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On this MADM, Josey Trawick shares a little bit about himself as he battles chronic myelogenous leukemia, vision loss, Meniere's Disease, and multiple mental health challenges that have left him unable to work. Listen & share. Donate: gofundme.com/support-josey-trawicks-journey-to-stability Sponsor: CoraNation Tailoring & Alterations
Hope you are having a lovely day! Today Ms. Andy has a cute kids book for you and she is very excited to read to you today! Today we have Ms. Andy reading "Llama Llama Red Pajama" by Anna Dewdney with a fun to say story!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
Glad to have you listening with us today! Join Ms. Andy as she reads a book from here in the Library! This author is fairly popular, and we were curious what they were like. Which got us thinking, maybe we could share a bit with you too! Today's book is "A Dangerous Man" by Robert Crais, which we read just a bit of here. We hope you enjoy this sneak peak, and as always if you enjoy the story then we invite you to visit your local library and ask them to reserve it for you!- 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/@pawls365 Original background track is The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle, music from the freemusicarchive.orghttps://freemusicarchive.org/music/Doctor_Turtle/none_given_1561/Doctor_Turtle_-_You_Um_Ill_Ah1/The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle is licensed under a Attribution 4.0 International License.Alterations were made by us to make it fit the length of our content.#library #books #pawlskids #kidsstorytime
On this Make A Difference Minute, I'm reminding listeners that one of the most meaningful things we can do is let people know they are not alone. Many carry silent burdens and feel unseen, even while surrounded by others. This segment encourages presence, compassion, and small acts of connection that can make a lasting difference. Sponsor: CoraNation Tailoring & Alterations
Hope you are having a lovely Valentines day! Today Ms. Andy has a cute kids book for you and she is very excited to read to you today! Today we have Ms. Andy reading "Be Kind" by Pat Zietlow Miller with cute moments of kindness!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 Make A Difference Minute, Chambers Ricketts shares a father's perspective after bringing his son, Ethan, home following his diagnosis of Polymicrogyria (PMG). Sponsor: CoraNation Tailoring & Alterations
Glad to have you listening with us today! Ms. Andy has picked this one mostly to offer you some variety, but also because this is a popular author in our library system. Today's book is "Goosebumps - My Best Friend is Invisible" by R.L. Stine, which we read just a bit of here. We hope you enjoy this sneak peak, and as always if you enjoy the story then we invite you to visit your local library and ask them to reserve it for you!- 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/@pawls365 Original background track is The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle, music from the freemusicarchive.orghttps://freemusicarchive.org/music/Doctor_Turtle/none_given_1561/Doctor_Turtle_-_You_Um_Ill_Ah1/The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle is licensed under a Attribution 4.0 International License.Alterations were made by us to make it fit the length of our content.#library #books #pawlskids #kidsstorytime
Dr. Joshua Reuss is back on the podcast to discuss the full update to the living guideline on stage IV NSCLC without driver alterations. He discusses the new evidence and how this impacts the latest recommendations on first-line and subsequent therapeutic options. Dr. Reuss emphasizes the need for shared decision-making between clinicians and patients. 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 Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0" at www.asco.org/thoracic-cancer-guidelines" TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-02825 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 am interviewing Dr. Joshua Reuss from Georgetown University, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It is great to have you back on the show today, Dr. Reuss. Dr. Joshua Reuss: Happy to be here, Brittany. Brittany Harvey: Just before we discuss this guideline, I would 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. Dr. Reuss, 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 basis. So, what prompted this latest update to the recommendations? Dr. Joshua Reuss: Our committee is tasked with making routine updates to the living guidelines and really keeping them living, right? So, evaluating new data as it is coming in to see, is this practice changing? Is this data that should inform and potentially alter our guideline recommendations so that practitioners and other care providers could really make the best treatment decisions for their patients? So that is something that happens on a more routine basis, but periodically, we are tasked with performing a more comprehensive update of our guideline where we really evaluate every one of our point recommendations, the data associated with these recommendations, to be sure that these are up to date, these are comprehensive, and to see if we need to alter anything in the language of these updates. Brittany Harvey: Excellent. Thank you for providing that background. And yes, this is truly a comprehensive update that goes through all the latest literature. Given that, I would like to review what has changed and what is new in the recommendations. So, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: So there are two main guidelines that we recommend from this panel. One is a driver mutation-positive guideline and the other is a driver mutation-negative guideline. And I think on first blush, one might look at kind of the recent flurry of approvals and new data and say, well, all the excitement, you know, is in the driver mutation-positive guideline. But I would say that the driver mutation-negative guideline is equally as important and really has several unique challenges associated with it. You know, first and foremost is that there are really a multitude of regimens that can be considered for any one patient. And how to choose between one can be quite difficult and a stressful challenge that clinicians can have, particularly since there are really no randomized studies comparing these regimens in a head-to-head fashion. In addition, you know, these guidelines are really broken down by two key factors. One is disease histology, so namely squamous versus non-squamous histology. And the other is PD-L1 status, broken down into one of three tertiles: PD-L1 high, which is greater than or equal to 50% expression; PD-L1 low, which is 1% to 49% expression; and then PD-L1 negative or unknown. So what you are really looking at, if you do that math, is really six unique patient subpopulations where we need to make a recommendation on one of the multitude of treatment regimens that is approved. And what that means is you are oftentimes really looking at subset and sub-subset level data to help inform clinicians in their treatment decision making, which can be quite challenging because as those small subsets of data is more and more parsed, there are many confounders that can be interjected there. And so I think the committee is tasked with really quite a challenge in terms of how to really communicate and broadcast that data in a way that informs clinicians in making a decision on what is the right treatment for their patient. Brittany Harvey: Absolutely. It can be challenging to interpret that subgroup data across several different studies that are reporting on different regimens and different outcomes. And I appreciate you mentioning the driver mutation-positive guideline as well. Listeners can check out the companion episode with Dr. Puri for more information on what is changed in the driver mutation-positive guideline. Based on that primer, what is new for first-line therapy for patients with stage IV non-small cell lung cancer without driver alterations? Dr. Joshua Reuss: Even though I will say there is not a lot of new trial data that was incorporated into this guideline, there were some updates and just some meaningful long-term data that we incorporated. I think first and foremost, there is a new top-level recommendation in this guideline pertaining to molecular testing, which is absolutely critical in both the driver mutation-positive and driver mutation-negative space. I think we tend to think that, oh, well, molecular testing really only pertains to then finding a driver mutation. But the lack of a mutation is absolutely critical as well, right? Because that is what leads us down the mutation-negative pathway. We also need this molecular testing to assess PD-L1 status. We are seeing emerging data on molecular mutations that might confer resistance to certain immunotherapy-based strategies. So the committee felt strongly that a recommendation on molecular testing is critical to include in both the driver mutation-positive guideline and the driver mutation-negative guideline. I will also say that we are now seeing five and six-year updates from some of the landmark trials of immunotherapy in driver mutation-negative non-small cell lung cancer. It is really incredible to see that in some of these trials, we are seeing very impressive durability of the treatment in the patient subsets that we are commenting on. In others, perhaps that durability is less clear, and I think that leads to challenges in making a recommendation on any one particular regimen. And I think that is nowhere more clear than in the squamous subset. I think that was one perhaps subtle change that is in this guideline where, particularly in the PD-L1 negative squamous population, the committee felt that no one regimen really was worthy of standing above the others. Sometimes I think it is important to really champion one unique regimen if we feel that the data is there to support it. But I think it is equally important to list multiple regimens where the data is less clear. I think another point is that while perhaps there were no new regimens that we have added or that led to other clear changes in the prioritization of one regimen over another, there are other unique data subsets that I think come into play in making a decision and that really are important when looking at the discussion on any one recommendation from this guideline. For example, we know there is emerging data on perhaps the significance of molecular alterations in KEAP1 or STK11 and how that might influence frontline decision-making. You know, there is not a prospective phase III trial in this population, but I think we still need to use that data in certain scenarios to make recommendations for a particular patient. Another example of a trial that, again, did not change our recommendations, but I think one can incorporate in their decision making is the KEYNOTE-598 trial. Now, this is not a new study, but what it studied was pembrolizumab versus pembrolizumab plus ipilimumab in a PD-L1 high subset, and found that the addition of ipilimumab to pembrolizumab in the PD-L1 high population did not significantly improve clinical efficacy. And so while pembrolizumab plus ipilimumab is not an approved regimen, it is hard to extrapolate that to our combination treatments that are approved. I think some clinicians might find that data valuable when making a frontline treatment decision on a patient who has PD-L1 high status. So a bit of a whirlwind tour, but I think there are still multiple factors that went into this guideline that are important to review when making treatment decisions for any one patient. Brittany Harvey: Absolutely. I think what you just mentioned in having that upfront molecular testing is really key for individualized patient care. And the evidence summaries that you provide in addition to the recommendations are really important for clinicians to be able to refer to as they are making decisions in their clinic. So then beyond those changes for first-line therapy, what is updated for second-line and subsequent therapies? Dr. Joshua Reuss: For second-line and subsequent therapies, we did see one new treatment recommendation join these ranks, and that was telisotuzumab vedotin. Telisotuzumab vedotin, quite a mouthful. That is an antibody-drug conjugate. I like to think of that as smart chemotherapy, targeted chemotherapy, where you are trying to utilize some aspect of a marker that is selectively expressed or overexpressed on the cancer surface to then shepherd in the anticancer molecule, a highly potent chemotherapeutic in the case of currently approved antibody-drug conjugates, to exert antitumor killing effect. So in this case, the antibody-drug conjugate telisotuzumab vedotin targets MET overexpression. So telisotuzumab is an antibody targeting MET, and that is conjugated to an MMAE highly potent chemotherapeutic payload called vedotin. So we know MET can be selectively expressed and overexpressed in non-small cell lung cancer in both driver mutation-positive and mutation-negative subsets. The data that led to this approval was from the phase II LUMINOSITY trial which evaluated telisotuzumab vedotin, or Teliso-V, in many subsets. But the subset that really showed promise and was expanded was the EGFR wild-type, non-squamous, non-small cell lung cancer population with MET overexpression. And so in 78 patients with high levels of expression, the response rate here was 34.6%, median progression-free survival of 5.5 months, and a median overall survival of 14.6 months. With an overall acceptable safety profile; grade 3 or higher adverse events, neuropathy was perhaps the most common at 7%, also increased ALT at 3.5%, and pneumonitis at 2.9%. Now this was phase II data that led to an accelerated approval. There is an ongoing phase III study randomizing patients with high expression to Teliso-V versus docetaxel. That is the phase III TeliMET study. But it is nice that we now have another option for patients, perhaps a more biomarker-directed option with, again, this MET overexpression. And again, it further reinforces the importance of molecular testing in patients with traditionally driver mutation-negative non-small cell lung cancer, whether that is upfront or at progression, and in particular utilizing immunohistochemistry to assess MET expression in these patients. And this does join another ADC that we had previously made an update in our recommendation, which is trastuzumab deruxtecan, which is approved for those patients with HER2-overexpressing non-small cell lung cancer. So just again to reiterate the importance of molecular testing in patients both at the outset of their treatment and upon progression on frontline therapy. Brittany Harvey: Definitely. It is great to have this new antibody-drug conjugate join the treatment options, and as you mentioned, very important in this case to have that molecular testing done at the outset and at progression. So then in your view, what should clinicians know as they implement this living guideline, and how do these changes impact patients with non-small cell lung cancer? Dr. Joshua Reuss: Because there are so many different regimens that one can consider for any one patient, I think it is easy to become overwhelmed and stress on, "Am I making the right choice for my patient?" And I think one of the key take home points is that in many cases, there is no one right regimen. And I think one has to weigh several factors. It is the treatment schedule. It is the toxicity profile. It is the molecular profile of the patient. It is the patient preference. You know, there are so many factors here. And I would like to draw the reader and viewer's attention to an important section of these guidelines, particularly the Patient and Clinician Communication section, where we have a box focused on discussion points between patients and clinicians, which I think focuses on several of the high-level points that one can emphasize in making these decisions, ranging on things from: what are the goals of the treatment? What are the risks and benefits to any one approach? What are comorbidities that should be factored in? Common concerns, toxicity management, clinical trial consideration. All of these factors that I think are incredibly important in making that frontline treatment decision and implementing a regimen that both the clinician and, more importantly, the patient feels comfortable with. Brittany Harvey: It is really important that there is shared decision-making in these scenarios. And I think that patient-clinician communication section can tease out some of those preferences from the patient end and talk through the risks and benefits of different regimens as well. As we mentioned at the top of this episode, this guideline is a living guideline and updated on an ongoing basis. So what is the panel examining and keeping an eye on for future updates to this guideline? Dr. Joshua Reuss: So I think there are a lot of exciting new therapies and more up-to-date trials that we are anxiously awaiting the results of on our committee, and I think the oncology community in general is awaiting the results of. When we will have these results, I think, is a bit of an open-ended question, but I can give some insight on several of the trials that our committee is really keeping a close eye on. One that we have mentioned for several guideline iterations is the ECOG-ACRIN INSIGNA trial. This is a phase III clinical trial comparing pembrolizumab versus pembrolizumab plus carboplatin and pemetrexed chemotherapy in PD-L1 positive, non-squamous, non-small cell lung cancer. We talk about there being different regimens that can be considered in PD-L1 positive and PD-L1 high subsets, namely immunotherapy alone or immunotherapy plus chemotherapy, but there is no direct head-to-head comparison here. So this trial hopefully will answer that question. It has now finished accrual. There are other very interesting molecules and trials. I think another interesting compound is ivonescimab. This is a PD-1/VEGF bispecific antibody that is currently approved in China as monotherapy in patients with PD-L1 positive non-small cell lung cancer based off of the HARMONi-2 trial, where the progression-free survival of this bispecific antibody, ivonescimab, appeared superior to pembrolizumab. And we are looking closely at ongoing trials to see if these results will be replicated in an ex-China population. And if so, I think it could have a real impact and change on our guidelines. Still other very interesting things. There are obviously confirmatory studies for antibody-drug conjugates, such as the TeliMET study that I alluded to earlier, and many promising antibody-drug conjugates, both bispecific and trispecific antibody-drug conjugates, that hopefully can inform practice. And then there are several unique subsets of populations that I think we now are utilizing data on to make decisions, but a lot of that is retrospective in small subsets where we do not have that prospective data. And there are several trials ongoing in some of these subsets to try to gain clarity on what regimen may be the best for patients. One example is the phase III TRITON trial, which is looking at comparing CTLA-4 containing regimen, particularly the POSEIDON regimen of durvalumab plus tremelimumab and chemotherapy, versus the KEYNOTE-189 regimen, which is pembrolizumab plus carboplatin and pemetrexed, in patients with non-squamous, non-small cell lung cancer that have alterations in either KRAS, KEAP1, and/or STK11. There is a lot of both preclinical and clinical data to suggest that patients with these alterations in STK11 and KEAP1 may be more resistant to a PD-1 based treatment approach, and perhaps the incorporation of CTLA-4 can lead to a more meaningful response in this unique subset. Obviously, that data, it is retrospective, it is in small subsets. And when you add in a CTLA-4 molecule, you are also introducing greater risk for toxicity. So this trial is going to be very important in elucidating: is there a benefit in that unique subset? Does that data that we see retrospectively in this small subset hold true when evaluated in a prospective fashion? So while our guideline, our most recent comprehensive panel update, may not have had a lot of new data in it that has influenced frontline treatment decision-making, I think the future is bright and there are a lot of novel studies and novel treatments on the horizon that will hopefully improve the outcomes for our patients. Brittany Harvey: Absolutely. We will look forward to the results of those ongoing trials to provide more options and particularly clarity for patients with non-small cell lung cancer and to inform this guideline and its many updates to come. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Reuss. 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 available in the Apple App Store or the Google Play Store. If you have enjoyed what you have 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. Sonam Puri discusses the full update to the living guideline on stage IV NSCLC with driver alterations. She shares a new overarching recommendation on biomarking testing and explains the new recommendations and the supporting evidence for first-line and subsequent therapies for patients with stage IV NSCLC and driver alterations including EGFR, MET, ROS1, and HER2. Dr. Puri talks about the importance of this guideline and rapidly evolving areas of research that will impact future updates. Read the full living guideline update "Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.0" at www.asco.org/thoracic-cancer-guidelines TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO-25-02822 Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I'm interviewing Dr. Sonam Puri from Moffitt Cancer Center, co-chair on "Therapy for Stage IV Non-Small Cell Lung Cancer with Driver Alterations: ASCO Living Guideline, Version 2026.3.0." It's great to have you here today, Dr. Puri. Dr. Sonam Puri: Thanks, Brittany. Brittany Harvey: And then just before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Puri, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then, to dive into the content that we're here today to talk about, Dr. Puri, this living clinical practice guideline for systemic therapy for patients with stage IV non-small cell lung cancer with driver alterations is updated on an ongoing basis. So, what data prompted this latest update to the recommendations? Dr. Sonam Puri: So Brittany, non-small cell lung cancer is one of the fastest-moving areas in oncology right now, particularly when it comes to targeted therapy for driver alterations. New data are emerging continuously from clinical trials, regulatory approvals, real-world experience, which is exactly why these are living guidelines. The goal is to rapidly integrate important advances as they happen, rather than waiting for years for a traditional update. Since the last full update of the ASCO Stage IV Non-small Cell Lung Cancer Guideline with Driver Alterations published in 2024, there have been seven new regulatory approvals and changes in first-line therapy for some driver alterations. [This version] of the "Stage IV Non-small Cell Lung Cancer Guidelines with Driver Alterations" represents a full update, which means that the panel reviewed and refreshed every applicable section of the guideline to reflect the most current evidence across therapies including sequencing and clinical decision-making. This is to ensure that clinicians have up-to-date practical guidelines that keep pace with how quickly the field is evolving. Brittany Harvey: Absolutely. As you mentioned, this is a very fast-moving space and this full update helps condense all of those versions that the panel reviewed before into one document, along with additional approvals and new trials that you reviewed during this time period. So then, the first aspect of the guideline is there's a new overarching recommendation on biomarker testing. Could you speak a little bit to that updated recommendation? Dr. Sonam Puri: Yeah, definitely. So the panel has discussed and provided recommendations on comprehensive biomarker testing and its importance in all patients diagnosed with non-small cell lung cancer. Ideally, biomarker testing should include a broad-based next-generation sequencing panel, rather than single-gene tests, along with immunohistochemistry for important markers such as PD-L1, HER2, and MET. These results really drive treatment decisions, both in frontline settings for all patients diagnosed with non-small cell lung cancer and in subsequent line settings for patients with non-small cell lung cancer harboring certain targetable alterations. Specifically in the frontline setting, it helps determine whether a patient should receive upfront targeted therapy or immunotherapy-based approach. We now have strong data that shows that complete molecular profiling results before starting first-line therapy is associated with better overall survival and actually more cost-effective care. Using both tissue and blood-based testing can improve likelihood of getting actionable results in a timely way, and we've also provided guidance on platforms that include RNA sequencing, which are specifically helpful for identifying gene fusions that might be otherwise missed with other platforms. On the flip side, outside of a truly resource-limited setting, single-gene PCR testing really should not be routine anymore. This is what the panel recommends. It's less sensitive and inefficient and increases the risk of missing important actionable alterations. Brittany Harvey: Understood. I appreciate you reviewing that recommendation. It really helps identify critical individual factors to match the best treatment option to each individual patient. So then, following that recommendation, what are the updated recommendations on first-line therapy for patients with stage IV non-small cell lung cancer with a driver alteration? Dr. Sonam Puri: Since the last full update in 2024, there have been four additional interim updates which were published across 2024 and 2025. Compared to the last version, there have been several updates which have been included in this full update. One of the most important shifts has been in first-line treatment of patients with non-small cell lung cancer harboring the classical, or what we call as typical, EGFR mutation. The current version of the recommendation is based on the updated survival data from the phase III FLAURA2 and MARIPOSA studies, based on which the panel recommended to offer either osimertinib combined with platinum-pemetrexed chemotherapy or the combination of amivantamab plus lazertinib in the first-line treatment of classical EGFR mutations. And these recommendations, as I mentioned, are grounded in the results of the FLAURA2 and MARIPOSA trials, both of which demonstrated improvement in progression-free survival and overall survival compared to osimertinib alone in patients with common EGFR mutations. That being said, the panel actually spent significant time discussing the toxicities associated with these treatments as well. These combination approaches come with higher toxicity, longer infusion time, increased treatment frequency. So while combination therapy is now recommended as preferred, the panel has recommended that osimertinib monotherapy remains a reasonable option, particularly for patients with poor performance status and for those who are not interested in treatment intensification after knowing the risks and benefits. Brittany Harvey: Absolutely. It's important to consider both those benefits and risks of those adverse events that you mentioned to match appropriately individualized patient care. So then, beyond those recommendations for first-line therapy, what is new for second-line and subsequent therapies? Dr. Sonam Puri: So this is a section that saw several major updates, particularly again in the EGFR space. The first was an update on treatment after progression on osimertinib for patients with classical EGFR mutation. Here the panel recommends the combination of amivantamab plus chemotherapy, and this recommendation was based on the phase III MARIPOSA-2 trial, which compared amivantamab plus chemotherapy with chemotherapy alone with progression-free survival as the primary endpoint. The study met its primary endpoint, showing an improvement in median PFS with the combination of amivantamab plus chemotherapy compared to chemotherapy alone. And as expected, the combination was associated with higher toxicity. So, although the panel recommends this regimen, the panel emphasizes that patients should be counseled on the side effects which may be moderate to severe with the combination therapy approach. In addition, a new recommendation was added for patients who are not candidates for amivantamab plus chemotherapy. In those cases, platinum-based chemotherapy with or without continuation of osimertinib may be offered, and the option of continuing osimertinib with chemotherapy was recommended and supported by data from a recently presented phase III COMPEL study, which randomized 98 patients with EGFR exon 19 deletion or L858R-mutated advanced non-small cell lung cancer who had experienced no CNS progression on first-line osimertinib, and these patients were randomized to receive platinum-pemetrexed chemotherapy with osimertinib or placebo. Although this study was small, it demonstrated a PFS benefit with continuation of osimertinib with chemotherapy, and this approach may be appropriate for patients without CNS progression who prefer or require alternatives to more intensive treatment strategies. Next was an update on options for patients with EGFR-mutated lung cancer after progression on osimertinib and platinum-based chemotherapy. Here the panel recommended that for patients whose disease has progressed after both osimertinib and platinum-based chemotherapy, a new drug known as datopotamab deruxtecan can be offered as a treatment option. And this treatment recommendation was based on evaluation of pooled data from the TROPION-Lung01 and TROPION-Lung05 study, in which in the pooled analysis about 114 patients with EGFR-mutant non-small cell lung cancer were treated with Dato-DXd, 57% of whom had received three or more prior lines of treatment, and what was observed was an overall response rate of 45% with a median duration of response of 6.5 months. So definitely promising results. Next, we focused on updates to subsequent therapy options for patients with another type of EGFR mutation known as EGFR exon 20 insertion mutations. In this section, the panel added sunvozertinib as a subsequent line option after progression on platinum-based chemotherapy with or without amivantamab. Sunvozertinib is an oral, irreversible, and selective EGFR tyrosine kinase inhibitor with efficacy demonstrated in the phase II WU-KONG6 study conducted in Chinese patient population. In this study, amongst 104 patients with platinum-pretreated EGFR exon 20 mutated non-small cell lung cancer, the observed response rate was 61%. Staying in the EGFR space, the panel added a recommendation for patients with acquired MET amplification following progression on EGFR TKI therapy. In these situations, the panel recommended that treatment may be offered with osimertinib in combination with either tepotinib or savolitinib. As our listeners may know, MET amplification occurs in approximately 10% to 15% of patients with EGFR-mutated non-small cell lung cancer when they progress on third-generation EGFR TKIs, and detection of MET amplification is done with various methods, such as tissue-based methods like FISH, NGS, and IHC, as well as ctDNA-based NGS with variable cut-offs. Over the last few years, several studies have informed this recommendation. I'm going to be discussing some of them. In the phase II ORCHARD trial, 32 patients with MET-amplified non-small cell lung cancer after progression on first-line osimertinib were evaluated, where the combination of osimertinib plus savolitinib achieved an overall response rate of 47% with a duration of response of 14.5 months. More recently, the phase II SAVANNAH trial reported outcomes in 80 patients with MET-amplified tumors after progression on osimertinib, and in this patient population, the combination of savolitinib and osimertinib achieved an overall response rate of 56% with a median PFS of 7.4 months. And lastly, the phase II single-arm INSIGHT 2 trial assessed the efficacy of osimertinib plus tepotinib in patients with advanced EGFR-mutant non-small cell lung cancer who had disease progression following first-line osimertinib therapy. And in this study, in a cohort of 98 patients with MET-amplified tumors confirmed by central testing, the overall response rate with the combination was 50% with a duration of response of 8.5 months. So definitely informing this guideline recommendation. Next, we had an update on recommendation in patients with ROS1-rearranged non-small cell lung cancer. For patients with ROS1-rearranged non-small cell lung cancer, the panel recommended specifically for patients who progressed after first-line ROS1 TKIs, the addition of taletrectinib as a new option alongside repotrectinib. And this recommendation was based on analysis of the results of the TRUST-I and TRUST-II studies, which showed that amongst 113 tyrosine kinase inhibitor-pretreated patients, taletrectinib achieved a confirmed overall response rate of 55.8% with a median duration of response of 16.6 months and a median PFS of 9.7 months, a very promising agent. Finally, for patients with HER2 exon 20 mutated non-small cell lung cancer, the panel added two new oral HER2 tyrosine kinase inhibitors, zongertinib and sevabertinib, as options in addition to T-DXd and after exposure to T-DXd. These recommendations are based on early phase data from two trials: the phase I Beamion LUNG-01 study, which evaluated zongertinib, and the phase I/II SOHO-01 study that evaluated sevabertinib. In this study, zongertinib demonstrated an overall response rate of 71% in previously treated patients, with an overall response rate of 48% amongst patients who had received prior HER2-directed ADCs including T-DXd. Sevabertinib in its early phase study showed an overall response rate of 64% in previously treated but HER2 therapy-naive patients, and an overall response rate of 38% in patients previously exposed to HER2-directed therapy. The panel believes that both agents had manageable toxicity profile and represent meaningful new options for this patient population. Brittany Harvey: Certainly, it's an active space of research, and I appreciate you reviewing the evidence underpinning all of these recommendations for our listeners. So, it's great to have these new options for patients in the later-line settings. And given all of these updates in both the first and the later-line settings, what should clinicians know as they implement this latest living guideline update, and how do these changes impact patients with non-small cell lung cancer? Dr. Sonam Puri: Some great questions, Brittany. I think for clinicians when implementing this update, I think about two practical steps. First is reiterating the importance of comprehensive biomarker testing. That is the only way to identify key drivers and resistance mechanisms that we are now targeting. And second, picking a first-line strategy that balances efficacy and toxicity and patient preference for your specific patient. I think informed decision-making, shared decision-making is more important than any time right now. It has always been important, but definitely very important now. For patients, this guideline brings recommendations on more personalized treatment options for both first-line and post-progression settings, which potentially means better outcomes. But it is also very important for our patients to continue to have informed conversations about side effects, time commitment, and what matters most to them with their providers. The panel in this version of the guideline specifically acknowledges the real-world barriers that prevent patients from receiving guideline-concordant therapy, including challenges with access to comprehensive molecular testing and treatment availability, and the panel emphasizes on the importance of shared decision-making, and we provide practical discussion points to help clinicians navigate these conversations with the patient. In addition, the panel has also addressed common real-world clinical complexities, such as treating elderly or frail patients, managing multiple chronic conditions, considerations around pregnancy and fertility, and certain disease scenarios such as oligoprogression or oligometastatic disease. And where available, the guideline summarizes this existing data to support informed individual decision-making in these complex situations. Brittany Harvey: Shared decision-making is really paramount, especially with all of the options and weighing the risks and benefits and considering the individual circumstances of each patient that comes before a clinician. We've talked a lot about all of the new studies that the panel has reviewed, but what other studies or areas of research is the panel examining for future updates to this living guideline as it continues to be updated on an ongoing basis? Dr. Sonam Puri: Yes, definitely, so much to look forward to, right? Looking ahead, the panel is closely monitoring several rapidly evolving areas that are likely to shape future updates of the guideline. This includes emerging data from ongoing later-phase studies, particularly the studies that are evaluating these new targeted agents moving to earlier lines of therapy, alongside studies evaluating additional combination strategies or more refined approaches to treatment sequencing. We're also closely watching advances in biomarker testing, the evolving understanding of resistance mechanisms, development of new targets, and promising therapeutic agents. I think ultimately the living guideline exists to help clinicians and patients navigate this rapidly evolving field, and we would like to ensure that scientific advances are rapidly translated into better, more personalized patient care. Brittany Harvey: Definitely. We'll look forward to those updates from those ongoing trials and future areas of research that you mentioned to provide better options for patients with non-small cell lung cancer and a driver alteration. So I want to thank you so much for your work to rapidly and continuously update this guideline, and thank you for your time today, Dr. Puri. Dr. Sonam Puri: Thanks so much. Thanks so much for the opportunity. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store or the Google Play Store. There's also a companion episode with Dr. Reuss on the related living guideline on stage IV non-small cell lung cancer without driver alterations that listeners can find in their feeds as well. And if you've enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
On this Make A Difference Minute, I'm reflecting on the Buddy Bench dedication at East Lawrence Elementary School in honor of Chris Hill, Jr., Ashanti Hill, and Shawntay Hill. This segment focuses on legacy, community support, and how small acts of kindness can carry meaning for generations of students. Sponsor: CoraNation Tailoring & Alterations
On this Make A Difference Minute, I'm reminding listeners that their own experiences with hurt can become a powerful source of compassion. This segment encourages listeners to remember what it feels like to be hurting and to use that understanding to respond to others with patience, grace, and empathy. Sponsor: CoraNation Tailoring & Alterations
Glad to have you listening with us today! Ms. Andy has picked this one mostly to offer you some variety, but also because this is a popular author in our library system. Today's book is "The Assassination Option" by W.E.B. Griffin, which we read just a bit of here. We hope you enjoy this sneak peak, and as always if you enjoy the story then we invite you to visit your local library and ask them to reserve it for you!- 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/@pawls365 Original background track is The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle, music from the freemusicarchive.orghttps://freemusicarchive.org/music/Doctor_Turtle/none_given_1561/Doctor_Turtle_-_You_Um_Ill_Ah1/The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle is licensed under a Attribution 4.0 International License.Alterations were made by us to make it fit the length of our content.#library #books #pawlskids #kidsstorytime
Glad to have you listening with us today! We wanted to read something for the holiday, and this book covers a lot of his life and influence! Today's book is "Martin Luther kin Jr. Preacher, Freedom Fighter, Peacemaker." by Pamela Hill Nettleton, which we read just a bit of here. We hope you enjoy this sneak peak, and as always if you enjoy the story then we invite you to visit your local library and ask them to reserve it for you!- 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/@pawls365 Original background track is The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle, music from the freemusicarchive.orghttps://freemusicarchive.org/music/Doctor_Turtle/none_given_1561/Doctor_Turtle_-_You_Um_Ill_Ah1/The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle is licensed under a Attribution 4.0 International License.Alterations were made by us to make it fit the length of our content.#library #books #pawlskids #kidsstorytime
On this Make A Difference Minute, you will hear from Hueytown Intermediate School Principal Cari McClellen as she shares why the Buddy Bench dedication in honor of 5th grader Jace Watkins matters so much to her school family. Principal McClellen also shares her vision for the future, using Buddy Benches to bring students together across campuses, creating safe places for friendship, empathy, and connection. Sponsor: CoraNation Tailoring & Alterations
On this MADM, I'm using a simple everyday example to remind listeners that you can't keep giving from an empty place. Just like an ice tray has to be refilled before it can produce anything, we have to take time to restore ourselves. This segment encourages balance, awareness, and the importance of refilling so we can continue to show up for others. Sponsor: CoraNation Tailoring & Alterations
Glad to have you listening with us today! Ms. Andy has picked this one since she loved the cover, and who doesn't like a love story? Today's book is "Secretly Yours" by Tessa Bailey, which we read just a bit of here. We hope you enjoy this sneak peak, and as always if you enjoy the story then we invite you to visit your local library and ask them to reserve it for you!- 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/@pawls365 Original background track is The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle, music from the freemusicarchive.orghttps://freemusicarchive.org/music/Doctor_Turtle/none_given_1561/Doctor_Turtle_-_You_Um_Ill_Ah1/The Talons Of Adventure, The Antlers Of Romance by Doctor Turtle is licensed under a Attribution 4.0 International License.Alterations were made by us to make it fit the length of our content.#library #books #pawlskids #kidsstorytime
On this Make A Difference Minute, Haley Schrimsher shares an honest update on her 9-year-old son, Ruger Ennis, as he continues to navigate kidney failure, dialysis, and daily challenges at school and home. It's a reminder of the strength of a child, the love of a mother, and the power of prayer and community support. Sponsor: CoraNation Tailoring & Alterations
Back from our holiday break! 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 "Lizzy and the Cloud" by The Fan Brothers and it is a cute book with fun illustrations.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
Some memories don't fade, they echo. A word, a glance, a moment that keeps the body on alert long after it's passed. Your brain remembers the pain, and your chemistry follows.In this episode of Migraine Heroes Podcast, host Diane Ducarme explores how holding on to anger, guilt, or resentment, keeps your nervous system locked in defense mode. Neuroscience shows that unforgiveness isn't just emotional; it's chemical. And Eastern philosophy has been teaching this for thousands of years: peace is not a mood, it's a biological state.You'll discover:
On this Make A Difference Minute, I'm reminding listeners that friendship teaches us lessons over time. Not everyone who has history with you will stand with you when things get uncomfortable, and that doesn't mean the friendship was never real. It simply means you learned what that relationship could and could not carry. This segment encourages reflection, grace, and discernment as we learn who we can truly count on and where to place our trust moving forward. Sponsor: CoraNation Tailoring & Alterations
On this Make A Difference Minute, Catharine Grimes, President of the Bristol Myers Squibb Foundation, shares how the Foundation's investment in the Winn Awards program has grown into a national effort to expand access to clinical research, build trust in communities, and improve health outcomes for patients across the country. Sponsor: CoraNation Tailoring & Alterations
Interview with Alfred E. Buxton, MD, and Marie-France Poulin, MD, authors of Mechanisms Underlying Alterations in Cardiac Conduction After Transcatheter Aortic Valve Replacement. Hosted by Kristen K. Patton, MD. Related Content: Mechanisms Underlying Alterations in Cardiac Conduction After Transcatheter Aortic Valve Replacement
Interview with Alfred E. Buxton, MD, and Marie-France Poulin, MD, authors of Mechanisms Underlying Alterations in Cardiac Conduction After Transcatheter Aortic Valve Replacement. Hosted by Kristen K. Patton, MD. Related Content: Mechanisms Underlying Alterations in Cardiac Conduction After Transcatheter Aortic Valve Replacement
Join the program for an in-depth discussion on low-grade glioma – from burden and diagnosis to therapies. Credit available for this activity expires: 12/10/26 Earn Credit / Learning Objectives & Disclosures: https://www.medscape.org/viewarticle/pediatric-low-grade-glioma-braf-alterations-stories-science-2025a1000x3w?ecd=bdc_podcast_libsyn_mscpedu
On this Make A Difference Minute, volunteer baker Connie Ash shares how she once doubted she had what it takes to serve as a Sugar Angel for Icing Smiles. She wondered if her skills were good enough and if she could truly make a difference for a family facing the critical illness of a child. But she took a chance, submitted her application, and was accepted without hesitation. Today, Connie creates cakes that bring joy, comfort, and moments of normalcy to families who need it most. Her story is a reminder that sometimes saying yes, even when we are unsure, leads to something beautiful. Sponsor: CoraNation Tailoring & Alterations
Episode 305 is the eighteenth episode of our mini-series on the Tippit murder. David Belin, the celebrated Warren Commission attorney called it the "Rosetta Stone" of the JFK assassination. It may very well be just that...but for other reasons! In this eighteenth episode, we tell the story of one of the most blatant evidence tampering episodes within the case. And perhaps one of the most blatant ever in any such high profile case. The police logs that officially capture the conversations and the exact time in which they occur were uniquely suited to pinpoint the time of Tippit's death, and thus prove or disprove Oswald's ability to even be at the scene of the crime in time to commit the murder. When it became clear that this information was going to prove the authorities wrong, they altered the transcripts and obfuscated other evidence contained in those logs in order to conceal the fact that many officers were in the Oak Cliff area even when they had no business being there. The combination of these changes were not only designed to shut door the on the case and ensure that Oswald was to be identified as the killer, but they also avoided the obvious questions of a wider conspiracy that may have involved a number of individuals within the Dallas Police Department. Yes…there is a grave possibility that the true "Rosetta Stone" of November 22nd, 1963, might just lie in the quiet Dallas suburb of Oak Cliff, waiting for us to finally put the pieces together. This is a wander I've created especially for you…and of all the wanders you have taken with me, this may be the most thrilling of all! And don't worry, as the fall winds turn cooler, we will all be vacationing once again, in Mexico…I think you know what I mean by that. But our new wander takes precedent. As we wind down the Tippit series, I hope that you will enjoy these last few episodes of what is one of the most riveting aspects of the JFK assassination story.
Coverage that provides news and analysis of national issues significant to regional Australians.
On this Make A Difference Minute, I'm reminding listeners that the people we criticize are human long before they are athletes, performers, or professionals. Everyone makes mistakes, and most of the time, the person who fell short is already carrying the weight of it. This segment encourages compassion over blame, patience over public shaming, and understanding over harsh judgment. The way we respond to someone's worst moment can either lift them up or leave a lasting wound. Sponsor: CoraNation Tailoring & Alterations
Facing a serious loss after a loved one has died is just so tough. Without meaning to we can compound the stress of it all by how we approach our grief.The mindful approach to grief involves noticing, not judging, and using compassionate curiosity. It makes space for grief because grief is part of life and love. Here is the reference mentioned in the episode: Huang FY, et al. Mindfulness-based cognitive therapy on bereavement grief: Alterations of resting-state network connectivity associate with changes of anxiety and mindfulness. Hum Brain Mapp. 2021 Feb 1;42(2):510-520. I'm glad you're here.Dr. Deliawww.integrativepalliative.comwww.DoctorDelia.com (coming soon)Coping Courageously: A Heart-Centered Guide for Navigating a Loved One's Illness Without Losing Yourself is available here: www.copingcourageously.com Please review this podcast wherever you listen and forward your favorite episode to a friend! And be sure to subscribe!Sign up to stay connected and learn about upcoming programs:https://trainings.integrativepalliative.com/IPI-stay-in-touchI'm thrilled to be listed in Feedspot's top 15 palliative podcasts!https://blog.feedspot.com/palliative_care_podcasts/
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
What do you do if you need a last minute alteration.
Highlights:1) Where do hybrid-program imprints lodge?2) Energetic consent with non-human intelligences and boundary protocols3) Timelines vs. Destinies4) Indications when a nonlocal intelligence is interfacing
Today I'm joined by Leslie Stanfield of Lace Envy Alterations in Spokane, WA. Leslie is known in our community for her endless energy, her willingness to always learn something new, and the beautiful work she delivers to her brides.In this episode, Leslie shares her story of starting out sewing from home while raising five kids, and how that eventually led to opening her own bridal studio. We talk about what it really looks like to make the leap from working for a shop to running your own space, including how to budget for rent, find the right location, and price your work with confidence.Leslie also opens up about some of the tougher sides of this business, from handling emotionally draining fittings to navigating a serious shoulder injury right in the middle of wedding season. Her perspective on boundaries, resilience, and leaning on your community is one that every bridal seamstress needs to hear.In this episode:Leslie's journey from sewing “fun money” projects at home to running a professional studioHow she found and afforded her first storefrontThe importance of setting boundaries in busy season (no more 4 a.m. sewing nights!)How she handled a shoulder injury and kept her business afloatHer encouragement to seamstresses who are thinking about taking the leap into business ownershipConnect with Leslie:Website: https://laceenvyalts.com/Join the membership here: https://secretsofabridalseamstress.com/Learn more about the retreats here: https://secretsofabridalseamstress.squarespace.com/new-pageConnect with Nadine on Instagram: https://www.instagram.com/secretsofabridalseamstress/
You don't need to “fix” your metabolism—because it's probably not broken.In this episode, I'm cutting through all the BS around metabolism, especially the myths that have kept women stuck, frustrated, and blaming their hormones, their carbs, or their age. Based on game-changing science (yes, real science), you'll learn what actually influences your metabolism—and how to take back control of your energy, body composition, and long-term health.Spoiler: it's not about eating less, working out more, or chasing hacks. It's about supporting your fat tissue so it supports you.Here's what we cover:The groundbreaking study that reshaped everything we thought about metabolismWhy your metabolism likely hasn't slowed down (even in your 40s or 50s)What fat tissue has to do with energy, cravings, and inflammationThe real impact of carbs, hormones, and “starvation mode”5 foundational shifts that actually improve metabolic healthYour metabolism isn't the villain. And you're not broken. You just need to stop fighting your body—and start working with it.Get Weekly Health Tips: thrivehealthcoachllc.comLet's Connect:@ashleythrivehealthcoach or via email: ashley@thrivehealthcoachingllc.comPodcast Produced by Virtually You! Sources:Hall, K. D., Kahan, S., & Gallagher, I. H. (2016). Energy balance and its components: Implications for body weight regulation. The American Journal of Clinical Nutrition, 104(4), 989–1003. https://doi.org/10.3945/ajcn.116.133280Koliaki, C., & Roden, M. (2016). Alterations of mitochondrial function and insulin sensitivity in human obesity and diabetes mellitus. Annual Review of Nutrition, 36, 337–367. Alterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes MellitusPontzer, H., Yamada, Y., Sagayama, H., Ainslie, P. N., Andersen, L. F., Anderson, L. J., … & Speakman, J. R. (2021). Daily energy expenditure through the human life course. Science, 373(6556), 808–812. Daily energy expenditure through the human life courseSpiegel, K., Tasali, E., Penev, P., & Van Cauter, E. (2004). Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Annals of Internal Medicine, 141(11), 846–850. Brief Communication: Sleep Curtailment in Healthy Young Men Is Associated with Decreased Leptin Levels, Elevated Ghrelin Levels, and Increased Hunger and Appetite | Annals of Internal Medicine
Yesterday, Building and Construction Minister Chris Penk announced changes to the earthquake-prone building regulations that will remove nearly 3000 buildings from the classification register. Previously, buildings would have to meet a 34%NBS (new building standard) threshold to predict likelihoods of withstanding seismic action. The new system instead prioritises identifying structures that pose a higher risk to human life. Alterations seek to measure risk in a manner that balances safety with more affordable and realistic remediation action for existing properties. Producer Jasmine Gray spoke to Dr. Megan Boston, Senior Lecturer for Civil Engineering, at the University of Waikato about what the new quake-prone building regulations mean for Aotearoa's community safety and heritage.
Interview with Sharmili Edwin Thanarajah, MD, author of Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations. Hosted by John Torous, MD. Related Content: Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations GLP-1 Receptor Agonists for Pharmacologically Induced Weight Gain
Interview with Sharmili Edwin Thanarajah, MD, author of Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations. Hosted by John Torous, MD. Related Content: Soft Drink Consumption and Depression Mediated by Gut Microbiome Alterations GLP-1 Receptor Agonists for Pharmacologically Induced Weight Gain
Prayer:Heavenly Father, in the mighty name of Jesus Christ, I come before Your throne of grace in humility and repentance. I confess and renounce every sin of sexual perversion in my life and in my bloodline — past, present, and hidden — known or unknown. I acknowledge that these sins are an abomination before You, and I plead the blood of Jesus over my spirit, soul, and body. Lord, cleanse me from all unrighteousness, purify my heart, and renew a steadfast spirit within me. I choose to walk in holiness, purity, and truth from this day forward.Become a supporter of this podcast: https://www.spreaker.com/podcast/apostolic-deliverance-teaching--1288300/support.
In this podcast, experts Erminia Massarelli, MD, PhD, MS; Jorge J. Nieva, MD; Sandip Patel, MD; and Ignacio I. Wistuba, MD, discuss new therapies for patients with c-Met–overexpressing non–small cell lung cancer.
The rabbis made a number of different kinds of edits to their version of what some call ‘Scripture' (i.e., the Rabbinic or Masoretic Text). In some places, they fiddled with numbers, in some they changed names, and in still others they deleted entire sections of the text. In this final episode of the Old Testament portion of the Septuagint series, we examine the changes the rabbis made to the timelines (particularly the genealogies), the Book of Job, the Book of Esther, and a few other miscellaneous matters. The next two episodes will round out the LXX series with an examination of how the New Testament uses the Old (to the surprise of none, Jesus and the Apostles used the Septuagint), and then the final episode in the series will give a roadmap for where we, as the Church, go from here. Show Notes Esther: LXX and MT Compared See Also Letter: Origen to Africanus Luther on the Rabbinic Book of Esther Further Reading Esther (Brenton) Esther (NETS) [PDF] Calendar Systems: Anno Domini Anno Mundi Byzantine Calendar “Setting the Record Straight on the Primeval Chronology of the Septuagint (Part 2)” Pyramids and Sea Creatures in the Limestone [Just an interesting read.] Parental Warnings None.
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
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.
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
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
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
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...
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
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