Podcasts about non small cell lung cancer

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, subscribe wherever you get your podcast. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:    Dr. Vamsi Velcheti   @VamsiVelcheti    Dr. Nathan Pennell   @n8pennell   Follow ASCO on social media:     @ASCO on Twitter     ASCO on Facebook     ASCO on LinkedIn   ASCO on BlueSky   Disclosures:   Dr. Vamsi Velcheti:   Honoraria: ITeos Therapeutics   Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus   Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline   Dr. Nathan Pennell:     Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron    Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi 

Oncology here & nowIn this interview Dr. Biagio Ricciuti of Dana Farber Cancer Institute (USA) talks to Dr. Marcelo Corassa of beneficência Portuguesa de São Paulo (Brazil) as they discuss Treatments in EGFR mutant Non Small Cell Lung Cancer. The discussion centers around the results of FLAURA, MARIPOSA and FLAURA2, future directions and much more.Join Us

Welcome to the Sterile Technique Podcast! It's the podcast about Surgical Technology. Whether you are a CST or CSFA, this podcast helps you earn CE credits and improve your surgery skills in the OR. This episode discusses an article in the March 2025 issue of The Surgical Technologist, the official journal of the Association of Surgical Technologists (AST). The article is titled, "Robot-Assisted Thoracic Surgery in Non-Small Cell Lung Cancer". "Scrub in" at steriletpodcast.com and on Twitter, @SterileTPodcast (twitter.com/SterileTPodcast). This podcast is a Dybas Media production. Sound effects adapted from GarageBand and sindhu.tms at https://freesound.org/people/sindhu.tms/sounds/169065/ and licensed courtesy of https://creativecommons.org/licenses/by-nc/3.0/.

What if a cancer treatment worked—until it suddenly didn't? A new case report, “Acquired RUFY1-RET rearrangement as a mechanism of resistance to lorlatinib in a patient with CD74-ROS1 rearranged non-small cell lung cancer: A case report,” published in Oncotarget, reveals how a non-small cell lung cancer (NSCLC) patient developed drug resistance through a rare genetic alteration, allowing the cancer to evade therapy. This unexpected finding highlights the importance of advanced genetic testing and personalized cancer treatments. Non-Small Cell Lung Cancer, Targeted Therapy and Drug Resistance Non-Small Cell Lung Cancer is the most common type of lung cancer, accounting for nearly 85% of all cases. Some patients with NSCLC have genetic mutations, such as ROS1 gene fusions, that drive tumor growth. These patients often respond well to targeted therapies like lorlatinib, a ROS1 inhibitor that blocks cancer growth. However, cancer is constantly evolving. Over time, it can develop resistance to targeted therapies, leading to treatment failure. Understanding these resistance mechanisms is crucial for precision oncology, the approach of tailoring cancer treatment based on a patient's unique genetic profile. Full. blog - https://www.oncotarget.org/2025/03/12/a-rare-genetic-shift-that-helped-lung-cancer-evade-treatment/ DOI - https://doi.org/10.18632/oncotarget.28682 Correspondence to - Wade T. Iams - wade.t.iams@vumc.org Video short - https://www.youtube.com/watch?v=HE_qSkcRZho About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Theralase Technologies CEO Roger DuMoulin-White joined Steve Darling from Proactive to announce a significant advancement in cancer treatment. The company's lead drug formulation, Rutherrin, has demonstrated a remarkable ability to enhance the efficacy of Cisplatin, a commonly prescribed chemotherapy drug, in treating chemotherapy-resistant Non-Small Cell Lung Cancer in a preclinical animal model. DuMoulin-White detailed the experimentation process, where mice were divided into two groups: a control group treated with Cisplatin alone and an active group treated with a combination of Cisplatin and Rutherrin. The results were striking. The mice in the active group showed a significantly higher enhancement of Cisplatin efficacy, marked by a notable increase in overall survival compared to the control group. The statistical significance of these results highlights the potential impact of Rutherrin in improving treatment outcomes for patients with aggressive NSCLC. Theralase Technologies believes that the efficacy of Rutherrin could be further improved by combining it with additional treatments such as radiation or Metformin, which could activate Rutherrin® while it resides in NSCLC cells. This promising preclinical data lays the groundwork for future studies and potential clinical applications, offering new hope for patients battling resistant forms of lung cancer. #proactiveinvestors #theralasetechnologiesinc #tsxv #tlt #otcqb #tftff #MedicalResearch #HealthcareInnovation #PatientCare #CancerResearch #ProactiveInvestors #invest #investing #investment #investor #stockmarket #stocks #stock #stockmarketnews#invest #investing #investment #investor #stockmarket #stocks #stock #stockmarketnews

Editor-in-Chief, Robert Amdur, MD, discusses using SBRT dose schedules to re-irradiate large volume recurrences of locally advanced Non-Small Cell Lung Cancer that has progressed following high-dose radiotherapy with conventional fractionation. The discussion is based on a paper published in the May 2024 issue of PRO titled "Thoracic Reirradiation with Stereotactic Body Radiation Therapy (SBRT) for Recurrent Advanced Non-Small Cell Lung Cancer (NSCLC)” (2024, Issue 3, May/June, PMID 38387781).

Today, OFTIM celebrates its 80th episode and presents its ESMO23 plenary session, including two practice-changing, paradigm-shifting trials. The first investigates the EGFR mutation Non-Small Cell Lung Cancer world with new drugs (amivantamab and lazertinib) to treat patients hose who progressed on osimertinib. The second trial is the EV-302/KEYNOTE-A39, which explores whether enfortumab vedotin (ADC) and pembrolizumab (immunotherapy) can best-platinum-based chemotherapy. No prior trial has ever done this, so the stakes are high. As the little engine once said, "I think I can", and, we, too, continue to see seismic shifts in cancer treatment in our quest for better therapy. For now, the OFTIM team is signing out and taking a small break after daily reporting, but we hope you loved it and can't wait to return with more from the fascinating world of Medical Oncology.StudiesEV-302/KEYNOTE-A39 - https://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/639614MARIPOSA-2 - https://esmocongress.esmo.org/esmo/esmo2023/en-GB/presentation/639283For more episodes, resources and blog posts, visit www.inquisitiveonc.comFind us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of Music Unlimited: https://pixabay.com/users/music_unlimited-27600023/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

Are you ready for a life-changing story? In this episode, In The Suite host, Tina Powell shares her incredible story of survival and strength that will leave you inspired. Tina's journey took an unexpected turn when she was diagnosed with non-small cell lung cancer. She underwent a life-saving robotic lobectomy procedure and shares her mental healing process, remarkable resilience, and faith.Tina Talks is more than just a cancer story. Tina dives deeper into wellness, good health, and leadership. She emphasizes the need for support and the importance of maintenance for a healthy life.Join Tina as she explores her treatment options, chemotherapy experiences, and targeted therapies' power. She's on a mission to raise awareness, provide advice, and offer hope to others facing challenging times.This is a story of triumph, determination, and resilience. Get ready to be inspired and motivated to take control of your well-being. 

Blurb In this posdcast Dr. Luigi Rolli, Dr. Chiara Ciniselli, Dr. Paola Perego and Dr. Giulia Bertolini discuss the biological role of the antimetastatic gene KiSS1 based on the results they obtained in Non Small Cell  Lung Cancer cellular models and in liquid biopsies obtained from patients and healthy subject

Drs Sumanta Pal and Scott Haake discuss the biology of kidney cancer and how to incorporate tissue biomarkers into prospective studies on renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/984237). The topics and discussions are planned, produced, and reviewed independently of advertisers. This podcast is intended only for US healthcare professionals. Resources W. Kimryn Rathmell, MD, PhD, MMHC https://www.vumc.org/viiii/person/w-kimryn-rathmell-md-phd-mmhc Novel Emerging Biomarkers to Immunotherapy in Kidney Cancer https://pubmed.ncbi.nlm.nih.gov/34868351/ PD1 and PD-L1 Inhibitors for the Treatment of Kidney Cancer: The Role of PD-L1 Assay https://pubmed.ncbi.nlm.nih.gov/32208115/ Oncogene-Specific Differences in Tumor Mutational Burden, PD-L1 Expression, and Outcomes From Immunotherapy in Non-Small Cell Lung Cancer https://pubmed.ncbi.nlm.nih.gov/34376553/ Multiomics in Primary and Metastatic Breast Tumors From the AURORA US Network Finds Microenvironment and Epigenetic Drivers of Metastasis https://pubmed.ncbi.nlm.nih.gov/36585450/ Avelumab Plus Axitinib Versus Sunitinib in Advanced Renal Cell Carcinoma: Biomarker Analysis of the Phase 3 JAVELIN Renal 101 Trial https://pubmed.ncbi.nlm.nih.gov/32895571/ Clinical Activity and Molecular Correlates of Response to Atezolizumab Alone or in Combination With Bevacizumab Versus Sunitinib in Renal Cell Carcinoma https://pubmed.ncbi.nlm.nih.gov/29867230/ Atezolizumab Plus Bevacizumab Versus Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma (IMmotion151): A Multicentre, Open-Label, Phase 3, Randomised Controlled Trial https://pubmed.ncbi.nlm.nih.gov/31079938/ Insights Into the Genetic Basis of the Renal Cell Carcinomas From the Cancer Genome Atlas https://pubmed.ncbi.nlm.nih.gov/27330105/ Genetic Testing to Select Therapy for the Treatment of Advanced or Metastatic Kidney Cancer, OPTIC RCC Study https://clinicaltrials.gov/ct2/show/NCT05361720

Year in Review: Clinical Investigator Perspectives on the Most Relevant New Data Sets and Advances in Targeted Therapy for Non-Small Cell Lung Cancer — Faculty Presentation 1: Management of Non-Small Cell Lung Cancer with an EGFR, ALK or ROS1 Abnormality — Dr Zofia Piotrowska CME information and select publications

  Vidcast:  https://youtu.be/eeZK_NIjhL8   The spike protein that CoVid uses to fuse with and infect human cells appears to be toxic to at least one deadly form of human cancer, Non-Small Cell Lung Cancer.  Investigators at Chicago's Rush University Medical Center tested purified CoVid spike protein against cell cultures of human non-small cell lung cancer, NSCLC, and mouse lung cancers induced by the tobacco carcinogen NNK   The S1 spike protein at very low doses led to the death of cultured NSCLC cells.  Antibodies against the spike protein blocked this effect as did heat-induced destruction of the spike protein.  Studies also showed that the spike protein's anti-cancer effect required interaction of the protein with ACE2 receptors on the cancer cells.  The mouse experiments showed that intranasal sprays of the Covid spike protein effectively blocked the growth of lung cancers as well as inducing the regression of the tumors.   This research is in its earliest stages.  It would be ironic, though, if the CoVid virus that has sickened and killed so many has a role in preventing the development and progression of cancer.   https://www.mdpi.com/2072-6694/14/22/5648   #covid #spikeprotein #cancer #nsclc #lungcancer  

Drs Sumanta Pal and Jennifer Wargo discuss how the gut microbiome impacts response to cancer therapy in patients with renal cell carcinoma. Relevant disclosures can be found with the episode show notes on Medscape (https://www.medscape.com/viewarticle/968742). The topics and discussions are planned, produced, and reviewed independently of advertiser. This podcast is intended only for US healthcare professionals. Resources Gut Microbiome Modulates Response to Anti-PD-1 Immunotherapy in Melanoma Patients https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827966/ The Microbiome in Cancer Immunotherapy: Diagnostic Tools and Therapeutic Strategies https://pubmed.ncbi.nlm.nih.gov/29567708/ Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates Anti-PD-L1 Efficacy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873287/ Anticancer Immunotherapy by CTLA-4 Blockade Relies on the Gut Microbiota https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721659/ Gut Microbiome Influences Efficacy of PD-1-Based Immunotherapy Against Epithelial Tumors https://pubmed.ncbi.nlm.nih.gov/29097494/ Dietary Fiber and Probiotics Influence the Gut Microbiome and Melanoma Immunotherapy Response https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970537/ Fiber in Diet Linked to Cancer Immunotherapy Response https://www.nih.gov/news-events/nih-research-matters/fiber-diet-linked-cancer-immunotherapy-response Fecal Microbiota Transplant Promotes Response in Immunotherapy-Refractory Melanoma Patients https://www.science.org/doi/10.1126/science.abb5920 Fecal Microbiota Transplant Overcomes Resistance to Anti-PD-1 Therapy in Melanoma Patients https://pubmed.ncbi.nlm.nih.gov/33542131/ Fecal Microbiota for Transplantation: Safety Alert - Risk of Serious Adverse Events Likely Due to Transmission of Pathogenic Organisms https://www.fda.gov/safety/medical-product-safety-information/fecal-microbiota-transplantation-safety-alert-risk-serious-adverse-events-likely-due-transmission Fecal Microbiota Transplantation Followed by Anti–PD-1 Treatment in Patients With Advanced Melanoma https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.9533 Tocilizumab, Ipilimumab, and Nivolumab for the Treatment of Advanced Melanoma, Non-Small Cell Lung Cancer, or Urothelial Carcinoma https://clinicaltrials.gov/ct2/show/NCT04940299 Nivolumab plus Ipilimumab With or Without Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma: A Randomized Phase 1 Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018425/

Dear Colleagues,Welcome to the ASCO22 RoundUp for Day one of the congressStarting with with KRYstal1 with a concomitant publication in the New EnglandPhase One report of Adagrasib in Non Small Cell Lung Cancer, targeting KRAS G12C shows promise in  clinical efficacy without new safety signalsLarge number of response median follow-up of 12.5 monthsthe median PFS 6.5 months  median OS 12.6 monthsThe EVEREST TrialAdjuvant everolimus improves RFS in resected renal cell carcinoma in over 1,500 patients6-year estimated RFS was 64% for everolimus Vs 61% placebo.Just missing respecified 0.0222 significance. That is a minimal improved RFS with significantly higher AEs.There was a 21% improvement in RFS in everolimus in those with high risk for recurrence with no benefit seen in those in an intermediate high-risk group.Update of COSMIC-021 TrialThis was first-line treatment in urothelial carcinoma Combining Cabo/Atezo shows encouraging results with manageable toxin patients who were ineligible for cisplatincisplatin eligible or with 1 prior immune checkpoint inhibitor and no prior VEGF TKIsOR 20% in cisplatin-ineligible patients,30% in cisplatin-eligible patients,10%for those w prior ICI.Lung-MAP S1800Ain Second-line pembrolizumab plus ramucirumab in Non Small Cell Lung CancerHere there was a possible survival benefit with immune checkpoint inhibitor resistance VS Standard of care This is the first successful trial in the second-line setting for advanced NSCLC in those withAcquired resistance to immune checkpoint inhibitor therapy with out a Chemo backboneGreat to see lung cancer patients who progressed on prior immunotherapy, living significantly longer when treated with the combo of Pembrolizumab plus ramucirumab OS 14.5 months vs 11.6 monthsVery encouragingCheckmate 9ERDepth of response to  nivolumab plus cabozantinib is associated with durable efficacy and improved prognosis in previously untreated advanced renal cell carcinomaThe 12-month PFS rate for patients with the deepest responses in nivo cabo was 46.2% Vs 27.4% in sunitinib.The 18-month OS rate was twice as high in nivolumab plus cabozantinib 37.9% vs 17.4%)An improvement in Prognosis!And those are just SOME of the top trials presented at DAY1 of ASCO22 Looking forward to an Amazing Day 2Reminding everyone to mask up and enjoy ASCO

Ashwagandha is an important herb used in the ancient Indian system of medicine known as Ayurveda to promote general health and well-being. In Ayurvedic practice, ashwagandha is classified as a Rasayana, which means an herb or preparation that rejuvenates, extends life, and promotes a youthful state of physical and mental health. Listen in to discover more about ashwagandha's incredible health benefits in general and a special potent “superhero” form known as KSM-66 ashwagandha.   What Does Ashwagandha Do? Ashwagandha's superpower is that it is an adaptogen. Adaptogens are non-toxic therapies that normalize our bodily functions – both physical and mental – that are thrown out of balance when we are exposed to chronic, uncontrolled stress. They do so by correcting imbalances in the neuroendocrine and immune systems [2]. In short, adaptogens enhance our ability to cope with stress. There are more than 35 natural compounds in ashwagandha including alkaloids, steroidal lactones, saponins, and with anolides. These compounds have been shown to have anti-stress activity in multiple laboratory models of chronic stress and in some human studies as well [1-5]. Additionally, ashwagandha extracts as well as specific bioactive compounds present in this plant – primarily in the roots – have been shown to help: counter pain and joint swelling associated with arthritis boost various components of the immune system protect the brain and nervous system slow down or even kill abnormal cells enhance both male and female sexual desire and function What Is KSM-66 Ashwagandha? KSM-66 Ashwagandha is a high-concentration ashwagandha root extract manufactured and sold by Ixoreal Biomed, located in Hyderabad, India [6]. Ashwagandha KSM-66 is made solely from ashwagandha roots, which contain its main bioactive ingredients, without using any other parts that are considered to be less effective. A unique feature of KSM-66 ashwagandha is that it's standardized to a withanolide content of at least 5 percent. Withanolides are a group of around 300 naturally occurring steroid compounds, some of which are naturally present in ashwagandha. One example is Withaferin A, an anti-inflammatory compound that has also been shown to stop tumors from growing their own blood vessels, slowing down their growth, and perhaps even shrinking them. Last but not least, KSM-66 ashwagandha is produced by a unique extraction process, based on the principles of “green chemistry,” without using alcohol or any synthetic solvents. Let's take a closer look now at some of KSM-66 ashwagandha's benefits for health.   What Too Much Cortisol Does to the Body Any stressful event in our lives causes our adrenal glands to produce cortisol, a steroid hormone that acts to control blood sugar levels, regulate metabolism, lower inflammation levels, influence memory formation, and manage salt and water balance [7]. The more stressed we are and the longer we're stressed, the more our adrenals respond by releasing cortisol into our bloodstream. Too much cortisol in the blood over a prolonged period of time can lead to: rapid weight gain high blood pressure osteoporosis muscle weakness mood swings anxiety, depression, or irritability increased thirst and frequency of urination [7] Ongoing high cortisol levels can also eventually cause a lack of sex drive in men. In women, periods typically become irregular, less frequent, or may even stop altogether (amenorrhea).   How Can Ashwagandha Help Us Cope With Stress? To answer this question, a double-blind, randomized, placebo-controlled trial was conducted to assess the safety and efficacy of KSM-66 ashwagandha (which, as mentioned above, is a high-concentration, full-spectrum ashwagandha root extract) in 64 adults [5]. After 60 days of treatment, the study authors observed a “substantial reduction” in four separate measures of stress in the study participants. KSM-66 ashwagandha also reduced levels of the hormone cortisol in the blood. By lowering cortisol, ashwagandha tones down the body's response to stressful situations, in effect “calming us down.”   No serious adverse events were reported [5] and the study researchers concluded that: “High-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.” Similarly, in another randomized, double-blind, placebo-controlled study, 60 stressed but otherwise healthy adults were randomly assigned to take either a placebo or an ashwagandha root extract once daily for 2 months [8]. At the end of the study, participants given ashwagandha showed a significant reduction in their stress, anxiety, and depression scores. Once again, ashwagandha consumption was associated with a greater reduction in the levels of cortisol in the blood, when compared with placebo [8].   The Connection Between Stress and Obesity Chronic stress has been associated with many illnesses, including obesity. In a double-blind, randomized, placebo-controlled trial, ashwagandha consumption was seen to lead to significant reductions in emotional and uncontrolled food cravings while also lowering cortisol, body weight, and body mass index (BMI) in 52 subjects subjected to chronic stress [9]. Indeed, laboratory experiments in mice have shown that one of the main active ingredients in ashwagandha known as Withaferin A can protect against obesity caused by a high-fat diet by reducing inflammation in the liver, oxidative stress, and insulin resistance [10]. These and other findings make it clear that ashwagandha is a powerful tool in our battle against ongoing stress, likely by regulating various specific aspects of our hypothalamus-pituitary-adrenal (HPA) axis. This is an interactive neuroendocrine system that plays a key role in maintaining our body's internal equilibrium, along with orchestrating our body's response to stress.   Ashwagandha Benefits for Joint Pain Ashwagandha is a key ingredient in many Ayurvedic formulations prescribed for joint-related conditions such as osteoarthritis. Indeed, many research studies show that ashwagandha and its bioactive ingredients help to manage and reduce inflammation levels. For instance, in a double-blind, placebo-controlled cross-over clinical trial published in 1991, 42 patients with osteoarthritis were randomized to receive a formula containing ashwagandha, frankincense, turmeric, and zinc – or placebo – for three months [11]. Clinical efficacy was evaluated every 15 days in terms of severity of pain, morning stiffness, Ritchie articular index (a weighted score of tenderness and swelling in 53 joint groups, each scored on a 0-3 scale), joint score, disability score, and grip strength. Throughout the study, the herbal formula was seen to significantly reduce the severity of joint pain and disability. No significant adverse effects were reported. In another study, 86 patients with joint pain were given 5 grams of ashwagandha powder twice a day for three weeks with lukewarm water or milk [12]. Then these patients took another Ayurvedic preparation known as Sidh Makardhwaj – a formulation used in rheumatoid arthritis and neurological disorders – daily for the next four weeks. Treatment with ashwagandha and Sidh Makardhwaj for seven weeks led to significantly improved scores of joint swelling, tenderness, and pain, indicating that this combination treatment is likely to be beneficial in rheumatoid arthritis. Indeed, in laboratory experiments, an ashwagandha root extract was seen to reduce inflammation in knee cartilage taken from chronic osteoarthritis patients [13].   Ashwagandha for Boosting Endurance, Muscle Strength, and Recovery Ashwagandha has long had the reputation of being able to enhance cardiovascular endurance and physical performance. As stated earlier, consuming this herb is said to impart the strength and stamina of a horse [1]. In a prospective, double-blind, randomized, and placebo-controlled study, KSM-66 ashwagandha was shown to significantly boost cardiorespiratory endurance and improve self-reported quality of life (QOL) in 50 healthy male and female athletic adults [14]. In another randomized, prospective, double-blind, placebo-controlled clinical study, 57 young men with little previous experience in resistance training were randomized into treatment and placebo groups [15]. Participants in the treatment group consumed 300 mg of ashwagandha root extract twice daily, while those in the control group took starch placebos instead. Multiple measurements – including muscle strength, muscle size, body composition, testosterone levels, and muscle recovery – were made before the start of the study. Both groups then went through resistance training for 8 weeks and the measurements were repeated when they were done. Promisingly, the group of men taking ashwagandha root extract had significantly greater increases in muscle strength and arm muscle size relative to the placebo group. They also showed significantly less exercise-induced muscle damage, higher testosterone levels, and a greater reduction in body fat percentage. In other words, ashwagandha supplementation is associated with significant increases in muscle mass, strength, and recovery after exercise. In another randomized, double-blind strength and conditioning study known as the STAR trial, 500 mg of an extract of ashwagandha roots and leaves was consumed by recreationally active young men for 12 weeks [16]. Body composition, muscular strength, power, and endurance, cycling time trial, and blood chemistry were measured before and after the study. Consuming the ashwagandha extract was seen to improve upper and lower body strength and improve distribution of body mass in these men, once again without causing any serious adverse effects.   Ashwagandha as an Immune System Enhancer Ashwagandha enhances immune function. In a small study, ashwagandha root extract was seen to activate multiple types of immune cells in the participants [17]. Similarly, a tea fortified with five herbs including ashwagandha was seen to activate so-called “natural killer” (NK) cells in not just one, but two independent double-blind intervention studies conducted in India on healthy volunteers [18]. NK cell activity is an important aspect of our body's early immune response to infections. Interestingly, in other situations, ashwagandha extracts have also been shown to suppress specific components of the immune system. For example, one of the characteristic features of rheumatoid arthritis (RA) is the continuous production of pro-inflammatory compounds known as cytokines in joint cavities, triggering inflammation and cartilage destruction. In laboratory experiments in rats, a root extract of ashwagandha was seen to suppress production of pro-inflammatory cytokines and reduce oxidative stress [19].   The Brain-Boosting Benefits of Ashwagandha Numerous laboratory studies show that ashwagandha – traditionally used in Ayurveda to boost intellect and memory – can slow, stop, and reverse damage to brain cells and may even help to reconstruct brain cell networks. For instance, ashwagandha extracts have been shown to promote nerve cell growth in culture [20]. Withanolide A, withanoside IV, and withanoside VI were identified as the bioactive compounds responsible. Ashwagandha extracts as well as specific bioactive compounds (e.g., withanolide A) have also been shown to protect nerve cells in culture against damage caused by various toxic agents [21]. Amazingly, the administration of withanoside IV for 21 days led to recovery in a rat model of spinal cord damage [20]. It is well known that toxic free radicals damage brain cells and contribute to both normal aging and aging-related health conditions. In a 2015 study, both ashwagandha extracts and a bioactive compound known as withanone were seen to protect nerve cells from oxidative damage [22]. Not surprisingly, ashwagandha has long been used in Ayurveda to enhance memory and improve mental faculties. In a randomized, double-blind, placebo-controlled pilot study, 50 adults suffering from mild cognitive impairment (MCI) – who are considered to be at a greater risk of developing dementia later in life – were treated with either 300 mg of KSM-66 ashwagandha twice daily or placebo for 8 weeks [23]. After 8 weeks, the ashwagandha KSM-66 group showed significant improvements in both their immediate or short-term as well as general memory, relative to the placebo group. The ashwagandha group also showed significant improvements in executive function, sustained attention, and information-processing abilities.   Can Ashwagandha Even Help Protect Against Abnormal Cell Growth? Ashwagandha and other species of Withania are well known in folk medicine traditions for their anti-cancer properties and their extracts have been shown to be toxic for multiple types of cancer cells in laboratory experiments [24]. They appear to act by slowing down or even stopping cancer cell growth by inducing programmed cell death or “apoptosis.” As stated earlier, Withaferin A, an anti-inflammatory withanolide, has been shown to act as an anti-angiogenic. In other words, it can help stop tumors from growing their own blood vessels, slowing down their growth, or perhaps even shrinking them. As reported in the journal Biochemical Pharmacology in August 2019, growing evidence suggests that Withaferin A is very effective against cancer [25]. For instance, low response rate and recurrence are common issues in lung cancer. Withaferin A has been shown to exhibit potent toxicity against several lung cancer cell lines in laboratory experiments. Not only that, the combination of Withaferin A and chemotherapeutic drugs were shown to have additive effects on lung cancer cell survival [26]. Withaferin A has also been shown to be toxic for breast cancer and cervical cancer (HeLa) cells in laboratory experiments [27,28]. Similarly, other bioactive compounds in ashwagandha have also been shown to be toxic for cancer cells in laboratory experiments [29].   KSM-66 Ashwagandha's Impact on Libido and Infertility Ashwagandha root extract has been shown to enhance sexual desire and function in both men and women. For instance, ashwagandha has been described in Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. In a pilot study conducted to evaluate the effects of ashwagandha in patients with a low sperm count (known as oligospermia), a total of 46 male patients were randomized either to treatment with KSM-66 Ashwagandha or placebo for 90 days [30]. At the end of the study, participants given KSM-66 ashwagandha showed a 167% increase in sperm count, a 53% increase in semen volume, and a 57% increase in sperm motility relative to baseline. In comparison, only minimal changes were seen in the placebo group. Further, a greater improvement in hormone levels was seen with KSM-66 ashwagandha. In other words, ashwagandha is likely to be very effective in treating oligospermia, which is a leading cause of male infertility. Similarly, a meta-analysis showed that ashwagandha significantly improved sperm concentration and sperm motility even in men with normal sperm parameters, without any adverse effects [31]. Ashwagandha has also been shown to enhance sexual function in women. At the Trupti Hospital and Santati Fertility Center located near Mumbai in India, 50 women were randomized to either ashwagandha treatment or placebo (300 mg twice daily) for 8 weeks [32]. In this study, ashwagandha supplementation was shown to lead to significantly higher scores in multiple markers of sexual desire and function.   But Is Ashwagandha Safe? Ashwagandha root powder has been used in Ayurvedic medicine for centuries, and it is believed to be completely safe and free of any toxicity. Extracts of ashwagandha made using alcohol and water will likely contain higher doses of its natural ingredients, relative to raw powder. So far animal studies with such extracts have shown no evidence of toxicity, even at relatively high doses [33]. However, it is always advisable to take an herbal supplement only after consulting your healthcare provider, especially if you have any ongoing health conditions or if you're pregnant or breastfeeding.   Organixx Turmeric 3D Contains KSM-66 Ashwagandha The Organixx Turmeric 3D formula has always contained ashwagandha extract. As part of our commitment to seeking out the cleanest and most effective supplement ingredients, we upgraded to KSM-66 Ashwagandha in 2019 – the most clinically studied ashwagandha on the market. KSM-66 is a full-spectrum extract produced using a unique proprietary extraction process, based on “Green Chemistry” principles, without using alcohol or any other chemical solvent.   Resources: [1] An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda. [2] Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha. [3] Scientific Basis for the Therapeutic Use of Withania somnifera (Ashwagandha): A Review. [4] Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. [5] A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. [6] KSM-66 Ashwagandha Documentary [7] Society for Endocrinology: You and Your Hormones – Cortisol. [8] An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. [9] Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. [10] Withaferin A Protects Against High-Fat Diet-Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance. [11] Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. [12] Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study. [13] The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. [14] Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults. [15] Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. [16] Effects of an Aqueous Extract of Withania somnifera on Strength Training Adaptations and Recovery: The STAR Trial. [17] In vivo effects of Ashwagandha (Withania somnifera) extract on the activation of lymphocytes. [18] In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs. [19] In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis. [20] Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. [21] Neuritic regeneration and synaptic reconstruction induced by withanolide A. [22] Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. [23] Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. [24] Medicinal Plants from Near East for Cancer Therapy. [25] Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug. [26] Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer. [27] Withaferin A inhibits expression of ataxia telangiectasia and Rad3-related kinase and enhances sensitivity of human breast cancer cells to cisplatin. [28] Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities. [29] Cytotoxic Withanolides from the Roots of Indian Ginseng (Withania somnifera). [30] Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. [31] Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis. [32] Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study. [33] Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study. KSM-66 Ashwagandha: A Superhero Herb for Body & Brain

Ashwagandha is an important herb used in the ancient Indian system of medicine known as Ayurveda to promote general health and well-being. In Ayurvedic practice, ashwagandha is classified as a Rasayana, which means an herb or preparation that rejuvenates, extends life, and promotes a youthful state of physical and mental health. Listen in to discover more about ashwagandha's incredible health benefits in general and a special potent “superhero” form known as KSM-66 ashwagandha.   What Does Ashwagandha Do? Ashwagandha's superpower is that it is an adaptogen. Adaptogens are non-toxic therapies that normalize our bodily functions – both physical and mental – that are thrown out of balance when we are exposed to chronic, uncontrolled stress. They do so by correcting imbalances in the neuroendocrine and immune systems [2]. In short, adaptogens enhance our ability to cope with stress. There are more than 35 natural compounds in ashwagandha including alkaloids, steroidal lactones, saponins, and with anolides. These compounds have been shown to have anti-stress activity in multiple laboratory models of chronic stress and in some human studies as well [1-5]. Additionally, ashwagandha extracts as well as specific bioactive compounds present in this plant – primarily in the roots – have been shown to help: counter pain and joint swelling associated with arthritis boost various components of the immune system protect the brain and nervous system slow down or even kill abnormal cells enhance both male and female sexual desire and function What Is KSM-66 Ashwagandha? KSM-66 Ashwagandha is a high-concentration ashwagandha root extract manufactured and sold by Ixoreal Biomed, located in Hyderabad, India [6]. Ashwagandha KSM-66 is made solely from ashwagandha roots, which contain its main bioactive ingredients, without using any other parts that are considered to be less effective. A unique feature of KSM-66 ashwagandha is that it's standardized to a withanolide content of at least 5 percent. Withanolides are a group of around 300 naturally occurring steroid compounds, some of which are naturally present in ashwagandha. One example is Withaferin A, an anti-inflammatory compound that has also been shown to stop tumors from growing their own blood vessels, slowing down their growth, and perhaps even shrinking them. Last but not least, KSM-66 ashwagandha is produced by a unique extraction process, based on the principles of “green chemistry,” without using alcohol or any synthetic solvents. Let's take a closer look now at some of KSM-66 ashwagandha's benefits for health.   What Too Much Cortisol Does to the Body Any stressful event in our lives causes our adrenal glands to produce cortisol, a steroid hormone that acts to control blood sugar levels, regulate metabolism, lower inflammation levels, influence memory formation, and manage salt and water balance [7]. The more stressed we are and the longer we're stressed, the more our adrenals respond by releasing cortisol into our bloodstream. Too much cortisol in the blood over a prolonged period of time can lead to: rapid weight gain high blood pressure osteoporosis muscle weakness mood swings anxiety, depression, or irritability increased thirst and frequency of urination [7] Ongoing high cortisol levels can also eventually cause a lack of sex drive in men. In women, periods typically become irregular, less frequent, or may even stop altogether (amenorrhea).   How Can Ashwagandha Help Us Cope With Stress? To answer this question, a double-blind, randomized, placebo-controlled trial was conducted to assess the safety and efficacy of KSM-66 ashwagandha (which, as mentioned above, is a high-concentration, full-spectrum ashwagandha root extract) in 64 adults [5]. After 60 days of treatment, the study authors observed a “substantial reduction” in four separate measures of stress in the study participants. KSM-66 ashwagandha also reduced levels of the hormone cortisol in the blood. By lowering cortisol, ashwagandha tones down the body's response to stressful situations, in effect “calming us down.”   No serious adverse events were reported [5] and the study researchers concluded that: “High-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.” Similarly, in another randomized, double-blind, placebo-controlled study, 60 stressed but otherwise healthy adults were randomly assigned to take either a placebo or an ashwagandha root extract once daily for 2 months [8]. At the end of the study, participants given ashwagandha showed a significant reduction in their stress, anxiety, and depression scores. Once again, ashwagandha consumption was associated with a greater reduction in the levels of cortisol in the blood, when compared with placebo [8].   The Connection Between Stress and Obesity Chronic stress has been associated with many illnesses, including obesity. In a double-blind, randomized, placebo-controlled trial, ashwagandha consumption was seen to lead to significant reductions in emotional and uncontrolled food cravings while also lowering cortisol, body weight, and body mass index (BMI) in 52 subjects subjected to chronic stress [9]. Indeed, laboratory experiments in mice have shown that one of the main active ingredients in ashwagandha known as Withaferin A can protect against obesity caused by a high-fat diet by reducing inflammation in the liver, oxidative stress, and insulin resistance [10]. These and other findings make it clear that ashwagandha is a powerful tool in our battle against ongoing stress, likely by regulating various specific aspects of our hypothalamus-pituitary-adrenal (HPA) axis. This is an interactive neuroendocrine system that plays a key role in maintaining our body's internal equilibrium, along with orchestrating our body's response to stress.   Ashwagandha Benefits for Joint Pain Ashwagandha is a key ingredient in many Ayurvedic formulations prescribed for joint-related conditions such as osteoarthritis. Indeed, many research studies show that ashwagandha and its bioactive ingredients help to manage and reduce inflammation levels. For instance, in a double-blind, placebo-controlled cross-over clinical trial published in 1991, 42 patients with osteoarthritis were randomized to receive a formula containing ashwagandha, frankincense, turmeric, and zinc – or placebo – for three months [11]. Clinical efficacy was evaluated every 15 days in terms of severity of pain, morning stiffness, Ritchie articular index (a weighted score of tenderness and swelling in 53 joint groups, each scored on a 0-3 scale), joint score, disability score, and grip strength. Throughout the study, the herbal formula was seen to significantly reduce the severity of joint pain and disability. No significant adverse effects were reported. In another study, 86 patients with joint pain were given 5 grams of ashwagandha powder twice a day for three weeks with lukewarm water or milk [12]. Then these patients took another Ayurvedic preparation known as Sidh Makardhwaj – a formulation used in rheumatoid arthritis and neurological disorders – daily for the next four weeks. Treatment with ashwagandha and Sidh Makardhwaj for seven weeks led to significantly improved scores of joint swelling, tenderness, and pain, indicating that this combination treatment is likely to be beneficial in rheumatoid arthritis. Indeed, in laboratory experiments, an ashwagandha root extract was seen to reduce inflammation in knee cartilage taken from chronic osteoarthritis patients [13].   Ashwagandha for Boosting Endurance, Muscle Strength, and Recovery Ashwagandha has long had the reputation of being able to enhance cardiovascular endurance and physical performance. As stated earlier, consuming this herb is said to impart the strength and stamina of a horse [1]. In a prospective, double-blind, randomized, and placebo-controlled study, KSM-66 ashwagandha was shown to significantly boost cardiorespiratory endurance and improve self-reported quality of life (QOL) in 50 healthy male and female athletic adults [14]. In another randomized, prospective, double-blind, placebo-controlled clinical study, 57 young men with little previous experience in resistance training were randomized into treatment and placebo groups [15]. Participants in the treatment group consumed 300 mg of ashwagandha root extract twice daily, while those in the control group took starch placebos instead. Multiple measurements – including muscle strength, muscle size, body composition, testosterone levels, and muscle recovery – were made before the start of the study. Both groups then went through resistance training for 8 weeks and the measurements were repeated when they were done. Promisingly, the group of men taking ashwagandha root extract had significantly greater increases in muscle strength and arm muscle size relative to the placebo group. They also showed significantly less exercise-induced muscle damage, higher testosterone levels, and a greater reduction in body fat percentage. In other words, ashwagandha supplementation is associated with significant increases in muscle mass, strength, and recovery after exercise. In another randomized, double-blind strength and conditioning study known as the STAR trial, 500 mg of an extract of ashwagandha roots and leaves was consumed by recreationally active young men for 12 weeks [16]. Body composition, muscular strength, power, and endurance, cycling time trial, and blood chemistry were measured before and after the study. Consuming the ashwagandha extract was seen to improve upper and lower body strength and improve distribution of body mass in these men, once again without causing any serious adverse effects.   Ashwagandha as an Immune System Enhancer Ashwagandha enhances immune function. In a small study, ashwagandha root extract was seen to activate multiple types of immune cells in the participants [17]. Similarly, a tea fortified with five herbs including ashwagandha was seen to activate so-called “natural killer” (NK) cells in not just one, but two independent double-blind intervention studies conducted in India on healthy volunteers [18]. NK cell activity is an important aspect of our body's early immune response to infections. Interestingly, in other situations, ashwagandha extracts have also been shown to suppress specific components of the immune system. For example, one of the characteristic features of rheumatoid arthritis (RA) is the continuous production of pro-inflammatory compounds known as cytokines in joint cavities, triggering inflammation and cartilage destruction. In laboratory experiments in rats, a root extract of ashwagandha was seen to suppress production of pro-inflammatory cytokines and reduce oxidative stress [19].   The Brain-Boosting Benefits of Ashwagandha Numerous laboratory studies show that ashwagandha – traditionally used in Ayurveda to boost intellect and memory – can slow, stop, and reverse damage to brain cells and may even help to reconstruct brain cell networks. For instance, ashwagandha extracts have been shown to promote nerve cell growth in culture [20]. Withanolide A, withanoside IV, and withanoside VI were identified as the bioactive compounds responsible. Ashwagandha extracts as well as specific bioactive compounds (e.g., withanolide A) have also been shown to protect nerve cells in culture against damage caused by various toxic agents [21]. Amazingly, the administration of withanoside IV for 21 days led to recovery in a rat model of spinal cord damage [20]. It is well known that toxic free radicals damage brain cells and contribute to both normal aging and aging-related health conditions. In a 2015 study, both ashwagandha extracts and a bioactive compound known as withanone were seen to protect nerve cells from oxidative damage [22]. Not surprisingly, ashwagandha has long been used in Ayurveda to enhance memory and improve mental faculties. In a randomized, double-blind, placebo-controlled pilot study, 50 adults suffering from mild cognitive impairment (MCI) – who are considered to be at a greater risk of developing dementia later in life – were treated with either 300 mg of KSM-66 ashwagandha twice daily or placebo for 8 weeks [23]. After 8 weeks, the ashwagandha KSM-66 group showed significant improvements in both their immediate or short-term as well as general memory, relative to the placebo group. The ashwagandha group also showed significant improvements in executive function, sustained attention, and information-processing abilities.   Can Ashwagandha Even Help Protect Against Abnormal Cell Growth? Ashwagandha and other species of Withania are well known in folk medicine traditions for their anti-cancer properties and their extracts have been shown to be toxic for multiple types of cancer cells in laboratory experiments [24]. They appear to act by slowing down or even stopping cancer cell growth by inducing programmed cell death or “apoptosis.” As stated earlier, Withaferin A, an anti-inflammatory withanolide, has been shown to act as an anti-angiogenic. In other words, it can help stop tumors from growing their own blood vessels, slowing down their growth, or perhaps even shrinking them. As reported in the journal Biochemical Pharmacology in August 2019, growing evidence suggests that Withaferin A is very effective against cancer [25]. For instance, low response rate and recurrence are common issues in lung cancer. Withaferin A has been shown to exhibit potent toxicity against several lung cancer cell lines in laboratory experiments. Not only that, the combination of Withaferin A and chemotherapeutic drugs were shown to have additive effects on lung cancer cell survival [26]. Withaferin A has also been shown to be toxic for breast cancer and cervical cancer (HeLa) cells in laboratory experiments [27,28]. Similarly, other bioactive compounds in ashwagandha have also been shown to be toxic for cancer cells in laboratory experiments [29].   KSM-66 Ashwagandha's Impact on Libido and Infertility Ashwagandha root extract has been shown to enhance sexual desire and function in both men and women. For instance, ashwagandha has been described in Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. In a pilot study conducted to evaluate the effects of ashwagandha in patients with a low sperm count (known as oligospermia), a total of 46 male patients were randomized either to treatment with KSM-66 Ashwagandha or placebo for 90 days [30]. At the end of the study, participants given KSM-66 ashwagandha showed a 167% increase in sperm count, a 53% increase in semen volume, and a 57% increase in sperm motility relative to baseline. In comparison, only minimal changes were seen in the placebo group. Further, a greater improvement in hormone levels was seen with KSM-66 ashwagandha. In other words, ashwagandha is likely to be very effective in treating oligospermia, which is a leading cause of male infertility. Similarly, a meta-analysis showed that ashwagandha significantly improved sperm concentration and sperm motility even in men with normal sperm parameters, without any adverse effects [31]. Ashwagandha has also been shown to enhance sexual function in women. At the Trupti Hospital and Santati Fertility Center located near Mumbai in India, 50 women were randomized to either ashwagandha treatment or placebo (300 mg twice daily) for 8 weeks [32]. In this study, ashwagandha supplementation was shown to lead to significantly higher scores in multiple markers of sexual desire and function.   But Is Ashwagandha Safe? Ashwagandha root powder has been used in Ayurvedic medicine for centuries, and it is believed to be completely safe and free of any toxicity. Extracts of ashwagandha made using alcohol and water will likely contain higher doses of its natural ingredients, relative to raw powder. So far animal studies with such extracts have shown no evidence of toxicity, even at relatively high doses [33]. However, it is always advisable to take an herbal supplement only after consulting your healthcare provider, especially if you have any ongoing health conditions or if you're pregnant or breastfeeding.   Organixx Turmeric 3D Contains KSM-66 Ashwagandha The Organixx Turmeric 3D formula has always contained ashwagandha extract. As part of our commitment to seeking out the cleanest and most effective supplement ingredients, we upgraded to KSM-66 Ashwagandha in 2019 – the most clinically studied ashwagandha on the market. KSM-66 is a full-spectrum extract produced using a unique proprietary extraction process, based on “Green Chemistry” principles, without using alcohol or any other chemical solvent.   Resources: [1] An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda. [2] Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha. [3] Scientific Basis for the Therapeutic Use of Withania somnifera (Ashwagandha): A Review. [4] Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. [5] A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. [6] KSM-66 Ashwagandha Documentary [7] Society for Endocrinology: You and Your Hormones – Cortisol. [8] An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. [9] Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. [10] Withaferin A Protects Against High-Fat Diet-Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance. [11] Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. [12] Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study. [13] The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. [14] Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults. [15] Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. [16] Effects of an Aqueous Extract of Withania somnifera on Strength Training Adaptations and Recovery: The STAR Trial. [17] In vivo effects of Ashwagandha (Withania somnifera) extract on the activation of lymphocytes. [18] In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs. [19] In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis. [20] Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. [21] Neuritic regeneration and synaptic reconstruction induced by withanolide A. [22] Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. [23] Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. [24] Medicinal Plants from Near East for Cancer Therapy. [25] Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug. [26] Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer. [27] Withaferin A inhibits expression of ataxia telangiectasia and Rad3-related kinase and enhances sensitivity of human breast cancer cells to cisplatin. [28] Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities. [29] Cytotoxic Withanolides from the Roots of Indian Ginseng (Withania somnifera). [30] Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. [31] Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis. [32] Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study. [33] Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study. KSM-66 Ashwagandha: A Superhero Herb for Body & Brain

As part of its OncView™ video series, CancerNetwork® spoke with Roy Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut, about currently available treatment options and strategies in immunotherapy for treating non–small cell lung cancer (NSCLC). In the video series, Herbst discussed the following: ·      Treatment Options in Non–Small Cell Lung Cancer ·      Monitoring Response to Therapy in NSCLC ·      Role of ctDNA in Monitoring Treatment Response in NSCLC ·      Clinical Decision-Making in NSCLC ·      Recap: Monitoring With ctDNA for Immunotherapy Response in Lung Cancer To watch more videos in CancerNetwork®'s OncView™ series, visit cancernetwork.com/oncview. Don't forget to subscribe to the “Oncology Peer Review On-The-Go” podcast on Apple Podcasts, Spotify or anywhere podcasts are available.

On this episode we hear from Thoracic Medical oncologist Dr. Thomas Stinchcombe. Dr. Stinchcombe is a member of Duke Cancer Institute, and Thoracic Oncology Program at Duke University in Durham, North Carolina. Dr. Stinchcombe explains whether or not they would recommend RET inhibitors as first line therapy for a RET-fusion positive metastatic Non-Small Cell Lung Cancer patient, what drugs are available to treat patients with Non-Small Lung Cancer and MET exon 14 skipping alterations, the significance of a metastatic Non-Small Cell Lung Cancer patient with a ERBB2 or HER2 alteration & whether there are specific mutations that are targetable for HER2. We conclude with a breakdown of the role of immune check point inhibitors in patients with resected Non-Small Cell Lung Cancer & the role of adjuvant therapy with atezolizumab. Visit www.precisca.com for more resources, content, and access to our entire catalogue of educational content. There you will have access to our complete library of educational videos. New episodes of the PrecisCa Oncology Podcast are released weekly. Please consider sharing our podcast, subscribing & turning on notifications to be the first to know about new releases. Together, we can raise the level of cancer care from diagnosis to recovery.

Ashwagandha is an important herb used in the ancient Indian system of medicine known as Ayurveda to promote general health and well-being. In Ayurvedic practice, ashwagandha is classified as a Rasayana, which means an herb or preparation that rejuvenates, extends life, and promotes a youthful state of physical and mental health. Listen in to discover more about ashwagandha's incredible health benefits in general and a special potent “superhero” form known as KSM-66 ashwagandha.   What Does Ashwagandha Do? Ashwagandha's superpower is that it is an adaptogen. Adaptogens are non-toxic therapies that normalize our bodily functions – both physical and mental – that are thrown out of balance when we are exposed to chronic, uncontrolled stress. They do so by correcting imbalances in the neuroendocrine and immune systems [2]. In short, adaptogens enhance our ability to cope with stress. There are more than 35 natural compounds in ashwagandha including alkaloids, steroidal lactones, saponins, and with anolides. These compounds have been shown to have anti-stress activity in multiple laboratory models of chronic stress and in some human studies as well [1-5]. Additionally, ashwagandha extracts as well as specific bioactive compounds present in this plant – primarily in the roots – have been shown to help: counter pain and joint swelling associated with arthritis boost various components of the immune system protect the brain and nervous system slow down or even kill abnormal cells enhance both male and female sexual desire and function What Is KSM-66 Ashwagandha? KSM-66 Ashwagandha is a high-concentration ashwagandha root extract manufactured and sold by Ixoreal Biomed, located in Hyderabad, India [6]. Ashwagandha KSM-66 is made solely from ashwagandha roots, which contain its main bioactive ingredients, without using any other parts that are considered to be less effective. A unique feature of KSM-66 ashwagandha is that it's standardized to a withanolide content of at least 5 percent. Withanolides are a group of around 300 naturally occurring steroid compounds, some of which are naturally present in ashwagandha. One example is Withaferin A, an anti-inflammatory compound that has also been shown to stop tumors from growing their own blood vessels, slowing down their growth, and perhaps even shrinking them. Last but not least, KSM-66 ashwagandha is produced by a unique extraction process, based on the principles of “green chemistry,” without using alcohol or any synthetic solvents. Let's take a closer look now at some of KSM-66 ashwagandha's benefits for health.   What Too Much Cortisol Does to the Body Any stressful event in our lives causes our adrenal glands to produce cortisol, a steroid hormone that acts to control blood sugar levels, regulate metabolism, lower inflammation levels, influence memory formation, and manage salt and water balance [7]. The more stressed we are and the longer we're stressed, the more our adrenals respond by releasing cortisol into our bloodstream. Too much cortisol in the blood over a prolonged period of time can lead to: rapid weight gain high blood pressure osteoporosis muscle weakness mood swings anxiety, depression, or irritability increased thirst and frequency of urination [7] Ongoing high cortisol levels can also eventually cause a lack of sex drive in men. In women, periods typically become irregular, less frequent, or may even stop altogether (amenorrhea).   How Can Ashwagandha Help Us Cope With Stress? To answer this question, a double-blind, randomized, placebo-controlled trial was conducted to assess the safety and efficacy of KSM-66 ashwagandha (which, as mentioned above, is a high-concentration, full-spectrum ashwagandha root extract) in 64 adults [5]. After 60 days of treatment, the study authors observed a “substantial reduction” in four separate measures of stress in the study participants. KSM-66 ashwagandha also reduced levels of the hormone cortisol in the blood. By lowering cortisol, ashwagandha tones down the body's response to stressful situations, in effect “calming us down.”   No serious adverse events were reported [5] and the study researchers concluded that: “High-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.” Similarly, in another randomized, double-blind, placebo-controlled study, 60 stressed but otherwise healthy adults were randomly assigned to take either a placebo or an ashwagandha root extract once daily for 2 months [8]. At the end of the study, participants given ashwagandha showed a significant reduction in their stress, anxiety, and depression scores. Once again, ashwagandha consumption was associated with a greater reduction in the levels of cortisol in the blood, when compared with placebo [8].   The Connection Between Stress and Obesity Chronic stress has been associated with many illnesses, including obesity. In a double-blind, randomized, placebo-controlled trial, ashwagandha consumption was seen to lead to significant reductions in emotional and uncontrolled food cravings while also lowering cortisol, body weight, and body mass index (BMI) in 52 subjects subjected to chronic stress [9]. Indeed, laboratory experiments in mice have shown that one of the main active ingredients in ashwagandha known as Withaferin A can protect against obesity caused by a high-fat diet by reducing inflammation in the liver, oxidative stress, and insulin resistance [10]. These and other findings make it clear that ashwagandha is a powerful tool in our battle against ongoing stress, likely by regulating various specific aspects of our hypothalamus-pituitary-adrenal (HPA) axis. This is an interactive neuroendocrine system that plays a key role in maintaining our body's internal equilibrium, along with orchestrating our body's response to stress.   Ashwagandha Benefits for Joint Pain Ashwagandha is a key ingredient in many Ayurvedic formulations prescribed for joint-related conditions such as osteoarthritis. Indeed, many research studies show that ashwagandha and its bioactive ingredients help to manage and reduce inflammation levels. For instance, in a double-blind, placebo-controlled cross-over clinical trial published in 1991, 42 patients with osteoarthritis were randomized to receive a formula containing ashwagandha, frankincense, turmeric, and zinc – or placebo – for three months [11]. Clinical efficacy was evaluated every 15 days in terms of severity of pain, morning stiffness, Ritchie articular index (a weighted score of tenderness and swelling in 53 joint groups, each scored on a 0-3 scale), joint score, disability score, and grip strength. Throughout the study, the herbal formula was seen to significantly reduce the severity of joint pain and disability. No significant adverse effects were reported. In another study, 86 patients with joint pain were given 5 grams of ashwagandha powder twice a day for three weeks with lukewarm water or milk [12]. Then these patients took another Ayurvedic preparation known as Sidh Makardhwaj – a formulation used in rheumatoid arthritis and neurological disorders – daily for the next four weeks. Treatment with ashwagandha and Sidh Makardhwaj for seven weeks led to significantly improved scores of joint swelling, tenderness, and pain, indicating that this combination treatment is likely to be beneficial in rheumatoid arthritis. Indeed, in laboratory experiments, an ashwagandha root extract was seen to reduce inflammation in knee cartilage taken from chronic osteoarthritis patients [13].   Ashwagandha for Boosting Endurance, Muscle Strength, and Recovery Ashwagandha has long had the reputation of being able to enhance cardiovascular endurance and physical performance. As stated earlier, consuming this herb is said to impart the strength and stamina of a horse [1]. In a prospective, double-blind, randomized, and placebo-controlled study, KSM-66 ashwagandha was shown to significantly boost cardiorespiratory endurance and improve self-reported quality of life (QOL) in 50 healthy male and female athletic adults [14]. In another randomized, prospective, double-blind, placebo-controlled clinical study, 57 young men with little previous experience in resistance training were randomized into treatment and placebo groups [15]. Participants in the treatment group consumed 300 mg of ashwagandha root extract twice daily, while those in the control group took starch placebos instead. Multiple measurements – including muscle strength, muscle size, body composition, testosterone levels, and muscle recovery – were made before the start of the study. Both groups then went through resistance training for 8 weeks and the measurements were repeated when they were done. Promisingly, the group of men taking ashwagandha root extract had significantly greater increases in muscle strength and arm muscle size relative to the placebo group. They also showed significantly less exercise-induced muscle damage, higher testosterone levels, and a greater reduction in body fat percentage. In other words, ashwagandha supplementation is associated with significant increases in muscle mass, strength, and recovery after exercise. In another randomized, double-blind strength and conditioning study known as the STAR trial, 500 mg of an extract of ashwagandha roots and leaves was consumed by recreationally active young men for 12 weeks [16]. Body composition, muscular strength, power, and endurance, cycling time trial, and blood chemistry were measured before and after the study. Consuming the ashwagandha extract was seen to improve upper and lower body strength and improve distribution of body mass in these men, once again without causing any serious adverse effects.   Ashwagandha as an Immune System Enhancer Ashwagandha enhances immune function. In a small study, ashwagandha root extract was seen to activate multiple types of immune cells in the participants [17]. Similarly, a tea fortified with five herbs including ashwagandha was seen to activate so-called “natural killer” (NK) cells in not just one, but two independent double-blind intervention studies conducted in India on healthy volunteers [18]. NK cell activity is an important aspect of our body's early immune response to infections. Interestingly, in other situations, ashwagandha extracts have also been shown to suppress specific components of the immune system. For example, one of the characteristic features of rheumatoid arthritis (RA) is the continuous production of pro-inflammatory compounds known as cytokines in joint cavities, triggering inflammation and cartilage destruction. In laboratory experiments in rats, a root extract of ashwagandha was seen to suppress production of pro-inflammatory cytokines and reduce oxidative stress [19].   The Brain-Boosting Benefits of Ashwagandha Numerous laboratory studies show that ashwagandha – traditionally used in Ayurveda to boost intellect and memory – can slow, stop, and reverse damage to brain cells and may even help to reconstruct brain cell networks. For instance, ashwagandha extracts have been shown to promote nerve cell growth in culture [20]. Withanolide A, withanoside IV, and withanoside VI were identified as the bioactive compounds responsible. Ashwagandha extracts as well as specific bioactive compounds (e.g., withanolide A) have also been shown to protect nerve cells in culture against damage caused by various toxic agents [21]. Amazingly, the administration of withanoside IV for 21 days led to recovery in a rat model of spinal cord damage [20]. It is well known that toxic free radicals damage brain cells and contribute to both normal aging and aging-related health conditions. In a 2015 study, both ashwagandha extracts and a bioactive compound known as withanone were seen to protect nerve cells from oxidative damage [22]. Not surprisingly, ashwagandha has long been used in Ayurveda to enhance memory and improve mental faculties. In a randomized, double-blind, placebo-controlled pilot study, 50 adults suffering from mild cognitive impairment (MCI) – who are considered to be at a greater risk of developing dementia later in life – were treated with either 300 mg of KSM-66 ashwagandha twice daily or placebo for 8 weeks [23]. After 8 weeks, the ashwagandha KSM-66 group showed significant improvements in both their immediate or short-term as well as general memory, relative to the placebo group. The ashwagandha group also showed significant improvements in executive function, sustained attention, and information-processing abilities.   Can Ashwagandha Even Help Protect Against Abnormal Cell Growth? Ashwagandha and other species of Withania are well known in folk medicine traditions for their anti-cancer properties and their extracts have been shown to be toxic for multiple types of cancer cells in laboratory experiments [24]. They appear to act by slowing down or even stopping cancer cell growth by inducing programmed cell death or “apoptosis.” As stated earlier, Withaferin A, an anti-inflammatory withanolide, has been shown to act as an anti-angiogenic. In other words, it can help stop tumors from growing their own blood vessels, slowing down their growth, or perhaps even shrinking them. As reported in the journal Biochemical Pharmacology in August 2019, growing evidence suggests that Withaferin A is very effective against cancer [25]. For instance, low response rate and recurrence are common issues in lung cancer. Withaferin A has been shown to exhibit potent toxicity against several lung cancer cell lines in laboratory experiments. Not only that, the combination of Withaferin A and chemotherapeutic drugs were shown to have additive effects on lung cancer cell survival [26]. Withaferin A has also been shown to be toxic for breast cancer and cervical cancer (HeLa) cells in laboratory experiments [27,28]. Similarly, other bioactive compounds in ashwagandha have also been shown to be toxic for cancer cells in laboratory experiments [29].   KSM-66 Ashwagandha's Impact on Libido and Infertility Ashwagandha root extract has been shown to enhance sexual desire and function in both men and women. For instance, ashwagandha has been described in Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. In a pilot study conducted to evaluate the effects of ashwagandha in patients with a low sperm count (known as oligospermia), a total of 46 male patients were randomized either to treatment with KSM-66 Ashwagandha or placebo for 90 days [30]. At the end of the study, participants given KSM-66 ashwagandha showed a 167% increase in sperm count, a 53% increase in semen volume, and a 57% increase in sperm motility relative to baseline. In comparison, only minimal changes were seen in the placebo group. Further, a greater improvement in hormone levels was seen with KSM-66 ashwagandha. In other words, ashwagandha is likely to be very effective in treating oligospermia, which is a leading cause of male infertility. Similarly, a meta-analysis showed that ashwagandha significantly improved sperm concentration and sperm motility even in men with normal sperm parameters, without any adverse effects [31]. Ashwagandha has also been shown to enhance sexual function in women. At the Trupti Hospital and Santati Fertility Center located near Mumbai in India, 50 women were randomized to either ashwagandha treatment or placebo (300 mg twice daily) for 8 weeks [32]. In this study, ashwagandha supplementation was shown to lead to significantly higher scores in multiple markers of sexual desire and function.   But Is Ashwagandha Safe? Ashwagandha root powder has been used in Ayurvedic medicine for centuries, and it is believed to be completely safe and free of any toxicity. Extracts of ashwagandha made using alcohol and water will likely contain higher doses of its natural ingredients, relative to raw powder. So far animal studies with such extracts have shown no evidence of toxicity, even at relatively high doses [33]. However, it is always advisable to take an herbal supplement only after consulting your healthcare provider, especially if you have any ongoing health conditions or if you're pregnant or breastfeeding.   Organixx Turmeric 3D Contains KSM-66 Ashwagandha The Organixx Turmeric 3D formula has always contained ashwagandha extract. As part of our commitment to seeking out the cleanest and most effective supplement ingredients, we upgraded to KSM-66 Ashwagandha in 2019 – the most clinically studied ashwagandha on the market. KSM-66 is a full-spectrum extract produced using a unique proprietary extraction process, based on “Green Chemistry” principles, without using alcohol or any other chemical solvent.   RESOURCES: [1] An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda. [2] Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha. [3] Scientific Basis for the Therapeutic Use of Withania somnifera (Ashwagandha): A Review. [4] Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. [5] A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. [6] KSM-66 Ashwagandha Documentary [7] Society for Endocrinology: You and Your Hormones – Cortisol. [8] An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. [9] Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. [10] Withaferin A Protects Against High-Fat Diet-Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance. [11] Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. [12] Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study. [13] The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. [14] Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults. [15] Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. [16] Effects of an Aqueous Extract of Withania somnifera on Strength Training Adaptations and Recovery: The STAR Trial. [17] In vivo effects of Ashwagandha (Withania somnifera) extract on the activation of lymphocytes. [18] In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs. [19] In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis. [20] Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. [21] Neuritic regeneration and synaptic reconstruction induced by withanolide A. [22] Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. [23] Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. [24] Medicinal Plants from Near East for Cancer Therapy. [25] Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug. [26] Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer. [27] Withaferin A inhibits expression of ataxia telangiectasia and Rad3-related kinase and enhances sensitivity of human breast cancer cells to cisplatin. [28] Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities. [29] Cytotoxic Withanolides from the Roots of Indian Ginseng (Withania somnifera). [30] Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. [31] Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis. [32] Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study. [33] Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study. KSM-66 Ashwagandha: A Superhero Herb for Body & Brain  

Ashwagandha is an important herb used in the ancient Indian system of medicine known as Ayurveda to promote general health and well-being. In Ayurvedic practice, ashwagandha is classified as a Rasayana, which means an herb or preparation that rejuvenates, extends life, and promotes a youthful state of physical and mental health. Listen in to discover more about ashwagandha's incredible health benefits in general and a special potent “superhero” form known as KSM-66 ashwagandha.   What Does Ashwagandha Do? Ashwagandha's superpower is that it is an adaptogen. Adaptogens are non-toxic therapies that normalize our bodily functions – both physical and mental – that are thrown out of balance when we are exposed to chronic, uncontrolled stress. They do so by correcting imbalances in the neuroendocrine and immune systems [2]. In short, adaptogens enhance our ability to cope with stress. There are more than 35 natural compounds in ashwagandha including alkaloids, steroidal lactones, saponins, and with anolides. These compounds have been shown to have anti-stress activity in multiple laboratory models of chronic stress and in some human studies as well [1-5]. Additionally, ashwagandha extracts as well as specific bioactive compounds present in this plant – primarily in the roots – have been shown to help: counter pain and joint swelling associated with arthritis boost various components of the immune system protect the brain and nervous system slow down or even kill abnormal cells enhance both male and female sexual desire and function What Is KSM-66 Ashwagandha? KSM-66 Ashwagandha is a high-concentration ashwagandha root extract manufactured and sold by Ixoreal Biomed, located in Hyderabad, India [6]. Ashwagandha KSM-66 is made solely from ashwagandha roots, which contain its main bioactive ingredients, without using any other parts that are considered to be less effective. A unique feature of KSM-66 ashwagandha is that it's standardized to a withanolide content of at least 5 percent. Withanolides are a group of around 300 naturally occurring steroid compounds, some of which are naturally present in ashwagandha. One example is Withaferin A, an anti-inflammatory compound that has also been shown to stop tumors from growing their own blood vessels, slowing down their growth, and perhaps even shrinking them. Last but not least, KSM-66 ashwagandha is produced by a unique extraction process, based on the principles of “green chemistry,” without using alcohol or any synthetic solvents. Let's take a closer look now at some of KSM-66 ashwagandha's benefits for health.   What Too Much Cortisol Does to the Body Any stressful event in our lives causes our adrenal glands to produce cortisol, a steroid hormone that acts to control blood sugar levels, regulate metabolism, lower inflammation levels, influence memory formation, and manage salt and water balance [7]. The more stressed we are and the longer we're stressed, the more our adrenals respond by releasing cortisol into our bloodstream. Too much cortisol in the blood over a prolonged period of time can lead to: rapid weight gain high blood pressure osteoporosis muscle weakness mood swings anxiety, depression, or irritability increased thirst and frequency of urination [7] Ongoing high cortisol levels can also eventually cause a lack of sex drive in men. In women, periods typically become irregular, less frequent, or may even stop altogether (amenorrhea).   How Can Ashwagandha Help Us Cope With Stress? To answer this question, a double-blind, randomized, placebo-controlled trial was conducted to assess the safety and efficacy of KSM-66 ashwagandha (which, as mentioned above, is a high-concentration, full-spectrum ashwagandha root extract) in 64 adults [5]. After 60 days of treatment, the study authors observed a “substantial reduction” in four separate measures of stress in the study participants. KSM-66 ashwagandha also reduced levels of the hormone cortisol in the blood. By lowering cortisol, ashwagandha tones down the body's response to stressful situations, in effect “calming us down.”   No serious adverse events were reported [5] and the study researchers concluded that: “High-concentration full-spectrum Ashwagandha root extract safely and effectively improves an individual's resistance towards stress and thereby improves self-assessed quality of life.” Similarly, in another randomized, double-blind, placebo-controlled study, 60 stressed but otherwise healthy adults were randomly assigned to take either a placebo or an ashwagandha root extract once daily for 2 months [8]. At the end of the study, participants given ashwagandha showed a significant reduction in their stress, anxiety, and depression scores. Once again, ashwagandha consumption was associated with a greater reduction in the levels of cortisol in the blood, when compared with placebo [8].   The Connection Between Stress and Obesity Chronic stress has been associated with many illnesses, including obesity. In a double-blind, randomized, placebo-controlled trial, ashwagandha consumption was seen to lead to significant reductions in emotional and uncontrolled food cravings while also lowering cortisol, body weight, and body mass index (BMI) in 52 subjects subjected to chronic stress [9]. Indeed, laboratory experiments in mice have shown that one of the main active ingredients in ashwagandha known as Withaferin A can protect against obesity caused by a high-fat diet by reducing inflammation in the liver, oxidative stress, and insulin resistance [10]. These and other findings make it clear that ashwagandha is a powerful tool in our battle against ongoing stress, likely by regulating various specific aspects of our hypothalamus-pituitary-adrenal (HPA) axis. This is an interactive neuroendocrine system that plays a key role in maintaining our body's internal equilibrium, along with orchestrating our body's response to stress.   Ashwagandha Benefits for Joint Pain Ashwagandha is a key ingredient in many Ayurvedic formulations prescribed for joint-related conditions such as osteoarthritis. Indeed, many research studies show that ashwagandha and its bioactive ingredients help to manage and reduce inflammation levels. For instance, in a double-blind, placebo-controlled cross-over clinical trial published in 1991, 42 patients with osteoarthritis were randomized to receive a formula containing ashwagandha, frankincense, turmeric, and zinc – or placebo – for three months [11]. Clinical efficacy was evaluated every 15 days in terms of severity of pain, morning stiffness, Ritchie articular index (a weighted score of tenderness and swelling in 53 joint groups, each scored on a 0-3 scale), joint score, disability score, and grip strength. Throughout the study, the herbal formula was seen to significantly reduce the severity of joint pain and disability. No significant adverse effects were reported. In another study, 86 patients with joint pain were given 5 grams of ashwagandha powder twice a day for three weeks with lukewarm water or milk [12]. Then these patients took another Ayurvedic preparation known as Sidh Makardhwaj – a formulation used in rheumatoid arthritis and neurological disorders – daily for the next four weeks. Treatment with ashwagandha and Sidh Makardhwaj for seven weeks led to significantly improved scores of joint swelling, tenderness, and pain, indicating that this combination treatment is likely to be beneficial in rheumatoid arthritis. Indeed, in laboratory experiments, an ashwagandha root extract was seen to reduce inflammation in knee cartilage taken from chronic osteoarthritis patients [13].   Ashwagandha for Boosting Endurance, Muscle Strength, and Recovery Ashwagandha has long had the reputation of being able to enhance cardiovascular endurance and physical performance. As stated earlier, consuming this herb is said to impart the strength and stamina of a horse [1]. In a prospective, double-blind, randomized, and placebo-controlled study, KSM-66 ashwagandha was shown to significantly boost cardiorespiratory endurance and improve self-reported quality of life (QOL) in 50 healthy male and female athletic adults [14]. In another randomized, prospective, double-blind, placebo-controlled clinical study, 57 young men with little previous experience in resistance training were randomized into treatment and placebo groups [15]. Participants in the treatment group consumed 300 mg of ashwagandha root extract twice daily, while those in the control group took starch placebos instead. Multiple measurements – including muscle strength, muscle size, body composition, testosterone levels, and muscle recovery – were made before the start of the study. Both groups then went through resistance training for 8 weeks and the measurements were repeated when they were done. Promisingly, the group of men taking ashwagandha root extract had significantly greater increases in muscle strength and arm muscle size relative to the placebo group. They also showed significantly less exercise-induced muscle damage, higher testosterone levels, and a greater reduction in body fat percentage. In other words, ashwagandha supplementation is associated with significant increases in muscle mass, strength, and recovery after exercise. In another randomized, double-blind strength and conditioning study known as the STAR trial, 500 mg of an extract of ashwagandha roots and leaves was consumed by recreationally active young men for 12 weeks [16]. Body composition, muscular strength, power, and endurance, cycling time trial, and blood chemistry were measured before and after the study. Consuming the ashwagandha extract was seen to improve upper and lower body strength and improve distribution of body mass in these men, once again without causing any serious adverse effects.   Ashwagandha as an Immune System Enhancer Ashwagandha enhances immune function. In a small study, ashwagandha root extract was seen to activate multiple types of immune cells in the participants [17]. Similarly, a tea fortified with five herbs including ashwagandha was seen to activate so-called “natural killer” (NK) cells in not just one, but two independent double-blind intervention studies conducted in India on healthy volunteers [18]. NK cell activity is an important aspect of our body's early immune response to infections. Interestingly, in other situations, ashwagandha extracts have also been shown to suppress specific components of the immune system. For example, one of the characteristic features of rheumatoid arthritis (RA) is the continuous production of pro-inflammatory compounds known as cytokines in joint cavities, triggering inflammation and cartilage destruction. In laboratory experiments in rats, a root extract of ashwagandha was seen to suppress production of pro-inflammatory cytokines and reduce oxidative stress [19].   The Brain-Boosting Benefits of Ashwagandha Numerous laboratory studies show that ashwagandha – traditionally used in Ayurveda to boost intellect and memory – can slow, stop, and reverse damage to brain cells and may even help to reconstruct brain cell networks. For instance, ashwagandha extracts have been shown to promote nerve cell growth in culture [20]. Withanolide A, withanoside IV, and withanoside VI were identified as the bioactive compounds responsible. Ashwagandha extracts as well as specific bioactive compounds (e.g., withanolide A) have also been shown to protect nerve cells in culture against damage caused by various toxic agents [21]. Amazingly, the administration of withanoside IV for 21 days led to recovery in a rat model of spinal cord damage [20]. It is well known that toxic free radicals damage brain cells and contribute to both normal aging and aging-related health conditions. In a 2015 study, both ashwagandha extracts and a bioactive compound known as withanone were seen to protect nerve cells from oxidative damage [22]. Not surprisingly, ashwagandha has long been used in Ayurveda to enhance memory and improve mental faculties. In a randomized, double-blind, placebo-controlled pilot study, 50 adults suffering from mild cognitive impairment (MCI) – who are considered to be at a greater risk of developing dementia later in life – were treated with either 300 mg of KSM-66 ashwagandha twice daily or placebo for 8 weeks [23]. After 8 weeks, the ashwagandha KSM-66 group showed significant improvements in both their immediate or short-term as well as general memory, relative to the placebo group. The ashwagandha group also showed significant improvements in executive function, sustained attention, and information-processing abilities.   Can Ashwagandha Even Help Protect Against Abnormal Cell Growth? Ashwagandha and other species of Withania are well known in folk medicine traditions for their anti-cancer properties and their extracts have been shown to be toxic for multiple types of cancer cells in laboratory experiments [24]. They appear to act by slowing down or even stopping cancer cell growth by inducing programmed cell death or “apoptosis.” As stated earlier, Withaferin A, an anti-inflammatory withanolide, has been shown to act as an anti-angiogenic. In other words, it can help stop tumors from growing their own blood vessels, slowing down their growth, or perhaps even shrinking them. As reported in the journal Biochemical Pharmacology in August 2019, growing evidence suggests that Withaferin A is very effective against cancer [25]. For instance, low response rate and recurrence are common issues in lung cancer. Withaferin A has been shown to exhibit potent toxicity against several lung cancer cell lines in laboratory experiments. Not only that, the combination of Withaferin A and chemotherapeutic drugs were shown to have additive effects on lung cancer cell survival [26]. Withaferin A has also been shown to be toxic for breast cancer and cervical cancer (HeLa) cells in laboratory experiments [27,28]. Similarly, other bioactive compounds in ashwagandha have also been shown to be toxic for cancer cells in laboratory experiments [29].   KSM-66 Ashwagandha's Impact on Libido and Infertility Ashwagandha root extract has been shown to enhance sexual desire and function in both men and women. For instance, ashwagandha has been described in Ayurvedic medicine as an aphrodisiac that can be used to treat male sexual dysfunction and infertility. In a pilot study conducted to evaluate the effects of ashwagandha in patients with a low sperm count (known as oligospermia), a total of 46 male patients were randomized either to treatment with KSM-66 Ashwagandha or placebo for 90 days [30]. At the end of the study, participants given KSM-66 ashwagandha showed a 167% increase in sperm count, a 53% increase in semen volume, and a 57% increase in sperm motility relative to baseline. In comparison, only minimal changes were seen in the placebo group. Further, a greater improvement in hormone levels was seen with KSM-66 ashwagandha. In other words, ashwagandha is likely to be very effective in treating oligospermia, which is a leading cause of male infertility. Similarly, a meta-analysis showed that ashwagandha significantly improved sperm concentration and sperm motility even in men with normal sperm parameters, without any adverse effects [31]. Ashwagandha has also been shown to enhance sexual function in women. At the Trupti Hospital and Santati Fertility Center located near Mumbai in India, 50 women were randomized to either ashwagandha treatment or placebo (300 mg twice daily) for 8 weeks [32]. In this study, ashwagandha supplementation was shown to lead to significantly higher scores in multiple markers of sexual desire and function.   But Is Ashwagandha Safe? Ashwagandha root powder has been used in Ayurvedic medicine for centuries, and it is believed to be completely safe and free of any toxicity. Extracts of ashwagandha made using alcohol and water will likely contain higher doses of its natural ingredients, relative to raw powder. So far animal studies with such extracts have shown no evidence of toxicity, even at relatively high doses [33]. However, it is always advisable to take an herbal supplement only after consulting your healthcare provider, especially if you have any ongoing health conditions or if you're pregnant or breastfeeding.   Organixx Turmeric 3D Contains KSM-66 Ashwagandha The Organixx Turmeric 3D formula has always contained ashwagandha extract. As part of our commitment to seeking out the cleanest and most effective supplement ingredients, we upgraded to KSM-66 Ashwagandha in 2019 – the most clinically studied ashwagandha on the market. KSM-66 is a full-spectrum extract produced using a unique proprietary extraction process, based on “Green Chemistry” principles, without using alcohol or any other chemical solvent.   RESOURCES: [1] An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda. [2] Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha. [3] Scientific Basis for the Therapeutic Use of Withania somnifera (Ashwagandha): A Review. [4] Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. [5] A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. [6] KSM-66 Ashwagandha Documentary [7] Society for Endocrinology: You and Your Hormones – Cortisol. [8] An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. [9] Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. [10] Withaferin A Protects Against High-Fat Diet-Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance. [11] Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. [12] Efficacy & safety evaluation of Ayurvedic treatment (Ashwagandha powder & Sidh Makardhwaj) in rheumatoid arthritis patients: a pilot prospective study. [13] The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. [14] Efficacy of Ashwagandha (Withania somnifera [L.] Dunal) in improving cardiorespiratory endurance in healthy athletic adults. [15] Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. [16] Effects of an Aqueous Extract of Withania somnifera on Strength Training Adaptations and Recovery: The STAR Trial. [17] In vivo effects of Ashwagandha (Withania somnifera) extract on the activation of lymphocytes. [18] In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs. [19] In vivo, Extract from Withania somnifera Root Ameliorates Arthritis via Regulation of Key Immune Mediators of Inflammation in Experimental Model of Arthritis. [20] Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. [21] Neuritic regeneration and synaptic reconstruction induced by withanolide A. [22] Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. [23] Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. [24] Medicinal Plants from Near East for Cancer Therapy. [25] Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug. [26] Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer. [27] Withaferin A inhibits expression of ataxia telangiectasia and Rad3-related kinase and enhances sensitivity of human breast cancer cells to cisplatin. [28] Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities. [29] Cytotoxic Withanolides from the Roots of Indian Ginseng (Withania somnifera). [30] Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. [31] Withania somnifera (Indian ginseng) in male infertility: An evidence-based systematic review and meta-analysis. [32] Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Improving Sexual Function in Women: A Pilot Study. [33] Safety assessment of Withania somnifera extract standardized for Withaferin A: Acute and sub-acute toxicity study. KSM-66 Ashwagandha: A Superhero Herb for Body & Brain

Join moderators Divya Patel, DO, and Vineesha Arelli, MD, and journal CHEST® authors Marc Fortin, MD, and Pascalin Roy, MD, as they discuss the article, "A Prediction Model to Optimize Invasive Mediastinal Staging Procedures for Non-Small Cell Lung Cancer in Patients With a Radiologically Normal Mediastinum: The Quebec Prediction Model," which was published in the December 2021 issue. DOI: https://doi.org/10.1016/j.chest.2021.05.062

November is Lung Cancer Awareness Month, and what better way is there to spend your time than getting to know the recent advances in adjuvant therapy for early-stage lung adenocarcinoma?  Learning Objectives -        Review work-up and treatment of lung adenocarcinoma -        Review evidence behind Osimertinib as an adjuvant therapy in EGFR mutation positive disease -        Review recent advances in gene expression profiles for targeted application of adjuvant chemotherapy -        Discuss future directions for research -        Discuss additional advancements in diagnosis, monitoring, and immunotherapy Referenced Material -        Wu Y, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med 2020; 383:1711-1723. DOI: 10.1056/NEJMoa2027071  https://www.nejm.org/doi/full/10.1056/NEJMoa2027071 -        Woodard GA, Wang SX, Kratz JR, et al. Adjuvant Chemotherapy Guided by Molecular Profiling and Improved Outcomes in Early Stage, Non-Small-Cell Lung Cancer. Clin Lung Cancer 2018;19(1):58-64. DOI: 10.1016/j.cllc.2017.05.015 https://www.clinical-lung-cancer.com/article/S1525-7304(17)30150-X/fulltext -        Woodard GA, Kratz JR, Haro G, et al. Molecular Risk Stratification is Independent of EGFR Mutation Status in Identifying Early-Stage Non-Squamous Non-Small Cell Lung Cancer Patients at Risk for Recurrence and Likely to Benefit From Adjuvant Chemotherapy. Clin Lung Cancer. 2021;20:S1525-7304(21)00212-6. DOI: 10.1016/j.cllc.2021.08.008 https://www.clinical-lung-cancer.com/article/S1525-7304(21)00212-6/fulltext Please visit behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  

It's been a while! I think we will call this the second season as it seems fitting as I head into another season of battling cancer. Devastated and angry are just two of the words that come to mind. But also with that come to surrender and faith. Thank you for being on the journey with me so far. Tag along as I fight cancer again. If you enjoyed this episode, make sure and give us a five star rating  and leave us a review on iTunes, Podcast Addict, Podchaser and Castbox. Sign up for the next DAC Bootcamp Follow me on Social Media:Amy on IGAmy on Facebook Resources:AmyLedin.comLean Bodies Consulting (LBC)LBC University 

In this episode I am joined by my father Buster Hitchcock. He shares about his story with his two types of Cancers at the same time and his Stage 4 Kidney Disease Diagnosis over the course of 4 years. He shares personal stories about his mental health and really dives deep in starting to be open with people in his life about what's going on. We talk about our relationship and the dynamic of me becoming his Primary Caregiver once my mother was diagnosed with Stage 4 Non-Small Cell Lung Cancer in June of 2020. https://www.facebook.com/radicalcarepodcasthttps://www.instagram.com/radicalcarepodcast/

On this episode of the Business of Biotech, we're going deep with Glympse Bio President & CEO Dr. Caroline Loew to explore the possibilities and implications of the in-vivo, bioengineered, tunable sensors the company is developing for diagnostic and prognostic purposes in protease-mediates diseases. Currently in the clinic with applications for Non-Alcoholic Steatohepatitis and other fibrotic diseases as well as Non-Small Cell Lung Cancer and other solid tumors, Glympse is unlocking an unprecedented view of near-real-time therapeutic response and therapeutic efficacy that could have big implications on the way biologics are developed, refined, and studied in the clinic.  

Health update on the diagnosis of Non Small Cell Lung Cancer. This is a continuation episode from our previous episode where we discussed host Michael's health. Results are looking good but there is still a long road ahead. If you would like to make a donation, there is a GoFundMe page available to do so. If you would like to send an email directly to Michael, the email address is michaelmatthewperry@gmail.com. 

FDA 连续批准2个针对MET外显子突变的非小细胞肺癌的靶向药NEJM 关于电子烟相关急性肺损伤的住院与死亡的报告Nature 抑制淋巴毒素β受体可诱导肺再生卡马替尼（capmatinib）在非小细胞肺癌患者中，MET外显子14跳跃突变发生在3~4%、MET扩增发生率1~6%。卡马替尼是一种选择性的MET受体抑制剂，在具有不同类型MET激活的癌症模型中显示出活性。2020年5月，FDA批准卡马替尼用于MET外显子14跳跃突变的非小细胞肺癌的一线治疗。《GEOMETRY mono-1研究：卡马替尼治疗MET外显子14突变或MET扩增的非小细胞肺癌的2期临床研究》New England Journal of Medicine，2020年9月 (1)参与者为364名晚期非小细胞肺癌患者，根据既往治疗和MET状态分组，接受卡马替尼治疗。其中MET外显子14跳跃突变的患者中，曾接受过治疗的整体缓解率41%，未接受过治疗的缓解率68%，中位缓解时间分别为9.7个月和12.6个月。在MET扩增的患者中，疗效有限。MET基因拷贝数

FDA 连续批准2个针对MET外显子突变的非小细胞肺癌的靶向药NEJM 关于电子烟相关急性肺损伤的住院与死亡的报告Nature 抑制淋巴毒素β受体可诱导肺再生卡马替尼（capmatinib）在非小细胞肺癌患者中，MET外显子14跳跃突变发生在3~4%、MET扩增发生率1~6%。卡马替尼是一种选择性的MET受体抑制剂，在具有不同类型MET激活的癌症模型中显示出活性。2020年5月，FDA批准卡马替尼用于MET外显子14跳跃突变的非小细胞肺癌的一线治疗。《GEOMETRY mono-1研究：卡马替尼治疗MET外显子14突变或MET扩增的非小细胞肺癌的2期临床研究》New England Journal of Medicine，2020年9月 (1)参与者为364名晚期非小细胞肺癌患者，根据既往治疗和MET状态分组，接受卡马替尼治疗。其中MET外显子14跳跃突变的患者中，曾接受过治疗的整体缓解率41%，未接受过治疗的缓解率68%，中位缓解时间分别为9.7个月和12.6个月。在MET扩增的患者中，疗效有限。MET基因拷贝数

In this episode we get to know cohost Jesus Fuentes. Not to be outdone by Chad, he too has suffer tragedy. He re-lives the night of Las Vegas shooting. Speaks candidly about the depression that followed. Next he tells the story of his diagnosis with stage 4 Non Small Cell Lung Cancer and how he's doing now. Another semi-serious episode, but we will be back to our regular shenanigans on the next episode. Until then, Happy Thanksgiving!

FDA D.I.S.C.O.: Osimertinib for Non-Small Cell Lung Cancer FDA medical oncologists discuss the approval of osimertinib for EGFR mutation-positive non-small cell lung cancer.