon Willison's Weblog: How I make annotated presentationsSurvey: Python Developers Survey 2023 ResultsPython Docs: What's new in Python 3.14Mentorship program: Djangonaut SpaceMentorship program: Media & Talks about Djangonaut SpacePodcast episode: Why mentor Postgres developers with Robert HaasSlides: PGConf EU 2024 talk by Claire Giordano about Contributions to Postgres, including maps showing how global the Postgres project isVideo of POSETTE 2024 talk by Paolo Melchiorre: Semantic search with Django, PostgreSQL, & pgvectorVideo of Citus Con 2023 talk: Maps with Django (and PostGIS), by Paolo MelchiorreVideo of Citus Con 2022 talk: Django with PostgreSQL superpowers, by Paolo MelchiorreConference: DjangoCon Africa 2025, happening August 11-15 in Tanzania Calendar invite: LIVE recording of Ep26 of Talking Postgres to happen on Wed Apr 02, 2025 with guest Bruce Momjian, to talk about Open Source Leadership 

BUFFALO, NY – March 12, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on March 10, 2025, titled “COMETgazing – interesting insights, lessons for clinical practice and a call for more precision using the biomarkerSCOPE.” Dr. Mangesh A. Thorat, affiliated with Queen Mary University of London, Homerton University Hospital, and King's College London, discusses new findings suggesting that some women diagnosed with early-stage breast cancer may not need immediate surgery. The editorial is based on results from the COMET trial, which studied women with low- to intermediate-grade ductal carcinoma in situ (DCIS). The findings raise questions about the necessity of surgery and highlight the importance of more precise screening methods for DCIS, ensuring that only those who truly need treatment receive it. Breast cancer screening programs are designed to detect cancer early, but this editorial reinforces the concern that some detected cancers may never become a real threat. The COMET trial compared two strategies for treating breast cancer: standard treatment, which includes surgery and possible additional therapy, versus active monitoring, where patients are closely observed without immediate intervention. The results indicate that many of the invasive cancers diagnosed in the monitoring group were likely present from the start rather than developing from DCIS over time. Dr. Thorat points out that these invasive cancers were often slightly larger, but they did not appear to be aggressive. These findings challenge the assumption that immediate treatment is necessary for all cases of DCIS. Researchers estimate that at least half of the invasive breast cancers in this study either take years to progress or may never progress at all. “The planned long-term follow-up of the trial may shed more light on the median length of lead-time and the proportion of IBCs regressing as well as DCIS progression under different lead-time assumptions.” Current methods for evaluating DCIS rely heavily on histological grading, which has limitations. Dr. Thorat emphasizes the need for more precise tools to determine which DCIS cases require treatment. His previous research suggests that biomarkers, such as multi-clonal estrogen receptor (ER) expression and tumor-infiltrating lymphocytes (TILs), may help predict which DCIS cases are truly at risk of becoming invasive. The editorial also highlights that many women prefer to avoid surgery when possible. In a related study, only 52% of patients in the standard care group followed through with it, indicating that more individuals are willing to consider alternatives to surgery. This fact underscores the importance of developing accurate biomarkers to guide treatment decisions and ensure that patients receive appropriate care without unnecessary interventions. As researchers continue to follow patients from the COMET trial, they hope to learn more about how invasive breast cancers behave over time. Finally, Dr. Thorat encourages clinicians and scientists to rethink breast cancer treatment and develop better ways to identify which patients truly need surgery—and which do not. DOI - https://doi.org/10.18632/oncotarget.28698 Correspondence to - Mangesh A. Thorat - m.thorat@qmul.ac.uk 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

A Warrny debrief & Three Peaks preview with Mark O'Brien.In this episode of The Domestiques, Hollywood and Tils catch up with former Melbourne to Warrnambool champion Mark O'Brien about his day in the winning break. We dive into his power numbers and nutrition, as well as his plan to break his own record at next month's Peaks Challenge by Bicycle Network.This is a long chat with a a true legend of Australian cycling.

We did things a bit different today. Tils was on the road and documented what has become the best day in Australian cycling each year. On the road interviews with some of Australian cycling's most prominent people.

It's Hollywood and Tils in the studio today to catch up on some Australian stalwart events: the Tour de Bright and the Great Victorian Bike Ride. Hollywood breaks down his questionable diet and race report from Bright, whilst Tils opens up on how shes feeling post-diagnosis and working the Great Victorian Bike Ride. Plus the latest news in global cycling. Thanks to Black Sheep Performance Apparel and Marsh Insurance

Dr. Ryan Augustin and Dr. Jason Luke discuss neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, promising new TIL therapy for advanced melanoma, and the emerging role of CD3 engagers in treatment strategies. TRANSCRIPT Dr. Ryan Augustin: Hello, I'm Dr. Ryan Augustin, your guest host of the ASCO Daily News Podcast today. I'm a medical oncology fellow at Mayo Clinic in Rochester, Minnesota. Joining me today is Dr. Jason Luke, an associate professor of medicine and the director of the Cancer Immunotherapeutic Center at the University of Pittsburgh Hillman Cancer Center. I had the privilege of working as a postdoc in Jason's translational bioinformatics lab, where we investigated mechanisms of resistance to immunotherapy in melanoma and other cancers.  Today, we'll be discussing 3 important topics, including neoadjuvant immunotherapy and the importance of multidisciplinary team coordination, the impact and practical considerations for incorporating TIL therapy into melanoma, and the current and future use of CD3 engagers in both uveal and cutaneous melanoma.  You'll find our full disclosures in the transcript of this episode.  Jason, it's great to have this opportunity to speak with you today. Dr. Jason Luke: Absolutely. Thanks, Ryan. It's great to see you. Dr. Ryan Augustin: So, to kick things off, Jason, we, of course, have seen tremendous advances in cancer immunotherapy, not only in metastatic disease but also the perioperative setting. Recent data have shown that the use of neoadjuvant therapy can provide not only critical prognostic information but can also help individualize post-resection treatment strategies and potentially even eliminate adjuvant therapy altogether in patients who achieve a pathologic, complete response. This signifies a conceptual shift in oncology with the goal of curing patients with immunotherapy. In triple-negative breast cancer, the KEYNOTE-522 regimen with pembrolizumab is standard of care. In non-small cell lung cancer, there are now four FDA approved chemo-IO regimens in both the neoadjuvant and perioperative settings. And, of course, in melanoma, starting with SWOG S1801 utilizing pembro mono therapy, and now with combined CTLA-4 PD-1 blockade based on results from the NADINA trial, neoadjuvant IO is the new standard of care in high-risk, resectable melanoma. It's important to highlight this because whereas other tumor types have more mature multidisciplinary care, for example, patients with breast cancer are reviewed by the whole team in every center, and every patient with lung cancer certainly benefits from multidisciplinary care conferences, that's not always the case with melanoma, given the relative frequency of cases compared to other tumor types.  Jason, would you say that we have now moved into an era where the integration of a multidisciplinary team and melanoma needs to be prioritized. And why is it important to have multidisciplinary team coordination from the onset of a patient's diagnosis? Dr. Jason Luke: Well, I think those are great questions, Ryan, and I think they really speak to the movement in our field and the great success that we've had integrating systemic therapy, particularly immunotherapy, into our treatment paradigms. And so, before answering your question directly, I would add even a little bit more color, which is to note that over the last few years, we've additionally seen the development of adjuvant therapy into stages of melanoma that, historically speaking, were considered low-risk, and medical oncologists might not even see the patient. To that, I'm speaking specifically about the stage 2B and 2C approvals for adjuvant anti-PD-1 with pembrolizumab or nivolumab. So this has been an emerging complication.  Classically, patients are diagnosed with melanoma by either their primary care doctor or a dermatologist. Again, classically, the next step was referral to a surgeon who had removed the primary lesion, with discussion around nodal evaluation as well. And that paradigm has really changed now, where I think integration of medical oncology input early on in the evaluation of the appropriate treatment plan for patients with melanoma is quite a pressing issue now, both because we have FDA approvals for therapeutics that can reduce risk of recurrence, and whether or not to pursue those makes a big difference to the patient for discussion early on.  And, moreover, the use of systemic therapies now, prior to surgery, of course, then, of course, requires the involvement of medical oncology. And just for an emphasis point on this, it's classically the case, for good reason, that surgeons complete their surgery and then feel confident to tell the patient, “Well, we got it all, and you're just in really good shape.” And while I understand where that's coming from, that often leaves aside the risk of recurrence. So you can have the most perfect surgery in the world and yet still be at very high risk of recurrence. And so it's commonly the case that we get patients referred to us after surgery who think they're just in totally good shape, quite surprised to find out that, in fact, they might have a 20% to 50% risk of recurrence. And so that's where this multidisciplinary integration for patient management really does make a big difference.  And so I would really emphasize the point you were making before, which is that we need multidisciplinary teams of med onc with derm, with surgery early on, to discuss “What are the treatment plans going to be for patients?” And that's true for neoadjuvant therapy, so, for palpable stage 3, where we might give checkpoint inhibitors or combinations before surgery. But it's true even in any reasonably high-risk melanoma, and I would argue in that state, anything more than stage 1 should be discussed as a group, because that communication strategy with the patient is so important from first principles, so that they have an expectation of what it's going to look like as they are followed out over time. And so we're emphasizing this point because I think it's mostly the case at most hospitals that there isn't a cutaneous oncology disease management meeting, and I think there needs to be.  It's important to point out that usually the surgeons that do this kind of surgery are actually either the GI surgeons who do colon cancer or the breast surgeons. And so, given that melanoma, it's not the most common kind of cancer, it could easily be integrated into the existing disease review groups to review these cases. And I think that's the point we really want to emphasize now. I think we're not going to belabor the data so much, but there are enormous advantages to either perioperative or adjuvant systemic therapy in melanoma. We're talking about risk reduction of more than 50%, 50-75% risk reduction. It's essential that we make sure we optimally offer that to patients. And, of course, patients will choose what they think is best for their care. But we need to message to them in a way that they can understand what the risks and benefits of those treatments are and then are well set up to understand what that treatment might look like and what their expectations would be out over time.  So I think this is a great art of medicine place to start. Instead of belaboring just the details of the trial to say, let's think about how we take care of our patients and how we communicate with them on first principles so that we can make the most out of the treatments that we do have available. Dr. Ryan Augustin: That's great, Jason. Very insightful points. Thank you.  So, shifting gears now, I'd also like to ask you a little bit about TIL therapy in melanoma. So our listeners will be aware that TIL is a promising new approach for treating advanced melanoma and leverages the power of a patient's cytotoxic T cells to attack cancer cells. While we've known about the potential of this therapy for some time, based on pioneering work at the NCI, this therapy is now FDA approved under the brand AMTAGVI (Lifileucel) from Iovance Biotherapeutics, making it the first cellular therapy to be approved for a solid tumor. Now, I know TIL therapy has been administered at your institution, Jason, for several years now, under trial status primarily for uveal melanoma using an in-house processing. But for many cancer centers, the only experience with cellular therapy has come under the domain of malignant hematology with CAR T administration. At our institution, for example, we have only recently started administering TIL therapy for melanoma, which has required a tremendous multidisciplinary effort among outpatient oncology, critical care, and an inpatient hematology service that has expertise in cytokine release syndrome.  Jason, where do you see TIL therapy fitting into the metastatic space? Which patients do you think are truly candidates for this intensive therapy? And what other practical or logistical considerations do you think we should keep in mind moving forward? Dr. Jason Luke: Well, thanks for raising this. I think the approval of lifileucel, which is the scientific name for the TIL product that's on the market now. It really is a shift, a landscape shift in oncology, and we're starting in melanoma again, as seems to be commonly the case in drug development. But it's really important to understand that this is a conceptually different kind of treatment, and therefore, it does require different considerations. Starting first with data and then actualization, maybe secondarily, when we see across the accelerated approval package that led to this being available, we quote patients that the response rate is likely in the range of 30%, maybe slightly lower than that, but a meaningful 25% to 30% response rate, and that most of those patients that do have response, it seems to be quite durable, meaning patients have been followed up to four years, and almost all the responders are still in response. And that's a really powerful thing to be able to tell a patient, particularly if the patient has already proceeded through multiple lines of prior standard therapy. So this is a very, very promising therapy.  Now, it is a complicated therapy as well. And so you highlighted that to do this, you have to have a tumor that's amenable for resection, a multidisciplinary team that has done a surgery to remove the tumor, sent it off to the company. They then need to process the TIL out of the tumor and then build them up into a personalized cell product, bring it back, you have to lympho-deplete the patient, re-introduce this TIL. So this is a process that, in the standard of care setting under best circumstances, takes roughly six weeks. So how to get that done in a timely fashion, I think, is evolving within our paradigms. But I think it is very important for people who practice in settings where this isn't already available to realize that referring patients for this should be a strong consideration. And thinking about how you could build your multidisciplinary team in a way to be able to facilitate this process, I think is going to be important, because this concept of TIL is relevant to other solid tumors as well. It's not approved yet in others, but we kind of assume eventually it probably will be. And so I think, thinking through this, how could it work, how do you refer patients is very important.  Now, coming back to the science, who should we treat with this? Well, of course, it's now an air quotes “standard of care option”, so really it ought to be available to anybody. I will note that currently, the capacity across the country to make these products is not really adequate to treat all the patients that we'd want. But who would we optimally want to treat, of course, would be people who have retained a good performance status after first line therapy, people who have tumors that are easily removable and who have not manifested a really rapid disease progression course, because then, of course, that six-week timeline probably doesn't make sense. The other really interesting data point out of the clinical trials so far is it has looked like the patients who got the least amount of benefit from anti-PD-1 immunotherapy, in other words, who progressed immediately without any kind of sustained response, those patients seem to have the best response to TILs, and that's actually sort of a great biomarker. So, this drug works the best for the population of patients where checkpoint inhibitors were not effective. And so as you think about who those patients might be in your practice, as you're listening, I think prioritizing it for primary progression on anti PD-1, again and giving it ahead thought about how would you get the patient through this process or referred to this process very quickly is really important because that lag time is a problem. Patients who have melanoma tend to progress reasonably quickly, and six weeks can be a long time in melanoma land. So, thinking ahead and building those processes is going to be important moving into the future Dr. Ryan Augustin: Definitely appreciate those practical considerations. Jason, thank you.  Moving on to our final topic, I was hoping to discuss the use of immune cell engagers in melanoma. So, similar to CAR T therapy, bispecific T-cell engagers, or BiTEs, as they're commonly known, are standard of care in refractory myeloma and lymphoma. But these antibodies engaging CD-3 on T cells and a tumor specific antigen on cancer cells are relatively new in the solid tumor space. Tarlatamab, which is a DLL-3 and CD-3 bispecific antibody, was recently approved in refractory small cell lung cancer, and, of course, tebentafusp, an HLA-directed CD-3 T cell engager was approved in uveal melanoma in 2022. Both T and NK cell engaging therapies are now offering hope in cancers where there has historically been little to offer. However, similar to our discussion with TIL therapy, bispecifics can lead to CRS and neurotoxicity, which require considerable logistical support and care coordination.  Jason, I was wondering if you could briefly discuss the current landscape of immune cell engagers in melanoma and how soon we may see these therapies enter the treatment paradigm for cutaneous disease. Dr. Jason Luke: I think it is an exciting, novel treatment strategy that I think we will only see emerge more and more. You alluded to the approval of tebentafusp in uveal melanoma, and those trials were, over the course of a decade, where those of us in solid tumor land learned how to manage cytokine release syndrome or the impact of these C3 bispecifics, in a way that we weren't used to. And what I'll caution people is that CRS, as this term, it sounds very scary because people have heard of patients that, of course, had difficult outcomes and hematological malignancies, but it's a spectrum of side effects. And so, when we think about tebentafusp, which is the approved molecule, really what we see is a lot of rash because GP100, the other tumor antigen target, is in the skin. So, patients get a rash, and then people do get fevers, but it's pretty rare to get more than that. So really what you have to have is the capacity to monitor patients for 12 hours, but it's really not more scary than that. So it really just requires treating a few people to kind of get used to these kinds of symptoms, because they're not the full-on ICU level CRS that we see with, say, CAR T-cells.  But where is the field going? Well, there's a second CD3 bispecific called brenetafusp that targets the molecule PRAME, that's in a phase 3 clinical trial now for frontline cutaneous melanoma. And tebentafusp is also being evaluated in cutaneous melanoma for refractory disease. So, it's very possible that these could be very commonly used for cutaneous melanoma, moving into, say, a two-to-four-year time horizon. And so therefore, getting used to what are these side effects, how do you manage them in an ambulatory practice for solid tumor, etc., is going to be something everyone's going to have to learn how to deal with, but I don't think it should be something that people should be afraid of.  One thing that we've seen with these molecules so far is that their kinetics of treatment effect do look slightly different than what we see with more classic oncology therapies. These drugs have a long-term benefit but doesn't always manifest as disease regression. So, we commonly see patients will have stable disease, meaning their tumor stops growing, but we don't see that it shrank a lot, but that can turn into a very meaningful long-term benefit. So that's something that we're also, as a community, going to have to get used to. It may not be the case we see tumors shrink dramatically upfront, but rather we can actually follow people with good quality- of-life over a longer period of time.  Where is the field going? You mentioned tarlatamab in small cell lung cancer, and I think we're only going to see more of these as appropriate tumor antigens are identified in different tumors. And then the other piece is these CD3 engagers generally rely upon some kind of engagement with a T cell, whether CD3 engagers, and so they can be TCR or T-cell receptor-based therapies, although they can be also SCFV-based. But that then requires new biomarkers, because TCR therapy requires HLA restriction. So, understanding that now we're going to need to profile patients based on their germline in addition to the genomics of the tumor. And those two things are separate. But I would argue at this point, basically everybody with cutaneous melanoma should be being profiled for HLA-A(*)0201, which is the major T-cell receptor HLA haplotype that we would be looking for, because whether or not you can get access immediately to tebentafusp, but therefore clinical trials will become more and more important.  Finally, in that T-cell receptor vein, there are also T cell receptor-transduced T cells, which are also becoming of relevance in the oncology community and people listening will be aware in synovial sarcoma of the first approval for a TCR-transduced T cell with afamitresgene autoleucel. And in melanoma, we similarly have TCR-transduced T cells that are coming forward in clinical trials into phase 3, the IMA203 PRAME-directed molecule particularly. And leveraging our prior conversation about TILs, we're going to have more and more cellular based therapies coming forward, which is going to make it important to understand what are the biomarkers that go with those, what are the side effect profiles of these, and how do you build your practice in a way that you can optimally get your patients access to all of these different treatments, because it will become more logistically complicated, kind of as more of these therapies come online over the next, like we said, two to four years kind of time horizon. So, it's very exciting, but there is more to do, both logistically and scientifically. Dr. Ryan Augustin: That's excellent. Thanks, Jason, and thank you so much for sharing your great insight with us today on the ASCO Daily News Podcast. Dr. Jason Luke: Thanks so much for the opportunity. Dr. Ryan Augustin: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode, and you can follow Dr. Luke on X, formerly known as Twitter, @jasonlukemd. And you can find me, @RyanAugustinMD. 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 today's speakers: @ryanaugustinmd Dr. Jason Luke @jasonlukemd   Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Ryan Augustin: No relationships to disclose Dr. Jason Luke: Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio

Send us a textIn this 14th episode of DigiPath Digest, I introduce a new course on AI in pathology, designed to help pathologists understand and confidently navigate AI technologies. The episode focuses on various research studies that highlight the integration and effectiveness of AI in pathology, particularly in colorectal biopsies and kidney transplant biopsies, emphasizing the importance of seamless workflow integration. You will also learn about challenges in manual assessment of tumor-infiltrating lymphocytes and HER2 expression in breast cancer. I  advocate for more consistent and precise AI-driven approaches. And there an opportunity for a discounted beta test of the new AI course.00:00 Welcome to DigiPath Digest #1400:24 New AI Course Announcement01:51 Deep Learning in Colorectal Biopsies09:17 AI in Kidney Biopsy Evaluation16:12 Automated Scoring of Tumor Infiltrating Lymphocytes24:22 AI for HER2 Expression in Breast Cancer31:13 Conclusion and Course DetailsTHIS EPISODE'S RESOURCES

Jedes Jahr begleitet das Podcast-Team zwei Teilnehmende des aktuellen PPP-Jahrgangs vom Abflug bis zu ihrer Rückkehr. Heute berichtet Til (41. PPP) über seine ersten Wochen in Portland, Oregon. _____ Direkt für das PPP bewerben und alle weiteren Infos: ⁠⁠⁠https://usa-ppp.de/⁠⁠⁠Als Bewerber könnt ihr neben Cultural Vistas als Hauptanlaufstelle gerne diskret behandelte Fragen an die PPP Alumni e. V. Bewerbungslotsen stellen und unabhängige Antworten von ehemaligen Teilnehmern des Programms erhalten. Dazu einfach bewerbungslosten[at]ppp-alumni.de kontaktieren.Mehr über das PPP und PPP Alumni e. V. erfahrt ihr auf ⁠⁠⁠https://www.ppp-alumni.de/⁠⁠Meldet euch -gerne auch als Nichtmitglied- zu unserem PPP Alumni e. V. Vereins-Newsletter an: http://newsletter.ppp-alumni.de/signup

Heute haben wir eine ganz besondere Folge für euch. Unsere Gästin Britta Tils teilt inspirierende Geschichten und wertvolle Einblicke in die Welt der Zahnmedizin. Hier sind einige der Highlights: ➡️ Von einer spontanen Entscheidung nach einer Feier mit Freunden bis zur Eröffnung einer kleinen, aber feinen Praxis am Marienplatz in München. ➡️ Wie ein lebensveränderndes Curriculum Britta dazu brachte, den Menschen als Ganzes zu betrachten und innovative Behandlungsmethoden wie Keramikimplantate und Eigenbluttherapie zu integrieren. ➡️ Die überraschenden Wendungen in ihrer Karriere, von einem Umzug in den Süden Deutschlands über die Herausforderungen bei der Praxisgründung bis hin zur Wiederentdeckung ihrer Leidenschaft für Weiterbildung. ➡️ Britta Tils über ihre Vision, Zahnmedizin, Coaching und Yoga zu kombinieren und somit Kollegen und Kolleginnen neue Möglichkeiten zu eröffnen. Macht euch bereit für eine Episode voller Inspiration und praktischer Tipps, die euch sicherlich neue Perspektiven eröffnen wird. Viel Spaß beim Zuhören! Shownotes: Hier findet ihr alles zu Britta und ihrer Praxis: https://www.zahnaerztin-am-marienplatz.de Unsere Weiterbildungsmöglichkeiten:

Tumor infiltrating lymphocyte (TIL) therapy uses a person's own immune cells to fight advanced melanoma, offering new hope for patients who have limited treatment options. This week, we have a conversation with Brian Gastman, EVP of medical affairs at Iovance Biotherapeutics, about TILs and the company's pipeline.Iovance recently submitted a marketing authorization application to the European Medicines Agency for lifileucel, a TIL cell therapy, for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. If approved, lifileucel will be the first and only approved therapy in this treatment setting in all European Union member states.The submission is supported by positive clinical data from the C-144-01 clinical trial in patients with advanced post-anti-PD1 melanoma.Iovance's Amtagvi is the first FDA-approved T cell therapy for a solid tumor indication. 00:47-04:44: About Iovance Biotherapeutics04:44-07:57: What is polyclonal tumor infiltrating lymphocyte treatment?07:57-14:55: What is the production process for TILs?14:55-18:32: Are there any limiting factors for TIL treatment?18:32-20:59: Is early intervention important?20:59-21:22: Does better psychology help?21:22-22:06: Are other companies working on TILs?22:06-27:25: Clinical trials 27:25-29:25: How do you address cost?29:25-34:21: Iovance's pipeline34:21-35:30: Can TILs be improved?35:30-37:21: Where does the TIL space go from here?Interested in being a sponsor of an episode of our podcast? Discover how you can get involved here! Stay updated by subscribing to our newsletter

"Let's go you good thing!” That's the call as The Domestiques urge on Aussie hope Ben O'Connor to victory at La Vuelta. With a brutal week remaining, and the shadow of Primoz Roglic looming, the team assesses what may or may not happen. Tils shares her debut commentary television experience to a national audience. You may be surprised what goes on behind the scenes in the wee-small hours. And “Hollywood” has his say at where the return of the Herald-Sun Tour should be held in 2025. Lots to unpack in the latest edition of The Domestiques!

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

Hvorfor OL-fotball for herrer ikke er helt rått, hva Danmarks rikeste fotballspiller skal bruke penger på og litt om TILs motstander i Serieligaen, Kilmarnock. Og selvsagt : hva er det beste navnet i årets Serieliga?Kast dere med i FPL-ligaen vår, med kode: k6eaej Hosted on Acast. See acast.com/privacy for more information.

We love to hear from our listeners. Send us a message.KSQ Therapeutics' CSO, Micah Benson, Ph.D., joins Erin Harris to discuss how Tumor-Infiltrating Lymphocytes (TILs) as a treatment modality have the potential to treat a variety of solid tumor types. Benson explains KSQ's Phase 1/2 clinical study, KSQ-001EX, which consists of TILs in which the SOCS1 gene is inactivated by CRISPR/Cas9 gene editing. In addition to solid tumors, Benson also addresses the therapeutic potential for autoimmune disease.

Last episode we learnt all about tumour infiltrating lymphocyte or TIL therapy through interviewing Dr. Simon Turcotte. We touched on his research, but what other research is going on within the TIL space in Canada? Well, in this episode we chatted with two students, Meghan Kates & Allyson Banville, all about their cool research on TILs! Want to learn more about cool immunotherapy research? Check out our other episodes and give us a follow on instagram @wthisimmunotherapy and twitter @WTHisImmunoT! Or feel free to reach out to us at wthisimmunotherapt@gmail.com if you have any questions or any ideas for episodes! Creators & Producers: Gillian Savage, Grace Bernard, and Dr. Pauline Loos  Podcast Logo is designed by Mia Portelance  Music is by Lara Antebi (https://laraantebi.bandcamp.com/)

Breast cancer immunotherapy has shown promise, but its clinical efficacy remains limited, especially for hormone receptor positive (HR+)/HER2-negative breast cancer. While immune checkpoint inhibitors combined with chemotherapy have benefitted some early-stage and metastatic triple-negative breast cancer patients, HR+/HER2-negative cases have seen fewer improvements. Recent neoadjuvant trials indicate that early-stage HR+/HER2-negative breast cancers might respond better to immunotherapy strategies that amplify tumor-infiltrating lymphocytes (TILs) through dual PD-(L)1/CTLA-4 checkpoint inhibition before surgery and chemotherapy. This approach could enhance the immune response in the tumor microenvironment and improve outcomes for this challenging breast cancer subtype. Increased TILs are associated with improved neoadjuvant chemotherapy (NACT) responses across breast cancer subtypes. Recently, researchers Haven R. Garber, Sreyashi Basu, Sonali Jindal, Zhong He, Khoi Chu, Akshara Singareeka Raghavendra, Clinton Yam, Lumarie Santiago, Beatriz E. Adrada, Padmanee Sharma, Elizabeth A. Mittendorf, and Jennifer K. Litton from the University of Texas MD Anderson Cancer Center, Brigham and Women's Hospital, Dana-Farber Brigham Cancer Center, and Harvard Medical School hypothesized that amplifying TILs via dual checkpoint blockade would enhance the response to subsequent NACT in breast tumors. Full blog - https://www.oncotarget.org/2024/06/20/impact-of-dual-immunotherapies-before-surgery-in-hr-her2-negative-breast-cancer/ Paper DOI -https://doi.org/10.18632/oncotarget.28567 Correspondence to - Haven R. Garber - hrgarber@mdanderson.org Video short - https://www.youtube.com/watch?v=PHpndZJHB_c Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28567 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, breast cancer, ER positive, immunotherapy, neoadjuvant chemotherapy, tumor microenvironment 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

The latest episode of The Domestiques features our very own. We hear from a modest Matilda Reynolds who, this week, rubbed shoulders with the big hitters at the Tour de Suisse. Hear her stories as she shared the road with cycling's elite. At a time when Tils predicted her best days were behind, the birthday girl is still punching well above. Don't miss The Domestiques with Hollywood + Tils. The Domestiques is presented by Black Sheep Cycling, Pillar Performance, Honan Insurance Group, and Ord Minnet.

Joan Peremiquel Pons és president de l'Arcat, l'Associació de Radioaficionats de Catalunya. Ens explica què és un radioaficionat i algunes de les activitats que fan a l'ARCAT.

Dr. John Sweetenham shares highlights from Day 4 of the 2024 ASCO Annual Meeting, including exciting new data from the IMROZ trial in multiple myeloma, adjuvant therapy for triple-negative breast cancer in A-BRAVE, and the front-line treatment of advanced renal cell carcinoma in JAVELIN Renal-101. TRANSCRIPT Dr. John Sweetenham: I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my top takeaways on selected abstracts from Day 4 of the 2024 ASCO Annual Meeting.   Today's selection features 3 randomized prospective trials in the first-line treatment of multiple myeloma, adjuvant therapy for triple negative breast cancer, and the frontline treatment of advanced renal cell carcinoma, all of which provide important new data.   My full disclosures are available in the transcript of this episode. The first of today's abstracts is number 7500. This abstract, presented by Dr. Thierry Facon from the Department of Hematology at the University of Lille in France, describes the results of the IMROZ study. This was a multicenter phase 3 study comparing a current standard first-line regimen for transplant ineligible patients with myeloma VRd with the same combination plus an additional agent, isatuximab.  The combination of bortezomib, lenalidomide and dexamethasone, known as VRd, is currently a standard first-line regimen for patients with multiple myeloma, both transplant eligible and ineligible. Previous phase 3 studies have shown that the addition of an anti-CD38 antibody to triplet regimens improves outcomes in newly diagnosed patients. Based on early phase clinical trial data showing promising response rates with isatuximab, the IMROZ study was conducted to compare isatuximab VRd with VRd alone in patients who were either ineligible for transplant or had no immediate indication for transplant. IMROZ was a global study conducted in 21 countries that involved 446 patients randomly assigned 3:2 to induction therapy with Isa-VRd followed by continuous Isa-Rd or induction therapy with VRd followed by Rd alone. The rate of complete response or better was approximately 75% with Isa-VRd compared with 64% with VRd alone. Very good partial response or better was achieved in 89% of patients with Isa-VRd, compared with around 83% of those with VRd alone. With a median follow-up at 5 years, Isa-VRd followed by Isa-Rd had reduced the risk of progression or death by 40.4% compared with VRd alone. The 60-month progression-free survival rate was 63% for Isa-VRd compared with around 45% with VRd alone, and the progression-free survival benefit was maintained in most of the analyzed subgroups. Minimal residual disease negativity was also measured in this study in both the intent to treat population and those patients who achieved a complete response. For example, in the intent to treat population, the MRD negative rate was 58% with Isa-VRd compared with around 43% with VRd alone. There were also higher rates of sustained MRD negativity for 12 months or longer among patients assigned to Isa-VRd compared with VRd alone, reflecting deeper responses in the Isa-VRd arm. Although overall survival data is still immature, data from an interim analysis showed a favorable trend in the Isa-VRd arm with 22.4% risk reduction compared with VRd alone. There was little additional toxicity from the inclusion of isatuximab with the VRd regimen and the quality-of-life data were comparable and stable in both arms of the study. The investigators concluded that although overall survival data are immature, there is a trend in favor of Isa-VRd and this, combined with the favorable response, toxicity and progression-free survival data, establish isatuximab VRd as a potential new standard of care for newly diagnosed multiple myeloma patients not eligible for transplant. There was some discussion regarding the potential use of this regimen in patients over 80 years of age since the upper age limit was capped in IMROZ at 80 years. Although there are concerns for tolerance of the 4-drug regimen in the older patient group, it seems likely that this will be adopted, especially for those with good performance status and without major comorbidities.   Next up is LBA500. This abstract reports results of the A-BRAVE trial. This trial, presented by Dr. Pier Franco Conte from the University of Padova, Italy, was a phase 3 randomized trial to assess the efficacy of the immune checkpoint inhibitor avelumab in 2 groups of patients: those with early triple negative breast cancer, with residual disease after neoadjuvant chemotherapy; and those at high risk after primary surgery and adjuvant chemotherapy. As Dr. Conte explained in the introduction to this trial, there is a fairly compelling rationale for the use of checkpoint inhibitors in triple negative breast cancer. The disease has been shown to be more immunogenic than the other breast cancer types with immune biomarkers such as TILs and PDL-1 expression associated with better prognosis, added to which, data in metastatic breast cancer show a correlation between PDL-1 expression and checkpoint inhibitor response. In the A-BRAVE study, 477 high risk patients who had completed local, regional, and systemic treatment with curative intent were stratified according to adjuvant or post neoadjuvant status and randomized 1:1 to receive avelumab at 2-week intervals for 52 weeks or to observation only. Results of the study showed a non-statistically significant improvement in three-year disease-free survival in the overall intent to treat population at 5.1% and in the post neoadjuvant patients at 6.2%. Overall survival was a secondary endpoint in this trial. The results show a significant improvement in overall survival of 8.1% in the intent-to-treat population and a very similar improvement in the post-neoadjuvant patients. The authors reported good tolerance of avelumab, although in total almost 30% discontinued treatment at some point. In their conclusion, the investigators state that the 34% reduction in the risk of death suggests a potential role for avelumab in early triple negative breast cancer patients at high risk after primary surgery or with invasive disease after neoadjuvant chemotherapy. Correlative studies are planned on tumor plasma and feces in this study. These are interesting and somewhat tantalizing results, suggesting a real effect from avelumab. Although confounded somewhat by the sample size, it will be important to see how these results mature with further follow-up.   Today's third selected abstract is number 4508 reporting the final analysis of the JAVELIN Renal 101 phase 3 trial in patients with advanced renal cell carcinoma. This study compared the combination of axitinib plus avelumab with sunitinib in this patient group. The trial included 886 patients, of whom around 61% of those in the combination group and around 65% of those in the monotherapy group were PDL-1 positive. In the initial analysis from the JAVELIN Renal 101 study, after at least 6 months of follow-up, avelumab and axitinib significantly improved progression-free survival over sunitinib in patients with PDL-1 positive tumors and in the overall population with advanced renal cell carcinoma. In the fall cohort, the median progression-free survival with the combination was 13.8 months compared with only 8.4 months with sunitinib, and based on those results, the combination received FDA approval as a first-line treatment for patients with advanced renal cell carcinoma in May of 2019. The progression-free survival observed in the initial analysis was confirmed with a new long-term analysis in the overall population. Median progression-free survival with avelumab and axitinib was 13.9 months compared with only 8.5 months with sunitinib and the median duration of response with the combination was 19.4 months versus 14.5 months with sunitinib. However, no difference in overall survival was seen. At 60 months, the overall survival in the combination group was 38.8% and 36.2% with sunitinib. In patients who were PDL-1 positive at 60 months, overall survival with a combination was 37.1% compared with 33.4% with sunitinib.  Despite the sustained difference in progression-free survival seen with this combination, the discussant at this session pointed out that most oncologists are unlikely to recommend a combination which has not been shown to improve overall survival when published studies have reported on 4 combinations which do positively impact overall survival in this patient group. Despite the good tolerance of this regimen, it seems unlikely to be a preferred frontline regimen in advanced renal carcinoma moving forward.  That concludes today's report. Thanks for listening and we hope you have enjoyed listening to our top takeaways from ASCO24. If you value the insights that you hear on the ASCO Daily News Podcast, please remember 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. Diwakar Davar and Dr. Jason Luke discuss key abstracts from the 2024 ASCO Annual Meeting that explore triplet therapy in advanced melanoma, TIL cell therapy in immune checkpoint inhibitor–naive patients, and other novel approaches that could shape the future of immunotherapy in melanoma and beyond.  TRANSCRIPT Dr. Diwakar Davar: Hello and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Diwakar Davar. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. I'm delighted to have my friend and colleague, Dr. Jason Luke, on the podcast today to discuss key abstracts in melanoma and immunotherapy that will be featured and highlighted at the 2024 ASCO Annual Meeting. Dr. Luke is an associate professor of medicine, the director of the Cancer Immunotherapeutic Center, as well as the associate director for clinical research at the University of Pittsburgh's Hillman Cancer Center.  You will find our full disclosures in the transcript of this episode.  Jason, as always, it's a pleasure to have you on this podcast to hear your key insights on trials in the immunotherapy space and melanoma development paradigm, and to have you back on this podcast to highlight some of this work.  Dr. Jason Luke: Thanks so much for the opportunity to participate. I always enjoy this heading into ASCO.  Dr. Diwakar Davar: We're going to go ahead and talk about three abstracts in the melanoma space, and we will be starting with Abstract 9504. Abstract 9504 essentially is the RELATIVITY-048 study. It describes the efficacy and safety of the triplet nivolumab, relatlimab, and ipilimumab regimen in advanced PD-1 naive melanoma. So in this abstract highlighted by Dr. Ascierto and colleagues, they report on the results of this phase 2 trial in this setting. By way of background, PD-1 inhibitors and immune checkpoint inhibitors starting in PD-1 and CTLA-4, as well as PD-1 and LAG-3, are all FDA-approved on the basis of several pivotal phase 3 trials, including KEYNOTE-006, CheckMate-066, CheckMate-067, and most recently, RELATIVITY-047. Jason, can you briefly summarize for this audience what we know about each of these drugs, at least the two combinations that we have at this time?  Dr. Jason Luke: For sure. And of course, these anti PD-1 agents, became a backbone in oncology and in melanoma dating back to more than 10 years ago now, that response rates in the treatment-naive setting to anti PD-1 with either pembrolizumab or nivolumab are roughly in the range of mid-30s to high-40s. And we've seen clinical trials adding on second agents. You alluded to them with the seminal study being CheckMate-067, where we combined a PD-1 antibody and CTLA-4 antibody or nivo + ipi. And there the response rate was increased to approximately 56%. And more recently, we have data combining PD-1 inhibitors with anti-LAG-3. So that's nivolumab and relatlimab. Now, in that trial, RELATIVITY-047, the overall response rate was described as 43%. And so that sounds, on a first pass, like a lower number, of course, than what we heard for nivolumab and ipilimumab. We have to be cautious, however, that the cross-trial comparison between those studies is somewhat fraught due to different patient populations and different study design. So I think most of us think that the response rate or the long-term outcomes between PD-1, CTLA-4, and PD-1 LAG-3 are probably roughly similar, albeit that, of course, we have much better or much longer follow up for the nivo + ipi combo.  The one other caveat to this, of course then, is that the side effect profile of these two combinations is distinct, where the incidence of high-grade immune-related adverse events is going to be roughly half with nivolumab and relatlimab, a combination of what you would see with the nivolumab and ipilimumab. So that has caused a lot of us to try to think about where we would use these different combinations. But we do see that all of these treatments can land a durable long-term response in the subset of patients that do have an initial treatment benefit. The landmark, I think, for the field has been the 7-and-a-half-year median overall survival that we've seen with PD-1 plus CTLA-4, nivo + ipi; of course, we don't have such long-term follow up for PD-1 and LAG-3. But I think that's the setting for thinking about the rationale for combining a triplet regimen of PD-1, CTLA-4, and LAG-3. Dr. Diwakar Davar: So, Jason, in your mind, given the difference in the disparity and durability of the responses for the 067 regimen of nivo-ipi, and the RELATIVITY-047 regiment of nivo-rela, what is the standard of care in the U.S., and how does it change in the rest of the world, knowing that nivo-rela is not necessarily approved in all jurisdictions? Dr. Jason Luke: So this is a major complication in our field, is that there is perhaps not complete agreement across the world in terms of what the frontline standard of care should be. I think most United States investigators, or those of us that really treat melanoma most of the time, would suggest that a combination regimen, given the enhanced response rate and longer-term outcomes, should be the consideration for the majority of patients. In fact, in my practice, it's hard to think of who I would treat with a monotherapy PD-1 approach in the PD-1 naive setting. So either nivo + ipi or nivo + rela. As you alluded to however, in other regulatory settings throughout the world, combinations might not actually even be approved at this point. So PD-1 monotherapy would be the backbone of that setting. It does set up some complications when you think about a comparator arm; say you were going to look at various combinations, probably PD-1 monotherapy would be the worldwide comparator. You have to understand though, in the United States, I think that that's a less attractive option. Dr. Diwakar Davar: So in RELATIVITY-047, Dr. Ascierto and his colleagues are looking at generating a triplet. And in this case, they looked at this in the context of frontline metastatic melanoma, 46 patients. Very interestingly, the dose of ipilimumab studied here was 1 mg/kg through 8 weeks, not the 3 mg/kg every three weeks times four doses using 067, or even the low dose ipilimumab regimen that you studied in the second line setting, which was 1 mg/kg every 3 weeks for 4 doses. So let's talk about the results and specifically the implications of potentially studying lower doses of ipi. Dr. Jason Luke: I appreciate you raising that point. I think it's really important as we think about this dataset because this triplet regimen is not by any means the only version of a triplet that could be developed using these agents. So just to give the high-level numbers from the abstract, we see from these data that the overall response rate is described as 59% and 78%, a disease control rate with patients having an unreached link. So duration of response of unreached, and then the progression-free survival at about 5 months. So those are really interesting data. But as was alluded to, it's not totally clear to me that that's the best that we could do with this regimen.   Now, you alluded to this low-dose ipilimumab schedule at 1 mg/kg every 8 weeks, and it's really important to note that we have no benchmark for that regimen in melanoma oncology. And in fact, the one study that used that regimen, which was the adjuvant study of nivolumab and ipilimumab, known as CheckMate915, is in fact the only immune checkpoint inhibitor study in melanoma oncology that was actually negative. That study noted no benefit to adding ipilimumab at 1 mg/kg every 8 weeks on top of nivolumab, again, the adjuvant setting. So it's a little bit curious to then understand what it means in this study to have that amount of ipilimumab added to the rela-nivo backbone. And that manifests in a few different ways. We see the response rate here at 59%. Again, if you compare that just against the standard nivo + ipi dosing schedule, it's about the same. So is that really an advantage to having the triplet as compared to just doing standard nivo + ipi?   We do see that it manifests in a slightly lower rate of grade 3/4 immune-related adverse events, at 39%. That's a little bit lower than what we'd expect for standard nivo + ipi. But again, I think that that emphasizes to me the possibility that some efficacy was left on the table by using this very low dose ipilimumab regimen. I think that's really a concern. It's not clear to me that these triplet data really differentiate from what we'd expect with the already approved regimen of nivo + ipi. Therefore, it makes it difficult to think about how would we really want to move this regimen forward, or should there be more work done about dose and schedule to optimize how we might want to do this?  Dr. Diwakar Davar: As far as triplet therapy in the context of frontline metastatic melanoma, meaning triplet immune therapy, because there are at least several targeted therapy triplets that are FDA-approved, [but] not necessarily widely utilized. How would you summarize the future for triplet therapy? Do you think it's potentially attractive? Do you think it's very attractive with some caveats? Dr. Jason Luke: Well, I think it's attractive, and we have 3 independently active agents. And so I do think it's a priority for the field to try to figure out how we could optimize the therapy. We've had such a revolution in melanoma oncology, talking about 7.5-year median survival from CheckMate-067, but that still implies that 7.5 years, half the patients have passed away. There's more to do here. And so I do think it should be a priority to sort this out. I guess I would be cautious, though, about advancing this regimen directly to a phase 3 trial because it doesn't seem clear to me that this is optimized in terms of what the outcome could be. If we're willing to tolerate higher rates of toxicity from other dose schedules of nivo-ipi alone, then I think we should do a little bit more here to potentially explore the space that might be possible to increase that overall response rate a little more without getting into a completely exaggerated toxicity profile that would be unacceptable. So, I do think it's exciting, but there's possibly more to do before really think about going big time with this. Dr. Diwakar Davar: Great. So now we'll switch gears and move from frontline metastatic melanoma to the second line and beyond looking at a new agent and contextualizing the effects of that actually in the frontline settings. So Abstract 9505 describes the efficacy and safety of lifileucel, which is essentially autologous tumor-infiltrating lymphocyte cell therapies, also known as TIL, in combination with pembrolizumab in patients with ICI naive, so not necessarily pretreated, but ICI naive metastatic or unresectable melanoma. This is data from the IOV-COM-202 Cohort 1A oral abstract presented by Dr. Thomas and colleagues. In this abstract, Dr. Thomas and colleagues are presenting data from the 1A cohort, which is the phase 2 portion of the frontline trial that is evaluating autologous TIL with pembro in checkpoint inhibited naive metastatic melanoma.  By way of background, TIL is FDA approved on the basis of several cohorts from a phase 2 trial. The data has been presented multiple times now by Drs. Sarli, Chesney, and multiple colleagues of ours. And essentially autologous TIL, which is generated from a surgical procedure in which a patient undergoes a surgery to extract a tumor from which T cells are then grown after ex vivo expansion and rapid expansion protocol. The entire procedure was essentially pioneered by several colleagues at the NCI, primarily Dr. Steve Rosenberg, and this approach produces objective response rates of approximately 31% to 36%. And the most recent publication demonstrated that at median follow up of approximately 2 years, the median duration of response was not reached. The median OS was about 14 months and PFS was about 4 months or so. So, can you contextualize the results of the abstract in the frontline setting? And then we'll talk a little bit about where we think this is going to go. Dr. Jason Luke: So I think this is a timely study given the recent approval. And in the abstract presented here, we see an early data cut from the PD-1 naive study, as you alluded to. So here we had 22 patients and distributed across various states of advanced melanoma. Ten out of the 22 had M1C, but there also were smatterings of earlier M1A and M1B at 18.2% and 9.1%. So this is important, as we think who the treatment population is that's going to be optimized with a TIL procedure. The median sum of diameters, meaning how much tumor burden the patients have, was about 5.5cm, and I'll note that that's a relatively modest amount of tumor burden, albeit not that unusual for an early-stage trial. So of the patients that participated, 8 had BRAF mutations so that's 36%. That's not that high, but it's reasonable. And I think the important overlying number, the response rate so far in the study, with about 17 months of follow up, was 63.6%, and that includes 22% or 23% having complete response. So those are interesting data.  And another point that was made in the abstract, which we've all seen, is that responses to TIL, all of immunotherapy but especially TIL, do seem to mature over time, meaning they deepen over time. So it's possible the response rate could go up some extent as we watch this study advance. So I think these are exciting data on some level. Also, a 63.6% response rate sounds pretty impressive, but we do have to put that in the context of a double checkpoint blockade, which we just got done discussing, gives you almost a 60% response rate, 59% response rate. So then the question really is: Is it worth the amount of effort that we could go into generating a TIL product in a treatment naive patient, and put them through the lymphodepletion that is associated with TIL and the high dose interleukin 2 treatment that accompanies the reinfusion of the TIL, if you're going to get a response rate that's roughly the same as what you would get if you gave them off the shelf nivo plus ipilimumab?  At this point it's a little bit hard to know the answer to that question. I think it could be possible that the answer is yes, because we don't know exactly which populations or patients are most likely to benefit from each of these therapies. And if it could be teased out who's not going to benefit to nivo + ipi from the get-go, then of course, we would want to offer them a therapy that has that frontline potential, durable, long-term response. But I have to say, on a one-to-one with TIL therapy, you get a lot of toxicity initially with the treatment; with nivo + ipi on the back end, you get a fair amount of toxicity with the treatment. How are we going to judge those two things? And I think we probably need a larger dataset to really have a good handle on that.  So these are interesting early data, but it's not totally clear to me that even if this holds up all the way through the trial, and we're going to talk about the design of the registration trial here in a second, a 60% response rate on its own without further biomarker stratification is a little bit hard for me to see in clinical practice why we would want to do that, given we can already just go off the shelf and give checkpoint inhibitors. Dr. Diwakar Davar: So that brings us to TILVANCE-301. So TILVANCE is a phase 3 trial. It's a registration intent trial by our Iovance colleagues evaluating the pembro-TIL regimen versus pembrolizumab alone. So in this phase 3 trial, approximately 670 patients will be randomized to either arm A, which is lifileucel + pembro. And in this arm A, patients are going to be getting lifileucel with the tumor resection, non-myeloablative lymphoid depletion, the lifileucel and abbreviated course of high-dose IL-2, and thereafter, continued pembro for the study mandated duration versus arm B, where patients will be getting just pembrolizumab monotherapy per label. Arm B patients, per the design, may cross over to receive TIL monotherapy at the time of central-blinded, radiology-confirmed disease progression.   The study design otherwise is fairly routine and, per most of our registration trials these days, patients have actually been permitted to receive neoadjuvant and adjuvant therapy, including checkpoint inhibitors, as long as the receipt of the therapy was more than 6 months prior to the inclusion of the patient in that registration trial. The dual primary efficacy endpoints as stated are BICR-assessed objective response rate as well as PFS, and the key secondary endpoint is overall survival.   So Jason, what are your thoughts on the study design and potentially the regulatory implications, particularly given, one, the control arm of pembro monotherapy, and two, the role of TIL crossover to receive TIL monotherapy at the time of BICR mandated progression for arm B? Dr. Jason Luke: So this goes to a few points that we've touched on already in the discussion here. When we think about the primary endpoints for this study, with one of them being overall response rate, one has to assume that that's a given that they would get that. I feel like that's a low bar. And we go back to that cross-trial comparison. If their results end up being that the response rates are about 60%, I don't know that that differentiates necessarily from what's already available in the field with combination immune checkpoint blockade. For the purposes of the study that would mean it's a positive study, so I think that would probably be good. But again, the comparator to pembrolizumab monotherapy, I think some of us would argue, isn't really consistent with what we would do with a patient in our clinic. So it's not that it's bad per se, but I think there's going to be a whole lot of cross-trial comparison. So if the study is positive, that would be good for getting the drug available. It's still a bit hard though, based on the preliminary data that I've seen, to imagine how this would have uptake in terms of utilization as a frontline therapy.  You alluded to the crossover, and I think there, the assumption is that patients who get TIL therapy as a second line perhaps would have an attenuated benefit. But I'm not sure that's really true. It certainly looks from the data that we have, like the patients who benefit most from TIL are going to be those who didn't respond to anti PD-1 in the front line. So I'm not sure how much difference there's going to be between first- and second-line TIL therapy, but those data will kind of wait to be seen. So I think it's an important study. Of course, the accelerated approval of TIL as a later line therapy is dependent on this trial being positive. So there is some risk that if this trial ended up not being positive, that that could have regulatory implications on the utility or availability of TILs, a subsequent line therapy. But all of these, I guess we'll have to wait to see the results. We do hope for a positive trial here, although I think it'll be nuanced to sort of interpret those data given that pembrolizumab monotherapy control arm.  Dr. Diwakar Davar: Fantastic. So we've learned a lot about TIL, both its use in the second-line setting and this very exciting but potentially risky frontline trial that is ongoing at some centers in the United States and certainly a lot of ex-U.S. enrollment.   So we'll now pivot to a related product which actually belongs to a much larger class of agents that are antigen specific T-cell therapies in a variety of different formats. And that is Abstract 9507, which is the “Phase 1 safety and efficacy of IMC-F106C, a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM).” Now, in this abstract, Dr. Omid Hamid and colleagues reported the results of this phase 1 trial. As a disclosure, I'm an investigator and the last author on this manuscript. Jason, it would be important for our audience, for us to maybe firstly, outline the PRAME as a target, and then the ImmTAC as a platform prior to discussing these results. So let's start with the target PRAME, which I think is a target that you know well. So why don't you start with the target and we'll talk a little bit about that and then the platform? Dr. Jason Luke: Yeah, so I think for the audience, being aware of PRAME, or the Preferentially Expressed Antigen in Melanoma, is going to be quite important moving into the future. So PRAME as a therapeutic target is a cancer testis antigen that's overexpressed in tumor tissues. And of course the name has melanoma in it, but it's not uniquely present in melanoma. So the expression patterns of PRAME as a target are very high in melanoma. So in cutaneous disease, this is upwards of almost 100%, somewhere between 95% and 100%, in metastatic melanoma tissues. And PRAME has several different roles on a molecular level, although I don't think for our purposes here, it's so much important to be aware of them, but rather that this is a very highly expressed target, which then can make it attractive for using T cell receptor-based therapies. And so in the case we're talking about here on the ImmTAC platform, that's a CD3 PRAME×CD3 bispecific approach. But of course there are other approaches that can also be taken, such as TCR T cells that directly go after PRAME itself. Dr. Diwakar Davar: Let's now talk about the platform and how it differs from some of the other antigen targeting platforms that you have just alluded to. I think the Immtac platform is basically a fusion protein comprising engineered TCRs with a CD3 specific short chain variable fragment. And then the engineered TCR therefore binds antigens in an HLA dependent fashion. But you know quite a lot about some of these alternative platforms, and I think it'll be important to contextualize for the audience the difference between ImmTAC, which is a prototype drug that is already approved in the context of tebentafusp. But how does this differ from some of the other more nuanced platforms, such as the Immatics TCR or TCR platform and TScan TCRT nanoplasmonic platform.  Dr. Jason Luke: Right. So the ImmTAC platform as alluded to is already approved on the market with tebentafusp, which is the gp100-CD3 bispecific molecule. And the advantage of that approach is infusion off the shelf of a drug. The downside of it is that it is a weekly dosing strategy as it stands now. And there are some complicated disease kinetics associated with treatment response, which we'll come back to in the context of the PRAME bispecific. Those are, in contrast with T-cell receptor-transduced T cells, as an alternative strategy, which is a form of adopted cell transfer. So we just got done talking about TIL therapy, which of course, is trying to take lymphocytes out of the tumor and grow them up and then give them back. Here with TCR-transduced T cells, we're talking about taking leukopak from the blood and then using different transfection approaches to try to insert into the lymphocytes of the patient a T cell receptor that recognizes to a certain cancer antigen, in this case, PRAME.  So you alluded to a couple of different companies that have different platforms to do this. Immatics has a molecule called IMA 203, for which there have been data disclosed in the past year, again showing some very interesting responses in patients who have highly refractory melanoma. That process, though, again, does require lymphodepletion before you reinfuse the cells. Again, in contrast, the ImmTAC, which is an off the shelf revenue administer, there you have to make the product and then bring the patient back, lymphodeplete, and give the cells back. Immatics platform uses a viral transfection vector. The T scan approach that you alluded to before uses an approach of a mixed system on multiple HLA backgrounds to try to get past HLA-A*02:01 only, and in this case, uses a plasmid-based transfection syndrome that perhaps can be more broadly utilized given the lack of a lentiviral vector.   So this is a complicated area of technology that starts to get into immune engineering, and I think for the purposes of this discussion, we don't want to belabor it. But both of these technologies, talking about the CD3 bispecific with the off the shelf aspect of it and the adoptive cell transfer, each of these using a T cell receptor-based therapy to try to go after PRAME, I think have very high upsides, and I think we'll initially see it in melanoma over the next year or so. But this is likely to be relevant to multiple tumor types beyond melanoma.  Dr. Diwakar Davar: So let's discuss the results of this phase 1 trial. IMC-F106C, like all other ImmTAC, is administered intravenously and does require step-up dosing. You alluded to the fact that the tebentafusp was approved, and it's one of those drugs that is fortunately otherwise administered weekly, which can be difficult for the patient and requires at least the patient spend the first 3 doses overnight under some kind of monitoring, whether it's in the hospital or extended outpatient monitoring, for at least 23 hours. The efficacy of this agent and this platform appears to be surprising in that you tend to see a relatively low RECIST response rate. We'll have you comment a little bit on why that is the case and what may be the role of ctDNA, as opposed to conventional RECIST in assessing response.   At least in this trial, they mandated pre-testing, but did not require it for study enrollment. And pre-positivity was defined using immunohistochemistry with a relatively low H-score of 1%. And the molecular response definition was a 0.5 log or a 68% ctDNA reduction just prior to the first imaging assessment. So how do you contextualize the results? But maybe before you talk a little bit about the results, the ctDNA aspect, that was a recent publication by Drs. Rich Carvajal, Alex Shoushtari, and I think you are also involved in that.  Dr. Jason Luke: So, I think an interesting observation around tebentafusp has been that ctDNA may be a better predictor of long-term outcomes. And how you define ctDNA response is still something that the field is grappling with, albeit that I think is going to be an important consideration as we think about these novel therapies, these ImmTACs and other CD3 engagers moving into the future. But for the purposes of the abstract here, we see that in the population of patients treated, there were 46 patients with cutaneous melanoma. The majority got monotherapy with IMC-F106C, and that's the PRAME bispecific. So 40 patients that got monotherapy and six who got a combination with checkpoint inhibitor. All these patients had prior treatment with immunotherapy, and most of them had PD-1 and CTLA-4 antibody with a small spanner that also had BRAF inhibitors.  In terms of that PRAME testing that you alluded to, based on the immunohistochemistry H-score greater than 1%, 35 out of 40 patients were positive, so they defined 5 as negative. And we could come back if we have time, but there are other ways to do PRAME testing as well that I think may become unique for different agents, maybe an important biomarker. In the data, 31 out of the 46 patients were RECIST evaluable. The outcomes of those patients were to note that the response rate was 13%, which was four partial responses. But 35% of patients had tumor regression with a disease control rate at 65%. It was clear that there was an enrichment by PRAME positivity for both progression free and overall survival. So those patients who had obvious positivity essentially had a doubling of the PFS and more than the doubling of the OS, 2.1 to 4.1 months for TFS and landmark OS, 40% to 94%. So I think these are quite intriguing data.  It does suggest that for the vast majority of patients, we do see some induction of the antitumor effect, albeit that RECIST might undercall the effect. And so this may become another area where the ctDNA monitoring might be able to help us to understand who is likely to have really long-term benefit from this therapy. And given the number of emerging treatments that we have for melanoma, we might be able to really focus in on that group of patients in terms of optimizing how we would use this drug moving into the future. Dr. Diwakar Davar: So you talked about a response rate, and at first glance, this response rate is a little underwhelming. We're talking about 4 out of 31 RECIST evaluable patients, 13%. So it's in the double digits, but barely. So how enthusiastic are you about the results? How does it contrast with at least the publicly known data from other brain targeting approaches, such as the IMA203 agent, understanding that while they may be all targeting somewhat the same target, they are actually extraordinarily different platforms. One's off the shelf, one's highly customized. How do you contextualize the results? How would it contrast with other cellular approaches?  Dr. Jason Luke: I think it's important, again, to emphasize the point you made, which is that they're very different kinds of treatments. So even though they both target PRAME, they're going to be differently useful, and they could be quite useful for different groups of patients. And so here we see that there is a subfraction of patients who are deriving long-term benefit. And we commonly have an argument in our field about, is overall response rate really a useful monitor that describes a patient-centric outcome? While, of course, patients like to know their tumors are shrinking, what they want the most is for the tumors not to get worse and for them not to pass away from cancer. So I think I'm enthusiastic about these results, but emphasizing the point that we need to better understand who is going to benefit the most from this CD3 bispecific PRAME approach and how we're going to be able to harness that into long term benefit for patients because there's no doubt that an off the shelf therapy has a high degree of value relative to adoptive cell transfer, which sort of requires a big wind up.   So when you say, what does it contrast with? Well, the data for IMA203 has shown more than a 50% response rate in patients with more than 5 lines of therapy for metastatic disease. That really looks quite exciting. And several of those patients are now out for quite an extended period, meaning 2 years or more given only a single dose of IMA203. But again, the caveat being, you have to make the cell product for the patient, and that takes time. You lymphodeplete the patient, not all patients can tolerate that in the refractory disease setting, and then they have to be able to tolerate the reinfusion of the cells. And so this drug, IMC-F106C, looks very promising. Moving into the earlier phase trial that we'll talk about, I think the TCR T cell program has a lot of upsides for patients, especially with refractory disease. And so I think these two different approaches are really on parallel tracks. They both target PRAME, but I don't think they necessarily need to be compared one to one, as if they're going to go head-to-head with each other. Dr. Diwakar Davar: So now we'll talk a little bit about the frontline setting, because on the basis of some of these results, Immunocore is now exploring IMC-F106C frontline melanoma. This trial is actually being presented as a trial in progress at this meeting by Georgina Long and colleagues. Some of us are co-authors in that abstract. And in this study, HLA-A*02:01 positive patients with advanced unresectable melanoma will be randomized one to one to the combination of IMC-F106C, which actually, I think after this meeting will be known as bre-ni in combination with nivolumab versus nivolumab regimens, which will either be nivo or nivo-rela, investigators choice and likely dependent on region. So what do you think of the challenge of this trial? We talked about some of the challenges of the TILVANCE trial earlier. But what is going to be the challenge of this trial and in this setting, particularly given the response rates that we've seen so far? Dr. Jason Luke: Yeah, so, similar to comments we had before, thinking about what the optimal control arm is for a study like this is difficult, and so that'll be important as we think about interpreting the results. One has to assume for the purpose of this conversation that it is a positive trial, and that adding the PRAME bispecific theory does lead to an improvement in progression free survival relative to those in checkpoint alone approaches. And I think the magnitude of that difference is going to be of some relevance. And then I think importantly, also figure out who needs this treatment and who's going to benefit long term are going to be really important considerations.  We alluded to how this drug requires an intensive dosing period at the get go, and so telling patients that they need to come in weekly or bi-weekly initially for some number of weeks before they switch to a longer-term intermittent regimen, that comes with real world considerations for patients, their families, their finances, etc. So the benefit has to be clearly obvious that makes it worthwhile doing that, again, because a default could be giving drugs that we've had for 10 years with the nivolumab and ipilimumab. So there's going to be a lot of cross-trial comparison that is going to necessarily have to take place here to think about what these results really mean in the context of other available therapies.  I think the study is reasonable to do. I think this is a very active agent. There's no doubt there's a subset of patients who seem to benefit a lot from it. And I would just emphasize the point that that's probably going to be the most important thing to really drill down on is under the assumption there's a positive trial, we need to know who those people are so we could optimize giving this kind of a treatment to them. Dr. Diwakar Davar: I guess one important point to underscore what Jason said about potential predictive biomarkers, I think as part of the presentation, Dr. Hamid and colleagues will be talking about a candidate predictive biomarker of this agent, which is potentially class specific and not necessarily agent specific of a T cell signature that potentially could define patients who are more likely to benefit from this agent.  So, Jason, as always, thank you for sharing your expertise and insights with the team today. We certainly look forward to catching up again for our wrap up episode after the annual meeting where we'll talk about some of the data that we could not talk about, particularly the late breaking abstracts and other key advances that will shape the future of, certainly the field of immunotherapy and melanoma, potentially the field of cancer immunotherapy at large. Dr. Jason Luke: Oh, thanks very much for the opportunity. Dr. Diwakar Davar: And thank you to our listeners today. You'll find the links to the abstracts discussed today in the transcript of this episode. And finally, if you value the insights that you hear on this podcast, please take a moment to rate, review, and subscribe wherever you get your podcast. So thank you, and we'll see you soon.   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 today's speakers:   Dr. Diwakar Davar   @diwakardavar   Dr. Jason Luke   @jasonlukemd      Follow ASCO on social media:    @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn      Disclosures:       Dr. Diwakar Davar:     Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences    Consulting or Advisory Role: Instil Bio, Vedanta Biosciences    Consulting or Advisory Role (Immediate family member): Shionogi    Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences    Research Funding (Inst.): Zucero Therapeutics    Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy       Dr. Jason Luke:    Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX    Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine    Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure    Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)    Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio      

Immunotherapy and cellular therapeutics represent the future of cancer care. These biological therapies involve manipulating the body's cells to reactivate and strengthen their abilities to attack cancer cells. Immunotherapy is a precision cancer treatment and is considered the future of cancer treatment by the National Cancer Institute. Other, more traditional, types of cancer treatment include surgery, chemotherapy and radiation. Immunotherapy is a type of treatment for a variety of cancers that harnesses one's own immune system to fight his or her specific cancer cells. Tumor infiltrating lymphocyte, or TIL therapy, is a type of immunotherapy and part of the body's natural response to cancer. TIL cells are naturally occurring immune cells that are on constant surveillance to recognize, attack and kill cancer cells. Recently, the Food and Drug Administration approved lifileucel (Amtagvi), the first treatment for cancer that uses TILs. On this episode, Dr. Roy Jensen, vice chancellor and director of KU Cancer Center speaks with Dr. Muhammad Mushtaq, associate professor of hematologic malignancies and cellular therapeutics at the University of Kansas Medical Center, about this exciting topic. Links from this Episode: Learn more about TIL therapy via the National Cancer Institute Read the frequently asked questions about immunotherapy on the KU Cancer Center website Learn about Dr. Mushtaq Read the FDA's announcement of approval for TIL therapy Learn more about cancer clinical trials at KU Cancer Center After listening to this episode, we invite YOU to be a part of the podcast! We want to hear your thoughts on the conversations we have here, topics you'd like to learn more about and any questions you may have for our guests. Call our Bench to Bedside hotline at 913-588-3880 and leave us a voicemail, or you can email your comments and questions to benchtobedside@kumc.edu. Your comments may be shared on a future episode!

In this episode, Michael and Josh welcome a very special guest: Michael's Labrador Beans. Beans is a world-renowned expert in eating snacks, but unfortunately, had very little to offer on their topic today: the treatment of progressive or recurrent cutaneous melanoma with primary and secondary resistance to immunotherapy. So, unfortunately, the discussion was left to your regular hosts. For approximately 50% of patients, this is fortunately not a question they need to worry about, as immunotherapy and BRAF/MEK inhibitors remain effective treatments. However, that still leaves half of all patients facing an uncertain future, as treatment beyond these two agents remains uncertain. Josh and Michael examine two studies that may shine a light in this dark corner of oncology: LEAP-004, a single-arm study of lenvatinib + pembrolizumab, and an article published in the New England Journal of Medicine examining the use of tumour-infiltrating lymphocytes (TILs) as a novel weapon against immunotherapy-resistant melanoma. Links to studies discussed in this episode (subscription may be required):LEAP-004: https://ascopubs.org/doi/full/10.1200/JCO.22.00221Rohaan et al: https://www.nejm.org/doi/full/10.1056/NEJMoa2210233For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

Topics covered in this episode: zoxide Smart CLIs with Typer Python recommended officially by the US Government Textual tutorials at Mouse vs Python Extras Joke Watch on YouTube About the show Sponsored by ScoutAPM: pythonbytes.fm/scout Connect with the hosts Michael: @mkennedy@fosstodon.org Brian: @brianokken@fosstodon.org Show: @pythonbytes@fosstodon.org Join us on YouTube at pythonbytes.fm/live to be part of the audience. Usually Tuesdays at 11am PT. Older video versions available there too. Michael #1: zoxide zoxide is a smarter cd command, inspired by z and autojump. It remembers which directories you use most frequently, so you can "jump" to them in just a few keystrokes. zoxide works on all major shells and platforms. Brian #2: Smart CLIs with Typer Rahul Pai Lots of TILs here, even though I've been using Typer for years. Examples of Auto-detection of arguments and types based on type hints Help text is a smidge clunkier Prompting for missing arguments Defaulting to an enviromental variable for missing args Print help if no args given Explicit app and subcommands with a comparison to argparse Reusable commands with result_callback Several topics covered in comparison with argparse See also Testing argparse Applications Michael #3: Python recommended officially by the US Government The US government explicitly recommends memory safe languages. Python is one of them The comparison to big tech by Samuel is interesting Brian #4: Textual tutorials at Mouse vs Python Mike Driscoll Most recently Creating a Modal Dialog For Your TUIs in Textual Textualize already has some pretty great documentation at textual.textualize.io But it's cool to see some different tutorials on it. Extras Brian: Is UV the FUTURE of Python PACKAGING?

Whilst down in Australia for the Tour Down Under and the Deakin University Road Race, our very own Matilda Raynolds sat down with Heidi Franz, rider for Lifeplus Wahoo, for a chat. They discussed Heidi's last couple of years in the sport, how cycling should differ from gymnastics, popular Aussie phrases you should know, and much more.We hope you enjoy this bonus Wheel Talk episode, and Abby, Loren and Gracie will be back later this week to chat about Setmana Valenciana and the upcoming Omloop Het Nieuwsblad.

Whilst down in Australia for the Tour Down Under and the Deakin University Road Race, our very own Matilda Raynolds sat down with Heidi Franz, rider for Lifeplus Wahoo, for a chat. They discussed Heidi's last couple of years in the sport, how cycling should differ from gymnastics, popular Aussie phrases you should know, and much more.We hope you enjoy this bonus Wheel Talk episode, and Abby, Loren and Gracie will be back later this week to chat about Setmana Valenciana and the upcoming Omloop Het Nieuwsblad.

Matilda Raynolds, or Tils as she's known to the members of the Wheel Talk Podcast Discord group (available to members of Escape Collective), joins Gracie and Abby on the podcast this week with some insider information on the Tour Down Under and some thoughts on the upcoming Cadel Evans Great Ocean Road Race.And, as promised, here is a link to G Flips's cover of Cruel Summer by Taylor Swift.

Matilda Raynolds, or Tils as she's known to the members of the Wheel Talk Podcast Discord group (available to members of Escape Collective), joins Gracie and Abby on the podcast this week with some insider information on the Tour Down Under and some thoughts on the upcoming Cadel Evans Great Ocean Road Race.And, as promised, here is a link to G Flips's cover of Cruel Summer by Taylor Swift.

Every so often, an area of medical oncology has so many interesting presentations at a seminal conference that it becomes impossible to leave them out. At such times, Josh and Michael merely shrug their shoulders and say "why don't we do all of them." ESMO 2023 is one such instance. Despite their best efforts, our intrepid duo were unable to narrow down their presentation of early breast cancer highlights to one episode, so they are going to do two (for the price of one).Articles discussed in this episode. Subscription may be requiredPrognostic and predictive impact of estrogen/progesterone receptor (ER/PR), and Ki-67 expression: An exploratory analysis from the monarchE trial in patients with high-risk, HR+, HER2-, early breast cancer (EBC). https://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/637956Association of tumor-infiltrating lymphocytes (TILs) with recurrence score (RS) in patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (BC): A translational analysis of four prospective multicentric studieshttps://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/637959Omission of breast surgery after neoadjuvant systemic therapy for invasive cancer: Three-year preplanned primary-endpoint on a phase II multicentre prospective trial https://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/637966For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

Quadruple Crowner (yes, you read that right!) Wesley "Megaman" Tils takes a brief respite from the trail to share some of the wildest thru hiking stories you have ever heard. Get comfortable and make sure you are either in a seated position or you have a good hold on your trekking poles as Megaman takes us through a rollicking tour of Type II Fun. During the chat, Megaman discusses how deprivation is the spice of life, imposter syndrome, Viking sword fighting, ego death, Bear Magnet, Hayduke Dies, Double Dip, the power of McDonald's toilet paper, finding joy where you can, overcoming an addiction to street fighting, the difference between Blue Springs and Independence kids, and the peculiar skill sets needed to hike the Fourth Crown Trail. Think you know what's going to happen in this one? Think again. You have no idea. Learn more about your ad choices. Visit megaphone.fm/adchoices

Welcome to the latest episode of The Hormone Prescription Podcast, hosted by Dr. Kyrin Dunston! In this informative and engaging episode, Dr. Kyrin Dunston talks to renowned guest Faraz Khan about reversing hair loss and regaining hair vitality at midlife. Faraz is an expert in the field of hair loss in women, founder of FullyVital, and host of the Anti-Aging Hacks Podcast.    Faraz's innovative thinking and empathetic approach towards hair health have made him a highly sought-after voice in the field. In this conversation, he delves into the molecular level of how testosterone and DHT, specifically around menopause, can affect hair follicle health, ultimately contributing to a broader understanding of hair loss patterns in women. Some highlights of the episode include: - Understanding the role of testosterone and DHT in hair health - Strategies to reverse hair loss during midlife - The complex interplay of hormones, diet, and lifestyle that impact hair health - Faraz's unique perspective and empathetic approach to hair health    It's an episode that you won't want to miss if you want to understand the root cause of hair loss and learn how to regain your hair's vitality at midlife. So, don't miss out on the valuable insights Faraz shares and the helpful knowledge he imparts.    Make sure to subscribe to The Hormone Prescription Podcast to stay updated on all the latest episodes and be a part of our community of listeners working towards better hormonal health. If you enjoyed this episode, please consider leaving us a review!** Your positive feedback helps others discover our podcast and benefit from the insightful conversations we have with experts like Faraz Khan. Together, we can help more people gain control of their hormonal health and enjoy fuller, more vital lives.   Speaker 1 (00:00): Our bodies are magical and they know exactly how to heal. We just have to give them time so they can kickstart the process. Stay tuned to learn how to heal your hair and reverse hair loss at midlife. Speaker 2 (00:15): So the big question is, how do women over 40 like us, keep weight off, have great energy, balance our hormones and our moods, feel sexy and confident, and master midlife? If you're like most of us, you are not getting the answers you need and remain confused and pretty hopeless to ever feel like yourself again. As an O B G Y N, I had to discover for myself the truth about what creates a rock solid metabolism, lasting weight loss, and supercharged energy after 40, in order to lose a hundred pounds and fix my fatigue, now I'm on a mission. This podcast is designed to share the natural tools you need for impactful results and to give you clarity on the answers to your midlife metabolism challenges. Join me for tangible, natural strategies to crush the hormone imbalances you are facing and help you get unstuck from the sidelines of life. My name is Dr. Kyrin Dunston. Welcome to the Hormone Prescription Podcast. Speaker 1 (01:08): Hi everybody. Welcome back to another episode of The Hormone Prescription with Dr. Kyrin. Thank you so much for joining me today as we dive into reversing hair loss at midlife. How to make it fully vital with my guest today, Faraz Khan. Hair loss is a huge problem for women at midlife and beyond, and it's not only a cosmetic issue. Sure, our identity is very tied up in our hair and we want our hair to look its best 'cause it is tied to our identity, and we feel our best when our hair looks good, but it's about so much more. Your hair is part of the trilogy of what I call the canary in the coal mine, and that's hair, skin, and nails. These three aspects of your body will out picture what's going on inside. So if your health is not optimized inside, if you're in hormonal poverty, for instance, which occurs for most women after 40, then your hair is not going to be as thick as it should, as long as it should, as vital as it should, as healthy as it should, and your identity is gonna suffer as a result. Speaker 1 (02:22): So just like erectile dysfunction in men is very often a harbinger of cardiac issues, right? It's not just about erectile dysfunction in women. Hair problems are not just about the hair, it's about your metabolism, your physiology, your biochemistry, what's happening inside the body. And so the hair is one of the places that will out picture this. So I really want you to pay attention. If you've got hair problems, it could be a sign of something deeper. And we're gonna dive in today into what are the deeper causes of hair loss. Yes, it's about hormones, but it's not only about hormones. So there are other dysfunctions and disruptions that can be going on that you need to pay attention to. And we're gonna dive into that and we're gonna talk about the quote that Farad shared that I shared with you and the teaser. And we're gonna give you some solutions. Speaker 1 (03:13): Best of all, what do you do about it? There's testing that can be done, there are treatments that are available to you. There's further diagnosis, more than your doctors and dermatologist's office. There are specialists in this. So we're gonna dive into all of this and really give you a good understanding. First, I'll tell you a little bit about for us Khan, and then we'll get started. He's the founder of Fully Vital and the host of the Anti-Aging Hacks podcast. He's a leading expert in the field of hair loss in women and has dedicated his career to understanding the complex interplay of hormones, diet, and lifestyle on hair health. His work focuses on the molecular level of how testosterone and D H T affect hair follicles, as well as the other factors that go into hair loss. He has innovative thinking and an empathetic approach. This has made him a sought after voice in the field. He's helped countless individuals regain confidence and control over their hair health. His insights into hormonal imbalances, particularly around menopause, perimenopause, hormonal poverty, have contributed to a broader understanding of hair loss patterns in women. So please help me welcome Rascon to the show. Thank Speaker 3 (04:23): You so much, Dr. Kyron. I'm a big fan and I'm glad to be here. Yeah, Speaker 1 (04:26): I'm super excited to talk about hair loss. Back over a decade ago when I weighed 243 pounds and had fibromyalgia and chronic fatigue and all the health problems that I had, and I looked and felt 20 years older than I was, hair loss was a huge component of my dysfunction. I would wash my hair and it would look like there was a small dog in the drain. It would just come out. It was diffuse hair loss. I didn't have any bald patches, and it wasn't growing like it should. It was dry and brittle, it was falling out. And of course, all that reversed when I did all the things that we're gonna talk about. But it's near and dear to my heart. I, I don't think that a lot of women understand something that you said to me before we started recording, that really, hair loss is not just a cosmetic issue. Speaker 1 (05:21): It's about so much more. And it, it really is an indicator that your longevity is being affected and your overall health is being affected. So if you're listening, I really want you to pay attention if you're having hair loss because it's a sign that something bigger is going on. I used to call it, I still call it the canary in the coal mine, hair, skin and nails. If you're having a problem with your hair, skin and nails, these are the canary in the coal mine. You just chalk it up as a cosmetic issue. You might not even address it, but I say it's kind of like erectile dysfunction in men could be an indicator of cardiac disease that if you've got this as a woman, you really need to pay attention. Right? Speaker 3 (06:05): Yeah, totally. It's very important. Thank you for bringing that up. And I'm a big fan of your message as well. What happens is that as women, especially after the age of 35, hormones start changing. And Dr. Karen, you talk about, you know, the other things that come with that. Hormonal changes, especially as women get closer to menopause and all of those factors can play a part in hair thinning and hair loss. And it's very, very tied to the health of your overall system, the stress levels. Because when you're, when you're losing hair, your stress levels go up, and when your stress levels go up, you lose more hair. So that's also challenging. You've gotta take that into consideration. In addition, women tell us that they stop going out, they start, they stop communicating as much. And so this leads to self isolating, which again, is very bad for longevity and very bad for a long life and a healthy life. Speaker 1 (06:53): Yeah, it's so true. So let's dive into what causes it. And I know there are a lot of women out there with hair loss. They're looking for the one quick fix. What's the one thing that I have to do? You know, it's really how we're trained to look at our health problems. I have a symptom. How do I fix that symptom when I fix that symptom? We claim victory, we think we're done. But what I wanna encourage everybody listening to understand is that symptoms are not the problem. They are the sign post, post pointing to the problem, and it's incumbent upon us to investigate, to figure out the cause. And usually there isn't one cause of a symptom. It's usually multifactorial. And I think this is no better illustrated than with hair loss. So let's dive into the factors that go into contributing to hair loss. Totally. Speaker 3 (07:45): And if I may, let me explain the hair cycle really, really quickly. Yeah. Speaker 1 (07:49): So Speaker 3 (07:49): There's context behind everything we're talking about in this interview. The hair cycle has three different distinct phases. The first one is the growth phase or the antigen phase that it's called. About 85 to 90% of your hair is in the growth phase at a particular time, which is why there's so much hair in your head. And then there's the second phase, which is very, very short. It's about 10 days, it's called kagen. That's just a transition phase from the growth phase to the third phase, which is called telogen, which is where your hair follicle is just resting for two to three months. And in those two to three months, it'll fall out at some point. And so at this, in this stage, it's not growing at all. And sometimes the hair may not grow back out of the stage back into the growth phase. So I'll come back to that in a second. Speaker 3 (08:32): So what can we do in terms of goals? The, there's three goals that we have for hair follicles, especially as we get after, get over the age of 35 or 40. Number one, you want to keep the hair follicle in the hair growth phase as much as possible. And there's ways to do that because the longer it's in the hair growth phase, the longer it's gonna grow and the thicker your hair is gonna gonna look. Number two, we wanna make sure your hair is healthy, it's thick, the scalp is healthy so that there's a very good environment for this to keep growing. And then thirdly, what we wanna do is if your hair follicle does go into the shedding or the transition phase, which normally they will do after three to seven years of growing, then we wanna make sure all of those hair follicles are able to grow back and a bunch of them don't decide not to come back, which will lead to a much thinner looking scalp, which is very bad. Speaker 3 (09:23): So those are the three phases that we talk about. Now when it comes back to the question that you asked me is what are the reasons for hair thinning? The number one reason is something that you talk about Dr. Kyron all the time is due to hormones. So again, after the age of 35, and especially after the age of 40, estrogen and progesterone in women start to fall. And this causes a relative imbalance with testosterone. And this testosterone converts to dihydrotestosterone or D H t and d h t goes to your hair follicles and it starts to shrink them, makes them smaller and smaller and starve them. So your hair goes from nice thick hair to a wisser and wisser and wisser hair until it can't even grow anymore. So that's what it does. The other thing, d h t does that, it keeps your hair in the resting phase for a much longer period. Speaker 3 (10:11): So it appears that you have less hair on your scalp. So both of those are bad, but D H T can also prevent your hair from growing back out after the hair cycle is done. So we wanna be very careful with, especially this one, because it's a progressive condition and if you don't address it, it will keep going. Just like you see with men. The same thing happens to men, but happens to younger men 'cause they have high testosterone levels in their late teens, early twenties. And so testosterone is converting to D H T, which is causing progressive thinning of the hair follicle. And eventually for men there's baldness. But luckily for women it's more diffused. It's not completely gone from every single area. But of course this causes a lot of anxiety and shame in women. So that's the number one reason. Speaker 1 (10:54): Yeah. And do you wanna talk a little bit about the different patterns of hair loss that women can experience and what that might tell you, whether it's diffuse or you could have male pattern or female pat pattern. Talk a little bit about that. Totally Speaker 3 (11:07): Love that. So the number one reason, like I said, is due to hormones or D H D. And that directly corresponds or correlates to what is known as female pattern hair loss or androgenetic alopecia. It's the same as male, male pattern hair loss. 'cause The hormone behind it is the same. And so what happens is women will experience hair loss right in their crowns. Their Christmas or their tree, or their part, I should say, is gonna get wider and wider and wider. And they'll notice it first over there, but they can also see loss on the temples or in the front as well. And for men, again, same thing happens because it starts in the crown or in the front or the temples. And for men it completely meets in the middle and it's all of it's gone. But for women, thankfully, they don't lose all their hair, but they will notice it first in the part area. Speaker 3 (11:53): So that is the female pattern. Hair loss. The other way to tell is I had a client call me or a customer call me and say, Hey, I don't know what type of hair loss I have. And I asked her to just do a simple exercise in the shower. So next time you're washing your hair to take a few hair strands that you have in your hand, because of course we all lose hair in the shower, especially when we're washing it. And then stick 'em on the TILs. And when you see a difference, when you see some hairs that are thicker and some hairs that are thinner, this is a telltale sign that this is hormonal or female pattern hair loss. And that D h C is causing your hair to thin progressively. So that's number one. This is the most common hair loss pattern in women. Speaker 3 (12:31): The next is called diffuse hair loss. And this happens all over the scalp, even in the back areas, which are pretty much immune to the hormonal aspects. So hair above the ears and hair on the back of your scalp is pretty immune to hormonal imbalances, which is why men, you see them, they lose the top of their scalp, but not the sides in the back, similar for women. But in the diffuse hair loss, what happens is that you lose hair everywhere, all over your scalp. And this is typically the causes are multifold for this, but it could be because of a nutritional deficiency. This could be because of chronic ongoing stress. This could be due to a big stressor that has happened in your life, like the virus or giving birth or you know, even moving to a different city or a breakup, divorce, for example, psychological or physical stressor, a big one. Speaker 3 (13:23): Then there's a medications that you might be taking that can cause hair thinning. Also, there's thyroid, especially low thyroid conditions, they seem to be becoming a little bit more common in the women as opposed to men. And so a lot of these factors can cause diffuse hair thinning. And then lastly, there's the, this type of hair thinning or hair loss, which is very rare, but it's autoimmune related, where you will see, you know, complete loss of hair, you'll see shiny bald patches in your scalp, that's an autoimmune condition. Anywhere from two to 5% of women will get that. So will experience that at some point in their life. And typically that's managed by going to a dermatologist and getting either steroid shots or something else to kind of calm down the immune system. Speaker 1 (14:09): Yes, thank you for going through that. You know, I remembered a patient as you were talking who actually had different bald spots on her head and ends up she had a rain worm infection, in her scalp. Yeah. Which is fungal, which is very unusual, but then it was causing the hair loss. And then of course when she treated the rain worm, the hair grew back, it wasn't a problem. Mm-Hmm. And I know that you mentioned also that you thank your mother for did you, were you thanking her for your baldness or tell me about your mother's involvement and you, your interest in, in hair. Speaker 3 (14:45): Totally. What a great question. So I, this, this is going back to me in college. I was a soccer athlete. I thought I was, you know, I was the man and I was pretty confident at that time. But one day in the shower I was washing my hair and I looked down on my hands and they're full of my beautiful hair. And my stress levels went from a four to an 11 in that moment. I'll never forget that moment. And so I started seeking help, but I also started asking the right questions of where is this coming from and how do I fight this? And so I looked through my dad's, you know, the, my dad's side of the family, and I said, all of them have gorgeous hair. My grandfather had more hair than me at the age of 90. So I go, that's not the problem. Speaker 3 (15:25): What about my mom's side? And all three uncles, my mom's brothers, all of them were balding or bald. And I go, oh my God, this is coming from my mother's side of the family. I'm screwed. And so that's what started off as a, what I thought was a genetic condition that was coming from my parents. And it turns out that that's a big reason for Hairing as well. And it come, it can come from both sides. So my mother also, over the years, while I was doing nothing about it, trying to solve my own hair loss, kept complaining that her part was getting wider. She was seeing more and more hair loss. And interestingly, right now she's visiting me, my parents are. And so every three or four days were microneedling her scalp and we're putting all the serums and we're trying to help her grow back her hair as well. So it, the reason I went down this path is not only to solve this for myself, but also help my mother and see what I can do for her . Speaker 1 (16:18): Yeah. And you know, she's lucky to have your help, but it brings me to a larger philosophical question about why are we so attached emotionally to our hair? Speaker 3 (16:30): Yeah. This goes back thousands of years, Dr. Karin. It's like, at least for women, it is their identity. And it is so I guess the media kind of celebrates big hair. If you see Marilyn Monroe back in the sixties or whatever, it was like big hair, right? Barbie dolls, big hair. It's just all over the media for generations and for thousands and thousands of years across cultures, Cleopatra beautiful, gorgeous hair. And so it's just ingrained in her culture that that is a woman's power. It's her identity. And for men, it's not the case because men, unfortunately, most of us experience hair thinning starting in our twenties and beyond. And so we just kind of lose that, lose the crown. And so it's not so, so much a part of our identity as much as it's for women. Mm-Hmm. . Speaker 1 (17:16): Yeah, I, I think I've read that for women it's actually a sign of fertility. So the sexual kind of appeal of women often historically, has come from signs of good fertility, like wide hips, long thick hair. And it, these are really signs of vitality. And so I think it gets back to what we were talking about earlier, that hair loss is, it should be like a level three alarm in your mind when you have it. Because it's not just, oh, I'm afraid that I'm not going to look the way that I want to look. It's, oh my God, what is happening inside my body that's so off that my hair is falling off? Because that's affecting your heart and contributing to heart disease. It's affecting your brain and contributing to potential future dementia, affecting your bones, and contributing to future osteoporosis. It's affecting every cell and every system in your body, not just your hair. Mm-Hmm. So see this as a red alarm. So we talked a little bit about hormones. Yes. We talked about the sex hormones and you mentioned stress. What about cortisol? ? Speaker 3 (18:29): Yeah, huge, huge part. Cortisol has been known to shorten the hair cycles. We talked about trying to keep your hair in the growth phase for as long as possible. So hair typically grows anywhere from two to seven years. And we want it to be on the side of the seven years as much as possible. 'cause A lot of women actually call in and they say, I can't grow any hair, I can't or I can't grow longer hair. And so this is a common complaint that we get, especially from women over 40 years. How do I grow my hair longer? Well, hair's the thing, your hair doesn't stop growing every day. Your body's growing 0.3 millimeters off your hair, every single hair. So it's, your body's doing its job, it's just that the hair is falling out, which is why you can't grow past a certain stage. Speaker 3 (19:16): And so the, the best thing we can do is to keep the hair in the hair growth phase as long as possible. Now, stress unfortunately shortens the hair growth phase from seven years to five, to even three, which means you're not gonna be able to grow long tresses like you want to. And so there's two types of stresses here. And I kind of briefly alluded to this, but I wanna come back to this. Number one is the big, big stressor, which could be, you know, a lot of my friends have gotten the virus and they experienced a huge shedding and we're talking 30 to 40 to 50% of their hair coming out. And they thought that they were gonna have to shave their head off. They were looking at wigs and luckily they were able to save their hair, all of them. So that's one. Speaker 3 (20:00): But it can also happen from, as a result of surgery, as a result of a breakup, as a result of a divorce or anything that's physical or you know, psychological. So those are big stressors. We wanna be very careful. And typically the big shed comes after the big stressor about two to three months after. So it's very hard for you to kind of correlate to what's causing this. But just know that if you're losing handfuls of hair every single day, it's because something happened two or three months back and there are strategies for you to make sure all of that hair comes back. Which goes back to my earlier point. If you are transitioning, you wanna make sure every single hair comes back. The other reason that stress kind of plays a part in this is if you have chronic ongoing stress. So my friend Ashley called me from LA and she goes, I'm losing a bunch of hair. Speaker 3 (20:44): And I said, so what's going on? She goes, well, my coworker left a few months ago and I'm having to cover for her. I'm having to do two jobs. So she's stressed out for the past four or five months and as a result, her hair cycle is shortening and she's losing a lot of hair. And so what we wanna do is balance the cortisol levels, balance the stress levels to ensure that we have the best possible hair growth. But also what cortisol will do is it will pull all of your resources towards your vital organs. 'cause Your body says, okay, what is expendable? Hair, nails? I can expend all those and still live. I have to protect the organism. And we are under big dur, we're under big stress. So let's bring all the blood flow, all the nutrients, let's repu redistribute them to the vital organs as opposed to the hair follicles, which happen to be furthest from your heart, vertically speaking. So your heart has to work even harder to pump that blood up. And the other thing that cortisol will do is it will shrink your blood vessels so your blood can't go as fast or as far and considering that has to go all the way to the top of your scalp. It's very important to have healthy levels of cortisol or balance them and to make sure your circulation is good as well. Speaker 1 (21:51): And so many women these days are under chronic stress constantly. They've got aging parents they have to care for, they have children, they have partners, they have jobs. And it's this constant, constant stress. So if you're listening and you haven't done your salivary cortisol test, you need to do it and then you need to address it. And you may need to change some things in your life, but stress can be not only coming from lifestyle and psychosocial interactions and situations, it can be coming from inside the body like toxicity and inflammation. And that can affect care growth as well. Right? Speaker 3 (22:28): Yeah, totally. So I'm glad you brought that up. The other things that we learn about as we talk to women is that the average woman, Dr. Kyron, you know this very well, is putting on 10 to 12 different chemicals on her face, on her body, on her scalp before she leaves the home in the morning. And this is a lot to do with the modern beauty products that we have that that include parabens, that include phalates, that include benzoates, formaldehyde, fragrances. We don't actually know what's in these beauty products. And so the best thing, especially if you're experiencing hair thinning, is to use as natural of products as possible. You can pick any brand but make sure that it's very, very natural. It doesn't have all of these chemicals be listed because they are adding oxidative stress to your hair follicles. And as your hair follicle is fighting to survive and grow during times of hair thinning, we don't wanna add any extra stress to it. Speaker 3 (23:20): The other thing you mentioned is inflammation. Inflammation has been directly linked to hair loss. It's been measured in the hair follicles from scientists that are studying hair loss. And so we also know that as we get older, inflammation is, is known as inflammaging. It's one of the reasons why we age faster. If there's more inflammation in your body, you're likely gonna age faster than others that are have less inflammation. So we wanna get that back under control. Some ways to do that is having very good sleep, having low oxidative stress, having low cortisol levels as Dr. Karin mentioned. But also you can take some natural supplements that can help balance stress inflammation levels in your body to normal range. Yeah, Speaker 1 (24:03): I always think about inflammation like fire in the body. Yeah. And you can think of a, like a lot of little fires or one big fire, but how do you stop a fire? Well, you stop feeding it. So get the firewood out. So stop putting, using the chemicals changed to natural products. Stop eating things with pesticides and artificial flavorings and colorings processed foods and get them out of your environment. So stop feeding the fire. But then also you can quench it with antioxidant types of supplementation, which can be helpful. But it's so funny 'cause some people will say, oh great, I'll, I'll take this, this anti-inflammation supplement. I'm good. No, you still need to, to detox your life and stop using all the toxic things and stop eating gluten and all those inflammatory foods. Alright, so inflammation, we've got hormones, we've talked about sex hormones, we've talked about cortisol. What else can contribute to hair loss? Speaker 3 (24:59): Yeah, totally. There are thyroid conditions. Mm-Hmm. Having too low thyroid and having too high thyroid can both lead to hair thinning. And, and I'm sure you talk to people all the time about having low thyroid, but the symptoms include, you could even be losing hair on the eyebrows, you could be gaining weight, you know, e or when you sit down you get pretty lethargic. You have cold hands and feet and of course hair thinning. So that's the low thyroid. When you have high thyroid then you're just, your engine's running very, very fast and very hot and you'll be jittery and you'll lose hair as well as a result. And so there's only two tests that we, for the most part, when we recommend, because we wanna make sure we're not asking women to spend too much money. One of them is the full thyroid panel with antibodies. Speaker 3 (25:45): And this gives us a very good indication that you have either low thyroidism or you have Hashimoto's, which is something that we have to deal with outside of our products to make sure that that is normal. And sometimes when the thyroid gland is being attacked by the immune system in the body, you wanna make sure to stop that progression as quickly as possible. Otherwise you will lose the thyroid gland and you'll have to take medications for the rest of your life. And so that is the one thing that we, if you do notice that you have low thyroid, we recommend getting, or if you feel like you have low thyroid, we recommend getting the full thyroid panel with antibodies. So that's one. And then the other thing I, I guess I didn't mention is that nutritional, there's some nutrition aspects which can cause hair thinning. Speaker 3 (26:25): There's the big five, as we like to call it, in the hair loss world. These are vitamins and minerals. So what are these? Iron is very important for hair. We've got zinc, that's very important. Vitamin D is very important. Folate and B 12, you've gotta have enough of these in your body to support hair health and to make sure that it's not falling out because you're, you're deficient in these, interestingly enough, vegans these days, veganism is, is getting more and more popular. And I have friends in Los Angeles and New York that, that have gone vegan and you know, if that's what you wanna do, that's totally fine. But vegans are at risk of being deficient in three of these five nutrients, which is iron B 12, and folate. So make sure that you're either getting enough from your foods and or taking a supplement that has these ingredients so that you can fulfill those needs and you're not, you're not losing your hair and then wondering what's going on. Yeah, Speaker 1 (27:19): I would just caution people that I, I remember a while back, years ago, I don't know if someone was on Oprah talking about biotin, I think Yeah. For hair. And everyone was taking these mega doses of biotin. And what a lot of people don't understand is that when you supplement certain B vitamins, which biotin is, or even other vitamins to the exclusion of others, especially in these humongous doses, you cause these relative deficiencies in the others. And you can actually cause your chemical processes in the body to malfunction and cause more problems. So I always say it's best to get your nutrients from nutrient dense food mm-hmm. and supplement if it's targeted, and maybe you've had a nutritional test to target those nutritional components, but then retest to see do you still need those doses of those nutrients? And other than that, to use more broad-based type supplementation. But yes, nutrition is important and then hair is dead protein, right? Yeah, Speaker 3 (28:27): Yeah. It's keratin. I, I do want to come back to the nutrition aspect that you mentioned. I love what you're saying in that there are certain nutrition or nutritional aspects meaning vitamins and minerals. If you take too many of them or too much of them, then you'll cause her, you'll cause hair loss as well. So it's very interesting that vitamin A iron, both of these selenium, all three of these taken too low or being deficient in can cause hair thinning. But if you have too many of these, it can also cause hair thinning. So you've gotta be very careful, like Dr. Kyron mentioned, don't take these for months and years on end if you're taking target supplements, but do get measured to make sure you're not going over the limit for any of these. And then of course, hair fo hair, the hair strands are actually dead proteins. They're made up of keratin. And there's also melanin in them, which is the color, which creates the color in the hair follicle. And, and so that's what it is. You've gotta make sure you've got enough protein in your diet too, so it can have the amino acids to create the actual strand for the hairs. And so lots of things that go into her follicle health and I'm glad we're discussing these. Speaker 1 (29:34): Yes. And most women are not getting enough protein. So that's why, to make sure to mention that, that it's super important to make sure you are getting enough protein. And you also mentioned something before we started recording, I think everyone would find fascinating is that the density of hairs on a woman's head varies by hair color. Can you talk a little bit about that? Speaker 3 (30:00): Yeah, this was shocking to me when I learned this as well. So blondes seem to have more fun because they have the most hair on their head. It's about 150,000 hair follicles that blondes have and brunettes like myself and yourself, Dr. Kan if that's your natural color, we have about a hundred to 120,000 hair follicles on our scalp. And then redheads have to have seem to have the, the worst luck when it comes to hair follicles to have about 80 to 90,000 hair follicles. But still, I just wanna mention that, that that's plenty of hair follicles that's gonna cover your scalp very, very effectively. But coming back to the point that you made, blondes do have to do, seem to have the most hair and it's the thickest for them, especially early on. Speaker 1 (30:45): Yeah. And I, after you told me that, I started thinking, I wonder why that is and because I love to think about questions like that. . Yeah, . And I had this thought that, you know, blonde hair is more, it's lighter and opaque so it doesn't look as dense and maybe you need more of it to be substantial, whereas darker hair is more visibly obvious. But then I thought hair isn't on us to be seen, it's for thermodynamics, it's to keep us warm. So I'm not sure exactly why that is. It's very interesting. If anyone listening has an answer, I'd love to hear about it to reach out on social media or maybe you know the answer. Yeah, Speaker 3 (31:30): I'd love to hear the answer as well, . Speaker 1 (31:33): So what else is important for a woman to know or investigate if she's noticing hair loss? Speaker 3 (31:42): Yeah, the number one reason that I believe that women are not successful with fixing their hair loss problems is because they're not sure of the reason. As we mentioned, there can be multiple reasons for hair thinning and the number one reason, of course is hormonal. But sometimes there can be an additional reason like stress is adding to the hormones or you're taking a certain medication, or you have, you're low nutritional deficiencies in certain aspects or certain vitamins and minerals. And so understanding where the hair loss is coming from and and addressing it in multiple ways that seems to get the best results. What I've seen in practice and what I've learned from all the interviews and all the discussions I've had with hair experts over the years and hair researchers over the years, is that to get the best results, to stop hair thinning and to regrow your hair regrow, thicker, fuller hair, you've got to stimulate hair follicles in multiple ways. Speaker 3 (32:39): And that multiple stimulation seems to have the best combined effect. It's all synergistic inside and outside. You know, either taking something nutritionally and or applying pressure or massage to your scalp, all of that and also derma rolling, all of that seems to have very good benefit synergistically. But by itself, I'm sure you've talked to dozens if not hundreds of women that have tried a hair pill or that, that have tried a hair serum and had little to no results to show for it. For some it can work because that is the cause of their hair thinning. But if you take a holistic approach and say, okay, what's going on in your life? And if I had to just, if I had to get products, how could I make sure that these products address 80 or 90% of the reasons of my hair thinning without me having to get a PhD in hair science? That is the best way to move forward. Speaker 1 (33:29): You know, as you're talking, I I'm thinking we should talk about, well, how do most doctors address this, right? So if you're having hair loss, having practiced regular corporate mainstream medicine for many years, we really weren't given the tools to be able to properly assess why hair loss, even dermatologists. And so if you're listening, and this is you, you've probably already talked to your doctor and you probably haven't gotten satisfying answers, so I'm glad you're here. But let's talk about some of the different treatments. I mean, Rogan is something that you can purchase over the, the counter minoxidil. You talk mentioned dermal rolling. I've heard of stem cell injections, their transplants. So can you talk a little bit about what the different treatments are? I mean, I would say you gotta first look at it as a warning sign from your body that there are hormonal imbalances, there are toxicities, there are nutritional deficiencies. You've got to examine and address those. And then once you address them though there may be other things available to you. What are some of those things? Speaker 3 (34:35): Totally. And so what I'd love to do is to walk this down through simple ways to stop hair thinning and to regrow your hair to more complicated and or expensive ways. And there's a whole ladder you can walk up or walk down depending on how you're coming at this. So the simplest things which you could do is make sure that if you were just looking for solutions, then maybe like a supplement or something that helps balance counterbalance some of the hormones inside of your body, gives you the nutritional supplements, reduces in inflammation, reduce oxidative stress with antioxidants that can be multifactorial and go after a lot of things could be beneficial to you. But like I said, you wanna combine these with multiple things. So a supplement may be good, but you want to combine it with the serum that you apply topically to your scalp that's acting on the area that you need it to work. Speaker 3 (35:24): And then the third thing that has scientific evidence behind it is the derma roller, just by itself, a derma roller has proven to grow 15% more hair with nothing else, no other interventions. So that's a good one as well. To add to your protocol, women already are familiar with derma roller of their face and it's easy to do it on the scalp. So that's the third. And the fourth one that we kind of recommend quite a bit is brushing your hair a hundred to 200 times a day. Because what happens the first thing that happens when you're losing your hair, you don't wanna touch it, you don't wanna wash it, you don't wanna heal it, right? That happened to me for many, many years. In fact, I was putting these hair fibers in my scalp because I was so afraid of my scalp showing through when I was going out in Los Angeles where you get judged for how you look. Speaker 3 (36:08): And so if you're gonna do that, then those are the, the base layers. You want to do multiple of those at the same time. And they're pretty cheap, right? They're pretty economical for most people. Then if you say, well, I wanna go to a doctor or a dermatologist and I wanna get professional advice one, I would say that yes, absolutely you can do that. I would say that dermatologists aren't spending a lot of their time focusing on hair science. And you can also, I'm sure validate this Dr. Kyron because you're just too busy. There's too many patients to see, there's too much to do, there's too many conditions to treat. So dermatologists in their offices, they're getting a lot of Botox, a lot of fillers, a lot of all kinds of aesthetic things where they don't have a lot of time to figure this out. Speaker 3 (36:47): So what they'll typically recommend at a dermatologist or even doctor's office is they'll recommend P R P or platelet rich plasma, which are basically, they draw blood outta your body and they centrif use a centrifuge to spin it and then they, they inject it back into your scalp. The idea being that there are some growth factors that are available in this hair that can help rejuvenate and thicken your hair follicles. And if you look at the studies, there's meta-analyses that have been done on P R P. It's very individual to the type of machine, used to the process of the centrifugation. Many dermatologists that are not aware of the different types of machines will go to Amazon and buy one or they'll buy one from a pushy sales rep from many, many companies that are selling these centrifuges. And so it's really a crapshoot on when it comes to results. Speaker 3 (37:33): So if you're going to go down that route, make sure to ask for before and afters, make sure to validate that this doctor has results. Because what they're gonna do is they're gonna ask you to sign up for three or four of these injections over three to four months and they're gonna be a thousand dollars each. So you're gonna be $4,000 in and you're not gonna know if it's gonna work or not. And they won't even guarantee it and there is no money back. So you're gonna be out a few thousand dollars. So again, just know that the other aspect with regenerative medicine, it appears that stem cells unfortunately don't have as much good data. Even though there's anecdotal evidence of some, some individuals getting results, but on the whole stem cells have do not have good data on hair growth. In fact, exosomes, which are basically made from stem cells or extract from stem cells, seem to have better data on the, the hair as opposed to both P R P and stem cell. Speaker 3 (38:27): So if you're gonna choose a therapy, I would recommend you at least ask your doctor or dermatologist about exosomes. Again, note that it's not, not gonna be cheap. This is in the thousands of dollars with exosomes, you're probably just gonna do one treatment and there, you know, you'll have to see how that turns out for you. For some it works good for others, it may not work at all. Then we get to the hair transplants. This is the easiest solution for at least some men that have lost a lot of hair. The way this works is that if you have lost a bunch of hair in a particular area, this is can be very effective because they can pull the hair from the back of your scalp, which is immune to the dihydrate testosterone or D H T and you, they can implant it in the front so this hair won't fall out again. Speaker 3 (39:09): But you've gotta be very careful to address the underlying causes of hair thinning, because even if you do transplant hairs in the front or the top, the other hair will continue. This is a progressive condition, they'll continue to thin and they'll continue to fall out. So I've heard of instances where some men at least have used the hair transplants to get a bunch of hairs in the front, and then they got a second transplant and a third transplant, and then they just ran out of donor hair in the back. And so now they have a bunch of hair in the front and nothing behind it. So they had to laser off $40,000 of hair transplants that they had done. So you wanna be careful. And in addition, women are typically not the best candidates for hair transplants because when you're injecting or when you're implanting new hair or transplanting new hair, that causes a shock loss around. Speaker 3 (39:59): So the existing hair that may be around that newly transplanted hair, when you transplant it, it gets a shock because there's a damage to the skin. And so that hair might go, that hair might be lost because of this transplant. So again, speak with a very, somebody that's got a lot of ears on in in their practice for a hair transplant surgeon. I guess the final thing I would say is that some women, when they experience hair thinning in the front of their scalp, they can get scalp reduction surgery as well. So they will just cut out maybe a centimeter or half an inch of your scalp in the front and then staple it back down, which then brings your hairline lower. And so it makes you look more youthful. It makes you look like you have more hair. And women seem to do this more compared to men that will do the hair crime, spine surgery. Speaker 1 (40:45): Interesting. I didn't, I wasn't aware of that surgery. Another thing to do to ourselves, Speaker 3 (40:52): Totally, but never stops. Speaker 1 (40:54): Our hair is such a part of our identity that only you as the person dealing with this problem can say what it's worth to you and what, what you would like to have done. So I say follow your heart when it comes to that. I do wanna mention there is a type of specialist called a ologist, which most people have never heard of who is a hair specialist. They're not doctors, but they have specialized training in the evaluation and management of the hair follicles, particularly on the head. And they have very specialized equipment where they can evaluate hair follicles and see what state they're in, the size of them, their health, whether they're able to grow hair or not. And so if you're really struggling with this and a lot, it's funny 'cause I've even met a lot of dermatologists who don't even know that trick exists. Speaker 1 (41:53): Yeah. So you can, oftentimes there aren't that many of them, but you can look on Google to find a trick and go to them for a full evaluation. And they're often very good guides. I won't say that they're necessarily good at helping you evaluate the systemic conditions that we've been discussing that can contribute not only to hair loss, but also to decreasing your longevity and vitality. They, I haven't found that they universally are aware of that or know how to do it, but when it comes to targeted treatment, they're, they're the experts. So I did wanna mention that. Yeah, Speaker 3 (42:32): Totally. I've been to, I have many psychologist friends of my own. I've been to them. They have looked at my hair and scalp and microscopes. Yeah, they have 50 x magnification so they can look at what's going on. They can give you advice about, so yeah, totally agree. Yeah. Speaker 1 (42:46): But this is great information and I'm glad to have you here. I know you've given hope to some women today who are really struggling. You now know the steps you need to take, evaluate your hormones, so your sex hormones, your cortisol, your thyroid, I'd say your insulin too. Look at your inflammation levels, your toxicity or to decrease that toxin fire. And then look at your nutrient inputs, where are you deficient and work to sup supplement those. And then there are local things that you can do that we've discussed for us. Thank you so much for coming on the show and sharing all this wonderful information. Tell everyone how we can find out more about you. Tell 'em about your Anti-Aging Hacks podcast. Where are you online? Speaker 3 (43:32): Totally. Thank you Dr. Karin. So a couple of places. Number one, I'm the host of the Anti-Aging Hacks podcast, where we talk about wge and anti-aging and how to bring typical or simple resources to help you slow down your aging now and then in time, also reverse it because that revolution is coming very soon. So that's what I talk about on the Anti-Aging Hacks Podcast. The other is, I'm the founder of a hair wellness and hair growth company called Fully Vital, where we combine different products to give you maximum coverage for the reasons for hair thinning. So we've got a, a supplement that we talked about. We've got a, a serum for the hair, we've got a derma roller they will sell and also a hairbrush. So we sell a bundle that you can get, which covers, in my opinion, 80% of more of all the hair thinning reasons that will give you the best results. Speaker 3 (44:23): And if you do go with us, then we recommend that you use the get the three month bundle because hair growth takes a little bit of time. So you've gotta be patient with it. Get the three month bundle. And the best part about us is that we have a four month money back guarantee, full money back guarantee. So try us out for three months. We're covering the most spaces out of anybody out there, and for some reason, if you don't get results, email us and we'll refund all of your money. So there's, there's no risk attached to that. And you can find that@fullyvital.com. And Dr. Kyron, if you would allow me, I'd love to offer your listeners a coupon code as well for this. Speaker 1 (44:59): Sure. We can put it in the show notes. Speaker 3 (45:02): Okay, perfect. Awesome. Speaker 1 (45:04): Thank you so much for Oz before coming and sharing your wisdom about hair. Thank Speaker 3 (45:09): You Dr. Karin, honored to be on your show. Speaker 1 (45:11): And thank you for joining us for another episode of The Hormone Prescription for Dr. Kieran. I hope that you have learned something today that you can put into practice to change your hair, but maybe even to change your hormones and your life. I look forward to hearing about it on social media, so please reach out and let me know, and I hope you have a great week Until next week, peace, love, and Speaker 2 (45:34): Hormones, Speaker 1 (45:34): Y'all. Speaker 2 (45:36): Thank you so much for listening. I know that incredible vitality occurs for women over 40 when we learn to speak hormone and balance these vital regulators to create the health and the life that we deserve. If you're enjoying this podcast, I'd love it if you'd give me a review and subscribe. It really does help this podcast out so much. You can visit the hormone prescription.com where we have some free gifts for you, and you can sign up to have a hormone evaluation with me on the podcast to gain clarity into your personal situation. Until next time, remember, take small steps each day to balance your hormones and watch the wonderful changes in your health that begin to unfold Speaker 1 (46:15): For you. Speaker 2 (46:16): Talk to you soon.   ► Get 10% discount on FullyVital hair growth products - CLICK HERE. ► Feeling tired? Can't seem to lose weight, no matter how hard you try? It might be time to check your hormones. Most people don't even know that their hormones could be the culprit behind their problems. But at Her Hormone Club, we specialize in hormone testing and treatment. We can help you figure out what's going on with your hormones and get you back on track. We offer advanced hormone testing and treatment from Board Certified Practitioners, so you can feel confident that you're getting the best possible care. Plus, our convenient online consultation process makes it easy to get started. Try Her Hormone Club for 30 days and see how it can help you feel better than before. CLICK HERE.   ► Do you feel exhausted, moody, and unable to do the things that used to bring you joy? It could be because of hormonal poverty! You can take our quiz now to find out if your hormone levels are at optimum level or not. Take this quiz and get ready to reclaim your life; say goodbye to fatigue and lack of energy for good. We want every woman to live her best life — free from any signs or symptoms of hormonal poverty, so they can relish their everyday moments with confidence and joy. Imagine having a strong immune system, vibrant skin, improved sleep quality… these are all possible when hormones are balanced! CLICK HERE now and take the #WWPHD Quiz to discover if you're in hormonal poverty — it only takes 2 minutes! Let's get started on optimizing your hormone health today.  

This week we will discuss a rare type of cancer.  Our guest on today's show is Chris White.  Mucosal melanoma is a rare but aggressive disease usually diagnosed in advanced stages. Unlike most melanomas, which start in the skin, mucosal melanoma starts in the moist membranes that line the inside of the body, including the digestive tract. All melanomas start in pigmented cells called melanocytes. Mucosal melanoma accounts for 1.4 percent of all melanomas, according to a 2018 review in Melanoma Management. ​Most mucosal melanoma cases start in the lining of the head, neck, anus, vagina or vulva. Cases inside the gastrointestinal tract are less prevalent. The disease may be called invasive if it's spread deep into the tissue and metastatic if it's spread to distant parts of the body, such as the liver or lungs. ​​Mucosal melanoma hasn't been linked to any specific causes. Generally, older people are diagnosed, with the median age being 70. While the rate of skin melanoma cases has risen in the past 20 years, the rate of mucosal melanoma has always been fairly similar over time. ​ More About Our Guest Chris's story begins in Colorado Springs where he was born in 1982. His parents and two siblings moved to Irvine California where he grew up before moving to North Texas. He received his Associates of Arts degree at Collin College, followed by his BA at University Texas Dallas in 2005. After college, his career path included time in the in the oil and gas industry, working with independent SAP contract consultants as well as working in the Golf department at Gleneagles Country Club in Plano, Texas. His career path took a turn in 2016 when he worked in the home building industry as a construction manager. An avid snowboarder, he has always been active, enjoying outdoor activities. His cancer journey began in the summer of 2018 when what he had believed was a hemorrhoid actually turned out to be cancer. Not just any cancer, but the diagnosis was Anorectal Mucosal Melanoma which is an extremely aggressive cancer with a low survival rate.  The following months included multiple surgeries, immunotherapies, chemotherapy and radiation. Despite the treatments, the cancer had metastasized throughout his body to his lungs, liver, kidneys and brain. His health was declining rapidly, and without any other options, he was fortunate enough to qualify as the last patient admitted to a TILs Therapy Clinical Trial at the University of Colorado Health Cancer Care located at the Philip Anschutz Medical Campus in Aurora Colorado. The TILs therapy was done in January of 2020 and within less than a year the tumors were gone. Not in remission but gone. The TILS therapy is revolutionary in that it eradicates the tumor rather than leaving it dormant. This clinical trial for TILS therapy saved his life. He was able to go back to work in homebuilding but realized his passion is sharing his cancer survival story. Currently he works as a Certified Melanoma Educator through the Melanoma Research Foundation. He is involved with many melanoma patient advocacy groups throughout the world listening to other stories while sharing his own via group chats, industry panels and forums any format that can offer some patient the comfort that there may a cure for their cancer. Any contribution to the MRF aids the fight against Melanoma and Chris thanks you for your support and generosity. ​  

In this episode of SurgOnc Today, Genevieve Boland, MD, PhD, FSSO, of Massachusetts General Hospital – Vice Chair of the SSO Melanoma Disease Site Working Group is joined by fellow committee members, Rogerio Neves, MD, PhD, FACS, FSSO, from Moffitt Cancer Center and Amanda Kirane, MD, FACS, FSSO, from Stanford University. They discuss the current clinical application of tumor infiltrating lymphocytes (TILs) in melanoma, recent clinical trial results, advances in TILs production that have allowed for expanded patient access, and insight on appropriate patient or tumor selection for therapy.

Afsnittet er sponseret af Dyrbar https://dyrbar.dk/ Få 10% rabat hos Dyrbar ved at bruge koden vinforbegyndere (Gælder på alle ikke nedsatte varer). Find udskæringerne her: 1) Edderkoppen - kalvhttps://dyrbar.dk/products/edderkoppen-kalv 2) Presa af tunggrishttps://dyrbar.dk/products/presa-af-tunggris 3) Krogmodnet Porchettahttps://dyrbar.dk/products/krogmodnet-porchetta ……………. I dette afsnit giver vi tre bud på måltider til påsken. Vi sætter tre vine til og snakker omkring vin og mad sammensætning. Man kan selvfølgelig også lave maden, når det ikke er påske.   Ponzu - Edderkop af kalv (Araignée)   Steg edderkoppen som anvist på Dyrbars hjemmeside i rigeligt smør, MEN... smid en lille håndfuld finthakkede stængler fra koriander i smørret midtvejs Lav en ponzu på følgende måde: 1 stk. tørret kombutang ½ dl. lagret japansk soja 1½ spsk. sake 1 spsk. mirin 1 spsk. risvineddike 1½ spsk. limesaft Varm kombu, sake, soja og mirin op i en lille gryde Lad det køle af. Fisk kombuen op og kaser den Rør eddike og limesaft i. Sesam-olivenolie Varm 3 spsk. ristet sesamolie op sammen med 3 spsk. olivenolie til rygepunktet Anret tynde skiver af edderkoppen på et fad, overhæld med den varme olie, 4-5 spsk. ponzu og ikke mindst den brunede koriandersmør. Spis med pinde. Presa med hasselbachkartoffel Brun og tilbered presaen som anvist på Dyrbar. Smid meget gerne rosmarinkviste ved stegen i panden. Læg mellemstore faste kartofler mellem to flade skærebrætter og skær med skarp kniv tynde lameller helt ned til skærebrættets højde, så kartoflen stadig hænger sammen. Pensl kartoflerne med rigeligt smeltet smør, drys med timian, salt og peber og stil dem i ildfast, smørsmurt fad og bag dem ved 210 grader varmluft ca. 45 minutter, så lamellerne bliver sprøde og brune. Lav brun sovs. Brug en rigtig god kalvefond eller bedre, rist griseben i ovnen og kog en grisefond med rodfrugter, lidt hvidvin og masser af urter. Kog panden med presa-rester af med ca. 3 dl. fond, kog den lidt ned. Tilsæt et skvæt rødvin, lad alkoholen fordampe lidt. Tilsæt 1 dl. fløde og lad koge lidt ind igen. Tilsæt kulør og jævn evt. med mørk jævner (ja det må man godt her!). Smag til med salt og peber. Anret skiver af presa med kartofler og rigelig sovs. Porchetta Bind porchettaen op og krydr under slaget med masser af groft kværnet peber, rosmarin, hvidløg, salvie... du bestemmer selv. Bind den sammen igen. Tilbered som anvist på Dyrbar. Server den i skiver med en bønnesalat af: 2 dåser borlotti-bønner, afdryppede 1 finthakket lille rødløg 3 stængler bladselleri finthakket 50 g parmiggiano hakket i små tern à ½ cm 50 g valnøddekerner hakket revet citronskal Rigeligt af din bedste toskanske olivenolie Friskkværnet peber Saml det hele i en skål Skær skiver af porchetta og anret med bønnesalaten     Vin 1) Vouvray - Le Haut Lieu - Sec 2021https://www.theis-vine.dk/products/vouvray-le-haut-lieu-sec-domaine-huet   2) COBRANA 2021 VERONICA ORTEGA, BIERZO, SPANIENhttps://www.jyskvin.dk/cobrana-2021-3159036   3) Rimosso Metodo Ancestrale Lambrusco di Sorbara DOC 2017 Cantina della Volta https://estrup-udsen.dk/shop/rimosso-metodo-ancestrale-lambrusco-di-sorbara-doc-2017-cantina-della-volta-mousserende-vin-roedvin-kopier/  

Dr. Tina Albertson is the Chief Medical Officer and Head of Development at Lyell, using cell therapy to fight solid tumors through epigenetic and genetic reprogramming methods. Tumors have their own mechanisms for suppressing the immune system. These are the types of pathways Lyell is targeting with their engineering to find ways to counter the exhaustion that the T cells exhibit so that T cells can stay functional and kill the solid tumor cells. Tina explains, "Our cell therapies are from the patient's own cells, so these are what we call autologous cell therapies. We take the cells from the patient and bring them, in our case to Seattle, to our manufacturing facility. We both genetically and epigenetically reprogram them during manufacturing so that the cells will be resistant to the suppressive microenvironment of the solid tumors."  " I think most people are familiar with the concept of stem cells, which can self-renew as well as make cells that are functional and can differentiate. So when we reprogram them, we make them more stem-like, and this allows us to infuse cells into the patient that should be more persistent and more functional."  "The second product we're also testing in trials is tumor infiltrating lymphocytes or TILs. This is a product where you need a piece of their cancer or their tumor and extract the T cells from the tumor itself. That requires surgery, then a piece of tissue is also sent to our manufacturing facility. Those T cells are extracted and expanded. That takes a little bit longer. But similarly, once those are expanded to the right cell number, we send them back to the site to be reinfused into the patient." #Lyell #CellTherapy #SolidTumors #Oncology #Cancer #TCells #TCellExhaustion #AutologousCellTherapy lyell.com Download the transcript here

Dr. Tina Albertson is the Chief Medical Officer and Head of Development at Lyell, using cell therapy to fight solid tumors through epigenetic and genetic reprogramming methods. Tumors have their own mechanisms for suppressing the immune system. These are the types of pathways Lyell is targeting with their engineering to find ways to counter the exhaustion that the T cells exhibit so that T cells can stay functional and kill the solid tumor cells. Tina explains, "Our cell therapies are from the patient's own cells, so these are what we call autologous cell therapies. We take the cells from the patient and bring them, in our case to Seattle, to our manufacturing facility. We both genetically and epigenetically reprogram them during manufacturing so that the cells will be resistant to the suppressive microenvironment of the solid tumors."  " I think most people are familiar with the concept of stem cells, which can self-renew as well as make cells that are functional and can differentiate. So when we reprogram them, we make them more stem-like, and this allows us to infuse cells into the patient that should be more persistent and more functional."  "The second product we're also testing in trials is tumor infiltrating lymphocytes or TILs. This is a product where you need a piece of their cancer or their tumor and extract the T cells from the tumor itself. That requires surgery, then a piece of tissue is also sent to our manufacturing facility. Those T cells are extracted and expanded. That takes a little bit longer. But similarly, once those are expanded to the right cell number, we send them back to the site to be reinfused into the patient." #Lyell #CellTherapy #SolidTumors #Oncology #Cancer #TCells #TCellExhaustion #AutologousCellTherapy lyell.com Listen to the podcast here

Tumor infiltrating lymphocytes, known as TILS, allowed people with advanced melanoma, a serious type of skin cancer, to live longer than those who received an antibody alone, a recent study showed. Kimmel Cancer Center director William Nelson at Johns Hopkins … A type of individualized T cell helps people with advanced melanoma, Elizabeth Tracey reports Read More »

What does the body of evidence say on the topic of osteoporosis? Plus: we look at a genuinely breakthrough therapy for metastatic melanoma, and Chris lets you in on a troubling “secret” when it comes to travel health insurance! You will also learn what a “dowager's hump” is and hear Chris sing, and for that we formally apologize.   Block 1: (2:01) Osteoporosis: what it is; bone cells and how they are assessed   Block 2: (9:02) Osteoporosis: bone mineral density, T-score and Z-score; can doctors see signs of osteoporosis in the clinic; causes of osteoporosis; treating it: lifestyle changes, supplements, bisphosphonates, and Prolia; screening guidelines   Block 3: (32:04) Breakthrough therapy for metastatic melanoma: TILs (vs. ipilimumab)   Block 4: (47:53) Travel insurance caveat     * Theme music: “Fall of the Ocean Queen“ by Joseph Hackl. * Assistant researcher: Nicholas Koziris   To contribute to The Body of Evidence, go to our Patreon page at: http://www.patreon.com/thebodyofevidence/.   To make a one-time donation to our show, you can now use PayPal! https://www.paypal.com/donate?hosted_button_id=9QZET78JZWCZE   Patrons get a bonus show on Patreon called “Digressions”! Check it out!     References:   1) Estrogen does reduce the risk of hip fracture from osteoporosis: https://doi.org/10.1001/jama.288.3.321   2) Exercise increases bone mineral density in post-menopausal women: https://doi.org/10.7326/0003-4819-108-6-824 & https://doi.org/10.1001/jama.288.18.2300   3) Calcium and vitamin D supplementation and the risk of fractures: https://doi.org/10.1001/jama.2017.19344   4) Medications can reduce the risk of osteoporotic fractures: https://jamanetwork.com/journals/jama/fullarticle/2685995   5) Screening guidelines from the US Preventive Services Task Force: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/osteoporosis-screening   6) Results from the phase III clinical trial comparing TILs to ipilumumab in advanced melanoma: https://www.nejm.org/doi/full/10.1056/NEJMoa2210233     It's Not Twitter, But It'll Do:   1) Jonathan on the Martial Culture Podcast: https://www.stitcher.com/show/the-martial-culture-podcast/episode/combating-pseudoscience-unscientific-thinkings-in-martial-arts-w-jonathan-jarry-209989826   2) Jonathan's article on the Healy: https://www.mcgill.ca/oss/article/critical-thinking-pseudoscience/healy-old-woo-new-clothes   3) The Hard Fork Podcast: https://www.nytimes.com/2022/10/04/podcasts/hard-fork-technology.html   4) The CTV Montreal News website: https://montreal.ctvnews.ca/video?binId=1.1332485   5) The CBC Player: https://www.cbc.ca/player/news   6) The CJAD website: https://www.iheartradio.ca/cjad   7) Odyssey TV: http://odysseytv.ca/   8) Chris on the CBC, interviewed about mpox: https://www.cbc.ca/news/politics/mpox-outbreak-canada-plateau-1.6696842     Time Machine:   1) Our episode on childbirth: https://bodyofevidence.ca/042-childbirth-and-crowdfunding-quackery   2) Our interview on conspirituality: https://bodyofevidence.ca/interview-matthew-remski-on-conspirituality     Music Credits:   The following music was used for this media project: Music: 3am Glowsticks by Tim Kulig Free download: https://filmmusic.io/song/9166-3am-glowsticks License (CC BY 4.0): https://filmmusic.io/standard-license    

A highly educational Wednesday crossword, with a slew of TIL (Today I Learned) entries, including the fascinating 9D, Metal next to tungsten on the periodic table, RHENIUM, which neither Jean nor Mike, in spite of having taken several chemistry classes, had ever heard of. It is true that a number of heavier elements have been added to the periodic table, um, periodically, but the lower numbered elements have generally remained unchanged.There were some other TILs, so to help improve your, oh, what's the word, oh yes, vocabulary

I episode 22 af Maxers julekalender er Søren i studiet. Han arbejder med personlig træning på Vesterbro i København især med optimering af styrketræning, kost og vaner. I denne episode snakker vi om de sagnomspundne sødestoffer - for det er et af de mest mytefyldte områder indenfor sundhed. Hør blandt andet om: * Er aspartam det rene gift? * Gør sødemidler, at du spiser mere og tager på? * Hvor stammer al misinformationen om aspartam og andre sødestoffer fra? * Ødelægger sødemidler dine tarme? * Hvad er E-numre egentlig? * Er det godt for dig, hvis du undgår al den “kemi”, der er i maden? * Hvilken effekt har tilsætningsstoffer overordnet set på madspild og på klimaet?

What is the relationship between gut microbiome and depressive symptoms?

Tumor-Infiltrating Lymphocytes (TILs) getting closer to entering practice. Updated survival results published from DESTINY-Breast03 (T-DXd vs. T-DM1). A new IDH1 inhibitor, olutasidenib, is FDA-approved for relapsed or refractory AML.

Afsnittet er sponseret af Dyrbar https://dyrbar.dk/ Få 10% rabat hos Dyrbar ved at bruge koden vinforbegyndere (Gælder på alle ikke nedsatte varer). Find udskæringerne her: 1) Krogmodnede brystbjælker https://dyrbar.dk/products/krogmodnet-bryst-gris 2) Braiserbøf https://dyrbar.dk/products/braiserbof-okse 3) Kalveroast https://dyrbar.dk/products/dyrbar-kalveroast …………………. Det skal igen handle om vin- og madsammensætning og vi har kreeret tre retter og sætter tre vine til. Vi begynder dog med en mere generel snak om vin og mad. Hvad og hvordan gør René, når han skal lave madanmeldelser for gastro? Hvad er udgangspunktet? Hvad er vigtigt og hvordan anmelder han maden i henhold til vinen? Vi snakker rundt omkring retterne og selvfølgelig også vinene og til slut svarer vi også på spørgsmålet, om der er vine, der skal drikkes alene og ikke med mad? OPSKRIFTER 1) Krogmodnet brystbjælker i banh mi Lav en marinade af 1 stk. hakket citrongræs, kun det hvide½ lille løg finthakket2 fed hvdløg finthakket1 spsk soja2 spsk fishsauceEt skvæt lime1 spsk. Peanutolie2 spsk sukker1 spsk løbende honning Mix det godt og læg med de fire stykker svinebryst i en pose i 2-3 timer Lav thai pickles af1 agurk – skåret i baner med kartoffelskræller2 gulerødder – skåret i baner med kartoffelskræller1 hakket rødløg½ frisk rød chiliKoriander hakket¾ dl. Risvinseddike1 spsk løbende honning1 tsk salt Bland det hele godt i en bøtte med låg og stil i køleskab i 1-2 timer Smør en flækket baguette med kewpie-majo, lav den selv af ca. 1 dl. god mayonnaise (pisk den selv eller brug Hellmann's) blandet med saften fra en halv lime Bag brystet på en rist med bakke under – det drypper og det brænder på! – 180 C varmluft – vend stykkerne hvert kvarter – kig på dem, de skal have brændte fedtkanter Tag dem ud, lad dem køle en smule og skær dem i skiver – det fedter helt vildt. Klask et yderblad fra spidskål i baguetten, smæk svineskiverne, rigeligt!, på kålbladet, læg thai pickles ovenpå, dryp overen af baguetten med shriracha sauce, tryk den sammen og smovs for satan!   2) BraiserbøfBrun bøffer i olie og smør, tilsæt hakket løg og gulerødder og brun med Tilsæt ½ fl. brunello eller chianti og god fond samt en dåse drænet hakket tomat af topkvalitet. Tilsæt en krydderbuket af timian, bredbladet persille og rosmarin Simr i 2-3 timer – tilsæt gode nicoise eller taggiasche oliven den sidste halve time Vurder om saucen kræver jævning til sidst – spis focaccia, surdejsbrød eller moste og ovnstegte kartofler til.   3) KalveroastTilbered som Dyrbar siger:Intervalstegning, 200 C, stegen i vandbad. Tag den ud efter 10 min, hvil i 10 min, herefter intervaller af 5 min, ud og ind indtil 52 C kernetemperatur, hviler til sidst, saltes og pebres i skæres. Lav en efterårssauté med små tern af kartoffel, selleri og pastinak med rigeligt peber, salt og salvie   VIN 1) Cabisehrnett, FIO Wines, Riesling, 2018 https://vinova.dk/vin/fio-cabisehrnett-2017/ 2) Buondonno, Chianti Classico Riserva, Sangiovese, 2019 https://vinova.dk/vin/buondonno-chianti-classico-riserva-2016/ 3) Garage Wine Co., Cabernet Franc, 2018 https://laudrup.dk/garage-wine-co-cabernet-franc-las-higueras-vineyard ....................... KØB BOGEN HER http://vinforbegyndere.com/ Besøg os på Facebook og Instagram, hvor man kan se billeder af vinene og få tips til vin og mad sammensætning. https://www.facebook.com/vinforbegyndere https://www.instagram.com/vinforbegyndere Web: https://www.radioteket.dk/ Kontakt: radioteket@radioteket.dk Musik: Jonas Landin

A new research paper was published in Oncotarget on July 28, 2022, entitled, “Chemoradiation-induced alteration of programmed death-ligand 1, CD8+ tumor-infiltrating lymphocytes and mucin expression in rectal cancer.” DNA damage and resulting neoantigen formation is considered a mechanism for synergy between radiotherapy and PD-1/PD-L1 pathway inhibition to induce antitumor immune response. In a new research study, by Marina Baretti, Qingfeng Zhu, Wei Fu, Jeffrey Meyer, Hao Wang, Robert A. Anders, and Nilofer S. Azad from Johns Hopkins University School of Medicine, researchers investigated neoadjuvant chemoradiotherapy (nCRT)-induced changes in CD8+ tumor infiltrating lymphocyte, PD-L1 and mucin expression in rectal cancer patients. “The synergistic effects of CRT and PD-1/PD-L1 immunotherapy has been supported by several retrospective analyses in different cancer types, including esophageal cancer, bladder cancer, and lung cancer also support[ed] [14, 21, 22]. However, the role of nCRT to interact synergistically with immune checkpoint inhibitor treatment to improve tumor control in rectal cancer remains uncertain.” Full press release - https://www.oncotarget.com/news/pr/oncotarget-chemoradiation-induced-alteration-of-programmed-death-ligand-cd-tumor-infiltrating-lymphocytes-and-mucin-expression-in-rectal-cancer/ DOI: https://doi.org/10.18632/oncotarget.28255 Correspondence to: Marina Baretti – Email: mbarett1@jh.edu Keywords: programmed death ligand 1, tumor-infiltrating lymphocytes, immune checkpoints, colorectal cancer, neoadjuvant chemoradiotherapy About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com

Where to start? In this instant classic, Wesley "Megaman" Tils drops into the studio with Doc to share some incredible stories. Self-described as a sensitive, goofy soul, Megaman talks about his childhood with 10 siblings in Missouri, bare-knuckled fighting at the railroad tracks to solve school disputes, making a run for it at a crucial time in his life, jenky poor man's gear, multiple near death experiences, and living on Snickers bars and Slim Jims on the trail. And, there's that whole thing about surviving a grizzly attack while on the CDT, too. When you look up "Epic" in the dictionary, you will find the title to this episode. --- Support this podcast: https://anchor.fm/johnfreakinmuir/support

An interview with Dr. Fabrice André from Institute Gustave Roussy in Paris, France, and Dr. Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, NY, authors on “Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update.” This updated guideline provides precise guidelines on previously endorsed genomic assays and recommendations on the use of new biomarkers to guide endocrine therapy and chemotherapy in patients with ER-positive HER2-negative tumors, and for those with HER2-positive or triple-negative breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines.   TRANSCRIPT Brittany Harvey: Hello and welcome to the ASCO guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows including this one asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Fabrice André from Institut Gustave Roussy in Paris, France, and Dr. Komal Jhaveri from Memorial Sloan Kettering Cancer Center in New York, NY, authors on “Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update.” Thank you for being here Dr. André and Dr. Jhaveri. Dr. Fabrice André and Dr. Komal Jhaveri: Thank you. Brittany Harvey: First, I'd like to note that ASCO takes great care in the development of guidelines and ensuring that the ASCO conflict of interest policies follow each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. André, do you have any relevant disclosures that are directly related to this guideline. Dr. Fabrice André: No. Brittany Harvey: Thank you. And Dr. Jhaveri, do you have any relevant disclosures that are related to this guideline topic? Dr. Komal Jhaveri: No. Brittany Harvey: Great, then let's talk about the content of this guideline update. So, Dr. Jhaveri, what prompted the update to the biomarkers for adjuvant endocrine therapy and chemotherapy in early-stage breast cancer, and what is the scope of this guideline update? Dr. Komal Jhaveri: So, since the biomarker guideline published in 2016, there were several new publications that came out between January 2016 and October 2021 that provided perspectives on the use of some of the genomic assays broadly, or specifically in women based on menopausal status, age or number of lymph nodes. Additionally, new biomarkers such as programmed cell death receptor ligand 1 or PD-L1, stromal TILs, circulating tumor DNA, or circulating tumor cells, or new applications, like extended endocrine therapy have also been developed. So, this updated guideline provides precise guidelines on previously endorsed genomic assays and also provides recommendations on the use of new biomarkers to guide endocrine therapy and chemotherapy in ER-positive HER2-negative, HER2-positive, and triple negative breast cancer. Brittany Harvey: Great. Thank you for setting the stage for this guideline. So, then Dr. André, I'd like to review the key recommendations of the guideline for our listeners. So, starting with, which biomarkers should be used to guide decisions on adjuvant endocrine and chemotherapy for patients with newly diagnosed ER-positive HER2-negative breast cancer? Dr. Fabrice André: Thank you. So, when we are focusing on a newly diagnosed patient with ER-positivity HER-2 negative in the context of the question about deciding on chemotherapy. First, the 21 gene recurrence score should be used in patients with node-negative and in patients with 1-3 node positive who are postmenopausal. In premenopausal, this test will be used only in patients with node-negative. The second test that is recommended is the MammaPrint 70-gene signature. And here the recommendation is to use this test if the patient is older than 50 and is node-negative or 1-3 node-positive. If the patient is 50 years or younger, the clinician should not use this test. Then also a recommendation is that the clinician could use the 12 gene risk score EndoPredict if the patient is postmenopausal and has breast cancer node negative or 1-3 positive-node. And finally, for the genomic test for the patient, the doctor could use PAM50. If the patient is postmenopausal and has breast cancer that is node-negative. Something new in this recommendation is the recommendation that the clinician could use Ki67. If the patient is postmenopausal and has stage I-II breast cancer with very specific recommendations on the cut off for positivity. Brittany Harvey: Great. Thank you for reviewing those recommendations, Dr. André, and highlighting the new Ki67. So, then, in your introduction, Dr. Jhaveri, you discuss the application of assays for extended endocrine therapy. So, which biomarkers should be used to guide decisions regarding extended endocrine therapy for patients with ER-positive HER2-negative breast cancer? Dr. Komal Jhaveri: Thank you. So, a quick word about extended endocrine therapy. I think extended adjuvant endocrine therapy, which is beyond five years of primary endocrine therapy, has certainly demonstrated improved outcomes, however, with modest absolute benefit and added toxicity and tolerability issues. Furthermore, while extended endocrine therapy is endorsed by clinical practice guidelines, clear guidance on individualized approaches to optimize patient selection for prolonged endocrine regimens, also remains limited. And this really underscores the need for prognostic and predictive information from genomic assays that can help guide this important clinical question we face. One such example that has now borne out has been the breast cancer index and really collected evidence from now five studies supports the prognostic and predictive utility of this assay, such that if a patient has node-negative or one to three positive nodes, and has been treated with five years of primary endocrine therapy, to guide decisions about extended endocrine therapy, the clinician may offer Breast Cancer Index with either tamoxifen or aromatase inhibitors or tamoxifen, followed by an aromatase inhibitor. Brittany Harvey: Great, thank you, Dr. Jhaveri. So, then, Dr. André, which biomarkers should be used to guide decisions on adjuvant therapy for early-stage HER2-positive breast cancer or triple-negative breast cancer? Dr. Fabrice André: Well, first, we have to be sure that we are good at defining HER2-positive breast cancer and triple-negative breast cancer. So, it's always good to remind colleagues to have quality control assessment in place for HER2, estrogen receptor, and progesterone receptor stainings. So far, when it's about predicting the benefit of adjuvant chemo or trastuzumab, there is no genomic test that is recommended in patients with HER2-positive or triple-negative breast cancer. Brittany Harvey: Great, thank you. So, then, Dr. Jhaveri, what recommendations did the expert panel make regarding emerging biomarkers? Dr. Komal Jhaveri: When we're talking about emerging biomarkers, we're referring to stromal TILs, we're referring to PD-L1, circulating tumor cells, and circulating tumor DNA. And while there is a lot of emerging data, currently, clinicians should not be utilizing these new biomarkers to guide decisions about adjuvant endocrine therapy or chemotherapy, as we do not have sufficient evidence to support their use. Brittany Harvey: Great and that's important for clinicians to know. So, then finally, Dr. André, in your view, how will these updated guideline recommendations impact both clinicians and patients? Dr. Fabrice André: So, we know Komal mentioned this at the beginning that now there is a very large amount of new publications, new data coming every day in the field of cancer. So, the only way for clinicians to deliver the best treatments for patients is to have the right guidelines with the right methodology, and ASCO is really putting in place a very rigorous methodology to deliver guidelines. And this is the best way to be sure that all patients will have access to the best decision by the doctor. So guidelines are also here to decrease the disparities in terms of the expert decision, and any patient in the world can have access to the best decision, thanks to guidelines delivered by ASCO and all the colleagues of the panel that worked very hard to deliver these guidelines. Brittany Harvey: Excellent! Well, thank you both so much, and the entire expert panel for your work to update these guidelines, and for taking the time to speak with me today, Dr. André and Dr. Jhaveri. Dr. Komal Jhaveri: Thank you. Dr. Fabrice André: Thank you, Brittany. Brittany Harvey: Thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast Series. To read the full guideline go to www.asco.org/breast-cancer-guidelines. You can also find many of our guidelines in interactive resources in the free ASCO guidelines app available in iTunes or Google Play Store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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 or service organization activity or therapy should not be construed as an ASCO endorsement.