Podcasts about Alterations

Okay so today we meet someone new! Today's story will be read by our newest member, Andrea, who you can call Ms. Andy. She will be reading our Kids Read Along stories going forward and she is very excited to read to you today! Today we have Ms. Andy reading "The Way Champs Play by Naomi Osaka" which is a cute book about what it means to be a champ!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

Welcome to our comprehensive seminar: "Essential Terms For Your Lease Agreement." Whether you're a new landlord or a seasoned property manager, this session is packed with practical advice and legal insights to help you navigate the complexities of rental agreements and tenant relationships. In this video, you'll learn: Why understanding local and state laws is crucial in today's litigious world How to exercise good judgment with tenants to avoid conflicts The importance of regular inspections and proper maintenance Why having the right insurance matters How your rental agreement serves as your last line of defense We'll also cover: Dealing with existing tenants and rent control rules Incentives for tenants to sign new agreements Best practices for new tenants and lease terms (month-to-month vs. fixed term) Essential Lease Terms Discussed: Listing all occupants Your right to enter for inspections (expanding on Civil Code 1954) Temporary relocation and renter's insurance Handling abandoned personal property Subletting and Airbnb considerations Parking rules Alterations, placards, and common area property Arbitration clauses Written repair requests and the importance of tenant notification Don't miss this valuable resource for protecting your property, your rights, and your peace of mind.  Like, subscribe, and hit the bell for more landlord tips and legal updates!

BUFFALO, NY - July 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Comprehensive genomic profiling of over 10,000 advanced solid tumors.” In this study, led by Jean-Paul De La O from Exact Sciences Corporation, researchers analyzed data from over 10,000 solid tumor samples from patients with advanced cancer and found that more than 90 percent contained genetic changes that could guide treatment. This work demonstrates the growing impact of large-scale tumor DNA and RNA testing on patient care. The researchers retrospectively analyzed OncoExTra assay information for 31 types of cancer, including breast, colorectal, prostate, lung, and ovarian cancers. Their analysis revealed that nearly a third of patients had alterations associated with approved drugs for their specific cancer, while another third had changes linked to therapies approved for other cancers. These results show that detailed genetic profiling could expand treatment choices. “Biomarkers associated with on- or off-label FDA-approved therapies were detected in 29.2% and 28.0% of samples, respectively.” Another relevant discovery was that many important mutations occurred at very low levels, which are often missed by simpler tests. By using a broad and highly sensitive approach, the scientists were able to identify these rare mutations. They also reported that 7.5 percent of samples carried gene fusions, unusual genetic events that can drive cancer growth. Such findings can be critical in selecting therapies that specifically target these abnormalities. The study also highlighted the value of RNA sequencing in detecting fusion events that traditional DNA tests might miss. Prostate cancer and certain sarcomas showed particularly high rates of these fusion alterations. This type of information can refine cancer diagnosis and improve therapy planning. In addition, the researchers identified changes in several major cancer-related pathways, including those that control cell growth, DNA repair, and immune system response. Alterations in these pathways can point to newer treatment options, such as immunotherapy or drugs designed to block specific cell signals. Overall, this study shows that comprehensive genomic profiling can guide more personalized cancer care by identifying mutations, gene fusions, and other molecular patterns. Advanced testing methods like the OncoExTra assay reveal treatment opportunities even in advanced cancers, ensuring that subtle but important genetic changes are detected. DOI - https://doi.org/10.18632/oncotarget.28757 Correspondence to - Jean-Paul De La O - jdelao@exactsciences.com Video short - https://www.youtube.com/watch?v=awiRhDfiMTE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28757 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, solid tumors, comprehensive genomic profiling, matched therapy, gene fusions, limit of detection 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

Glad to have you listening with us today! Today we have Ms. Sarah reading "Every Monday Mable by Jashar Awan" and this story has a cute but simple illustration style!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday Stories until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "Echo by Adam Rex" where a good friend always agrees with what you say... right?As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

Dr. Lyudmila Bazhenova is back on the podcast to discuss the latest update of the living guideline on therapy for stage IV NSCLC without driver alterations. She shares the studies the Expert Panel reviewed in the first- and second-line settings, including NIPPON, HARMONi-2, and DUBLIN-3. Although these studies do not impact the existing guideline recommendations, Dr. Bazhenova provides context and comments on ongoing trials that will influence the next iteration of the living guideline. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2025.1” at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-01062 Brittany Harvey: Hello, and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2025.1." It's great to have you back on the show today, Dr Bazhenova. Dr. Lyudmila Bazhenova: It's my pleasure to be here. Brittany Harvey: And then before we discuss this guideline update, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Bazhenova, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into the content here, Dr. Bazhenova, this living clinical practice guideline for systemic therapy for patients with stage IV non–small cell lung cancer without driver alterations is updated on an ongoing continuous basis. So what prompted this latest update to the recommendations? Dr. Lyudmila Bazhenova: Living ASCO guidelines are designed to keep pace with rapidly evolving evidence that impacts treatment of our patients with lung cancer. As a committee, we are tasked with regular review of the published literature and determine if the new data warrants changes to existing recommendations. So in this recently published update, we evaluated new trials related to treatment of patients with metastatic lung cancer without driver alterations. Brittany Harvey: Excellent. Thank you for that explanation of the process. So, you just mentioned that the panel reviewed new trials for this update. So, which particular updated evidence did the panel review on first-line treatment options for patients with good performance status across histology and PD-L1 expression status, and how did this impact the recommendations? Dr. Lyudmila Bazhenova: For the first-line treatment option for patients without driver alterations, two studies met our criteria for review. One was the NIPPON trial from Japan, the second was the HARMONi trial. None of those two trials resulted in change in our guidelines, but I think they are giving us some additional information that would be useful for the way we treat patients with non–small cell lung cancer without driver alterations. For example, if we take those patients, we currently have several treatment options as a first line. One is monotherapy immunotherapy. You can give pembrolizumab as an example, and that was based on the KEYNOTE-024 and KEYNOTE-042 trials. Then we have a platinum doublet plus immunotherapy, and there are several trials that did that pathway. And then we have also an option of giving our patients dual IO immunotherapy combination, such as CheckMate 9LA and POSEIDON. At this point, we do not have any randomized trials comparing those three treatment modalities head-to-head. And the NIPPON trial was interesting to us because it was the first trial to compare CheckMate 9LA regimen, which is again, dual immunotherapy plus chemo, versus KEYNOTE-189 or KEYNOTE-407, which is a chemotherapy plus immunotherapy. And as a result of the study, while chemotherapy plus ipilimumab-nivolumab led to numerically higher overall survival, the difference was not statistically significant. And what is concerning in that trial is that we saw a higher number of treatment-related death occurring in nivolumab and ipilimumab arm compared to the pembrolizumab-chemotherapy arm. As a matter of fact, the trial was terminated early because of the increased risk of death. If you look at the treatment-related death in CheckMate 9LA, the 9LA study reported the treatment-related death to be 2%, and then in the NIPPON trial, the treatment-related death was 7%. Why is that happening? It's really difficult to say. The study was done in Japan. Maybe there is some pharmacogenomic differences between global population and Japan population. But certainly the higher rate of adverse events needs to be taken into account. Another interesting thing about this trial is that it did not show any differences in a subset analysis for patients with squamous histology as well as PD-L1 negative tumor. So while this does not change our current guidelines and CheckMate 9LA treatment still remains an appropriate treatment option, it kind of raises the possibility that this combination could be associated with a higher toxicity. And we do have a randomized US-based trial that is ongoing, and we are hoping that eventually we will be able to answer that question after the trial will be completed. The second trial we reviewed is HARMONi-2. So HARMONi-2 was a randomized, double-blind study which is conducted primarily in China, looking at bispecific PD-L1 and VEGF antibody called ivonescimab. And that took patients who were PD-L1 positive, as defined as more than 1% expression, and patients were randomized to pembrolizumab versus bispecific ivonescimab. And the study was positive. It showed improvement in median progression-free survival of 11 months versus almost 6 months in bispecific versus pembrolizumab. There were, however, higher grade 3 events in the ivonescimab arm. At this point, we are not changing our recommendations because this trial was done in an ex-US population, and we are awaiting a similar trial ongoing in the United States before we change recommendations and decide if ivonescimab needs to be included in our guidelines. Brittany Harvey: This context is very helpful when clinicians think through the data behind these options. And it's important that the panel reviews this evidence, even if it doesn't prompt a change to the recommendations. And we'll await results of those trials that you mentioned to further inform this guideline. So then beyond those studies for first line, what updated evidence did the panel review for second-line and subsequent treatment options for patients with good performance status, and how did this impact the recommendations? Dr. Lyudmila Bazhenova: So for second line, only one trial met the criteria, and that was DUBLIN-3. DUBLIN-3 is a phase 3 single-blind randomized trial comparing docetaxel versus docetaxel plus plinabulin. And the study enrolled patients with second or third line. They have to have had platinum-based chemotherapy and progressed. Plinabulin is an interesting compound. It's a small molecule tubulin binder that prevents polymerization of tubulin and appears to impact dendritic cell maturation and T-cell activation. This study enrolled 559 patients, randomly assigned them to two groups. And one important information about this study is that was a study that was envisioned before immunotherapy became a standard mainstream treatment for first-line therapy. And only 20% of patients had prior PD-1 exposure. So therefore, the results of that study need to be taken into context of this population no longer existing in the United States because we use PD-L1 inhibitors in the first line. And we saw that interesting in the plinabulin arm had lower rates of neutropenia but higher rates of serious adverse events. And at this point, we are not changing our guidelines for mainly two reasons. Number one, low number of patients that received prior treatment with first-line immune checkpoint inhibitors, as well as a modest overall survival benefit of this trial. Brittany Harvey: Understood. I appreciate you describing that study as well and why that evidence didn't prompt a change to those particular recommendations. So then, what should clinicians know as they implement this living guideline, and how does this new evidence impact clinicians and patients? Dr. Lyudmila Bazhenova: At this point, none of the studies that we reviewed resulted in a change in guidelines. We are still waiting for more global results from some of the studies that I highlighted. It shows that there's still a lot of questions we need to be answering in those patients. And I'm hoping that with future clinical trials, we will be able to definitively maybe recommend one treatment over another. But at this point, all the treatments that I mentioned before remain appropriate for patients with stage IV non–small cell lung cancer without driver alterations. Brittany Harvey: Definitely. And then you just mentioned that there's still a lot of outstanding questions in this field. You've mentioned a couple different studies where we're awaiting evidence. Beyond those that you already mentioned, what is the panel examining for future updates to this living guideline? Dr. Lyudmila Bazhenova: Right now, our next task is to come up with a full guidelines update. ASCO have certain rules for the guidelines committee members. And so we are gearing for a full guideline update, which hopefully will be ready by the end of 2025. Brittany Harvey: Excellent. We'll look forward to that full update of the living guideline, and we'll still await results of these ongoing trials to further inform this living guideline. So I want to thank you so much for your work to rapidly and continuously update this living guideline, and thank you for the time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: My pleasure. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. 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.  

Dr. Joshua Reuss joints that podcast to discuss the latest changes to the living guideline on stage IV NSCLC with driver alterations. He discusses the new evidence for NSCLC with EGFR mutations and NRG1 fusions and how this impacts the latest recommendations from the panel. He shares ongoing research that the panel will review in the future for further updates to this living guideline, and puts the updated recommendations into context for clinicians treating patients with stage IV NSCLC. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1” at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-01061 Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2025.1." It's great to have you here today, Dr. Reuss. Dr. Joshua Reuss: Thank you. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Reuss, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So to dive into what we're here today to talk about, Dr. Reuss, this living clinical practice guideline for systemic therapy for patients with stage IV non–small cell lung cancer with driver alterations is updated on an ongoing basis. So what prompted this latest update to the recommendations? Dr. Joshua Reuss: Yes, thank you. It's very important that we have living guidelines that are continuously updated. We obviously don't live in a static environment where things are non-changing, and we really need to apply the most up-to-date and current evidence to treat our patients with the most effective strategies, the most groundbreaking strategies. And so to have guidelines that can be disseminated, particularly these ASCO guidelines, to treating providers is incredibly important. So, with any of these updates, we review ongoing studies, published work, for the quality of evidence to see if it's something that warrants making adjustments to our guidelines or at least incorporating the information so that providers can review it and incorporate this into their own personal decision-making. So in this particular update, we reviewed evidence particularly pertaining to EGFR-mutated non–small cell lung cancer and non–small cell lung cancer harboring an NRG1 fusion. Brittany Harvey: Yes, certainly there's a lot of new evidence in the advanced non–small cell lung cancer field, and so we appreciate the panel's continuous review of this evidence. So then you just mentioned two separate areas where the panel reviewed new evidence. So starting with that first one, what updated evidence did the panel review on first-line treatment options for patients with EGFR alterations, and how did this impact the recommendations? Dr. Joshua Reuss: Yes, so advanced EGFR-mutated non–small cell lung cancer, at least with classical activating alterations - that is our exon 19 deletions and our exon 21 L858R mutations - is something that's really evolved rapidly in the last few years. You know, for many years, we basically, for the frontline treatment setting, were saying, "Okay, we have a targeted therapy, osimertinib. We're going to give that, and we're going to see what effect we can get out of that," with, you know, a median time of duration of treatment response averaging around 18 months, knowing that there are some that that's a lot longer and some that are a lot shorter. But recently, we've seen a lot of data emerging on combination strategies. The guideline has already been updated to incorporate two of these combinations: osimertinib with chemotherapy based off of the FLAURA2 trial, and then the combination of amivantamab with lazertinib based off of the MARIPOSA trial. And that was data on progression-free survival that was published and led to those particular recommendations. Now, more recently, we've seen data come out in smaller, randomized studies for other combinations. And more recently, we reviewed the RAMOSE study. So this was a phase II, open-label, randomized trial for patients with tyrosine kinase inhibitor–naive and really, treatment-naive advanced EGFR-mutated non–small cell lung cancer harboring one of these two classical EGFR alterations, randomized to either osimertinib alone or osimertinib with the combination of ramucirumab, which is an anti-VEGF agent. There's been a lot of data, preclinical and clinical, for the role of VEGF blockade, particularly in EGFR-mutated non–small cell lung cancer, so exploring the combination of this for synergy in the frontline setting really made a lot of sense. So again, this was a phase II trial that randomized patients prospectively to one of these two regimens. The population here is really what we typically see with EGFR-mutated non–small cell lung cancer, predominantly a younger population - median age on this study was 65 - predominantly female - 71% female - and predominantly nonsmokers. Now, what this study showed was that at a median follow-up of 16.6 months, the progression-free survival favored the combination arm with a median progression-free survival of 24.8 months with the combination of osimertinib plus ramucirumab versus 15.6 months for osimertinib alone, for a hazard ratio of benefit of 0.55. The landmark one- and two-year endpoints for progression-free survival also favored the combination arm, and response rates were relatively comparable between groups, with overall adverse events being more frequent in the combination group, specifically high blood pressure, proteinuria, and epistaxis, which are our common adverse events related to VEGF-blocking agents. So, it's good to see data in this space. Now, of note, though, this was a phase II study, so not a phase III level of evidence. In addition, when looking at the population, this was a randomized, multicenter study, but it was a US-only population. There was also some imbalance in the number of visits between arms, so the combination arm was seen more frequently than the arm that got osimertinib alone. Now, the imaging assessments were no different, but obviously this could lead to potential confounding, at least in timing of awareness of potential side effects and and things being brought to the attention of investigators. So very promising data here, but because, you know, of this being a phase II study, this actually led to no changes in the guideline at this time. Brittany Harvey: Understood. Yes, as you mentioned prior, it's important to understand the full body of evidence and to review the trials even when it doesn't impact the recommendations. Dr. Joshua Reuss: And I will say that, you know, there is an ongoing phase III study looking at a very similar combination. It's the phase III ECOG-ACRIN trial of the combination of osimertinib plus bevacizumab versus osimertinib alone in this specific population. So, you know, I think we will see phase III–level data for a combination of VEGF with osimertinib, but again, promising phase II data that did not lead to a change in the recommendation at this time. Brittany Harvey: Absolutely. We'll look forward to that ongoing trial to learn more about combination in this patient population. So then moving to that second patient population that you mentioned earlier where the panel reviewed evidence, what is the updated evidence and recommendation for patients with NRG1 fusions? Dr. Joshua Reuss: Yeah, so this was an exciting update that we made more recently with this unique iteration of the living guidelines. So, NRG1 fusions, this is perhaps a newer kid on the block in terms of driver alterations that has been known to be identified in non–small cell lung cancer among other solid tumors. It is very rare, occurring in less than 1% of solid tumors, but something that we know is a unique oncogenic pathway that can lead to oncogenesis and cancer development, including in non–small cell lung cancer. So up until now, unfortunately, there have not been targeted therapies that target this unique alteration. It's somewhat different than other driver alterations where there's a top-level signaling change in a protein. This is more of a ligand alteration that then alters, that then enables activation of more classical pathways, but again, through upregulation of a unique ligand. So a slightly different pathway but something that we know should be able to be targeted to promote patient survival for those with NRG1 fusions. So the therapy here is a therapy called zenocutuzumab. It's an IgG1 bispecific antibody against HER2 and HER3. So it prevents the downstream dimerization and signaling that occurs as a result of this NRG1 fusion and upregulation of the NRG1 signal. This was, as you can imagine with a rare alteration, a large phase II registrational study that examined this in advanced solid tumors containing the NRG1 fusion. This is the NRG1 registrational trial. And this study enrolled patients with advanced solid tumors who had progressed on prior therapy. Patients were treated with zenocutuzumab 750 milligrams IV every two weeks. Among 158 response-evaluable solid tumor patients, the response rate was 30%, median duration of response of 11.1 months, and a median progression-free survival of 6.8 months. Now, in those with non–small cell lung cancer, that made up 93 response-evaluable patients, very similar outcomes there: a response rate of 29%, median duration of response of 12.7 months, and a median progression-free survival of 6.8 months. This therapy did appear to be well tolerated. The most common higher-grade emergent side effects - grade 3 or higher - were anemia occurring in 5% and elevated liver numbers occurring in 3%. So this is a subsequent-line study, so this led to the updated recommendation that clinicians may offer zenocutuzumab in the subsequent-line setting for patients with advanced non–small cell lung cancer who harbor NRG1 fusions. So I think this does speak toward the incredible importance of next-generation sequencing and molecular testing for patients, particularly to include testing that looks at the RNA. These large fusions can sometimes be very challenging to detect on DNA sequencing platforms alone, so it's important to, if you have a high level of suspicion for an alteration like this, perhaps some of the mucinous adenocarcinomas where it's been challenging to find a driver alteration, and it's someone who is a never-smoker, really would want to include molecular testing that assesses the RNA level and not just the DNA. Brittany Harvey: Absolutely. It's important to have all the biomarkers available so that clinicians are able to use that to inform their decision-making. So then, given these changes in the guideline, what should clinicians know as they implement this latest living guideline update? And how do these changes impact patients? Dr. Joshua Reuss: Yeah, I think talking in reverse order of what we just discussed here, there is a new guideline update for NRG1 fusions. So I think making sure that that's being evaluated, that clinicians are testing for that and really looking for that result that should be incorporated in in most next-generation large sequencing assays to get that result, but it's very important that that is not overlooked now that we do have a therapy that's available in the subsequent-line setting, though it is important to note that patients with NRG1 fusions, at least the limited data that there is suggests that the efficacy to standard chemoimmunotherapy regimens is overall poor. So physicians unfortunately might be facing this question for second-line therapy in patients with NRG1 fusions sooner rather than later. For the former, for EGFR-altered non–small cell lung cancer and how do we incorporate VEGF-containing regimens into these patients? Our guideline top-level update did not change based off of review of this new study, but it's important for clinicians to know what other combinations may exist. You know, there are phase III studies looking at this combination in the frontline setting. And of course, there is data on other bispecific molecules that incorporate VEGF in the subsequent-line setting, particularly a combination that includes the VEGF/PD-1 bispecific antibody ivonescimab that's being studied in the HARMONi-A trial for patients with EGFR-mutated advanced non–small cell lung cancer, for which we hope to get some more definitive data in the coming months. Brittany Harvey: Definitely. And then you've just mentioned a few ongoing trials where we're looking for evidence to inform future updates. But thinking beyond that, into the future, what is the panel examining for future updates to this living guideline? Dr. Joshua Reuss: It's a very exciting time to be in the world of treating advanced non–small cell lung cancer, particularly patients with driver alterations, because there is so much evolving data that's changing our practice in real time, again highlighting the importance of these living guideline updates. I'd say there's many things that we're excited to see. You know, a lot of the combination regimens in EGFR-mutated non–small cell lung cancer for which there are approvals and current recommendations in our guideline, particularly osimertinib plus chemotherapy and amivantamab plus lazertinib - those are the two approved combination strategies in the front line - we are now seeing the emergence of overall survival data for those combinations. So obviously that is something that's going to be very important for the committee to review and incorporate into guideline updates. There are several new therapies coming down the road for other driver populations. We recently saw an approval for taletrectinib for ROS1 fusion–positive non–small cell lung cancer, so it's going to be important that the committee reviews the data and the publications regarding that therapy. And then there are other novel therapies that we're looking to see updated data on. There are multiple antibody-drug conjugates, which take the potent power of a chemotherapy molecule and attempt to make that targeted with an antibody targeting to a unique feature on the cancer cell. And there are several antibody-drug conjugates that are in development at various levels of promise in this space, particularly in EGFR-mutated non–small cell lung cancer, and I anticipate seeing some emerging data for that coming up in the near future as well. So really, lots to be excited in the space and lots for our committee to review to give guidance on so that these patients can really receive the top-level care wherever they are being treated in the country and throughout the world. Brittany Harvey: Yes, we'll await this new data to continue to provide optimal options for patients with stage IV non–small cell lung cancer with driver alterations. So, Dr. Reuss, I want to thank you so much for your work to rapidly and continuously update and review the evidence for this guideline and thank you for your time today. Dr. Joshua Reuss: Thank you so much. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available on the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday Stories until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "Amy Wu and the Lantern Festival by Kat Zhang" and this book has pretty illustrations of the lanterns so we recommend you to check it out!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

Episode 562 - Kate Maruyama - The Collective and The Alterations - Hollywood History, Horror and Family DynamicsKate Maruyama is the author of Harrowgate, Bleak Houses, and The Collective and her novella Family Solstice was named Best Fiction Book of 2021 by Rue Morgue Magazine. Her short work has appeared in numerous journals and anthologies and she is a two-time Pushcart Prize nominee, and winner of the Uncharted Short Story Prize. She served on the working Board for Women Who Submit, and the Board for the Shirley Jackson Awards. She writes, teaches, cooks, and eats in Los Angeles.https://www.katemaruyama.com/Support the show___https://livingthenextchapter.com/podcast produced by: https://truemediasolutions.ca/Coffee Refills are always appreciated, refill Dave's cup here, and thanks!https://buymeacoffee.com/truemediaca

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday Stories until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "Waiting for Hanami by J.P. Takahashi" which is full of pretty illustrations in this beautiful book set in Japan! As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

BUFFALO, NY - July 7, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience.” In this study, a research team led by first author Fei Fei and corresponding author Michelle Afkhami from the City of Hope Comprehensive Cancer Center investigated a rare and aggressive type of blood cancer called blastic plasmacytoid dendritic cell neoplasm (BPDCN). Their research uncovered frequent mutations in key genes and identified CCDC50 as a potential biomarker for diagnosis and disease monitoring. These findings could help improve how this cancer is detected and treated in the future. BPDCN most often affects older adults and is known for its rapid progression and poor survival rates. The researchers performed genetic sequencing on 21 patients to better understand the disease. They found that two genes, TET2 and ASXL1, were frequently mutated in these patients and were linked to worse survival, especially in those over 65 years old. “Our study revealed that TET2 (57%) and ASXL1 (33%) were the most frequently mutated genes, followed by NRAS (29%), SRSF2 (14%), ZRSR2 (14%), and KMT2D (14%).” The study also discovered that a gene called CCDC50 was expressed at much higher levels in BPDCN samples compared to other blood cancers, such as acute myeloid leukemia and chronic monomyelocytic leukemia. This suggests that CCDC50 may help clinicians distinguish BPDCN from other similar diseases. Importantly, CCDC50 levels dropped significantly in patients whose disease went into remission, highlighting its potential as a tool for tracking disease activity over time. Researchers further observed that patients who received stem cell transplants lived longer than those who did not, reinforcing the importance of this treatment approach. However, BPDCN remains a challenging disease with an overall poor outlook, making these findings an important step toward better care. This research provides new insights into the genetic changes behind BPDCN and points to CCDC50 as a promising marker to improve diagnosis and monitor treatment success. Larger studies will be needed to confirm these results and bring these discoveries closer to use in routine medical practice. DOI - https://doi.org/10.18632/oncotarget.28742 Correspondence to - Michelle Afkhami - mafkhami@coh.org Video short - https://www.youtube.com/watch?v=wUjr3uU3onI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28742 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50 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

Intro - Vince Welcome back to another episode of Let's Go Hunt -  Incognito Mode! - Now with 100% more chances of dying for Israel: Mike Gonçalves,  Dave Packard, who has a five day weekend Sam Alexander, who'd die for a pack of Marlboros and a kind word   And, letting the intrusive thoughts win at the Cabela's fish tank, I'm Vince H   Around the Campfire - Tonight we are talking about Mike's man bun and giggle switches   Five Star Alterations Questions:  Is there any truth to the rumors that you're still pillaging cloaks from the set of the Lord of the Rings? What got you started making wool ponchos? Did you have a background in textiles or gear design before this?   Why wool? What makes it stand out compared to modern synthetic materials? Where do you source your wool from? What kind of wool are you using—Merino, Pendleton-style, recycled military surplus? Do you treat the ponchos for water resistance? Have you heard stories from customers using them on hunts? How heavy are they, and how do they pack down? Do you offer different sizes or cuts for movement while carrying a rifle or bow? Are there any features built in—like pockets, slits for arms, or snaps? Do you make or plan to make ponchos with blaze orange or reversible designs?   What's your take on balancing traditional gear with modern hunting tech? Are there any new designs or products you're working on? If someone's never used wool in the field before, what would you tell them? Where can people find your work or order a poncho?   Eventual Ad Slot   Personal Gear Chat and Updates: Mike Range report with the hunting glock Dave Fuck plumbing, seriously Scouting/camping trip Wife bought me some pretty neat stuff for daddy day Sam   I have beer.   Vince Done did my controlled hunt application Mullein: what is it and what is it good for? Got some slides back  News and World Events Spotlighting With Dave:    What are some other uses for thermals? Subsonic 22LR: so  many ammo options, so what's the difference? What the Rut is going on here? or The Otter Creek Labs Polonium 30. What's it good for?   Reviews: Operation Shameless Bribery Gideon Optics affiliate coupon code: MOIST Camorado affiliate code: LETSGOHUNT Five Star Alterations code: MOIST  10% (11%) off!   Outro - Dave Support the sport and take a buddy hunting! If you like that buddy, tell them about our show! If you don't, tell him his mom has a regular cloak and it makes him look like a bad cosplay. Hit us up at lghpodcast.com.  Thanks for listening and Let's Go Hunt!    EMAIL: contact@lghpodcast.com Let's Go Hunt Archives - Firearms Radio Network

In this podcast, Dr. Brittany M. Szymaniak from the Feinberg School of Medicine at Northwestern University, Chicago, IL, USA, Dr. Alicia K. Morgans from the Dana-Farber Cancer Institute, Boston, MA, USA, and Dr. Neal D. Shore from the Carolina Urologic Research Center, Myrtle Beach, SC, USA, aim to identify obstacles to testing for homologous recombination repair (HRR) gene alterations in patients with prostate cancer that healthcare professionals encounter in day-to-day clinical practice, as well as discuss ways to potentially overcome them. This podcast is published open access in Targeted Oncology and is fully citeable. You can access the original published podcast article through the Targeted Oncology website and by using this link: https://link.springer.com/article/10.1007/s11523-025-01159-z. All conflicts of interest can be found online. Open Access This podcast is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The material in this podcast is included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday Stories until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "The Fantastic Bureau of Imagination by Brad Montague" which is about one of my favorite outdoor activities, birding! Have you ever watched birds before or went looking for one?As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

One of my fave guest/friends, Kate Maruyama, rejoins the show to celebrate her wonderful new novel, ALTERATIONS (Running Wild Press)! We talk about the book's long gestation/publishing history, Kate's love of old Hollywood & costume design, closeted movie stars and how she told the story of a gay relationship in the '30s & '40s, and how it felt to write a non-horror horror story. We get into her own Hollywood experience in the '90s, how it informs Alterations, and how it felt to repeatedly smash into the glass ceiling, as well as how ghosts creep into everything she writes, how older people become invisible but have stories to tell, and how important it was to have a champion in Toni Ann Johnson for this novel. We also discuss present-moment Los Angeles, the craft book about novella-writing she's co-writing, the need to decolonize her writing students, the (maybe non-existent) influence of Jodie Foster's Home For The Holidays on Alterations, the essay she wrote around the decline & death of her mother, Kit Reed, and more. Follow Kate on Bluesky and Instagram • More info at our site • Support The Virtual Memories Show via Stripe, Patreon, or Paypal, and subscribe to our e-newsletter

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday storytimes until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "Sun Bird by Lindsay Moore" and this book has pretty illustrations so we recommend you to check it out!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

Budget Reconciliation Update House Passes Funding Rescissions Request Secretary Kennedy Fires Entire Vaccine Advisory Panel Sens. Grassley, Wyden Release Report on OPO Oversight GOP Rep. Mark Green, Emergency Physician, to Retire from Congress Dept. of Health and Human Services No. 2 Sworn In MACPAC Releases June Report to Congress and more...

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday Storytimes until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "Dancing Dumplings for my one and only by Eva Wong Nava" A sweet book about loved ones and dumplings!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

On this MADM, Debra Barrett is sharing about the role of caregivers as she promotes Bradley Cooper's new documentary called Caregiving. Listen & share. Sponsor: CoraNation Tailoring & Alterations

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday storytimes until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "Camping Land by Ame Dyckman" where a family goes to Camping Land! Is it REALLY better than real camping? Let's find out!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

Billy Corgan discusses his unconventional record collecting philosophy while revealing the complex saga behind the Machina albums, the 25 legendary vinyl copies, the upcoming Machines of God boxset, Mellon Collie vinyl releases and more. Topics Include: Billy working on book for 10 years, restarted multiple times Billy buys lots of records but isn't fussy collector Prioritizes clean vinyl condition over perfect covers or variants Worked at record store in 80s, understands collector mindset Collects obscure major label releases from 60s and 70s Searches for forgotten bands with no online information trace Loves jazz on 10-inch records from late 50s/early 60s Record collection has no organization, total mess at home Bought thousand records on last tour, resells some Machina originally sprawling concept record about band breaking up Virgin Records treated band poorly despite massive previous sales Never finished complete Machina vision during original 2000 sessions Released truncated 15-song Machina I album through Virgin/EMI Band toured 11 months knowing they'd break up afterward Three weeks before breakup, Billy rushed to finish leftover recordings Record company rejected finished Machina II Billy dumped complete Machina II free on internet in 2000 First major band to release album free online, predating Radiohead Machina II became viral sensation, fans loved the record Produced only 25 hand-cut vinyl copies of Machina II Each copy uniquely wrapped in printed tape, all different Sent copies to Robert Smith, fans; now worth thousands Years of legal battles with Universal over complete release Initial "Mellon Collie and the Infinite Sadness" vinyl release Alterations for Mellon Collie running order New Machina box set finally coming through Madame ZuZu's Box contains 80 songs: complete vision plus extra tracks Universal separately reissuing original Machina I album remastered ZWAN vinyl reissue underway Archive contains over 60,000 pieces of physical media Hundreds of live concert recordings from 90s tours available Billy passionate about rewarding dedicated fans who dig crates Enter to win a record from us to celebrate Ep500 High resolution version of this podcast is available at: www.Patreon.com/VinylGuide Listen on Apple: https://apple.co/2Y6ORU0 Listen on Spotify: https://spoti.fi/36qhlc8

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday storytimes until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "I Quit by Kristen Tracy" Have you ever wanted to just quit? Well so does this cute cat! As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

·         In this podcast, the authors discuss the current therapeutic landscape of NSCLC with actionable alterations and provide their perspectives on treatment algorithms, and how to optimally sequence therapies for patients with tumors harboring actionable alterations, using patient cases to illustrate key principles. This podcast is published open access in Advances in Therapy and is fully citeable. You can access the original published podcast article through the Advances in Therapy website and by using this link: https://link.springer.com/article/10.1007/s12325-025-03195-7. All conflicts of interest can be found online. This podcast is intended for medical professionals. Open Access This podcast is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The material in this podcast is included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. 

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday storytimes until the rush for the Summer programs end somewhere after July 20th! Glad to have you listening with us today! Today we have Ms. Sarah reading "Everyone is Awake by Colin Meloy" in which our imaginations run wild with what everyone gets up to while we're trying to sleep! This book has very fun illustrations and we couldn't help but laugh at some of the silly scenes. Hope you enjoy it!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

We will be taking a break from our podcasts while Sarah prepares for the Summer Reading programs! We will have our regular Friday storytimes until the rush for the Summer programs end somewhere after July 20th!Glad to have you listening with us today! Today we have Ms. Sarah reading "Otter Carries On by Maya Tatsukawa" a story where an Otter learns having a handful of your favorite things isn't always the best, and I loved seeing the illustrations in this cute book!As always this book was selected from our library! Kids and Parents can read along with us, in this read aloud story time! Be sure to check out your local Library to check out what books they may have! If you prefer E-Books, sign into the Hoopla or Libby app using your Library Card and follow along from there!- Check out the Library Systems official website where you can find links to free resources, school and career guides, and news about our upcoming events! ⁠⁠⁠⁠⁠⁠⁠⁠⁠https://www.pawls.org/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ -Follow us on YouTube and enjoy our backlog of digital story hours and other great content! ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠www.youtube.com/@pawls365⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Original background track is Concerto for Two Violins by Bach.Alterations were made by us to make it fit the length of our content.Brought to you from the Pike-Amite-Walthall Library system.#library #books #pawlskids #kidsstorytime

The Creative ReUse Center in Norfolk gathered volunteers to alter donated dresses and suits for students to wear to the LGBTQ+ prom.

This week we are talking about things needed to prepare for your alteration process. Note that you do not need a strapless bra - pads will be sewn into your dress. Your seamstress will guide you on this. For daily content, follow @weddingfashionexpert on Instagram! www.weddingfashionexpert.com www.lovellabridal.com FOLLOW @WEDDINGFASHIONEXPERT ON SOCIAL: Instagram & TikTok SUBSCRIBE ON YOUTUBE! NEW Episode every Wednesday for #WeddingWednesday  READ MY BOOK  FREE DOWNLOADS Online Education for Wedding Professionals Speaking & Appearances SHOP MY AMAZON STORE GET SOCIAL WITH LOVELLA:  Instagram: @lovellabridal @lovellaplus  TikTok: @lovellabridal Pinterest

Drs. Sabari and Yu discuss the molecular landscape of HER2-mutant lung cancer, including its genomic characteristics, common co-mutations, and differences between HER2 mutations and HER2 amplification. This discussion also explores the prevalence and clinical patterns of HER2 mutations, their oncogenic mechanisms, their impact on tumor behavior and metastases, and potential environmental or genetic contributors to their development.

We start by discussing the difficult reality of intentional abandonment with 1Xtra's Fee Mak. We also hear from fitness influencer Ashley Cain, with the launch of his new BBC Three series, Into The Danger Zone. We then get into embracing heritage on stage with actress Cherrelle Skeete, who is leading in The National Theatre's play, Alterations.

Jo Johnson's explorations in sound have ranged from free-form punk with Huggy Bear in the 90s, to underground techno in the 00s, and, for the last decade, deeply expressive electronic minimalism that pays tribute to the many women who pioneered this genre. She has released with respected labels including Further Records and Mysteries of the Deep in the US and Frequency Domain and Castles in Space in the UK. Her latest project, Alterations, is a 'slow' album that she is recording and self-releasing track-by-track throughout 2025. For the fourth edition of Waves, Jo Johnson presents a mix of absolute celestial beauty, building delicately with deep and lush ambiance into a trip of interstellar melodies, this is the perfect way to start your week off right. Follow: https://soundcloud.com/werkhouse https://jojohnson.bandcamp.com/ https://www.instagram.com/jojohnson.tinysilences/

Mickey-Jo recently headed to the National Theatre in London to see their latest production, a new staging of Michael Abbensetts' ALTERATIONS.The play stars Arinzé Kene and is directed by Lynette Linton in its largest ever staging, with additional material contributed by Trish Cooke.Check out this new review for Mickey-Jo's thoughts on this production, its performances, and what it has to say about immigration, identity, and the black experience in 1970s Britain.•00:00 | introduction02:19 | synopsis05:56 | characters / themes11:43 | creative choices15:14 | performances•About Mickey-Jo:As one of the leading voices in theatre criticism on a social platform, Mickey-Jo is pioneering a new medium for a dwindling field. His YouTube channel: ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠MickeyJoTheatre⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ is the largest worldwide in terms of dedicated theatre criticism, where he also share features, news and interviews as well as lifestyle content for over 75,000 subscribers. Since establishing himself as a theatre critic he has been able to work internationally. With a viewership that is largely split between the US and the UK he has been fortunate enough to be able to work with PR, Marketing, and Social Media representatives for shows in New York, London, Edinburgh, Hamburg, Toronto, Sao Pãolo, and Paris. He has also twice received accreditation from the world renowned Edinburgh Festival Fringe. His reviews and features have also been published by WhatsOnStage, for whom he was a panelist to help curate nominees for their 2023 and 2024 Awards as well as BroadwayWorldUK, Musicals Magazine and LondonTheatre.co.uk. He has been invited to speak to private tour groups, at the BEAM 2023 new musical theatre conference at Oxford Playhouse, and on a panel of critics at an event for young people considering a career in the arts courtesy of Go Live Theatre Projects. Instagram/TikTok/X: @MickeyJoTheatre

Drs. Amy Mathers and Julie Ann Justo join Dr. Erin McCreary to talk all things Stenotrophomonas maltophilia, a water-loving organism and frequent colonizer. Hear from the experts on why this organism is so difficult to treat, which agents have in vitro activity, and how to optimize antimicrobial regimens, including the use of combination therapy, in the setting of true infections. This medical education was provided by an unrestricted grant from Shionogi. References: Infectious Diseases Society of America 2024 Guidance on the Treatment of Antimicrobial-Resistant Gram-Negative Infections. Clin Infect Dis. 2024 Aug 7:ciae403. doi: 10.1093/cid/ciae403. PMID: 39108079. Clinical challenges treating Stenotrophomonas maltophilia infections: an update. JAC Antimicrob Resist. 2022 May 5;4(3):dlac040. doi: 10.1093/jacamr/dlac040. PMID: 35529051. Alterations of the Oral Microbiome and Cumulative Carbapenem Exposure Are Associated With Stenotrophomonas maltophilia Infection in Patients With Acute Myeloid Leukemia Receiving Chemotherapy. Clin Infect Dis. 2021 May 4;72(9):1507-1513. doi: 10.1093/cid/ciaa778. PMID: 32544947. An Overview of the Treatment of Less Common Non–Lactose-Fermenting Gram-Negative Bacteria. Pharmacotherapy. 2020 Sep;40(9):936-951. doi: 10.1002/phar.2447. PMID: 32687670.

Dr. Jyoti Patel is back on the podcast to discuss the updates to the living guideline on therapy for stage IV NSCLC with driver alterations. She shares updated recommendations in the first- and second-line settings for patients with stage IV NSCLC and classical EGFR mutations, and the impact of these updates for clinicians and patients. We also look to the future to discuss ongoing developments in the field. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02785     Brittany Harvey: Welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows including this one at asco.org/podcasts.   My name is Brittany Harvey and today I'm interviewing Dr. Jyoti Patel from Northwestern University, co-chair on “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.3.” It's great to have you back on the show today, Dr. Patel. Dr. Jyoti Patel: Thanks so much. Happy to be here. Brittany Harvey: And then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Patel, who has joined us here today, are available online with the publication of the guideline and in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content of this update, Dr. Patel, this clinical practice guideline for systemic therapy for patients with stage IV non small cell lung cancer with driver alterations is living, meaning that it's continuously reviewed and updated. So what data prompted this latest change to the recommendations? Dr. Jyoti Patel: Thanks so much. So it's really been an exciting time in the treatment of EGFR lung cancer, particularly this past year has required us to rethink approaches to front- and second-line therapy. In this particular update, we examined what patients in the front-line setting may be offered by their clinicians. And so we're talking about the population of classical EGFR mutations, so exon 19 and exon 21 L858R substitution. And so certainly for this population, osimertinib has a high level of evidence and should be offered to all patients at the time of diagnosis when they present with advanced disease. Our last update included a recommendation that patients could also get platinum doublet chemotherapy with osimertinib or osimertinib alone. This current recommendation also introduces another alternative therapy and that's the combination of amivantamab plus lazertinib. And so now, clinicians are faced with three really good options for their patients with EGFR exon19 deletion or L858R. Brittany Harvey: It's great to hear that there's this advance in the space, particularly for patients with these classical EGFR mutations that you mentioned. So what should clinicians know as they implement these new first-line recommendations? Dr. Jyoti Patel:  I think it's become more complex than ever. Certainly, we know again that patients should get osimertinib in the frontline setting. But we've been kind of stuck at progression-free survival that's between a year and a half and two years. And so we've really been looking at opportunities to intensify therapy. So one could certainly be with chemotherapy or switching over to amivantamab, the bispecific antibody that targets EGFR and MET plus lazertinib, an oral TKI that's very similar in structure to osimertinib. And when you're talking to a patient, it's really a conversation about balancing efficacy with toxicity. Unfortunately, as we know, there aren't that many free lunches. And so if we think about what a patient is hoping for in their therapy and how we can further personalize treatment options, really is important to look at some of the analyses for this study. So in the study of amivantamab plus lazertinib, we know that there were increased toxicities with a combination of both therapies. In fact, up to 75% of patients had over grade 3 toxicities, versus about 43% of patients with osimertinib monotherapy. And we know if we look back at FLAURA2, almost two thirds of patients with osimertinib and chemotherapy had grade 3 toxicities, compared to 27% of patients with osimertinib alone. So we certainly see an increase in toxicities. Then we have to ask ourselves, are those paper toxicities or ones that really impact patients? And we know that amivantamab, for example, causes significant cutaneous toxicities. With both of these therapies, whether it's chemotherapy or adding amivantamab, there's the burden of infusional visits and increased time in the doctor's office. Certainly with chemotherapy, there can be an increased incidence of myelosuppression. And so when we're thinking about advising our patients, certainly we need to talk about the toxicities. But one thing that we've been able to do is to look at the patients that were included in this trial. And what we really find is that in higher risk cohorts, particularly those that we know historically have done less well with standard osimertinib, so patients, for example, with CNS metastasis, for those patients with co-mutations, it may be that that additive benefit is significant. And so one example I think would be from the MARIPOSA study, again, the study of amivantamab and lazertinib versus chemotherapy. What we can say is that patients who had co-mutations, so patients with EGFR mutations as well as TP53, lazertinib and amivantamab led to a hazard ratio of 0.65 compared to osimertinib alone. So that was 18.2 months versus 12.9 months. And so this may be really important to patients. And we also see conversely that patients with wild type TP53, so those patients who didn't have the mutation, probably had equivalent survival regardless of therapy. So certainly, we need to prospectively study some of these high-risk cohorts. We've only seen progression-free survival in these studies. And so at this juncture, we can advise our patients about toxicity, the improvements in certain categories of progression-free survival, but we really still don't know how this pans out in overall survival. In many of these studies, all patients do not necessarily cross over to the study arm and so they may have lost the benefit of subsequent therapy. Brittany Harvey: Absolutely. It's very important to talk about that balance of benefits and risks and particularly those toxicities that you discussed. So I appreciate reviewing that recommendation and the considerations for clinicians for first-line therapy. This update also included a second-line treatment update. What is that update for patients with EGFR alterations? Dr. Jyoti Patel: So this is where it gets super tricky because we have a frontline option with amivantamab and now we've had an update in the second line option. So what we said is that for patients who have progressed on an EGFR TKI, and in the United States, certainly that's predominantly osimertinib, or those in other parts of the world that may have gotten an earlier generation TKI, but do not have evidence of T790M or other targetable mutations, we can offer patients chemotherapy with or without amivantamab. And so certainly we have seen that this again leads to improved survival. There have also been a number of studies looking at incorporation of PD-L1 and anti-VEGF therapies. And what we can say, I think pretty clearly is that multiple phase 3 trials have really shown no benefit of the addition of PD-1 to platinum chemotherapy. But there are some emerging bispecific antibodies that may target PD-1 as well as VEGF, or combinations of antibodies that target both of those pathways that may improve outcome. At this juncture, I think we feel that the evidence surrounding chemotherapy plus amivantamab is strongest, but there is certainly work in this space that will be of interest. Now, what happens if your patient received amivantamab and lazertinib in the frontline setting and then has progression? And so we're trying to understand resistance mechanisms and opportunities for treatment. What the panel decided to recommend, based on the available evidence, was that certainly those patients should get platinum-based chemotherapy, but there may also be a role for antivascular endothelial growth factor targeting therapy such as bevacizumab in patients in whom it would be safe. Brittany Harvey: Great. I appreciate you detailing those recommendations when it gets complicated in the second-line setting. So what should clinicians know as they implement these second-line recommendations too? Dr. Jyoti Patel: So certainly the frontline setting matters significantly. So if a patient gets osimertinib in the frontline setting, we generally suggest that patients undergo repeat testing to see if they have another targetable mutation. If they don't, then I think preferred therapy would be chemotherapy with or without amivantamab. And amivantamab leads to a significant improvement in progression-free survival and response rate at the cost of increased risk of toxicity. For patients who get FLAURA2 in the frontline setting, chemotherapy plus osimertinib, it's a little bit of an unclear space. Those patients most likely would get docetaxel with or without ramucirumab. But there are other agents that we hope to have available to our patients in the near future. For patients who receive amivantamab and osimertinib, we recommend that those patients get chemotherapy probably with anti-VEGF as demonstrated by multiple trials that have shown the improved progression-free survival with introduction of an anti-VEGF agent. And we've seen evidence of amivantamab in the third line setting, so it is likely that this question about sequencing really takes center stage in our next set of trials. When you're talking to a patient, I think again, it's absolutely important to discuss: What are their goals? How symptomatic or how fast is their progression? Are there ways in which patients may benefit from spot treatment oligoprogression such as radiation? When is the right time for introduction of amivantamab and when do we think patients need chemotherapy? Is it up front or predominantly in the second-line setting? Brittany Harvey: Definitely. And then you've just touched on the goals of treatment for individual patients. So in your view, what does this update mean for patients with stage IV non-small cell lung cancer and an EGFR alteration? Dr. Jyoti Patel: For patients, this is a time in which shared decision making really needs to take center stage. So our best patients are those patients that are best informed not only about their disease but also have a good understanding about what is important to them and their families in terms of care. And so bringing that shared understanding to the table again helps us think about this particular cancer as more of a journey rather than just a one off treatment. Therapy will hopefully be prolonged, and so it's absolutely important that we address toxicities, make therapies more tolerable, again, with the shared goal of living long and living well. Brittany Harvey: Absolutely. Those are key points to making sure that patients are living both longer and have a good quality of life during that time as well. So then, before you mentioned the possibility of future sequencing trials and other ongoing developments. What additional studies or future directions is the panel examining for future updates to this living guideline? Dr. Jyoti Patel: So certainly we're thinking about trials that look at, for example, cfDNA clearance. So are there patients that do well and can we detect that early on without having to intensify therapy on day 1 so it may be that we add chemotherapy a little bit later. I think really exciting are some of the new bispecific. The HARMONi-A trial was a trial in China of a novel bispecific, ivonescimab. And this drug targets both PD-1 and VEGF and it was combined with chemotherapy. And this trial found almost a doubling of progression-free survival with this drug in combination chemotherapy in an EGFR patient population. That study is being planned and being run in the United States to see if we have similar outcomes with a more diverse population. So certainly that's exciting. There are a number of antibody drug conjugates that are being studied in the post-chemotherapy setting as well. And I think we'll likely soon see a better understanding of what co-mutations and burden of disease really mean when we're thinking about assigning treatment. So which patients, again, need intensification of therapy and which patients may do really well on just an oral agent that they're taking at home with more tolerable toxicity than dual treatment. Brittany Harvey: Yes, we'll look forward to continued developments in these fields and seeing some of those studies come to fruition. So with that, I want to thank you for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Patel. Dr. Jyoti Patel: Thanks so much, Brittany. It's really an exciting time for lung cancer and we hope that these updates really help physicians decide the best treatments for their patients. Again, it's a rapidly evolving landscape which is fantastic, but it does become more cumbersome to stay ahead of the literature. Brittany Harvey: Definitely. And so we appreciate your time and the panel's time spent reviewing this literature and providing this much needed information to clinicians everywhere. So finally, thank you to all of our listeners for tuning into the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the  Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.  

Dr. Lyudmila Bazhenova joins us again to share the newest changes to the living guideline on therapy for stage IV NSCLC without driver alterations. She discusses new evidence reviewed by the panel and changes to second-line recommendations for patients with good performance status and HER2 overexpression, and what these updates mean in practice. We discuss ongoing evidence generation as we await further updates to these living guidelines. Read the full living guideline update “Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02786     Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, co-chair on “Therapy for Stage IV Non–Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2024.3.” It's great to have you back on the show today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It's my pleasure to be here as always. Brittany Harvey: Great. Then before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the entire guideline panel, including Dr. Bazhenova, who has joined us here today, are available online with the publication of the guide in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into the content here, first, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer without driver alterations has frequent updates to the recommendations. What prompted this latest update? Dr. Lyudmila Bazhenova: Living ASCO guidelines are created to keep up with rapidly changing evidence which affect treatment of our patients with lung cancer. As a committee, we review published literature on a specific topic at the regular intervals and determine if it alters any recommendations. This time, upon our literature review, we felt that there are new data that requires an update in the guidelines and therefore the guidelines were updated. Brittany Harvey: Great. Thank you for that updated information. So then it looks like the panel updated recommendations for second line and subsequent treatment options for patients with good performance status and HER2 overexpression. What is that updated recommendation from the panel? Dr. Lyudmila Bazhenova: Yes, this is correct. We now added an extra recommendation for patients with stage IV non-small cell lung cancer who have overexpression of the protein called HER2. HER2 overexpression with 2+/3+ level via immunohistochemistry is seen in approximately 8% to 20% of patients with lung cancer. And the data behind our recommendation comes from the DESTINY-Lung01 trial where patients with HER2 overexpression were treated with trastuzumab deruxtecan. And we saw that if patients with stage IV non-small cell lung cancer had a HER2 IHC score of 3+, overall response rate was seen at 53% and median duration of response was 6.9 months and, therefore, that in our opinion qualified for updated recommendation. We are still waiting for additional results that will be released later on another clinical trial where we see preliminary data presented at the World Conference of Lung Cancer in 2024. They looked at 36 patients also with HER2 overexpression and saw the overall response rate of almost 45%. It is important to highlight in this smaller study that a majority of the patients in the study were actually having EGFR mutation and the response rate in those patients who had an EGFR mutation was higher than the response rate in patients without EGFR mutations who just had a HER2 overexpression. So for now this is updated in the guidelines, but we will wait for additional data or formal publication of a World Lung Conference presentation and see if those recommendations need to be changed. Brittany Harvey: Understood, and I appreciate you providing the context of some of those ongoing developments as well. So then what should clinicians know as they implement this updated recommendation? Dr. Lyudmila Bazhenova: Number one, we should all start from remembering to test for HER2 via immunohistochemistry. There is a slight difference in what considers HER2 positive in lung versus breast. In lung, we use what's called the gastric scoring and the difference is the circumferential versus non circumferential staining of the membrane. And number two, immunohistochemistry is not always included in next generation sequencing panels. So when you order your next generation sequencing, I think it's important to know if your company that you're using is testing for HER2 via immunohistochemistry. And if it's not, make sure that you find a company that does or work with your local pathology department to make sure that this testing is offered. It is also important to know the difference between HER2 overexpression and HER2 exon 20 insertion mutation even though the treatment for those two abnormalities is the same, which is trastuzumab deruxtecan. But the benefit that you can cite your patients and the rigor of the literature supporting the usage of trastuzumab deruxtecan in mutation versus overexpression is different. Brittany Harvey: Yes. And as you mentioned, it's essential that, in the first place, patients are actually receiving the testing so that we know if they're eligible for these treatment options. So what additionally does this change mean for patients with stage IV non-small cell lung cancer and HER2 overexpression? Dr. Lyudmila Bazhenova: So for patients, it adds another treatment modality which is now FDA approved. So if there are patients listening to me, make sure that your physician has tested your tumor for HER2 overexpression. So I think proactive asking of your physician would be very appropriate in this situation. Brittany Harvey: Absolutely. And then earlier you mentioned an ongoing trial that the panel was looking to for the future. But what other additional trials did the panel review during this guideline update and what is the panel examining for future updates to this living guideline? Dr. Lyudmila Bazhenova: So at this point we reviewed three additional studies. The results of those studies did not make it into a change in guidelines. So we reviewed the HARMONi-2 trial.  HARMONi-2 trial so far does not have an official publication and, as per our strategy on how we come up with ASCO guidelines, we need to wait for an official publication. So this is one thing we're going to be expecting in the future. Once this is published, we will review it and decide if we need to make an additional change in recommendations. For those of you who are not aware, HARMONi-2 trial used bispecific monoclonal antibody against VEGF and PD-1 and was a phase III randomized trial comparing their investigational product which is called ivonescimab over pembrolizumab for patients with PD-L1 more than 50. And again, we are waiting for the final publication to make our recommendation. The second trial we reviewed was a LUNAR trial and the LUNAR trial looked at addition of tumor treating fields to chemotherapy or immunotherapy in patients whose cancer progressed with platinum doublet. The key point about this study is that immunotherapy was not required to be administered in a first line setting which is a current standard of care in the United States. And even though the study met their primary endpoint of overall survival, there were more benefits in patients who were immunotherapy naive in the second line. And we felt that given the potential lifestyle implication of wearing a device for 18 hours per day, and the lack of evidence in immunotherapy-pretreated population, and the absence of data in the first-line setting where we currently using immunotherapy in the United States, we felt that there is insufficient data to definitely recommend addition of tumor treating fields to systemic chemotherapy for most patients. And we are waiting for additional trials that are ongoing in this setting to formalize or change our recommendations. And we also reviewed- the final study that we reviewed was TROPION-Lung01. TROPION-Lung01 study was a phase III study in post platinum doublet setting which compared efficacy of Dato-DXd and docetaxel and trials showed improvement in progression free survival but not in overall survival. And progression free survival benefit was more pronounced in non-squamous carcinoma histology subgroup and we felt that the results do appear promising, but the strength of evidence which was based on unplanned subgroup analysis was not sufficient enough to make a change in treatment recommendation at this time. Brittany Harvey: I appreciate your transparency on why some of that data did not prompt a change to recommendations at this time. And additionally, we'll look forward to those future published results and potential incorporation of new data into future versions of this living guideline. So, I want to thank you so much for your work to rapidly and continuously update this guideline and for your time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It is my pleasure. Thank you so much. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the  Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.  

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/CPE/AAPA/IPCE information, and to apply for credit, please visit us at PeerView.com/VMG865. CME/MOC/NCPD/CPE/AAPA/IPCE credit will be available until February 5, 2026.Targeting PIK3CA/AKT1/PTEN and Other Alterations in HR+, HER2- MBC: Navigating the Evidence and Guidance for Use In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an independent educational grant from AstraZeneca.Disclosure information is available at the beginning of the video presentation.

Episode 211 NPTEFF Gait Step Length Alterations

Now for the next in our regular slots here on RNIB Connect Radio highlighting what is on offer at the National Theatre in London for blind and partially sighted people with audio description. Our Toby Davey was joined again by David Bellwood, Head of Access at the National Theatre to chat about a few up-coming audio described shows at the National Theatre and a couple that are available online with audio description too via NTatHome.com. Audio described performances included: Lynette Linton Directing Michael Abbensetts' seminal comedy, illuminating the Guyanese experience of 1970s London and the aspirations and sacrifices of the Windrush generation in ‘Alterations' 'Alterations' audio described performances - Saturday 15 March, 2.30pm, touch tour 12.30pm and Friday 28 March, 7.30pm, touch tour 5.30pm, national Theatre's Lyttleton Theatre. Then to the return to the National Theatre of ‘Dear England', James Graham's Olivier-Award winning examination of nation and game which reflects on Gareth Southgate's final chapter as England manager. ‘Dear England' audio described performances - Saturday 12 April, 2pm, touch tour 12noon and Friday 23 May, 7.30pm, touch tour 5.30pm, National Theatre's Olivier Theatre.  From NTAtHome.com with audio description David recommended ‘The Hot Wing King' and ‘Dear Octopus' both available from NTAtHome.com. To find out more about the National Theatre's audio description offer and services for blind and partially sighted people do either call the NT on 020 7452 3961 or visit the NT website - https://www.nationaltheatre.org.uk And for more about NTatHome.com and to view many theatre productions online with audio description do visit - https://www.ntathome.com (Image shows National Theatre logo, A capital N and T in black against a white background)

In this episode, we dive straight into the essentials of wedding attire alterations with Cora Mercer from Tailored in White. Discover actionable tips on how to save money on tailoring while ensuring your attire fits like a glove on the day of. Cora explains the intricacies behind alteration costs, gives advice on handling size changes, and shares the best bustling techniques to enhance both comfort and style. She also covers when to seek out a tailor and the expected timeline for the alteration process. Listen in for invaluable insights that will help you navigate wedding attire adjustments smartly and creatively! Want to listen to us Ad-free? Click HERE to become a premium subscriber. What you will learn The Importance of Tailoring: Why proper fitting should be a key aspect of your wedding planning. Bustling Techniques: How to choose the right bustling for your dress and the importance of practicing before the big day. Cost Factors: Understanding what drives the cost of alterations and how to budget for them. Accommodating Changes: Tips for handling alterations related to pregnancy or weight loss. Undergarments and Structure: The role of undergarments and built-in support in enhancing the fit and look of your wedding attire. Fabric Considerations: How different materials and details like lace and beading affect the tailoring process. Preservation Tips: Advice on preserving your gown post-wedding, whether for sentimental reasons or practical future use. Links We Referenced Tailored in White Website Tailored in White on Tik Tok Tailored in White on Instagram Pinterest: @tailoredinwhite The Big Wedding Planning Podcast is... Hosted and produced by Michelle Martinez & Shaun Gray Music by Steph Altman of Mophonics On Instagram @thebigweddingplanningpodcast and be sure to use #planthatwedding when posting, so you can get our attention! Easy to get in touch with. Email us at hello@thebigweddingplanningpodcast.com or Call and leave a message at 415-723-1625 and you might hear your voice on an episode Learn more about your ad choices. Visit megaphone.fm/adchoices

This week, we had the pleasure of sitting down with Carol Olson, the owner and creative genius behind Alterations by Carol, a studio that's redefining what's possible in the world of sewing and design. Carol's deep love for sewing and costume design has grown into a successful business, where she helps brides, prom-goers, and clients of all kinds achieve the perfect fit for their big moments. In this episode, we explore: ✨ How Carol turned her passion for sewing into a business. ✨ Her favorite part of working with brides and getting to know the stories behind their wedding days. ✨ The incredible versatility of her services—from wedding gowns to vintage gown restyling, prom attire, and everyday alterations. ✨ What it's like to serve over 400 happy clients in her new studio since opening in 2023. Get inspired by Carol's journey and discover how her expertise ensures every garment is tailored to perfection. Whether you're a bride preparing for your wedding, looking for prom dress magic, or just need to transform your wardrobe, Carol has you covered.

Ready to ground yourself in proven wisdom as you step into 2025? This conversation lights the way forward.In this illuminating episode, Myra Lewin shares her insights on what Ayurveda looks like in our modern world. Interviewed by Samantha, Myra delves into the origins of this 5,000-year-old science and how its core principles remain relevant today, beyond wellness trends and quick fixes.What does it mean to be aligned with the roots of Ayurveda? Ever wondered if you're getting the real deal or a Westernized version of Ayurveda? From dosha quizzes to quick-fix herbs, Myra and Samantha uncover the common pitfalls of modern adaptations and explore what it means to practice Ayurveda in its most potent form. They cut through the confusion, exploring how these ancient practices have evolved, what's been influenced by western thought, and how to recognize teachings that honor Ayurveda's original principles and efficiency.Topics covered:The origins and evolution of Ayurvedic wisdom.How colonialism influenced the way Ayurveda is practiced today.Spotting the difference between pure and diluted teachings.Why spiritual connection matters in healing and is often overlooked.Simple, powerful ways to honor Ayurveda's original intention and feel the true potency and benefits.Happy New Year!Enrollment for our 200-hour Ayurvedic Health Advisor and 600-hour Ayurvedic Health Counselor trainings are open all year. If leading others on the path of healing feels like your dharma, we invite you to book a free 1:1 call here with a member of our team so you can determine if one of our trainings is the right fit for you.Thanks for tuning in to the Everyday Ayurveda and Yoga at Hale Pule podcast. If this series inspires you to live a more holistic and balanced lifestyle, we invite you to join our free private community, the Hale Pule Sangha. Need a reset for your digestion and your life? Check out our 4-week Agni Therapy program - It includes Ayurveda and Yoga practices, a 1:1 consultation, energy work, a private support group, and a library of Q&As with Myra to support your healing process.If you enjoyed this podcast and received value from it, we'd appreciate if you left a heartfelt review. It supports our mission at Hale Pule and helps us reach more people.

References Guerra, DJ 2024. Biochemistry lectures de novo. Zevon, W. 1980. "Empty Handed Heart" https://open.spotify.com/track/2jqAdzGsLts2SPcDxNjqGJ?si=a3d0cf83804641c3 Manfred Mann [solo], Colin Pattenden, Peter Thomas .1976 "The Road to Babylon" https://open.spotify.com/track/7cUBAZwaFjPkdEkFMAGy7Y?si=210544d489544d29 Haydn, Michael. 1794. Excerpts from his Catholic Masses https://open.spotify.com/album/67v4gHJdnVWAn4erEtbuIc?si=3FHMYbRGQJaTHGbqYHHo8Q --- Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

TSP content is for entertainment purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or qualified healthcare provider with any questions you may have regarding a medical condition.FDA Text for disclaimer.This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.Laura Eisenhower is a Researcher, Author and an Astrologer.  She is an internationally acclaimed speaker who has presented her work world wide.  Laura is the great-granddaughter of President Dwight David Eisenhower and she reveals Exopolitical information about his administration that has been largely held in secrecy. She is considered by many to be one of North Americas leading researchers and experts on: Health,  Exopolitics, Alchemy, Metaphysics, Astrology and Galactic History. Laura works to free us from the 3-D holographic time-loop, False Archonic systems and Military Industrial Complex and exposes hidden agendas so we can take our power back. Laura Eisenhower Website:https://cosmicgaia.org/Laura Eisenhower Rumble Channels:https://rumble.com/user/LauraEisenhower13https://rumble.com/c/LauraEisenhowershow support for the Typical skeptic podcast https://paypal.me/typicalskepticmedia cashapp $kalil1121 venmo @robert-kalil or buy me a coffee at https://buymeacoffee.com/typicalskeptic

In this week's episode we'll learn more about how clonal hematopoiesis affects prognosis in patients with telomere biology disorders, consider recently uncovered molecular subtypes of extracutaneous juvenile xanthogranulomas, and discuss a clinical trial of the BCMA-CD3 bispecific antibody teclistamab in patients with relapsed/refractory multiple myeloma who have received previous BCMA-targeted therapy.Featured Articles:Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutationsRecurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissueEfficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies

In this episode, I'm  joined by Anna, the talented and compassionate owner of The Heart-Centered Seamstress. Anna shares how she transformed her passions for sewing and holistic wellness into a business dedicated to providing not only stunning bridal alterations, but also a calming and supportive environment for brides-to-be.  If you're a bridal seamstress, a wedding industry professional, or a bride-to-be seeking a more holistic approach to your wedding preparations, this conversation is packed with insights on balancing passion with purpose, infusing wellness into your work, and finding joy in the small, intentional moments. In this episode: Anna's Journey into Sewing. Anna's story of realizing her passion for both sewing and wellness, leading her to create a business focused on both. How Anna integrates wellness techniques like Reiki, energy balancing, and meditation into her fittings, giving brides a peaceful and supportive experience. The importance of creating a safe, empathetic space where brides can truly be themselves, turning fittings into a comfortable and memorable experience. Anna's approach to balancing work and personal wellness to avoid burnout, and her advice for other seamstresses and entrepreneurs on prioritizing rest as part of a healthy business strategy. Tips on finding your niche in the world of seamstresses.  How Anna is celebrating "No-Stress November" Connect with Anna: Instagram: https://www.instagram.com/theheartcenteredseamstressWebsite: https://www.theheartcenteredseamstress.com/ Connect with Nadine:  Check out the exclusive private podcast series, Fitting Packages 101: https://enchanting-sun-77080.myflodesk.com/privatepodcast Become a member: https://secretsofabridalseamstresspodcast.com/membership Instagram: https://www.instagram.com/secretsofabridalseamstress/ TikTok: https://www.tiktok.com/@nadinebozeman YouTube: https://www.youtube.com/@secretsofabridalseamstress

Dr. Lyudmila Bazheova share the latest updates to the ASCO living guideline on therapy for stage IV non-small cell lung cancer with driver alterations. She discusses changes for patients with EGFR driver alterations in both the first- and second-line setting, and reviews the evidence supporting these updated recommendations, from trials such as MARIPOSA, MARIPOSA-2, CheckMate 722, and KEYNOTE-789. Stay tuned for future updates to this continuously updated guideline. Read the full update, “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2.” at www.asco.org/living-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/living-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-24-02133   Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts.   My name is Brittany Harvey and today I'm interviewing Dr. Lyudmila Bazhenova from University of California San Diego Moores Cancer Center, lead author on “Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.2.” Thank you for being here, Dr. Bazhenova. Dr. Lyudmila Bazhenova: It is my pleasure. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Bazhenova, who has joined us on this episode today, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes. So then, to kick us off on the content here, Dr. Bazhenova, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer with driver alterations is being updated routinely as a living guideline. So what prompted the update to the recommendations in this latest version? Dr. Lyudmila Bazhenova: Living ASCO Guidelines are developed to keep up with rapidly changing evidence which affect treatment of our patients with lung cancer. In this recently published guideline, we reviewed new evidence for patients with metastatic lung cancer harboring driver alterations. We reviewed evidence from four published studies, MARIPOSA, MARIPOSA-2, CheckMate 722 and KEYNOTE-789 that resulted in updated guidelines. Brittany Harvey: Great. And then based off those four trials that you just mentioned, what are the updated recommendations for patients with stage IV non-small cell lung cancer and an EGFR exon 19 deletion or exon 21 L858R substitution? Dr. Lyudmila Bazhenova: In the previous guideline, we detailed FLAURA 2 study which was presented and published in the past. In this guideline, we specifically highlighted a phase 3 MARIPOSA trial which took patients with untreated advanced non-small cell lung cancer which harbored classical EGFR mutations such as EGFR deletion 19 and L858R. In this study, patients were randomly assigned to receive amivantamab plus lazertinib or osimertinib or lazertinib alone. And the study showed that the primary endpoint which was progression-free survival was longer with amivantamab plus lazertinib compared to osimertinib, and numerically the progression free survival was 23.7 months with ami-lazertinib versus 16.6 months with osimertinib which was statistically significant. The challenge that we have to face when discussing that option with our patients is increased toxicity with amivantamab and lazertinib combination. For example grade 3 treatment adverse events were 75% with amivantamab and lazertinib and 43% with osimertinib. So this will require shared decision making between our patients and ourselves. We also noticed in the guidelines that there was a subgroup analysis of that study showing that the patients with a higher disease burden, central nervous metastasis or brain metastasis as well as disease which considered to be a higher risk such as commutation, for example, p53 and liver metastasis, they might benefit from intensified therapy. However, another thing that we are highlighting in the guideline is that at this point we do not know how the intensification of therapy will change overall survival of our patients. So one needs to take into account increased toxicity with that combination. Brittany Harvey: So then Dr. Bazhenova, in addition to those updates for first line therapy, what are the updated recommendations for second line therapy? Dr. Lyudmila Bazhenova: For patients who have progressive disease on osimertinib or other EGFR tyrosine kinase inhibitors, we also updated our guidelines highlighting MARIPOSA 2 study. In the MARIPOSA 2 study, patients were assigned to chemotherapy versus amivantamab plus lazertinib plus chemotherapy versus amivantamab plus chemotherapy. And both of the amivantamab arms showed superiority in progression-free survival compared to chemotherapy alone arm and therefore this becomes an additional treatment option for our patients who develop resistance to osimertinib. In addition, we also updated the results which highlight the lack of efficacy of immunotherapy in the patients who progressed on osimertinib. There were two studies that we highlighted. One of them was a CheckMate 722 which randomly assigned patients with metastatic non-small cell lung cancer whose cancer has progressed on EGFR tyrosine kinase inhibitor to receive either chemotherapy or chemotherapy plus nivolumab which is an immune checkpoint inhibitor. And the second study was KEYNOTE-789 which had a very similar study design. Again, patients who progressed on EGFR TKI also were assigned to receive chemotherapy plus pembrolizumab or chemotherapy alone and in both of those studies there was no improvement in progression-free survival when adding immunotherapy to chemotherapy. So for all your patients who are progressing on EGFR tyrosine kinase inhibitors and you're thinking if additional immunotherapy is necessary, we now have two randomized phase 3 studies telling us that immunotherapy should not be used in addition to chemotherapy for patients who develop progression on osimertinib. Brittany Harvey: Understood. I appreciate you talking about the evidence that supports these latest recommendations from the expert panel. So then you've already touched on this a little bit in mentioning shared decision making and discussing toxicity with these new therapies, but what should clinicians know as they implement these new recommendations and how do these new recommendations fit into the previous recommendations made by the panel? Dr. Lyudmila Bazhenova: Our previous recommendations did not include a MARIPOSA trial, so did not include amivantamab and lazertinib. So in our current guidelines for patients with newly diagnosed treatment-naive EGFR classical mutations, we have three options. Number one is osimertinib, number two is osimertinib plus chemotherapy based on the FLAURA study that we highlighted in the prior version of the guidelines. And the third is amivantamab plus lazertinib. At this point, we do not have any randomized head-to-head studies of those combinations with an exception of FLAURA 2 which is osimertinib plus chemo versus osimertinib. And so the decisions will have to be made on a cross-trial comparison, taking into account patient wishes if they would like to receive chemotherapy or amivantamab plus lazertinib, understanding that this combination will result in increased toxicity. Brittany Harvey: Absolutely. I appreciate you detailing those considerations. So then finally, what do these new options mean for patients with non-small cell lung cancer and an EGFR alteration? Dr. Lyudmila Bazhenova: As a patient, it is important to also be aware of what options we have and have a direct dialogue with the physician, with the treating physician, trying to understand what option will fit with each individual patient's goals, life goals, as well as toxicity concerns. Brittany Harvey: Definitely. It's always great to have more options for patients and it's also important to discuss all of those options with their clinician as well. So I want to thank you so much for your work on this update and thank you for your time today, Dr. Bazhenova. Dr. Lyudmila Bazhenova: My pleasure. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/living-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.   The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

Today on the Wedding Planning Podcast, we're doing a thorough review of wedding dress alterations, styling & accessories, & post-wedding preservation ideas, and so much more. Our conversation covers the dress alterations process in detail, including pricing, money-saving tips, a timeline for when to get started, and alternative options for having your dress altered. We also cover: What's a bustle, do I need one, and how much does it cost? (article on bustling I mentioned in today's show can be found here) Styling and shape wear options like bras, corsets, and compression garments, The importance of COMFORTABLE SHOES, Getting your dress home & last minute wrinkle patrol (the handheld steamer I mentioned can be found here) And some creative ways to preserve and / or repurpose your gown after the wedding. I hope you love it, and congratulations on that beautiful dress! Cheers, Kara   PS - A special THANK YOU to this week's show sponsors, who made this free weekly episode possible:   Enjoy early access to ad-free episodes each week when you subscribe to WEDDING PLANNING PODCAST PREMIUM in Apple Podcasts.     Get professional help planning your dream honeymoon when you email susan@susanstravelservices.com . Don't forget to mention the Wedding Planning Podcast for $50 off your booking.   FREE Wedding Websites designed by independent artists?  Yes please!  Get started building your wedding website today with www.weddingplanningpodcast.co/minted and take advantage of exclusive listener perks on save the dates, invitations & more.   Shop Etsy for one-of-a-kind wedding day details, personalized just for you >>> www.weddingplanningpodcast.co/etsy

In today's episode, we delve into a groundbreaking new study that explores brain changes following spinal adjustments. We'll unpack the study "The Application of Spinal Manipulation Results in Alterations in Thalamic Neural Metabolites Among Patients Experiencing Nonspecific Chronic Low Back Pain." This research illuminates how chiropractic adjustments can significantly affect brain function and pain perception, offering deeper insights into the mechanisms behind the relief and functional improvements our patients experience.Episode Notes: The Application of Spinal Manipulation Results in Alterations in Thalamic Neural Metabolite among Patients Experiencing Nonspecific Chronic Low Back PainJane is an online platform for health and wellness practitioners that makes it simple to book, chart, schedule, bill, and get paid. I you're ready to get started, click here and use the code EBC1MO for a 1-month grace period on your new account.The Best Objective Assessment of the Cervical Spine- Provide reliable assessments and exercises for Neuromuscular Control, Proprioception, Range of Motion, and Sensorimotor-Integration. Learn more at NeckCare.comInterested in ShockWave technology? I built a practice using StemWave and can't recommend it enough. Learn more at- https://gostemwave.com/theevidencebasedchiropractor Patient Pilot by The Smart Chiropractor is the fastest, easiest to generate weekly patient reactivations on autopilot…without spending any money on advertising. Click here to schedule a call with our team.Our members use research to GROW their practice. Are you interested in increasing your referrals? Discover the best chiropractic marketing you aren't currently using right here!